A novel CEP57 gene mutation in mosaic variegated aneuploidy syndrome 2: case report

Mosaic variegated aneuploidy syndrome 2 (MVA2) is an uncommon autosomal recessive genetic condition caused by mutations in the CEP57 gene. It is characterized by intrauterine growth restriction, severe short stature, facial dysmorphism, and skeletal abnormalities. Most affected individuals also show congenital cardiac defects and delayed development. To date, only 16 patients have been reported.

We report a 6-year-old girl of consanguineous Moroccan parents, presenting with severe short stature, clinodactyly, and dysmorphic facial features including prominent forehead, triangular face, micro-retrognathia, and low set ears. Neurodevelopment was initially normal, but mild intellectual disability was then noted. Genetic testing including karyotype, array-CGH, and Silver-Russell syndrome were normal. Finally, whole exome sequencing revealed a homozygous c.834_844dupCAATGTTCAGC variant in CEP57, classified as likely pathogenic. Familial segregation confirmed heterozygosity in both parents and siblings.

This report describes a novel homozygous variant of CEP57, expanding the clinical and genetic spectrum of MVA2 syndrome. Although, karyotype should be firstly requested if MVA is suspected, whole exome sequencing is crucial. Growth hormone therapy shows limited response in this syndrome, and the association with cancer predisposition should be further studied.