Hereditary mucoepithelial dysplasia: a disease apparently of desmosome and gap junction formation

A previously unrecognized autosomal dominant syndrome affecting oral, nasal, vaginal, urethral, anal, bladder, and conjunctival mucosa with cataracts, follicular keratosis, nonscarring alopecia, and terminal lung disease is described in a four-generation kindred of German extraction. Severe photophobia, tearing, and nystagmus in infancy heralds the development of keratitis, corneal vascularization, and lens cataracts. Repeated corneal transplants have failed. Red, periorificial mucosal lesions involving the above structures are noted by 1 year of age and may persist throughout life. Chronic rhinorrhea and repeated upper respiratory infections frequently progress to bilateral pneumonia accompanied by loss of hair, diarrhea, occasional melena, enuresis, pyuria, and hematuria. Spontaneous pneumothorax is frequent, terminating in fibrocystic-type lung disease and cor pulmonale. Women have had repeated abnormal vaginal PAP smears. Histologically the mucosal epithelium shows dyshesion, thinning of the epithelial layer, and dyskeratosis. Mucosal PAP smears show lack of epithelial maturation, cytoplasmic vacuoles and inclusions, and individual cell dyskeratosis. Histochemically there is a lack of cornification and keratinization. Ultrastructural studies show lack of keratohyalin granules, a paucity of desmosomes, intercellular accumulations, cytoplasmic vacuolization, and formation of bands and aggregates of filamentous fibers and structures in the cytoplasm resembling desmosomes and gap junctions. The condition is probably a panepithelial cell defect of desmosomal and gap junction structure most prominently affecting mucosal epithelia associated with an increased susceptibility to a variety of adventitious organisms.