Tetramelic Monodactyly With Neonatal Encephalopathy: A Case Report

Congenital limb defects are etiologically heterogeneous congenital malformations, with genetic causes being one of the major contributors. We report a neonate with limb anomalies and severe encephalopathy in whom rapid trio whole-genome sequencing identified a pathogenic duplication at 10q24.31q24.32. A near-term male neonate presented with bilateral radial and tibial ray aplasia, with preserved ulnar and fibular elements, resulting in tetramelic monodactyly of the fifth digits. Family history revealed an apparent autosomal dominant pattern, with the patient's father and older sister similarly affected. In the first days of life, the patient developed unexplained apnea, respiratory failure requiring mechanical ventilation, and severe diffuse encephalopathy on continuous EEG monitoring. Brain MRI, head ultrasound, and metabolic workup were unremarkable. Echocardiography showed normal cardiac anatomy. Trio rapid whole-genome sequencing demonstrated a 10q24 duplication, a locus previously associated with split-hand/foot malformation. This genetic variant in this family leads to tetramelic monodactyly of the fifth digits across at least two generations.