C Syndrome

C syndrome is a rare multiple congenital anomaly/intellectual disability syndrome characterized by trigonocephaly and metopic suture synostosis, dysmorphic facial features, short neck, skeletal anomalies, and variable intellectual disability.

Epidemiology

The prevalence has been estimated to be between 1/800,000 and 1/1,000,000. Less than 60 cases have been reported so far.

Clinical description

C syndrome is a congenital disorder characterized by trigonocephaly, dysmorphic craniofacial features that include upslanting palpebral fissures, thick epicanthic folds, strabismus, depressed nasal bridge with short/thick nasal septum and columella, flat philtrum, thin vermilion borders, micrognathia, highly arched palate, buccal-gingival frenula, and multiple minor ear anomalies along with frontal midline capillary hemangioma. Cleft palate (see this term) is an occasional finding. The neck is apparently short, but this appears to be related to residual nuchal lymphedema, which may be generalized. Skeletal defects include short rhizo- and acromelic limb segments, hypermobile elbows with crepitus, polydactyly (usually postaxial), syndactyly (see these terms) of toes, sacral dimple and deformed chest. Intellectual disability may be severe, but normal intelligence quotient (IQ) has also been described in a few patients. Seizures and neonatal hypotonia have also been reported. Additional anomalies may include congenital heart malformations (50% of cases, and include interauricular communication, ventricular septal defect, tetralogy of Fallot, Eisenmenger syndrome), hernia (in particular diaphragmatic hernia), renal malformations (unilateral renal agenesis, multicystic dysplastic kidney or horseshoe kidney) (see these terms), genital anomalies (enlarged clitoris, small penis), and anal stenosis. Perinatal mortality rate appears to be around 50%.

Etiology

The etiology of C syndrome is still unknown.

Genetic counseling

Although most of the reported patients are sporadic, rare cases of familial occurrence have been described. Reports of recurrence in sibs with unaffected parents suggest that familial cases may be caused by germinal mosaicism. As recurrence in siblings has been reported, subsequent pregnancies in affected families should be monitored.