TaoMedAI/RareMedData huggingface dataset:
46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency (ORPHA:168558)
A rare, genetic, developmental defect during embryogenesis disorder characterized by severe, early-onset, salt-wasting adrenal insufficiency and ambiguous/female external genitalia (irrespective of chromosomal sex) due to mutations in the CYP11A1 gene. Milder cases may present delayed onset of adrenal gland dysfunction and genitalia phenotype may range from normal male to female in individuals with 46,XY karyotype. Imaging studies reveal hypoplastic/absent adrenal glands and biochemical findings include low serum cortisol, mineralocorticoids, androgens, and sodium, with elevated potassium levels.
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome (ORPHA:168563)
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is a rare, genetic, developmental defect during embryogenesis disorder characterized by partial (unilateral testis, persistence of Müllerian duct structures) or complete (streak gonads only) gonadal dysgenesis, usually manifesting with primary amenorrhea in individuals with female phenotype but 46,XY karyotype, and sensorimotor dysmyelinating minifascicular polyneuropathy, which presents with numbness, weakness, exercise-induced muscle cramps, sensory disturbances and reduced/absent deep tendon reflexes. Germ cell tumors (seminoma, dysgerminoma, gonadoblastoma) may develop from the gonadal tissue.
46,XY ovotesticular difference of sex development (ORPHA:325345)
46,XY ovotesticular disorder of sex development is a rare, genetic disorder of sex development characterized by either the coexistence of both male and female reproductive gonads or, more frequently, by the presence of one or both gonads containing a mixture of both testicular and ovarian tissue (ovotestes) in an individual with a normal male 46, XY karyotype. External genitalia are usually ambiguous, but can range from normal male to normal female and if a uterus and/or fallopian tubes are present, they are generally hypoplastic. Cryptorchidism, hypospadias, infertility and increased risk of gonadal tumours are frequently associated.
47,XYY syndrome (ORPHA:8)
A rare sex chromosome aneuploidy where males receive an additional Y chromosome, that is characterized clinically by tall stature evident from childhood, macrocephaly, facial features (mild hypertelorism, low set ears, a mildly flat malar region), speech delay and an increased risk for social and emotional difficulties, attention deficit hyperactive disorder and autistic spectrum disorder.
48,XXXY syndrome (ORPHA:96263)
The 48,XXXY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of two extra X chromosomes in males.
Epidemiology
There is an annual incidence of 1/50,000 male births.
Clinical description
The 48,XXXY syndrome differs from Klinefelter syndrome by the presence of moderate intellectual deficit (average IQ of 50), more marked genital hypoplasia (microorchidism, micropenis, hypoplasia of the scrotum) and by more frequently observed facial dysmorphism (flat nose, epicanthus, prognathism, short neck, hypertelorism, facial asymmetry). Other dysmorphic characteristics (clinodactyly of the fifth finger, coxa valga, etc.) are often associated with this syndrome. Congenital skeletal malformations (kyphoscoliosis, radioulnar synostosis, epiphyseal dysplasia) canalso be present in addition to genital anomalies (cryptorchidism) and gynecomastia. With age, other manifestations can also appear such as arthropathies, obesity, behavioral problems (hyperactivity, irritability, anxiety, immaturity, passivity, anger, communication and socialization problems) and language retardation.
Etiology
The most likely etiology is the non disjunction of homologous chromosomes (during the first meiotic division) or sister chromatids (during the second meiotic division) in the parental germ cells. There is no known factor responsible for or favoring the development of this syndrome.
Diagnostic methods
The metaphase karyotype allows for the confirmation of a clinical diagnosis. Mosaicism with other polygonosomies is not uncommon (48,XXXY/ 48,XXYY/ 49,XXXXY).
Differential diagnosis
Differential diagnoses include other aneuploidies, such as Klinefelter syndrome (47,XXY), 48,XXYY syndrome and 49,XXXXY syndrome (see these terms).
Antenatal diagnosis
Antenatal diagnosis is possible by amniocentesis.
