Nail Disorder, Nonsyndromic Congenital, 1

Description

Many types of nonsyndromic congenital nail disorders (NDNC) have been described. Twenty-nail dystrophy (TND), also known as trachyonychia (from the Greek for 'rough nails'), is an autosomal dominant nail dystrophy characterized by excessive longitudinal striations and numerous superficial pits on the nails, which have a distinctive rough sandpaper-like appearance. Occasionally some nails are spared. The slowly progressive condition is usually apparent at birth and may be self-limiting, with spontaneous resolution in some patients (summary by Sehgal, 2007). TND is referred to here as nonsyndromic congenital nail disorder-1 (NCNC1).

Genetic Heterogeneity of Nonsyndromic Congenital Nail Disorders

Other nonsyndromic congenital nail disorders include koilonychia (NDNC2; 149300); leukonychia (NDNC3; 151600) caused by mutation in the PLCD1 gene (602142) on chromosome 3p22; anonychia/hyponychia (NDNC4; 206800) caused by mutation in the RSPO4 gene (610673) on chromosome 20p13; partial onycholysis with scleronychia (NDNC5; 164800); anonychia of thumbs with onychodystrophy of other nails (NDNC6; 107000); onychodystrophy mapping to chromosome 17p13 (NDNC7; 605779); toenail dystrophy (NDNC8; 607523) caused by mutation in the COL7A1 gene (120120) on chromosome 3p21; onychodystrophy mapping to chromosome 17q25.1-q25.3 (NDNC9; 614149); and onychodystrophy (NDNC10; 614157) caused by mutation in the FZD6 gene (603409) on chromosome 8q22.

Clinical Features

Tobias (1925) reported a 4-generation family segregating autosomal dominant nail dystrophy, with at least 12 affected individuals. In 2 cases that were examined, the nails of the fingers became involved early in life. The thumb nails were practically absent, being replaced by rough hyperkeratotic tissue, and the other nails bore longitudinal fissures and were split at the ends. The skin under the free border of the nails was considerably thickened and verrucous. Physical examination revealed no other abnormalities.

Thompson (1928) reported a family in which 16 of 65 family members over 4 generations were affected with dystrophy of all finger and toe nails. The proband was a 5-year-old girl who was normal except for her nails: the base of the nails appeared nearly normal, but the nails increased in thickness toward the distal ends, appearing to grow in thickness at the expense of length, and were very brittle and dry. Occasionally 1 or more nails became infected and gradually loosened and came off in 1 piece, without much soreness; the new nail would gradually repeat this process. Radiation treatments were instituted, and although initially the new portion of the nail appeared thinner and more nearly normal, the nails gradually returned to approximately the previous condition.

Arias et al. (1982) examined 4 of 21 affected members of a 5-generation family with dystrophic nail changes. The proband was a 34-year-old woman who had thin, rough, and opalescent nails, with numerous ridges running the length of the nail plate. In addition, longitudinal splitting and pterygia affected 3 of her toenails. The nails remained adherent to the nail bed, with mild distal onycholysis and subungual hyperkeratosis. Proximal nail folds, hair, mucous surfaces, and sweating were all normal, as was ophthalmologic examination. Dental evaluation revealed class I malocclusion. Hematoxylin-eosin staining of a longitudinal nail biopsy showed atrophy and irregular thinning of the nail plate. The nail matrix showed foci of hypergranulosis, whereas the dermis was free of inflammatory infiltrate. One affected individual was born without nails, with the dystrophic nails appearing at 3 years of age; another reported sparing of 2 of her fingernails. All 4 of the examined affected individuals had class I malocclusion of the teeth; Arias et al. (1982) noted that the occurrence of dental malocclusion could be either coincidental or possibly linked with the nail changes.

Hazelrigg et al. (1977) reported 6 unrelated, sporadic children with dystrophy of all 20 nails, involving thin, fragile nails with prominent, close-set, longitudinal ridges and ragged distal edges. Nails lacked normal luster, appearing opalescent and dull. The thumbnails and great toenails were sometimes thickened, yellow, and rough. Potassium hydroxide preparations and Sabouraud agar culture for dermatophytes and yeasts were consistently negative. Onset was insidious and asymptomatic, occurring between 18 months and 12 years of age; in 1 child, changes were first noted in the fingernails at 7 years of age, followed in several months by similar changes in the toenails. None of the patients had any evidence of skin, hair, or teeth disorders, and none had a family history of nail or skin disease.

Pavone et al. (1982) reported 20-nail dystrophy in 4 males over 3 successive generations of a Sicilian family. The proband was a 17-year-old farmer who had uniformly thin, opalescent nails with longitudinal striations noted at birth. Lamellar splitting of all nails resulted in almost complete nail loss by 10 years of age. The proband's 41-year-old father and 7-year-old brother had similar nail changes. Hair, teeth, and bones were normal in all 3 examined individuals, and cultures for dermatophytes and yeasts were repeatedly negative. Histologic examination in 2 excluded lichen planus or other underlying disorder. The authors noted that although it had been suggested that 20-nail dystrophy is a self-limiting disorder, that was not the case in this family, in which the proband's affected grandfather reportedly died at 77 years of age with no nails and his father had steadily worsening nail alterations for 25 years. Pavone et al. (1982) concluded that the hereditary form of 20-nail dystrophy is a distinct clinical entity.

