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nord_0_0 | Overview of 47, XXY (Klinefelter Syndrome) | SummaryKlinefelter Syndrome (47, XXY) is a chromosomal variation in males in which one extra X chromosome is present, resulting in a 47,XXY karyotype. The extra X chromosome typically affects physical, neurodevelopmental, behavioral, and neurocognitive functioning. Common physical features may include tall stature, reduced muscle tone, small testes (hypogonadism), delayed pubertal development and lack of secondary male sex characteristics such as decreased facial and body hair. Increased breast growth (gynecomastia) may occur later in puberty without appropriate biological care. With proper treatment, the incidence of gynecomastia typically occurs in less than 10% of boys with 47,XXY (KS).There is great variability to the neurodevelopmental profile or phenotype in boys with 47,XXY (KS). Common cognitive and behavioral features may include speech and language delays, ADHD and emotional and social functioning challenges. The features of 47, XXY (KS) are typically associated with decreased testosterone level and elevated gonadotropin levels. Early hormonal treatment (EHT) with three monthly injections of 25 mg. of testosterone enanthate, typically given between 4-12 months of age, may optimize brain development and neurodevelopmental outcomes. Testosterone should be administered based upon an evaluation with a pediatrician and pediatric endocrinologist familiar with 47,XXY (KS). | Overview of 47, XXY (Klinefelter Syndrome). SummaryKlinefelter Syndrome (47, XXY) is a chromosomal variation in males in which one extra X chromosome is present, resulting in a 47,XXY karyotype. The extra X chromosome typically affects physical, neurodevelopmental, behavioral, and neurocognitive functioning. Common physical features may include tall stature, reduced muscle tone, small testes (hypogonadism), delayed pubertal development and lack of secondary male sex characteristics such as decreased facial and body hair. Increased breast growth (gynecomastia) may occur later in puberty without appropriate biological care. With proper treatment, the incidence of gynecomastia typically occurs in less than 10% of boys with 47,XXY (KS).There is great variability to the neurodevelopmental profile or phenotype in boys with 47,XXY (KS). Common cognitive and behavioral features may include speech and language delays, ADHD and emotional and social functioning challenges. The features of 47, XXY (KS) are typically associated with decreased testosterone level and elevated gonadotropin levels. Early hormonal treatment (EHT) with three monthly injections of 25 mg. of testosterone enanthate, typically given between 4-12 months of age, may optimize brain development and neurodevelopmental outcomes. Testosterone should be administered based upon an evaluation with a pediatrician and pediatric endocrinologist familiar with 47,XXY (KS). | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_1 | Symptoms of 47, XXY (Klinefelter Syndrome) | At birth, most neonates with 47, XXY (KS) have no significant dysmorphic or unusual features. Most individuals with 47, XXY (KS) are identified though prenatal diagnosis or when the child does not progress through puberty completely or adequately. Infants and young children with 47, XXY (KS) are sometimes initially identified because of an abnormality in the location of the urinary opening in the penis (hypospadias), small penis or testes, or developmental delay (e.g. speech delay). Older children and teenagers are sometimes diagnosed with 47, XXY (KS) if secondary sexual characteristics do not develop completely, puberty is delayed, testes are small, or breast development occurs. Many males with 47, XXY (KS) are not identified until they have low fertility problems as adults. Men with 47, XXY (KS) may have a relatively increased risk to develop breast cancer but not until after 60 years of age. Most males with 47, XXY (KS) have normal intelligence but there is an increased risk of language based learning disorders, dyslexia and mild social and executive functioning challenges. Often, boys and men with 47, XXY (KS) will present with verbal communication delays due to language-based learning disorders and subtle motor planning deficits. Research has shown, however, that nonverbal capacities in males with 47, XXY (KS), such as perceptual reasoning and receptive language skills, may be intact or even advanced. Thus, PIQ (nonverbal IQ) is often higher than VIQ (verbal IQ) on neurodevelopmental testing. Socially, males with 47, XXY (KS) may have difficulty perceiving social cues and regulating their emotions in stressful situations.Men with 47, XXY (KS) may have an increased risk for endocrine conditions such as diabetes mellitus, hypothyroidism and hypoparathyroidism and autoimmune diseases such as systemic lupus erythematosus, Sjogren syndrome and rheumatoid arthritis. Many of these conditions can be treated with medications and lifestyle changes. | Symptoms of 47, XXY (Klinefelter Syndrome). At birth, most neonates with 47, XXY (KS) have no significant dysmorphic or unusual features. Most individuals with 47, XXY (KS) are identified though prenatal diagnosis or when the child does not progress through puberty completely or adequately. Infants and young children with 47, XXY (KS) are sometimes initially identified because of an abnormality in the location of the urinary opening in the penis (hypospadias), small penis or testes, or developmental delay (e.g. speech delay). Older children and teenagers are sometimes diagnosed with 47, XXY (KS) if secondary sexual characteristics do not develop completely, puberty is delayed, testes are small, or breast development occurs. Many males with 47, XXY (KS) are not identified until they have low fertility problems as adults. Men with 47, XXY (KS) may have a relatively increased risk to develop breast cancer but not until after 60 years of age. Most males with 47, XXY (KS) have normal intelligence but there is an increased risk of language based learning disorders, dyslexia and mild social and executive functioning challenges. Often, boys and men with 47, XXY (KS) will present with verbal communication delays due to language-based learning disorders and subtle motor planning deficits. Research has shown, however, that nonverbal capacities in males with 47, XXY (KS), such as perceptual reasoning and receptive language skills, may be intact or even advanced. Thus, PIQ (nonverbal IQ) is often higher than VIQ (verbal IQ) on neurodevelopmental testing. Socially, males with 47, XXY (KS) may have difficulty perceiving social cues and regulating their emotions in stressful situations.Men with 47, XXY (KS) may have an increased risk for endocrine conditions such as diabetes mellitus, hypothyroidism and hypoparathyroidism and autoimmune diseases such as systemic lupus erythematosus, Sjogren syndrome and rheumatoid arthritis. Many of these conditions can be treated with medications and lifestyle changes. | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_2 | Causes of 47, XXY (Klinefelter Syndrome) | 47, XXY (KS) is not inherited. Males with 47, XXY (KS) have one extra X chromosome because of a nondisjunction error that randomly occurs during the division of the sex chromosomes in the egg or sperm. Some males with 47, XXY (KS) are mosaic, meaning that some cells have an extra X chromosome and other cells do not. Mosaic 47, XXY (KS) occurs because of an error in the division of the sex chromosomes in the zygote after fertilization. The extra X chromosome typically results in primary testicular failure leading to androgen deficiency. | Causes of 47, XXY (Klinefelter Syndrome). 47, XXY (KS) is not inherited. Males with 47, XXY (KS) have one extra X chromosome because of a nondisjunction error that randomly occurs during the division of the sex chromosomes in the egg or sperm. Some males with 47, XXY (KS) are mosaic, meaning that some cells have an extra X chromosome and other cells do not. Mosaic 47, XXY (KS) occurs because of an error in the division of the sex chromosomes in the zygote after fertilization. The extra X chromosome typically results in primary testicular failure leading to androgen deficiency. | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_3 | Affects of 47, XXY (Klinefelter Syndrome) | 47, XXY (KS) is the most common human sex chromosome disorder and occurs in approximately 1 in 500-1,000 males. It is estimated that 3,000 affected boys are born each year in the United States. | Affects of 47, XXY (Klinefelter Syndrome). 47, XXY (KS) is the most common human sex chromosome disorder and occurs in approximately 1 in 500-1,000 males. It is estimated that 3,000 affected boys are born each year in the United States. | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_4 | Related disorders of 47, XXY (Klinefelter Syndrome) | Kallmann syndrome is a rare inherited disorder that mostly, but not exclusively, affects men. The major characteristics of Kallmann syndrome, in both men and women, are the failure to experience puberty and the complete or partial loss of the sense of smell. Failure to go through puberty reflects a hormonal imbalance that is caused by a failure of a part of the brain known as the hypothalamus. Patients with Kallmann syndrome show evidence of small genitalia, sterile gonads that cannot produce the sex cells (hypogonadism), and a loss of the sense of smell (anosmia). The impaired production of hormones as well as sperm and egg cells causes delayed puberty, growth and infertility. (For more information on this disorder, choose “Kallmann syndrome” as your search term in the Rare Disease Database.) | Related disorders of 47, XXY (Klinefelter Syndrome). Kallmann syndrome is a rare inherited disorder that mostly, but not exclusively, affects men. The major characteristics of Kallmann syndrome, in both men and women, are the failure to experience puberty and the complete or partial loss of the sense of smell. Failure to go through puberty reflects a hormonal imbalance that is caused by a failure of a part of the brain known as the hypothalamus. Patients with Kallmann syndrome show evidence of small genitalia, sterile gonads that cannot produce the sex cells (hypogonadism), and a loss of the sense of smell (anosmia). The impaired production of hormones as well as sperm and egg cells causes delayed puberty, growth and infertility. (For more information on this disorder, choose “Kallmann syndrome” as your search term in the Rare Disease Database.) | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_5 | Diagnosis of 47, XXY (Klinefelter Syndrome) | Males with 47, XXY (KS) are most commonly identified before birth (e.g. through prenatal screenings for chromosomal disorders), at puberty or later in life because of low fertility. 47, XXY (KS) is diagnosed by a chromosome karyotype analysis on a blood sample or by a chromosomal microarray (CMA) test. CMA consists of an oral cheek (buccal) swab and is an easy and painless way to detect abnormalities of chromosome numbers and provide a definitive diagnosis. 47, XXY (KS) can also be diagnosed prenatally on chorionic villous or amniotic fluid cells. | Diagnosis of 47, XXY (Klinefelter Syndrome). Males with 47, XXY (KS) are most commonly identified before birth (e.g. through prenatal screenings for chromosomal disorders), at puberty or later in life because of low fertility. 47, XXY (KS) is diagnosed by a chromosome karyotype analysis on a blood sample or by a chromosomal microarray (CMA) test. CMA consists of an oral cheek (buccal) swab and is an easy and painless way to detect abnormalities of chromosome numbers and provide a definitive diagnosis. 47, XXY (KS) can also be diagnosed prenatally on chorionic villous or amniotic fluid cells. | 0 | 47, XXY (Klinefelter Syndrome) |
nord_0_6 | Therapies of 47, XXY (Klinefelter Syndrome) | Treatment
One of the hallmarks of Klinefelter syndrome is hypergonadotropic hypogonadism, a condition that results in testosterone deficiency. Treatment involves the targeted administration of male hormones (androgens), such as testosterone enanthate, cypionate, or androgel. Early hormonal treatment (EHT), three monthly injections of 25 mg of testosterone enanthate, is typically administered between 4-12 months of age. These hormones are given to promote the development of secondary male sexual characteristics (virilization) and alleviate feminization effects that have occurred due to insufficient testosterone levels. Hormone replacement therapy is effective when initiated during early infancy or around pubertal development or even later in life. Some men with 47, XXY (KS) who have gynecomastia may elect to have surgical breast reduction for cosmetic purposes. This procedure often may be avoided if proper and timely dosage of testosterone as well as estrogen inhibitor is administered to an individual, although it varies with each individual.As infants, these boys need to be monitored for positional torticollis which can be treated with pediatric physical therapy. Speech and language therapy, physical therapy and occupational therapy are often helpful for boys with 47, XXY (KS). These interventions are shown to significantly improve academic, physical, cognitive, and social outcomes in boys with 47, XXY (KS). A comprehensive psychoeducational evaluation is recommended to determine what resources may be helpful in the classroom. Social skills training classes can also be beneficial.Men with 47, XXY (KS) have low fertility, and with novel assistive and reproductive techniques, more men with 47, XXY (KS) have the opportunity to reproduce a child. Men with mosaic 47, XXY (KS) have higher likelihood of fewer complications with reproduction. Surgical extraction of sperm from the testes and intracytoplasmic sperm injection (ICSI) directly into an ovum is a medical technology available to assist men with 47, XXY (KS) father children. | Therapies of 47, XXY (Klinefelter Syndrome). Treatment
One of the hallmarks of Klinefelter syndrome is hypergonadotropic hypogonadism, a condition that results in testosterone deficiency. Treatment involves the targeted administration of male hormones (androgens), such as testosterone enanthate, cypionate, or androgel. Early hormonal treatment (EHT), three monthly injections of 25 mg of testosterone enanthate, is typically administered between 4-12 months of age. These hormones are given to promote the development of secondary male sexual characteristics (virilization) and alleviate feminization effects that have occurred due to insufficient testosterone levels. Hormone replacement therapy is effective when initiated during early infancy or around pubertal development or even later in life. Some men with 47, XXY (KS) who have gynecomastia may elect to have surgical breast reduction for cosmetic purposes. This procedure often may be avoided if proper and timely dosage of testosterone as well as estrogen inhibitor is administered to an individual, although it varies with each individual.As infants, these boys need to be monitored for positional torticollis which can be treated with pediatric physical therapy. Speech and language therapy, physical therapy and occupational therapy are often helpful for boys with 47, XXY (KS). These interventions are shown to significantly improve academic, physical, cognitive, and social outcomes in boys with 47, XXY (KS). A comprehensive psychoeducational evaluation is recommended to determine what resources may be helpful in the classroom. Social skills training classes can also be beneficial.Men with 47, XXY (KS) have low fertility, and with novel assistive and reproductive techniques, more men with 47, XXY (KS) have the opportunity to reproduce a child. Men with mosaic 47, XXY (KS) have higher likelihood of fewer complications with reproduction. Surgical extraction of sperm from the testes and intracytoplasmic sperm injection (ICSI) directly into an ovum is a medical technology available to assist men with 47, XXY (KS) father children. | 0 | 47, XXY (Klinefelter Syndrome) |
nord_1_0 | Overview of 48, XXYY Syndrome | 48, XXYY is a genetic disorder that occurs in males and is characterized by additional sex chromosomes compared to the typical male karyotype of 46, XY. 48, XXYY syndrome has previously been described as a variant of Klinefelter syndrome because affected males have similar physical characteristics (tall stature and small, dysfunctional testes), however the medical and neurodevelopmental features are more complex than typically seen in 47, XXY/Klinefelter syndrome. | Overview of 48, XXYY Syndrome. 48, XXYY is a genetic disorder that occurs in males and is characterized by additional sex chromosomes compared to the typical male karyotype of 46, XY. 48, XXYY syndrome has previously been described as a variant of Klinefelter syndrome because affected males have similar physical characteristics (tall stature and small, dysfunctional testes), however the medical and neurodevelopmental features are more complex than typically seen in 47, XXY/Klinefelter syndrome. | 1 | 48, XXYY Syndrome |
nord_1_1 | Symptoms of 48, XXYY Syndrome | In infancy and early childhood, delayed milestones in speech and motor skills are common, as are medical features including low muscle tone (hypotonia), feeding disorders, delayed appearance of teeth, crossed eyes (strabismus) and a twisted neck (torticollis) with flattening on one side of the head. Other physical features can include a skin fold of the upper eyelid covering the inner corner of the eye (epicanthal fold), an abnormally large distance between the eyes (hypertelorism) and an abnormally bend or curved 5th finger (clinodactyly). There are also increased risks for congenital heart defects, kidney malformations and skeletal abnormalities including pes planus, club foot, radioulnar synostosis, cubitus varus (with prominent elbows), scoliosis and kyphosis.Other medical conditions that are more frequent in 48, XXYY syndrome include epilepsy (~15%), tremor (~60% of adults), asthma/allergies (~60%), significant dental problems (~90%), gastrointestinal problems (feeding intolerance, reflux, constipation, eosinophilic esophagitis), joint laxity, sleep apnea, thrombosis (~18%) and type 2 diabetes (~20% in adulthood). Tall stature is another common physical feature that can be more noticeable in adolescence.Small testes (microorchidism) and resulting testicular dysfunction leads to hypergonadotropic hypogonadism (low testosterone levels) that is nearly universal which starts in adolescence and persists throughout the lifetime. Low testosterone levels can be associated with incomplete pubertal development (decreased development of facial and body hair), decreased muscle bulk and strength, fatigue, low endurance and mental health effects such as depression. Testicular dysfunction is also associated with impaired fertility. Undescended testes (cryptorchidism), inguinal hernias, micropenis, and enlargement of breast tissue (gynecomastia) can also be associated, however gynecomastia can be prevented or minimized with appropriate testosterone management starting in adolescence.48, XXYY syndrome presents with more significant cognitive impairments and behavior challenges compared to 47, XXY. Developmental delays are often present in the first 3 years of life in the areas of speech and motor development. Overall cognitive abilities tend to be in the borderline range (IQ of 70 – 80) with approximately 1/3 of males with 48, XXYY with full scale IQ in the intellectual disability range (<70). Cognitive profiles often show significantly lower verbal reasoning skills compared to nonverbal and visual-spatial skills (which are often areas of strength). Language disorders and learning disabilities (especially with reading) are very common. Adaptive functioning (life skills) also commonly show deficits in communication, social skills, self-care and self-direction. Motor coordination deficits are also common.Behavioral characteristics can include executive function impairments, difficulties with attention, impulsivity and hyperactivity. