The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved]
Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study...
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| Format: | Article |
| Language: | English |
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Wellcome
2018-04-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/3-46/v1 |
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doaj-c02e7b8508cf4bac9ec09604f83723ec |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Katrina Tatton-Brown Anna Zachariou Chey Loveday Anthony Renwick Shazia Mahamdallie Lise Aksglaede Diana Baralle Daniela Barge-Schaapveld Moira Blyth Mieke Bouma Jeroen Breckpot Beau Crabb Tabib Dabir Valerie Cormier-Daire Christine Fauth Richard Fisher Blanca Gener David Goudie Tessa Homfray Matthew Hunter Agnete Jorgensen Sarina G. Kant Cathy Kirally-Borri David Koolen Ajith Kumar Anatalia Labilloy Melissa Lees Carlo Marcelis Catherine Mercer Cyril Mignot Kathryn Miller Katherine Neas Ruth Newbury-Ecob Daniela T. Pilz Renata Posmyk Carlos Prada Keri Ramsey Linda M. Randolph Angelo Selicorni Deborah Shears Mohnish Suri I. Karen Temple Peter Turnpenny Lionel Val Maldergem Vinod Varghese Hermine E. Veenstra-Knol Naomi Yachelevich Laura Yates Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study Deciphering Developmental Disorders (DDD) Study Nazneen Rahman |
| spellingShingle |
Katrina Tatton-Brown Anna Zachariou Chey Loveday Anthony Renwick Shazia Mahamdallie Lise Aksglaede Diana Baralle Daniela Barge-Schaapveld Moira Blyth Mieke Bouma Jeroen Breckpot Beau Crabb Tabib Dabir Valerie Cormier-Daire Christine Fauth Richard Fisher Blanca Gener David Goudie Tessa Homfray Matthew Hunter Agnete Jorgensen Sarina G. Kant Cathy Kirally-Borri David Koolen Ajith Kumar Anatalia Labilloy Melissa Lees Carlo Marcelis Catherine Mercer Cyril Mignot Kathryn Miller Katherine Neas Ruth Newbury-Ecob Daniela T. Pilz Renata Posmyk Carlos Prada Keri Ramsey Linda M. Randolph Angelo Selicorni Deborah Shears Mohnish Suri I. Karen Temple Peter Turnpenny Lionel Val Maldergem Vinod Varghese Hermine E. Veenstra-Knol Naomi Yachelevich Laura Yates Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study Deciphering Developmental Disorders (DDD) Study Nazneen Rahman The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] Wellcome Open Research |
| author_facet |
Katrina Tatton-Brown Anna Zachariou Chey Loveday Anthony Renwick Shazia Mahamdallie Lise Aksglaede Diana Baralle Daniela Barge-Schaapveld Moira Blyth Mieke Bouma Jeroen Breckpot Beau Crabb Tabib Dabir Valerie Cormier-Daire Christine Fauth Richard Fisher Blanca Gener David Goudie Tessa Homfray Matthew Hunter Agnete Jorgensen Sarina G. Kant Cathy Kirally-Borri David Koolen Ajith Kumar Anatalia Labilloy Melissa Lees Carlo Marcelis Catherine Mercer Cyril Mignot Kathryn Miller Katherine Neas Ruth Newbury-Ecob Daniela T. Pilz Renata Posmyk Carlos Prada Keri Ramsey Linda M. Randolph Angelo Selicorni Deborah Shears Mohnish Suri I. Karen Temple Peter Turnpenny Lionel Val Maldergem Vinod Varghese Hermine E. Veenstra-Knol Naomi Yachelevich Laura Yates Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study Deciphering Developmental Disorders (DDD) Study Nazneen Rahman |
| author_sort |
Katrina Tatton-Brown |
| title |
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] |
| title_short |
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] |
| title_full |
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] |
| title_fullStr |
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] |
| title_full_unstemmed |
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved] |
| title_sort |
tatton-brown-rahman syndrome: a clinical study of 55 individuals with de novo constitutive dnmt3a variants [version 1; referees: 2 approved] |
| publisher |
Wellcome |
| series |
Wellcome Open Research |
| issn |
2398-502X |
| publishDate |
2018-04-01 |
| description |
Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novo DNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS |
| url |
https://wellcomeopenresearch.org/articles/3-46/v1 |
