{
  "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.",
  "authors": [
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Clarissa Modafferi"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Pino D’Ambrosio"
    },
    {
      "affiliations": [
        "Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Silvia Andaloro"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Giulia Lauretti"
    },
    {
      "affiliations": [
        "Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Fulvia Antignani"
    },
    {
      "affiliations": [
        "Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy",
        "Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Maurizio Pompili"
    },
    {
      "affiliations": [
        "Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy",
        "Department of Gastroenterological, Endocrine, Metabolic and Nephro-Urological Sciences, General Surgery and Hepatobiliary Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Felice Giuliante"
    },
    {
      "affiliations": [
        "UOC Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario Gemelli IRCCS, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Marco Biolato"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Benedetta Niccolini"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Arcangelo Fargnoli"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy"
      ],
      "name": "Francesco Bogliardi"
    },
    {
      "affiliations": [
        "Departmental Unit of Molecular and Genomic Diagnostics, Policlinico Gemelli IRCCS Foundation, Rome, Italy",
        "Genomics Research Core Facility, Gemelli Science and Technology Park, Policlinico Gemelli IRCCS Foundation, Rome, Italy"
      ],
      "name": "Paola Concolino"
    },
    {
      "affiliations": [
        "Center for Rare Disease and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy"
      ],
      "name": "Giuseppe Zampino"
    },
    {
      "affiliations": [
        "Departmental Unit of Molecular and Genomic Diagnostics, Policlinico Gemelli IRCCS Foundation, Rome, Italy"
      ],
      "name": "Angelo Minucci"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy",
        "Dipartimento di Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Maurizio Genuardi"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy",
        "Dipartimento di Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Elisabetta Tabolacci"
    },
    {
      "affiliations": [
        "UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy",
        "Dipartimento di Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Rome, Italy"
      ],
      "name": "Pietro Chiurazzi"
    }
  ],
  "title": "GAPO syndrome: a comprehensive examination and review of 105 clinical cases",
  "uid": "de48abf1-f0d8-5e87-a995-c774994f6dc4"
}