Rhizomelic short stature with dysmorphism in two siblings due to <i>PKDCC</i> 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 (<i>PKDCC</i>) gene, also known as vertebrate lonesome kinase. Pathogenic variants in the <i>PKDCC</i> 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 <i>PKDCC</i> 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 <i>PKDCC</i> pathogenic variant, underscoring the importance of genetic screening in cases of short stature accompanied by dysmorphism and dysplasia.