Cohen syndrome – an important differenzial diagnosis for children with mental retardation and secondary microcephaly

Introduction: Cohen syndrome (CS; OMIM 216550) is a rare autosomal recessive inherited disorder. Main features are global developmental delay, secondary microcephaly, muscular hypotonia, early-onset myopia or retinal dystrophy, intermittend isolated neutropenia and typical facial dysmorphism. In addition, truncal obesity and characteristic sociable behaviour are often present. Cohen syndrome is caused by mutations in the COH1 (VPS13B) gene located on chromosome 8q22-q23.

Case report: We report about four children aged between 2 and 16 from three different families. These patients show a significant developmental delay, hypotonia, myopia respectivily retinopathy and neutropenia. Three of the four children have a secondary microcephaly, one has a primary microcephaly accompanied with low birth weight. Our patients reveal characteristic facial features including low hairline, thick eyebrows, prominent nasal root and short philtrum. The two elder patients additionally exhibit truncal obesity and narrow hands with tapering fingers. The clinically anticipated diagnosis of Cohen syndrome could be confirmed by molecular genetic testing of the four patients.

Discussion: Several symptoms should raise the diagnostic suspicion of Cohen syndrome. Those are psychomotor retardation, acquired microcephaly and at least two of the three following symptoms: distinct facial gestalt, progressive chorioretinal dystrophy or myopia and isolated neutropenia. Due to the large size of the COH1 locus genetic testing results to be laborious and costly. Therefore, it should only be requested for patients manifesting clear signs of Cohen syndrome.