ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome is a multisystem condition that primarily alters tissues derived from the ectoderm, including skin, hair, nails, eyes, and the lining of the mouth and respiratory tract. It is caused by pathogenic variants in the TP63 gene, which provides instructions for a protein that controls early formation and maintenance of these tissues. Features usually become apparent at birth or in early infancy, so both boys and girls are affected equally from the start of life. Precise prevalence figures are not available, but the condition is considered very uncommon worldwide. Because presentation can differ greatly between individuals, diagnosis and care often require input from several medical specialists.

Severity and symptoms vary widely between individuals. The most characteristic early findings are ankyloblepharon filiforme adnatum, in which thin strands of tissue partially fuse the upper and lower eyelids, and clefting of the lip and/or palate that may interfere with feeding and speech. Nearly all affected individuals show signs of ectodermal dysplasia such as sparse scalp or body hair, missing or brittle nails, and an inability to sweat (anhidrosis) that increases the risk of overheating. Eye-related problems commonly include reduced tear production (alacrima) and obstruction of the tear ducts. Breathing difficulties can occur because of choanal atresia, a blockage of the nasal passages present in virtually all reported cases. As children grow, additional features may emerge. Dental enamel may be thin, hair shafts can appear twisted (pili torti), and the skin may be dry or prone to infection. Feeding challenges in infancy sometimes require temporary nasogastric support. Genitourinary differences such as hypospadias are reported in a subset of affected boys. Not all individuals experience all features, and the combination and intensity of findings can differ even among family members who share the same genetic change (variable expressivity).

Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome results from pathogenic variants in the TP63 gene. TP63 encodes a transcription factor that orchestrates development of ectoderm-derived tissues; when the gene is altered, these tissues may form incompletely or abnormally, leading to the clinical features described above. The condition is inherited in an autosomal dominant pattern, meaning one altered copy of TP63 is sufficient to cause symptoms. A parent with the variant has a 50 percent chance of passing it to each child. Because expressivity is variable, the severity in a child cannot be precisely predicted from how the parent is affected. Families are encouraged to discuss testing of relatives and family-planning options with a genetic counselor.

Currently, management focuses on supportive care and symptom management. Surgical procedures are often required early in life to separate fused eyelids, repair cleft lip or palate, and open blocked nasal passages. Ongoing care involves a multidisciplinary team that may include plastic surgeons, otolaryngologists, dermatologists, ophthalmologists, dentists, and speech-language specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. For example, monitoring body temperature and ensuring adequate hydration reduce risks associated with anhidrosis, while routine eye examinations address chronic dryness and protect vision. Genetic counseling is recommended for affected individuals and their families to clarify inheritance and reproductive options. Patients should discuss individualized treatment plans with their healthcare team to determine which interventions are most appropriate.

Outcomes depend on many factors including the severity of structural anomalies, access to timely surgical repair, and ongoing management of ectodermal issues. With coordinated multidisciplinary care, many individuals lead active lives, although challenges such as heat intolerance, ocular irritation, or dental problems may require lifelong attention. The clinical spectrum ranges from mild cosmetic concerns to complex medical needs in infancy. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialty centers familiar with ectodermal dysplasia syndromes and to engage with genetic counselors for guidance and support.