bowang0911/MedQuAD huggingface dataset:
These resources address the diagnosis or management of Proteus syndrome:  - Gene Review: Gene Review: Proteus Syndrome  - Genetic Testing Registry: Proteus syndrome  - Proteus Syndrome Foundation: Diagnostic Criteria and FAQs   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals.  The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other health problems. More severely affected people have myopathy along with severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening.  Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome.  Cytochrome c oxidase deficiency is frequently fatal in childhood, although some individuals with mild signs and symptoms survive into adolescence or adulthood.
Cytochrome c oxidase deficiency is caused by mutations in one of at least 14 genes. In humans, most genes are found in DNA in the cell's nucleus (nuclear DNA). However, some genes are found in DNA in specialized structures in the cell called mitochondria. This type of DNA is known as mitochondrial DNA (mtDNA). Most cases of cytochrome c oxidase deficiency are caused by mutations in genes found within nuclear DNA; however, in some rare instances, mutations in genes located within mtDNA cause this condition.  The genes associated with cytochrome c oxidase deficiency are involved in energy production in mitochondria through a process called oxidative phosphorylation. The gene mutations that cause cytochrome c oxidase deficiency affect an enzyme complex called cytochrome c oxidase, which is responsible for one of the final steps in oxidative phosphorylation. Cytochrome c oxidase is made up of two large enzyme complexes called holoenzymes, which are each composed of multiple protein subunits. Three of these subunits are produced from mitochondrial genes; the rest are produced from nuclear genes. Many other proteins, all produced from nuclear genes, are involved in assembling these subunits into holoenzymes.  Most mutations that cause cytochrome c oxidase alter proteins that assemble the holoenzymes. As a result, the holoenzymes are either partially assembled or not assembled at all. Without complete holoenzymes, cytochrome c oxidase cannot form. Mutations in the three mitochondrial genes and a few nuclear genes that provide instructions for making the holoenzyme subunits can also cause cytochrome c oxidase deficiency. Altered subunit proteins reduce the function of the holoenzymes, resulting in a nonfunctional version of cytochrome c oxidase. A lack of functional cytochrome c oxidase disrupts the last step of oxidative phosphorylation, causing a decrease in energy production.  Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in other sensitive tissues may also contribute to the features of cytochrome c oxidase deficiency.
Cytochrome c oxidase deficiency can have different inheritance patterns depending on the gene involved.  When this condition is caused by mutations in genes within nuclear DNA, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  When this condition is caused by mutations in genes within mtDNA, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.
These resources address the diagnosis or management of cytochrome c oxidase deficiency:  - Cincinnati Children's Hospital: Acute Liver Failure  - Cincinnati Children's Hospital: Cardiomyopathies  - Genetic Testing Registry: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency  - Genetic Testing Registry: Cytochrome-c oxidase deficiency  - The United Mitochondrial Disease Foundation: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
X-linked hyper IgM syndrome is a condition that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. There are several classes of antibodies, and each one has a different function in the immune system. Although the name of this condition implies that affected individuals always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with X-linked hyper IgM syndrome have low levels of three other classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this disorder to fight off infections.  Individuals with X-linked hyper IgM syndrome begin to develop frequent infections in infancy and early childhood. Common infections include pneumonia, sinus infections (sinusitis), and ear infections (otitis). Infections often cause these children to have chronic diarrhea and they fail to gain weight and grow at the expected rate (failure to thrive). Some people with X-linked hyper IgM syndrome have low levels of white blood cells called neutrophils (neutropenia). Affected individuals may develop autoimmune disorders, neurologic complications from brain and spinal cord (central nervous system) infections, liver disease, and gastrointestinal tumors. They also have an increased risk of lymphoma, which is a cancer of immune system cells.  The severity of X-linked hyper IgM syndrome varies among affected individuals, even among members of the same family. Without treatment, this condition can result in death during childhood or adolescence.
