Du Pan Syndrome with Autoamputation of Digits in a Neonate: A Case Report

Background: Du Pan Syndrome (DPS) (OMIM 228900) is a rare autosomal recessive skeletal dysplasia caused by variants in the GDF5 gene. It is distinguished by complex brachydactyly and fibular aplasia/hypoplasia, a type of acromesomelic dysplasia. Clinical Description: A term male neonate born out of third-degree consanguineous marriage, presented with abnormalities of the digits of the upper and lower limbs. Antenatal scans had detected soft tissue swelling around the second great toe. Examination revealed a length <10 th percentile, normal weight, and head circumference, associated with necrosed right great toe. There was severe brachydactyly in all digits of the upper and lower limbs. Management: Radiographs confirmed fibular aplasia. Doppler evaluation on Day 1 showed absent arterial flow in the left great toe and normal vasculature in the proximal limbs. Both great toes underwent autoamputation. A homozygous mutation in the GDF5 gene c. 1322T>C(p.Leu441Pro) was discovered by whole-exome sequencing. The neonate was managed conservatively. Genetic counselling was provided to the parents. On follow-up, the infant had normal neurodevelopment with persistent brachydactyly. Conclusion: This case broadens the phenotypic spectrum of DPS by demonstrating a new vascular phenotype, suggesting the possible role of the GDF5 gene in angiogenesis.