Cleft palate in a multigenerational family with a microdeletion of 20p12.3 involving BMP2

Area of Science:

• Genetics and Developmental Biology
• Craniofacial Development
• Human Genetics

Background:

• Cleft palate (CP) is a common birth defect with diverse causes, including genetic factors.
• Bone morphogenetic proteins (BMPs) are crucial for embryonic development, particularly bone formation and palate morphogenesis.
• BMP2 haploinsufficiency has been linked to syndromic CP.

Observation:

• A multigenerational family presented with a history of CP due to a 2.3 Mb deletion on chromosome 20p12.3, encompassing the BMP2 gene.
• The proband exhibited submucous CP, failure to thrive (FTT), global developmental delays (DD), and dysmorphic features.
• The affected father had an overt CP and similar dysmorphic features but no FTT or DD, indicating variable expressivity.

Findings:

• The deletion directly implicates BMP2 in the etiology of syndromic CP within this family.
• The variable clinical presentation (high penetrance, variable expressivity) of BMP2 haploinsufficiency was observed.
• This case provides additional evidence for BMP2's role in syndromic cleft palate.

Implications:

• Understanding the genetic basis of CP, particularly the role of BMP2, can inform diagnosis and genetic counseling.
• Further research into BMP2 function may reveal therapeutic targets for craniofacial development disorders.
• This study contributes to the broader understanding of genetic contributions to birth defects and developmental syndromes.