bowang0911/MedQuAD huggingface dataset:
Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.  An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.  Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).  In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older.
Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides instructions for making a receptor protein that attaches (binds) to another protein called NGF. The NTRK1 receptor is important for the survival of nerve cells (neurons).  The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons). When the NGF protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.
These resources address the diagnosis or management of CIPA:  - Gene Review: Gene Review: Congenital Insensitivity to Pain with Anhidrosis  - Genetic Testing Registry: Hereditary insensitivity to pain with anhidrosis   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
Hypochondrogenesis is a rare, severe disorder of bone growth. This condition is characterized by a small body, short limbs, and abnormal bone formation (ossification) in the spine and pelvis.  Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Bones in the skull develop normally, but the bones of the spine (vertebrae) and pelvis do not harden (ossify) properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. Individuals with hypochondrogenesis have an enlarged abdomen and may have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.  As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with hypochondrogenesis usually die at birth or shortly thereafter from respiratory failure. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related but milder disorder that similarly affects bone development.
Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.
Krabbe disease (also called globoid cell leukodystrophy) is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). This disorder is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that usually have more than one nucleus.  The symptoms of Krabbe disease usually begin before the age of 1 year (the infantile form). Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and slowed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures.  Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals.
These resources address the diagnosis or management of Krabbe disease:  - Baby's First Test  - Gene Review: Gene Review: Krabbe Disease  - Genetic Testing Registry: Galactosylceramide beta-galactosidase deficiency  - MedlinePlus Encyclopedia: Krabbe 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
Septo-optic dysplasia is a disorder of early brain development. Although its signs and symptoms vary, this condition is traditionally defined by three characteristic features: underdevelopment (hypoplasia) of the optic nerves, abnormal formation of structures along the midline of the brain, and pituitary hypoplasia.  The first major feature, optic nerve hypoplasia, is the underdevelopment of the optic nerves, which carry visual information from the eyes to the brain. In affected individuals, the optic nerves are abnormally small and make fewer connections than usual between the eyes and the brain. As a result, people with optic nerve hypoplasia have impaired vision in one or both eyes. Optic nerve hypoplasia can also be associated with unusual side-to-side eye movements (nystagmus) and other eye abnormalities.  The second characteristic feature of septo-optic dysplasia is the abnormal development of structures separating the right and left halves of the brain. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain. In the early stages of brain development, these structures may form abnormally or fail to develop at all. Depending on which structures are affected, abnormal brain development can lead to intellectual disability and other neurological problems.  The third major feature of this disorder is pituitary hypoplasia. The pituitary is a gland at the base of the brain that produces several hormones. These hormones help control growth, reproduction, and other critical body functions. Underdevelopment of the pituitary can lead to a shortage (deficiency) of many essential hormones. Most commonly, pituitary hypoplasia causes growth hormone deficiency, which results in slow growth and unusually short stature. Severe cases cause panhypopituitarism, a condition in which the pituitary produces no hormones. Panhypopituitarism is associated with slow growth, low blood sugar (hypoglycemia), genital abnormalities, and problems with sexual development.  The signs and symptoms of septo-optic dysplasia can vary significantly. Some researchers suggest that septo-optic dysplasia should actually be considered a group of related conditions rather than a single disorder. About one-third of people diagnosed with septo-optic dysplasia have all three major features; most affected individuals have two of the major features. In rare cases, septo-optic dysplasia is associated with additional signs and symptoms, including recurrent seizures (epilepsy), delayed development, and abnormal movements.
In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.  At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in embryonic development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.  Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia.
Septo-optic dysplasia is usually sporadic, which means that the condition typically occurs in people with no history of the disorder in their family.  Less commonly, septo-optic dysplasia has been found to run in families. Most familial cases appear to have an autosomal recessive pattern of inheritance, which means that both copies of an associated 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. In a few affected families, the disorder has had an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the condition.