Mutations in the CD40LG gene cause X-linked hyper IgM syndrome. This gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches like a key in a lock to its receptor protein, which is located on the surface of immune system cells called B cells. B cells are involved in the production of antibodies, and initially they are able to make only IgM antibodies. When CD40 ligand and its receptor protein are connected, they trigger a series of chemical signals that instruct the B cell to start making IgG, IgA, or IgE antibodies.  CD40 ligand is also necessary for T cells to interact with other cells of the immune system, and it plays a key role in T cell differentiation (the process by which cells mature to carry out specific functions).  Mutations in the CD40LG gene lead to the production of an abnormal CD40 ligand or prevent production of this protein. If CD40 ligand does not attach to its receptor on B cells, these cells cannot produce IgG, IgA, or IgE antibodies. Mutations in the CD40LG gene also impair the T cell's ability to differentiate and interact with other immune system cells. People with X-linked hyper IgM syndrome are more susceptible to infections because they do not have a properly functioning immune system.
These resources address the diagnosis or management of X-linked hyper IgM syndrome:  - Gene Review: Gene Review: X-Linked Hyper IgM Syndrome  - Genetic Testing Registry: Immunodeficiency with hyper IgM type 1  - MedlinePlus Encyclopedia: Immunodeficiency Disorders   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head."  Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.  MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.  People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.
MCPH can result from mutations in at least seven genes. Mutations in the ASPM gene are the most common cause of the disorder, accounting for about half of all cases.  The genes associated with MCPH play important roles in early brain development, particularly in determining brain size. Studies suggest that the proteins produced from many of these genes help regulate cell division in the developing brain.  Mutations in any of the genes associated with MCPH impair early brain development. As a result, affected infants have fewer nerve cells (neurons) than normal and are born with an unusually small brain. The reduced brain size underlies the small head size, intellectual disability, and developmental delays seen in many affected individuals.
These resources address the diagnosis or management of MCPH:  - Gene Review: Gene Review: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders  - Genetic Testing Registry: Primary autosomal recessive microcephaly 1  - Genetic Testing Registry: Primary autosomal recessive microcephaly 2  - Genetic Testing Registry: Primary autosomal recessive microcephaly 3  - Genetic Testing Registry: Primary autosomal recessive microcephaly 4  - Genetic Testing Registry: Primary autosomal recessive microcephaly 5  - Genetic Testing Registry: Primary autosomal recessive microcephaly 6  - Genetic Testing Registry: Primary autosomal recessive microcephaly 7  - MedlinePlus Encyclopedia: Head Circumference   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The first symptom in people with this disorder is usually droopy eyelids (ptosis), followed by difficulty swallowing (dysphagia). The swallowing difficulties begin with food, but as the condition progresses, liquids can be difficult to swallow as well. Many people with this condition have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition. Some affected individuals also have weakness in other facial muscles.  Individuals with oculopharyngeal muscular dystrophy frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. The weakness progresses slowly over time, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.  There are two types of oculopharyngeal muscular dystrophy, which are distinguished by their pattern of inheritance. They are known as the autosomal dominant and autosomal recessive types.
In Europe, the prevalence of oculopharyngeal muscular dystrophy is estimated to be 1 in 100,000 people. The autosomal dominant form of this condition is much more common in the French-Canadian population of the Canadian province of Quebec, where it is estimated to affect 1 in 1,000 individuals. Autosomal dominant oculopharyngeal muscular dystrophy is also seen more frequently in the Bukharan (Central Asian) Jewish population of Israel, affecting 1 in 600 people.  The autosomal recessive form of this condition is very rare; only a few cases of autosomal recessive oculopharyngeal muscular dystrophy have been identified.
Mutations in the PABPN1 gene cause oculopharyngeal muscular dystrophy. The PABPN1 gene provides instructions for making a protein that is active (expressed) throughout the body. In cells, the PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. The protein alters a region at the end of the mRNA molecule that protects the mRNA from being broken down and allows it to move within the cell.  The PABPN1 protein contains an area where the protein building block (amino acid) alanine is repeated 10 times. This stretch of alanines is known as a polyalanine tract. The role of the polyalanine tract in normal PABPN1 protein function is unknown.  Mutations in the PABPN1 gene that cause oculopharyngeal muscular dystrophy result in a PABPN1 protein that has an extended polyalanine tract. The extra alanines cause the PABPN1 protein to form clumps within muscle cells that accumulate because they cannot be broken down. These clumps (called intranuclear inclusions) are thought to impair the normal functioning of muscle cells and eventually cause cell death. The progressive loss of muscle cells most likely causes the muscle weakness seen in people with oculopharyngeal muscular dystrophy. It is not known why dysfunctional PABPN1 proteins seem to affect only certain muscle cells.
