Mutations of CDH1 cause a wide spectrum of disorders, ranging from cleft lip/palate (CLP) with or without history of cancer, to Blepharocheilodontic (BCD) syndrome. CLP due to mutations in CDH1 has been reported in at least 57 individuals from 19 families. Cases are mostly sporadic, but large families have been described, in whom some mutation-carriers have no CLP. In a small portion of the families affected with hereditary diffuse gastric cancer (HDGC), mutation carriers show CLP. It is unknown why in these families HDGC and CLP are associated. In BCD syndrome, all patients have eyelid, hair and dental anomalies. Eyelid anomalies comprise euryblepharon (bilateral horizontal enlargement of the palpebral fissure), lagophthalmos (inability to close the eyelids completely), ectropion (outward turning of the eyelid margin) and lacrimal duct abnormalities. Patients also show distichiasis (extra row of eyelashes) and ankyloblepharon (partial or complete fusion of the eyelids by webs of skin). Hair and dental anomalies consist of sparse hair, delayed dentition and hypodontia (absence of one or more teeth). CLP is observed in almost all patients, but can be absent. Patients usually show facial particularities as hypertelorism (increased distance between orbits), flat face, and high forehead. Additional rare features could be observed as congenital hypothyroidism, anal atresia and neural tube defect (spinal meningocele). Significant interindividual and intrafamilial variability has been reported. Some patients show a severe form of the disease, when others only show slight enlargement of the palpebral fissures and hypodontia. Diagnosis could be made retrospectively in patients’ relatives, when the condition is confirmed by genetic testing.
CDH1