Campomelic dysplasia (CD) is a rare, often lethal skeletal dysplasia characterized by angular bowing and shortening of the long bones, severe respiratory distress, and XY sex reversal. It is caused by chromosome abnormalities or mutations affecting expression of the SOX9 gene located on chromosome 17q24.3-q25.1. Approximately 75% of patients with CD that have a 46,XY karyotype exhibit partial or complete sex reversal, ranging from ambiguous genitalia to normal female external genitalia. In addition to bowing of the long bones, skeletal features of CD include club feet, a bell-shaped and underdeveloped thorax, eleven pairs of ribs, and hypoplastic scalpulae.
CD is also associated with distinctive facial features including micrognathia, midfacial hypoplasia, a long philtrum, depressed nasal bridge, hypertelorism, and Pierre Robin cleft palate. Macrocephaly, congenital heart defects, absence of the olfactory bulbs, renal malformations, and pancreatic abnormalities have also been reported. Many infants die shortly after birth from respiratory compromise due to cervical spine instability, laryngotracheomalacia, hypoplastic lungs, and/or narrow airways. Children who survive the neonatal period often develop hearing loss, developmental delay, short stature, and progressive kyphoscoliosis.
A small subgroup of patients with CD lack significant bowing of the limbs and are described as having acampomelic campomelic dysplasia (ACD). Patients with ACD have other typical features of campomelic dysplasia, and in some cases radiographs may reveal mild campomelia.