Most cases of oculopharyngeal muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. People with autosomal dominant oculopharyngeal muscular dystrophy have a mutation resulting in a PABPN1 protein with an expanded polyalanine tract of between 12 and 17 alanines.  Less commonly, oculopharyngeal muscular dystrophy can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In autosomal recessive oculopharyngeal muscular dystrophy, PABPN1 mutations lead to a polyalanine tract that is 11 alanines long. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of oculopharyngeal muscular dystrophy:  - Gene Review: Gene Review: Oculopharyngeal Muscular Dystrophy  - Genetic Testing Registry: Oculopharyngeal muscular dystrophy  - MedlinePlus Encyclopedia: Ptosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Von Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury. People with this condition often experience easy bruising, long-lasting nosebleeds, and excessive bleeding or oozing following an injury, surgery, or dental work. Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. Women with this condition typically have heavy or prolonged bleeding during menstruation (menorrhagia), and some may also experience reproductive tract bleeding during pregnancy and childbirth. In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause bleeding symptoms to become less frequent.  Von Willebrand disease is divided into three types, with type 2 being further divided into four subtypes. Type 1 is the mildest and most common of the three types, accounting for 75 percent of affected individuals. Type 3 is the most severe and rarest form of the condition. The four subtypes of type 2 von Willebrand disease are intermediate in severity. Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene mutations. Acquired von Willebrand syndrome is typically seen along with other disorders, such as diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood.
Mutations in the VWF gene cause von Willebrand disease. The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor, which is essential for the formation of blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. Von Willebrand factor acts as a glue to hold blood clots together and prevents the breakdown of other blood clotting proteins. If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly. Abnormally slow blood clotting causes the prolonged bleeding episodes seen in von Willebrand disease.  The three types of von Willebrand disease are based upon the amount of von Willebrand factor that is produced. Mutations in the VWF gene that reduce the amount of von Willebrand factor cause type 1 von Willebrand disease. People with type 1 have varying amounts of von Willebrand factor in their bloodstream. Some people with a mild case of type 1 never experience a prolonged bleeding episode. Mutations that disrupt the function of von Willebrand factor cause the four subtypes of type 2 von Willebrand disease. People with type 2 von Willebrand disease have bleeding episodes of varying severity depending on the extent of von Willebrand factor dysfunction, but the bleeding episodes are typically similar to those seen in type 1. Mutations that result in an abnormally short, nonfunctional von Willebrand factor generally cause type 3 von Willebrand disease. Because there is no functional protein, people with type 3 von Willebrand disease usually have severe bleeding episodes.
Von Willebrand disease can have different inheritance patterns.  Most cases of type 1 and type 2 von Willebrand disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.  Type 3, some cases of type 2, and a small number of type 1 cases of von Willebrand disease are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.
These resources address the diagnosis or management of von Willebrand disease:  - Gene Review: Gene Review: von Willebrand Disease  - Genetic Testing Registry: von Willebrand disorder  - MedlinePlus Encyclopedia: von Willebrand Disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Shprintzen-Goldberg syndrome is a disorder that affects many parts of the body. Affected individuals have a combination of distinctive facial features and skeletal and neurological abnormalities.  A common feature in people with Shprintzen-Goldberg syndrome is craniosynostosis, which is the premature fusion of certain skull bones. This early fusion prevents the skull from growing normally. Affected individuals can also have distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward.  People with Shprintzen-Goldberg syndrome are often said to have a marfanoid habitus, because their bodies resemble those of people with a genetic condition called Marfan syndrome. For example, they may have long, slender fingers (arachnodactyly), unusually long limbs, a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). People with Shprintzen-Goldberg syndrome can have other skeletal abnormalities, such as one or more fingers that are permanently bent (camptodactyly) and an unusually large range of joint movement (hypermobility).  People with Shprintzen-Goldberg syndrome often have delayed development and mild to moderate intellectual disability.  Other common features of Shprintzen-Goldberg syndrome include heart or brain abnormalities, weak muscle tone (hypotonia) in infancy, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia).  Shprintzen-Goldberg syndrome has signs and symptoms similar to those of Marfan syndrome and another genetic condition called Loeys-Dietz syndrome. However, intellectual disability is more likely to occur in Shprintzen-Goldberg syndrome than in the other two conditions. In addition, heart abnormalities are more common and usually more severe in Marfan syndrome and Loeys-Dietz syndrome.