These resources address the diagnosis or management of septo-optic dysplasia:  - Genetic Testing Registry: Septo-optic dysplasia sequence  - MedlinePlus Encyclopedia: Growth Hormone Deficiency  - MedlinePlus Encyclopedia: Hypopituitarism   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
Spondylothoracic dysostosis is a condition characterized by the malformation of the bones of the spine and ribs. The bones of the spine (vertebrae) do not develop properly, which causes them to be misshapen and abnormally joined together (fused). The ribs are also fused at the part nearest the spine (posteriorly), which gives the rib cage its characteristic fan-like or "crab" appearance in x-rays. Affected individuals have short, rigid necks and short midsections because of the bone malformations. As a result, people with spondylothoracic dysostosis have short bodies but normal length arms and legs, called short-trunk dwarfism.  The spine and rib abnormalities cause other signs and symptoms of spondylothoracic dysostosis. Infants with this condition are born with a small chest that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand, the narrow chest forces the muscle that separates the abdomen from the chest cavity (the diaphragm) down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia) or belly-button (umbilical hernia).  Spondylothoracic dysostosis is sometimes called spondylocostal dysostosis, a similar condition with abnormalities of the spine and ribs. The two conditions have been grouped in the past, and both are referred to as Jarcho-Levin syndrome; however, they are now considered distinct conditions.
The MESP2 gene provides instructions for a protein that plays a critical role in the development of vertebrae. Specifically, it is involved in separating vertebrae from one another during early development, a process called somite segmentation. Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, somite segmentation does not occur properly, which results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.
These resources address the diagnosis or management of spondylothoracic dysostosis:  - Cleveland Clinic: Spine X-ray  - Gene Review: Gene Review: Spondylocostal Dysostosis, Autosomal Recessive   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
Familial osteochondritis dissecans is a condition that affects the joints and is associated with abnormal cartilage. Cartilage is a tough but flexible tissue that covers the ends of the bones at joints and is also part of the developing skeleton. A characteristic feature of familial osteochondritis dissecans is areas of bone damage (lesions) caused by detachment of cartilage and a piece of the underlying bone from the end of the bone at a joint. People with this condition develop multiple lesions that affect several joints, primarily the knees, elbows, hips, and ankles. The lesions cause stiffness, pain, and swelling in the joint. Often, the affected joint feels like it catches or locks during movement. Other characteristic features of familial osteochondritis dissecans include short stature and development of a joint disorder called osteoarthritis at an early age. Osteoarthritis is characterized by the breakdown of joint cartilage and the underlying bone. It causes pain and stiffness and restricts the movement of joints.  A similar condition called sporadic osteochondritis dissecans is associated with a single lesion in one joint, most often the knee. These cases may be caused by injury to or repetitive use of the joint (often sports-related). Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected joint, especially if the lesion occurs later in life after the bone has stopped growing. Short stature is not associated with this form of the condition.
Mutation of the ACAN gene can cause familial osteochondritis dissecans. The ACAN gene provides instructions for making the aggrecan protein, which is a component of cartilage. Aggrecan attaches to the other components of cartilage, organizing the network of molecules that gives cartilage its strength. In addition, aggrecan attracts water molecules and gives cartilage its gel-like structure. This feature enables the cartilage to resist compression, protecting bones and joints.  The ACAN gene mutation associated with familial osteochondritis dissecans results in an abnormal protein that is unable to attach to the other components of cartilage. As a result, the cartilage is disorganized and weak. It is unclear how the abnormal cartilage leads to the lesions and osteoarthritis characteristic of familial osteochondritis dissecans. Researchers suggest that a disorganized cartilage network in growing bones impairs their normal growth, leading to short stature.  Sporadic osteochondritis dissecans is not caused by genetic changes and is not inherited.