Commens (1988) described 12-year-old identical twin girls who were noted to have abnormal nails at birth. Their nails were uniformly affected with roughness, loss of luster, and excessive longitudinal ridging (trachyonychia). There was no onycholysis but the nails were fragile. The nail disease was static with no evidence of progression, and their hair was always normal. Treatments including oral vitamin A, occlusive therapy, and antifungal and steroid agents were unsuccessful.

Tosti et al. (1994) reported clinical and pathologic data of 23 patients with idiopathic trachyonychia, 9 of whom had involvement of all 20 nails. In 15 patients, the nail changes consisted of severe longitudinal ridging of the nail plate, which was thin, rough, opaque, and lusterless, with the typical 'sandpapered' appearance. The surface of the nail was brittle, friable, and covered by small scales of keratin, and koilonychia was present in 3 cases. In 4 patients, the nail plate abnormalities were less severe, with milder nail roughness caused by numerous small, closely aggregated, superficial pits, which gave the nail plate surface a shiny appearance. Four patients had mixed nails, with some having the sandpapered appearance and others the shiny appearance. In 22 of the 23 patients, the cuticle of the affected nails was thickened and ragged, and 2 patients had mild distal onycholysis with scaling of the fingertips of the affected digits. The onychodystrophy was asymptomatic, with patients complaining only of brittleness and cosmetic disability. The duration of the nail changes ranged from 1 month to 15 years (mean, 2.3 years). A longitudinal nail biopsy was taken from a fingernail in 12 patients and from a toenail in 11 patients. In 19 patients, histology revealed spongiotic changes in the nail apparatus, with a mild to moderate lymphocytic infiltrate present in the superficial dermis of the proximal nail fold and nail matrix; the nail epithelia showed exocytosis of lymphocytes, associated with mild to moderate spongiosis. The ventral portion of the proximal nail fold showed the most prominent pathologic changes, with hyperkeratosis of the cuticle. The nail matrix keratogenous zone was focally replaced by areas of hypergranulosis, and the nail plate originating from those areas had an abnormal eosinophilic appearance, resembling the compact horny layer of the palms and soles. In 3 patients, histology showed psoriasiform changes, and 1 patient had typical features of nail lichen planus. Follow-up results were available for 18 patients, for a mean period of 2 years (range, 6 months to 4 years), during which none of the patients developed alopecia areata or mucocutaneous lesions. The patient with lichen planus was successfully treated with oral prednisone and had no relapse of nail lesions in 3 years of follow-up, whereas treatment for the 3 patients with nail psoriasis was unsuccessful and nails remained unchanged during the 2.6 years of follow-up. The 14 patients with spongiotic trachyonychia did not receive any treatment, and 11 had spontaneous improvement of their nail changes during follow-up whereas in 3 the nail abnormalities persisted unchanged. Tosti et al. (1994) concluded that idiopathic trachyonychia is a consequence of several inflammatory disorders, producing a multifocal mild disturbance of nail matrix kinetics and keratinization without interrupting the mitotic activity of the germinative cells, and that the course and extent of the inflammatory process within the nail matrix produce 2 different patterns of nail plate surface abnormalities.

Karakayali et al. (1999) reported 4-year-old monozygotic twin boys with fingernail and toenail dystrophy since birth. The boys had no other skin, hair, or dental diseases, and there was no family history of similar conditions. On examination, all 20 nails of 1 boy and 19 nails of the other (excluding his right great toenail) were rough, thickened, opalescent, discolored, and split distally. Potassium hydroxide scrapings and cultures were negative for fungi and yeast. Histologic examination of toenail matrix biopsies showed psoriasiform epithelial hyperplasia, with absence of inflammatory infiltrate in the dermis.

Sehgal (2007) provided a review of twenty-nail dystrophy.

Developmental Pattern of Normal Nails

Okada et al. (2008) examined X-inactivation patterns of normal human nails from the finger and toe nail plates of 9 female volunteers using the androgen receptor gene (AR; 313700). The X-inactivation pattern of each nail was unique and constant for at least 2 years, indicating the maintenance of the composition of precursor cells of each nail through several cycles of regeneration time. Approximately 25.9% of the nails had exclusive inactivation of 1 of the X chromosomes. Nails with 2 types of cells with X-chromosome inactivation showed a patchy longitudinal band mosaic pattern, each band consisting of cells with only 1 of the X chromosomes inactivated. The number of progenitor cells that gives rise to the nail plate during development was estimated to be about 3, under the assumption that the process follows the binomial distribution model. There was a strong correlation among the big, index and little fingers, and among the corresponding toes.