B4.2 CLINICAL AND PATHOLOGICAL CORRELATIONS IN GENETICALLY DISTINCT FORMS OF ATRICHIA

¹Zlotogorski A., ²Hochberg Z., ³Mirmirani P., ⁴Metzker A., ⁵Ben-Amitai D., ⁶Martinez-Mir A., ⁶Panteleyev AA., ^6,7Christiano AM.

Departments of Dermatology, ¹Hadassah- Hebrew University Medical Center, Jerusalem, ⁴Sourasky Medical Center, Tel-Aviv, and ⁵Rabin Medical Center, Petah-Tikva, Israel; and ³University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio, USA; ²Division of Endocrinology, Meyer Children's Hospital, Haifa, Israel; and the Departments of ⁶Dermatology and ⁷Genetics and Development, Columbia University, New York, NY; USA.

The genetic basis of two distinct forms of atrichia with papules has recently been defined at the molecular level. In atrichia with papular lesions (APL; Online Mendelian Inheritance in Man [OMIM] 209500), mutations in the hairless gene on chromosome 8p21 have been identified. Atrichia with papules also occurs in the clinical setting of vitamin D-dependent rickets type IIA (VDDR IIA; OMIM 277440), resulting from mutations in the vitamin D receptor gene on chromosome 12q12-q14. Despite the distinct genetic basis for both forms of atrichia, the clinical findings are strikingly similar and exhibit classic pathognomonic features unique to this phenotype.

Molecular analysis of the hairless and vitamin D receptor genes was performed on genomic DNA from probands and family members from 3 families with APL and 2 with VDDR IIA. We present a clinical and histologic comparison of atrichia in patients with APL and VDDR IIA and highlight the genetically heterogeneous basis of atrichia by identification of pathogenetic mutations.

Increased awareness of these diseases will allow early diagnosis and potential therapeutic intervention for the rickets in VDDR IIA and avoidance of treatment of the atrichia in both APL and VDDR IIA. Their phenotype similarities suggest the possibility of a functional relationship between HR and VDR.