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed. Mood instability, short frustration tolerance, anxiety, compulsive behaviors and emotional immaturity are also characteristic of 48, XXYY. Additional features can include nail biting, sugar cravings and intense interests. There is increased risk for social difficulties, including difficulties in social skills, reciprocal social interactions and insight into social relationships. As a result, there is an increased risk for an autism spectrum disorder (ASD) diagnosis, and approximately half of males with 48, XXYY met DSM-5 criteria for ASD in a research study. Common strengths include artistic skills, computer skills and navigation skills. | Symptoms of 48, XXYY Syndrome. In infancy and early childhood, delayed milestones in speech and motor skills are common, as are medical features including low muscle tone (hypotonia), feeding disorders, delayed appearance of teeth, crossed eyes (strabismus) and a twisted neck (torticollis) with flattening on one side of the head. Other physical features can include a skin fold of the upper eyelid covering the inner corner of the eye (epicanthal fold), an abnormally large distance between the eyes (hypertelorism) and an abnormally bend or curved 5th finger (clinodactyly). There are also increased risks for congenital heart defects, kidney malformations and skeletal abnormalities including pes planus, club foot, radioulnar synostosis, cubitus varus (with prominent elbows), scoliosis and kyphosis.Other medical conditions that are more frequent in 48, XXYY syndrome include epilepsy (~15%), tremor (~60% of adults), asthma/allergies (~60%), significant dental problems (~90%), gastrointestinal problems (feeding intolerance, reflux, constipation, eosinophilic esophagitis), joint laxity, sleep apnea, thrombosis (~18%) and type 2 diabetes (~20% in adulthood). Tall stature is another common physical feature that can be more noticeable in adolescence.Small testes (microorchidism) and resulting testicular dysfunction leads to hypergonadotropic hypogonadism (low testosterone levels) that is nearly universal which starts in adolescence and persists throughout the lifetime. Low testosterone levels can be associated with incomplete pubertal development (decreased development of facial and body hair), decreased muscle bulk and strength, fatigue, low endurance and mental health effects such as depression. Testicular dysfunction is also associated with impaired fertility. Undescended testes (cryptorchidism), inguinal hernias, micropenis, and enlargement of breast tissue (gynecomastia) can also be associated, however gynecomastia can be prevented or minimized with appropriate testosterone management starting in adolescence.48, XXYY syndrome presents with more significant cognitive impairments and behavior challenges compared to 47, XXY. Developmental delays are often present in the first 3 years of life in the areas of speech and motor development. Overall cognitive abilities tend to be in the borderline range (IQ of 70 – 80) with approximately 1/3 of males with 48, XXYY with full scale IQ in the intellectual disability range (<70). Cognitive profiles often show significantly lower verbal reasoning skills compared to nonverbal and visual-spatial skills (which are often areas of strength). Language disorders and learning disabilities (especially with reading) are very common. Adaptive functioning (life skills) also commonly show deficits in communication, social skills, self-care and self-direction. Motor coordination deficits are also common.Behavioral characteristics can include executive function impairments, difficulties with attention, impulsivity and hyperactivity. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed. Mood instability, short frustration tolerance, anxiety, compulsive behaviors and emotional immaturity are also characteristic of 48, XXYY. Additional features can include nail biting, sugar cravings and intense interests. There is increased risk for social difficulties, including difficulties in social skills, reciprocal social interactions and insight into social relationships. As a result, there is an increased risk for an autism spectrum disorder (ASD) diagnosis, and approximately half of males with 48, XXYY met DSM-5 criteria for ASD in a research study. Common strengths include artistic skills, computer skills and navigation skills. | 1 | 48, XXYY Syndrome |
nord_1_2 | Causes of 48, XXYY Syndrome | 48, XXYY syndrome is not inherited, Males with 48, XXYY have an extra X and Y chromosome because of a nondisjunction error that randomly occurs during the division of the sex chromosomes in the egg or sperm cells. There are no commonly known factors predisposing to the specific occurrence of these nondisjunction events resulting in 48, XXYY. | Causes of 48, XXYY Syndrome. 48, XXYY syndrome is not inherited, Males with 48, XXYY have an extra X and Y chromosome because of a nondisjunction error that randomly occurs during the division of the sex chromosomes in the egg or sperm cells. There are no commonly known factors predisposing to the specific occurrence of these nondisjunction events resulting in 48, XXYY. | 1 | 48, XXYY Syndrome |
nord_1_3 | Affects of 48, XXYY Syndrome | There is an estimated incidence of 48, XXYY in 1/18,000 to 1/50,000 male births. | Affects of 48, XXYY Syndrome. There is an estimated incidence of 48, XXYY in 1/18,000 to 1/50,000 male births. | 1 | 48, XXYY Syndrome |
nord_1_4 | Related disorders of 48, XXYY Syndrome | The hypergonadotropic hypogonadism present in 48, XXYY can be seen in other male sex chromosome aneuploidies including Klinefelter (47, XXY) syndrome, 48, XXXY syndrome and 49, XXXXY syndrome as well as 45, X/46, XY mosaicism and 46, XX sex reversal. Other genetic conditions that may have overlap with some of the behavioral and cognitive/neurodevelopmental features seen in 48, XXYY syndrome include Fragile X syndrome, Jacob syndrome, Prader Willi syndrome, Soto syndrome, Börjeson-Forssman-Lehman syndrome, Weaver syndrome and Cohen syndrome. Due to tall stature and joint laxity, some males with 48, XXYY are also identified during genetic evaluation for Marfan syndrome or other connective tissue disorders. Also, many of the neurodevelopmental disorders often diagnosed in males with XXYY syndrome are commonly found in 46, XY males as well, including intellectual disability, autism spectrum disorder, learning disabilities, language disorders and ADHD. | Related disorders of 48, XXYY Syndrome. The hypergonadotropic hypogonadism present in 48, XXYY can be seen in other male sex chromosome aneuploidies including Klinefelter (47, XXY) syndrome, 48, XXXY syndrome and 49, XXXXY syndrome as well as 45, X/46, XY mosaicism and 46, XX sex reversal. Other genetic conditions that may have overlap with some of the behavioral and cognitive/neurodevelopmental features seen in 48, XXYY syndrome include Fragile X syndrome, Jacob syndrome, Prader Willi syndrome, Soto syndrome, Börjeson-Forssman-Lehman syndrome, Weaver syndrome and Cohen syndrome. Due to tall stature and joint laxity, some males with 48, XXYY are also identified during genetic evaluation for Marfan syndrome or other connective tissue disorders. Also, many of the neurodevelopmental disorders often diagnosed in males with XXYY syndrome are commonly found in 46, XY males as well, including intellectual disability, autism spectrum disorder, learning disabilities, language disorders and ADHD. | 1 | 48, XXYY Syndrome |
nord_1_5 | Diagnosis of 48, XXYY Syndrome | 48, XXYY is usually identified by a standard karyotype or chromosomal microarray (CMA) performed on peripheral blood, amniotic fluid or buccal swab. Fluorescence In Situ Hybridization (FISH) is another approach to investigate the presence of extra copies of chromosomes X and Y on a larger sample of cells. Prenatal diagnosis is possible, but 48, XXYY is usually diagnosed during childhood during evaluation of physical and/or developmental concerns that warrant genetic testing. A 2008 study looking at 95 males with 48, XXYY syndrome reported the mean age of diagnosis to be 7.7 years of age. | Diagnosis of 48, XXYY Syndrome. 48, XXYY is usually identified by a standard karyotype or chromosomal microarray (CMA) performed on peripheral blood, amniotic fluid or buccal swab. Fluorescence In Situ Hybridization (FISH) is another approach to investigate the presence of extra copies of chromosomes X and Y on a larger sample of cells. Prenatal diagnosis is possible, but 48, XXYY is usually diagnosed during childhood during evaluation of physical and/or developmental concerns that warrant genetic testing. A 2008 study looking at 95 males with 48, XXYY syndrome reported the mean age of diagnosis to be 7.7 years of age. | 1 | 48, XXYY Syndrome |
nord_1_6 | Therapies of 48, XXYY Syndrome | Treatment Comprehensive interdisciplinary care is important to evaluate and manage developmental, medical, and psychological conditions that may be associated with 48, XXYY syndrome. At diagnosis, a thorough physical exam, renal ultrasound and echocardiography should be performed to evaluate for congenital defects. Vision and hearing screening and routine dental care are important throughout the lifespan. Physical examination should focus on common physical features and medical findings described above. Starting around age 10, pubertal examinations and serum hormone profiles should be monitored by endocrinology and testosterone supplementation should be considered when evidence of hypogonadism is present. Routine screening for hyperlipidemia, diabetes and thyroid disease is recommended starting in adolescence. Eosinophilic esophagitis should be considered in males with XXYY who have feeding problems, dysphagia (pain with swallowing), reflux, choking or other feeding problems, especially in patients with food allergies. Symptoms suggestive of any other associated medical conditions should be promptly evaluated and treated as appropriate.The neurodevelopmental and behavioral phenotype in 48, XXYY warrants a comprehensive interdisciplinary evaluation to include psychological functioning (cognitive, learning, executive, social, emotional, and behavioral functioning), speech/language skills, motor skills and self-care skills. For infants and young children, close developmental screening is important to identify delays and the need for early intervention therapies. Further, speech-language therapy to target developmentally appropriate goals around oral-motor planning deficits, apraxia of speech, expressive and receptive language skills and pragmatic language may be necessary through early adulthood. Occupational and/or physical therapies to target decreased motor skills, dyspraxia, coordination, sensory sensitivities and overall self-care are also often warranted.Documentation of psychological diagnoses (such as learning or intellectual disability, ADHD, anxiety and/or autism spectrum disorder) is important for qualification and access to community-based services. Interventions are recommended when psychological diagnoses are present, and treatments for emotional and behavioral disorders should be evidence-based, individualized, and chosen with consideration of language deficits, learning disabilities and other associated diagnoses. Social skills therapy can also address difficulties with social understanding, relationships and communication. Services that are tailored to the developmental disability or ASD population and delivered by providers who specialize in developmental disabilities and/or ASD are often a good fit for 48, XXYY. School-based supports including services outlined by an individualized education plan (IEP) are most often a part of the treatment plan, and evidence-based interventions for learning disabilities do not differ from those used with the general population. Through adolescence and early adulthood, adaptive skills, transition services and community-based supports are important areas of focus.In addition to endocrinology, consultation with other medical specialists including developmental pediatrics, psychiatry and/or neurology may also help to develop treatment plans and provide medication management. Psychopharmacologic medications, in conjunction with behavioral therapy, may be warranted for behavioral and emotional symptoms and are commonly part of the treatment plan. Positive response to standard medication treatments for ADHD, anxiety and externalizing behaviors has been seen in males with 48, XXYY. There are specialized clinics primarily in the US that have experience supporting individuals with 48, XXYY. For a list of clinics, please go to the AXYS website: https://genetic.org/im-adult-looking-answers/clinics/acrc-clinics-list/ | Therapies of 48, XXYY Syndrome. Treatment Comprehensive interdisciplinary care is important to evaluate and manage developmental, medical, and psychological conditions that may be associated with 48, XXYY syndrome. At diagnosis, a thorough physical exam, renal ultrasound and echocardiography should be performed to evaluate for congenital defects. Vision and hearing screening and routine dental care are important throughout the lifespan. Physical examination should focus on common physical features and medical findings described above. Starting around age 10, pubertal examinations and serum hormone profiles should be monitored by endocrinology and testosterone supplementation should be considered when evidence of hypogonadism is present. Routine screening for hyperlipidemia, diabetes and thyroid disease is recommended starting in adolescence. Eosinophilic esophagitis should be considered in males with XXYY who have feeding problems, dysphagia (pain with swallowing), reflux, choking or other feeding problems, especially in patients with food allergies. Symptoms suggestive of any other associated medical conditions should be promptly evaluated and treated as appropriate.The neurodevelopmental and behavioral phenotype in 48, XXYY warrants a comprehensive interdisciplinary evaluation to include psychological functioning (cognitive, learning, executive, social, emotional, and behavioral functioning), speech/language skills, motor skills and self-care skills. For infants and young children, close developmental screening is important to identify delays and the need for early intervention therapies. Further, speech-language therapy to target developmentally appropriate goals around oral-motor planning deficits, apraxia of speech, expressive and receptive language skills and pragmatic language may be necessary through early adulthood. Occupational and/or physical therapies to target decreased motor skills, dyspraxia, coordination, sensory sensitivities and overall self-care are also often warranted.Documentation of psychological diagnoses (such as learning or intellectual disability, ADHD, anxiety and/or autism spectrum disorder) is important for qualification and access to community-based services. Interventions are recommended when psychological diagnoses are present, and treatments for emotional and behavioral disorders should be evidence-based, individualized, and chosen with consideration of language deficits, learning disabilities and other associated diagnoses. Social skills therapy can also address difficulties with social understanding, relationships and communication. Services that are tailored to the developmental disability or ASD population and delivered by providers who specialize in developmental disabilities and/or ASD are often a good fit for 48, XXYY. School-based supports including services outlined by an individualized education plan (IEP) are most often a part of the treatment plan, and evidence-based interventions for learning disabilities do not differ from those used with the general population. Through adolescence and early adulthood, adaptive skills, transition services and community-based supports are important areas of focus.In addition to endocrinology, consultation with other medical specialists including developmental pediatrics, psychiatry and/or neurology may also help to develop treatment plans and provide medication management. Psychopharmacologic medications, in conjunction with behavioral therapy, may be warranted for behavioral and emotional symptoms and are commonly part of the treatment plan. Positive response to standard medication treatments for ADHD, anxiety and externalizing behaviors has been seen in males with 48, XXYY. There are specialized clinics primarily in the US that have experience supporting individuals with 48, XXYY. For a list of clinics, please go to the AXYS website: https://genetic.org/im-adult-looking-answers/clinics/acrc-clinics-list/ | 1 | 48, XXYY Syndrome |
nord_2_0 | Overview of Aarskog Syndrome | Aarskog syndrome is a rare genetic condition characterized by short stature and multiple facial, limb and genital abnormalities. Additionally, some types of cognitive disorders may occasionally be present. Up to now, the FGD1 gene on the X chromosome is the only gene known to be associated with Aarskog syndrome. | Overview of Aarskog Syndrome. Aarskog syndrome is a rare genetic condition characterized by short stature and multiple facial, limb and genital abnormalities. Additionally, some types of cognitive disorders may occasionally be present. Up to now, the FGD1 gene on the X chromosome is the only gene known to be associated with Aarskog syndrome. | 2 | Aarskog Syndrome |
nord_2_1 | Symptoms of Aarskog Syndrome | Aarskog syndrome primarily affects males. Affected boys exhibit a characteristic set of facial, skeletal, and genital abnormalities. Clinical signs may vary from person to person (clinical heterogeneity), even within families. Males with Aarskog syndrome often have a rounded face with a broad forehead. Additional characteristic facial features include widely spaced eyes (ocular hypertelorism), drooping (ptosis) of the eyelids, downwardly slanting eyelid folds (palpebral fissures), a small nose with nostrils that are flared forward (anteverted nares), an underdeveloped upper jawbone (maxilliary hypoplasia), and a widow’s peak. Affected individuals may also have an abnormally long groove in the upper lip (philtrum) and a broad nasal bridge.These children may also have a variety of abnormalities affecting the ears and teeth. Ear abnormalities include low-set ears and thickened, “fleshy” earlobes. Dental abnormalities include missing teeth at birth, delayed eruption of teeth, and underdevelopment of the hard outer covering of teeth (enamel hypoplasia).Aarskog syndrome is basically a skeletal dysplasia and affected males develop characteristic malformations of the skeletal system including disproportionate short stature; broad, short hands and feet; short, stubby fingers (brachydactyly) with permanent fixation of the fifth fingers in a bent position (clinodactyly); abnormally extendible finger joints; and wide flat feet with bulbous toes. In addition, affected individuals may have a sunken chest (pectus excavatum), protrusion of portions of the large intestine through an abnormal opening in the muscular lining of the abdominal cavity (inguinal hernia), and a prominent navel (umbilicus). Individuals with Aarskog syndrome may have spinal abnormalities such as incomplete closure of the bones of the spinal column (spina bifida occulta), fusion of the upper bones of the spinal column (cervical vertebrae), and underdevelopment of the “peg-like” projection of the second cervical vertebra (odontoid hypoplasia).Signs that help to make a diagnosis in males with Aarskog syndrome are the genital abnormalities, including a characteristic abnormal fold of skin extending around the base of the penis (“shawl” scrotum) and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism). In addition, the urinary opening (meatus) may be located on the underside of the penis (hypospadias) and the scrotum may appear clefted or divided (bifid scrotum).Intellectual disability has been described in some affected boys but it is not a consistent feature of the disorder. Affected individuals may present with a range of mild learning difficulty and/or behavioral disorders: affected children may exhibit developmental delay during infancy, hyperactivity, attention deficit, impulsivity and opposition. Due to this possible spectrum of characteristics, the condition is also referred to as an ADHD syndromic disorder (MRXS16). Failure to gain weight and grow at the expected rate (failure to thrive) and development of chronic respiratory infections have also been described.An additional spectrum of signs and/or symptoms may occur less frequently, including congenital heart defects; abnormal side-to-side curvature of the spine (scoliosis); additional pairs of ribs; incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip); mild webbing of the fingers; and a short neck with or without webbing. Additional eye abnormalities may be present including crossed eyes (strabismus), farsightedness (hyperopia), and paralysis of certain eye muscles (ophthalmoplegia). Some patients have been reported to have a tendency to be overweight. | Symptoms of Aarskog Syndrome. Aarskog syndrome primarily affects males. Affected boys exhibit a characteristic set of facial, skeletal, and genital abnormalities. Clinical signs may vary from person to person (clinical heterogeneity), even within families. Males with Aarskog syndrome often have a rounded face with a broad forehead. Additional characteristic facial features include widely spaced eyes (ocular hypertelorism), drooping (ptosis) of the eyelids, downwardly slanting eyelid folds (palpebral fissures), a small nose with nostrils that are flared forward (anteverted nares), an underdeveloped upper jawbone (maxilliary hypoplasia), and a widow’s peak. Affected individuals may also have an abnormally long groove in the upper lip (philtrum) and a broad nasal bridge.These children may also have a variety of abnormalities affecting the ears and teeth. Ear abnormalities include low-set ears and thickened, “fleshy” earlobes. Dental abnormalities include missing teeth at birth, delayed eruption of teeth, and underdevelopment of the hard outer covering of teeth (enamel hypoplasia).Aarskog syndrome is basically a skeletal dysplasia and affected males develop characteristic malformations of the skeletal system including disproportionate short stature; broad, short hands and feet; short, stubby fingers (brachydactyly) with permanent fixation of the fifth fingers in a bent position (clinodactyly); abnormally extendible finger joints; and wide flat feet with bulbous toes. In addition, affected individuals may have a sunken chest (pectus excavatum), protrusion of portions of the large intestine through an abnormal opening in the muscular lining of the abdominal cavity (inguinal hernia), and a prominent navel (umbilicus). Individuals with Aarskog syndrome may have spinal abnormalities such as incomplete closure of the bones of the spinal column (spina bifida occulta), fusion of the upper bones of the spinal column (cervical vertebrae), and underdevelopment of the “peg-like” projection of the second cervical vertebra (odontoid hypoplasia).Signs that help to make a diagnosis in males with Aarskog syndrome are the genital abnormalities, including a characteristic abnormal fold of skin extending around the base of the penis (“shawl” scrotum) and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism). In addition, the urinary opening (meatus) may be located on the underside of the penis (hypospadias) and the scrotum may appear clefted or divided (bifid scrotum).Intellectual disability has been described in some affected boys but it is not a consistent feature of the disorder. Affected individuals may present with a range of mild learning difficulty and/or behavioral disorders: affected children may exhibit developmental delay during infancy, hyperactivity, attention deficit, impulsivity and opposition. Due to this possible spectrum of characteristics, the condition is also referred to as an ADHD syndromic disorder (MRXS16). Failure to gain weight and grow at the expected rate (failure to thrive) and development of chronic respiratory infections have also been described.An additional spectrum of signs and/or symptoms may occur less frequently, including congenital heart defects; abnormal side-to-side curvature of the spine (scoliosis); additional pairs of ribs; incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip); mild webbing of the fingers; and a short neck with or without webbing. Additional eye abnormalities may be present including crossed eyes (strabismus), farsightedness (hyperopia), and paralysis of certain eye muscles (ophthalmoplegia). Some patients have been reported to have a tendency to be overweight. | 2 | Aarskog Syndrome |
