Two‐Year Follow‐Up of Ectodermal Dysplasia‐Syndactyly Syndrome 1 in a Palestinian Child Successfully Treated With Topical Minoxidil and Tretinoin: A Case Report

We report a 5.5‐year‐old Palestinian girl presenting with hypotrichosis of the scalp, eyebrows, and eyelashes; peg‐shaped widely spaced teeth with enamel defects; hypoplastic brittle nails; palmoplantar keratoderma; periorbital wrinkling; and partial cutaneous syndactyly of the second to fourth toes bilaterally, consistent with Ectodermal Dysplasia‐Syndactyly Syndrome 1 (EDSS1). EDSS1 is a rare autosomal recessive ectodermal dysplasia caused by biallelic pathogenic variants in the NECTIN4 ( PVRL4 ) gene. It is characterized by abnormalities of hair, teeth, nails, and cutaneous syndactyly. The presence of a similarly affected sibling and parental consanguinity supported autosomal recessive inheritance. Genetic testing was offered but declined, and the diagnosis was made clinically based on the constellation of phenotypic features including hypotrichosis, dental anomalies (peg‐shaped teeth with enamel hypoplasia), nail hypoplasia, palmoplantar keratoderma, and toe‐only syndactyly, in conjunction with positive family history and parental consanguinity. Given the lack of definitive therapy for EDSS1‐associated hypotrichosis, off‐label topical minoxidil 2% and topical tretinoin 0.025% were initiated after written informed consent was obtained from the patient's parent. Minoxidil acts as a potassium channel opener that prolongs the anagen phase and increases follicular blood supply, while tretinoin, a topical retinoid, enhances follicular penetration of minoxidil, normalizes follicular keratinization, and upregulates growth factor expression; the combination is synergistic. After 3 months, clinical examination, trichoscopy evaluation, and serial photography demonstrated an increase in hair density and thickness without adverse effects. Discontinuation of tretinoin was followed by partial relapse, while reintroduction of combination therapy led to sustained improvement over a 2‐year follow‐up. This case highlights the importance of clinical recognition of EDSS1 and may suggest a potential adjunctive role for topical retinoids in managing hypotrichosis, though this finding cannot be generalized from a single case and requires validation in larger prospective studies.