What are the early signs that a child might have Cohen syndrome, and when should I seek a genetics referral?

Look for developmental delay, low muscle tone, unusually shaped eyes, thick eyebrows, a bulbous nasal tip, and a tendency toward truncal obesity after age 5. If two or more of these features are present, especially with a family history of consanguinity, ask your pediatrician for a referral to a clinical geneticist for VPS13B testing.

What eye problems are common, and how often should ophthalmology follow‑up be scheduled?

Progressive myopia, retinal dystrophy, and cataracts are typical. Baseline comprehensive eye exam at diagnosis, then yearly dilated retinal examinations. If visual acuity declines rapidly or new retinal changes appear, increase visits to every 6 months and discuss low‑vision aids or surgical options as needed.

My teen is gaining excess weight despite a normal diet. What lifestyle measures help control obesity in Cohen syndrome?

Focus on a structured, calorie‑controlled diet rich in fruits, vegetables, lean protein, and whole grains; limit sugary drinks and processed snacks. Encourage daily aerobic activity (e.g., swimming, brisk walking) for at least 30 minutes, and incorporate strength‑training twice weekly to preserve lean muscle. A dietitian familiar with metabolic aspects of Cohen syndrome can tailor a plan.

How should the chronic neutropenia seen in Cohen syndrome be monitored and treated?

Regular complete blood counts (CBC) every 3–6 months are recommended. If neutrophil counts fall below 500 cells/µL or the child has recurrent bacterial infections, a hematologist may start prophylactic antibiotics and consider granulocyte colony‑stimulating factor (G‑CSF) injections to boost neutrophil production.

Cohen syndrome

Cohen syndrome is a rare inherited disorder characterized by developmental delay, intellectual disability, and distinctive facial features, often accompanied by obesity and eye problems.

Overview

Cohen syndrome is an inherited disorder that affects many parts of the body. It is characterized by developmental delay, intellectual disability, small head size, and weak muscle tone (hypotonia). Other common features include worsening nearsightedness, retinal dystrophy, hypermobility, and distinctive facial features such as thick hair and eyebrows, unusually-shaped eyes, a bulbous nasal tip, a shortened philtrum, prominent upper central teeth, and an open mouth. Additional signs and symptoms may include low white blood cell counts (neutropenia), overly friendly behavior, and obesity that develops in late childhood or adolescence, typically truncal obesity with slender arms and legs. Individuals may also have narrow hands and feet.

Frequency

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

Causes

Mutations in the VPS13B gene (also called the COH1 gene) cause Cohen syndrome. The protein produced from this gene is part of the Golgi apparatus, a cell structure where newly produced proteins are modified for function. The VPS13B protein is involved in glycosylation—attachment of sugar molecules to proteins—and in sorting and transporting proteins inside the cell. It is thought to play a role in normal growth and development of neurons and adipocytes, and may influence fat storage and distribution.

Learn more about the gene associated with Cohen syndrome

VPS13B

Inheritance

This condition is inherited in an autosomal recessive manner, meaning both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms of the condition.

Other Names for This Condition

Hypotonia, obesity, and prominent incisors
Norio syndrome
Obesity-hypotonia syndrome
Pepper syndrome
Prominent incisors-obesity-hypotonia syndrome

Additional Information & Resources

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

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.
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.
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.
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.
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.
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.
Wang H, Xin B, Wensel C, Traboulsi EI. Cohen Syndrome. 2006 Aug 29 [updated 2025 Dec 4]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle; 1993-2026.

Medical Encyclopedia

Genetics
Hypotonia
Intellectual disability

Understanding Genetics

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