nord_2_2 | Causes of Aarskog Syndrome | Although Aarskog syndrome is a clinically and genetically heterogeneous condition, the best characterized form of the disorder is inherited as an X-linked trait and caused by changes (mutations) in the FGD1 gene. Aarskog syndrome primarily affects males. However, females who carry a single copy of a FGD1 gene mutation (heterozygotes) may exhibit some of the symptoms associated with the disorder. FGD1 gene mutations have been identified in approximately 22% of affected males; therefore, it is likely that other genes not yet identified may also be associated with this condition.X-linked recessive genetic disorders are conditions caused by mutations in a gene located on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” to correct a dosage imbalance and almost all of the genes on that chromosome are silenced (inactivated) through a process defined as X-chromosome inactivation. Females who have a disease causing mutation on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “silenced”. Males have one only X chromosome and, if they inherit the X chromosome that contains a disease gene, they will develop the disease. In turn, males with a X-linked disorder will pass the disease gene to all of their daughters, who will be carriers of the trait (obligate carriers). Males cannot pass X-linked traits to their sons because they always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter (like themselves), a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. | Causes of Aarskog Syndrome. Although Aarskog syndrome is a clinically and genetically heterogeneous condition, the best characterized form of the disorder is inherited as an X-linked trait and caused by changes (mutations) in the FGD1 gene. Aarskog syndrome primarily affects males. However, females who carry a single copy of a FGD1 gene mutation (heterozygotes) may exhibit some of the symptoms associated with the disorder. FGD1 gene mutations have been identified in approximately 22% of affected males; therefore, it is likely that other genes not yet identified may also be associated with this condition.X-linked recessive genetic disorders are conditions caused by mutations in a gene located on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” to correct a dosage imbalance and almost all of the genes on that chromosome are silenced (inactivated) through a process defined as X-chromosome inactivation. Females who have a disease causing mutation on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “silenced”. Males have one only X chromosome and, if they inherit the X chromosome that contains a disease gene, they will develop the disease. In turn, males with a X-linked disorder will pass the disease gene to all of their daughters, who will be carriers of the trait (obligate carriers). Males cannot pass X-linked traits to their sons because they always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter (like themselves), a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. | 2 | Aarskog Syndrome |
nord_2_3 | Affects of Aarskog Syndrome | Approximately 60 reports of Aarskog syndrome confirmed by identification of a FGD1 gene mutation have been published worldwide. However, it is possible that some mildly affected children may be unrecognized, making it difficult to determine the true frequency of this condition in the general population. An estimated population prevalence of Aarskog syndrome is equal to or slightly lower than to 1/25,000. | Affects of Aarskog Syndrome. Approximately 60 reports of Aarskog syndrome confirmed by identification of a FGD1 gene mutation have been published worldwide. However, it is possible that some mildly affected children may be unrecognized, making it difficult to determine the true frequency of this condition in the general population. An estimated population prevalence of Aarskog syndrome is equal to or slightly lower than to 1/25,000. | 2 | Aarskog Syndrome |
nord_2_4 | Related disorders of Aarskog Syndrome | Symptoms of the following disorders can be similar to those of Aarskog syndrome. Comparisons may be useful for a differential diagnosis:Noonan syndrome is a relatively common genetic disorder characterized by short stature, dysmorphic facial features and congenital heart disease. The disorder is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low posterior hairline; a typical chest deformity and short stature. Characteristic abnormalities of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); skin folds that may cover the eyes’ inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia); a depressed nasal root; a short nose with broad base; and low-set, posteriorly rotated ears (pinnae). Distinctive skeletal malformations are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart (cardiac) defects, such as obstruction of proper blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Additional abnormalities may include malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, learning difficulties or mild intellectual disability, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings. Noonan syndrome is may be caused by mutations in a number of genes, including PTPN11, KRAS, SOS1, RAF1, NRAS, RIT1 and SOS2 (For more information on this disorder, choose “Noonan” as your search term in the Rare Disease Database.)Robinow syndrome is a rare genetic disorder that can be inherited in either a dominant or recessive pattern and is characterized by mild to moderate short stature due to growth delays after birth (postnatal growth retardation); distinctive abnormalities of the head and facial (craniofacial) area; additional skeletal malformations; and/or genital abnormalities. The facial features of infants with Robinow syndrome resemble those of an eight-week-old fetus; within the medical literature, this condition is often referred to as “fetal face.” Characteristic craniofacial features may include an abnormally large head (macrocephaly) with a bulging forehead (frontal bossing); widely spaced eyes (ocular hypertelorism) that are abnormally prominent; a small, upturned nose with nostrils that are flared forward (anteverted); and/or a sunken (depressed) nasal bridge. Skeletal malformations may include forearm bones (radius and ulna) that are unusually short (forearm brachymelia), abnormally short fingers and toes, permanent fixation of the fifth fingers in a bent position (clinodactyly), unusually small hands with broad thumbs, malformation of the ribs, abnormal side-to-side curvature of the spine (scoliosis), and/or underdevelopment of one side of the bones in the middle (thoracic) portion of the spinal column (hemivertebrae). Genital abnormalities associated with Robinow syndrome may include an abnormally small penis (micropenis) and failure of the testes to descend into the scrotum (cryptorchidism) in affected males and underdevelopment (hypoplasia) of the clitoris and the outer, elongated folds of skin on either side of the vaginal opening (labia majora) in affected females. The range and severity of symptoms vary from person to person. The Robinow syndrome may be caused by mutations in different genes, such as WNT5A, ROR2, DVL3 and DVL1 (For more information on this disorder, choose “Robinow” as your search term in the Rare Disease Database.)Noonan syndrome with multiple lentigines (NSML) is a rare genetic disorder characterized by abnormalities of the skin, the structure and function of the heart, the inner ear, the head and facial (craniofacial) area, and/or the genitals. In individuals with the disorder, the range and severity of symptoms and physical characteristics may vary from person to person. LEOPARD is an acronym for the characteristic abnormalities associated with the disorder: L stands for (L)entigines (multiple black or dark brown spots on the skin); (E)lectrocardiographic conduction defects (abnormalities of the electrical activity and the coordination of proper contractions of the heart); (0)cular hypertelorism (widely-spaced eyes); (P)ulmonary stenosis (obstruction of the normal outflow of blood from the right ventricle of the heart); (A)bnormalities of the genitals; (R)etarded growth resulting in short stature; and (D)eafness or hearing loss due to malfunction of the inner ear (sensorineural deafness). Some affected individuals may also exhibit mild intellectual disability, speech difficulties, and/or, in some cases, additional physical abnormalities. NSML is an autosomal dominant genetic disorder. NSML and Noonan syndrome are both caused by mutations in the PTPN11 and RAF1 genes. (For more information on this disorder, choose “LEOPARD” as your search term in the Rare Disease Database.) | Related disorders of Aarskog Syndrome. Symptoms of the following disorders can be similar to those of Aarskog syndrome. Comparisons may be useful for a differential diagnosis:Noonan syndrome is a relatively common genetic disorder characterized by short stature, dysmorphic facial features and congenital heart disease. The disorder is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low posterior hairline; a typical chest deformity and short stature. Characteristic abnormalities of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); skin folds that may cover the eyes’ inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia); a depressed nasal root; a short nose with broad base; and low-set, posteriorly rotated ears (pinnae). Distinctive skeletal malformations are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart (cardiac) defects, such as obstruction of proper blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Additional abnormalities may include malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, learning difficulties or mild intellectual disability, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings. Noonan syndrome is may be caused by mutations in a number of genes, including PTPN11, KRAS, SOS1, RAF1, NRAS, RIT1 and SOS2 (For more information on this disorder, choose “Noonan” as your search term in the Rare Disease Database.)Robinow syndrome is a rare genetic disorder that can be inherited in either a dominant or recessive pattern and is characterized by mild to moderate short stature due to growth delays after birth (postnatal growth retardation); distinctive abnormalities of the head and facial (craniofacial) area; additional skeletal malformations; and/or genital abnormalities. The facial features of infants with Robinow syndrome resemble those of an eight-week-old fetus; within the medical literature, this condition is often referred to as “fetal face.” Characteristic craniofacial features may include an abnormally large head (macrocephaly) with a bulging forehead (frontal bossing); widely spaced eyes (ocular hypertelorism) that are abnormally prominent; a small, upturned nose with nostrils that are flared forward (anteverted); and/or a sunken (depressed) nasal bridge. Skeletal malformations may include forearm bones (radius and ulna) that are unusually short (forearm brachymelia), abnormally short fingers and toes, permanent fixation of the fifth fingers in a bent position (clinodactyly), unusually small hands with broad thumbs, malformation of the ribs, abnormal side-to-side curvature of the spine (scoliosis), and/or underdevelopment of one side of the bones in the middle (thoracic) portion of the spinal column (hemivertebrae). Genital abnormalities associated with Robinow syndrome may include an abnormally small penis (micropenis) and failure of the testes to descend into the scrotum (cryptorchidism) in affected males and underdevelopment (hypoplasia) of the clitoris and the outer, elongated folds of skin on either side of the vaginal opening (labia majora) in affected females. The range and severity of symptoms vary from person to person. The Robinow syndrome may be caused by mutations in different genes, such as WNT5A, ROR2, DVL3 and DVL1 (For more information on this disorder, choose “Robinow” as your search term in the Rare Disease Database.)Noonan syndrome with multiple lentigines (NSML) is a rare genetic disorder characterized by abnormalities of the skin, the structure and function of the heart, the inner ear, the head and facial (craniofacial) area, and/or the genitals. In individuals with the disorder, the range and severity of symptoms and physical characteristics may vary from person to person. LEOPARD is an acronym for the characteristic abnormalities associated with the disorder: L stands for (L)entigines (multiple black or dark brown spots on the skin); (E)lectrocardiographic conduction defects (abnormalities of the electrical activity and the coordination of proper contractions of the heart); (0)cular hypertelorism (widely-spaced eyes); (P)ulmonary stenosis (obstruction of the normal outflow of blood from the right ventricle of the heart); (A)bnormalities of the genitals; (R)etarded growth resulting in short stature; and (D)eafness or hearing loss due to malfunction of the inner ear (sensorineural deafness). Some affected individuals may also exhibit mild intellectual disability, speech difficulties, and/or, in some cases, additional physical abnormalities. NSML is an autosomal dominant genetic disorder. NSML and Noonan syndrome are both caused by mutations in the PTPN11 and RAF1 genes. (For more information on this disorder, choose “LEOPARD” as your search term in the Rare Disease Database.) | 2 | Aarskog Syndrome |
nord_2_5 | Diagnosis of Aarskog Syndrome | A diagnosis of Aarskog syndrome may be considered based upon a thorough clinical evaluation, a detailed patient and family history, and the identification of characteristic findings. Molecular genetic testing for FGD1 gene mutations is available to confirm the diagnosis. If a FGD1 gene mutation is not identified, molecular genetic testing for genes associated with similar conditions may be suggested, such as the ROR2 and WNT5A genes associated with Robinow syndrome.
The transition from the classic sequencing of single genes to protocols of next generation sequencing (NGS), recommends at least the use of panels that include, in addition to FGD1, the genes that cause overlapping conditions such as ROR2, WNT5A, PIK3R1, SRCAP, KMT2D, KDM6A, SHOX, CUL7. | Diagnosis of Aarskog Syndrome. A diagnosis of Aarskog syndrome may be considered based upon a thorough clinical evaluation, a detailed patient and family history, and the identification of characteristic findings. Molecular genetic testing for FGD1 gene mutations is available to confirm the diagnosis. If a FGD1 gene mutation is not identified, molecular genetic testing for genes associated with similar conditions may be suggested, such as the ROR2 and WNT5A genes associated with Robinow syndrome.
The transition from the classic sequencing of single genes to protocols of next generation sequencing (NGS), recommends at least the use of panels that include, in addition to FGD1, the genes that cause overlapping conditions such as ROR2, WNT5A, PIK3R1, SRCAP, KMT2D, KDM6A, SHOX, CUL7. | 2 | Aarskog Syndrome |
nord_2_6 | Therapies of Aarskog Syndrome | Treatment
The treatment of Aarskog syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, dental specialists, speech pathologists, specialists who asses and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Surgery may be necessary to treat specific congenital or structural malformations sometimes associated with Aarskog syndrome (hypospadias, inguinal or umbilical hernias, cryptorchidism, unusually severe craniofacial features). Individuals with Aarskog syndrome should receive complete eye and dental evaluations. Growth hormone treatment has been reported to improve height in some children, but confirmation is needed to determine appropriate management and expectations for response. For the possibly neurodevelopmental symptoms, a neuropsychiatric evaluation and input may be indicated. Other treatment is symptomatic and supportive.Genetic counseling is recommended for affected individuals and their families to clarify the genetic and clinical characteristics, the inheritance, and the recurrence risks of the condition in their families. | Therapies of Aarskog Syndrome. Treatment
The treatment of Aarskog syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, dental specialists, speech pathologists, specialists who asses and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Surgery may be necessary to treat specific congenital or structural malformations sometimes associated with Aarskog syndrome (hypospadias, inguinal or umbilical hernias, cryptorchidism, unusually severe craniofacial features). Individuals with Aarskog syndrome should receive complete eye and dental evaluations. Growth hormone treatment has been reported to improve height in some children, but confirmation is needed to determine appropriate management and expectations for response. For the possibly neurodevelopmental symptoms, a neuropsychiatric evaluation and input may be indicated. Other treatment is symptomatic and supportive.Genetic counseling is recommended for affected individuals and their families to clarify the genetic and clinical characteristics, the inheritance, and the recurrence risks of the condition in their families. | 2 | Aarskog Syndrome |
nord_3_0 | Overview of Abetalipoproteinemia | SummaryAbetalipoproteinemia is a rare inherited disorder affecting fat absorption by the intestine and mobilization by the liver. Inability to absorb fat results in deficiencies of lipids and various essential vitamins. Affected individuals experience progressive neurological deterioration, muscle weakness, difficulty walking and blood abnormalities including a condition in which the red blood cells are malformed (acanthocytosis) resulting in low levels of circulating red blood cells (anemia). Affected individuals may also develop degeneration of the retina of the eyes potentially resulting in loss of vision, a condition known as retinitis pigmentosa. Abetalipoproteinemia is inherited in an autosomal recessive pattern and is caused by changes (mutations or variants) in the microsomal triglyceride transfer protein (MTTP) gene.IntroductionAbetalipoproteinemia was first reported in the medical literature by doctors Bassen and Kornzweig in 1950 and is also known as Bassen-Kornzweig syndrome. The disorder is sometimes classified as a neuroacanthocytosis syndrome, which refers to a group of disorders characterized by spiky or burr-shaped red blood cells (acanthocytosis) and neurological disorders, especially movement disorders. | Overview of Abetalipoproteinemia. SummaryAbetalipoproteinemia is a rare inherited disorder affecting fat absorption by the intestine and mobilization by the liver. Inability to absorb fat results in deficiencies of lipids and various essential vitamins. Affected individuals experience progressive neurological deterioration, muscle weakness, difficulty walking and blood abnormalities including a condition in which the red blood cells are malformed (acanthocytosis) resulting in low levels of circulating red blood cells (anemia). Affected individuals may also develop degeneration of the retina of the eyes potentially resulting in loss of vision, a condition known as retinitis pigmentosa. Abetalipoproteinemia is inherited in an autosomal recessive pattern and is caused by changes (mutations or variants) in the microsomal triglyceride transfer protein (MTTP) gene.IntroductionAbetalipoproteinemia was first reported in the medical literature by doctors Bassen and Kornzweig in 1950 and is also known as Bassen-Kornzweig syndrome. The disorder is sometimes classified as a neuroacanthocytosis syndrome, which refers to a group of disorders characterized by spiky or burr-shaped red blood cells (acanthocytosis) and neurological disorders, especially movement disorders. | 3 | Abetalipoproteinemia |
