Ablepharon macrostomia syndrome

Ablepharon macrostomia syndrome (AMS) is an extremely rare congenital disorder characterized by absent or severely underdeveloped eyelids (ablepharon or microblepharon) and an abnormally wide mouth (macrostomia). The condition is caused by mutations in the TWIST2 gene (also known as DERMO1), which plays a critical role in the development of skin and other ectodermal structures. AMS is present at birth and affects multiple body systems, most prominently the face, skin, and external genitalia. Key craniofacial features include absent or rudimentary eyelids, absent or sparse eyebrows and eyelashes, a wide fish-like mouth, small nose with underdeveloped nostrils, and abnormal ears. The skin is often thin, dry, and redundant, with a coarse or wrinkled appearance. Affected individuals may also have ambiguous or underdeveloped external genitalia, absent or hypoplastic nipples, and variable degrees of intellectual disability. Additional features can include growth delay, abdominal wall defects, syndactyly (fused fingers or toes), and sparse or absent hair. The eyes are particularly vulnerable due to the lack of eyelid protection, leading to corneal damage, dryness, and potential vision loss if not managed promptly. AMS shares clinical overlap with Barber-Say syndrome, which is also caused by TWIST2 mutations, and the two conditions are now considered part of a phenotypic spectrum. There is no cure for ablepharon macrostomia syndrome. Treatment is supportive and multidisciplinary, focusing on protecting the eyes through lubricating drops, ointments, and surgical reconstruction of the eyelids. Surgical correction of macrostomia and other craniofacial anomalies may be performed to improve function and appearance. Regular ophthalmologic, dermatologic, and developmental assessments are essential components of long-term management.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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