Campomelia, Cumming Type

Clinical Features

Cumming et al. (1986) described a stillborn male infant, born at 27 weeks' gestation of an Egyptian couple related as first cousins once removed, who had bowed limbs, marked cervical lymphocele (a term the authors preferred to cystic hygroma), polycystic dysplasia of the kidneys, pancreas, and liver, short gut, and polysplenia. Two apparently identically affected stillborn infants, a male and a female, had been born previously at 28 weeks' gestation.

Urioste et al. (1991) described 2 female sibs, the offspring of healthy nonconsanguineous parents, who died shortly after birth. They showed generalized lymphedema, cervical lymphocele, shortness of limbs, bowed long bones, and multicystic kidneys with fibrotic liver or pancreas.

Ming et al. (1997) described a fetus with tetramelic campomelia, polysplenia, multicystic dysplastic kidneys, and cervical lymphocele. In addition, there were anomalies not previously described in this condition, including abnormal lung lobation with bilateral left bronchial morphology, dextrocardia, total anomalous pulmonary venous return, left superior vena cava, and right aortic arch. The pancreas was short, with absence of the body and tail. Ming et al. (1997) suggested that the syndrome reported by Cumming et al. (1986) could be expanded to include polysplenia with heterotaxia and that Cumming syndrome may be considered another autosomal recessive condition associated with a laterality defect.

Perez del Rio et al. (1999) reported the cases of 2 sisters born to young parents of unknown consanguinity. The clinical and autopsy findings were considered to be consistent with the diagnosis of Cumming syndrome. The first fetus was stillborn at 36 weeks and showed hydrops, cloverleaf skull, and a severely deformed face, with a considerable amount of redundant subcutaneous tissue, massive cervical edema, and microphthalmia. The facial appearance was said to be similar to that of a 40-day embryo. The chest was narrow and the abdomen swollen with mild ascites. All 4 limbs were short and bowed. Autopsy revealed lung hypoplasia, enlarged cystic kidneys, and hepatomegaly. The second fetus, delivered by cesarean section at 31 weeks, died within minutes after delivery. The external appearance was similar to that of her sister, with cloverleaf skull and redundant soft tissue in the occipital and facial regions. Again, lung hypoplasia and enlarged cystic kidneys were found. The liver likewise showed polycystic dysplasia.

Watiker et al. (2005) reported 2 patients originally diagnosed as having Cumming syndrome who were subsequently found to have mutations in the SOX9 gene, prompting reassessment of the cases and reclassification as campomelic dysplasia (114290). Features consistent with Cumming syndrome included campomelia of prenatal onset, cystic hygroma, and a small chest; 1 patient also had a cleft palate and multicystic kidneys, and the other had a complex congenital heart defect. The patients also had short, irregular chondrocyte columns, whereas chondroosseous morphology appears normal in campomelic dysplasia except at the diaphyseal bend. Watiker et al. (2005) concluded that the presence of a narrow, tall pelvis, hypoplastic scapulae, and sex reversal are key findings in campomelic dysplasia that allow it to be differentiated from Cumming syndrome.

Inheritance

Consanguinity in the families with Cumming syndrome reported by Cumming et al. (1986) and Perez del Rio et al. (1999) is consistent with autosomal recessive inheritance.