Genetic counseling
The risk of recurrence is very low as cases of 48,XXXY are sporadic.
Management and treatment
Management needs to be handled by a multidisciplinary team and includes the treatment of cardiac and skeletal malformations, management of sensory, neurological, hormonal (testosterone-based hormone therapy), metabolic (supervising obesity), psychological and psychiatric care and dental follow-up.
Prognosis
Patients have an essentially normal life expectancy but will need to attend regular medical visits, in particular for their endocrine and infectious problems, and to undergo regular psychiatric monitoring.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Carole CORSINI  - Pr Pierre SARDA
48,XYYY syndrome (ORPHA:99329)
A rare Y chromosome number anomaly that affects only males and is characterized by mild-moderate developmental delay (especially speech), normal to mild intellectual disability, large, irregular teeth with poor enamel, tall stature and acne. Radioulnar synostosis and clinodactyly have also been associated. Boys generally present normal genitalia, while hypogonadism and infertility is frequently reported in adult males.
49,XXXXY syndrome (ORPHA:96264)
The 49,XXXXY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of three extra X chromosomes in males.
Epidemiology
It has an annual incidence of 1/85,000 to 1/100,000 male births.
Clinical description
The 49,XXXXY syndrome differs from Klinefelter syndrome by its variable IQ with an often subtle intellectual deficit in childhood but a progressive (moderate to severe) deterioration with age (IQ varying between 70 and 20), by the absence of tall stature with delayed growth often already visible in utero and under the third percentile after birth, and sometimes by a small stature and a deficit in growth hormones. Hypogonadism is severe with a micropenis, microorchidism, hypoplasia of the scrotum and cryptorchidism. Gynecomastia is uncommon. Remarkable facial dysmorphism (hypertelorism, large flat nose with a depressed nasal curvature, upslanting palpebral fissures, epicanthus, prognathism, folded-over ears, short neck) and other dysmorphic characteristics (cubitus valgus, flat feet, clinodactyly of the fifth finger, joint laxity) appear frequently. Congenital heart defects (arterial canal) as well as skeletal defects (radioulnar synostosis, epiphyseal dysplasia, coxa valga, kyphoscoliosis, hip and knee dislocation), cerebral (hypoplastic corpus callosum, arhinencephaly) and renal defects (renal hypoplasia) can also be present. Axial hypotonia is often seen in children. With age, the intellectual deficit worsens and is associated with a major delay in language development. Strabismus or severe and progressive myopia can occur which can lead to declining vision. Behavioral problems such as shyness can also become apparent.
Etiology
The etiology is the non disjunction of homologous chromosomes (during the first meiotic division) or of sister chromatids (during the second meiotic division) in the maternal germ cells. There is no known factor responsible for or favoring the appearance of this syndrome.
Diagnostic methods
The metaphase karyotype allows for the confirmation of a clinical diagnosis.
Antenatal diagnosis
Antenatal diagnosis is possible by an amniocentesis screening for a wide range of conditions.
Genetic counseling
The risk of recurrence is very unlikely as cases of 49,XXXXY are sporadic.
Management and treatment
Management needs to be handled by a multidisciplinary team and includes the treatment of cardiac and skeletal defects, the monitoring of psychomotor development with physiotherapy, psychomotricity, speech therapy, orthopedic and sensory management (ophthalmological examination), neurological, hormonal (if necessary) and psychological care and regular dental follow-up.
Prognosis
Patients have an essentially normal life expectancy but will need to attend regular medical visits.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Carole CORSINI  - Pr Pierre SARDA
49,XXXYY syndrome (ORPHA:261534)
49,XXXYY syndrome is a rare gonosome anomaly syndrome characterized by a eunuchoid habitus with gynecoid fat distribution and shape, normal to tall stature, moderate to severe intellectual disability, distinctive facial features (e.g. prominent forehead, epicanthic folds, broad nasal bridge, prognathism), gynecomastia, hypogonadism, cryptorchidism, small penis and behavioral abnormalities (incl. solitary, passive disposition but prone to aggressive outbursts, autistic). Skeletal malformations, such as delayed bone age, fifth finger clinodactyly, elbow malformations and slow molar development, may also be associated.