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doaj-c02e7b8508cf4bac9ec09604f83723ec2020-11-24T23:03:43ZengWellcomeWellcome Open Research2398-502X2018-04-01310.12688/wellcomeopenres.14430.115708The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved]Katrina Tatton-Brown0Anna Zachariou1Chey Loveday2Anthony Renwick3Shazia Mahamdallie4Lise Aksglaede5Diana Baralle6Daniela Barge-Schaapveld7Moira Blyth8Mieke Bouma9Jeroen Breckpot10Beau Crabb11Tabib Dabir12Valerie Cormier-Daire13Christine Fauth14Richard Fisher15Blanca Gener16David Goudie17Tessa Homfray18Matthew Hunter19Agnete Jorgensen20Sarina G. Kant21Cathy Kirally-Borri22David Koolen23Ajith Kumar24Anatalia Labilloy25Melissa Lees26Carlo Marcelis27Catherine Mercer28Cyril Mignot29Kathryn Miller30Katherine Neas31Ruth Newbury-Ecob32Daniela T. Pilz33Renata Posmyk34Carlos Prada35Keri Ramsey36Linda M. Randolph37Angelo Selicorni38Deborah Shears39Mohnish Suri40I. Karen Temple41Peter Turnpenny42Lionel Val Maldergem43Vinod Varghese44Hermine E. Veenstra-Knol45Naomi Yachelevich46Laura Yates47Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research StudyDeciphering Developmental Disorders (DDD) StudyNazneen Rahman48Division of Genetics and Epidemiology, Institute of Cancer Research, London, UKDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UKDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UKDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UKDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UKDepartment of Clinical Genetics, Copenhagen University Hospital, Copenhagen, DenmarkHuman Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southhampton, UKDepartment of Clinical Genetics, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Clinical Genetics, Chapel Allerton Hospital, Leeds, UKElver Intellectual Disability Centre, Nieuw Wehl, NetherlandsCenter for Human Genetics, University Hospitals and KU Leuven, Leuven, BelgiumGenetics Department, Children's Hospitals and Clinics of Minneapolis, Minneapolis, MN, USANorthern Ireland Regional Genetics Centre, Clinical Genetics Service, Belfast City Hospital, Belfast, UKINSERM UMR1163, IMAGINE Institute affiliate, Paris, FranceDivision of Human Genetics, Medical University Innsbruck, Innsbruck, AustriaTeesside Genetics Unit, The James Cook University Hospital, Middlesbrough, UKDepartment of Genetics, Cruces University Hospital, Biocruces Health Research Institute, centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Basque Country, SpainDepartment of Human Genetics, Ninewells Hospital and Medical School, Dundee, UKSouth West Thames Regional Genetics Service, St George’s University Hospitals NHS Foundation Trust, London, UKMonash Genetics, Monash Health, Melbourne, AustraliaDivision of Child and Adolescent Health, Department of Medical Genetics, University Hospital of North Norway, Tromsø, NorwayDepartment of Clinical Genetics, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Health, Genetic Services of Western Australia, Subiaco, AustraliaDepartment of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsNorth East Thames Regional Genetics Service and Department of Clinical Genetics, Great Ormond Street Hospital, London, UKDepartment of Pediatrics, University of Cincinnati, College of Medicine, Division of Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USANorth East Thames Regional Genetics Service and Department of Clinical Genetics, Great Ormond Street Hospital, London, UKDepartment of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, NetherlandsHuman Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southhampton, UKDépartement de Génétique and Centre de Référence Déficiences Intellectuelles de Causes Rares, Assistance Publique – Hôpitaux de Paris , Paris, FranceAlbany Medical Center, New York, NY, USAGenetic Health Service New Zealand, Wellington, New ZealandUniversity Hospitals Bristol NHS Trust/University of Bristol, Bristol, UKWest of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital,, Glasgow, UKDepartment of Clinical Genetics, Podlaskie Medical Center, Bialystok, PolandDepartment of Pediatrics, University of Cincinnati, College of Medicine, Division of Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USACenter for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, AZ, USADivision of Medical Genetics, Children's Hospital Los Angeles, University of Southern California/ Keck School of Medicine, Los Angeles, CA, USAUOC Pediatria ASST Laraina, Como, ItalyOxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UKNottingham Clinical Genetics Service, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UKHuman Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southhampton, UKPeninsula Clinical Genetics, University of Exeter Medical School, Royal Devon & Exeter NHS Foundation Trust, Exeter, UKCentre de Génétique Humaine and Integrative and Cognitive Neuroscience Research Unit EA481, Besançon, Besançon, FranceInstitute of Medical Genetics, University Hospital of Wales, Cardiff, UKDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsClinical Genetics Services, New York University Hospitals Center, New York University, New York, NY, USATeesside Genetics Unit, The James Cook University Hospital, Middlesbrough, UKDivision of Genetics and Epidemiology, Institute of Cancer Research, London, UKTatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novo DNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRShttps://wellcomeopenresearch.org/articles/3-46/v1 |