Ectodermal Dysplasia of Hair and Nail


Disease group Ectodermal Dysplasia
Synonymous Pure Hair and Nail Ectodermal Dysplasia-4
Estimated prevalence < 1 / 1 000 000
OMIM 602032
Inheritance Autosomal Dominant, Autosomal Recessive
Gene (s) KRT85 (602767)


Ectodermal Dysplasias are characterized by abnormal development of two or more ectodermal structures, such as hair, nails, teeth and sweat glands without other systemic findings. Ectodermal Dysplasias comprise a very heterogeneous group of phenotypes with more than 200 different forms described so far, but only about 30 have been characterized on the molecular level. Ectodermal Dysplasia of Hair and Nail (EDHN) is a rare congenital disorder characterized by hypotrichosis and nail dystrophy [1]. Mutations in two genes have been identified as causative for EDHN so far, the keratin gene KRT85 and the homeobox gene HOXC13. This section refers only to the KRT85 based form.

Clinical Description

Many EDHN show associated abnormalities, such as keratoderma and ichthyosis. Skeletal problems, cardiac irregularities, haematological problems and even mental or psychomotor retardation have been reported [2].

In a Brazilian family with autosomal dominant EDHN, all affected individuals showed hypotrichosis on the whole body and short and fragile nails [3]. Clinical features may also include complete absence of eyebrows and eyelashes [4].

A family with autosomal recessive EDHN has been reported. The main clinical features of affected

family members were onychodysplasia and alopecia involving the scalp, beard, axillary and pubic hair, as well as absence of eyebrows and eyelashes [5].


In a Pakistani family, affected with EDHN, a mutation (R78H) in the V1 head domain of KRT85 has been identified as causative for the disease [6]. During hair growth, KRT85 is expressed very early 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 [7]. Due to this specific expression pattern, a mutated or completely absent KRT85 protein explains the disease phenotype [8].


Besides the clinical appearance of a patient, diagnosis of EDHN is complicated due to the clinical heterogeneity of ectodermal dysplasias and by the fact, that pure hair and nail ectodermal dysplasias are very rare and often involve associated abnormalities. Diagnosis on the molecular level includes DNA sequencing of the KRT85 gene.


Currently no treatment is available.


Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. (2011) Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys 508:123-137.

Pinheiro M, Freire-Maia N. (1994) Ectodermal dysplasias: a clinical classification and a causal review. Am J Med Genet 53:153-162.

Pinheiro M, Freire-Maia N. (1992) Hair-nail dysplasia – a new pure autosomal dominant ectodermal dysplasia. Clin Genet 41:296-298.

Harrison S, Sinclair R. (2004) Hypotrichosis and nail dysplasia: a novel hidrotic ectodermal dysplasia. Aust J Dermatol 45:103-105.

Calzavara-Pinton P, Carlino A, Benetti A, De Panfilis G. (1991) Pili torti and onychodysplasia. Dermatologica 182:184-187.

Naeem M, Wajid M, Lee K, Leal SM, Ahmad W. (2006) A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. J Med Genet 43:274-279.

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Schweizer J, Langbein L, Rogers MA, Winter H. (2007) Hair follicle-specific keratins and their diseases. Exp Cell Res 313:2010-2020.