bowang0911/MedQuAD huggingface dataset:
Mucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV.  Approximately 95 percent of individuals with this condition have the severe form. People with typical mucolipidosis type IV have delayed development of mental and motor skills (psychomotor delay). Motor skills include sitting, standing, walking, grasping objects, and writing. Psychomotor delay is moderate to severe and usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements. Most people with typical mucolipidosis type IV are unable to walk independently. In about 15 percent of affected individuals, the psychomotor problems worsen over time.  Vision may be normal at birth in people with typical mucolipidosis type IV, but it becomes increasingly impaired during the first decade of life. Individuals with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens, affected individuals have severe vision loss or blindness.  People with typical mucolipidosis type IV also have impaired production of stomach acid (achlorhydria). Achlorhydria does not cause any symptoms in these individuals, but it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Individuals with mucolipidosis type IV may not have enough iron in their blood, which can lead to a shortage of red blood cells (anemia). People with the severe form of this disorder usually survive to adulthood; however, they may have a shortened lifespan.  About 5 percent of affected individuals have atypical mucolipidosis type IV. These individuals usually have mild psychomotor delay and may develop the ability to walk. People with atypical mucolipidosis type IV tend to have milder eye abnormalities than those with the severe form of the disorder. Achlorhydria also may be present in mildly affected individuals.
Mutations in the MCOLN1 gene cause mucolipidosis type IV. This gene provides instructions for making a protein called mucolipin-1. This protein is located in the membranes of lysosomes and endosomes, compartments within the cell that digest and recycle materials. While its function is not completely understood, mucolipin-1 plays a role in the transport (trafficking) of fats (lipids) and proteins between lysosomes and endosomes. Mucolipin-1 appears to be important for the development and maintenance of the brain and retina. In addition, this protein is likely critical for normal functioning of the cells in the stomach that produce digestive acids.  Most mutations in the MCOLN1 gene result in the production of a nonfunctional protein or prevent any protein from being produced. A lack of functional mucolipin-1 impairs transport of lipids and proteins, causing these substances to build up inside lysosomes. Conditions that cause molecules to accumulate inside the lysosomes, including mucolipidosis type IV, are called lysosomal storage disorders. Two mutations in the MCOLN1 gene account for almost all cases of mucolipidosis type IV in people with Ashkenazi Jewish ancestry. It remains unclear how mutations in this gene lead to the signs and symptoms of mucolipidosis type IV.
These resources address the diagnosis or management of mucolipidosis type IV:  - Gene Review: Gene Review: Mucolipidosis IV  - Genetic Testing Registry: Ganglioside sialidase deficiency  - MedlinePlus Encyclopedia: Gastrin   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
Thrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of a bone called the radius in each forearm. Affected individuals also have a shortage (deficiency) of blood cells involved in clotting (platelets). This platelet deficiency (thrombocytopenia) usually appears during infancy and becomes less severe over time; in some cases the platelet levels become normal.  Thrombocytopenia prevents normal blood clotting, resulting in easy bruising and frequent nosebleeds. Potentially life-threatening episodes of severe bleeding (hemorrhages) may occur in the brain and other organs, especially during the first year of life. Hemorrhages can damage the brain and lead to intellectual disability. Affected children who survive this period and do not have damaging hemorrhages in the brain usually have a normal life expectancy and normal intellectual development.  TAR syndrome is unusual among similar malformations in that affected individuals have thumbs, while people with other conditions involving an absent radius typically do not. TAR syndrome is also associated with short stature and additional skeletal abnormalities, including underdevelopment of other bones in the arms and legs. Affected individuals may also have malformations of the heart and kidneys. TAR syndrome is associated with unusual facial features including a small lower jaw (micrognathia), a prominent forehead, and low-set ears. About half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with this disorder.
Mutations in the RBM8A gene cause TAR syndrome. The RBM8A gene provides instructions for making a protein called RNA-binding motif protein 8A. This protein is believed to be involved in several important cellular functions involving the production of other proteins.  Most people with TAR syndrome have a mutation in one copy of the RBM8A gene and a deletion of genetic material from chromosome 1 that includes the other copy of the RBM8A gene in each cell. A small number of affected individuals have mutations in both copies of the RBM8A gene in each cell and do not have a deletion on chromosome 1. RBM8A gene mutations that cause TAR syndrome reduce the amount of RNA-binding motif protein 8A in cells. The deletions involved in TAR syndrome eliminate at least 200,000 DNA building blocks (200 kilobases, or 200 kb) from the long (q) arm of chromosome 1 in a region called 1q21.1. The deletion eliminates one copy of the RBM8A gene in each cell and the RNA-binding motif protein 8A that would have been produced from it.  People with either an RBM8A gene mutation and a chromosome 1 deletion or with two gene mutations have a decreased amount of RNA-binding motif protein 8A. This reduction is thought to cause problems in the development of certain tissues, but it is unknown how it causes the specific signs and symptoms of TAR syndrome. No cases have been reported in which a deletion that includes the RBM8A gene occurs on both copies of chromosome 1; studies indicate that the complete loss of RNA-binding motif protein 8A is not compatible with life.  Researchers sometimes refer to the deletion in chromosome 1 associated with TAR syndrome as the 200-kb deletion to distinguish it from another chromosomal abnormality called a 1q21.1 microdeletion. People with a 1q21.1 microdeletion are missing a different, larger DNA segment in the chromosome 1q21.1 region near the area where the 200-kb deletion occurs. The chromosomal change related to 1q21.1 microdeletion is often called the recurrent distal 1.35-Mb deletion.
