Severe limb malformations in a WDR37-related disorder: A report of a rare case

WDR37-related disorders are rare multisystem conditions primarily involving the brain, eyes, and heart, with skeletal features such as limb or spine defects having been rarely reported. Here, we present a 4-month-old male infant of Arab ethnicity with a new heterozygous variant in WDR37 (c.8 C>G, p.Thr3Arg) exhibiting severe skeletal malformations, including left upper-limb amelia, right radial aplasia with wrist drop, a split foot, a rocker-bottom foot, cervical and thoracic hemivertebrae with kyphoscoliosis, and a syrinx. Brain imaging also showed ventriculomegaly and dysgenesis of the corpus callosum; he additionally had distinctive facial features and congenital heart defects. Whole-exome sequencing revealed additional variants of uncertain significance in ARF3 and ANKRD17 , raising the possibility of an oligogenic effect. The infant's presentation significantly broadens the WDR37 phenotype to include dramatic limb and spinal malformations and highlights the gene as a potential cause of complex skeletal disorders, warranting deeper study of oligogenic roles. • Novel heterozygous WDR37 c.8 C>G (p.Thr3Arg) variant identified by WES • Unprecedented limb and spinal malformations including amelia and hemivertebrae • Case broadens WDR37 phenotype beyond neurological, ocular, and facial anomalies • Possible oligogenic contribution from ARF3 and ANKRD17 variants • Multidisciplinary care essential for optimal orthopedic and neurologic outcomes