Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous SMARCA4 Deletion Detected by High-Resolution aCGH

Anastasios Mitrakos; Leandros Lazaros; Amelia Pantou; Ariadni Mavrou; Emmanuel Kanavakis; Maria Tzetis

doi:10.1159/000508563

Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous SMARCA4 Deletion Detected by High-Resolution aCGH

Mol Syndromol. 2020 Jul;11(3):141-145. doi: 10.1159/000508563. Epub 2020 Jun 13.

Authors

Anastasios Mitrakos^{1

2}, Leandros Lazaros¹, Amelia Pantou¹, Ariadni Mavrou¹, Emmanuel Kanavakis¹, Maria Tzetis²

Affiliations

¹ Genesis Genoma Lab, Genetic Diagnosis, Clinical Genetics & Research, Athens, Greece.
² Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Coffin-Siris Syndrome 4 is an autosomal dominant congenital malformation syndrome caused by heterozygous mutations in the SMARCA4 gene with its main features being intellectual disability, developmental delay, behavioral abnormalities, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Here, we report a young woman with developmental delay, moderate intellectual disability, and bilateral sensorineural hearing loss, referred for genetic testing. High-resolution chromosomal microarray analysis identified a 428-kb deletion in chromosome 19 which included the SMARCA4 gene. We conclude that haploinsufficiency of SMARCA4 may be a valid pathophysiological mechanism leading to milder Coffin-Siris syndrome phenotypes.

Keywords: Array CGH; Chromosomal microarray analysis; Cognitive delay; Deletion; Haploinsufficiency; Intellectual disability; Language impairment.