49,XYYYY syndrome (ORPHA:99330)
A rare Y chromosome number anomaly with a variable phenotype mainly characterized by moderate to severe intellectual disability, speech delay, hypotonia, and mild dysmorphic features, including facial asymmetry, hypertelorism, bilateral low set 'lop' ears, and micrognatia. Skeletal abnormalities (such as skull deformities, radioulnar synostosis, elbow flexion, clinodactyly, brachydactyly) and behavourial problems have also been associated with this condition. Genitalia are normal at birth, although hypogonadism and azoospermia has been reported in adults.
4p16.3 microduplication syndrome (ORPHA:96072)
4p16.3 microduplication syndrome is a rare genetic syndrome that results from the partial duplication of the short arm of chromosome 4. It has a highly variable phenotype, principally characterized by psychomotor and language delay, seizures and dysmorphic features such as high forehead with frontal bossing, hypertelorism, prominent glabella, long narrow palpebral fissures, low set ears and short neck. Eye abnormalities (glaucoma, irregular iris pigmentation, hyperopia) have also been reported.
4q21 microdeletion syndrome (ORPHA:238750)
The 4q21 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, progressive growth restriction, severe intellectual deficit and absent or severely delayed speech.
Epidemiology
It has been reported in nine unrelated patients.
Clinical description
The most common facial feature includes high or broad forehead, hypertelorism and short philtrum. Short hands and feet are frequently observed.
Etiology
This microdeletion was identified by comparative genomic hybridisation (CGH) microarray. The critical region encompasses two candidate genes, PRKG2 and RASGEF1B, in which haploinsufficiency could participate to the phenotype.

                            Last update: 
                            October 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
4q25 proximal deletion syndrome (ORPHA:502437)
A partial deletion of the long arm of chromosome 4 characterized by complex behavioral difficulties, developmental and delay/ intellectual disability, and minor dysmorphic features, including subtle facial asymmetry (most prominent in the mandible), mild hypotelorism, long nasal bridge, small low-set ears, narrow mouth, and mild hand deformities, such as bilateral short 5th metacarpals, and short hands.
5-fluorouracil poisoning (ORPHA:217064)
A rare intoxication caused by the prolonged, low-dose administration of 5-fluorouracil, which is the mainstay of both adjuvant and advanced-disease chemotherapy regimens in colon cancer. 5-fluorouracil poisoning is characterized by gastrointestinal (nausea, emesis, diarrhea, anorexia, stomatitis) and hematologic (myelosuppression) toxicities as well as mucositis, alopecia and, occasionally, palmar-plantar dysesthesia (more commonly known as hand-foot syndrome). Women have been reported to experience more 5-fluorouracil-related toxicity than men.
5-oxoprolinase deficiency (ORPHA:33572)
A very heterogeneous condition characterized by 5-oxoprolinuria.
Epidemiology
It has been detected in eight patients worldwide. All affected patients have been identified because of 5-oxoprolinuria.
Clinical description
Symptoms reported in individual patients include renal stone formation, enterocolitis, intellectual deficiency, neonatal hypoglycemia, microcytic anemia and microcephaly.
Etiology
5-Oxoprolinase catalyses a step in the gamma-glutamyl cycle (glutathione metabolism).
Diagnostic methods
The diagnosis is based on the finding of 5-oxoprolinuria and on the low activity of 5-oxoprolinase.
Differential diagnosis
Other causes of 5-oxoprolinuria include glutathione synthetase deficiency (see this term), diet (certain infant formulas and tomato juice), severe burns, Stevens-Johnson syndrome (see this term), inborn errors of metabolism not involving the gamma-glutamyl cycle, e.g. X-linked ornithine trancarbamylase deficiency, urea cycle defects, or tyrosinemia, as well as homocystinuria (see these terms), drug metabolism (paracetamol, vigabatrin, flucloxacillin, netilmicin), prematurity, malnutrition, pregnancy and nephropatic cystinosis.
