Case Report: Novel rare ZMPSTE24 variation in a Han Chinese family with early onset mandibuloacral dysplasia type B lipodystrophy

Background Mandibuloacral dysplasia type B (MADB) is a rare autosomal recessive disorder characterized by heterogeneous manifestations, which is an extremely rare disorder with only a limited number of reported cases. Mutations in ZMPSTE24 are associated with MADB. Methods and results We reported a newborn who presented with core MADB manifestations (lipodystrophy, mandibular hypoplasia, joint contractures, shortened phalanges, and hypoplastic nails). We performed whole-genome sequencing and identified a rare novel a compound heterozygous ZMPSTE24 variant [GRCh37] del(1) (p34.2) NC_000001.10:g.40747005_41013142del and g.40737681C > T. To date, only 12 pediatric MADB cases have been reported overall. Affected individuals typically exhibit heterogeneous manifestations, including skeletal abnormalities (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, and joint contractures), cutaneous atrophy, lipodystrophy, and mottled cutaneous pigmentation. Conclusions This study expands the genotypic and clinical phenotypic spectrum of ZMPSTE24 -related MADB and reinforces the utility of whole-genome sequencing in early diagnosis and genetic counseling.