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Overview

Cohen syndrome is typically associated with characteristic facies, truncal obesity, microcephaly, moderate to profound neurodevelopmental delay and progressive visual impairment.

Clinical features

The cardinal features of Cohen syndrome are:

  • global developmental delay;
  • early-onset myopia (age is five standard deviations above the mean) with progressive pigmentary retinopathy;
  • truncal obesity from mid childhood, with relatively short stature;
  • joint hypermobility;
  • facial dysmorphism: thick hair, eyebrows and eyelashes, down-slanting palpebral fissures, short, upturned philtrum, hypotonic facial expression with open mouth and prominent upper central incisors;
  • acquired microcephaly;
  • neutropenia (sometimes associated with aphthous ulcers); and
  • friendly disposition.

Other features include:

  • significant feeding difficulties in the neonatal period, requiring artificial feeding techniques;
  • failure to thrive;
  • neonatal hypotonia;
  • small or narrow hands or feet; and
  • increased chance of autoimmunity (diabetes mellitus, coeliac disease, thyroid conditions).

A clinical diagnosis of Cohen syndrome can be made in a proband with six of the eight cardinal features listed above.

Genetics

Cohen syndrome is caused by biallelic pathogenic variants (gene changes on both copies) in the VPS13B gene (previously referred to as COH1). VPS13B is involved in glycosylation, whereby glycans (sugars) are attached to lipids or proteins. Glycoproteins and glycolipids have important functions in all tissues and organs. When errors in glycosylation occur, therefore, multiple organs can be affected, and there will nearly always be a neurological feature.

Pathogenic variants are typically those that cause loss of function of the gene, including whole gene deletions of VPS13. Common founder pathogenic variants in VPS13 have been identified in the Finnish and Amish populations (see resources section to read more).

For information about testing, see Presentation: Child with developmental delay or intellectual disability.

Inheritance and genomic counselling

Cohen syndrome is an autosomal recessive condition. The parents of most affected individuals are carriers of the condition and therefore have a 25% (one-in-four) chance of having another affected child.

Management

Management of children with Cohen syndrome is complex and should be delivered via a multidisciplinary team, including an ophthalmology and haematology assessment. Management approach guidelines have been published by several authors – see our resources list. Treatment is directed toward the clinical manifestation of the individual patient. Medications known to decrease the neutrophil count should be used with caution.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 19/03/2023
  • Next review due: 19/03/2025
  • Authors: Dr Lianne Gompertz
  • Reviewers: Dr Ellie Hay