Evidence map›Paper›PMID 41552915›Full record

Observational studyMovement disorders : official journal of the Movement Disorder Society2026

International Registry of NKX2-1-Related Disorders: Clinical, Genetic, and Imaging Perspectives.

Laia Nou-Fontanet, Claudia Ravelli, Lydie Burglen, Sol Balsells Mejia, Angel Valls-Villalba, Elies Roman Schiffels, Alice Innocenti, Beatriz Villafuerte, Ainara Salazar-Villacorta, Vicente Quiroz and 38 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Approach to the patient: genetics and management of congenital hypothyroidism.The Journal of clinical endocrinology and metabolism · 2026
    Article
  2. Distinct Brain Drivers and Shared Cerebello-Cortical Input in ADCY5 and SGCE Hyperkinetic Movements.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

48 authors.

Laia Nou-FontanetNeurology Department, Coordinating Member of the ERN EpiCARE and ERN-RND Member, Barcelona Children's Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0001-7381-3983
Claudia RavelliPediatric Neurology Department, Neurogenetic Reference Centre for Rare Neurological Diseases, Armand Trousseau Hospital APHP, Sorbonne Université, Paris, France.
Lydie BurglenReference Center for Cerebellar Malformations and Congenital Diseases and Pediatric Neurogenetics Laboratory, Department of Genetics, AP-HP. Sorbonne University, Armand Trousseau Hospital, Paris, France.
Sol Balsells MejiaStatistician, Sant Joan de Déu Research Foundation, University of Barcelona, Barcelona, Spain.
Angel Valls-VillalbaInternal Medicine Department, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
Elies Roman SchiffelsStatistician, Sant Joan de Déu Research Foundation, University of Barcelona, Barcelona, Spain.
Alice InnocentiNeurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of EpiCARE, Rome, Italy.
Beatriz VillafuerteThyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), Madrid, Spain.
Ainara Salazar-VillacortaDevelopmental Neurosciences Department, UCL GOS Institute of Child Health/Zayed Center for Research into Rare Disease in Children, London, UK.
Vicente QuirozPediatric Neurology Department, Boston Children's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.
Andrea Sariego JamardoPediatric Neurology Unit, Marques de Valdecilla University Hospital, Santander, Spain.
Giulia BonatoParkinson and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN-RND), University of Padova, Padova, Italy.
Asun Díaz-GomezPediatric Neurology Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Alexandra AfenjarReference Center for Cerebellar Malformations and Congenital Diseases and Pediatric Neurogenetics Laboratory, Department of Genetics, AP-HP. Sorbonne University, Armand Trousseau Hospital, Paris, France.
Catheline VilainDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.
Patricia Dumke da Silva MöllerNeurology Department, Jose Alencar Brasilia Children's Hospital, Brasilia, Brazil.
Deyanira Garcia-Navas NuñezPediatric Neurology Unit, Cáceres University Hospital Complex, Cáceres, Spain.
Magdalena KrygierDepartment of Developmental Neurology, Medical University of Gdansk, Gdansk, Poland.ORCID https://orcid.org/0000-0002-6607-5983
Maria Judit MolnarInstitute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
Łukasz MilanowskiNeurology Department, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland.
Katrin ÕunapInstitute of Clinical Medicine, University of Tartu and Genetics and Personalized Medicine Clinic, Member of the ERN-ITHACA, Tartu University Hospital, Tartu, Estonia.
Micaela PauniPediatric Neurology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
Patricia VegaPediatric Neurology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
Raphael BorieUniversité Paris Cité, UMR Inserm 1149, CRI, Hôpital Bichat, AP-HP, Service de Pneumologie Allergologie et Transplantation, Centre Constitutif du Centre de Référence des Maladies Pulmonaires Rares, FHU INFIRE, Paris, France.
Milena Villamil-OsorioPediatric Respiratory Department, Fundación Hospital Pediátrico la Misericordia HOMI, Bogotá, Colombia.
Sanem YilmazPediatric Neurology Department, Ege University Medical Faculty, Izmir, Turkey.ORCID https://orcid.org/0000-0002-8719-0665
Dénes ZádoriNeurology Department, University of Szeged, Szeged, Hungary.ORCID https://orcid.org/0000-0003-0749-7980
Marta ZawadzkaDepartment of Developmental Neurology, Medical University of Gdansk, Gdansk, Poland.
Tahsin Stefan BarakatDepartment of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Sebastian NeuensDepartment of Genetics, Hôpital Universitaire des Enfants Reine Fabiola, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.
Daniel de Natera-de BenitoNeurology Department, Coordinating Member of the ERN EpiCARE and ERN-RND Member, Barcelona Children's Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Dídac Casas-AlbaGenetics Department, Barcelona Children's Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
Luca SolianiIRCCS Istituto delle Scienze Neurologiche di Bologna UOC Neuropsichiatria dell'età Pediatrica, Bologna, Italy.
Claudio M de GusmaoPediatric Neurology Department, University of Sao Paulo, Sao Paulo, Brazil.
Giacomo GaroneNeurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of EpiCARE, Rome, Italy.ORCID https://orcid.org/0000-0002-3029-8536
Nicola SpecchioNeurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of EpiCARE, Rome, Italy.
Miryam CarecchioParkinson and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN-RND), University of Padova, Padova, Italy.
José C MorenoThyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), Madrid, Spain.
Francesca MagrinelliDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID https://orcid.org/0000-0003-4706-6245
Kailash P BhatiaDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID https://orcid.org/0000-0001-8185-286X
Darius Ebrahimi-FakhariPediatric Neurology Department, Boston Children's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-0026-4714
Claudia CastiglioniPediatric Neurology Department, Clinica Meds Santiago, Santiago, Chile.ORCID https://orcid.org/0000-0002-1981-7550
Manju Ann KurianDevelopmental Neurosciences Department, UCL GOS Institute of Child Health/Zayed Center for Research into Rare Disease in Children, London, UK.ORCID https://orcid.org/0000-0003-3529-5075
João Nuno CarvalhoPediatric Neurology, Centro de Desenvolvimento da Criança Torrado da Silva, Garcia de Orta Hospital, Almada, Portugal.
Roser PonsPediatric Neurology Department, Children's Hospital Agia Sofia, Athens, Greece.ORCID https://orcid.org/0000-0001-6749-1906
Emmanuel RozeSorbonne University, INSERM, CNRS, Paris Brain Institute, AP-HP, Institute of Neurology, Paris, France.
Diane DoummarPediatric Neurology Department, Neurogenetic Reference Centre for Rare Neurological Diseases, Armand Trousseau Hospital APHP, Sorbonne Université, Paris, France.
Juan Darío Ortigoza-EscobarNeurology Department, Coordinating Member of the ERN EpiCARE and ERN-RND Member, Barcelona Children's Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0002-6320-2641

