TY - JOUR
T1 - The Tatton-Brown-Rahman Syndrome
T2 - A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 3 approved]
AU - Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study
AU - Deciphering Developmental Disorders (DDD) Study
AU - Tatton-Brown, Katrina
AU - Zachariou, Anna
AU - Loveday, Chey
AU - Renwick, Anthony
AU - Mahamdallie, Shazia
AU - Aksglaede, Lise
AU - Baralle, Diana
AU - Barge-Schaapveld, Daniela
AU - Blyth, Moira
AU - Bouma, Mieke
AU - Breckpot, Jeroen
AU - Crabb, Beau
AU - Dabir, Tabib
AU - Cormier-Daire, Valerie
AU - Fauth, Christine
AU - Fisher, Richard
AU - Gener, Blanca
AU - Goudie, David
AU - Homfray, Tessa
AU - Hunter, Matthew
AU - Jorgensen, Agnete
AU - Kant, Sarina G
AU - Kirally-Borri, Cathy
AU - Koolen, David
AU - Kumar, Ajith
AU - Labilloy, Anatalia
AU - Lees, Melissa
AU - Marcelis, Carlo
AU - Mercer, Catherine
AU - Mignot, Cyril
AU - Miller, Kathryn
AU - Neas, Katherine
AU - Newbury-Ecob, Ruth
AU - Pilz, Daniela T
AU - Posmyk, Renata
AU - Prada, Carlos
AU - Ramsey, Keri
AU - Randolph, Linda M
AU - Selicorni, Angelo
AU - Shears, Deborah
AU - Suri, Mohnish
AU - Temple, I. Karen
AU - Turnpenny, Peter
AU - Val Maldergem, Lionel
AU - Varghese, Vinod
AU - Veenstra-Knol, Hermine E
AU - Yachelevich, Naomi
AU - Yates, Laura
AU - Rahman, Nazneen
N1 - K.T.-B. is supported by funding from the Child Growth Foundation (GR01/13) and the Childhood Overgrowth Study is funded by the Wellcome Trust [100210]. The CAUSES Study is funded by Mining for Miracles, British Columbia Children’s Hospital Foundation and Genome British Columbia. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [HICF-1009-003], a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute [098051]. The DDD study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. This study makes use of DECIPHER (http://decipher.sanger.ac.uk), which is funded by the Wellcome Trust.
PY - 2018/4/23
Y1 - 2018/4/23
N2 - 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
AB - 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
KW - DNMT3A
KW - Intellectual disability
KW - Overgrowth
KW - Tatton-Brown-Rahman
UR - http://www.scopus.com/inward/record.url?scp=85048267542&partnerID=8YFLogxK
U2 - 10.12688/wellcomeopenres.14430.1
DO - 10.12688/wellcomeopenres.14430.1
M3 - Article
C2 - 29900417
SN - 2398-502X
VL - 3
SP - 1
EP - 16
JO - Wellcome Open Research
JF - Wellcome Open Research
M1 - 46
ER -
