L-26   SINGLE GENE MUTATIONS IN CONGENITAL HAIR DISEASE

A. Zlotogorski Department of Dermatology, Hadassah Medical Center, Jerusalem, Israel.

'Alopecia' can be defined as the reversible or permanent non-congenital process of hair loss, which may progress to partial or complete baldness. 'Hypotrichosis' is a term that may be kept to the diffuse or localized, congenital or acquired, forms of hair loss leading to paucity of hair. The term 'atrichia' is reserved for the most dramatic and severe forms of hair loss, in particular, those that are characterized by an absence of hair follicles. Atrichia is manifested by the congenital or early-onset hair loss, which ends rapidly in complete smooth bald scalp. The genetic basis of several forms of congenital hair disease, hypotrichosis and atrichia, has recently been defined at the molecular level. Hypotrichotic disorders have been associated with mutations in different components of the desmosomal complex. Mutations in the plakoglobin gene and desmoplakin are responsible for two similar conditions; Naxos disease (palmoplantar keratoderma with arrhythmogenic right ventricular cardiomyopathy and woolly hair) and dilated cardiomyopathy, woolly hair and keratoderma accordingly. Trauma-induced skin fragility and congenital ectodermal dysplasia affecting hairs, nails and sweat glands are the components of the ectodermal dysplasia/skin fragility syndrome caused by mutations in the plakophilin 1 gene. Recently, mutations in a new desmosomal cadherin, desmoglein 4, were shown to underlie localized hypotrichosis. In addition to the desmosomal components, mutations in the classical cadherin, P-cadherin, were also found to underlie juvenile macular dystrophy with congenital diffuse hypotrichosis. Mutations in SPINK5 gene, encoding a serine protease inhibitor cause Netherton's syndrome. Perifollicular hyperkeratosis and beaded hair are part of monilethrix caused by mutations in the hair cortex keratin genes hHb1 or hHb6. In two other diseases, simple hypotrichosis and Marie-Unna hypotrichosis, the underlying genes were not found yet, but linkage to chromosomes 6 and 8 was established. Genes with a role in transcription may cause different forms of atrichia. In atrichia with papular lesions, mutations in the hairless gene have recently been identified. Atrichia with papules also occurs in the clinical setting of vitamin D-dependent rickets type IIA, resulting from mutations in the vitamin D receptor gene. Atrichia, nail dystrophy and a severe T-cell immunodeficiency are caused by winked helix nude gene mutations.