{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:19:55Z","timestamp":1783005595573,"version":"3.54.5"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Palmoplantar epidermal differentiation disorder associated with pachyonychia congenita is a rare autosomal dominant genodermatosis characterized by painful palmoplantar hyperkeratosis and nail dystrophy. Treatment options remain limited, particularly in young children, in whom systemic therapies carry safety concerns. Herein, we report a 2-year-old girl who presented with palmoplantar hyperkeratosis since 1 month of age, with progressive nail dystrophy involving all 20 nails. Whole-exome sequencing identified a hemizygous multi-exon deletion in keratin 16 (ClinVar: SUB16259296; OMIM: #167200), and orthogonal validation using amplicon-based high-throughput sequencing confirmed a 437-nucleotide deletion predicted to result in a frameshift with premature termination codon (PTC). American College of Medical Genetics and Genomics classification supported likely pathogenicity. Twice-daily application of topical 2.5% simvastatin\/cholesterol cream for 11 weeks produced substantial improvement in plantar hyperkeratosis, resolution of painful fissures, and visibly improved morphology of nascent nail growth. No local or systemic adverse effects were observed. This case provides preliminary evidence that topical simvastatin may be an effective and well-tolerated therapy for keratin 16-associated palmoplantar epidermal differentiation disorder in young children, and highlights the potential importance of topical drug delivery in achieving therapeutic efficacy for this genetic subtype.<\/jats:p>","DOI":"10.3389\/fped.2026.1891570","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:08:00Z","timestamp":1783004880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Successful topical simvastatin therapy in a 2-year-old girl with keratin 16-associated palmoplantar epidermal differentiation disorder"],"prefix":"10.3389","volume":"14","author":[{"given":"Qingmei","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Dermatology, Dermatology Hospital of Fuzhou First General Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Dermatology Hospital of Fuzhou First General Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Dermatology Hospital of Fuzhou First General Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Fujian Provincial Geriatric Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Dermatology Hospital of Fuzhou First General Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1093\/bjd\/ljaf054","article-title":"Palmoplantar epidermal differentiation disorders: a new classification toward pathogenesis-based therapy","volume":"193","author":"Sprecher","year":"2025","journal-title":"Br J Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1001\/jamadermatol.2013.6448","article-title":"Pachyonychia congenita in pediatric patients: natural history, features, and impact","volume":"150","author":"Shah","year":"2014","journal-title":"JAMA Dermatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.jid.2023.10.030","article-title":"Pachyonychia congenita: a research agenda leading to new therapeutic approaches","volume":"144","author":"O'Toole","year":"2024","journal-title":"J Invest Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/bjd.18033","article-title":"Pathophysiology of pachyonychia congenita-associated palmoplantar keratoderma: new insights into skin epithelial homeostasis and avenues for treatment","volume":"182","author":"Zieman","year":"2020","journal-title":"Br J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/jid.2011.41","article-title":"Statins downregulate K6a promoter activity: a possible therapeutic avenue for pachyonychia congenita","volume":"131","author":"Zhao","year":"2011","journal-title":"J Invest Dermatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/bjd.17276","article-title":"Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation","volume":"181","author":"Abdollahimajd","year":"2019","journal-title":"Br J Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e480","DOI":"10.1111\/jdv.16393","article-title":"Successful treatment of pachyonychia congenita with rosuvastatin","volume":"34","author":"Frommherz","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e356","DOI":"10.1111\/jdv.19630","article-title":"Successful treatment of pachyonychia congenita with simvastatin","volume":"38","author":"Iqneibi","year":"2024","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1111\/bjd.18254","article-title":"Stopping pachyonychia congenita plantar pain with a statin","volume":"181","author":"Theocharopoulos","year":"2019","journal-title":"Br J Dermatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1111\/1346-8138.17900","article-title":"Oral statin therapy in KRT16- and KRT17-associated palmoplantar epidermal differentiation disorder (pachyonychia congenita)","volume":"52","author":"Itamoto","year":"2025","journal-title":"J Dermatol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1891570\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:08:02Z","timestamp":1783004882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1891570\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":10,"alternative-id":["10.3389\/fped.2026.1891570"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1891570","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1891570"}}