Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Nievergelt syndrome (NS) is an autosomal dominant mesomelic dysplasia with characteristic limb and tibia deformities.
• The pathogenesis of NS and phenotypically similar conditions like Savarirayan-type mesomelic dysplasia remains largely unknown.

Observation:

• A patient presented with fibular agenesis, abnormal tibiae, urogenital tract malformations, failure to thrive, convulsions, and recurrent apneas.
• Skeletal findings aligned with Savarirayan-type mesomelic dysplasia, but the patient also exhibited central nervous system and urogenital anomalies.

Findings:

• Array comparative genomic hybridization identified a de novo 500 kb microdeletion on chromosome 2q11.1.
• This deletion encompasses the LAF4/AFF3 (lymphoid-nuclear-protein-related AF4) gene, crucial for embryonic development.

Implications:

• LAF4/AFF3 gene haploinsufficiency is linked to limb, brain, and urogenital malformations.
• This finding expands the phenotypic spectrum of Nievergelt syndrome and provides insight into its genetic basis.