TAR syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell are altered. In this disorder, either both copies of the RBM8A gene in each cell have mutations or, more commonly, one copy of the gene has a mutation and the other is lost as part of a deleted segment on chromosome 1. The affected individual usually inherits an RBM8A gene mutation from one parent. In about 75 percent of cases, the affected person inherits a copy of chromosome 1 with the 200-kb deletion from the other parent. In the remaining cases, the deletion occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. Although parents of an individual with TAR syndrome can carry an RBM8A gene mutation or a 200-kb deletion, they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of TAR syndrome:  - Gene Review: Gene Review: Thrombocytopenia Absent Radius Syndrome  - Genetic Testing Registry: Radial aplasia-thrombocytopenia syndrome  - MedlinePlus Encyclopedia: Skeletal Limb Abnormalities   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
Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend.  The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth.  In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life.  Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy.
Mutations in the CHRNG gene cause most cases of multiple pterygium syndrome, Escobar type and a smaller percentage of cases of lethal multiple pterygium syndrome. The CHRNG gene provides instructions for making the gamma () protein component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein is found in the membrane of skeletal muscle cells and is critical for signaling between nerve and muscle cells. Signaling between these cells is necessary for movement. The AChR protein consists of five subunits. The  subunit is found only in the fetal AChR protein. At about the thirty-third week of pregnancy, the  subunit is replaced by another subunit to form adult AChR protein. The replacement of fetal AChR by adult AChR is the reason most people with multiple pterygium syndrome, Escobar type do not have problems with muscle movement after birth.  CHRNG gene mutations result in an impaired or missing  subunit. The severity of the CHRNG gene mutation influences the severity of the condition. Typically, mutations that prevent the production of any  subunit will result in the lethal type, while mutations that allow the production of some  subunit will lead to the Escobar type. Without a functional  subunit, the fetal AChR protein cannot be assembled or properly placed in the muscle cell membrane. As a result, the fetal AChR protein cannot function and the communication between nerve cells and muscle cells in the developing fetus is impaired. A lack of signaling between nerve and muscle cells leads to akinesia and pterygium before birth, and may result in many of the other signs and symptoms of multiple pterygium syndrome.  Mutations in other genes, most providing instructions for other AChR protein subunits, have been found to cause multiple pterygium syndrome. Changes in these genes can cause both the lethal and Escobar types of this condition, although they account for only a small number of cases. Some people with multiple pterygium syndrome do not have an identified mutation in any of the known genes associated with this condition. The cause of the disease in these individuals is unknown.
Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.  Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.  In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.  Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.
It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.  People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 80 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.  When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.  These CDH1 gene mutations also lead to a 40 to 50 percent chance of lobular breast cancer in women, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.  About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown.
These resources address the diagnosis or management of hereditary diffuse gastric cancer:  - American Cancer Society: How is Stomach Cancer Diagnosed?  - Gene Review: Gene Review: Hereditary Diffuse Gastric Cancer  - Genetic Testing Registry: Hereditary diffuse gastric cancer  - MedlinePlus Encyclopedia: Gastric Cancer  - Memorial Sloan-Kettering Cancer Center: Early Onset and Familial Gastric Cancer Registry  - National Cancer Institute: Gastric Cancer Treatment Option Overview   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
Chronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20.  Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally, which usually causes the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia) or rapidly switches from being too fast to being too slow (tachycardia-bradycardia syndrome). Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue).  In intestinal pseudo-obstruction, impairment of peristalsis leads to a buildup of partially digested food in the intestines, abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those caused by an intestinal blockage (obstruction) such as a tumor, but in intestinal pseudo-obstruction no such blockage is found.
CAID is caused by mutations in the SGO1 gene. This gene provides instructions for making part of a protein complex called cohesin. This protein complex helps control the placement of chromosomes during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Cohesin holds the sister chromatids together, and in doing so helps maintain the stability of chromosomal structure during cell division.  Researchers suggest that SGO1 gene mutations may result in a cohesin complex that is less able to hold sister chromatids together, resulting in decreased chromosomal stability during cell division. This instability is thought to cause early aging (senescence) of cells in the intestinal muscle and in the SA node, resulting in problems maintaining proper rhythmic movements of the heart and intestines and leading to the signs and symptoms of CAID.  It is unclear why SGO1 gene mutations specifically affect the heart and intestines in CAID. Researchers suggest that the activity (expression) of the SGO1 gene in certain embryonic tissues or a particular function of the SGO1 protein in the SA node and in cells that help control peristalsis may account for the features of the disorder.
These resources address the diagnosis or management of chronic atrial and intestinal dysrhythmia:  - Children's Hospital of Pittsburgh: Chronic Intestinal Pseudo-obstruction  - Genetic Testing Registry: Chronic atrial and intestinal dysrhythmia  - MedlinePlus Encyclopedia: Heart Pacemakers  - MedlinePlus Health Topic: Nutritional Support  - MedlinePlus Health Topic: Pacemakers and Implantable Defibrillators  - National Heart, Lung, and Blood Institute: What is a Pacemaker?   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