Clarissa Modafferi, Pino D'Ambrosio, Silvia Andaloro, Giulia Lauretti, Fulvia Antignani, Maurizio Pompili, Felice Giuliante, Marco Biolato, Benedetta Niccolini, Arcangelo Fargnoli, Francesco Bogliardi, Paola Concolino, Giuseppe Zampino, Angelo Minucci, Maurizio Genuardi, Elisabetta Tabolacci, Pietro Chiurazzi
{"title":"GAPO syndrome: a comprehensive examination and review of 105 clinical cases.","authors":"Clarissa Modafferi, Pino D'Ambrosio, Silvia Andaloro, Giulia Lauretti, Fulvia Antignani, Maurizio Pompili, Felice Giuliante, Marco Biolato, Benedetta Niccolini, Arcangelo Fargnoli, Francesco Bogliardi, Paola Concolino, Giuseppe Zampino, Angelo Minucci, Maurizio Genuardi, Elisabetta Tabolacci, Pietro Chiurazzi","doi":"10.1136/jmg-2025-110832","DOIUrl":null,"url":null,"abstract":"<p><p>Growth retardation, alopecia, pseudoanodontia and optic atrophy (GAPO) syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the <i>ANTXR1</i> gene. While significant progress has been made in understanding its molecular basis, no systematic description of the clinical phenotype is available.We conducted a comprehensive review of 105 cases reported in the available literature since the first description of GAPO syndrome in 1947. We summarise here the current understanding of the clinical phenotype and the genetic basis of the condition.Our findings point out the multisystemic nature of GAPO syndrome, primarily featuring skeletal, dermatological and ophthalmological manifestations. The condition is caused by the biallelic loss-of-function of <i>ANTXR1</i> Histological findings throughout the reported cases underscore the critical role of excessive extracellular matrix deposition in the pathogenesis of GAPO syndrome. The evidence gathered suggests <i>ANTXR1</i> as an important regulator of extracellular matrix homeostasis.This study highlights the clinical and molecular spectrum of GAPO syndrome. Early recognition, multidisciplinary care and genetic counselling are essential for improving patient outcomes. Future studies should focus on targeted therapies addressing extracellular matrix dysregulation.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2025-110832","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Growth retardation, alopecia, pseudoanodontia and optic atrophy (GAPO) syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the ANTXR1 gene. While significant progress has been made in understanding its molecular basis, no systematic description of the clinical phenotype is available.We conducted a comprehensive review of 105 cases reported in the available literature since the first description of GAPO syndrome in 1947. We summarise here the current understanding of the clinical phenotype and the genetic basis of the condition.Our findings point out the multisystemic nature of GAPO syndrome, primarily featuring skeletal, dermatological and ophthalmological manifestations. The condition is caused by the biallelic loss-of-function of ANTXR1 Histological findings throughout the reported cases underscore the critical role of excessive extracellular matrix deposition in the pathogenesis of GAPO syndrome. The evidence gathered suggests ANTXR1 as an important regulator of extracellular matrix homeostasis.This study highlights the clinical and molecular spectrum of GAPO syndrome. Early recognition, multidisciplinary care and genetic counselling are essential for improving patient outcomes. Future studies should focus on targeted therapies addressing extracellular matrix dysregulation.
期刊介绍:
Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.