Cohen Syndrome

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Cohen Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Pepper Syndrome

Disorder Subdivisions

  • None

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.

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 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


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



Gunay-Aygun M. Cohen Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:172-73.

Jones KL. Ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:206-07.

Gorlin RJ, Cohen MMJr, Levin LS. Eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:349-50.


Kivitie-Kallio S, Norio R. Cohen syndrome: essential features, natural history, and heterogeneity. Am J Med Genet. 2001;102:125-35.


Falk MJ, Feiler HS, Neilson DE, et al. Cohen syndrome in the Ohio Amish. Am J Med Genet. 2004;128A:23-28.

Hennies HC, Rauch A, Seifert W, et al. Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome. Am J Hum Genet. 2004;75:138-45.

Kolehmainen J, Wilkerson R, Lehesjoki AE, et al. Delineation of the Cohen syndrome following a large-scale genotype-phenotype screen. Am J Hum Genet. 2004;75:122-27.

Karpf J, Turk J, Howlin P. Cognitive, language, and adaptive behavior profiles in individuals with a diagnosis of Cohen syndrome. Clin Genet. 2004;65:327-32.

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.


Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223


Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766



Cohen Syndrome Association

DDC Special Needs Clinic

14567 Madison Rd.

Middlefield, OH 44062


Tel: (410)632-1668

Fax: (410)632-1697


For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see