White Sponge Nevus 2

A number sign (#) is used with this entry because of evidence that white sponge nevus-2 (WSN2) is caused by heterozygous mutation in the KRT13 gene (148065) on chromosome 17q21.

For a discussion of genetic heterogeneity of white sponge nevus, see WSN1 (193900).

Clinical Features

Shibuya et al. (2003) described a Japanese family in which a 36-year-old woman, her 17-year-old daughter, and her 14-year-old son each had unexplained white oral lesions. The mother noted onset of oral lesions in early adolescence, whereas the oral lesions of her children were reported as congenital. The lesions in all 3 patients were asymptomatic and consisted of soft, white, spongy mucosal plaques with thick, folded surfaces. The lesions were bilaterally distributed in a variety of mucosal sites: the mother had similar lesions of the nasal mucosa, esophagus, pharynx, vagina, and rectum, and her daughter also had vaginal involvement. Review of family history revealed that the mother's father, sister, and nephew had similar oral lesions. Histopathologic examination of biopsies from the buccal mucosa of the mother and her 2 children showed changes consistent with white sponge nevus, including epithelial thickening with hyperparakeratosis, acanthosis, an orderly basal cell layer, mild chronic inflammatory cell infiltration of the submucosal connective tissue by lymphocytes, intracellular edema with the characteristic 'basket weave' and cell-within-a-cell appearance, and typical perinuclear cytoplasmic condensations.

Molecular Genetics

In affected members of a multigenerational Italian family segregating white sponge nevus (WSN) showing linkage to chromosome 17, Richard et al. (1995) identified heterozygosity for a missense mutation in the 1A domain of the KRT13 gene (L15P; 148065.0001). Keratin intermediate filaments are assembled from heterodimeric subunits comprised of a type I and a type II protein. In WSN, the restriction of lesions to mucosal epithelia and the suprabasal cell histopathology parallels the tissue-specific expression of KRT4 (123940) and KRT13 in the differentiating cell layers.

In a Japanese mother and 2 children with WSN, who were negative for mutation in the KRT4 gene, Shibuya et al. (2003) identified heterozygosity for a missense mutation in the KRT13 gene (L111P; 148065.0002).