{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T09:01:50Z","timestamp":1792918910711,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Background: Macrodactyly (megalodactyly or digital gigantism) is a rare condition of overgrowth affecting one or more fingers or toes. Methods: We report a case of a 16-year-old Caucasian male with macrodactyly, lipomas, nevi, dysmorphic features, and autism. The clinical suspicion for a Proteus-like syndrome was high. Results: Targeted PIK3CA, AKT1, and PTEN sequencing for the affected tissue was negative. Subsequent genetic testing revealed a 16p11.2 duplication along with a heterozygous pathogenic variant in PRRT2 (not causally associated with digit malformation). Conclusions: The clinical management of syndromic macrodactyly is well described by consensus guidelines, but isolated macrodactyly also needs pediatricians\u2019 attention and warrants a multidisciplinary approach. After reviewing the literature, a diagnostic algorithm for the approach and differential diagnosis of macrodactyly is provided. Phenotypes associated with PI3K\/AKT\/mTOR pathway mutations (including PIK3CA-related overgrowth spectrum PROS) are described. Late effects, follow-up schedules, and surveillance for cancer are discussed.<\/jats:p>","DOI":"10.3390\/pediatric17020032","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T04:29:59Z","timestamp":1741321799000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-9643","authenticated-orcid":false,"given":"Ioannis","family":"Kyriakidis","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology-Oncology & Autologous Hematopoietic Stem Cell Transplantation Unit, University Hospital of Heraklion & Laboratory of Blood Diseases and Childhood Cancer Biology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5737-3770","authenticated-orcid":false,"given":"Iordanis","family":"Pelagiadis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology & Autologous Hematopoietic Stem Cell Transplantation Unit, University Hospital of Heraklion & Laboratory of Blood Diseases and Childhood Cancer Biology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0421-7712","authenticated-orcid":false,"given":"Nikolaos","family":"Katzilakis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology & Autologous Hematopoietic Stem Cell Transplantation Unit, University Hospital of Heraklion & Laboratory of Blood Diseases and Childhood Cancer Biology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3343-5110","authenticated-orcid":false,"given":"Eftichia","family":"Stiakaki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology & Autologous Hematopoietic Stem Cell Transplantation Unit, University Hospital of Heraklion & Laboratory of Blood Diseases and Childhood Cancer Biology, School of Medicine, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","first-page":"55","article-title":"An Analysis of the Pathogenic Genes and Mutation Sites of Macrodactyly","volume":"15","author":"Li","year":"2022","journal-title":"Pharmgenomics Pers. 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