Congenital brachydactyly and nail hypoplasia: clue to bone-dependent nail formation

Abstract

Congenital hyponychia and anonychia are rare malformations which may form part of syndromes such as nail-patella syndrome, ectodermal dysplasias and brachydactylies, or may occur as an isolated finding. Congenital hyponychia and anonychia are frequently accompanied by underlying skeletal abnormalities. A 20-year-old woman showed congenital bilateral hypoplasia or aplasia of the second, third and fourth toenails with corresponding phalanx dysplasia or aplasia of the affected toes. Malformations of the hands or other congenital defects were absent. The findings in this patient do not exactly fit any known entities. Our clinical observation prompted us to review the literature on congenital hyponychia/anonychia and to summarize recent advances in understanding molecular events in nail development. In conclusion, the association of nail anomalies with aplasia and/or hypoplasia of corresponding middle and/or distal phalanges supports the hypothesis of bone-dependent nail formation.

The Wnt signalling ligand RSPO4, causing inherited anonychia, is not mutated in a patient with congenital nail hypoplasia/aplasia with underlying skeletal defects

“…It can be hypothesized that RSPO4 mutations may also lead to a more severe phenotype with skeletal involvement and reduction defects of distal limbs. This hypothesis is in line with the long‐standing argument of bone‐dependent nail formation and the observation that nail development depends on correct dorsoventral polarization with proper epithelial‐mesenchymal interactions at different developmental stages that require temporospatially balanced expression of Wnt7a , Noggin , Bmp4 and Lmx1b , among others 6–9 . A crucial role for Wnt signalling in limb development has recently been corroborated by the finding of mutations in the WNT ligand 7A as the cause of a wide range of limb malformations 10 .…”

“…This hypothesis is in line with the long-standing argument of bone-dependent nail formation and the observation that nail development depends on correct dorsoventral polarization with proper epithelial-mesenchymal interactions at different developmental stages that require temporospatially balanced expression of Wnt7a, Noggin, Bmp4 and Lmx1b, among others. [6][7][8][9] A crucial role for Wnt signalling in limb development has recently been corroborated by the finding of mutations in the WNT ligand 7A as the cause of a wide range of limb malformations. 10 LMX1B, mutations in which cause nail-patella syndrome, is required for dorsal specification and hence for nail development.…”

Isolated recessive nail dysplasia caused byFZD6mutations: report of three families and review of the literature

“…Nail development begins around week 9 of the embryonic period, starting at the dorsal aspect of the distal end of the digits with mesenchymal condensation, which is shortly followed by the development of the transverse nailfold . Beneath the transverse nailfold the matrix primordium, containing proliferating keratinocytes, forms.…”

A novel missense mutation in the geneFZD6underlies autosomal recessive nail dysplasia

“…The matrix induces the nail bed and, subsequently, formation of the nail plate occurs. Nail formation starts from the upper limb and then proceeds to the hindlimb 1 …”