Supernumerary ring chromosome 7 mosaicism: Case report, investigation of the gene content, and delineation of the phenotype

Abstract

We report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage‐dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro.