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Cohen Syndrome

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Synonyms of Cohen Syndrome

Disorder Subdivisions

General Discussion

Cohen syndrome is an extremely variable genetic disorder characterized by diminished muscle tone (hypotonia), abnormalities of the head, face, hands and feet and mental retardation. Affected individuals usually have heads that are smaller than average and a short upper lip through which the incisors are exposed. In many, but not all cases, obesity is present, especially around the torso and is associated with slender arms and legs. A lowered level of white blood cells (neutropenia) is present from birth in some affected individuals.

Cohen syndrome is an autosomal recessive genetic disease caused by an abnormal gene located on chromosome 8 at 8q22-q23.


Children with Cohen syndrome usually have a low birthweight, delayed growth, and obesity of the trunk that occurs during mid-childhood. Other characteristics of this disorder may include muscle weakness, an unusually small head (microcephaly), large ears, high nasal bridge, an abnormally short groove in the middle of the upper lip (philtrum), and upper central incisors. The jaw may develop abnormally, and there may be a mild slant of the eyelids. Diminished vision in bright light (hemeralopia), decreased clarity of vision, a narrowing of the visual field, and degeneration of the retina (retinitis pigmentosa) may also occur.

Other characteristics of Cohen syndrome may include unusual increased extension (hyperextensible) of the joints, narrow hands and feet with long fingers and toes, a single crease (simian) on the palms of the hands, and deformities of the knees, elbows, and spine. Undescended testicles in males (cryptorchidism), delayed puberty, and mild to moderate mental retardation are also symptomatic of this rare disorder.

In rare cases, people with Cohen syndrome may also exhibit additional abnormalities, such as mild webbing of the fingers (syndactyly) a reduced number of white blood cells (leukopenia), seizures, and a mitral valve prolapse in the heart.

The disorder occurs disproportionately in the Finnish population. Non-Finnish individuals with Cohen syndrome have extremely variable symptoms that do not include obesity. In many instances the signs and symptoms associated with Cohen syndrome are not obvious so that many clinicians believe the symptom to be under-diagnosed.


Cohen syndrome is an autosomal recessive genetic disease caused by an abnormal gene located on chromosome 8 at 8q22-q23. Mutations in the VPS13B gene casue Cohen Syndrome

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 8q22-q2313" refers to a region on the long arm of chromosome 8 between band 22 and band 23. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Cohen syndrome affects males and females in about equal numbers. It appears to occur more frequently in people of Finnish or Ashkenazi Jewish descent.

Related Disorders

Symptoms of the following disorders can be similar to those of Cohen Syndrome. Comparisons may be useful for a differential diagnosis:

Prader-Willi Syndrome is a complex, multi-system disorder present more often in males born following a long gestation period. Females can also be affected. The primary features of the disease include infantile muscle weakness, failure to thrive, hypogonadism, and developmental delay. Severe obesity, which can be life threatening, develops after the first year of life. Short stature and abnormal intellectual and behavioral functioning is characteristic of this disorder. (For more information on this disorder, choose "Prader-Willi" as your search term in the Rare Disease Database.)

Hypothyroidism may be a genetic or acquired condition that occurs alone or as a symptom of another illness. Major symptoms may include the development of an enlarged thyroid gland (goiter) in the neck, a dull facial expression, puffiness and swelling around the eyes, drooping eyelids and thinning hair which is coarse and dry. Intelligence may or may not be affected. Untreated childhood hypothyroidism is characterized by slowed growth, delay in the development of teeth, and mental retardation. (For more information on this disorder, choose "Hypothyroidism" as your search term in the Rare Disease Database.)

Sotos Syndrome is a rare hereditary disorder characterized by excessive growth during the first 4 to 5 years of life. Other symptoms are an unusual aggressiveness or irritability, clumsiness and an awkward gait. People with this disorder have abnormal patterns on the ridges of the skin on fingers, palms, toes and soles. Bone age tends to be 2 to 4 years advanced, and patients have a disproportionately large and long head with a slightly protrusive forehead, large hands and feet. Mild mental retardation also occurs. (For more information on this disorder, choose "Sotos" as your search term in the Rare Disease Database.)

Marfan Syndrome is an inherited disorder of the connective tissues that affects the bones and ligaments (skeletal system), muscles, lungs, eyes, blood vessels and heart. People with this disorder are unusually tall and can move their joints beyond the normal range. (For more information on this disorder, choose "Marfan" as your search term in the Rare Disease Database.)

Retinitis Pigmentosa (RP) is one of a group of inherited eye diseases causing degeneration of the retina. When the retina degenerates, the vision decreases and may occasionally be lost. Retinitis Pigmentosa may be associated with other symptoms such as deafness, central nervous system disorders, metabolic disorders and even chromosomal abnormalities. Some people with Cohen's Syndrome may also have Retinitis Pigmentosa. (For more information on this disorder, choose "Retinitis Pigmentosa" as your search term in the Rare Disease Database.)

Standard Therapies

Treatment of Cohen syndrome may include surgery to correct facial deformities, visual problems, webbed fingers and/or undescended testicles. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Cohen Syndrome Resources



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Kolehmainen J, Black GC, Saarinen A, et al. Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. Am J Hum Genet. 2003;72:1359-69.

Chandler KE, Kidd A, Al-Gazali L, et al. Diagnostic criteria, clinical characteristics, and natural history of Cohen syndrome. J Med Genet. 2003;40:233-41.

Chandler KE, Biswas S, Lloyd IC, et al. The ophthalmic findings in Cohen syndrome. Br J Ophthalmol. 2002;86:1395-98.

Kivitie-Kallio S, Larsen A, Kajasto K, et al. Neurological and psychological findings in patients with Cohen syndrome: a study of 18 patients aged 11 months to 57 years. Neuropediatrics. 1999;30:181-89.

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Cohen Syndrome; COH1. Entry Number; 216550: Last Edit Date; 7/23/2004.

Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. Cohen syndrome. nd. 2pp.

Cohen Syndrome: Contact a Family. nd. 2pp.

Cohen syndrome. Orphanet. nd. 2pp.

Garcia Ballesta C, Perez Lajarin L, Cortes Lillo O. Cohen syndrome. Orphanet. November 2003. 5pp.

Cohen Syndrome. The GAPS INDEX. nd. 17pp.

Cohen Syndrome Support Group. Specific Eye Conditions (SPECS). nd. 2pp.

Report last updated: 2008/05/27 00:00:00 GMT+0