[Translated article] Congenital and Hereditary Nail Disease.

Nail disorders in newborns can show independently or as components of systemic illnesses or genodermatoses. The examination of these abnormalities is complex and sometimes challenging. However, familiarity with these disorders can significantly contribute to uncovering potential underlying conditions. This review includes the physiological nail changes seen within the first few months of life, such as Beau's lines, onychoschizia, koilonychia, congenital nail fold hypertrophy of the first digit, and onychocryptosis. This review also focuses on the most relevant congenital disorders reported and how to perform differential diagnosis. Finally, this review highlights those hereditary diseases in which nail involvement is crucial for diagnosis, such as nail-patella syndrome, congenital pachyonychia, or congenital dyskeratosis, among others.

PLACK syndrome is potentially treatable with intralipids.

We describe an 11-year-old girl with PLACK Syndrome (peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads), who was found to have a novel homozygous variant in CAST, the pathogenicity of which was confirmed using blood-derived RNA. There is no established treatment for PLACK syndrome. However, we demonstrate for the first time that this condition is associated with low levels of vitamin A and essential fatty acids, which prompted us to consider a potential treatment strategy. Indeed, we initiated this patient on intravenous lipid infusion (Vitalipid®; an emulsion of fat-soluble vitamins and lipofundin-MCT/LCT 20%) and the response was dramatic. Following the fourth monthly course of treatment, pruritis disappeared and the skin lesions showed remarkable objective improvement. PLACK syndrome is a very rare genodermatosis and only six families have been described to date with pathogenic CAST variants. This is the first report of an objective response to a therapeutic agent, which suggests that PLACK is a potentially treatable condition. The remarkable response we report and the relative safety of the intervention should prompt healthcare providers who care for PLACK syndrome patients to explore this as a potential treatment strategy in future studies.

A case of idiopathic acquired leukonychia totalis in a 17-year-old boy.

Whitening of the nail, or leukonychia, can have a wide range of etiologies including genetic disorders, trauma, poisoning, autoimmune disorders, and infections. Here we detail a case of idiopathic acquired leukonychia totalis in a 17-year-old boy. This condition has been reported 13 times in the literature previously, with only young boys being affected. Proper diagnosis may help minimize unnecessary investigations and prevent additional psychological stress over whether an underlying disease is present.

Developmental delay, intellectual disability, short stature, subglottic stenosis, hearing impairment, onychodysplasia of the index fingers, and distinctive facial features: A newly reported autosomal recessive syndrome.

We report on a multiply consanguineous Syrian family where two siblings, a boy and a girl, presented with a compilation of symptoms including developmental delay, severe intellectual disability, absent speech, hearing impairment, short stature, subglottic stenosis, increased length of the palpebral fissures, onychodysplasia of index fingers, scoliosis, genu valgum, and malpositioned toes. Two other individuals from the extended family with similar clinical features are also described. Array-CGH did not reveal any pathological copy number variation. Exome sequencing failed to find any causal variants. Differential diagnoses and the possibility that we might be reporting a hitherto unknown syndrome are discussed.

Paediatric nail consultation in an academic centre in Belgium: a 10-year retrospective study.

BACKGROUND: Very few studies have been conducted to establish the nature and prevalence of nail disorders in children. OBJECTIVES: To determine the frequency of various nail conditions in the paediatric setting and to report their management and follow-up. METHODS: This was a retrospective study between 2007 and 2017 of children under 18. All the patients were evaluated in our paediatric nail clinic at the dermatology department of Queen Fabiola Children's University Hospital. The data were synthesized from information obtained through medical records as well as from photographs taken during consultation. Follow-up was completed by phone interview. RESULTS: Three hundred and one patients were included. The majority of nail abnormalities involved the toenails (57.6%). The most common clinical signs were, in descending order, Beau's lines, pachyonychia, subungual hyperkeratosis and onycholysis. The most frequent diagnoses were fever-related Beau's lines or onychomadesis (9.7%), trachyonychia (8.4%), longitudinal melanonychia (8.1%) and congenital malalignment of the great toenail (8.1%). The main diagnoses by age group were as follows: congenital hypertrophy of the lateral nail folds (21.4%) [0-2 years old]; fever-related Beau's lines or onychomadesis (21%) [2-6 years old]; trachyonychia (22%) [6-12 years old]; and juvenile ingrown nail (21.4%) [12-18 years old]. Management included clinical observation for 119 patients and specific advices for 108 patients. A treatment was prescribed for 134 patients, topical in 76.5% of cases. Follow-up demonstrated complete healing in 50.6% of patients and improvement in 19.7%. CONCLUSION: The most frequent nail disorders are benign, and their distribution varies with age. Management mainly involves conservative care, and the prognosis is favourable in the majority.

Whole exome sequencing identifies a novel dominant missense mutation underlying leukonychia in a Pakistani family.

Hereditary leukonychia (also known as porcelain nails or white nails) is a genetic disorder. It may exist as an isolated feature or associated with other cutaneous or systemic disorders. Although a number of genes have been described to cause leukonychia, still the underlying genetic etiologies of many cases remain unknown. Here, we report a Pakistani family presenting leukonychia and koilonychia nails in mother and five of her kids. All the affected individuals had white to pale nails in appearance exhibiting complete and partial leukonychia, respectively. Similarly, nails of finger and toe appeared brittle and concave, showing the characteristics features of koilonychia. Whole exome sequencing and subsequent Sanger sequencing identified a pathogenic novel missense mutation (c.1390G>A, p.Glu464Lys) in PLCD1, co-segregating with the disorder in an autosomal dominant pattern. In silico prediction tools supported the pathogenicity of the identified mutation. Literature review determined that mutations in PLCD1 only cause leukonychia. Therefore, our findings add another pathogenic variant to the PLCD1 mutation pool causing leukonychia that would help to understand the underlying molecular mechanism.

Congenital isolated leukonychia.

Congenital leukonychia is a rare nail disorder that may occur in isolation or in association with a number of syndromic disorders. In the following letter, we describe a case of isolated congenital true leukonychia to add to the current literature. This case is particularly unique in that it does not appear to be inherited in an autosomal dominant fashion, in contrast to the majority of reported cases.

Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges.

Isolated recessive nail dysplasia caused by FZD6 mutations: report of three families and review of the literature.

Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20-nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in families presenting with abnormal nails consistent with IRND. These reports have highlighted the role of Wnt-FZD signalling in the process of nail formation. We report three families presenting with features of IRND, in whom we identified mutations in FZD6, including one previously unreported mutation.

[Leukonychia totalis]. / Leukonychia totalis.

Our patient presented with leukonychia totalis at the age of 15 years. Other malformations such as syndromes or underlying internal diseases did not exist. The patient's family history was unremarkable. In the classification of leukonychias, the real, usually hereditary leukonychia can be distinguished from the acquired form. The white color of the nails can be isolated, depending on its present form, appear as part of a syndrome, or as a result of internal disease. An effective treatment of hereditary leukonychia is not known.

A case and review of congenital leukonychia.

Leukonychia refers to a white discoloration of the nails. Although several conditions may cause white nails, a rare, isolated, congenital form of the disease is hypothesized to stem from disordered keratinization of the nail plate. Herein, we report a case of a 41-year-old woman with congenital leukonychia and review prior cases.

Genetics of human isolated hereditary nail disorders.

Human hereditary nail disorders constitute a rare and heterogeneous group of ectodermal dysplasias. They occur as isolated and/or syndromic ectodermal conditions where other ectodermal appendages are also involved, and can occur associated with skeletal dysplasia. 'Nail disorder, nonsyndromic congenital' (OMIM; Online Mendelian Inheritance in Man) is subclassified into 10 different types. The underlying genes identified thus far are expressed in the nail bed and play important roles in nail development and morphogenesis. Here, we review the current literature on nail disorders and present a coherent review on the genetics of nail disorders. This review will pave the way to identifying putative genes and pathways involved in nail development and morphogenesis.

Hereditary leukonychia, or porcelain nails, resulting from mutations in PLCD1.

Hereditary leukonychia (porcelain nails or white nails) is a rare nail disorder with an unknown genetic basis. To identify variants in a gene underlying this phenotype, we identified four families of Pakistani origin showing features of hereditary leukonychia. All 20 nails of each affected individual were chalky and white in appearance, consistent with total leukonychia, with no other cutaneous, appendageal, or systemic findings. By using Affymetrix 10K chip, we established linkage to chromosome 3p21.3-p22 with a LOD score (Z) of 5.1. We identified pathogenic mutations in PLCD1 in all four families, which encodes phosphoinositide-specific phospholipase C delta 1 subunit, a key enzyme in phosphoinositide metabolism. We then identified localization of PLCD1 in the nail matrix. It was recently shown that PLCD1 is a component of the human nail plate by proteomic analysis and is localized in the matrix of human nails. Furthermore, mutations detected in PLCD1 resulted in reduced enzymatic activity in vitro. Our data show that mutations in PLCD1 underlie hereditary leukonychia, revealing a gene involved in molecular control of nail growth.

Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia.

Inherited and isolated nail malformations are rare and heterogeneous conditions. We identified two consanguineous pedigrees in which some family members were affected by isolated nail dysplasia that suggested an autosomal-recessive inheritance pattern and was characterized by claw-shaped nails, onychauxis, and onycholysis. Genome-wide SNP array analysis of affected individuals from both families showed an overlapping and homozygous region of 800 kb on the long arm of chromosome 8. The candidate region spans eight genes, and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes and differentiation through several signaling pathways. We expressed the FZD(6) missense mutation and observed a quantitative shift in subcellular distribution from the plasma membrane to the lysosomes, where the receptor is inaccessible for signaling and presumably degraded. Analysis of human fibroblasts homozygous for the nonsense mutation showed an aberrant response to both WNT-3A and WNT-5A stimulation; this response was consistent with an effect on both canonical and noncanonical WNT-FZD signaling. A detailed analysis of the Fzd(6)(-/-) mice, previously shown to have an altered hair pattern, showed malformed claws predominantly of the hind limbs. Furthermore, a transient Fdz6 mRNA expression was observed in the epidermis of the digital tips at embryonic day 16.5 during early claw morphogenesis. Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways.

Nail disorders in infants and children.

PURPOSE OF REVIEW: Nail diseases in infants and children are an uncommon cause of consultation and are often difficult to diagnose and to manage. This review will cover nail diseases that are most commonly seen in clinical practice, including congenital and hereditary disorders and inflammatory, infective, and neoplastic nail diseases. The purpose of the review is to help the reader to recognize nail disorders at an early age and to manage them appropriately. RECENT FINDINGS: Two recent large studies have reported the clinical findings of genetic disorders involving the nails, that is, pachyonychia congenita and epidermolysis bullosa. Only a few articles gave a comprehensive review of a disease, as occurred for onychomycosis, while the majority of the reports published in the recent literature involve single cases. SUMMARY: Nail diseases in children and neonates are not easy to diagnose by nonexperts. Basic knowledge of the anatomy and biology of the nail facilitates their diagnosis as the understanding of their pathophysiology. This review gives hints at the most common nail diseases that affect infants and children.

Idiopathic acquired true leukonychia totalis.

Idiopathic acquired true leukonychia totalis is a rare nail disorder not associated with other abnormalities. We present a case in a 12-year-old Egyptian boy.

Congenital onychodysplasia of the index finger presenting as a congenital bifid nail.

Congenital onychodysplasia of the index finger (COIF) is a rare disorder characterized by various nail dystrophies, often with underlying bony deformity. We report a case of a COIF presenting as a congenital bifid nail deformity with underlying bone deformity.

Idiopathic acquired true leukonychia: a unique entity.

Idiopathic acquired true leukonychia is a rare benign acquired disorder that typically affects adults. Diagnosis is made clinically, with investigations required to exclude any underlying cause. The cause of this condition is largely unknown, yet it understandably causes significant anxiety to patients due to concerns about underlying systemic disease. We report a case of idiopathic acquired true leukonychia totalis in a healthy 20-year-old man. Intermittent complete whitening of some of the fingernails was reported over a 7-year period. No underlying medical cause or laboratory abnormality was identified. This case highlights the importance of considering idiopathic acquired true leukonychia as a differential diagnosis of nail whitening. In addition, increased awareness of this unique entity is needed for patient reassurance, as well as avoidance of unnecessary investigations and prolonged systemic treatment.