Laryngo-onycho-cutaneous syndrome: an inherited epithelial defect.

Abstract

Three children with an unusual but clearly defined combination of clinical findings that appear to have been inherited in an autosomal recessive manner are described. All had developed laryngeal abnormalities, chronic skin ulceration, nail dystrophy, and conjunctival disease in infancy. In every case, dental enamel was hypoplastic and both skin and mucosal surfaces demonstrated increased susceptibility to trauma. Progression of disease occurred, to life threatening respiratory obstruction in two cases and to effective blindness and fatal respiratory obstruction in the third child. All of these children came from the Pakistani ethnic group. No medical treatment has halted progression of this disease but laser therapy has been partially successful in alleviating laryngeal manifestations. Ultrastructural and immunohistological examination of unaffected skin was undertaken in each child. No abnormality was found in the child with the mildest clinical disease. Both of the other children showed abnormal hemidesmosomes on ultrastructural examination. The most severely affected child also had abnormally weak immunoreactivity with antibodies G71 and GB3 directed against basal cell alpha 6 beta 4 integrin and the basement membrane glycoprotein nicein respectively. These abnormal findings are also seen in skin from patients with junctional epidermolysis bullosa. These three children have the laryngo-onycho-cutaneous syndrome, which may not be rare in their ethnic group. The available clinical and pathological evidence is consistent with this syndrome being caused by an inherited defect affecting the lamina lucida of the skin basement membrane zone. The laryngo-onycho-cutaneous syndrome may therefore represent a new and distinctive type of junctional epidermolysis bullosa.