Rhizomelic short stature with dysmorphism in two siblings due to PKDCC gene pathogenic variants

Skeletal dysplasias are a common cause of short stature and are often linked with multisystemic features. The Hedgehog signaling pathway plays a vital role in skeletal development and is regulated by the protein kinase domain-containing cytoplasmic (PKDCC) gene, also known as vertebrate lonesome kinase. Pathogenic variants in the PKDCC gene have been reported in very few patients worldwide and are inherited in an autosomal recessive pattern. We report 2 siblings—a 6-year-old girl and a 3-year-old boy—who present with rhizomelic short stature, facial dysmorphism, low-set ears, and umbilical hernia. The girl has a history of cardiac septal defects and camptodactyly, while her younger brother shows no systemic complications. A comprehensive laboratory panel was normal in both siblings, and whole exome sequencing revealed a homozygous splice acceptor variant of the PKDCC gene on chromosome 2:g.42280377A>T, (NM_138370.3, c.640-2A>T), leading to a diagnosis of rhizomelic limb shortening with dysmorphic features. To our knowledge, this is the first report of siblings from India with a PKDCC pathogenic variant, underscoring the importance of genetic screening in cases of short stature accompanied by dysmorphism and dysplasia.