Management of CDH1-related disorders is supportive and symptomatic.
Cleft lip/palate
Cleft lip management is surgical, dental, and orthodontic. Speech therapy, otolaryngology and audiologic evaluations are usually recommended.
Dental anomalies
Early orthodontic follow-up should be proposed. In patients with oligodontia, dental implants or dental prostheses should be considered.
Eyelid malformations
Ankyloblepharon usually requires surgery. Blepharoplasty could be considered in patients with severe eyelid anomalies. Lagophthalmos, can lead to corneal abrasion and scarring, and should therefore be medically treated. Ophthalmologic evaluation is indicated to assess eye movement and possible diminished tearing.
Hypothyroidism
Hypothyroidism is due to thyroid gland hypoplasia or aplasia and is usually diagnosed through neonatal screening. Hypothyroidism is treated with thyroid replacement therapy.
Risk of cancer
Germline mutations in CDH1 also cause hereditary diffuse gastric cancer (HDGC). Carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer (also called signet ring cell gastric cancer) and lobular breast cancer. Owing to the high penetrance of these mutations, prophylactic total gastrectomy is currently recommended for CDH1-mutation carriers. Nineteen families have been described with Non-Syndromic Cleft Lip with or without cleft Palate (NSCLP), among whom three carry CDH1 truncating mutations, but have no history of cancer. To date, in BCD syndrome, neither HDGC nor lobular breast cancer (LBC) have been reported, even in large families. Gastric cancer history is noted only in the mother of one patient. Therefore, one would have reservations about recommending an invasive procedure with high morbidity and mortality to a family with little or no history of cancer. Nevertheless, risk-reducing measures must be discussed with patients and their families.
Genetic counselling
Patients harboring BCD syndrome features and carrying a variant in CDH1 have a 50% risk to transmit the pathogenic variant to their offspring. However, due to intrafamilial variability, it is difficult to predict the severity. Prenatal testing is achievable, but if the pathogenic variant is identified in the fetus, the possibility of a mild form of the condition should be discussed. Detailed ultrasound fetal anatomic examination must be performed for the early-detection of severe Cleft Lip with or without cleft Palate (CLP) and neural-tube defects. Patients affected with NSCLP or HDGC and carrying a variant of CDH1, also have a 50% risk to transmit the pathogenic variant. However, estimation of the risk of CLP or BCD syndrome in their offspring is undetermined. Detailed ultrasound fetal anatomic examination must be proposed.