nord_3_1 | Symptoms of Abetalipoproteinemia | Individuals with abetalipoproteinemia may experience a wide variety of symptoms affecting various parts of the body including the gastrointestinal tract, neurological system, eyes and blood.Affected infants often present with symptoms relating to gastrointestinal disease, which occur secondary to poor fat absorption. Such symptoms include pale, bulky foul-smelling stools (steatorrhea), diarrhea, vomiting and swelling (distension) of the abdomen. Affected infants often fail to gain weight and grow at the expected rate (failure to thrive). These symptoms result from poor absorption of fat from the diet. In addition to poor fat absorption, fat-soluble vitamins such as vitamins A, E, and K are also poorly absorbed potentially resulting in fat-soluble vitamin deficiency. Further, patients do not have any apoB-containing lipoproteins in their plasma, and consequently they have very low levels of triglycerides, cholesterol, phospholipids and ceramides. Thus, lipids and fat-soluble vitamins are inadequately transported throughout the blood stream. Some patients may also have reduced non-apoB-containing lipoproteins (high density lipoproteins) or apoA1 levels in their plasma.Between the ages of 2 and 20 years, a variety of neurological complications occur that resemble spinocerebellar degeneration, a general term for a group of disorders characterized by progressive impairment of the ability to coordinate voluntary movements due to degeneration of certain structures in the brain (cerebellar ataxia). Ataxia results in a lack of coordination and, eventually, difficulty in controlling the range of voluntary movement (dysmetria). Additional neurological symptoms include loss of deep tendon reflexes such as at the kneecap, difficulty speaking (dysarthria), tremors, motor tics and muscle weakness. Intelligence is usually normal, but developmental delays or intellectual disability has been reported.In some people, the damage or malfunction of the peripheral nervous system (peripheral neuropathy) may occur. The peripheral nervous system contains all the nerves outside of the central nervous system. The associated symptoms can vary greatly from one person to another but can include weakness of the muscles of the arms and legs or abnormal sensations such as tingling (paresthesias), burning or numbness.Some individuals with abetalipoproteinemia may develop skeletal abnormalities including backward curvature (lordosis) or backward and sideways curvature of the spine (kyphoscoliosis), a highly arched foot (pes cavus) or clubfoot. These skeletal abnormalities may result from muscle imbalances during crucial stages of bone development. Eventually, affected individuals may be unable to stand or to walk unaided due to progressive neurological and skeletal abnormalities.Some affected individuals may develop a rare eye condition called retinitis pigmentosa in which progressive degeneration of the nerve-rich membrane lining the eyes (retina) results in tunnel vision (loss of peripheral vision), loss of color vision and night blindness. Affected individuals may eventually develop loss of visual acuity. Retinitis pigmentosa occurs most often around the age of 10 years and may be due to vitamin A and/or E deficiency. If left untreated, visual acuity may deteriorate to virtual blindness by the fourth decade of life.Less often, additional symptoms that affect the eyes have been reported including rapid, involuntary eye movements (nystagmus), irregular concentric and some fine radial streaks (algioid streaks), droopy upper eyelid (ptosis), crossed eyes (strabismus), unequal size of the pupils (anisocoria) and weakness or paralysis of muscles that control eye movements (ophthalmoplegia).Individuals with abetalipoproteinemia may also have blood abnormalities including a condition called acanthocytosis in which deformed (i.e., burr-shaped) red blood cells (acanthocytes) are present in the body. Acanthocytosis may result in low levels of circulating red blood cells (anemia). Anemia may result in tiredness, increased need for sleep, weakness, lightheadedness, dizziness, irritability, palpitations, headaches and pale skin color. Additional blood abnormalities may be due to vitamin K deficiency. Blood clotting factor levels may be reduced resulting in bleeding tendencies such as severe gastrointestinal bleeding.Patients may have fatty liver, which can cause liver damage. In rare cases, fibrosis or scarring of the liver (cirrhosis) has also been reported. | Symptoms of Abetalipoproteinemia. Individuals with abetalipoproteinemia may experience a wide variety of symptoms affecting various parts of the body including the gastrointestinal tract, neurological system, eyes and blood.Affected infants often present with symptoms relating to gastrointestinal disease, which occur secondary to poor fat absorption. Such symptoms include pale, bulky foul-smelling stools (steatorrhea), diarrhea, vomiting and swelling (distension) of the abdomen. Affected infants often fail to gain weight and grow at the expected rate (failure to thrive). These symptoms result from poor absorption of fat from the diet. In addition to poor fat absorption, fat-soluble vitamins such as vitamins A, E, and K are also poorly absorbed potentially resulting in fat-soluble vitamin deficiency. Further, patients do not have any apoB-containing lipoproteins in their plasma, and consequently they have very low levels of triglycerides, cholesterol, phospholipids and ceramides. Thus, lipids and fat-soluble vitamins are inadequately transported throughout the blood stream. Some patients may also have reduced non-apoB-containing lipoproteins (high density lipoproteins) or apoA1 levels in their plasma.Between the ages of 2 and 20 years, a variety of neurological complications occur that resemble spinocerebellar degeneration, a general term for a group of disorders characterized by progressive impairment of the ability to coordinate voluntary movements due to degeneration of certain structures in the brain (cerebellar ataxia). Ataxia results in a lack of coordination and, eventually, difficulty in controlling the range of voluntary movement (dysmetria). Additional neurological symptoms include loss of deep tendon reflexes such as at the kneecap, difficulty speaking (dysarthria), tremors, motor tics and muscle weakness. Intelligence is usually normal, but developmental delays or intellectual disability has been reported.In some people, the damage or malfunction of the peripheral nervous system (peripheral neuropathy) may occur. The peripheral nervous system contains all the nerves outside of the central nervous system. The associated symptoms can vary greatly from one person to another but can include weakness of the muscles of the arms and legs or abnormal sensations such as tingling (paresthesias), burning or numbness.Some individuals with abetalipoproteinemia may develop skeletal abnormalities including backward curvature (lordosis) or backward and sideways curvature of the spine (kyphoscoliosis), a highly arched foot (pes cavus) or clubfoot. These skeletal abnormalities may result from muscle imbalances during crucial stages of bone development. Eventually, affected individuals may be unable to stand or to walk unaided due to progressive neurological and skeletal abnormalities.Some affected individuals may develop a rare eye condition called retinitis pigmentosa in which progressive degeneration of the nerve-rich membrane lining the eyes (retina) results in tunnel vision (loss of peripheral vision), loss of color vision and night blindness. Affected individuals may eventually develop loss of visual acuity. Retinitis pigmentosa occurs most often around the age of 10 years and may be due to vitamin A and/or E deficiency. If left untreated, visual acuity may deteriorate to virtual blindness by the fourth decade of life.Less often, additional symptoms that affect the eyes have been reported including rapid, involuntary eye movements (nystagmus), irregular concentric and some fine radial streaks (algioid streaks), droopy upper eyelid (ptosis), crossed eyes (strabismus), unequal size of the pupils (anisocoria) and weakness or paralysis of muscles that control eye movements (ophthalmoplegia).Individuals with abetalipoproteinemia may also have blood abnormalities including a condition called acanthocytosis in which deformed (i.e., burr-shaped) red blood cells (acanthocytes) are present in the body. Acanthocytosis may result in low levels of circulating red blood cells (anemia). Anemia may result in tiredness, increased need for sleep, weakness, lightheadedness, dizziness, irritability, palpitations, headaches and pale skin color. Additional blood abnormalities may be due to vitamin K deficiency. Blood clotting factor levels may be reduced resulting in bleeding tendencies such as severe gastrointestinal bleeding.Patients may have fatty liver, which can cause liver damage. In rare cases, fibrosis or scarring of the liver (cirrhosis) has also been reported. | 3 | Abetalipoproteinemia |
nord_3_2 | Causes of Abetalipoproteinemia | Abetalipoproteinemia is caused by changes (mutations or variants) in the MTTP gene and is inherited as an autosomal recessive genetic condition. Genetic diseases are determined by two alleles, one received from the father and one from the mother. An allele refers to one of two or more alternate forms of a particular gene.Recessive genetic disorders occur when an individual inherits two abnormal alleles for the same trait from each parent. If an individual receives one normal allele and one allele for the disease, the person will be a carrier for the disease, but usually will not show symptoms. When both parents are carriers, then the risk of an affected child is 25%. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.All individuals carry some abnormal genes. Parents who are close relatives have a higher chance than unrelated parents of both carrying the same altered gene. Some individuals with abetalipoproteinemia have had parents who were blood relatives (consanguineous). This increases the risk of having children with a recessive genetic disorder.The MTTP gene contains instructions for producing (encoding) a protein known as microsomal triglyceride transfer protein (MTTP or MTP). This protein is required for the proper assembly and secretion of apoB-containing lipoproteins in the liver and intestines. Variants in the MTTP gene lead to low levels of functional MTP, which in turn, hinders the liver and intestines from making and secreting apoB-containing lipoproteins. This, in turn, results in the inability to properly absorb and transport fats and fat-soluble vitamins throughout the body. Therefore, a deficiency in MTP results in the absence of lipoproteins such as very low-density lipoproteins (VLDLs), low density lipoproteins (LDLs) and chylomicrons in the blood. Lipoproteins are macromolecular complexes consisting of lipids and proteins. These lipid and protein complexes act as transporters that carry fats and fat-soluble vitamins (e.g., vitamin E) throughout the body. The symptoms of abetalipoproteinemia are caused by the lack of these apoB-containing lipoproteins in the plasma and fat-soluble vitamin deficiency.Recent research has determined that MTP is also involved in the maturation of a family of proteins known as CD1, which are involved in lipid antigen-presentation to immune cells. MTP has also been shown to modulate fat hydrolysis in adipose tissue by inhibiting adipose triglyceride lipase. More research is necessary to determine the complete functions of the MTP protein and the exact underlying mechanisms that cause disease in abetalipoproteinemia.Additionally, several studies have shown that MTP is expressed in the heart and is involved in exporting lipids out of the heart. Low levels of MTP may lead to fat accumulation in the heart and affect heart function. | Causes of Abetalipoproteinemia. Abetalipoproteinemia is caused by changes (mutations or variants) in the MTTP gene and is inherited as an autosomal recessive genetic condition. Genetic diseases are determined by two alleles, one received from the father and one from the mother. An allele refers to one of two or more alternate forms of a particular gene.Recessive genetic disorders occur when an individual inherits two abnormal alleles for the same trait from each parent. If an individual receives one normal allele and one allele for the disease, the person will be a carrier for the disease, but usually will not show symptoms. When both parents are carriers, then the risk of an affected child is 25%. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.All individuals carry some abnormal genes. Parents who are close relatives have a higher chance than unrelated parents of both carrying the same altered gene. Some individuals with abetalipoproteinemia have had parents who were blood relatives (consanguineous). This increases the risk of having children with a recessive genetic disorder.The MTTP gene contains instructions for producing (encoding) a protein known as microsomal triglyceride transfer protein (MTTP or MTP). This protein is required for the proper assembly and secretion of apoB-containing lipoproteins in the liver and intestines. Variants in the MTTP gene lead to low levels of functional MTP, which in turn, hinders the liver and intestines from making and secreting apoB-containing lipoproteins. This, in turn, results in the inability to properly absorb and transport fats and fat-soluble vitamins throughout the body. Therefore, a deficiency in MTP results in the absence of lipoproteins such as very low-density lipoproteins (VLDLs), low density lipoproteins (LDLs) and chylomicrons in the blood. Lipoproteins are macromolecular complexes consisting of lipids and proteins. These lipid and protein complexes act as transporters that carry fats and fat-soluble vitamins (e.g., vitamin E) throughout the body. The symptoms of abetalipoproteinemia are caused by the lack of these apoB-containing lipoproteins in the plasma and fat-soluble vitamin deficiency.Recent research has determined that MTP is also involved in the maturation of a family of proteins known as CD1, which are involved in lipid antigen-presentation to immune cells. MTP has also been shown to modulate fat hydrolysis in adipose tissue by inhibiting adipose triglyceride lipase. More research is necessary to determine the complete functions of the MTP protein and the exact underlying mechanisms that cause disease in abetalipoproteinemia.Additionally, several studies have shown that MTP is expressed in the heart and is involved in exporting lipids out of the heart. Low levels of MTP may lead to fat accumulation in the heart and affect heart function. | 3 | Abetalipoproteinemia |
nord_3_3 | Affects of Abetalipoproteinemia | The exact prevalence and incidence of abetalipoproteinemia is unknown, but it is estimated to affect less than 1 in 1,000,000 people in the general population. Abetalipoproteinemia affects both males and females. There are no known racial or ethnic preferences for the disorder. Abetalipoproteinemia is more prevalent in populations with a high incidence of consanguineous marriages. Symptoms usually become apparent during infancy. | Affects of Abetalipoproteinemia. The exact prevalence and incidence of abetalipoproteinemia is unknown, but it is estimated to affect less than 1 in 1,000,000 people in the general population. Abetalipoproteinemia affects both males and females. There are no known racial or ethnic preferences for the disorder. Abetalipoproteinemia is more prevalent in populations with a high incidence of consanguineous marriages. Symptoms usually become apparent during infancy. | 3 | Abetalipoproteinemia |
nord_3_4 | Related disorders of Abetalipoproteinemia | Symptoms of the following disorders can be similar to those of abetalipoproteinemia. Comparisons may be useful for a differential diagnosis.Familial hypobetalipoproteinemia due to secretion defect 2 (FHBL-SD2) is a rare genetic disorder that is highly variable in its expression and is due to variants in the APOB gene. Severe cases are nearly indistinguishable from individuals with abetalipoproteinemia. Symptoms can include steatorrhea, ataxia, retinitis pigmentosa and neuropathy. Acanthocytosis occurs in some patients as well. Treatment of individuals with FHBL is similar to treatment for individuals with abetalipoproteinemia. FHBL-SD2 is inherited in an autosomal dominant pattern. Contrary to abetalipoproteinemia, the presence of only one altered allele is sufficient to display symptoms of the disease.Celiac disease is a digestive disorder characterized by intolerance to dietary gluten, which is a protein found in wheat, rye, and barley. Consumption of gluten leads to abnormal changes of the mucous membrane (mucosa) of the small intestine, impairing its ability to properly absorb fats and additional nutrients during digestion (intestinal malabsorption). Symptom onset may occur during childhood or adulthood. In affected children, such symptoms may include diarrhea, vomiting, weight loss or lack of weight gain, painful abdominal bloating, irritability and/or other abnormalities. Affected adults may have diarrhea or constipation; abdominal cramping and bloating; abnormally bulky, pale, frothy stools that contain increased levels of fat (steatorrhea); weight loss; anemia; muscle cramping; bone pain; exhaustion (lassitude); and/or other symptoms and indications. Although the exact cause of celiac disease is unknown, genetic, immunologic, and environmental factors are thought to play some role. Friedreich’s ataxia (FRDA) is a genetic, progressive, neurodegerative movement disorder, with a mean age of onset between 10 and 15 years. Initial symptoms may include unsteady posture, frequent falling and progressive difficulty walking due to impaired ability to coordinate voluntary movements (ataxia). Affected individuals may also develop slurred speech (dysarthria), characteristic foot deformities; and irregular lateral or sideways curvature of the spine (scoliosis). FRDA is often associated with cardiomyopathy, a disease of cardiac muscle that may lead to heart failure, which could present as shortness of breath upon exertion and chest pain. Some individuals may also experience irregularities in heart rhythm (cardiac arrhythmias). Some individuals may develop diabetes mellitus. The symptoms and clinical findings associated with FRDA result primarily from degenerative changes in the sensory nerve fibers at the point where they enter the spinal cord in structures known as dorsal root ganglia. This results in secondary degeneration of nerve fibers in the spinal cord which leads to a deficiency of sensory signals to the cerebellum, the part of the brain that helps to coordinate voluntary movements. FRDA is caused by variants in the FXN gene and follows autosomal recessive inheritance. (For more information on this disorder, choose “Friedreich’s Ataxia” as your search term in the Rare Disease Database.)Ataxia with vitamin E deficiency (AVED) is a rare inherited neurodegenerative disorder characterized by impaired ability to coordinate voluntary movements (ataxia) and disease of the peripheral nervous system (peripheral neuropathy). AVED is a progressive disorder that can affect many different systems of the body (multisystem disorder). Specific symptoms vary from person to person. In addition to neurological symptoms, affected individuals may experience eye abnormalities, disorders affecting the heart muscles (cardiomyopathy) and abnormal curvature of the spine (scoliosis). AVED is extremely similar to a more common disorder known as Friedreich’s ataxia. AVED is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Ataxia with Vitamin E Deficiency” as your search term in the Rare Disease Database.) | Related disorders of Abetalipoproteinemia. Symptoms of the following disorders can be similar to those of abetalipoproteinemia. Comparisons may be useful for a differential diagnosis.Familial hypobetalipoproteinemia due to secretion defect 2 (FHBL-SD2) is a rare genetic disorder that is highly variable in its expression and is due to variants in the APOB gene. Severe cases are nearly indistinguishable from individuals with abetalipoproteinemia. Symptoms can include steatorrhea, ataxia, retinitis pigmentosa and neuropathy. Acanthocytosis occurs in some patients as well. Treatment