Clinical Guidance
To date, more than 300 individuals have been identified with biallelic pathogenic variants in VPS13B [, , , , , , ]. The following description of the phenotypic features associated with Cohen syndrome is based on these reports. Phenotypic features of Cohen syndrome are variable and include developmental delay, hypotonia, progressive retinal dystrophy and myopia, acquired microcephaly, joint laxity, characteristic facial features, truncal obesity, cheerful disposition, and neutropenia. The spectrum of these clinical findings ranges from severe to milder. Note: Certain statistics presented here are from the National Cohen Syndrome Database (NCSD) in which approximately 50% of individuals are Old Order Amish; the diagnosis of Cohen syndrome has been confirmed by molecular genetic testing in most individuals [H Wang, personal observation]. Table 2. Cohen syndrome: Frequency of Select Features
Feature | % of Persons w/Feature | Comment |
|---|
Developmental delay/ intellectual disability | 100% | Non-progressive; severity varies even between sibs |
Hypotonia | 90%-100% | Improves over time |
Microcephaly | 90%-100% | Develops during or after 1st yr of life |
Neutropenia | 90%-100% | Neutropenia may be overlooked or diagnosed in early infancy. |
Progressive high myopia | 90%-100% | — |
Retinal dystrophy | 90%-100% | Range reflects that some younger persons may not have reached the age that retinal dystrophy is typically diagnosed. |
Truncal obesity | 80% | Appearing in or after mid-childhood w/rapid onset |
Neurobehavioral/psychiatric manifestations | 75% | Cheerful friendly disposition |
Short stature | 65% | Hypotonia. Half of mothers whose children are included in the NCSD recalled reduced fetal movement during an otherwise normal pregnancy. Most newborns with Cohen syndrome are hypotonic; feeding and breathing difficulties, likely related to hypotonia, are common during the first days of life. |
Developmental Milestone | Age at Milestone Achievement Finnish Cohort1 | English Cohort2 |
Roll over | 4-12 mos | -- |
Sit independently | 10-18 mos | 12 months |
Walk independently | 2-5 yrs | 2.5 yrs |
Speak first words | 1-5 yrs | 2.5 yrs |
Speak in sentences | 5-6 yrs | 5 yrs |
Source: GeneReviews — "Cohen Syndrome"
