Natural Standard Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
Autosomal recessive inheritance, consanguineous, Joubert syndrome, Joubert syndrome and related disorders (JSRD).
Cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis, also known as COACH syndrome, is a rare genetic condition that affects many parts of the body, including the brain, eyes, and liver. COACH syndrome is the result of an abnormality in the cerebellar vermis, a part of the brain that controls coordination and balance. COACH syndrome is one of a number of disorders known as Joubert syndrome and related disorders (JSRD). Joubert syndrome is a rare genetic condition that also affects the cerebellar vermis, which is located between the left and right sides of the brain. In Joubert syndrome, the cerebellar vermis is absent or underdeveloped. These disorders share some signs and symptoms but are considered distinct syndromes.
Patients diagnosed with COACH syndrome characteristically exhibit the following features: underdevelopment (hypoplasia) or complete lack (aplasia or agenesis) of the cerebellar vermis, usually indicated by the "molar tooth" sign seen on an axial view of a magnetic resonance imaging (MRI) brain scan; developmental delays and intellectual disabilities; difficulty coordinating voluntary muscle movements; uncoordinated movements (ataxia); a malformation of the retina or other parts of the eye (coloboma); abnormalities of the liver, including hepatic fibrosis; and decreased muscle tone (hypotonia).
Although COACH syndrome is believed to be caused by a genetic mutation or defect, the exact mutation is currently not known. COACH syndrome is inherited or passed down among family members as an autosomal recessive trait. This means that an individual must inherit two copies of the defective gene for the condition to occur. No genes have been identified that specifically cause COACH syndrome. It is likely that alterations in multiple genes cause this condition.
The prevalence of COACH syndrome is not known but seems to be higher among people whose parents are closely related (consanguineous). Only about 20 cases have been reported in the scientific literature.
There is no cure for COACH syndrome. Treatment aims to reduce symptoms and prevent complications. Life expectancy of individuals with COACH depends on the severity of liver and kidney failure.
COACH syndrome (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis) is believed to be inherited; therefore, the only known risk factor is a family history of the disease.
Environmental factors may increase the risk of developing genetically linked diseases.
Genetic mutations: Although COACH syndrome is believed to be caused by a genetic mutation or defect, the exact mutation is not known. Researchers believe that COACH syndrome may be caused by multiple genetic mutations.
Autosomal recessive inheritance: COACH syndrome is inherited or passed down among family members as an autosomal recessive trait, meaning that a person must inherit two copies of the defective gene (one from each parent). Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers because they can pass on the disorder to their children.
If one parent is a carrier, or has only one copy of the defective gene, then each child has a 50% chance of inheriting one defective gene and also being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have COACH syndrome.
Random occurrence: It is unknown whether COACH can occur in individuals with no family history of the disorder, either from a spontaneous genetic mutation in the egg or sperm cells or in the developing embryo.
Signs and Symptoms
General: COACH (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis) syndrome is a rare genetic condition that affects many parts of the body, including the brain, kidneys, and liver. Symptoms, such as brain abnormality, can be seen while the fetus is still in the womb. Other features of the disorder, such as developmental delays, intellectual disabilities, ataxia (uncoordinated muscle movements), and decreased muscle tone, can be observed during childhood. Kidney and liver problems typically develop and may progress, leading to failure of these organs.
Brain tissue: A key feature of COACH syndrome is the absence or underdevelopment of the cerebellar vermis, the part of the brain that regulates balance and coordination. The cerebellar vermis is found between the right and left sides of the brain. When the brain is imaged as though looking through the top of the head, this brain abnormality may resemble a tooth, and is thus called the molar tooth sign. This brain abnormality is likely the cause of problems with balance and coordination (ataxia).
Breathing: People with COACH syndrome and some JSRDs tend to have rapid breathing or panting (hyperpnea) and tend to pause between breaths (apnea). When breathing is rapid, it may be three times as fast as normal breathing. Periods of apnea can last for up to 90 seconds. Rapid breathing is more likely to occur during periods of wakefulness, while apnea is more likely to occur during sleep. These breathing abnormalities can make newborns with COACH syndrome susceptible to sudden death or coma. Breathing tends to become more normal after the first year of life.
Cognitive function: People with COACH syndrome may have intellectual disabilities that are present in early childhood. These disabilities are variable, ranging from severe to mild; a few individuals with COACH syndrome have attended college. Intellectual ability is commonly in the moderate range. Individuals with COACH syndrome may experience apraxia of speech, which may result in an inability to coordinate between speech comprehension and verbal communication.
Coordination: Because of abnormalities in the cerebellar vermis, people with COACH syndrome often have poor coordination, which may include an unsteady gait and delayed achievement of normal developmental milestones such as sitting and walking.
Eyes: People with COACH syndrome may have rapid involuntary eye movements (nystagmus). Other eye symptoms may include problems with the optic nerve or retina, and a split iris; these problems can result in blindness. The occurrence of eye problems may be lower in individuals with COACH compared with individuals with other JSRDs.
