Nail Disorder, Nonsyndromic Congenital, 7

Description

Isolated congenital onychodysplasia, here referred to as nonsyndromic congenital nail disorder-7 (NDNC7), is characterized by longitudinal streaks, thinning, and impaired formation of the nail plates leading to increased vulnerability of the free nail margins. The most characteristic finding is a conspicuous reddish dome-shaped prominence of the proximal nail plate from which the longitudinal ridges originate, but this is present in only about half of patients. In most cases, all fingernails and toenails are involved, with some accentuation of the changes in the thumb nails and great toe nails (summary by Hamm et al., 2000 and Krebsova et al., 2000).

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

Clinical Features

Hamm et al. (2000) characterized an unusual congenital nail dysplasia in a large kindred from southern Germany. They described the history and clinical features in 22 affected family members (13 females and 9 males, aged 5 to 74 years). There were no other associated anomalies. The pedigree, which spanned 5 consecutive generations, was best compatible with autosomal dominant inheritance with complete penetrance. Nail alterations were mostly present since birth and soon reached an individually variable degree of severity. Affected persons showed longitudinal streaks and thinning of nail plates, mostly of all fingernails and toenails, with some accentuation of the thumbnail and big toenails, poorly developed lunulae, longitudinal angular ridges of individual nail plates occasionally starting proximally from a reddish prominence, platonychia and koilonychia of individual nails often overgrowing the lateral folds, and notches and fissures of the free margins. Findings were generally more severe in children less than 12 years old, and males tended to be more severely affected than females. Nail biopsy samples were taken from 2 patients. Histologic abnormalities included a prominent granular layer of the nail matrix and epithelial strands and buds extending from the nail bed. Hamm et al. (2000) excluded other nail dystrophies in this kindred, including twenty-nail dystrophy (NDNC1; 161050), by differences in clinical and histologic features.

Mapping

Krebsova et al. (2000) performed linkage analysis in the family reported by Hamm et al. (2000). They first ruled out linkage to the keratin gene clusters on 12q12 and 17q21. The isolated congenital nail dysplasia locus, designated NDIC, mapped to a 6-cM interval between markers D17S926 and D17S1528 on 17p13. Markers at D17S849, D17S1840, and D17S1529 cosegregated completely with the NDIC locus. A maximum 2-point lod score of 6.72 with theta of zero was found at marker D17S1840. The identified region harbored no genes known to be involved in skin or nail abnormalities.