Genetic counseling
The disease is transmitted as an autosomal recessive trait.
Management and treatment
No specific treatment has been proposed or tested.
Prognosis
The prognosis is difficult to predict as only eight patients with different clinical symptoms have been described.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Dr Agne LARSSON  - Dr Ellinor RISTOFF
5p13 microduplication syndrome (ORPHA:329802)
A rare partial autosomal trisomy/tetrasomy characterized by global developmental delay, intellectual disability, autistic behavior, muscular hypotonia, macrocephaly and facial dysmorphism (frontal bossing, short palpebral fissures, low set, dysplastic ears, short or shallow philtrum, high arched or narrow palate, micrognathia). Other associated clinical features include sleep disturbances, seizures, aplasia/hypoplasia of the corpus callosum, skeletal abnormalities (large hands and feet, long fingers and toes, talipes).
5q14.3 microdeletion syndrome (ORPHA:228384)
The newly described 5q14.3 microdeletion syndrome includes severe intellectual deficit with no speech, stereotypic movements and epilepsy.
Epidemiology
To date, fourteen patients have been reported.
Clinical description
Miscellaneous dysmorphic facial features are present in all cases, but some common features are noticed, high and wide forehead, pronounced eyebrows, anteverted nostrils, short and prominent philtrum, down-turned corners of the mouth and small chin. Stereotypic movements and poor eye contact are present in many patients, suggesting the diagnosis of autism spectrum disorder. In most patients brain imaging is reported to be abnormal, including anomalies of the corpus callosum, enlarged ventricles, periventricular white matter, hyperintensities and cortical atrophy.
Etiology
The microdeletion was identified by microarray-based comparative genomic hybridization (CGH). The size of deletions varies, the minimal common deleted region encompasses only MEF2C, suggesting that haploinsufficiency of MEF2C is responsible for the phenotype.

                            Last update: 
                            May 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
5q35 microduplication syndrome (ORPHA:228415)
The newly described 5q35 microduplication syndrome is associated with microcephaly, short stature, developmental delay and delayed bone maturation.
Epidemiology
It has been reported in two unrelated patients.
Clinical description
There is no remarkable facial dysmorphism. The clinical picture is opposite to that of patients with Sotos syndrome (macrocephaly, overgrowth and advanced bone age; see this term).
Etiology
This microduplication was identified by microarray-based comparative genomic hybridization (aCGH). The breakpoints of the duplication in both patients map to the proximal and distal low-copy repeats (LCRs), which flank the Sotos critical region. These findings support a non-allelic homologous recombination (NAHR) as the mechanism of duplication, and a dosage effect of the Sotos gene NSD1 (5q35).

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
6-phosphogluconate dehydrogenase deficiency (ORPHA:99135)
A rare constitutional hemolytic anemia characterized by a low 6-phosphogluconate dehydrogenase activity in the erythrocytes, which clinically manifests with a well-compensated chronic nonspherocytic hemolytic anemia and transient hemolytic periods with jaundice.
6p22 microdeletion syndrome (ORPHA:251046)
6p22 microdeletion syndrome is a newly described syndrome associated with a variable clinical phenotype including developmental delay, facial dysmorphism, short neck and diverse malformations.
Epidemiology
Eight cases have been reported to date.
Clinical description
The most common facial features include eye anomalies: strabismus, deeply set eyes, and epicanthic folds and ear anomalies such as over-folded helices and low-set ears. This microdeletion was identified by fluorescence in situ hybridization (FISH) or comparative genomic hybridisation (CGH) microarray. Reported patients have deletions of variable size. The critical region for the 6p22 deletion phenotype is 2.2 Mb and encompasses 12 genes; their function is still largely unknown.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
6q terminal deletion syndrome (ORPHA:75857)
A rare partial deletion of the long arm of chromosome 6 characterized by a variable clinical phenotype that includes a characteristic craniofacial dysmorphism (including microcephaly, broad nose with prominent nasal root and bulbous nasal tip, large ears that may be malformed and low-set, characteristic downturned mouth, and short neck), global development delay, intellectual disability, and variable, non-specific, congenital malformations. Muscular hypotonia, seizures, retinal anomalies, and variable brain abnormalities have been reported in association.
