047 Mapping of Monilethrix and Papular Atrichia

A. Zlotogorski1, A.M. Christiano2. Dept. of Dermatology, Hadassah Medical Center, Jerusalem, Israel1 and Dept of Dermatology and Genetics & Development, Columbia University, NY, USA2

Monilethrix is a rare autosomal dominant inherited defect of the hair shaft resulting in hair fragility, hair loss, and follicular hyperkeratosis. Light microscopic examination is diagnostic and reveals alternating regions of thin and thick hair. Seven mutations in monilethrix were found only in the helix initiation motif and the helix termination motif of keratins hHb6 and hHb1 (chromosome 12q13). In 6 out of 12 Israeli families with monilethrix, mutations were found in the helix termination motif of keratin hHb6, which was found to be the most common cause for this disease. One of the families with the E413D mutation had 15 clinically affected members who were available for study. Three members who were found to be homozygous for this mutation had a more severe involvement in terms of both hair and skin involvement. Twelve subjects were heterozygous for the mutation and showed variable expression. Atrichia with papular lesions is a rare form of irreversible alopecia which is inherited in an autosomal recessive pattern. In individuals affected with this form of hair loss, hairs are typically absent from the scalp, axilla and body, and patients are almost completely devoid of eyebrows and eyelashes. APL patients are unique in that, along with total atrichia, papules and follicular cysts filled with cornified material start to appear during the first year of life, particularly under the midline of the eye, on the face and extremities. Recently, this form of atrichia was linked to chromosome 8p12, and fourteen mutations have been identified in the human hairless (hr) gene in Arab families and others from around the world showing a similar phenotype. Based on personal observation of ten Arab families and retrospective analysis of other families described in the literature, we propose an algorithm that easily differentiates this disorder from alopecia universalis.