Parents

Mutations in CDH1 have been initially identified as a cause of multigenerational hereditary diffuse gastric cancer (HDGC) and lobular breast cancer (LBC). In a small number of families affected with HDGC, cleft lip with or without cleft Palate (CLP) has been found in mutation-carriers. Subsequently, mutations of CDH1 have been identified in patients with CLP without history of HDGC or LBC. Recently, mutation of CDH1 and CTNND1 have been found to cause Blepharocheilodontic (BCD) syndrome. BCD syndrome is a rare disease characterized by eyelid malformations, CLP, sparse hair and dental anomalies (i.e., conical teeth and tooth agenesis). In addition, hypothyroidism due to thyroid gland hypoplasia or aplasia, imperforate anus, neural tube defect, and syndactyly have been reported in a few patients. BCD syndrome is usually sporadic, but large affected families have been described. Identification of CDH1 and CTNND1 as causing genes, confirmed the autosomal-dominant inheritance of the condition. It means that one affected individual has a 50% risk to transmit the condition to his offspring. To date, about 26 patients from 18 families have been reported, with a mutation in CDH1. Prevalence of the diseases is not known and there is no genotype/phenotype correlation explaining the wide phenotypic spectrum of the CDH1-related disorders.