Face: Some people with COACH syndrome have a distinctive facial appearance that includes wide-set eyes, underdeveloped mid-face, small ear lobes, a broad forehead, arched eyebrows, and a wide mouth. Other facial features may include a prominent jaw, droopy eyelids, and abnormal lower lip.
Kidneys: Some people with COACH syndrome may have renal insufficiency (decreased kidney function). If left untreated, this condition can progress to kidney failure. Renal insufficiency often presents as frequent urination and increased thirst.
Liver: Some people with COACH syndrome develop fibrous tissue in the liver, which can eventually lead to cirrhosis. This condition is characterized by scar tissue that replaces normal healthy tissue, blocking the flow of blood through the liver and preventing it from working properly. Cirrhosis can possibly result in liver failure. Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces more healthy cells, liver function starts to fail and a person may experience fatigue, loss of appetite, nausea, and weight loss. As the disease progresses, the scar tissue blocks the flow of blood returning to the heart from the intestines and raises the pressure in the portal vein (portal hypertension). Toxic substances accumulate in the blood, resulting in decreased brain function. Liver cancer may also develop.
Muscle tone: Many people with COACH syndrome have decreased muscle tone, which may delay achievement of developmental milestones, such as acquiring gross and fine motor skills. These skills are normally developed in early childhood and allow the child to walk, run, and stand up (gross motor skills), or use a spoon (fine motor skill), and develop speech.
Neurological: Some people with COACH syndrome appear to have difficulty processing information received by the five senses of hearing, sight, taste, touch, and smell.
General: COACH syndrome (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis) is typically diagnosed after a thorough physical exam and complete family history. If COACH syndrome is suspected, prenatal diagnosis can be based on the characteristic brain abnormality; however, not all fetuses or infants will display all symptoms of the disorder. A clinician should ask probing questions about attainment of developmental milestones, including sitting, walking, and speech, and should examine the patient for the distinctive features of the eyes, face, and muscles. A clinician should also look for characteristic facial features, including a large head, prominent forehead, high and rounded eyebrows, low-set ears, and droopy eyelids. Patients' mouths may hang open and appear oval in shape. The tongue may stick out of the mouth and quiver. Involuntary eye movements, evidence of breathing abnormalities, muscular weakness, and lack of coordination may also be present.
Genetic testing: Because no specific genetic mutation has been identified as the cause of COACH syndrome, genetic testing is currently not available.
Imaging studies: Imaging studies include X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). MRI is a noninvasive imaging technique that uses magnetic and radio waves to create an image of tissues within the body. A CT scan is a noninvasive imaging technique that uses a series of X-rays to build a picture of the inside of the body. These imaging techniques may help identify some of the key features of COACH syndrome, including an enlarged kidney or liver. An MRI of the brain may reveal the absence or underdevelopment of the cerebellar vermis, the part of the brain responsible for coordination and balance. The abnormal cerebellar vermis may resemble a tooth (molar tooth sign) when it is viewed as though looking through the top of the head during an MRI.
Coma: Breathing abnormalities characteristic of COACH syndrome may cause coma in young people with this disorder.
Coordination and development: Because of abnormalities in the cerebellar vermis, people with COACH syndrome often have problems with balance and coordination (ataxia). People with COACH syndrome may also have delayed development of overall motor and speech skills. Problems with coordination and development depend on how severely the brain is affected in this condition.
Kidney failure: Progressive decline in kidney function may eventually lead to kidney failure in people with COACH syndrome. Decline in kidney function often presents as frequent urination and increased thirst.
Liver failure: Progressive development of fibrous tissue in the liver may eventually lead to cirrhosis, a condition characterized by scar tissue replacing normal healthy tissue, blocking the flow of blood through the liver and preventing it from working properly. Cirrhosis can possibly result in liver failure. Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue continues to replace healthy cells, liver function starts to fail and a person may experience fatigue, loss of appetite, nausea, and weight loss. As the disease progresses, the scar tissue blocks the flow of blood returning to the heart from the intestines and raises the pressure in the portal vein (portal hypertension). Toxic substances accumulate in the blood, resulting in decreased brain function. Liver cancer may also develop.
Portal hypertension: People with COACH syndrome may be at increased risk for developing high blood pressure, especially in the portal vein, which carries blood from the small and large intestine, spleen, and stomach to the liver.
Gastrointestinal bleeding: High blood pressure in the portal vein may cause blood vessels in the esophagus to become dilated or distended and prone to rupture, leading to massive, and potentially fatal, blood loss.
Sudden death: Breathing abnormalities characteristic of COACH syndrome may cause sudden death, especially in young people with the disorder.
General: There is no known cure for COACH (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis) syndrome. Instead, treatment aims to reduce symptoms and prevent complications. People with COACH syndrome should be regularly examined by an ophthalmologist (eye specialist), neurologist (nerve specialist), gastroenterologist (liver specialist), and nephrologist (kidney specialist). Life expectancy of individuals with COACH depends on the severity of liver and kidney failure.
