Prevalence pattern, phenotypic manifestation, and descriptive genetics of congenital limb deficiencies in Pakistan

Abstract

Background: Congenital limb deficiency (CLD) is a group of very rare disorders characterized by substantial hypoplasia or the complete absence of 1 or more bones of limbs. Congenital limb deficiency has a significant physical, clinical, and psychological burden on the affected individuals and their families. This cross-sectional study aimed to describe the prevalence pattern, phenotypic manifestations, and biodemographic factors associated with CLD in a cohort assembled from the Pakistani population from the Northwestern region. Methods: Through a prospective cross-sectional study, 141 individuals having 166 limbs with CLD were recruited during 2017‐2021. Results: There were 77 (55%) individuals with transverse defects, 61 (43%) with longitudinal defects, and 3 (2%) with Intercalary defects. Among the patients with transverse defects, 52 had terminal amputations and 25 had symbrachydactyly. Among the longitudinal defects, thumb aplasia/hypoplasia was the most common presentation (20 patients), followed by oligodactyly (18), and radial hemimelia (18). Eighty six percent had upper-limb deficiencies, 83% had unilateral deficiencies, and 92% were sporadic in nature. The parental consanguinity was observed in 33% individuals, and 79% cases had an isolated presentation which may be indicative of the substantial role of nongenetic factors in the etiology of CLD. Conclusions: This study demonstrates marked heterogeneity in CLD subtypes in the involvement of limbs and associated variables. There is a need to establish a national registry for CLD, molecular genetic diagnosis, and multidisciplinary medical and social rehabilitation services for these individuals.