Ectodermal Dysplasia 9, Hair/nail Type

A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-9 (ECTD9) can be caused by homozygous mutation in the HOXC13 gene (142976) on chromosome 12q13.

Description

Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings.

Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia) (summary by Lin et al., 2012).

Clinical Features

Lin et al. (2012) described a 5-generation consanguineous Chinese Hui family segregating ectodermal dysplasia-9. The 3 affected individuals showed congenital atrichia and severe nail dystrophy. All vellus, lanugo, and terminal hairs were absent on the scalp and body, and axillary and pubic hairs never developed during puberty. Soft and small keratinized structures developed later on all digits and presented as micronychia. The affected individuals described that they never need their nails trimmed. The 2 male affected individuals underwent surgical management for unilateral cryptorchidism and inguinal hernia, and urologists suspected a diagnosis of persistent Mullerian duct syndrome (261550). No genital anomalies were observed in the affected female individual. No abnormalities of the nervous system, skeleton, sweat glands, sebaceous glands, eyes, or teeth were observed. Histopathological examination of scalp skin of the index individual showed an apparently reduced number of hair follicles with disorganized hair shafts lacking the normal layered structure. Lin et al. (2012) also described a 21-year-old Afghan female who presented with severe congenital hypotrichosis and nail dystrophy. She had her nails trimmed once a month and had never cut her hair.

Inheritance

Lin et al. (2012) reported 2 unrelated families segregating ectodermal dysplasia-9 in which affected children were born to healthy first-cousin parents, which is consistent with an autosomal recessive mode of inheritance.

Mapping

By haplotype analysis using microsatellite markers on chromosome 12p11.1-q21.1 in a consanguineous Syrian family with autosomal recessive ectodermal dysplasia of the hair/nail type, Farooq et al. (2013) showed linkage to a 17-Mb region on chromosome 12q13.13-12q14.3, between markers D12S390 and D12S43, within which the entire HOXC13 gene is located.

Molecular Genetics

Lin et al. (2012) performed whole-exome sequencing in a consanguineous Chinese family segregating ectodermal dysplasia-9 and identified a homozygous nonsense mutation (Y130X; 142976.0001) in the HOXC13 gene in all 3 affected individuals. In a female with hypotrichosis and nail dystrophy from a consanguineous Afghan family, they identified a homozygous 27.6-kb deletion involving the first exon of the HOXC13 gene (142976.0002).

In a 7-month-old girl with autosomal recessive ectodermal dysplasia of the hair/nail type, who was born to consanguineous Syrian parents, Farooq et al. (2013) identified homozygosity for a single nucleotide deletion in the HOXC13 gene (c.355delC; 142976.0003). Expression studies in cultured cells showed that the mutant HOXC13 protein mislocalized within the cytoplasm and failed to upregulate the promoter activities of its target genes.