Genotype-Phenotype Correlation of Distal 2q37 Deletions

Area of Science:

• Genetics
• Human Molecular Genetics
• Developmental Biology

Background:

• Brachydactyly mental retardation syndrome (BDMR) is typically associated with large deletions (>2-9 Mb) in the distal 2q37 region.
• Haploinsufficiency of the HDAC4 gene has been proposed as the primary genetic cause of BDMR, though incomplete penetrance is noted.

Observation:

• A 4-year-old African American male presented with a small deletion (827.1 kb) in 2q37.3, distal to HDAC4.
• The deletion encompasses 16 OMIM genes, including HDLBP.
• Clinical features included language delay, behavioral issues, mild facial dysmorphism (frontal bossing), and bilateral 5th finger abnormalities (brachydactyly and clinodactyly).

Findings:

• This represents the smallest reported 2q37.3 deletion distal to HDAC4.
• The patient inherited the deletion from his mother, who had learning difficulties and similar facial features.
• The findings suggest that a region distal to HDAC4, potentially involving the HDLBP gene, contributes to a subset of BDMR-like phenotypes.

Implications:

• This case provides critical genotype-phenotype correlation data for 2q37 deletions.
• It expands the understanding of genetic contributions to BDMR and related developmental disorders.
• Further research into the role of genes distal to HDAC4 in 2q37 deletions is warranted.