Funding

American Parkinson Disease Association 1282403Edmond J. Safra Movement Disorders Research Career Development Award MJFF-023893Estonian Research Competency Council PRG2040NIHR UCLH BRC Translational Neuroscience Intermediate Fellowship BRC1287/TN/FM/101410Parkinson's UK G-2401
6 · The paper itself

Abstract

backgroundNKX2-1-related disorders result from heterozygous variants in NKX2-1, a gene crucial for brain, lung, and thyroid development. Although movement disorders, hypothyroidism, and neonatal respiratory distress are recognized, the full phenotype and genotype-phenotype relationships remain incompletely defined.

objectivesTo delineate neurological, respiratory, and endocrine features across ages, characterize movement disorder trajectories - particularly chorea - and explore genotype-phenotype associations with clinical relevance.

methodsWe conducted a multicenter, cross-sectional study recruiting participants through referral clinicians and European networks. Standardized clinical and genetic data were captured in an electronic database and analyzed with descriptive and inferential statistics.

resultsSixty-eight individuals (37 female; median age 16 years, range 2-60 years) were included. Motor delay was the commonest presenting feature (~60%); neonatal respiratory distress syndrome occurred in one-third of cases. The brain-lung-thyroid triad was present in almost half. Chorea affected over 90% and began in early childhood; it was more frequent with single nucleotide variants than with deletions. Deletions are associated with better gross motor function. Frameshift or nonsense variants showed greater respiratory involvement, and variants in the exon-3 homeobox region were associated with age-related reduction of chorea. Neonatal respiratory distress predicted later respiratory symptoms. Greater abnormal involuntary movement severity correlated with poorer manual and gross motor function. Hypotonia and untreated hypothyroidism are associated with more severe chorea. Psychiatric comorbidity occurred in over one-third of cases, mainly attention-deficit/hyperactivity symptoms.

conclusionsThis largest cohort to date shows early neurological onset, genotype-specific outcomes, and frequent psychiatric comorbidity in NKX2-1-related disorders, refining clinical expectations and supporting genotype-informed diagnosis, counseling, and management. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Movement DisordersThyroid Nuclear Factor 1AdolescentAdultAthetosisChildChild, PreschoolChoreaCongenital HypothyroidismCross-Sectional StudiesFemaleGenetic Association StudiesHumansHypothyroidismMaleMiddle AgedNKX2-1 protein, humanThyroid Nuclear Factor 1benign hereditary choreabrain‐lung‐thyroid syndromechoreahypothyroidismneonatal respiratory distress syndromeneurodevelopmental delayNKX2‐1TTF‐1

Identifiers

PMID41552915
PMCPMC13067339

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.