Cohen syndrome is an inherited disorder that affects many parts of the body and is characterized by developmental delay, intellectual disability, small head size (microcephaly), and weak muscle tone (hypotonia). Other features common in this condition include worsening nearsightedness (myopia), breakdown (degeneration) of the light-sensitive tissue at the back of the eye (retinal dystrophy), an unusually large range of joint movement (hypermobility), and distinctive facial features. These facial features typically include thick hair and eyebrows, long eyelashes, unusually-shaped eyes (down-slanting and wave-shaped), a bulbous nasal tip, a smooth or shortened area between the nose and the upper lip (philtrum), and prominent upper central teeth. The combination of the last two facial features results in an open mouth.

The features of Cohen syndrome vary widely among affected individuals. Additional signs and symptoms in some individuals with this disorder include low levels of white blood cells (neutropenia), overly friendly behavior, and obesity that develops in late childhood or adolescence. When obesity is present, it typically occurs around the torso, with the arms and legs remaining slender (called truncal obesity). Individuals with Cohen syndrome may also have narrow hands and feet, and slender fingers.

The exact incidence of Cohen syndrome is unknown. It has been diagnosed in fewer than 1,000 people worldwide. More cases are likely undiagnosed.

Mutations in the VPS13B gene (also called the COH1 gene) cause Cohen syndrome. The protein produced from this gene is a part of the Golgi apparatus, which is a cell structure in which newly produced proteins are modified so they can carry out their functions. In particular, the VPS13B protein is involved in a modification called glycosylation, which is the attachment of sugar molecules to proteins. The VPS13B protein also appears to be involved in the sorting and transporting of proteins inside the cell. This protein is thought to be involved in normal growth and development of nerve cells (neurons) and fat cells (adipocytes), and may play a role in the storage and distribution of fats in the body.

Most mutations in the VPS13B gene are believed to prevent the production of functional VPS13B protein. Studies suggest that a loss of this protein disrupts the organization of the Golgi apparatus and impairs normal glycosylation. However, it is not known how a lack of functional VPS13B protein or these cellular changes lead to the signs and symptoms of Cohen syndrome. Researchers speculate that problems with neuron development underlie microcephaly, intellectual disability, and retinal dystrophy and that abnormal fat storage may cause truncal obesity in people with Cohen syndrome.

Genetic Testing Information

• Genetic Testing Registry: Cohen syndrome

Genetic and Rare Diseases Information Center

• Cohen syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• COHEN SYNDROME; COH1

Scientific Articles on PubMed

• PubMed

• Duplomb L, Duvet S, Picot D, Jego G, El Chehadeh-Djebbar S, Marle N, Gigot N, Aral B, Carmignac V, Thevenon J, Lopez E, Riviere JB, Klein A, Philippe C, Droin N, Blair E, Girodon F, Donadieu J, Bellanne-Chantelot C, Delva L, Michalski JC, Solary E, Faivre L, Foulquier F, Thauvin-Robinet C. Cohen syndrome is associated with major glycosylation defects. Hum Mol Genet. 2014 May 1;23(9):2391-9. doi: 10.1093/hmg/ddt630. Epub 2013 Dec 13. Citation on PubMed
• Kolehmainen J, Black GC, Saarinen A, Chandler K, Clayton-Smith J, Traskelin AL, Perveen R, Kivitie-Kallio S, Norio R, Warburg M, Fryns JP, de la Chapelle A, Lehesjoki AE. 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 Jun;72(6):1359-69. doi: 10.1086/375454. Epub 2003 May 2. Citation on PubMed or Free article on PubMed Central
• Limoge F, Faivre L, Gautier T, Petit JM, Gautier E, Masson D, Jego G, El Chehadeh-Djebbar S, Marle N, Carmignac V, Deckert V, Brindisi MC, Edery P, Ghoumid J, Blair E, Lagrost L, Thauvin-Robinet C, Duplomb L. Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome. Hum Mol Genet. 2015 Dec 1;24(23):6603-13. doi: 10.1093/hmg/ddv366. Epub 2015 Sep 10. Citation on PubMed
• Seifert W, Holder-Espinasse M, Spranger S, Hoeltzenbein M, Rossier E, Dollfus H, Lacombe D, Verloes A, Chrzanowska KH, Maegawa GH, Chitayat D, Kotzot D, Huhle D, Meinecke P, Albrecht B, Mathijssen I, Leheup B, Raile K, Hennies HC, Horn D. Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome. J Med Genet. 2006 May;43(5):e22. doi: 10.1136/jmg.2005.039867. Citation on PubMed or Free article on PubMed Central
• Seifert W, Kuhnisch J, Maritzen T, Horn D, Haucke V, Hennies HC. Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein required for Golgi integrity. J Biol Chem. 2011 Oct 28;286(43):37665-75. doi: 10.1074/jbc.M111.267971. Epub 2011 Aug 24. Citation on PubMed or Free article on PubMed Central
• Seifert W, Kuhnisch J, Maritzen T, Lommatzsch S, Hennies HC, Bachmann S, Horn D, Haucke V. Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. J Biol Chem. 2015 Feb 6;290(6):3349-58. doi: 10.1074/jbc.M114.608174. Epub 2014 Dec 9. Citation on PubMed or Free article on PubMed Central
• Wang H, Falk MJ, Wensel C, Traboulsi EI. Cohen Syndrome. 2006 Aug 29 [updated 2016 Jul 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1482/ Citation on PubMed