of individuals with FHBL is similar to treatment for individuals with abetalipoproteinemia. FHBL-SD2 is inherited in an autosomal dominant pattern. Contrary to abetalipoproteinemia, the presence of only one altered allele is sufficient to display symptoms of the disease.Celiac disease is a digestive disorder characterized by intolerance to dietary gluten, which is a protein found in wheat, rye, and barley. Consumption of gluten leads to abnormal changes of the mucous membrane (mucosa) of the small intestine, impairing its ability to properly absorb fats and additional nutrients during digestion (intestinal malabsorption). Symptom onset may occur during childhood or adulthood. In affected children, such symptoms may include diarrhea, vomiting, weight loss or lack of weight gain, painful abdominal bloating, irritability and/or other abnormalities. Affected adults may have diarrhea or constipation; abdominal cramping and bloating; abnormally bulky, pale, frothy stools that contain increased levels of fat (steatorrhea); weight loss; anemia; muscle cramping; bone pain; exhaustion (lassitude); and/or other symptoms and indications. Although the exact cause of celiac disease is unknown, genetic, immunologic, and environmental factors are thought to play some role. Friedreich’s ataxia (FRDA) is a genetic, progressive, neurodegerative movement disorder, with a mean age of onset between 10 and 15 years. Initial symptoms may include unsteady posture, frequent falling and progressive difficulty walking due to impaired ability to coordinate voluntary movements (ataxia). Affected individuals may also develop slurred speech (dysarthria), characteristic foot deformities; and irregular lateral or sideways curvature of the spine (scoliosis). FRDA is often associated with cardiomyopathy, a disease of cardiac muscle that may lead to heart failure, which could present as shortness of breath upon exertion and chest pain. Some individuals may also experience irregularities in heart rhythm (cardiac arrhythmias). Some individuals may develop diabetes mellitus. The symptoms and clinical findings associated with FRDA result primarily from degenerative changes in the sensory nerve fibers at the point where they enter the spinal cord in structures known as dorsal root ganglia. This results in secondary degeneration of nerve fibers in the spinal cord which leads to a deficiency of sensory signals to the cerebellum, the part of the brain that helps to coordinate voluntary movements. FRDA is caused by variants in the FXN gene and follows autosomal recessive inheritance. (For more information on this disorder, choose “Friedreich’s Ataxia” as your search term in the Rare Disease Database.)Ataxia with vitamin E deficiency (AVED) is a rare inherited neurodegenerative disorder characterized by impaired ability to coordinate voluntary movements (ataxia) and disease of the peripheral nervous system (peripheral neuropathy). AVED is a progressive disorder that can affect many different systems of the body (multisystem disorder). Specific symptoms vary from person to person. In addition to neurological symptoms, affected individuals may experience eye abnormalities, disorders affecting the heart muscles (cardiomyopathy) and abnormal curvature of the spine (scoliosis). AVED is extremely similar to a more common disorder known as Friedreich’s ataxia. AVED is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Ataxia with Vitamin E Deficiency” as your search term in the Rare Disease Database.) | 3 | Abetalipoproteinemia |
nord_3_5 | Diagnosis of Abetalipoproteinemia | A diagnosis of abetalipoproteinemia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including tests to measure lipids (triglyceride and cholesterol) and apoB-containing lipoproteins in the plasma, determine the form and structure (morphology) of red blood cells and an eye (ophthalmological) exam.Blood tests will detect low levels of both lipids, such as cholesterol and triglycerides, and lipid-soluble vitamins such as A, E, and K. ApoB-containing lipoproteins, such as chylomicrons or very low-density lipoproteins, are not detectable in the plasma.The identification of malformed red blood cells (acanthocytosis) may also be detected by blood tests.A complete neurological assessment, an eye examination, an endoscopy and a liver (hepatic) ultrasound may be performed to evaluate the presence of potentially associated symptoms.Molecular genetic testing to detect pathogenic variants in the MTTP gene is available to confirm the diagnosis. | Diagnosis of Abetalipoproteinemia. A diagnosis of abetalipoproteinemia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including tests to measure lipids (triglyceride and cholesterol) and apoB-containing lipoproteins in the plasma, determine the form and structure (morphology) of red blood cells and an eye (ophthalmological) exam.Blood tests will detect low levels of both lipids, such as cholesterol and triglycerides, and lipid-soluble vitamins such as A, E, and K. ApoB-containing lipoproteins, such as chylomicrons or very low-density lipoproteins, are not detectable in the plasma.The identification of malformed red blood cells (acanthocytosis) may also be detected by blood tests.A complete neurological assessment, an eye examination, an endoscopy and a liver (hepatic) ultrasound may be performed to evaluate the presence of potentially associated symptoms.Molecular genetic testing to detect pathogenic variants in the MTTP gene is available to confirm the diagnosis. | 3 | Abetalipoproteinemia |
nord_3_6 | Therapies of Abetalipoproteinemia | Treatment
The treatment of abetalipoproteinemia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Neurologists, liver specialists (hepatologists), eye specialists (ophthalmologists), specialists in the study of fats (lipidologists), gastroenterologists, nutritionists and other healthcare professionals may need to plan an affected child’s treatment systematically, comprehensively and collaboratively. Patients should be closely monitored every 6-12 months. Neurological and eye exams should be performed routinely to measure any ophthalmological or neurological deteriorations. Further, amino transaminases in the blood should be measured every year to determine if there is liver damage. Hepatic ultrasound can be performed to detect the presence of fatty liver. Echocardiography should be performed every three years to ensure the heart is working properly.Most affected individuals respond to dietary therapy consisting of a diet low in long-chain saturated fatty acids. The reduction of the intake of dietary fats generally relieves gastrointestinal symptoms. Patients should receive frequent dietary counseling. Diets in infants may be supplemented with medium chain fatty acids, which can be transported in the blood without apoB-containing lipoproteins, to promote normal growth and development.The oral administration of high doses of fat-soluble vitamins (e.g., A, E, K) helps to prevent or improve many of the symptoms associated with abetalipoproteinemia. For example, treatment with vitamin E (i.e., tocopherol therapy) and vitamin A supplementation may prevent the neurological and retinal complications associated with abetalipoproteinemia. Vitamin D supplementation may help alleviate some of the symptoms associated with bone growth. Blood levels of fat-soluble vitamins should be measured at each follow up because the blood levels do not always correlate with the amount of vitamins ingested. Doses should be adjusted based on the results of blood panels, neurological exams, and ophthalmological exams. It should be noted that vitamin E levels are not reliably measurable in these patients even after high dose supplementations. Despite this, vitamin E therapy should continue in these patients. The prognosis of patients is highly variable. Early detection, treatment and fat-soluble vitamin supplementation can help curtail some of the neurological and ophthalmological deficiencies. Patients should be carefully monitored if receiving fat soluble drug treatments (i.e., for diseases unrelated to abetalipoproteinemia) as their pharmacokinetics, absorption and transport may also be affected. Additional treatment is symptomatic and supportive.Genetic counseling is recommended for families of children with abetalipoproteinemia. | Therapies of Abetalipoproteinemia. Treatment
The treatment of abetalipoproteinemia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Neurologists, liver specialists (hepatologists), eye specialists (ophthalmologists), specialists in the study of fats (lipidologists), gastroenterologists, nutritionists and other healthcare professionals may need to plan an affected child’s treatment systematically, comprehensively and collaboratively. Patients should be closely monitored every 6-12 months. Neurological and eye exams should be performed routinely to measure any ophthalmological or neurological deteriorations. Further, amino transaminases in the blood should be measured every year to determine if there is liver damage. Hepatic ultrasound can be performed to detect the presence of fatty liver. Echocardiography should be performed every three years to ensure the heart is working properly.Most affected individuals respond to dietary therapy consisting of a diet low in long-chain saturated fatty acids. The reduction of the intake of dietary fats generally relieves gastrointestinal symptoms. Patients should receive frequent dietary counseling. Diets in infants may be supplemented with medium chain fatty acids, which can be transported in the blood without apoB-containing lipoproteins, to promote normal growth and development.The oral administration of high doses of fat-soluble vitamins (e.g., A, E, K) helps to prevent or improve many of the symptoms associated with abetalipoproteinemia. For example, treatment with vitamin E (i.e., tocopherol therapy) and vitamin A supplementation may prevent the neurological and retinal complications associated with abetalipoproteinemia. Vitamin D supplementation may help alleviate some of the symptoms associated with bone growth. Blood levels of fat-soluble vitamins should be measured at each follow up because the blood levels do not always correlate with the amount of vitamins ingested. Doses should be adjusted based on the results of blood panels, neurological exams, and ophthalmological exams. It should be noted that vitamin E levels are not reliably measurable in these patients even after high dose supplementations. Despite this, vitamin E therapy should continue in these patients. The prognosis of patients is highly variable. Early detection, treatment and fat-soluble vitamin supplementation can help curtail some of the neurological and ophthalmological deficiencies. Patients should be carefully monitored if receiving fat soluble drug treatments (i.e., for diseases unrelated to abetalipoproteinemia) as their pharmacokinetics, absorption and transport may also be affected. Additional treatment is symptomatic and supportive.Genetic counseling is recommended for families of children with abetalipoproteinemia. | 3 | Abetalipoproteinemia |
nord_4_0 | Overview of Ablepharon-Macrostomia Syndrome | SummaryAblepharon-macrostomia syndrome (AMS) is a rare genetic disorder characterized by absent or underdeveloped eyelids (ablepharon or microblepharon) and a wide mouth (macrostomia). Characteristics mainly involve the face and skin and rarely involve the internal organs (viscera). Common signs and symptoms in addition to eye and mouth findings include low-set ears with attached earlobes, distortion or fusion of the digits (syndactyly or camptodactyly), bulging cheeks, absent or very small nipples, wrinkled and redundant skin, absent or sparse hair and genital malformations. Other, less frequently reported findings include umbilical abnormalities, growth delay and intellectual disability. AMS has been grouped within the category of diseases called ectodermal dysplasias (genetic disorders that involve defects in the skin, hair, nails, sweat glands, and/or teeth) but because many characteristics involve tissues that are not derived from the ectoderm, it would be better to define AMS as a genuine malformation syndrome. AMS is caused by changes (mutations) in the TWIST2 gene. The pattern of inheritance is autosomal dominant, and most cases arise as spontaneous mutations, so occur sporadically.Mutations in TWIST2 also cause the Barber Say syndrome and Setleis syndrome, which have very similar features. Indeed, it has been suggested the three disorders in fact form a continuum (De Maria 2016).IntroductionABS was originally described in 1977 (McCarthy and West 1977) in two unrelated boys. Advances have been made in the surgical techniques that improve visual function and cosmetic appearance. | Overview of Ablepharon-Macrostomia Syndrome. SummaryAblepharon-macrostomia syndrome (AMS) is a rare genetic disorder characterized by absent or underdeveloped eyelids (ablepharon or microblepharon) and a wide mouth (macrostomia). Characteristics mainly involve the face and skin and rarely involve the internal organs (viscera). Common signs and symptoms in addition to eye and mouth findings include low-set ears with attached earlobes, distortion or fusion of the digits (syndactyly or camptodactyly), bulging cheeks, absent or very small nipples, wrinkled and redundant skin, absent or sparse hair and genital malformations. Other, less frequently reported findings include umbilical abnormalities, growth delay and intellectual disability. AMS has been grouped within the category of diseases called ectodermal dysplasias (genetic disorders that involve defects in the skin, hair, nails, sweat glands, and/or teeth) but because many characteristics involve tissues that are not derived from the ectoderm, it would be better to define AMS as a genuine malformation syndrome. AMS is caused by changes (mutations) in the TWIST2 gene. The pattern of inheritance is autosomal dominant, and most cases arise as spontaneous mutations, so occur sporadically.Mutations in TWIST2 also cause the Barber Say syndrome and Setleis syndrome, which have very similar features. Indeed, it has been suggested the three disorders in fact form a continuum (De Maria 2016).IntroductionABS was originally described in 1977 (McCarthy and West 1977) in two unrelated boys. Advances have been made in the surgical techniques that improve visual function and cosmetic appearance. | 4 | Ablepharon-Macrostomia Syndrome |
nord_4_1 | Symptoms of Ablepharon-Macrostomia Syndrome | AMS is apparent at birth from features of the head and facial (craniofacial) region. The absence of, or underdevelopment of eyelids and a wide mouth are cardinal features. The abnormalities around the eyes, poor eyelid development and absent eyebrows and eyelashes cause the upper and lower lids to turn outwards (ectropion), exposing the inner mucous membranes and prohibiting complete closure of the eyes (lagophthalmos). This results in dry eyes and corneal clouding, which, if left untreated, can lead to light sensitivity (photophobia) and vision loss. Other potential eye issues include inability to produce tears (alacrimia); repeated involuntary eye movements (nystagmus); an unequal, inward deviation of the eyes (strabismus); and/or complete or partial separation of the retina, the nerve-rich membrane lining the inner layer of the back of the eye, from membranes (choroids) in the outer layer (detached retina).Infants affected with AMS may have additional, characteristic craniofacial features. Prominent features include a wide nasal bridge, long groove between the nose and lips (philtrum), flared nostrils and thick-flared edges of nostrils (alae nasi). The cheeks superolateral to the corners of mouth may bulge; a sign called “cheek pads”. In addition, in some patients, the zygomatic arches of the skull may be absent. Zygomotic arches are the two bony arches spanning from the lower portion of the orbits of the eyes, across the prominence of the cheekbones to the bones forming part of the lower skull. A small chin, low set ears with attached earlobes and impaired hearing can also be present.The absence of the soft, downy hair at birth that typically covers most of the body (lanugo), sparse scalp hair, redundant and wrinkled skin, small or absent nipples and underdeveloped genitalia can be found. Unusually formed genitalia can include undescended testis (cryptochordism), urethral opening on the underside of the penis (hypospadias), and a small penis in males or small labia minora in females. Sometimes there is an abdominal hernia, so protrusion of portions of the large intestine through an abnormal opening in the abdominal wall which is covered by skin. At the extremities, it is common to find syndactyly and camptodactyly; the skin over the hands may be abnormally loose, the fingers may be permanently flexed due to tight skin over the finger joints. While physical growth is generally undisturbed, cognitive development may be delayed. It is possible that many of these signs and symptoms do not capture the entirety of the syndrome, as there are relatively few cases and presentations vary in severity from person to person. | Symptoms of Ablepharon-Macrostomia Syndrome. AMS is apparent at birth from features of the head and facial (craniofacial) region. The absence of, or underdevelopment of eyelids and a wide mouth are cardinal features. The abnormalities around the eyes, poor eyelid development and absent eyebrows and eyelashes cause the upper and lower lids to turn outwards (ectropion), exposing the inner mucous membranes and prohibiting complete closure of the eyes (lagophthalmos). This results in dry eyes and corneal clouding, which, if left untreated, can lead to light sensitivity (photophobia) and vision loss. Other potential eye issues include inability to produce tears (alacrimia); repeated involuntary eye movements (nystagmus); an unequal, inward deviation of the eyes (strabismus); and/or complete or partial separation of the retina, the nerve-rich membrane lining the inner layer of the back of the eye, from membranes (choroids) in the outer layer (detached retina).Infants affected with AMS may have additional, characteristic craniofacial features. Prominent features include a wide nasal bridge, long groove between the nose and lips (philtrum), flared nostrils and thick-flared edges of nostrils (alae nasi). The cheeks superolateral to the corners of mouth may bulge; a sign called “cheek pads”. In addition, in some patients, the zygomatic arches of the skull may be absent. Zygomotic arches are the two bony arches spanning from the lower portion of the orbits of the eyes, across the prominence of the cheekbones to the bones forming part of the lower skull. A small chin, low set ears with attached earlobes and impaired hearing can also be present.The absence of the soft, downy hair at birth that typically covers most of the body (lanugo), sparse scalp hair, redundant and wrinkled skin, small or absent nipples and underdeveloped genitalia can be found. Unusually formed genitalia can include undescended testis (cryptochordism), urethral opening on the underside of the penis (hypospadias), and a small penis in males or small labia minora in females. Sometimes there is an abdominal hernia, so protrusion of portions of the large intestine through an abnormal opening in the abdominal wall which is covered by skin. At the extremities, it is common to find syndactyly and camptodactyly; the skin over the hands may be abnormally loose, the fingers may be permanently flexed due to tight skin over the finger joints. While physical growth is generally undisturbed, cognitive development may be delayed. It is possible that many of these signs and symptoms do not capture the entirety of the syndrome, as there are relatively few cases and presentations vary in severity from person to person. | 4 | Ablepharon-Macrostomia Syndrome |
nord_4_2 | Causes of Ablepharon-Macrostomia Syndrome | AMS is caused by changes (mutations) in the gene called TWIST2. The mutation has often occurred spontaneously in the affected individual (so not inherited from one of the parents) but inheritance from one of the parents in an autosomal dominant pattern has been reported. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Ablepharon-Macrostomia Syndrome. AMS is caused by changes (mutations) in the gene called TWIST2. The mutation has often occurred spontaneously in the affected individual (so not inherited from one of the parents) but inheritance from one of the parents in an autosomal dominant pattern has been reported. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | 4 | Ablepharon-Macrostomia Syndrome |
nord_4_3 | Affects of Ablepharon-Macrostomia Syndrome | Between 1977 and 2020, there have been 16 documented cases of AMS in the literature and a worldwide prevalence of less than <1/1,000,000. No apparent sex or ethnic disparity exists, and males and females present with similar signs and symptoms.
| Affects of Ablepharon-Macrostomia Syndrome. Between 1977 and 2020, there have been 16 documented cases of AMS in the literature and a worldwide prevalence of less than <1/1,000,000. No apparent sex or ethnic disparity exists, and males and females present with similar signs and symptoms.
