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The Keio Journal of Medicine Sep 2023Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma,...
Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma, plantar pain, and hypertrophic nail dystrophy. It can be debilitating, causing significantly impaired mobility. PC is diagnosed clinically alongside identification of a heterozygous pathogenic mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. Each keratin gene mutation is associated with a distinct clinical phenotype, with variable age of onset and additional features, which has allowed classification by genotype. Additional features include pilosebaceous cysts, follicular hyperkeratosis, natal teeth, oral leukokeratosis, hidradenitis suppurativa, itching, and neurovascular structures. Although classed as rare, the prevalence of PC is likely to be underestimated. There is no cure or specific treatment for PC at present. Current treatments are limited to conservative measures to reduce plantar friction and trauma, mechanical debridement, topical treatments, and treatments for associated features or complications, most commonly infection. However, through active research in collaboration with PC Project, a patient-advocacy group, and the International PC Research Registry, a global registry of PC patients, there are now many new potential therapeutic options on the horizon. This review summarizes the clinical features associated with PC and highlights the current and future treatment of its manifestations.
PubMed: 37766547
DOI: 10.2302/kjm.2023-0012-IR -
The Keio Journal of Medicine Dec 2023Pachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This...
Pachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This condition is a painful and debilitating skin disorder caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16,or KRT17. Through two primary programs, namely the International Pachyonychia Congenita Consortium (IPCC) and the International Pachyonychia Congenita Research Registry (IPCRR), PC Project provides comprehensive patient support and diagnostics while uniting patients, researchers, physicians, and industry partners on a global level to advance research and drug development for meaningful treatments and, ultimately, a cure for PC.
PubMed: 38072449
DOI: 10.2302/kjm.2023-0015-IR -
Pediatrics and Neonatology Jul 2023Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). PC is an...
BACKGROUND
Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). PC is an extremely rare condition. To our knowledge, this is the largest genotype-phenotype study of PC in a Vietnamese population to date.
MATERIALS AND METHODS
We investigated keratin gene mutations and clinical features of seven Vietnamese children with PC.
RESULTS
The seven Vietnamese patients were from six different families (two patients in the same family) from across Northern, Central, and Southern Vietnam. All children displayed PC symptoms before 1 year of age, but diagnosis was delayed in 4/7 patients. Thick fingernails, thick toenails, oral leukokeratosis, and follicular hyperkeratosis were the most common features recorded by all seven patients. Plantar keratoderma and thick fingernails were the clinical features associated with the most significant effect on daily function. All patients had mutations in KRT6A (PC-K6a) focused on the 1A and 2B domains. We found three distinct types of mutations (K6a R466P, K6a N171K, and K6a N172del). One mutation (N172del) was common to 5/7 (71.4%) of the patients.
CONCLUSIONS
Individuals displaying nail dystrophy, oral leukokeratosis, follicular hyperkeratosis, and plantar keratoderma should be referred for genetic testing given the high likelihood of a PC-K6a-related mutation in patients with this constellation of clinical signs.
Topics: Humans; Child; Pachyonychia Congenita; Keratin-6; Southeast Asian People; Vietnam; Genotype; Phenotype; Mutation; Keratins; Exanthema; Leukoplakia, Oral
PubMed: 36658016
DOI: 10.1016/j.pedneo.2022.09.018 -
Archives of Plastic Surgery Nov 2023Pachyonychia congenita is a rare genetic disorder characterized by hypertrophic nail plates, hyperkeratotic nail beds, and thickened hyponychium of the fingers and toes,...
Pachyonychia congenita is a rare genetic disorder characterized by hypertrophic nail plates, hyperkeratotic nail beds, and thickened hyponychium of the fingers and toes, impairing manual dexterity and resulting in poor aesthetics. The current body of literature describes various treatment modalities, but no singular approach has been defined as the gold standard. In this case, the authors employed different surgical techniques for treating pachyonychia congenita to evaluate the most effective approach. A 3-year-old boy presented with hypertrophic nail growth involving all digits of both hands and feet. Three surgical procedures were performed on the patient's fingers and toes using germinal matrix excision (GME) alone, GME plus partial sterile matrix excision (pSME), or GME plus complete sterile matrix excision (cSME). The digits treated with GME + cSME exhibited no recurrence of nail growth. Those treated with GME alone exhibited recurrence of hypertrophic nail growth, although their growth slowed. Excision of GME + cSME prevented recurrence of hypertrophic nails, while GME alone or with pSME led to slower-growing hypertrophic nails. Complete excision of the germinal and sterile matrices with skin graft closure may be a definitive treatment for pachyonychia congenita, but further studies are needed to validate these findings.
PubMed: 38143838
DOI: 10.1055/s-0043-1771520 -
Indian Dermatology Online Journal 2023
PubMed: 37727554
DOI: 10.4103/idoj.idoj_533_22 -
Cureus Sep 2023Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative,...
Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management. Methods This observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee. Results Among the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes. Conclusions Beyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.
PubMed: 37701161
DOI: 10.7759/cureus.45007 -
Indian Journal of Dermatology,... 2023Background Plantar keratoderma is a common finding in pachyonychia congenita, significantly impairing ambulation and quality of life. Due to the variation of pain...
Background Plantar keratoderma is a common finding in pachyonychia congenita, significantly impairing ambulation and quality of life. Due to the variation of pain reporting in pachyonychia congenita clinical studies, it is difficult to evaluate the efficacy of treatment outcomes for painful plantar keratodermas. Objectives To objectively analyse associations between plantar pain and activity levels in pachyonychia congenita patients using a wristband tracker. Methods Pachyonychia congenita patients and matched normal controls wore wristband activity trackers and completed a daily digital survey to record their highest and total pain scores (0-10 scale) each day for 28 consecutive days during four different seasons. Results Twenty four participants (12 pachyonychia congenita patients and 12 matched normal controls) completed the study. Pachyonychia congenita patients walked 1801.30 fewer steps/day (95% CI, -3666.4, 64.1) than normal controls (P = 0.072) and had greater average total [5.26; SD, 2.10] and highest (6.92; SD, 2.35) daily pain than normal controls [0.11 (SD, 0.47), 0.30 (SD, 0.22), respectively] (P < 0.001, both). On average, for each one unit increase in daily highest pain level, pachyonychia congenita activity decreased 71.54 steps/day (SE, 38.90, P = 0.066). Limitation The study had a small number of participants, limiting statistical power. Only pachyonychia congenita patients, ages 18 years or older, with keratin 6a, keratin 16, and keratin 17 mutations were included, limiting generalizability. Conclusion Pachyonychia congenita patients were less active with significantly higher pain than normal controls. There was an inverse correlation between pain and activity. Our findings suggest that wristband tracker technology may be used to evaluate treatment efficacy in future trials on severe plantar pain; therapeutic interventions that decrease plantar pain should correlate with significant increases in activity using wristband trackers.
Topics: Humans; Pachyonychia Congenita; Quality of Life; Fitness Trackers; Shoes; Keratin-6; Pain; Mutation; Walking
PubMed: 37317732
DOI: 10.25259/IJDVL_939_2022 -
Balkan Medical Journal Apr 2024
PubMed: 38619174
DOI: 10.4274/balkanmedj.galenos.2024.2024-2-23 -
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 -
JAAD International Mar 2024
PubMed: 38274397
DOI: 10.1016/j.jdin.2023.11.002