P A Mulder1, I D C van Balkom1,2, A M Landlust1, M Priolo3, L A Menke4, I H Acero5, F S Alkuraya6, P Arias7, L Bernardini8, E K Bijlsma9, T Cole10, C Coubes11, I Dapia7, S Davies12, N Di Donato13, N H Elcioglu14, J A Fahrner15, A Foster16, N G González17, I Huber18, M Iascone19, A-S Kaiser20, A Kamath12, K Kooblall21, P Lapunzina7, J Liebelt22, S A Lynch23, S M Maas24, C Mammì3, I B Mathijssen24, S McKee25, G M Mirzaa26, T Montgomery27, D Neubauer28, T E Neumann29, L Pintomalli3, M A Pisanti30, A S Plomp24, S Price31, C Salter32, F Santos-Simarro7, P Sarda11, D Schanze28, M Segovia33, C Shaw-Smith34, S Smithson35, M Suri36, K Tatton-Brown37, J Tenorio7, R V Thakker21, R M Valdez38, A Van Haeringen9, J M Van Hagen39, M Zenker28, M Zollino40, W W Dunn41, S Piening1,2, R C Hennekam1,4. 1. Autism Team Northern-Netherlands, Jonx Department of (Youth) Mental Health and Autism, Lentis Psychiatric Institute, Groningen, Netherlands. 2. Rob Giel Research Centre, Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands. 3. Unità Operativa di Genetica Medica, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. 4. Department of Paediatrics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 5. Genetics Unit, Hospital Universitario Central de Asturias, Oviedo, Spain. 6. 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. 7. 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. 8. Cytogenetics Unit, Casa Sollievo della Sofferenza Foundation, San Giovanni Rotondo, Italy. 9. Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands. 10. Department of Clinical Genetics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK. 11. Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France. 12. Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK. 13. Institute for Clinical Genetics, TU Dresden, Dresden, Germany. 14. Department of Pediatric Genetics, Marmara University Medical School, Istanbul and Eastern Mediterranean University, Mersin, Turkey. 15. McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 16. Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. 17. Unit Hospital Universitario Central de Asturias, Oviedo, Spain. 18. Sørland Hospital, Kristiansand, Norway. 19. Medical Genetics Laboratory, ASST Papa Giovanni XXIII, Bergamo, Italy. 20. Institute of Human Genetics, Heidelberg University, Heidelberg, Germany. 21. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. 22. South Australian Clinical Genetics Services, Women's and Children's Hospital, North Adelaide, Australia. 23. 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. 24. Department of Clinical Genetics, Academic Medical Center, Amsterdam, Netherlands. 25. Northern Ireland Regional Genetics Service, Belfast Health and Social Care Trust, Belfast, UK. 26. Center for Integrative Brain Research, Seattle Children's Research Institute, and Division of Genetic Medicine, University of Washington School of Medicine, Seattle, WA, USA. 27. Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. 28. Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany. 29. Mitteldeutscher Praxisverbund Humangenetik, Halle, Germany. 30. Medical Genetic and Laboratory Unit, "Antonio Cardarelli" Hospital, Naples, Italy. 31. Department of Clinical Genetics, Northampton General Hospital NHS Trust, Northampton, UK. 32. Wessex Clinical Genetics Service, Princess Ann Hospital, Southampton, UK. 33. CENAGEM, Centro Nacional de Genética, Buenos Aires, Argentina. 34. Royal Devon and Exeter NHS Foundation Trust, Exeter, UK. 35. University Hospitals Bristol NHS Trust, Bristol, UK. 36. Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK. 37. 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. 38. Genetics Unit, Hospital Militar Central "Cirujano Mayor Dr. Cosme Argerich", Buenos Aires, Argentina. 39. Department of Clinical Genetics, VU University Medical Centre, Amsterdam, Netherlands. 40. Department of Laboratory Medicine, Institute of Medical Genetics, Catholic University, Rome, Italy. 41. Department of Occupational Therapy Education, School of Health Professions, University of Missouri, Columbia, MO, USA.
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.
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: Valérie Malan; Diana Rajan; Sophie Thomas; Adam C Shaw; Hélène Louis Dit Picard; Valérie Layet; Marianne Till; Arie van Haeringen; Geert Mortier; Sheela Nampoothiri; Silvija Puseljić; Laurence Legeai-Mallet; Nigel P Carter; Michel Vekemans; Arnold Munnich; Raoul C Hennekam; Laurence Colleaux; Valérie Cormier-Daire Journal: Am J Hum Genet Date: 2010-07-30 Impact factor: 11.025
Authors: Siddharth Srivastava; Colleen Landy-Schmitt; Bennett Clark; Antonie D Kline; Matt Specht; Marco A Grados Journal: Am J Med Genet A Date: 2014-04-09 Impact factor: 2.802
Authors: Manuela Priolo; Denny Schanze; Katrin Tatton-Brown; Paul A Mulder; Jair Tenorio; Kreepa Kooblall; Inés Hernández Acero; Fowzan S Alkuraya; Pedro Arias; Laura Bernardini; Emilia K Bijlsma; Trevor Cole; Christine Coubes; Irene Dapia; Sally Davies; Nataliya Di Donato; Nursel H Elcioglu; Jill A Fahrner; Alison Foster; Noelia García González; Ilka Huber; Maria Iascone; Ann-Sophie Kaiser; Arveen Kamath; Jan Liebelt; Sally Ann Lynch; Saskia M Maas; Corrado Mammì; Inge B Mathijssen; Shane McKee; Leonie A Menke; Ghayda M Mirzaa; Tara Montgomery; Dorothee Neubauer; Thomas E Neumann; Letizia Pintomalli; Maria Antonietta Pisanti; Astrid S Plomp; Sue Price; Claire Salter; Fernando Santos-Simarro; Pierre Sarda; Mabel Segovia; Charles Shaw-Smith; Sarah Smithson; Mohnish Suri; Rita Maria Valdez; Arie Van Haeringen; Johanna M Van Hagen; Marcela Zollino; Pablo Lapunzina; Rajesh V Thakker; Martin Zenker; Raoul C Hennekam Journal: Hum Mutat Date: 2018-06-25 Impact factor: 4.878
Authors: Danyon Harkins; Tracey J Harvey; Cooper Atterton; Ingrid Miller; Laura Currey; Sabrina Oishi; Maria Kasherman; Raul Ayala Davila; Lucy Harris; Kathryn Green; Hannah Piper; Robert G Parton; Stefan Thor; Helen M Cooper; Michael Piper Journal: Cells Date: 2022-08-02 Impact factor: 7.666
Authors: Paolo Alfieri; Marina Macchiaiolo; Martina Collotta; Federica Alice Maria Montanaro; Cristina Caciolo; Francesca Cumbo; Paolo Galassi; Filippo Maria Panfili; Fabiana Cortellessa; Marcella Zollino; Maria Accadia; Marco Seri; Marco Tartaglia; Andrea Bartuli; Corrado Mammì; Stefano Vicari; Manuela Priolo Journal: J Clin Med Date: 2022-07-14 Impact factor: 4.964