| 4 | Ablepharon-Macrostomia Syndrome |
nord_4_4 | Related disorders of Ablepharon-Macrostomia Syndrome | Barber-Say syndrome (BSS) and Setleis syndrome (also known as focal facial dermal dysplasia 3) fall within the spectrum of disorders resulting from TWIST2 mutations. Key features that differentiate BSS from AMS are presence of excessive hair (hypertrichosis), less marked eye findings, narrow ear canals and relatively normal hands and genitalia. Setleis syndrome presents with some overlap to AMS and BSS but is typically milder and can be differentiated by the finding of inward folding eyelids (entropion), bitemporal narrowing and absence of cheek pads. | Related disorders of Ablepharon-Macrostomia Syndrome. Barber-Say syndrome (BSS) and Setleis syndrome (also known as focal facial dermal dysplasia 3) fall within the spectrum of disorders resulting from TWIST2 mutations. Key features that differentiate BSS from AMS are presence of excessive hair (hypertrichosis), less marked eye findings, narrow ear canals and relatively normal hands and genitalia. Setleis syndrome presents with some overlap to AMS and BSS but is typically milder and can be differentiated by the finding of inward folding eyelids (entropion), bitemporal narrowing and absence of cheek pads. | 4 | Ablepharon-Macrostomia Syndrome |
nord_4_5 | Diagnosis of Ablepharon-Macrostomia Syndrome | A diagnosis of AMS may be suspected at birth based upon a thorough clinical evaluation, a detailed patient and family history and identification of characteristic physical findings; typically, a reliable diagnosis is possible on clinical grounds only. Differentiation from BSS and Setleis syndrome may sometimes be difficult. The clinical diagnosis can be confirmed by molecular genetic testing for mutations in TWIST2.Clinical Testing and Work-Up
Computerized tomography (CT) scanning may be helpful in demonstrating absence of the zygomatic arch, improper union of portions of the upper and lower jawbones (maxillary and mandibular prominences), although this rarely will have consequences for management. Thorough examination and specialized testing may be conducted by eye specialists (ophthalmologists) to appropriately characterize eyelid characteristics, detect any additional or associated eye abnormalities and ensure appropriate preventive steps or treatment. | Diagnosis of Ablepharon-Macrostomia Syndrome. A diagnosis of AMS may be suspected at birth based upon a thorough clinical evaluation, a detailed patient and family history and identification of characteristic physical findings; typically, a reliable diagnosis is possible on clinical grounds only. Differentiation from BSS and Setleis syndrome may sometimes be difficult. The clinical diagnosis can be confirmed by molecular genetic testing for mutations in TWIST2.Clinical Testing and Work-Up
Computerized tomography (CT) scanning may be helpful in demonstrating absence of the zygomatic arch, improper union of portions of the upper and lower jawbones (maxillary and mandibular prominences), although this rarely will have consequences for management. Thorough examination and specialized testing may be conducted by eye specialists (ophthalmologists) to appropriately characterize eyelid characteristics, detect any additional or associated eye abnormalities and ensure appropriate preventive steps or treatment. | 4 | Ablepharon-Macrostomia Syndrome |
nord_4_6 | Therapies of Ablepharon-Macrostomia Syndrome | Treatment
The currently accepted treatment is corrective and reconstructive surgery aimed at preserving vision and reducing visual complications such as corneal clouding (opacification) during the neonatal period. Providing supportive therapy such as lubricant eye drops early on may improve symptoms of eye dryness. Additional surgery at a later age can be aimed at improving function and appearance. Severe ectropion and underdevelopment of eyelids is managed with the transfer of skin flaps to the lid region, thus improving the ability to close the eyes. A possible complication of this procedure is the inability to completely close the eyes (lagophthalmos). Corrective surgery can also be pursued for the fingers, skin, or ears, but there is minimal evidence to support this. These surgical procedures include local flaps, face-lift procedures, forehead lifting, Botox injections, fat grafting, orthognathic surgery and nasal reconstruction with rib cartilage grafts (De Maria 2016). These procedures may be riskier in younger individuals because craniofacial growth may be impaired. Psychosocial support for children with AMS is also important as they grow and face the societal pressures related to physical appearance. Receiving care from a well-informed team of healthcare providers may be beneficial, as they are able to offer care for both the medical and psychosocial aspects of the condition. Testimonies from individuals with AMS report positive experiences from corrective surgery and emphasize the importance of building self-esteem and having continued support from family members. Despite the challenges that are posed by this condition, patients report that they are aware it is mainly external and does not affect their intellectual and physical abilities or their capacity to pursue their ambitions (De Maria 2017).Genetic counseling is recommended for affected individuals and their families to understand the genetics and natural history of AMS, and to provide psychosocial support. | Therapies of Ablepharon-Macrostomia Syndrome. Treatment
The currently accepted treatment is corrective and reconstructive surgery aimed at preserving vision and reducing visual complications such as corneal clouding (opacification) during the neonatal period. Providing supportive therapy such as lubricant eye drops early on may improve symptoms of eye dryness. Additional surgery at a later age can be aimed at improving function and appearance. Severe ectropion and underdevelopment of eyelids is managed with the transfer of skin flaps to the lid region, thus improving the ability to close the eyes. A possible complication of this procedure is the inability to completely close the eyes (lagophthalmos). Corrective surgery can also be pursued for the fingers, skin, or ears, but there is minimal evidence to support this. These surgical procedures include local flaps, face-lift procedures, forehead lifting, Botox injections, fat grafting, orthognathic surgery and nasal reconstruction with rib cartilage grafts (De Maria 2016). These procedures may be riskier in younger individuals because craniofacial growth may be impaired. Psychosocial support for children with AMS is also important as they grow and face the societal pressures related to physical appearance. Receiving care from a well-informed team of healthcare providers may be beneficial, as they are able to offer care for both the medical and psychosocial aspects of the condition. Testimonies from individuals with AMS report positive experiences from corrective surgery and emphasize the importance of building self-esteem and having continued support from family members. Despite the challenges that are posed by this condition, patients report that they are aware it is mainly external and does not affect their intellectual and physical abilities or their capacity to pursue their ambitions (De Maria 2017).Genetic counseling is recommended for affected individuals and their families to understand the genetics and natural history of AMS, and to provide psychosocial support. | 4 | Ablepharon-Macrostomia Syndrome |
nord_5_0 | Overview of Acanthocheilonemiasis | Acanthocheilonemiasis is a rare tropical infectious disease caused by a parasite known as Acanthocheilonema perstans, which belongs to a group of parasitic diseases known as filarial diseases (nematode). This parasite is found, for the most part, in Africa. Symptoms of infection may include red, itchy skin (pruritis), abdominal and chest pain, muscular pain (myalgia), and areas of localized swelling (edema). In addition, the liver and spleen may become abnormally enlarged (hepatosplenomegaly). Laboratory testing may also reveal abnormally elevated levels of certain specialized white blood cells (eosinophilia). The parasite is transmitted through the bite of small flies (A. coliroides). | Overview of Acanthocheilonemiasis. Acanthocheilonemiasis is a rare tropical infectious disease caused by a parasite known as Acanthocheilonema perstans, which belongs to a group of parasitic diseases known as filarial diseases (nematode). This parasite is found, for the most part, in Africa. Symptoms of infection may include red, itchy skin (pruritis), abdominal and chest pain, muscular pain (myalgia), and areas of localized swelling (edema). In addition, the liver and spleen may become abnormally enlarged (hepatosplenomegaly). Laboratory testing may also reveal abnormally elevated levels of certain specialized white blood cells (eosinophilia). The parasite is transmitted through the bite of small flies (A. coliroides). | 5 | Acanthocheilonemiasis |
nord_5_1 | Symptoms of Acanthocheilonemiasis | Initially people with Acanthocheilonemiasis may have no symptoms. Symptoms occur more frequently in people who visit the areas where this parasite is common (endemic), than in people who are native to that area. One common laboratory finding, in people who have recently returned from infected areas, is abnormally high levels of specialized white blood cells (eosinophilia). Generally there are no symptoms associated with the laboratory finding.When symptoms appear they may include itchy skin (pruritis), abdominal pain, chest pain, muscle pains (myalgias), and/or areas of swelling under the skin (subcutaneous). Examination by a physician may reveal an abnormally enlarged liver and spleen (hepatosplenomegaly), and abnormally high levels of granular white blood cells (eosinophilia). The adult worm (nematode) may lodge in the tissues of the abdomen and chest causing inflammation and immune reactions. This may result in inflammation of the lining of the lungs (pleuritis) and/or the membranes that surround the heart (pericarditis).The early or prelarval form (microfilariae) of Acanthocheilonema perstans can be isolated from the blood from patients with Acanthocheilonemiasis. Generally this disease is diagnosed by the examination under a microscope of a thick blood smear taken from the patient. | Symptoms of Acanthocheilonemiasis. Initially people with Acanthocheilonemiasis may have no symptoms. Symptoms occur more frequently in people who visit the areas where this parasite is common (endemic), than in people who are native to that area. One common laboratory finding, in people who have recently returned from infected areas, is abnormally high levels of specialized white blood cells (eosinophilia). Generally there are no symptoms associated with the laboratory finding.When symptoms appear they may include itchy skin (pruritis), abdominal pain, chest pain, muscle pains (myalgias), and/or areas of swelling under the skin (subcutaneous). Examination by a physician may reveal an abnormally enlarged liver and spleen (hepatosplenomegaly), and abnormally high levels of granular white blood cells (eosinophilia). The adult worm (nematode) may lodge in the tissues of the abdomen and chest causing inflammation and immune reactions. This may result in inflammation of the lining of the lungs (pleuritis) and/or the membranes that surround the heart (pericarditis).The early or prelarval form (microfilariae) of Acanthocheilonema perstans can be isolated from the blood from patients with Acanthocheilonemiasis. Generally this disease is diagnosed by the examination under a microscope of a thick blood smear taken from the patient. | 5 | Acanthocheilonemiasis |
nord_5_2 | Causes of Acanthocheilonemiasis | Acanthocheilonemiasis is a rare infectious disease caused by long “thread-like” worms, Acanthocheilonema perstans, also known as Dipetalonema perstans. The disease is transmitted by a small black insect (midge), called A. Culicoides. | Causes of Acanthocheilonemiasis. Acanthocheilonemiasis is a rare infectious disease caused by long “thread-like” worms, Acanthocheilonema perstans, also known as Dipetalonema perstans. The disease is transmitted by a small black insect (midge), called A. Culicoides. | 5 | Acanthocheilonemiasis |
nord_5_3 | Affects of Acanthocheilonemiasis | Acanthocheilonema perstans, the parasite that causes Acanthocheilonemiasis is common in central Africa and in some areas of South America. This disorder affects males and females in equal numbers. | Affects of Acanthocheilonemiasis. Acanthocheilonema perstans, the parasite that causes Acanthocheilonemiasis is common in central Africa and in some areas of South America. This disorder affects males and females in equal numbers. | 5 | Acanthocheilonemiasis |
nord_5_4 | Related disorders of Acanthocheilonemiasis | Symptoms of the following disorders can be similar to those of Acanthocheilonemiasis. Comparisons may be useful for a differential diagnosis:Filariasis is a group of rare infectious diseases caused by parasitic worms. These disorders are characterized by abnormal changes with the lymph glands (lymphadenopathy) and chronic obstruction of the flow of lymphatic fluid. This may result in the extreme swelling of the legs and/or genitalia (elephantiasis). This parasite enters the body by a mosquito bite. (For more information on this disorder, choose “Filariasis” as your search term in the Rare Disease Database.)Other tropical diseases can cause similar symptoms to Acanthocheilonemiais. For more information choose “Tropical” as your search term in the Rare Disease Database. | Related disorders of Acanthocheilonemiasis. Symptoms of the following disorders can be similar to those of Acanthocheilonemiasis. Comparisons may be useful for a differential diagnosis:Filariasis is a group of rare infectious diseases caused by parasitic worms. These disorders are characterized by abnormal changes with the lymph glands (lymphadenopathy) and chronic obstruction of the flow of lymphatic fluid. This may result in the extreme swelling of the legs and/or genitalia (elephantiasis). This parasite enters the body by a mosquito bite. (For more information on this disorder, choose “Filariasis” as your search term in the Rare Disease Database.)Other tropical diseases can cause similar symptoms to Acanthocheilonemiais. For more information choose “Tropical” as your search term in the Rare Disease Database. | 5 | Acanthocheilonemiasis |
nord_5_5 | Diagnosis of Acanthocheilonemiasis | Diagnosis of Acanthocheilonemiasis. | 5 | Acanthocheilonemiasis |
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nord_5_6 | Therapies of Acanthocheilonemiasis | Acanthocheilonemiasis is treated by means of the administration of antifilarial drugs, some of which are newer than others. Ivermectin or diethyl-carbamazine (DEC) are frequently prescribed. Occasionally, surgery may be required to remove large adult worms. Mild cases of acanthocheilonemiasis do not require treatment. | Therapies of Acanthocheilonemiasis. Acanthocheilonemiasis is treated by means of the administration of antifilarial drugs, some of which are newer than others. Ivermectin or diethyl-carbamazine (DEC) are frequently prescribed. Occasionally, surgery may be required to remove large adult worms. Mild cases of acanthocheilonemiasis do not require treatment. | 5 | Acanthocheilonemiasis |
nord_6_0 | Overview of Aceruloplasminemia | Aceruloplasminemia is a rare genetic disorder characterized by the abnormal accumulation of iron in the brain and various internal organs. Affected individuals develop neurological symptoms including cognitive impairment and movement disorders. Degeneration of the retina and diabetes may also occur. Symptoms usually become apparent during adulthood between 20 and 60 years of age. Aceruloplasminemia is caused by mutations of the ceruloplasmin (CP) gene. This mutation is inherited in an autosomal recessive pattern.Aceruloplasminemia is classified as a neurodegenerative disorder with brain iron accumulation (NBIA). NBIA are a group of rare inherited disorders characterized by iron accumulation in the brain. Aceruloplasminemia is also classified as an iron overload disorder. | Overview of Aceruloplasminemia. Aceruloplasminemia is a rare genetic disorder characterized by the abnormal accumulation of iron in the brain and various internal organs. Affected individuals develop neurological symptoms including cognitive impairment and movement disorders. Degeneration of the retina and diabetes may also occur. Symptoms usually become apparent during adulthood between 20 and 60 years of age. Aceruloplasminemia is caused by mutations of the ceruloplasmin (CP) gene. This mutation is inherited in an autosomal recessive pattern.Aceruloplasminemia is classified as a neurodegenerative disorder with brain iron accumulation (NBIA). NBIA are a group of rare inherited disorders characterized by iron accumulation in the brain. Aceruloplasminemia is also classified as an iron overload disorder. | 6 | Aceruloplasminemia |
nord_6_1 | Symptoms of Aceruloplasminemia | The symptoms and severity of aceruloplasminemia vary from one person to another even among members of the same family. The age of onset varies as well, ranging from anywhere between the 20s and 60s. The three main findings associated with aceruloplasminemia are retinal degeneration, neurological symptoms and diabetes mellitus.Some individuals with aceruloplasminemia develop mild anemia (low levels of circulating red blood cells), which can cause fatigue, weakness, shortness of breath and pale skin. Anemia often occurs before the development of other symptoms commonly associated with aceruloplasminemia.Many affected individuals develop progressive degeneration of the retinas. The retinas are the thin layers of nerve cells that line the inner surface of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. The damage to the retinal tissue can result from iron deposition or be related to the diabetes that develops as part of aceruloplasminemia.A variety of neurological symptoms occur in individuals with aceruloplasminemia because of the accumulation of iron in the brain. Specific symptoms may vary, but often include movement disorders, an inability to coordinate voluntary movements (ataxia), slurred speech or difficulty speaking (dysarthria), behavioral changes and cognitive impairment.Movement disorders associated with aceruloplasminemia include tremors, chorea (rapid, involuntary, jerky movements) and dystonia, which refers to a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). An example of dystonia is blepharospasm, a condition characterized by involuntary muscle spasms and contractions of the muscles around the eyes.Some affected individuals develop symptoms may resemble those found in Parkinson’s disease, which is sometimes referred to as Parkinsonism. These symptoms include tremors, abnormal slowness of movement and an inability to remain in a stable or balanced position. Some individuals with aceruloplasminemia develop cognitive impairment, which can progress to dementia. Behavioral or emotional changes (e.g., depression) may also occur.Iron accumulation in individuals with aceruloplasminemia may also occur in the pancreas. The pancreas is a small organ located behind the stomach that secretes enzymes that travel to the intestines and aid in digestion. The pancreas also secretes other hormones such as insulin, which helps break down sugar. Damage to the pancreas may ultimately lead to diabetes mellitus. Diabetes is a common disorder in which the body does not produce enough or is unable to properly use insulin. Therefore, the body is not able to properly convert nutrients into the energy necessary for daily activities. The most obvious symptoms are unusually excessive thirst and urination. | Symptoms of Aceruloplasminemia. The symptoms and severity of aceruloplasminemia vary from one person to another even among members of the same family. The age of onset varies as well, ranging from anywhere between the 20s and 60s. The three main findings associated with aceruloplasminemia are retinal degeneration, neurological symptoms and diabetes mellitus.Some individuals with aceruloplasminemia develop mild anemia (low levels of circulating red blood cells), which can cause fatigue, weakness, shortness of breath and pale skin. Anemia often occurs before the development of other symptoms commonly associated with aceruloplasminemia.Many affected individuals develop progressive degeneration of the retinas. The retinas are the thin layers of nerve cells that line the inner surface of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. The damage to the retinal tissue can result from iron deposition or be related to the diabetes that develops as part of aceruloplasminemia.A variety of neurological symptoms occur in individuals with aceruloplasminemia because of the accumulation of iron in the brain. Specific symptoms may vary, but often include movement disorders, an inability to coordinate voluntary movements (ataxia), slurred speech or difficulty speaking (dysarthria), behavioral changes and cognitive impairment.Movement disorders associated with aceruloplasminemia include tremors, chorea (rapid, involuntary, jerky movements) and dystonia, which refers to a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). An example of dystonia is blepharospasm, a condition characterized by involuntary muscle spasms and contractions of the muscles around the eyes.Some affected individuals develop symptoms may resemble those found in Parkinson’s disease, which is sometimes referred to as Parkinsonism. These symptoms include tremors, abnormal slowness of movement and an inability to remain in a stable or balanced position. Some individuals with aceruloplasminemia develop cognitive impairment, which can progress to dementia. Behavioral or emotional changes (e.g., depression) may also occur.Iron accumulation in individuals with aceruloplasminemia may also occur in the pancreas. The pancreas is a small organ located behind the stomach that secretes enzymes that travel to the intestines and aid in digestion. The pancreas also secretes other hormones such as insulin, which helps break down sugar. Damage to the pancreas may ultimately lead to diabetes mellitus. Diabetes is a common disorder in which the body does not produce enough or is unable to properly use insulin. Therefore, the body is not able to properly convert nutrients into the energy necessary for daily activities. The most obvious symptoms are unusually excessive thirst and urination. | 6 | Aceruloplasminemia |
