Study of Human Leukocyte Antigen (HLA) in 13 cases of familial frontal fibrosing alopecia: CYP21A2 gene p.V281L mutation from congenital adrenal hyperplasia linked to HLA class I haplotype HLA-A*33:01; B*14:02; C*08:02 as a genetic marker.

BACKGROUND/OBJECTIVES: The aetiology of frontal fibrosing alopecia is unknown, and its genetic aspect remains uncharacterised. The aim of this report is to elucidate if major histocompatibility complex is associated with familial frontal fibrosing alopecia. METHODS: A case-control study was performed of 13 patients with frontal fibrosing alopecia belonging to six families. Their human leukocyte antigen profiles were compared to the data of 636 healthy controls without frontal fibrosing alopecia. Patients underwent high-resolution genomic typing for human leukocyte antigen class I and II loci by PCR-SSO for Luminex. In addition, CYP21A2 gene (major histocompatibility complex class III) mutations were detected by PCR-SSO on strips. RESULTS: 61.5% of patients shared CYP21A2 gene p.V281L linked to the F16A human leukocyte antigen class I haplotype (HLA-A*33:01; B*14:02; C*08:02; Pc < 0.000001). The patients F16A-negative shared other human leukocyte antigen class I haplotypes: Y16A (3/13) and S26 (2/13). CONCLUSION: CYP21A2 gene p.V281L mutation can be used as a genetic marker for susceptibility to familial frontal fibrosing alopecia. Both the linkage of the mutation to F16A and the fact that F16A-negative patients share other human leukocyte antigen class I haplotype, point to an antigen-driven mechanism in susceptible patients with these haplotypes.

Familial frontal fibrosing alopecia: A cross-sectional study of 20 cases from nine families.

BACKGROUND/OBJECTIVES: Frontal fibrosing alopecia (FFA) is a scarring alopecia whose prevalence is increasing. The pathogenesis of this disease is not well known. Genetic, environmental, hormonal and autoimmunity related factors have been considered; however, only a few cases of familial frontal fibrosing alopecia have been reported. MATERIAL AND METHODS: A cross-sectional study was performed at University Hospital in Granada (Spain). Twenty patients with frontal fibrosing alopecia belonging to nine different families were included, and clinical and dermoscopic features were analysed. RESULTS: Overall, 90% of the patients studied were women (mean age 61.4 years). About 50% of the patients had grade II frontal fibrosing alopecia at the time of diagnosis, whilst 35% had grades III or V. Mean recession was 2.83 cm in the frontal area and 1.99 cm in the temporo-parietal area. Daughters presented a shorter recession area and earlier debut of the disease than mothers. Androgenetic alopecia was found in only two patients (10%). The dermoscopic signs most commonly found were perifollicular erythema (85%), hyperkeratosis (85%), and absence of vellus hair in the hairline (78.9%). CONCLUSION: This study adds to the growing evidence that there is a genetic component to frontal fibrosing alopecia. The clinical pattern of frontal fibrosing alopecia was not different from that found in non-familial cases, but the debut of the disease in daughters of mothers with frontal fibrosing alopecia may be earlier.