{
  "abstract": "Background\n\nBiallelic FIG4 variants classically cause distinct conditions characterized by peripheral neuropathy (Charcot-Marie-Tooth disease type 4J) or skeletal dysplasia (Yunis-Varón syndrome). However, central nervous system involvement is increasingly recognized. The prevalence and specific characteristics of movement disorders within FIG4-related disease remain poorly characterized, prompting a need to redefine its clinical continuum.Objective\n\nTo delineate the phenotypic spectrum of FIG4-related disorders beyond established entities (Yunis-Varón syndrome, Charcot-Marie-Tooth disease type 4J, bilateral temporooccipital polymicrogyria, and amyotrophic lateral sclerosis type 11) using an international multicentre cohort.Methods\n\nWe retrospectively analyzed clinical, genetic, and neurophysiological data from patients with biallelic FIG4 variants to redefine genotype-phenotype correlations, focusing on motor development, cognitive status, and movement disorders.Results\n\nEvaluating 14 pediatric FIG4 patients revealed a continuous phenotypic spectrum rather than the clinical entities previously described in the literature. Instead of the typical peripheral neuropathy classically associated with pathogenic FIG4 variants, the predominant clinical picture in this age group was a severe neurodevelopmental disorder. Patients showed profound motor and cognitive delay, with a subset additionally displaying distinct movement abnormalities such as dystonia and bradykinesia.Conclusion\n\nLoss of functional FIG4 causes a broader and more severe disease spectrum with central nervous system involvement, including intellectual disability and movement abnormalities such as dystonia and bradykinesia. Recognizing these features should prompt clinicians to consider FIG4-associated disorders, allowing for optimized patient care and tailored therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Neurology, University Duisburg-Essen, Essen, Germany.",
    "Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.",
    "Neuromuscular Unit, Neurology Department, Hospital Sant Joan de Déu, Barcelona, Spain.",
    "Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children, London, UK.",
    "Children's Neurosciences, Evelina London Children's Hospital at Guy's and St Thomas' National Health Service Foundation Trust, London, UK.",
    "Metabolic Unit, Movement Disorders Unit, Neurology Department, Hospital Sant Joan de Déu, Barcelona, Spain.",
    "Department of Pediatric Neurology, DRK-Kinderklinik Siegen gGmbH, Siegen, Germany.",
    "Department of Neurology and Center for Rare Diseases, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.",
    "Pediatric Neurology, Clínic Universitary Hospital of Valencia, Valencia, Spain.",
    "Pediatric Neurology Department, Center of Expertise for Rare Diseases in Pediatric Neurology, \"Prof. Dr. Alexandru Obregia\" Clinical Psychiatry Hospital, Bucharest, Romania.",
    "Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.",
    "Pediatric Neurology, Consorci Sanitari de Terrassa, Barcelona, Spain.",
    "Faculty of Life Sciences and Medicine, Randall Centre for Cell and Molecular Biophysics, King's College London, London, UK.",
    "Department of Pediatrics and Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.",
    "Max-Planck-Institute for Biology of Ageing, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany.",
    "Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104, University of Strasbourg, Illkirch, France.",
    "Brain and Mind Research Institute, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.",
    "Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Bochum, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Andrea Gangfuß",
      "orcid": "0000-0002-9975-0092"
    },
    {
      "affs": [
        1
      ],
      "name": "Vykuntaraju K Gowda"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniel Natera-de Benito",
      "orcid": "0000-0001-7764-2085"
    },
    {
      "affs": [
        3
      ],
      "name": "Pinki Munot"
    },
    {
      "affs": [
        4
      ],
      "name": "Maria Vanegas"
    },
    {
      "affs": [
        5
      ],
      "name": "Alejandra Darling"
    },
    {
      "affs": [
        6
      ],
      "name": "Constanze Reutlinger"
    },
    {
      "affs": [
        2
      ],
      "name": "Laura Carrera-Garcia"
    },
    {
      "affs": [
        7
      ],
      "name": "Gilbert Wunderlich"
    },
    {
      "affs": [
        0
      ],
      "name": "Heike Kölbel"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Burkhard Stüve"
    },
    {
      "affs": [
        0
      ],
      "name": "David Muhmann"
    },
    {
      "affs": [
        8
      ],
      "name": "Lucía Monfort Belenguer"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Diana-Gabriela Barca"
    },
    {
      "affs": [
        1
      ],
      "name": "Viveka Santhosh Reddy C"
    },
    {
      "affs": [
        1
      ],
      "name": "Varunvenkat M Srinivasan"
    },
    {
      "affs": [
        11
      ],
      "name": "Cristina Molina Anguita"
    },
    {
      "affs": [
        4,
        12
      ],
      "name": "Heinz Jungbluth",
      "orcid": "0000-0002-7159-3427"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Hormos Salimi Dafsari",
      "orcid": "0000-0003-3483-5009"
    },
    {
      "affs": [
        4
      ],
      "name": "Thomas Rossor"
    },
    {
      "affs": [
        15
      ],
      "name": "Johann Böhm",
      "orcid": "0000-0001-8019-9504"
    },
    {
      "affs": [
        0
      ],
      "name": "Ulrike Schara-Schmidt"
    },
    {
      "affs": [
        0,
        16,
        17
      ],
      "name": "Andreas Roos"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7wtk42hr3w8d2.bib",
  "cited_by": 0,
  "doi": "10.1002/acn3.70561",
  "fulltext_url": "https://europepmc.org/articles/PMC13729235",
  "id": "7wtk42hr3w8d2",
  "issns": [
    "2328-9503"
  ],
  "landing_url": "https://europepmc.org/article/MED/42974926",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Hereditary Neurological Disorders"
    ]
  ],
  "openalex": "W7225137462",
  "pdf_url": "https://europepmc.org/articles/PMC13729235?pdf=render",
  "pmcid": "PMC13729235",
  "pmid": "42974926",
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7wtk42hr3w8d2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42974926",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974926"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Hereditary Neurological Disorders",
      "subfield": "neuroscience"
    }
  ],
  "title": "Clinical Variability and Genotype Driven Outcomes in an International Cohort of 14 Pediatric FIG4 Patients.",
  "title_text": "Clinical Variability and Genotype Driven Outcomes in an International Cohort of 14 Pediatric FIG4 Patients.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T03:20:59Z",
  "url": "https://research.draconitic.com/paper/7wtk42hr3w8d2",
  "venue": "Annals of clinical and translational neurology",
  "versions": []
}