Genotype-Phenotype Correlation of Distal 2q37 Deletions

Cytogenet Genome Res. 2022;162(5):237-243. doi: 10.1159/000526660. Epub 2022 Dec 14.

Abstract

Brachydactyly mental retardation syndrome (BDMR) typically results from large deletions (>2-9 Mb) in distal 2q37. Haploinsufficiency of HDAC4 with incomplete penetrance has been proposed as the primary genetic cause of BDMR. To date, pure 2q37 deletions distal to HDAC4 were reported only in a limited number of individuals who share a subset of the clinical manifestations seen in cases with 2q37 deletions encompassing HDAC4. Here, we present a 4-year-old African American male who carries the smallest established 2q37.3 deletion distal to HDAC4 (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 HDAC4 encompassing the HDLBP gene may contribute to a subset of clinical features overlapping with those seen in individuals with BDMR.

Keywords: 2q37 deletion; Brachydactyly mental retardation syndrome; Deletion distal to HDAC4; Genotype-phenotype correlation.

Publication types

  • Case Reports

MeSH terms

  • Brachydactyly* / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 2
  • Genetic Association Studies
  • Humans
  • Intellectual Disability* / genetics
  • Male
  • Phenotype

Supplementary concepts

  • Chromosome 2q37 deletion syndrome