nord_6_2 | Causes of Aceruloplasminemia | Aceruloplasminemia is caused by mutations of the ceruloplasmin (CP) gene and is inherited in an autosomal recessive pattern. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. In most recessive conditions, individuals with one working gene and one gene for the disease (carriers) do not develop symptoms, however, in aceruloplasminemia carriers may, in rare cases develop cerebellar ataxia (problems coordinating movements).The CP gene contains instructions for producing the enzyme ceruloplasmin. This enzyme is essential for the proper function and transport of iron within the body. Mutations of the CP gene result in deficient levels of functional ceruloplasmin, which ultimately results in the accumulation of iron in the brain and other organs of the body. Iron accumulation damages the tissue of affected organs causing the characteristic symptoms of aceruloplasminemia.Iron is a critical mineral that is found in all cells of the body and is essential for the body to function and grow properly. Iron is found many types of food including red meat, poultry, eggs and vegetables. Iron levels must remain in a specific range within the body, otherwise they can cause anemia (due to low iron levels) or damage affected organs (due to high iron levels).In most individuals with aceruloplasminemia, iron accumulates within the basal ganglia, a part of the brain that consists of three clusters of brain cells (neurons). The basal ganglia processes information involved in involuntary movements, coordination and cognition. The specific neurological symptoms that develop in aceruloplasminemia depend on the exact location and extent of iron accumulation within the brain.Diabetes associated with aceruloplasminemia results from iron accumulation in the pancreas. Iron can also accumulate elsewhere in the body such as the retinas or liver. Liver damage does not occur in aceruloplasminemia. | Causes of Aceruloplasminemia. Aceruloplasminemia is caused by mutations of the ceruloplasmin (CP) gene and is inherited in an autosomal recessive pattern. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. In most recessive conditions, individuals with one working gene and one gene for the disease (carriers) do not develop symptoms, however, in aceruloplasminemia carriers may, in rare cases develop cerebellar ataxia (problems coordinating movements).The CP gene contains instructions for producing the enzyme ceruloplasmin. This enzyme is essential for the proper function and transport of iron within the body. Mutations of the CP gene result in deficient levels of functional ceruloplasmin, which ultimately results in the accumulation of iron in the brain and other organs of the body. Iron accumulation damages the tissue of affected organs causing the characteristic symptoms of aceruloplasminemia.Iron is a critical mineral that is found in all cells of the body and is essential for the body to function and grow properly. Iron is found many types of food including red meat, poultry, eggs and vegetables. Iron levels must remain in a specific range within the body, otherwise they can cause anemia (due to low iron levels) or damage affected organs (due to high iron levels).In most individuals with aceruloplasminemia, iron accumulates within the basal ganglia, a part of the brain that consists of three clusters of brain cells (neurons). The basal ganglia processes information involved in involuntary movements, coordination and cognition. The specific neurological symptoms that develop in aceruloplasminemia depend on the exact location and extent of iron accumulation within the brain.Diabetes associated with aceruloplasminemia results from iron accumulation in the pancreas. Iron can also accumulate elsewhere in the body such as the retinas or liver. Liver damage does not occur in aceruloplasminemia. | 6 | Aceruloplasminemia |
nord_6_3 | Affects of Aceruloplasminemia | Aceruloplasminemia is an extremely rare disorder that affects males and females in equal numbers. The exact incidence of aceruloplasminemia is unknown. It may be more prevalent in Japan, where it is estimated to affect 1 individual per 2,000,000 in the general population. Because many cases of aceruloplasminemia go undiagnosed or misdiagnosed, determining the disorder’s true frequency in the general population is difficult. Aceruloplasminemia was first described in the medical literature in 1992. | Affects of Aceruloplasminemia. Aceruloplasminemia is an extremely rare disorder that affects males and females in equal numbers. The exact incidence of aceruloplasminemia is unknown. It may be more prevalent in Japan, where it is estimated to affect 1 individual per 2,000,000 in the general population. Because many cases of aceruloplasminemia go undiagnosed or misdiagnosed, determining the disorder’s true frequency in the general population is difficult. Aceruloplasminemia was first described in the medical literature in 1992. | 6 | Aceruloplasminemia |
nord_6_4 | Related disorders of Aceruloplasminemia | Symptoms of the following disorders can be similar to those of aceruloplasminemia. Comparisons may be useful for a differential diagnosis.Neurodegeneration with brain iron accumulation (NBIA) is a general term for a rare group of genetic disorders characterized by the accumulation of iron in the brain. These disorders may develop during childhood (early-onset, rapid progression) or adulthood (late-onset, slow progression) and iron accumulation most often occurs in the basal ganglia. A variety of neurological symptoms may develop. In addition to aceruloplasminemia, NBIAs include pantothenate kinase associated neurodegeneration (formerly Hallervorden-Spatz disease) and infantile neuroaxonal dystrophy (Seitelberger disease), which are childhood onset recessive conditions, and neuroferritinopathy, which is an autosomal dominant adult onset disorder. (For more information, choose the specific disorder name as your search term in the Rare Disease Database.)Wilson’s disease is a rare genetic disorder characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and, if left untreated, it may cause liver (hepatic) disease, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life threatening complications. Treatment is aimed at reducing the amount of copper that has accumulated in the body and maintaining normal copper levels thereafter. (For more information on this disorder, choose “Wilson” as your search term in the Rare Disease Database.)Iron overload disorders are a group of disorders characterized by the accumulation of iron in the body, especially in internal organs such as the liver and heart. Aceruloplasminemia is considered a type of iron overload disorder, although, in the other disorders in this group, the brain is not usually affected. These disorders include hemochromatosis, neonatal hemochromatosis, astransferrinemia, and African iron overload disease. (For more information choose the specific disorder name as your search term in the Rare Disease Database.)A variety of neurological disorders have symptoms that are similar to aceruloplasminemia including Parkinson’s disease, dystonia, hereditary ataxias, Huntington’s disease, multiple system atrophy, and dentatorubral-pallidoluysian atrophy. (For more information choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Aceruloplasminemia. Symptoms of the following disorders can be similar to those of aceruloplasminemia. Comparisons may be useful for a differential diagnosis.Neurodegeneration with brain iron accumulation (NBIA) is a general term for a rare group of genetic disorders characterized by the accumulation of iron in the brain. These disorders may develop during childhood (early-onset, rapid progression) or adulthood (late-onset, slow progression) and iron accumulation most often occurs in the basal ganglia. A variety of neurological symptoms may develop. In addition to aceruloplasminemia, NBIAs include pantothenate kinase associated neurodegeneration (formerly Hallervorden-Spatz disease) and infantile neuroaxonal dystrophy (Seitelberger disease), which are childhood onset recessive conditions, and neuroferritinopathy, which is an autosomal dominant adult onset disorder. (For more information, choose the specific disorder name as your search term in the Rare Disease Database.)Wilson’s disease is a rare genetic disorder characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and, if left untreated, it may cause liver (hepatic) disease, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life threatening complications. Treatment is aimed at reducing the amount of copper that has accumulated in the body and maintaining normal copper levels thereafter. (For more information on this disorder, choose “Wilson” as your search term in the Rare Disease Database.)Iron overload disorders are a group of disorders characterized by the accumulation of iron in the body, especially in internal organs such as the liver and heart. Aceruloplasminemia is considered a type of iron overload disorder, although, in the other disorders in this group, the brain is not usually affected. These disorders include hemochromatosis, neonatal hemochromatosis, astransferrinemia, and African iron overload disease. (For more information choose the specific disorder name as your search term in the Rare Disease Database.)A variety of neurological disorders have symptoms that are similar to aceruloplasminemia including Parkinson’s disease, dystonia, hereditary ataxias, Huntington’s disease, multiple system atrophy, and dentatorubral-pallidoluysian atrophy. (For more information choose the specific disorder name as your search term in the Rare Disease Database.) | 6 | Aceruloplasminemia |
nord_6_5 | Diagnosis of Aceruloplasminemia | A diagnosis of aceruloplasminemia is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Blood tests can reveal certain findings associated with aceruloplasminemia including absent blood ceruloplasmin and low concentrations of copper and iron in serum. Magnetic resonance imaging (MRI) of the brain and liver can reveal characteristic findings that indicate the accumulation of iron. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. A genetic test to demonstrate mutations in the CP gene is the definitive diagnostic test. | Diagnosis of Aceruloplasminemia. A diagnosis of aceruloplasminemia is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Blood tests can reveal certain findings associated with aceruloplasminemia including absent blood ceruloplasmin and low concentrations of copper and iron in serum. Magnetic resonance imaging (MRI) of the brain and liver can reveal characteristic findings that indicate the accumulation of iron. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. A genetic test to demonstrate mutations in the CP gene is the definitive diagnostic test. | 6 | Aceruloplasminemia |
nord_6_6 | Therapies of Aceruloplasminemia | Treatment
The treatment of aceruloplasminemia is directed toward the specific symptoms that are apparent in each individual. Individuals with aceruloplasminemia may be treated with a drug called desferrioxamine, an iron chelator. Iron chelators are drugs that bind to the excess iron in the body allowing it to be dissolved in water and excreted from the body through the kidneys. It has not been conclusively established that iron chelation improves symptoms in aceruloplasminemia. Individuals with aceruloplasminemia should avoid substances that increase the levels of iron in the body.Other treatment is symptomatic and supportive. Of particular importance is management of diabetes, with appropriate diet, tablets and insulin injects as needed.Genetic counseling is recommended for affected individuals and their families. | Therapies of Aceruloplasminemia. Treatment
The treatment of aceruloplasminemia is directed toward the specific symptoms that are apparent in each individual. Individuals with aceruloplasminemia may be treated with a drug called desferrioxamine, an iron chelator. Iron chelators are drugs that bind to the excess iron in the body allowing it to be dissolved in water and excreted from the body through the kidneys. It has not been conclusively established that iron chelation improves symptoms in aceruloplasminemia. Individuals with aceruloplasminemia should avoid substances that increase the levels of iron in the body.Other treatment is symptomatic and supportive. Of particular importance is management of diabetes, with appropriate diet, tablets and insulin injects as needed.Genetic counseling is recommended for affected individuals and their families. | 6 | Aceruloplasminemia |
nord_7_0 | Overview of Achalasia | Achalasia is a rare disorder of the esophagus, the tube that carries food from the throat to the stomach. It is characterized by impaired ability to push food down toward the stomach (peristalsis), failure of the ring-shaped muscle at the bottom of the esophagus, the lower esophageal sphincter (LES), to relax. It is the contraction and relaxation of the sphincter that moves food through the tube. | Overview of Achalasia. Achalasia is a rare disorder of the esophagus, the tube that carries food from the throat to the stomach. It is characterized by impaired ability to push food down toward the stomach (peristalsis), failure of the ring-shaped muscle at the bottom of the esophagus, the lower esophageal sphincter (LES), to relax. It is the contraction and relaxation of the sphincter that moves food through the tube. | 7 | Achalasia |
nord_7_1 | Symptoms of Achalasia | The symptoms of achalasia typically appear gradually. Most people with this disorder experience an impairment in the ability to swallow (dysphagia) as a major and early symptom. There may also be mild chest pain that comes and goes. Some affected individuals experience pain that is very intense.Retention of saliva and ingested food in the esophagus may often cause regurgitation of these contents; in addition, such contents may also be propelled into the lungs during breathing (tracheobronchial aspiration). Other symptoms of this disorder may include a cough during the night and significant weight loss, because of difficulty in swallowing, in cases that remain untreated. Dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) are not unusual in patients with achalasia.The aspiration of saliva and food contents by people with achalasia may cause pneumonia, other pulmonary infections, or even death. The incidence of esophageal cancer is significantly increased in patients with achalasia. | Symptoms of Achalasia. The symptoms of achalasia typically appear gradually. Most people with this disorder experience an impairment in the ability to swallow (dysphagia) as a major and early symptom. There may also be mild chest pain that comes and goes. Some affected individuals experience pain that is very intense.Retention of saliva and ingested food in the esophagus may often cause regurgitation of these contents; in addition, such contents may also be propelled into the lungs during breathing (tracheobronchial aspiration). Other symptoms of this disorder may include a cough during the night and significant weight loss, because of difficulty in swallowing, in cases that remain untreated. Dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) are not unusual in patients with achalasia.The aspiration of saliva and food contents by people with achalasia may cause pneumonia, other pulmonary infections, or even death. The incidence of esophageal cancer is significantly increased in patients with achalasia. | 7 | Achalasia |
nord_7_2 | Causes of Achalasia | The exact cause of achalasia is not known. Some clinical researchers suspect that the condition may be caused by the degeneration of a group of nerves located in the chest (Auerbach’s plexus). It is believed that there may be a rare, inherited form of achalasia, but this is not yet well understood at this time. | Causes of Achalasia. The exact cause of achalasia is not known. Some clinical researchers suspect that the condition may be caused by the degeneration of a group of nerves located in the chest (Auerbach’s plexus). It is believed that there may be a rare, inherited form of achalasia, but this is not yet well understood at this time. | 7 | Achalasia |
nord_7_3 | Affects of Achalasia | Achalasia is a rare disorder that typically affects adults between the ages of 25 and 60 years. However, this disorder may occur at any age, including during childhood. Achalasia affects males and females in equal numbers except in cases that appear to reflect an inherited form. In those cases, it appears that males are twice as likely as females to be diagnosed with this disorder. | Affects of Achalasia. Achalasia is a rare disorder that typically affects adults between the ages of 25 and 60 years. However, this disorder may occur at any age, including during childhood. Achalasia affects males and females in equal numbers except in cases that appear to reflect an inherited form. In those cases, it appears that males are twice as likely as females to be diagnosed with this disorder. | 7 | Achalasia |
nord_7_4 | Related disorders of Achalasia | Symptoms of the following disorders can be similar to those of achalasia. Comparisons may be useful for a differential diagnosis:Esophageal cancer
The symptoms of esophageal cancer resemble those associated with achalasia. Esophageal cancer may begin at almost any point in the tube. Small cancers may be asymptomatic or may be present without symptoms. As the tumor grows, the first sign may be difficulty in swallowing and/or pain upon swallowing and/or feeling as if food were stuck behind the breastbone. Difficulty in swallowing may be accompanied by indigestion, heartburn and choking. Weight loss is not uncommon.Swallowing disorders
Swallowing disorders come in a variety of forms. Some are the result of disturbances of the brain such as Parkinson’s disease, multiple sclerosis or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). Others are the result of malfunctioning of parts of the throat involved in swallowing. For example, the pharynx may malfunction after a stroke. | Related disorders of Achalasia. Symptoms of the following disorders can be similar to those of achalasia. Comparisons may be useful for a differential diagnosis:Esophageal cancer
The symptoms of esophageal cancer resemble those associated with achalasia. Esophageal cancer may begin at almost any point in the tube. Small cancers may be asymptomatic or may be present without symptoms. As the tumor grows, the first sign may be difficulty in swallowing and/or pain upon swallowing and/or feeling as if food were stuck behind the breastbone. Difficulty in swallowing may be accompanied by indigestion, heartburn and choking. Weight loss is not uncommon.Swallowing disorders
Swallowing disorders come in a variety of forms. Some are the result of disturbances of the brain such as Parkinson’s disease, multiple sclerosis or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). Others are the result of malfunctioning of parts of the throat involved in swallowing. For example, the pharynx may malfunction after a stroke. | 7 | Achalasia |
nord_7_5 | Diagnosis of Achalasia | X-ray examination (radiology) is frequently useful in the diagnosis of achalasia. Radiological examination, especially with the use of barium, may show enlargement (dilation) of the esophagus and the retention of food and secretions within the esophagus. Devices that measure fluid pressure (manometers) within the esophagus are used to confirm the diagnosis of achalasia. | Diagnosis of Achalasia. X-ray examination (radiology) is frequently useful in the diagnosis of achalasia. Radiological examination, especially with the use of barium, may show enlargement (dilation) of the esophagus and the retention of food and secretions within the esophagus. Devices that measure fluid pressure (manometers) within the esophagus are used to confirm the diagnosis of achalasia. | 7 | Achalasia |
nord_7_6 | Therapies of Achalasia | TreatmentThe treatment of achalasia is aimed at removing obstructions caused by the failure of the lower esophageal sphincter muscle to relax. This may be done with the administration of drugs, expanding the cross-section (manual dilation) of the sphincter muscle, or through surgery.The drug isosorbide, (a long-acting nitrate) or nifedipine (a calcium channel blocker) may provide some relief for people with achalasia.Approximately 70 percent of cases of achalasia may be treated effectively by the enlargement of the lower esophageal sphincter muscle through a procedure known as pneumatic balloon dilation. In many people, repeated dilations may be necessary to obtain improvement of symptoms.Surgical treatments of achalasia may be effective in approximately 85-90 percent of cases. During these procedures, the muscle fibers in the lower esophageal sphincter are cut (laparoscopic Heller myotomy or peroral endoscopic myotomy). About 15 percent of people with achalasia experience the symptoms of gastroesophageal reflux after this surgical procedure. | Therapies of Achalasia. TreatmentThe treatment of achalasia is aimed at removing obstructions caused by the failure of the lower esophageal sphincter muscle to relax. This may be done with the administration of drugs, expanding the cross-section (manual dilation) of the sphincter muscle, or through surgery.The drug isosorbide, (a long-acting nitrate) or nifedipine (a calcium channel blocker) may provide some relief for people with achalasia.Approximately 70 percent of cases of achalasia may be treated effectively by the enlargement of the lower esophageal sphincter muscle through a procedure known as pneumatic balloon dilation. In many people, repeated dilations may be necessary to obtain improvement of symptoms.Surgical treatments of achalasia may be effective in approximately 85-90 percent of cases. During these procedures, the muscle fibers in the lower esophageal sphincter are cut (laparoscopic Heller myotomy or peroral endoscopic myotomy). About 15 percent of people with achalasia experience the symptoms of gastroesophageal reflux after this surgical procedure. | 7 | Achalasia |
nord_8_0 | Overview of Achard Thiers Syndrome | Achard-Thiers syndrome is a rare disorder that occurs primarily in postmenopausal women and is characterized by type 2 (insulin-resistant) diabetes mellitus and signs of androgen excess. The exact cause of this syndrome is unknown. | Overview of Achard Thiers Syndrome. Achard-Thiers syndrome is a rare disorder that occurs primarily in postmenopausal women and is characterized by type 2 (insulin-resistant) diabetes mellitus and signs of androgen excess. The exact cause of this syndrome is unknown. | 8 | Achard Thiers Syndrome |
nord_8_1 | Symptoms of Achard Thiers Syndrome | The original description and usual emphasis in this syndrome is on the affected individual as a bearded woman with diabetes mellitus. In older women, the first clinical symptoms are often those associated with classic diabetes and may include abnormally high blood glucose due to the body's inability to utilize insulin properly.Those affected may also have abnormally high levels of glucose in the urine, frequent urination, excessive thirst and hunger, and weight loss. Other signs of the syndrome are directly due to the overproduction of androgens, and may include an increase in body hair, particularly on the face, chest, back, and other areas, receding hairline, deepening of the voice, enlargement of the clitoris; infertility; and obesity. Typically, a detailed patient history shows the development of infrequent or very light menstrual periods in someone who has previously had normal menstruation (oligomenorrhea) or the absence of menstrual periods (amenorrhea) soon after the first menstrual period (menarche), commonly followed by development of excess body hair (hirsutism) and rapid weight gain. Many women with the disorder have acanthosis nigricans.The constellation of clinical androgen excess and failure of the blood sugar control system to work properly (hyperinsulinemia) is now commonly identified earlier in a woman's life, typically during adolescence and young adulthood, as polycystic ovary syndrome or PCOS. | Symptoms of Achard Thiers Syndrome. The original description and usual emphasis in this syndrome is on the affected individual as a bearded woman with diabetes mellitus. In older women, the first clinical symptoms are often those associated with classic diabetes and may include abnormally high blood glucose due to the body's inability to utilize insulin properly.Those affected may also have abnormally high levels of glucose in the urine, frequent urination, excessive thirst and hunger, and weight loss. Other signs of the syndrome are directly due to the overproduction of androgens, and may include an increase in body hair, particularly on the face, chest, back, and other areas, receding hairline, deepening of the voice, enlargement of the clitoris; infertility; and obesity. Typically, a detailed patient history shows the development of infrequent or very light menstrual periods in someone who has previously had normal menstruation (oligomenorrhea) or the absence of menstrual periods (amenorrhea) soon after the first menstrual period (menarche), commonly followed by development of excess body hair (hirsutism) and rapid weight gain. Many women with the disorder have acanthosis nigricans.The constellation of clinical androgen excess and failure of the blood sugar control system to work properly (hyperinsulinemia) is now commonly identified earlier in a woman's life, typically during adolescence and young adulthood, as polycystic ovary syndrome or PCOS. | 8 | Achard Thiers Syndrome |