Adaptive equipment: Equipment such as wheelchairs, walkers, and braces are available to help individuals with COACH syndrome perform daily tasks. Many people with COACH syndrome can use their arms to roll the wheels of a wheelchair on their own, and can move around without much difficulty. There are also motorized wheelchairs available. This type of wheelchair has a motor that moves the wheels, and may be particularly accessible for a child to operate on his or her own. A walker is usually made out of light metal, most often with four adjustable legs. Some people with COACH syndrome can walk but have poor balance and may fall, so a walker may help them avoid falls.
Because of the fine motor problems often associated with COACH syndrome, patients may have a hard time using eating utensils. Special handles or grips are available for those who have trouble grasping small objects, such as a fork or spoon. Specially designed eating utensils for individuals with fine motor problems also exist and may be curved or bent to fit specific needs. Specialized grips and handles are also used on pencils and pens to make them easier to hold.
Corrective lenses: Individuals with COACH syndrome and vision problems (such as nearsightedness) may benefit from corrective lenses or glasses. However, neither glasses nor corrective lenses can improve optic atrophy, which may occur in COACH syndrome.
Diet: A protein-restricted diet may be recommended to decrease the burden on the kidneys, because COACH syndrome patients are at risk for declining kidney function. Protein contains 16% nitrogen, which the body eliminates in the urine as urea. In cases where liver or kidney function is impaired, ammonia or nitrogen metabolites may build up in the blood, creating a toxic environment. A customized diet adequate in calories and nutrients can be planned with the help of a registered dietitian (RD).
Education: By law, patients with COACH syndrome who suffer from intellectual disabilities must have access to education tailored to their specific strengths and weaknesses. According to the Individuals with Disabilities Education Act, all children with disabilities must receive free and appropriate education. This law states that staff members of the patient's school must consult with the patient's parents or caregivers to design and write an individualized education plan based on the child's needs. The school faculty must document the child's progress in order to ensure that the child's needs are being met.
Educational programs vary among patients depending on the child's specific learning disabilities. In general, most experts believe that children with disabilities should be educated alongside their nondisabled peers. The idea is that nondisabled students will help the patient learn appropriate behavioral, social, and language skills. Therefore, some COACH syndrome patients are educated in mainstream classrooms. Others attend public schools but take special education classes. Still others attend specialized schools that are equipped to teach children with disabilities
Physical therapy: Patients with COACH syndrome may benefit from seeing a physical therapist. A physical therapist can help patients maintain muscle tone and keep muscles strong and flexible through performing different exercises. A speech therapist may help a patient retrain the tongue and facial muscles to improve speech.
Occupational therapy: Patients with COACH syndrome may benefit from occupational therapy. During sessions, a therapist helps the individual learn skills needed to perform basic daily tasks, such as eating, dressing, and communicating with others. Some patients work with therapists who specialize in disorders and disabilities such as COACH syndrome. Parents and caregivers can ask their child's pediatrician for recommended therapists.
Speech-language therapy: Some patients with COACH syndrome may benefit from speech-language therapy because individuals often develop communication skills more slowly than normal. During speech-language therapy, a qualified speech-language professional (SLP) works with the patient on a one-to-one basis, in a small group, or in a classroom to help the patient improve speech, language, and communication skills. Programs are tailored to the patient's individual needs. Speech pathologists use a variety of exercises to improve the patient's communication skills. Exercises typically start off simple and become more complex as therapy continues. For instance, the therapist may ask the patient to name objects, tell stories, or explain the purpose of an object.
Dialysis: When the kidneys begin to fail, patients can undergo dialysis to restore the filtering function of the kidneys. In hemodialysis, a patient's blood is circulated into an external filter and cleaned. The filtered blood is then returned to the body. In peritoneal dialysis, a fluid containing dextrose is introduced into the abdomen through a tube. This solution absorbs the wastes in the body and is then removed.
Transplantation: Some patients who experience kidney or liver failure may undergo kidney or liver transplantation. An individual with end-stage renal disease or liver failure may receive a healthy kidney or liver from either a living or a deceased donor. However, transplantation is associated with complications, including infection and the possibility of rejection of the new organ. To reduce the chance of rejection, patients may need to take immunosuppressant drugs, such as tacrolimus, mycophenolate, prednisone, cyclosporine, rapamycin, or azathioprine. Cyclosporine, considered a breakthrough immunosuppressant when first discovered in the 1980s, ironically causes kidney toxicity and can result in damage to the newly transplanted kidney or liver.
Sleep apnea treatment: Lifestyle changes (including avoiding alcohol and medications that cause drowsiness, as well as weight loss), mouthpieces, breathing devices, or surgery are used to treat sleep apnea.
Currently there is limited scientific evidence on the use of integrative therapies for the treatment or prevention of COACH syndrome.
Because COACH (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis) syndrome is believed to be inherited, there is no known means of preventing it. Regular monitoring of people with COACH syndrome can help prevent complications, including gastrointestinal bleeding and kidney and liver failure.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
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Joubert Syndrome Foundation & Related Cerebellar Disorders. www.jsfrcd.org.
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National Eye Institute. www.nei.nih.gov.
Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.
The ARC, an advocacy organization for individuals with disabilities. www.thearc.org.
Uemura T, Sanchez EQ, Ikegami T, et al. Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up. Clin Transplant. 2005 Dec;19(6):717-20. View Abstract
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Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017