Evidence map›Paper›PMID 39700446›Full record

ArticleNeurology2025

Exome and Genome Sequencing to Diagnose the Genetic Basis of Neonatal Hypotonia: An International Consortium Study.

Sarah U Morton, Gregory Costain, Courtney E French, Emma Wakeling, Anna Szuto, John Christodoulou, Ronald Cohn, Basil T Darras, Monica H Wojcik, Alissa M D'Gama and 8 more

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

Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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4 citing papers in PubMed.

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5 · Who and what money

Authors and funding

18 authors.

Sarah U MortonFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-7816-2646
Gregory CostainFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0003-0099-9945
Courtney E FrenchFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0001-7620-1544
Emma WakelingFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0001-5712-0044
Anna SzutoFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0001-9140-6193
John ChristodoulouFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-8431-0641
Ronald CohnFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-6775-1496
Basil T DarrasFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-1536-8145
Monica H WojcikFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-8162-5031
Alissa M D'GamaFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.
James J DowlingFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-3984-4169
Sebastian LunkeFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-7168-0723
Francesco MuntoniFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-9102-5232
Lucy RaymondFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0003-2652-3355
David RowitchFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0002-0079-0060
Alan H BeggsFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0001-8818-0568
Zornitza StarkFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.ORCID 0000-0001-8640-1371
Pankaj B AgrawalFrom the Division of Newborn Medicine (S.U.M., M.H.W., A.M.D.G.), Boston Children's Hospital; Department of Pediatrics (S.U.M., M.H.W., A.M.D.G., A.H.B., P.B.A.), Harvard Medical School; The Manton Center for Orphan Disease Research (S.U.M., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital; The Broad Institute of MIT and Harvard (S.U.M., M.H.W., A.H.B., P.B.A.), Cambridge, MA; Division of Clinical and Metabolic Genetics (G.C., R.C.), The Hospital for Sick Children; Program in Genetics and Genome Biology (G.C.,. R.C., J.J.D.), SickKids Research Institute; Department of Paediatrics (G.C., R.C., J.J.D.), Department of Molecular Genetics (G.C., A.S., J.J.D.), University of Toronto, Ontario, Canada; Division of Genetics and Genomics (C.E.F., M.H.W., A.H.B., P.B.A.), Boston Children's Hospital, MA; North East Thames Regional Genetic Service (E.W., F.M.), Great Ormond Street Hospital Trust, London, United Kingdom; Department of Genetic Counselling (A.S.), The Hospital for Sick Children, Toronto, OntarioN, Canada; Murdoch Children's Research Institute and Department of Paediatrics (J.C., S.L., Z.S.), University of Melbourne, Victoria; Discipline of Child and Adolescent Health (J.C.), Sydney Medical School, University of Sydney, New South Wales, Australia; Department of Neurology (B.T.D.), Boston Children's Hospital; Epilepsy Genetics Program (A.M.D.G.), Department of Neurology, Boston Children's Hospital, MA; Division of Neurology (J.J.D.), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pathology (S.L.), University of Melbourne, Australia; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (F.M.), Great Ormond Street Institute of Child Health, University College London; Departments of Medical Genetics and Paediatrics (L.R., D.R.), University of Cambridge, United Kingdom; Division of Neonatology (D.R.), Department of Pediatrics, UCSF, San Francisco, CA; Australian Genomics Health Alliance (Z.S.); and Division of Neonatology (P.B.A.), Department of Pediatrics, University of Miami and Holtz Children's Hospital, Jackson Health System, FL.

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
NICHD NIH HHS P50 HD105351
6 · The paper itself

Abstract

BACKGROUND AND

objectivesHypotonia is a relatively common finding among infants in the neonatal intensive care unit (NICU). Consideration of genetic testing is recommended early in the care of infants with unexplained hypotonia. We aimed to assess the diagnostic yield and overall impact of exome and genome sequencing (ES and GS).

methodsConsecutive infants with hypotonia were identified from research and clinical databases across 5 teaching hospitals in United States, Canada, United Kingdom, and Australia. Inclusion criteria included NICU admission and genetic evaluation. Infants with a known explanation for hypotonia were excluded. Data regarding infant characteristics, genetic testing, and diagnoses were collected. The primary outcome was identification of a molecular diagnosis. Impact on care was a secondary outcome. The Fisher exact and Wilcoxon rank-sum tests were used for statistical analysis.

resultsWe identified 147 infants with unexplained hypotonia. The median gestational age was 39 weeks (interquartile range [IQR] 36-42 weeks), 77 (52%) were female, and the median age was 8 days at the time of evaluation (IQR 2-19 days). Eighty (54%) had hypotonia as the main clinical feature while 67 (46%) had additional multisystem involvement. Seventy-five (51%) underwent rapid ES, 44 (30%) rapid GS, 2 (1%) both ES and GS, and 26 (18%) were admitted before ES or GS became available. Of the 121 infants who underwent ES and/or GS, 72 (60%) had the primary outcome of a molecular diagnosis. In addition, 2 infants with mitochondrial genome variants were diagnosed by mitochondrial GS after negative ES, and one infant needed targeted testing to identify a short tandem repeat expansion missed by GS. The proportion diagnosed by ES and GS was not different between infants with hypotonia as the primary finding (37/56, 66%) and infants with multisystemic symptoms (35/65, 54%, odds ratio [OR] 1.7, CI 0.8-3.7, DISCUSSION: Rapid ES and GS provided a molecular diagnosis for most of the infants with unexplained hypotonia who underwent testing. Further studies are needed to assess the generalizability of these findings as increased access to genetic testing becomes available. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in unexplained neonatal hypotonia, rapid ES or GS adds diagnostic specificity.

Indexed as

Muscle HypotoniaAustraliaCanadaExomeExome SequencingFemaleGenetic TestingHumansInfant, NewbornMaleUnited StatesWhole Genome Sequencing

Identifiers

PMID39700446
PMCPMC11666248

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