Ectodermal Dysplasia of Hair and Nail
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||ECTODERMAL DYSPLASIA OF HAIR AND NAIL|
|Synonymous||Pure Hair and Nail Ectodermal Dysplasia-4|
|Estimated prevalence||< 1 / 1 000 000|
|OMIM||602032, 614929, 614931|
|Inheritance||Autosomal Dominant, Autosomal Recessive|
|Gene (s)||KRT85 (602767), HOXC13 (143976), KRT74 (608248)|
Ectodermal Dysplasia of Hair and Nail (EDHN) is a rare congenital disorder characterized by hypotrichosis and nail dystrophy without any other (ectodermal or non-ectodermal) features.1 Mutations in three genes have been identified as causative for EDHN, the keratin gene KRT85, the homeobox gene HOXC13 and KRT74. 2-4
Hair abnormalities range from mild hair loss to complete absence of hairs (scalp, eyebrows, eyelashes, whole body hair) with broad variations even intrafamilial. Hair can be thin, fragile, slow-growing or broken (pili torti). Association with folliculitis decalvans of the neck has been reported. Nail lesions include onychodystrophy with micronychia, onychorrhexis and triangular nails as well as spoon-shaped nails, fragile or short nails. 5-8
In a Pakistani family with cases of EDHN, a mutation (R78H) in the V1 head domain of KRT85 has been identified as pathogenic.2 During hair growth, KRT85 is expressed in the lower part of the cortex and cuticle of the hair fiber. In nails, it is expressed in the basal compartment and the lower keratogenous zone of the apical and ventral nail matrix. This specific expression pattern explains the manifestation restricted to hairs and nails.9, 10 HOXC13 encodes a protein that regulates the transcriptional activity of various hair keratin genes and KRT74 belongs to the family of type II keratins that are specifically expressed in hair follicles’ inner root sheath as well as in nail matrix, nail bed and hyponychium.3, 11
Diagnosis is based on typical clinical features as well as molecular investigation of the KRT85, HOXC13 and KRT74 genes. Heterozygous dominant mutations in KRT74 have also been identified in Pakistani patients with woolly hair.
Currently no treatment is available.
1. Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys. 2011;508(2):123-137.
2. Naeem M, Wajid M, Lee K, Leal SM, Ahmad W. A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. J Med Genet. 2006;43(3):274-279.
3. Raykova D, Klar J, Azhar A, Khan TN, Malik NA, Iqbal M, et al. Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis. PLoS One. 2014;9(4):e93607.
4. Lin Z, Chen Q, Shi L, Lee M, Giehl KA, Tang Z, et al. Loss-of-function mutations in HOXC13 cause pure hair and nail ectodermal dysplasia. Am J Hum Genet. 2012;91(5):906-911.
5. Harrison S, Sinclair R. Hypotrichosis and nail dysplasia: a novel hidrotic ectodermal dysplasia. Australas J Dermatol. 2004;45(2):103-105.
6. Pinheiro M, Freire-Maia N. Hair-nail dysplasia--a new pure autosomal dominant ectodermal dysplasia. Clin Genet. 1992;41(6):296-298.
7. Calzavara-Pinton P, Carlino A, Benetti A, De Panfilis G. Pili torti and onychodysplasia. Report of a previously undescribed hidrotic ectodermal dysplasia. Dermatologica. 1991;182(3):184-187.
8. Barbareschi M, Cambiaghi S, Crupi AC, Tadini G. Family with "pure" hair-nail ectodermal dysplasia. Am J Med Genet. 1997;72(1):91-93.
9. Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol. 2008;129(6):705-733.
10. Schweizer J, Langbein L, Rogers MA, Winter H. Hair follicle-specific keratins and their diseases. Exp Cell Res. 2007;313(10):2010-2020.
11. Langbein L, Rogers MA, Praetzel S, Winter H, Schweizer J. K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-specific type II epithelial keratins of the human hair follicle. J Invest Dermatol. 2003;120(4):512-522.