Development, behaviour and sensory processing in Marshall–Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes
Journal of Intellectual Disability Research, vol. 64, pp. 956–969
Abstract
BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.
Authors 57
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Paul A. Mulder corresponding
Affiliation as printed
Autism Team Northern‐Netherlands, Jonx Department of (Youth) Mental Health and Autism Lentis Psychiatric Institute Groningen Netherlands
Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands
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University Medical Center Groningen · Lentis
Affiliation as printed
Autism Team Northern‐Netherlands, Jonx Department of (Youth) Mental Health and Autism Lentis Psychiatric Institute Groningen Netherlands
Rob Giel Research Centre, Department of Psychiatry University Medical Center Groningen Groningen Netherlands
Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands
Rob Giel Research Centre, Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands
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Affiliation as printed
Autism Team Northern‐Netherlands, Jonx Department of (Youth) Mental Health and Autism Lentis Psychiatric Institute Groningen Netherlands
Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands
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Azienda ospedaliera "Bianchi-Melacrino-Morelli"
Affiliation as printed
Unità Operativa di Genetica Medica Grande Ospedale Metropolitano Bianchi‐Melacrino‐Morelli Reggio Calabria Italy
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Paediatrics, Amsterdam UMC University of Amsterdam Amsterdam Netherlands
Department of Paediatrics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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Hospital Universitario Central de Asturias
Affiliation as printed
Genetics Unit Hospital Universitario Central de Asturias Oviedo Spain
Genetics Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
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King Abdulaziz City for Science and Technology · King Faisal Specialist Hospital & Research Centre
Affiliation as printed
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, and Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, and Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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Hospital Universitario La Paz · Centre for Biomedical Network Research on Rare Diseases · Universidad Autónoma de Madrid
Affiliation as printed
Institute of Medical and Molecular Genetics (INGEMM) Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, and CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
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Casa Sollievo della Sofferenza
Affiliation as printed
Cytogenetics Unit Casa Sollievo della Sofferenza Foundation San Giovanni Rotondo Italy
Cytogenetics Unit, Casa Sollievo della Sofferenza Foundation, San Giovanni Rotondo, Italy
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Emilia K. Bijlsma Aachen Department of Clinical Genetics Leiden University Medical Centre Leiden Netherlands Department of Clinical Genetics
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics Leiden University Medical Centre Leiden Netherlands
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands
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Birmingham Women’s and Children’s NHS Foundation Trust
Affiliation as printed
Department of Clinical Genetics Birmingham Women's and Children's NHS Foundation Trust Birmingham UK
Department of Clinical Genetics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
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Affiliation as printed
Département de Génétique Médicale Hôpital Arnaud de Villeneuve, CHRU Montpellier Montpellier France
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Hospital Universitario La Paz · Centre for Biomedical Network Research on Rare Diseases · Universidad Autónoma de Madrid
Affiliation as printed
Institute of Medical and Molecular Genetics (INGEMM) Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, and CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
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Affiliation as printed
Institute of Medical Genetics University Hospital of Wales Cardiff UK
Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK
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Technische Universität Dresden
Affiliation as printed
Institute for Clinical Genetics TU Dresden Dresden Germany
Institute for Clinical Genetics, TU Dresden, Dresden, Germany
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Affiliation as printed
Department of Pediatric Genetics Marmara University Medical School, Istanbul and Eastern Mediterranean University Mersin Turkey
Department of Pediatric Genetics, Marmara University Medical School, Istanbul and Eastern Mediterranean University, Mersin, Turkey
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Johns Hopkins University · Johns Hopkins Medicine
Affiliation as printed
McKusick‐Nathans Institute of Genetic Medicine, Department of Pediatrics Johns Hopkins University School of Medicine Baltimore MD USA
McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Affiliation as printed
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences University of Birmingham Birmingham UK