6q16 microdeletion syndrome (ORPHA:171829)
A rare Prader-Willi like syndrome due to an interstitial deletion located at 6q16.1q16.2 and characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.
6q25.2q25.3 microdeletion syndrome (ORPHA:251056)
6q25 microdeletion syndrome is a recently described syndrome characterized by developmental delay, facial dysmorphism and hearing loss.
Epidemiology
It has been clinically and molecularly characterized in 4 patients.
Clinical description
All of them presented with microcephaly, developmental delay, dysmorphic features and hearing loss, whereas two of them had agenesis of the corpus callosum. Dysmorphic features include midface hypoplasia, hypertelorism, broad nasal root and posteriorly rotated ears.
Etiology
This syndrome is caused by an interstitial deletion encompassing 6q25.2-q25.3. These de novo deletions were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). They have a variable size with the smallest region of overlap (SRO) of 3.52 Mb.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
7p22.1 microduplication syndrome (ORPHA:314034)
7p22.1 microduplication syndrome is a rare chromosomal anomaly syndrome, resulting from a partial interstitial microduplication of the short arm of chromosome 7, characterized by intellectual disability, psychomotor and speech delays, craniofacial dysmorphism (including macrocephaly, frontal bossing, hypertelorism, abnormally slanted palpebral fissures, anteverted nares, low-set ears, microretrognathia) and cryptorchidia. Cardiac (e.g., patent foramen ovale and atrial septal defect), as well as renal, skeletal and ocular abnormalities may also be associated.
7q11.23 microduplication syndrome (ORPHA:96121)
7q11.23 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 7 characterized by a highly variable phenotype that typically manifests with mild-moderate intellectual delay (patients could be in the normal range), speech disorders (particularly of expressive language), and distinctive craniofacial features (brachycephaly, broad forehead, straight eyebows, broad nasal tip, short philtrum, thin upper lip and facial asymmetry). Hypotonia, developmental coordination disorders, behavioral problems (such as anxiety, ADHD and oppositional disorders) and various congenital anomalies, such as heart defects, diaphragmatic hernia, renal malformations and cryptorchidism, are frequently presented. Neurological abnormalities (visible on MRI) have been reported.
7q31 microdeletion syndrome (ORPHA:251061)
7q31 microdeletion syndrome is a rare chromosomal anomaly characterized by speech and language disorder, predominantly presenting as an apraxia of speech, sometimes associated with oral motor dyspraxia, dysarthria, receptive and expressive language disorder, and hearing loss. Individuals with larger deletions in this region have also been reported to display intellectual disability and autism.
8p11.2 deletion syndrome (ORPHA:251066)
8p11.2 deletion syndrome is a contiguous gene syndrome characterized by the association of congenital spherocytosis, dysmorphic features, growth delay and hypogonadotropic hypogonadism.
Epidemiology
It has been described in 8 patients to date.
Clinical description
Common dysmorphic features include micrognathia, microcephaly, preauricular pits, high-arched palate and abnormal ears. All patients except one have intellectual deficit. In one patient, the association of anosmia was suggestive of Kallmann syndrome (see this term).
Etiology
The syndrome is caused by deletions of the proximal part of the short arm of chromosome 8 (8p11.1 to 8p21). The deletions can be cytogenetically detected and their size is variable. The loss of the ankyrin-1 gene (ANK1) results in congenital spherocytosis.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
8p23.1 duplication syndrome (ORPHA:251076)
8p23.1 duplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 8, with a highly variable phenotype, principally characterized by mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly).