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Hand Surgery & Rehabilitation Apr 2024Congenital nail disorders are an uncommon presenting symptom which can be difficult to diagnose and manage. Nail diseases in the pediatric population differ from those... (Review)
Review
Congenital nail disorders are an uncommon presenting symptom which can be difficult to diagnose and manage. Nail diseases in the pediatric population differ from those in adults in terms of diagnosis, approach and management. In most cases, they do not require treatment and resolve with growth. Physicians need to be able to recognize them, to reassure the parents. The most frequently encountered pathologies associated with nail disorder are syndactyly, acrosyndactyly, symbrachydactyly, macrodactyly, Wassel I thumb duplication, Kirner's deformity and congenital onychodysplasia of the index finger. Treatment usually consists in surgical correction of the deformity. Nail malformation can also be an aspect of a systemic disease. It may provide a clue for screening, and should not be overlooked. Nail conditions can be the first sign of nail-patella syndrome, ectodermal dysplasia, dyskeratosis congenita, epidermolysis bullosa, pachyonychia congenita or lung disease. Medical treatment is therefore discussed on a case-by-case basis.
Topics: Humans; Nails, Malformed; Nail Diseases; Ectodermal Dysplasia
PubMed: 38879228
DOI: 10.1016/j.hansur.2023.01.011 -
The Journal of Neuroscience : the... Jun 2024SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss of function mutations in SLURP1...
SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss of function mutations in SLURP1 lead to a rare autosomal recessive Palmoplantar Keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as Pachyonychia congenita (PC) and Olmsted syndrome (OS) show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knockout and Slurp2X knockout, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals including augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed increased paw pad skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knockout mice. Primary sensory neurons innervating hind paw glabrous skin from Slurp2X knockout mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knockout mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability, and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain. Palmoplantar keratodermas (PPKs) are rare human skin disorders associated with thickening of the skin on the palms and soles. Pain is a common feature of some PPKs, yet the causes of PPK-associated pain are not understood. Here we show that two mouse models of one PPK, SLURP1 knockout mice and SLURP2 knockout mice, exhibit enhanced pain sensitivity and increased activity of pain-associated sensory neurons. These mouse lines will therefore be of value in defining causes of pain in PPKs and possibly developing improved therapies for that pain.
PubMed: 38866482
DOI: 10.1523/JNEUROSCI.0260-23.2024 -
Clinical and Experimental Dermatology May 2024Pachyonychia congenita is an autosomal dominant genodermatosis characterized by a triad of chronic severe plantar pain, focal palmoplantar keratoderma, and hypertrophic...
Pachyonychia congenita is an autosomal dominant genodermatosis characterized by a triad of chronic severe plantar pain, focal palmoplantar keratoderma, and hypertrophic nail dystrophy. Plantar pain can be debilitating and have a profound impact on quality of life. Current therapeutic options for pain in PC are limited to lifestyle adjustment and mechanical techniques, with a small subgroup of patients benefiting from oral retinoids. This review investigates the pathogenesis of pain in pachyonychia congenita and provides a summary of the current and future therapeutic options.
PubMed: 38805703
DOI: 10.1093/ced/llae199 -
Clinical, Cosmetic and Investigational... 2024Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to...
Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient's 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.
PubMed: 38770089
DOI: 10.2147/CCID.S462273 -
Actas Dermo-sifiliograficas Apr 2024Nail disorders in newborns can show independently or as components of systemic illnesses or genodermatoses. The examination of these abnormalities is complex and... (Review)
Review
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.
PubMed: 38663727
DOI: 10.1016/j.ad.2024.04.002 -
Balkan Medical Journal Apr 2024
PubMed: 38619174
DOI: 10.4274/balkanmedj.galenos.2024.2024-2-23 -
The British Journal of Dermatology Apr 2024
PubMed: 38584300
DOI: 10.1093/bjd/ljae143 -
Heliyon Mar 2024Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and...
Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely , , , or . Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.
PubMed: 38468954
DOI: 10.1016/j.heliyon.2024.e27195 -
European Journal of Dermatology : EJD Dec 2023
Topics: Humans; Human Papillomavirus Viruses; Epidermal Cyst; Steatocystoma Multiplex; Warts
PubMed: 38465555
DOI: 10.1684/ejd.2023.4550 -
JAAD International Mar 2024
PubMed: 38274397
DOI: 10.1016/j.jdin.2023.11.002