Genotype-Phenotype Correlation of Distal 2q37 Deletions

Abstract

Brachydactyly mental retardation syndrome (BDMR) typically results from large deletions (>2–9 Mb) in distal 2q37. Haploinsufficiency of <i>HDAC4</i> with incomplete penetrance has been proposed as the primary genetic cause of BDMR. To date, pure 2q37 deletions distal to <i>HDAC4</i> were reported only in a limited number of individuals who share a subset of the clinical manifestations seen in cases with 2q37 deletions encompassing <i>HDAC4</i>. Here, we present a 4-year-old African American male who carries the smallest established 2q37.3 deletion distal to <i>HDAC4</i> (827.1 kb; 16 OMIM genes). His clinical features that overlap with BDMR phenotypes include expressive-receptive language delay, behavioral issues, mild facial dysmorphism such as frontal bossing, and bilateral 5th finger brachydactyly and clinodactyly. The deletion was inherited from his mother with a history of learning difficulties and similar facial dysmorphism. This case provides important genotype-phenotype correlation information and suggests a 2q37 region distal to <i>HDAC4</i> encompassing the <i>HDLBP</i> gene may contribute to a subset of clinical features overlapping with those seen in individuals with BDMR.