Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms

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-lik...

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Main Authors: Ioannis Kyriakidis, Iordanis Pelagiadis, Nikolaos Katzilakis, Eftichia Stiakaki
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pediatric Reports
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Online Access:https://www.mdpi.com/2036-7503/17/2/32
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author Ioannis Kyriakidis
Iordanis Pelagiadis
Nikolaos Katzilakis
Eftichia Stiakaki
author_facet Ioannis Kyriakidis
Iordanis Pelagiadis
Nikolaos Katzilakis
Eftichia Stiakaki
author_sort Ioannis Kyriakidis
collection DOAJ
description 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 <i>PIK3CA</i>, <i>AKT1</i>, and <i>PTEN</i> sequencing for the affected tissue was negative. Subsequent genetic testing revealed a 16p11.2 duplication along with a heterozygous pathogenic variant in <i>PRRT2</i> (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’ 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.
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spelling doaj-art-48cceaa6dc4d401ab26dff5d3be0e6102025-08-20T02:18:00ZengMDPI AGPediatric Reports2036-75032025-03-011723210.3390/pediatric17020032Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated FormsIoannis Kyriakidis0Iordanis Pelagiadis1Nikolaos Katzilakis2Eftichia Stiakaki3Department 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, GreeceDepartment 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, GreeceDepartment 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, GreeceDepartment 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, GreeceBackground: 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 <i>PIK3CA</i>, <i>AKT1</i>, and <i>PTEN</i> sequencing for the affected tissue was negative. Subsequent genetic testing revealed a 16p11.2 duplication along with a heterozygous pathogenic variant in <i>PRRT2</i> (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’ 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.https://www.mdpi.com/2036-7503/17/2/32macrodactylycongenital deformitiesmegalodactylyPI3Kovergrowth syndrome
spellingShingle Ioannis Kyriakidis
Iordanis Pelagiadis
Nikolaos Katzilakis
Eftichia Stiakaki
Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
Pediatric Reports
macrodactyly
congenital deformities
megalodactyly
PI3K
overgrowth syndrome
title Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
title_full Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
title_fullStr Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
title_full_unstemmed Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
title_short Approach to Macrodactyly: A Case Report and Diagnostic Algorithm for Syndromic and Isolated Forms
title_sort approach to macrodactyly a case report and diagnostic algorithm for syndromic and isolated forms
topic macrodactyly
congenital deformities
megalodactyly
PI3K
overgrowth syndrome
url https://www.mdpi.com/2036-7503/17/2/32
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AT nikolaoskatzilakis approachtomacrodactylyacasereportanddiagnosticalgorithmforsyndromicandisolatedforms
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