SG16 A case of laryngo-onycho-cutaneous syndrome: a rare form of junctional epidermolysis bullosa

Abstract

A 3-year-old girl of Punjabi descent was born at term to consanguineous parents, with no perinatal concerns. At 11 months, she presented with bilateral upper-eyelid granulomas, which responded well to combination topical therapy with dexamethasone, neomycin and polymyxin B. She presented to ear, nose and throat at 16 months of age, having had progressive stridor and dysphonia from 4 months. Evolving laryngeal stenosis from upper-airway granulation tissue was identified, requiring an urgent tracheostomy and repeated surgical procedures. She presented to dermatology at 22 months of age, with recurrent bleeding and exuberant granulation tissue affecting both fifth toenails, resulting in nail loss. The first toenails exhibited hyperkeratosis and clippings were negative for mycology. She also developed periungual swelling and bleeding of the left index finger, exacerbated by finger sucking, which resolved leaving residual subungual hyperkeratosis. Topical betamethasone with clioquinol three times weekly in the long term led to significant improvement. Genetic testing on extracted DNA identified a homozygous loss-of-function pathogenic variant in the LAMA3 gene, in keeping with laryngo-onycho-cutaneous (LOC) syndrome. LOC syndrome is a rare autosomal recessive subtype of junctional epidermolysis bullosa, with fewer than 50 reported cases worldwide. It is predominantly seen in those of Punjabi descent. It is caused by a loss-of-function mutation in LAMA3, encoding laminin-332. This protein is essential in epidermal adhesion to the basement membrane and in regulating cell migration. Its deficiency results in increased cutaneous fragility and an aberrant inflammatory wound-healing response. The clinical signs are exuberant mucocutaneous granulation tissue affecting the ocular surface, nail apparatus and upper airway, with potential for life-­threatening airway compromise. This case demonstrates phenotypic variability in LOC syndrome, with minimal cutaneous fragility seen. It also highlights the late presentation of airway compromise. Recognition of these signs in children of Punjabi descent is crucial to guide genetic testing, optimize multidisciplinary care and reduce morbidity.