Snijders Blok-Campeau syndrome: a novel neurodevelopmental genetic disorder

Abstract

Snijders Blok-Campeau syndrome is a recently discovered genetic disorder characterized by childhood apraxia of speech, delays in intellectual development, and a plethora of other neurodevelopmental disorders (e.g., vision disorders, muscle atony, etc.). In most cases, Snijders Blok-Campeau syndrome results from de novo mutations in the CHD3 gene, which encodes chromodomain-helicase-DNA-binding protein 3 (CHD3). However, the lite­rature also describes cases of inherited mutations in CHD3. In these cases, heterozygous parents carrying a mutant variant in the CHD3 gene may lack features of Snijders Blok-Campeau syndrome or exhibit a mild manifestation of the syndrome, while their offspring, carrying the same CHD3 mutations in heterozygous form, exhibit a complete set of features of Snijders Blok-Campeau syndrome. This phenomenon has yet to be clearly explained. Only two cases of Snijders Blok-Campeau syndrome caused by homozygous CHD3 mutations have been described in the literature. Notably, the majority of described mutations in CHD3 are point missense mutations. CHD3 is a chromatin remodeling protein and a crucial component of the nucleosome remodeling and deacetylase (NuRD) complex, which is important for gene regulation during brain development. The two-domain region of CHD3 with ATP-dependent helicase activity is the most important part of the protein. Although the majority of mutations causing Snijders Blok-Campeau syndrome are found in the part of CHD3 encoding this region with ATP-dependent helicase activity, it has been impossible to draw a clear correlation between the localization of the mutations and the severity of the phenotype. To date, no documented cases of Snijders Blok-Campeau syndrome have been reported in Ukraine. In this work, we aim to provide a comprehensive review of the features of Snijders Blok-Campeau syndrome to facilitate identification and genetic diagnostics of the syndrome.