The campomelic syndrome: Review, report of 17 cases, and follow‐up on the currently 17‐year‐old boy first reported by Maroteaux et al in 1971

Abstract

We report 17 cases of the campomelic syndrome (CS) and a follow-up of one of the original patients of Maroteaux et al who is now 17 years old. Our review is based on 97 patients, including our own. An infant with the CS presents at birth with spectacularly short and bowed femora and tibiae. The initial chest radiograph confirms the diagnosis by demonstrating extremely small bladeless scapulae and hypoplastic pedicles of many thoracic vertebrae. Ossification of the sternal segments, pubis, talus, and knee epiphyses is also retarded. Usually the hips are dislocated and talipes equinovarus deformities are present. There is a small chondrocranium and a disproportionately large neurocranium. The bell-shaped chest, narrow superiorly, does not explain the degree of respiratory distress that soon ensues. Narrow airways from defective tracheo-bronchial cartilage can often be demonstrated on the radiograph, but micrognathia, retroglossia, cleft palate, hypoplastic lungs, and even CNS-based hypotonia contribute to the respiratory problem. Internal anomalies include frequent absence of olfactory bulbs and tracts and dilatation of cerebral ventricles, heart defects (PDA, VSD, stenosis of aortic isthmus), hydroureter and hydronephrosis, renal hypoplasia, renal hypoplasia, and rarely renal cysts.

Radiology and histopathology of the bent limbs in campomelic dysplasia: implications in the aetiology of the disease and review of theories

“…With regard to aetiology, in the first reports attention was addressed to an exogenous factor [7,19,20,29,30,38,43], while later it shifted to a genetic defect [1,5,6,12,13,17,25,26,34,36,47].…”

MiniSOX9, a dominant-negative variant in colon cancer cells

“…SOX members are conserved across species and are involved in a number of developmental processes. Heterozygous mutations of the SOX9 gene are responsible for campomelic dysplasia (Foster et al, 1994), an autosomal dominant disorder resulting in skeletal and developmental abnormalities and in frequent neonatal death because of respiratory deficiencies (Houston et al, 1983). SOX9 was then shown to be a key regulator of chondrogenesis (Akiyama et al, 2002), neurogenesis (Stolt et al, 2003), male sex determination (Chaboissier et al, 2004), neural crest development (Cheung et al, 2005) and biliary development (Antoniou et al, 2009).…”

Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

“…Congenital birth defects associated with these disorders can affect many different organ systems, including the respiratory system. Infants that are born with CD/ACD often die in the neonatal period as a result of respiratory distress, which can be a result of abnormal upper airway development or hypoplastic lungs (20)(21)(22)(23)(24)(25). In other tissues, Sox9 has a diverse array of functions.…”