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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Hospital Universitario Central de Asturias
Affiliation as printed
Unit Hospital Universitario Central de Asturias Oviedo Spain
Unit Hospital Universitario Central de Asturias, Oviedo, Spain
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Affiliation as printed
Sørland Hospital Kristiansand Norway
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Affiliation as printed
Medical Genetics Laboratory ASST Papa Giovanni XXIII Bergamo Italy
Medical Genetics Laboratory, ASST Papa Giovanni XXIII, Bergamo, Italy
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Affiliation as printed
Institute of Human Genetics Heidelberg University Heidelberg Germany
Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
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Affiliation as printed
Institute of Medical Genetics University Hospital of Wales Cardiff UK
Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK
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Affiliation as printed
Academic Endocrine Unit, Radcliffe Department of Medicine University of Oxford Oxford UK
Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Hospital Universitario La Paz · Centre for Biomedical Network Research on Rare Diseases · Universidad Autónoma de Madrid
Affiliation as printed
Institute of Medical and Molecular Genetics (INGEMM) Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, and CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
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Women's and Children's Hospital · Women's and Children's Health Network
Affiliation as printed
South Australian Clinical Genetics Services Women's and Children's Hospital North Adelaide Australia
South Australian Clinical Genetics Services, Women's and Children's Hospital, North Adelaide, Australia
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University College Dublin · Temple Street Children's University Hospital
Affiliation as printed
UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences University College Dublin, and Clinical Genetics, Temple Street Children's University Hospital Dublin Ireland
UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, and Clinical Genetics, Temple Street Children's University Hospital, Dublin, Ireland
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Department of Clinical Genetics Academic Medical Center Amsterdam Netherlands
Department of Clinical Genetics, Academic Medical Center, Amsterdam, Netherlands
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Azienda ospedaliera "Bianchi-Melacrino-Morelli"
Affiliation as printed
Unità Operativa di Genetica Medica Grande Ospedale Metropolitano Bianchi‐Melacrino‐Morelli Reggio Calabria Italy
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Department of Clinical Genetics Academic Medical Center Amsterdam Netherlands
Department of Clinical Genetics, Academic Medical Center, Amsterdam, Netherlands
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Belfast Health and Social Care Trust
Affiliation as printed
Northern Ireland Regional Genetics Service Belfast Health and Social Care Trust Belfast UK
Northern Ireland Regional Genetics Service, Belfast Health and Social Care Trust, Belfast, UK
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University of Washington · Seattle Children's Research Institute
Affiliation as printed
Center for Integrative Brain Research, Seattle Children's Research Institute, and Division of Genetic Medicine University of Washington School of Medicine Seattle WA USA
Center for Integrative Brain Research, Seattle Children's Research Institute, and Division of Genetic Medicine, University of Washington School of Medicine, Seattle, WA, USA
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Newcastle upon Tyne Hospitals NHS Foundation Trust
Affiliation as printed
Newcastle upon Tyne NHS Foundation Trust Newcastle upon Tyne UK
Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK
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Affiliation as printed
Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany
Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany
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Azienda ospedaliera "Bianchi-Melacrino-Morelli"
Affiliation as printed
Unità Operativa di Genetica Medica Grande Ospedale Metropolitano Bianchi‐Melacrino‐Morelli Reggio Calabria Italy
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Affiliation as printed
Medical Genetic and Laboratory Unit "Antonio Cardarelli" Hospital Naples Italy
Medical Genetic and Laboratory Unit, "Antonio Cardarelli" Hospital, Naples, Italy
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Department of Clinical Genetics Academic Medical Center Amsterdam Netherlands
Department of Clinical Genetics, Academic Medical Center, Amsterdam, Netherlands
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Northampton General Hospital · Northampton General Hospital NHS Trust
Affiliation as printed
Department of Clinical Genetics Northampton General Hospital NHS Trust Northampton UK
Department of Clinical Genetics, Northampton General Hospital NHS Trust, Northampton, UK
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Affiliation as printed
Wessex Clinical Genetics Service Princess Ann Hospital Southampton UK
