Early Diagnostic Signs and the Natural History of Typical Findings in Cohen Syndrome

J Pediatr. 2023 Jan:252:93-100. doi: 10.1016/j.jpeds.2022.08.052. Epub 2022 Sep 5.


Objective: To describe the clinical presentation and long-term clinical features of a molecularly confirmed cohort with Cohen syndrome.

Study design: Twelve patients with Cohen syndrome aged 0.2-13.9 years from 8 families with a median follow-up of 7 years were enrolled to the study. Genetic analyses were made by VPS13B and whole-exome sequencing analyses.

Results: Biallelic VPS13B variants, including 3 nonsense, 1 frameshift, and 1 splice-site variant, and a multiexon deletion were detected. Prader-Willi syndrome-like features such as hypotonia, small hands, round face with full cheeks, almond-shaped eyes, and micrognathia were observed in all infantile patients. Beginning from age 4 years, it was noticed that the face gradually elongated and became oval. The typical facial features of Cohen syndrome such as a long face, beak-shaped nose, and open-mouth appearance with prominent upper central incisors became evident at age 9. Other Cohen syndrome features including retinopathy (11/11), neutropenia (11/12), truncal obesity (5/12), and myopia (5/11) were detected at the median ages of 7.8, 7, 7.5, and 5 years, respectively. Eleven patients aged older than 5 years at their last examination had severe speech delay.

Conclusions: A differential diagnosis of Cohen syndrome in the infancy should be made with Prader-Willi syndrome, and that the typical facial features for Cohen syndrome is prominent at age 9 years, when retinopathy, neutropenia, and truncal obesity become evident. Moreover, adding the severe speech delay to the diagnostic criteria should be considered.

Keywords: Cohen syndrome; VPS13B; chorioretinal dystrophy; facial features; hypotonia; neutropenia; speech delay.

MeSH terms

  • Child
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics
  • Language Development Disorders*
  • Microcephaly* / diagnosis
  • Microcephaly* / genetics
  • Muscle Hypotonia / diagnosis
  • Muscle Hypotonia / genetics
  • Myopia* / diagnosis
  • Myopia* / genetics
  • Neutropenia*
  • Obesity / diagnosis
  • Obesity / genetics
  • Prader-Willi Syndrome*
  • Retinal Degeneration* / genetics
  • Vesicular Transport Proteins / genetics


  • Vesicular Transport Proteins

Supplementary concepts

  • Cohen syndrome