CTNND1

Clinical Characteristics

Variants of CTNND1 cause Non-Syndromic Cleft Lip with or without Cleft Palate (NSCLP) and Blepharocheilodontic (BCD) syndrome. NSCLP has been reported in 23 patients from 9 families. In BCD syndrome, based on the description of 10 individuals, all patients have eyelid anomalies and ectodermal dysplasia, which are cardinal features. Eyelid anomalies comprise euryblepharon (9/10), lagophthalmos (8/10), and ectropion (8/10). Patients also show distichiasis (8/10) and ankyloblepharon (4/7). Features of ectodermal dysplasia consist of delayed dentition (4/5), hypodontia (9/10) and sparse hair (6/10). Cleft lip/palate (CLP), thought to be constant, is reported in only 6/10 patients. Patients also exhibit typical dysmorphism consisting of hypertelorism (6/7), flat face and high forehead (2/7). Congenital hypothyroidism is reported in only 1 patient. Unlike patients with a CDH1 variant, neither anal atresia nor neural tube defect are reported in patients with CTNND1 variants. BCD syndrome due to CTNND1 is assumed to be less severe, but the cohort size is too small to ascertain this. Significant interindividual and intrafamilial variability has been reported. Diagnosis could be made retrospectively in patients’ relatives, when the condition is confirmed by genetic testing.