Wessex Clinical Genetics Service, Princess Ann Hospital, Southampton, UK
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Hospital Universitario La Paz · Centre for Biomedical Network Research on Rare Diseases · Universidad Autónoma de Madrid
Affiliation as printed
Institute of Medical and Molecular Genetics (INGEMM) Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, and CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
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Affiliation as printed
Département de Génétique Médicale Hôpital Arnaud de Villeneuve, CHRU Montpellier Montpellier France
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Affiliation as printed
Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany
Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany
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Affiliation as printed
CENAGEM, Centro Nacional de Genética Buenos Aires Argentina
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Royal Devon & Exeter NHS Foundation Trust
Affiliation as printed
Royal Devon and Exeter NHS Foundation Trust Exeter UK
Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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University Hospitals Bristol NHS Foundation Trust
Affiliation as printed
University Hospitals Bristol NHS Trust Bristol UK
University Hospitals Bristol NHS Trust, Bristol, UK
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Nottingham University Hospitals NHS Trust
Affiliation as printed
Nottingham Clinical Genetics Service Nottingham University Hospitals NHS Trust Nottingham UK
Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
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St George's Hospital · Institute of Cancer Research · St George’s University Hospitals NHS Foundation Trust
Affiliation as printed
Division of Genetics and Epidemiology, Institute of Cancer Research London and South West Thames Regional Genetics Service, St. George's University Hospitals NHS Foundation Trust London UK
Division of Genetics and Epidemiology, Institute of Cancer Research, London and South West Thames Regional Genetics Service, St. George's University Hospitals NHS Foundation Trust, London, UK
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Hospital Universitario La Paz · Centre for Biomedical Network Research on Rare Diseases · Universidad Autónoma de Madrid
Affiliation as printed
Institute of Medical and Molecular Genetics (INGEMM) Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, and CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII Madrid Spain
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Affiliation as printed
Academic Endocrine Unit, Radcliffe Department of Medicine University of Oxford Oxford UK
Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Affiliation as printed
Genetics Unit Hospital Militar Central "Cirujano Mayor Dr. Cosme Argerich" Buenos Aires Argentina
Genetics Unit, Hospital Militar Central "Cirujano Mayor Dr. Cosme Argerich", Buenos Aires, Argentina
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Arie van Haeringen Aachen Department of Clinical Genetics Leiden University Medical Centre Leiden Netherlands Department of Clinical Genetics
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics Leiden University Medical Centre Leiden Netherlands
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Clinical Genetics VU University Medical Centre Amsterdam Netherlands
Department of Clinical Genetics, VU University Medical Centre, Amsterdam, Netherlands
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Affiliation as printed
Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany
Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany
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Università Cattolica del Sacro Cuore
Affiliation as printed
Department of Laboratory Medicine, Institute of Medical Genetics Catholic University Rome Italy
Department of Laboratory Medicine, Institute of Medical Genetics, Catholic University, Rome, Italy
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Affiliation as printed
Department of Occupational Therapy Education, School of Health Professions University of Missouri Columbia MO USA
Department of Occupational Therapy Education, School of Health Professions, University of Missouri, Columbia, MO, USA
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University Medical Center Groningen · Lentis
Affiliation as printed
Autism Team Northern‐Netherlands, Jonx Department of (Youth) Mental Health and Autism Lentis Psychiatric Institute Groningen Netherlands
Rob Giel Research Centre, Department of Psychiatry University Medical Center Groningen Groningen Netherlands
Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands
Rob Giel Research Centre, Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands
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Lentis · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Autism Team Northern‐Netherlands, Jonx Department of (Youth) Mental Health and Autism Lentis Psychiatric Institute Groningen Netherlands
Department of Paediatrics, Amsterdam UMC University of Amsterdam Amsterdam Netherlands
Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands
Department of Paediatrics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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