Cargando…
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
F1000 Research Limited
2018
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964628/ https://www.ncbi.nlm.nih.gov/pubmed/29900417 http://dx.doi.org/10.12688/wellcomeopenres.14430.1 |
| _version_ | 1783325214523785216 |
|---|---|
| author | Tatton-Brown, Katrina Zachariou, Anna Loveday, Chey Renwick, Anthony Mahamdallie, Shazia Aksglaede, Lise Baralle, Diana Barge-Schaapveld, Daniela Blyth, Moira Bouma, Mieke Breckpot, Jeroen Crabb, Beau Dabir, Tabib Cormier-Daire, Valerie Fauth, Christine Fisher, Richard Gener, Blanca Goudie, David Homfray, Tessa Hunter, Matthew Jorgensen, Agnete Kant, Sarina G. Kirally-Borri, Cathy Koolen, David Kumar, Ajith Labilloy, Anatalia Lees, Melissa Marcelis, Carlo Mercer, Catherine Mignot, Cyril Miller, Kathryn Neas, Katherine Newbury-Ecob, Ruth Pilz, Daniela T. Posmyk, Renata Prada, Carlos Ramsey, Keri Randolph, Linda M. Selicorni, Angelo Shears, Deborah Suri, Mohnish Temple, I. Karen Turnpenny, Peter Van Maldergem, Lionel Varghese, Vinod Veenstra-Knol, Hermine E. Yachelevich, Naomi Yates, Laura Rahman, Nazneen |
| author_facet | Tatton-Brown, Katrina Zachariou, Anna Loveday, Chey Renwick, Anthony Mahamdallie, Shazia Aksglaede, Lise Baralle, Diana Barge-Schaapveld, Daniela Blyth, Moira Bouma, Mieke Breckpot, Jeroen Crabb, Beau Dabir, Tabib Cormier-Daire, Valerie Fauth, Christine Fisher, Richard Gener, Blanca Goudie, David Homfray, Tessa Hunter, Matthew Jorgensen, Agnete Kant, Sarina G. Kirally-Borri, Cathy Koolen, David Kumar, Ajith Labilloy, Anatalia Lees, Melissa Marcelis, Carlo Mercer, Catherine Mignot, Cyril Miller, Kathryn Neas, Katherine Newbury-Ecob, Ruth Pilz, Daniela T. Posmyk, Renata Prada, Carlos Ramsey, Keri Randolph, Linda M. Selicorni, Angelo Shears, Deborah Suri, Mohnish Temple, I. Karen Turnpenny, Peter Van Maldergem, Lionel Varghese, Vinod Veenstra-Knol, Hermine E. Yachelevich, Naomi Yates, Laura Rahman, Nazneen |
| author_sort | Tatton-Brown, Katrina |
| collection | PubMed |
| 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 |
| format | Online Article Text |
| id | pubmed-5964628 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | F1000 Research Limited |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-59646282018-06-12 The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants Tatton-Brown, Katrina Zachariou, Anna Loveday, Chey Renwick, Anthony Mahamdallie, Shazia Aksglaede, Lise Baralle, Diana Barge-Schaapveld, Daniela Blyth, Moira Bouma, Mieke Breckpot, Jeroen Crabb, Beau Dabir, Tabib Cormier-Daire, Valerie Fauth, Christine Fisher, Richard Gener, Blanca Goudie, David Homfray, Tessa Hunter, Matthew Jorgensen, Agnete Kant, Sarina G. Kirally-Borri, Cathy Koolen, David Kumar, Ajith Labilloy, Anatalia Lees, Melissa Marcelis, Carlo Mercer, Catherine Mignot, Cyril Miller, Kathryn Neas, Katherine Newbury-Ecob, Ruth Pilz, Daniela T. Posmyk, Renata Prada, Carlos Ramsey, Keri Randolph, Linda M. Selicorni, Angelo Shears, Deborah Suri, Mohnish Temple, I. Karen Turnpenny, Peter Van Maldergem, Lionel Varghese, Vinod Veenstra-Knol, Hermine E. Yachelevich, Naomi Yates, Laura Rahman, Nazneen Wellcome Open Res Research Article 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 F1000 Research Limited 2018-04-23 /pmc/articles/PMC5964628/ /pubmed/29900417 http://dx.doi.org/10.12688/wellcomeopenres.14430.1 Text en Copyright: © 2018 Tatton-Brown K et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| spellingShingle | Research Article Tatton-Brown, Katrina Zachariou, Anna Loveday, Chey Renwick, Anthony Mahamdallie, Shazia Aksglaede, Lise Baralle, Diana Barge-Schaapveld, Daniela Blyth, Moira Bouma, Mieke Breckpot, Jeroen Crabb, Beau Dabir, Tabib Cormier-Daire, Valerie Fauth, Christine Fisher, Richard Gener, Blanca Goudie, David Homfray, Tessa Hunter, Matthew Jorgensen, Agnete Kant, Sarina G. Kirally-Borri, Cathy Koolen, David Kumar, Ajith Labilloy, Anatalia Lees, Melissa Marcelis, Carlo Mercer, Catherine Mignot, Cyril Miller, Kathryn Neas, Katherine Newbury-Ecob, Ruth Pilz, Daniela T. Posmyk, Renata Prada, Carlos Ramsey, Keri Randolph, Linda M. Selicorni, Angelo Shears, Deborah Suri, Mohnish Temple, I. Karen Turnpenny, Peter Van Maldergem, Lionel Varghese, Vinod Veenstra-Knol, Hermine E. Yachelevich, Naomi Yates, Laura Rahman, Nazneen The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants |
| title | The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with
de novo constitutive
DNMT3A variants |
| title_full | The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with
de novo constitutive
DNMT3A variants |
| title_fullStr | The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with
de novo constitutive
DNMT3A variants |
| title_full_unstemmed | The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with
de novo constitutive
DNMT3A variants |
| title_short | The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with
de novo constitutive
DNMT3A variants |
| title_sort | tatton-brown-rahman syndrome: a clinical study of 55 individuals with
de novo constitutive
dnmt3a variants |
| topic | Research Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964628/ https://www.ncbi.nlm.nih.gov/pubmed/29900417 http://dx.doi.org/10.12688/wellcomeopenres.14430.1 |