These resources address the diagnosis or management of familial osteochondritis dissecans:  - Cedars-Sinai  - Genetic Testing Registry: Osteochondritis dissecans  - Seattle Children's: Osteochondritis Dissecans Symptoms and Diagnosis   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
Sensorineural deafness and male infertility is caused by a deletion of genetic material on the long (q) arm of chromosome 15. The signs and symptoms of sensorineural deafness and male infertility are related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals. Researchers have determined that the loss of a particular gene on chromosome 15, the STRC gene, is responsible for hearing loss in affected individuals. The loss of another gene, CATSPER2, in the same region of chromosome 15 is responsible for the sperm abnormalities and infertility in affected males. Researchers are working to determine how the loss of additional genes in the deleted region affects people with sensorineural deafness and male infertility.
Sensorineural deafness and male infertility is inherited in an autosomal recessive pattern, which means both copies of chromosome 15 in each cell have a deletion. The parents of an individual with sensorineural deafness and male infertility each carry one copy of the chromosome 15 deletion, but they do not show symptoms of the condition.  Males with two chromosome 15 deletions in each cell have sensorineural deafness and infertility. Females with two chromosome 15 deletions in each cell have sensorineural deafness as their only symptom because the CATSPER2 gene deletions affect sperm function, and women do not produce sperm.
These resources address the diagnosis or management of sensorineural deafness and male infertility:  - Cleveland Clinic: Male Infertility  - Gene Review: Gene Review: CATSPER-Related Male Infertility  - Genetic Testing Registry: Deafness, sensorineural, and male infertility  - MedlinePlus Health Topic: Assisted Reproductive Technology  - RESOLVE: The National Infertility Association: Semen Analysis   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
Unverricht-Lundborg disease is a rare inherited form of epilepsy. Affected individuals usually begin showing signs and symptoms of the disorder between the ages of 6 and 15.  Unverricht-Lundborg disease is classified as a type of progressive myoclonus epilepsy. People with this disorder experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.  Affected individuals also usually have seizures involving loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years but may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.  Eventually people with Unverricht-Lundborg disease may develop problems with balance and coordination (ataxia), involuntary rhythmic shaking that worsens during movement (intentional tremor), difficulty speaking (dysarthria), depression, and a slow, mild decline in intellectual functioning.  People with Unverricht-Lundborg disease typically live into adulthood. Depending on the severity of the condition and a person's response to treatment, life expectancy may be normal.
Mutations in the CSTB gene cause Unverricht-Lundborg disease. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes (compartments in the cell that digest and recycle materials). While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.  In almost all affected individuals, Unverricht-Lundborg disease is caused by an increase in size of the CSTB gene. One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is normally repeated two or three times within the gene and is called a dodecamer repeat. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene. A small number of people with Unverricht-Lundborg disease carry other mutations.  The increased number of dodecamer repeats in the CSTB gene seems to interfere with the production of the cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder.
These resources address the diagnosis or management of Unverricht-Lundborg disease:  - Gene Review: Gene Review: Unverricht-Lundborg Disease  - Genetic Testing Registry: Unverricht-Lundborg syndrome   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
Bietti crystalline dystrophy is a disorder in which numerous small, yellow or white crystal-like deposits of fatty (lipid) compounds accumulate in the light-sensitive tissue that lines the back of the eye (the retina). The deposits damage the retina, resulting in progressive vision loss.  People with Bietti crystalline dystrophy typically begin noticing vision problems in their teens or twenties. They experience a loss of sharp vision (reduction in visual acuity) and difficulty seeing in dim light (night blindness). They usually lose areas of vision (visual field loss), most often side (peripheral) vision. Color vision may also be impaired.  The vision problems may worsen at different rates in each eye, and the severity and progression of symptoms varies widely among affected individuals, even within the same family. However, most people with this condition become legally blind by their forties or fifties. Most affected individuals retain some degree of vision, usually in the center of the visual field, although it is typically blurry and cannot be corrected by glasses or contact lenses. Vision impairment that cannot be improved with corrective lenses is called low vision.