nord_8_2 | Causes of Achard Thiers Syndrome | These syndromes appear to be transmitted within families. Approximately 50% of the sisters of women with PCOS have some form of the syndrome. The exact mechanism of genetic transmission is unknown. | Causes of Achard Thiers Syndrome. These syndromes appear to be transmitted within families. Approximately 50% of the sisters of women with PCOS have some form of the syndrome. The exact mechanism of genetic transmission is unknown. | 8 | Achard Thiers Syndrome |
nord_8_3 | Affects of Achard Thiers Syndrome | Achard-Thiers Syndrome is a rare disorder that affects females after menopause. The incidence of this disorder in the general population is not known. | Affects of Achard Thiers Syndrome. Achard-Thiers Syndrome is a rare disorder that affects females after menopause. The incidence of this disorder in the general population is not known. | 8 | Achard Thiers Syndrome |
nord_8_4 | Related disorders of Achard Thiers Syndrome | Symptoms of the following disorders can be similar to those of Achard-Thiers. Comparisons may be useful for a differential diagnosis:Acquired adrenogenital syndrome is a rare endocrine disorder that occurs because of a tumor in the adrenal glands which causes the overproduction of androgens. In an adult female the symptoms may include a male pattern of hair growth, loss of hair on the head, acne, deepening voice, and abnormally large muscles.Empty sella syndrome is a rare brain disorder that may be inherited or acquired. The acquired form of the disease may occur as a result of a tumor in the pituitary gland or radiation to that area. Symptoms may include headaches, impaired vision, and/or obesity. Some people with empty sella syndrome cannot tolerate cold temperatures and may also have abnormally high blood pressure (hypertension). In women this disorder is associated with an increase in body hair and a male pattern of hair growth. (For more information on this disorder, choose “Empty Sella” as your search term in the Rare Disease Database.)Diabetes is a complex endocrine disease that occurs when the pancreas does not produce enough insulin or the body is not able to use insulin properly. There are two main groups of diabetes: Type I (insulin-dependent) and type II (noninsulin-dependent). The symptoms of diabetes usually include frequent urination, extreme thirst, constant hunger, and unexplained weight loss. Long-term complications of diabetes may affect many organs of the body including the nervous system, heart, kidneys, and eyes. (For more information on this disorder, choose “Diabetes” as your search term in the Rare Disease Database.)Polycystic ovary syndrome (PCOS) affects women and is a complex of symptoms that are not necessarily all present in all cases. Some, but not all, affected women have multiple cysts on the ovaries. Other characteristics include absent or irregular menstruation, failure of the ovary to release eggs (anovulation), elevated levels of the male hormones known as androgens (hyperandrogenism), excessive amounts of body hair (hirsutism), a high rate of miscarriage, and infertility. Three criteria often used for a diagnosis are menstrual irregularity, hyperandrogenism, and exclusion of other disease. There is some evidence that PCOS is an inherited condition. | Related disorders of Achard Thiers Syndrome. Symptoms of the following disorders can be similar to those of Achard-Thiers. Comparisons may be useful for a differential diagnosis:Acquired adrenogenital syndrome is a rare endocrine disorder that occurs because of a tumor in the adrenal glands which causes the overproduction of androgens. In an adult female the symptoms may include a male pattern of hair growth, loss of hair on the head, acne, deepening voice, and abnormally large muscles.Empty sella syndrome is a rare brain disorder that may be inherited or acquired. The acquired form of the disease may occur as a result of a tumor in the pituitary gland or radiation to that area. Symptoms may include headaches, impaired vision, and/or obesity. Some people with empty sella syndrome cannot tolerate cold temperatures and may also have abnormally high blood pressure (hypertension). In women this disorder is associated with an increase in body hair and a male pattern of hair growth. (For more information on this disorder, choose “Empty Sella” as your search term in the Rare Disease Database.)Diabetes is a complex endocrine disease that occurs when the pancreas does not produce enough insulin or the body is not able to use insulin properly. There are two main groups of diabetes: Type I (insulin-dependent) and type II (noninsulin-dependent). The symptoms of diabetes usually include frequent urination, extreme thirst, constant hunger, and unexplained weight loss. Long-term complications of diabetes may affect many organs of the body including the nervous system, heart, kidneys, and eyes. (For more information on this disorder, choose “Diabetes” as your search term in the Rare Disease Database.)Polycystic ovary syndrome (PCOS) affects women and is a complex of symptoms that are not necessarily all present in all cases. Some, but not all, affected women have multiple cysts on the ovaries. Other characteristics include absent or irregular menstruation, failure of the ovary to release eggs (anovulation), elevated levels of the male hormones known as androgens (hyperandrogenism), excessive amounts of body hair (hirsutism), a high rate of miscarriage, and infertility. Three criteria often used for a diagnosis are menstrual irregularity, hyperandrogenism, and exclusion of other disease. There is some evidence that PCOS is an inherited condition. | 8 | Achard Thiers Syndrome |
nord_8_5 | Diagnosis of Achard Thiers Syndrome | The diagnosis of Achard-Thiers syndrome should be suspected based on the clinical findings. Because affected women are hyperinsulinemic, a two-hour oral glucose tolerance test shows abnormally elevated levels of glucose in the blood. | Diagnosis of Achard Thiers Syndrome. The diagnosis of Achard-Thiers syndrome should be suspected based on the clinical findings. Because affected women are hyperinsulinemic, a two-hour oral glucose tolerance test shows abnormally elevated levels of glucose in the blood. | 8 | Achard Thiers Syndrome |
nord_8_6 | Therapies of Achard Thiers Syndrome | TreatmentDiabetes may be managed by diet and/or insulin or other medications, as required. Cosmetic measures (for example, waxing and electrolysis) can be used to facilitate hair removal. For younger women with PCOS, treatment with an oral contraceptive is the most common therapy, whereas for postmenopausal women with Achard-Thiers syndrome, hormone replacement therapy is usually recommended. Antiandrogens have also been used. | Therapies of Achard Thiers Syndrome. TreatmentDiabetes may be managed by diet and/or insulin or other medications, as required. Cosmetic measures (for example, waxing and electrolysis) can be used to facilitate hair removal. For younger women with PCOS, treatment with an oral contraceptive is the most common therapy, whereas for postmenopausal women with Achard-Thiers syndrome, hormone replacement therapy is usually recommended. Antiandrogens have also been used. | 8 | Achard Thiers Syndrome |
nord_9_0 | Overview of Achondrogenesis | SummaryAchondrogenesis is a group of rare skeletal dysplasias characterized by extreme shortening of the arms and legs in relation to the trunk, abnormal development of ribs, vertebra and other skeletal abnormalities. The health problems associated with these conditions are life-threatening and most affected infants are stillborn or die shortly after birth due to respiratory failure. All types of achondrogenesis are genetic conditions; type IA and type IB, are autosomal recessive disorders, whereas achondrogenesis type II is an autosomal dominant disorder. All types of achondrogenesis are very severe skeletal dysplasias usually detected by prenatal ultrasound examination as early as week 14-17 of gestational age.IntroductionThe term achondrogenesis was first used in the medical literature in 1952 by an Italian pathologist named Marco Fraccaro. Achondrogenesis is derived from Greek and means “not producing cartilage.” Achondrogenesis belongs to group of skeletal dysplasias, (also called osteochondrodysplasias), a broad term for a group of disorders (about 450 clinical diagnoses) characterized by abnormal growth or development of cartilage and bone. | Overview of Achondrogenesis. SummaryAchondrogenesis is a group of rare skeletal dysplasias characterized by extreme shortening of the arms and legs in relation to the trunk, abnormal development of ribs, vertebra and other skeletal abnormalities. The health problems associated with these conditions are life-threatening and most affected infants are stillborn or die shortly after birth due to respiratory failure. All types of achondrogenesis are genetic conditions; type IA and type IB, are autosomal recessive disorders, whereas achondrogenesis type II is an autosomal dominant disorder. All types of achondrogenesis are very severe skeletal dysplasias usually detected by prenatal ultrasound examination as early as week 14-17 of gestational age.IntroductionThe term achondrogenesis was first used in the medical literature in 1952 by an Italian pathologist named Marco Fraccaro. Achondrogenesis is derived from Greek and means “not producing cartilage.” Achondrogenesis belongs to group of skeletal dysplasias, (also called osteochondrodysplasias), a broad term for a group of disorders (about 450 clinical diagnoses) characterized by abnormal growth or development of cartilage and bone. | 9 | Achondrogenesis |
nord_9_1 | Symptoms of Achondrogenesis | Achondrogenesis is characterized by premature birth, abnormal accumulation of fluid in the body (hydrops fetalis), and a head that may be abnormal in shape and less ossified. The head may look disproportionately large, because the body is small. In addition, affected individuals have extremely short limbs and ribs, short neck, flat vertebrae and many other bones of the skeleton are not properly developed. In infants born with this disorder the abdomen is prominent and the thoracic cage is small. Other abnormalities are incomplete closure of the roof of the mouth (cleft palate), corneal clouding, and ear deformities. The disorder is life-threatening either before birth or shortly after birth usually due to underdeveloped thorax and small lungs.Achondrogenesis type IA (Houston-Harris type) is characterized by varying facial abnormalities (flat face, protruding eyes and protruding tongue or only minor facial anomalies), short trunk and limbs, short beaded ribs and thin skull bones (deficient ossification of the skull). Bone formation is abnormal in the spine, pelvis and extremities, but the degree of the severity of skeletal involvement may be variable. However, small thorax leads to underdevelopment of lungs and death soon after birth.Achondrogenesis type IB (Fraccaro type) is characterized by short trunk and limbs, narrow chest, and prominent abdomen. Affected infants may have a protrusion around the belly-button (umbilical hernia), or near the groin (inguinal hernia), and have short fingers and toes with feet turned inward. The face may be flat, the palate may be cleft and the neck is usually short. In some cases, the soft tissue of the neck may be abnormally thickened. Achondrogenesis type IB is sub-classified as a sulfation disorder, a small group of disorders associated with mutations in the gene SLC26A2. This group includes diastrophic dysplasia and recessive multiple epiphyseal dysplasia, which are milder conditions. It is important to note that one diagnosis does not change to another while the baby is developing, even if the genetic changes are located in the same gene.Achondrogenesis type II (Langer-Saldino type) is characterized by a narrow chest, abnormally small or short bones in the arms and/or legs, thin ribs, flat vertebra or deficient ossification of vertebral bodies, underdeveloped lungs, small chin, cleft palate and club feet. Bone formation is abnormal in the spine and pelvis. Abnormal accumulation of fluid may occur (hydrops fetalis) and the abdomen may be enlarged. | Symptoms of Achondrogenesis. Achondrogenesis is characterized by premature birth, abnormal accumulation of fluid in the body (hydrops fetalis), and a head that may be abnormal in shape and less ossified. The head may look disproportionately large, because the body is small. In addition, affected individuals have extremely short limbs and ribs, short neck, flat vertebrae and many other bones of the skeleton are not properly developed. In infants born with this disorder the abdomen is prominent and the thoracic cage is small. Other abnormalities are incomplete closure of the roof of the mouth (cleft palate), corneal clouding, and ear deformities. The disorder is life-threatening either before birth or shortly after birth usually due to underdeveloped thorax and small lungs.Achondrogenesis type IA (Houston-Harris type) is characterized by varying facial abnormalities (flat face, protruding eyes and protruding tongue or only minor facial anomalies), short trunk and limbs, short beaded ribs and thin skull bones (deficient ossification of the skull). Bone formation is abnormal in the spine, pelvis and extremities, but the degree of the severity of skeletal involvement may be variable. However, small thorax leads to underdevelopment of lungs and death soon after birth.Achondrogenesis type IB (Fraccaro type) is characterized by short trunk and limbs, narrow chest, and prominent abdomen. Affected infants may have a protrusion around the belly-button (umbilical hernia), or near the groin (inguinal hernia), and have short fingers and toes with feet turned inward. The face may be flat, the palate may be cleft and the neck is usually short. In some cases, the soft tissue of the neck may be abnormally thickened. Achondrogenesis type IB is sub-classified as a sulfation disorder, a small group of disorders associated with mutations in the gene SLC26A2. This group includes diastrophic dysplasia and recessive multiple epiphyseal dysplasia, which are milder conditions. It is important to note that one diagnosis does not change to another while the baby is developing, even if the genetic changes are located in the same gene.Achondrogenesis type II (Langer-Saldino type) is characterized by a narrow chest, abnormally small or short bones in the arms and/or legs, thin ribs, flat vertebra or deficient ossification of vertebral bodies, underdeveloped lungs, small chin, cleft palate and club feet. Bone formation is abnormal in the spine and pelvis. Abnormal accumulation of fluid may occur (hydrops fetalis) and the abdomen may be enlarged. | 9 | Achondrogenesis |
nord_9_2 | Causes of Achondrogenesis | Each type of achondrogenesis is caused by a mutation in a specific gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The gene mutations that cause achondrogenesis type IA and type IB are inherited in an autosomal recessive manner. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person is a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.All individuals carry several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than non-consanguineous parents to carry the same abnormal gene, which increases the risk to have children with a rare recessive genetic disorder.Achondrogenesis type IA is caused by mutations in the TRIP11 gene. Achondrogenesis type IB is caused by mutations in the SLC26A2 gene. These two genes are required for the efficient cellular transport of certain cartilage proteins needed to build skeleton and other tissues. Mutations of the TRIP11 gene results in deficiency of the Golgi microtubule associated protein 210. This protein is found in most cell types of the body. The protein product of the SLC26A2 gene is a sulfate transporter that is involved in the proper development and function of cartilage. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone.The gene mutation that causes achondrogenesis type II is caused by so called autosomal dominant change in the COL2A1 gene. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. Most cases of achondrogenesis type II are caused by a new (de novo) mutation in the COL2A1 gene, which means that risk for the parents of an affected infant to get another child with the same disease is not higher then 1%. This gene encodes collagen type II. Collagen is one of the most abundant proteins in the body and a major building block of connective tissue, which is the material between cells of the body that gives the tissue form and strength. There are many different types of collagen, which are indicated by Roman numerals. Collagen type II is most prevalent in cartilage and the jelly-like fluid that fills the center of the eye (vitreous). Collagen is also found in bone.There are very rare cases where siblings of infants with achondrogenesis type II have been affected. This is most likely due to the presence of more than one cell line in the egg or sperm from a parent (germline mosaicism). In germline mosaicism, some of a parent’s reproductive cells (germ cells) carry the COL2A1 gene mutation, while other germ cells contain normal COL2A1 genes (“mosaicism”). The other cells in the parent’s body do not have the mutation, so these parents are unaffected. As a result, one or more of the parent’s children may inherit the germ cell gene COL2A1 mutation, leading to the development of achondrogenesis II, while the parent does not have this disorder (asymptomatic carrier). Germline mosaicism may be suspected when apparently unaffected parents have more than one child with the same autosomal dominant genetic condition. The likelihood of a parent passing on a mosaic germline mutation to a child depends upon the percentage of the parent’s germ cells that have the mutation versus the percentage that do not. There is no test for germline mutation prior to pregnancy. Testing during early pregnancy may be available and is best discussed directly with a genetic specialist. | Causes of Achondrogenesis. Each type of achondrogenesis is caused by a mutation in a specific gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The gene mutations that cause achondrogenesis type IA and type IB are inherited in an autosomal recessive manner. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person is a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.All individuals carry several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than non-consanguineous parents to carry the same abnormal gene, which increases the risk to have children with a rare recessive genetic disorder.Achondrogenesis type IA is caused by mutations in the TRIP11 gene. Achondrogenesis type IB is caused by mutations in the SLC26A2 gene. These two genes are required for the efficient cellular transport of certain cartilage proteins needed to build skeleton and other tissues. Mutations of the TRIP11 gene results in deficiency of the Golgi microtubule associated protein 210. This protein is found in most cell types of the body. The protein product of the SLC26A2 gene is a sulfate transporter that is involved in the proper development and function of cartilage. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone.The gene mutation that causes achondrogenesis type II is caused by so called autosomal dominant change in the COL2A1 gene. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. Most cases of achondrogenesis type II are caused by a new (de novo) mutation in the COL2A1 gene, which means that risk for the parents of an affected infant to get another child with the same disease is not higher then 1%. This gene encodes collagen type II. Collagen is one of the most abundant proteins in the body and a major building block of connective tissue, which is the material between cells of the body that gives the tissue form and strength. There are many different types of collagen, which are indicated by Roman numerals. Collagen type II is most prevalent in cartilage and the jelly-like fluid that fills the center of the eye (vitreous). Collagen is also found in bone.There are very rare cases where siblings of infants with achondrogenesis type II have been affected. This is most likely due to the presence of more than one cell line in the egg or sperm from a parent (germline mosaicism). In germline mosaicism, some of a parent’s reproductive cells (germ cells) carry the COL2A1 gene mutation, while other germ cells contain normal COL2A1 genes (“mosaicism”). The other cells in the parent’s body do not have the mutation, so these parents are unaffected. As a result, one or more of the parent’s children may inherit the germ cell gene COL2A1 mutation, leading to the development of achondrogenesis II, while the parent does not have this disorder (asymptomatic carrier). Germline mosaicism may be suspected when apparently unaffected parents have more than one child with the same autosomal dominant genetic condition. The likelihood of a parent passing on a mosaic germline mutation to a child depends upon the percentage of the parent’s germ cells that have the mutation versus the percentage that do not. There is no test for germline mutation prior to pregnancy. Testing during early pregnancy may be available and is best discussed directly with a genetic specialist. | 9 | Achondrogenesis |
nord_9_3 | Affects of Achondrogenesis | Achondrogenesis affect males and females in equal numbers. Achondrogenesis type IA and type IB are very rare disorders and prevalence for them is unknown. Achondrogenesis type II occurs in approximately 1/40,000-1/60,000 newborns. | Affects of Achondrogenesis. Achondrogenesis affect males and females in equal numbers. Achondrogenesis type IA and type IB are very rare disorders and prevalence for them is unknown. Achondrogenesis type II occurs in approximately 1/40,000-1/60,000 newborns. | 9 | Achondrogenesis |
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Dataset Card for ReCOP
What's for?
The data for ReCOP is sourced from the National Organization for Rare Disorders (NORD) database, which compiles reports on rare diseases. NORD is committed to the identification, treatment, and cure of rare diseases through education, advocacy, research, and service programs. The primary objective of developing ReCOP using the NORD database is to provide comprehensive expertise on rare diseases for LLMs. This expertise can be leveraged to enhance the diagnostic capabilities of LLMs through retrieval-augmented generation.
Corpus Overview
ReCOP divides each rare disease report into chunks: overview, symptoms, causes, effects, related disorders, diagnosis, and standard therapies. Each property of the disease corresponds to a specific chunk in ReCOP. In this manner, ReCOP generates 9268 chunks based on the reports of 1324 rare diseases for the NORD database, with each report producing seven chunks corresponding to the properties of a rare disease.
Using ReCOP for Retrieval Augmentation Generations
Simply follow our benchmark repository ReDis-QA-Bench to run the retrieval augmentation generations on the ReDis-QA dataset:
git clone https://github.com/guanchuwang/redis-bench.git
cd redis-bench
bash rag-bench/scripts/run_exp.sh
Benchmark Results of Retrieval Augmentation Generations
Benchmark results of retrieval augmentation generations based on ReCOP, where the LLMs take Llama-2-7B-chat, Mistral-7B-instruct-v0.2, Phi-3-7B-instruct, Gemmma-1.1-7B-it, and Qwen-2-7B-Instruct.
Citation Information
If you find this corpus useful to your project, we appreciate you citing this work:
@article{wang2024assessing,
title={Assessing and Enhancing Large Language Models in Rare Disease Question-answering},
author={Wang, Guanchu and Ran, Junhao and Tang, Ruixiang and Chang, Chia-Yuan and Chuang, Yu-Neng and Liu, Zirui and Braverman, Vladimir and Liu, Zhandong and Hu, Xia},
journal={arXiv preprint arXiv:2408.08422},
year={2024}
}
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