3C syndrome

We were very interested to read the article by Stevenson and Carey [2007] reporting two sisters with enlarged cisterna magna, agenesis/ hypoplasia of the corpus callosum, Pierre Robin sequence, camptodactyly, colobomas, seizures, and global developmental delay. Interestingly, we have recently seen siblings with features reminiscent of the patients Stevenson and Carey describe, and in whom we also considered a diagnosis of Ritscher–Schinzel or 3C syndrome. The girl was born at 37 weeks gestation following an uneventful pregnancy with a birth weight on the 2nd centile. Anomalies noted in the neonatal period included downslanting palpebral fissures, micrognathia and overlapping fingers. Investigations revealed marked cerebellar vermis hypoplasia (Fig. 1a,b) and a ventriculoseptal defect (VSD). By 30 months she showed moderate global developmental delay. At 15 years of age she was attending a mainstream school with one-to-one assistance because of moderate learning difficulties. She remains small (<0.4th centile for height and weight) and microcephalic (OFC 0.4th centile). She has downslanting palpable fissures and a prominent nasal bridge (Fig. 2a). She also demonstrates contractures of the fingers (for which she has undergone two operations) with a ‘‘wind swept appearance,’’ marked flexion contractures of the hips, elbows, and knees, and a positional scoliosis (Fig. 2c). She has had spontaneous closure of her VSD but has significant mitral valve stenosis. Her younger brother was delivered at 39 weeks gestation following a normal pregnancy. He was the 5th child and first boy born to his parents. His birth weight was 2.26 kg (25th centile). On neonatal examination he was recorded to have dysmorphic features similar to his sister. An echocardiogram demonstrated normal cardiac anatomy and neuro-imaging was also normal (Fig. 1c). At 20 months his height and weight are on the 25th centile and his head circumference is on the 0.4th centile. He demonstrates global developmental delay with skills comparable to those of a 9to 12month-old child. He shows similar involvement of the face (Fig. 2b) and hands to his sister, has overlapping of the toes but no has contractures of the large joints (Fig. 2d). Both siblings have normal karyotypes. There have been no further cytogenetic or molecular investigations. Neither child demonstrated a cleft palate/Robin sequence. Our cases are a brother and sister born to a consanguineous Pakistani couple who have three other healthy children. There is no family history of note except that a second born female sibling has, like the children described above, flexion contractures of the 4th and 5th digits at the proximal interphalangeal joints bilaterally. In all other respects she is normal. Our first case fulfils the diagnostic criteria for 3C syndrome as proposed by Leonardi et al. [2001]. Interestingly, her brother has neither a posterior fossa abnormality nor a heart defect. Such