| work_keys_str_mv | AT tattonbrownkatrina thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT zachariouanna thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT lovedaychey thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT renwickanthony thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mahamdallieshazia thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT aksglaedelise thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT barallediana thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT bargeschaapvelddaniela thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT blythmoira thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT boumamieke thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT breckpotjeroen thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT crabbbeau thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT dabirtabib thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT cormierdairevalerie thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT fauthchristine thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT fisherrichard thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT generblanca thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT goudiedavid thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT homfraytessa thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT huntermatthew thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT jorgensenagnete thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kantsarinag thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kirallyborricathy thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT koolendavid thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kumarajith thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT labilloyanatalia thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT leesmelissa thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT marceliscarlo thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mercercatherine thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mignotcyril thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT millerkathryn thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT neaskatherine thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT newburyecobruth thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT pilzdanielat thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT posmykrenata thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT pradacarlos thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT ramseykeri thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT randolphlindam thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT selicorniangelo thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT shearsdeborah thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT surimohnish thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT templeikaren thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT turnpennypeter thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT vanmaldergemlionel thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT varghesevinod thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT veenstraknolherminee thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT yachelevichnaomi thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT yateslaura thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT rahmannazneen thetattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT tattonbrownkatrina tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT zachariouanna tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT lovedaychey tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT renwickanthony tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mahamdallieshazia tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT aksglaedelise tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT barallediana tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT bargeschaapvelddaniela tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT blythmoira tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT boumamieke tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT breckpotjeroen tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT crabbbeau tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT dabirtabib tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT cormierdairevalerie tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT fauthchristine tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT fisherrichard tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT generblanca tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT goudiedavid tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT homfraytessa tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT huntermatthew tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT jorgensenagnete tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kantsarinag tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kirallyborricathy tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT koolendavid tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT kumarajith tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT labilloyanatalia tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT leesmelissa tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT marceliscarlo tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mercercatherine tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT mignotcyril tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT millerkathryn tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT neaskatherine tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT newburyecobruth tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT pilzdanielat tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT posmykrenata tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT pradacarlos tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT ramseykeri tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT randolphlindam tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT selicorniangelo tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT shearsdeborah tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT surimohnish tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT templeikaren tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT turnpennypeter tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT vanmaldergemlionel tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT varghesevinod tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT veenstraknolherminee tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT yachelevichnaomi tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT yateslaura tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants AT rahmannazneen tattonbrownrahmansyndromeaclinicalstudyof55individualswithdenovoconstitutivednmt3avariants |