Nail Disorder, Nonsyndromic Congenital, 10

A number sign (#) is used with this entry because of evidence that nonsyndromic congenital nail disorder-10 (NDNC10) can be caused by homozygous mutation in the FZD6 gene (603409) on chromosome 8q22.3-q23.1.

Description

Nonsyndromic congenital nail disorder-10 is characterized by onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals (summary by Frojmark et al., 2011).

For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).

Clinical Features

Frojmark et al. (2011) examined 4 affected individuals from 2 unrelated consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia. Affected members from one of the families had more severe nail dystrophy than affected individuals from the other family, but all showed a variable degree of onychauxis, hyponychia, and onycholysis of fingernails and toenails, with the fingernails having a claw-like appearance. No other disorders or anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, were noted, and individuals with dysplastic nails had normal hearing and normal psychomotor development.

Mapping

In 1 of 2 consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia, Frojmark et al. (2011) performed autozygosity mapping and detected 1 large homozygous region spanning 17 Mb on chromosome 8q. Within this region, affected members of the other Pakistani family were homozygous over 800 kb. Linkage analysis using polymorphic microsatellite markers yielded a maximum cumulative 2-point lod score of 3.87 (theta = 0). Each family had a distinctive haplotype.

Inheritance

Nonsyndromic congenital nail disorder-10 is an autosomal recessive disorder (Frojmark et al., 2011).

Molecular Genetics

In 2 unrelated consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia mapping to 8q, Frojmark et al. (2011) analyzed the candidate gene FZD6 and identified homozygosity for a nonsense (603409.0001) and a missense (603409.0002) mutation in affected members of each family, respectively. Frojmark et al. (2011) noted that affected individuals in both families retained regenerative capacity of the nail plate, suggesting that the nail matrix was intact; thus, the primary defect associated with FZD6 mutations seemed to be related to perturbed formation and attachment of the nail plate (onycholysis).