blepharocheilodontic syndrome 1

Blepharocheilodontic syndrome 1 (BCDS1) is a congenital condition that primarily affects the eyes, facial structures, and teeth, but can involve several other body systems. It is caused by alterations in the CDH1 gene, which encodes E-cadherin, a protein important for cell–cell adhesion during early development. Children are usually born with visible craniofacial differences that prompt early medical attention, and both males and females can be affected because the condition follows an autosomal dominant inheritance pattern. Precise prevalence figures have not been established, but reported cases suggest it is uncommon. Severity and symptoms vary widely between individuals, even within the same family.

The most characteristic features of BCDS1 involve the eyelids and mid-face. Nearly all affected individuals have outward turning of the lower eyelids (ectropion), redundant eyelid tissue (euryblepharon) with incomplete eye closure (lagophthalmos), double rows of eyelashes (distichiasis), a broad space between the eyes (hypertelorism), a high forehead, and a generally flat facial profile. A cleft of the upper lip, with or without involvement of the palate, is very common and often identified at birth. Dental anomalies such as conical or peg-shaped teeth frequently become evident when primary teeth erupt. Over time, additional findings may emerge. Many people develop sparse or thin scalp hair and abnormal nails. Less consistently, cutaneous syndactyly, scalp defects known as aplasia cutis, or congenital narrowing of the nasal passages (choanal atresia) can be seen. Rarely, malformations such as neural tube defects or anal atresia have been reported. Not all individuals experience all features, and the range of manifestations can differ considerably, highlighting the variable expressivity of the syndrome.

BCDS1 results from pathogenic variants in the CDH1 gene. CDH1 provides instructions for making E-cadherin, a protein that helps neighboring cells stick together to form well-organized tissues. When E-cadherin function is reduced or absent, embryonic tissues that form the eyelids, lip, palate, and teeth do not fuse or develop normally, leading to the clinical signs described above. The condition is inherited in an autosomal dominant manner, meaning a change in just one copy of the CDH1 gene is sufficient to cause disease. A person who has BCDS1 has a 50 percent chance of passing the altered gene to each child, regardless of sex. In some families the variant arises for the first time in the affected individual, but precise de novo rates are not yet defined. Genetic counseling is recommended for affected individuals and their relatives to discuss testing options, variability of symptoms, and family-planning choices.

Currently, management focuses on supportive care and individualized treatment of each feature rather than on a single disease-specific medication. Early involvement of a multidisciplinary craniofacial team that includes plastic surgeons, ophthalmologists, dentists or orthodontists, speech-language specialists, and genetic counselors is strongly encouraged. Surgical repair of a cleft lip or palate is usually performed in infancy, followed by orthodontic interventions to address conical or missing teeth. Ophthalmologic surgery or lubricating eye care may be needed to protect the cornea from exposure due to incomplete eyelid closure. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Ongoing monitoring by an ophthalmologist can detect dryness or corneal irritation, while periodic dental evaluations support oral health and speech development. Psychological support and access to speech therapy can assist with feeding and communication challenges. Families should discuss treatment options and follow-up schedules with their healthcare team to determine what is appropriate for their specific situation.

Most individuals with BCDS1 lead active lives, particularly when cleft repair, dental reconstruction, and eye protection are addressed in a timely manner. Long-term outlook largely depends on the severity of facial clefts and eyelid abnormalities and on access to specialized surgical and rehabilitative care. Serious medical complications are uncommon, although untreated eye exposure can threaten vision, and speech or feeding difficulties may affect quality of life if not managed. Outcomes described in medical literature continue to evolve as standards of care improve. Because experiences differ significantly, families are encouraged to work closely with specialists familiar with the syndrome, and to seek genetic counseling for guidance on family planning, available resources, and emerging research opportunities.

Clinical trials are underway exploring new treatment approaches and long-term outcomes for individuals with CDH1-related disorders. Interested individuals can search ClinicalTrials.gov or consult their care team about eligibility and potential participation.