The CHD8 overgrowth syndrome: A detailed evaluation of an emerging overgrowth phenotype in 27 patients

被引：35

作者：

Ostrowski, Philip J. ^{[1
]}

Zachariou, Anna ^{[2
]}

Loveday, Chey ^{[3
]}

Beleza-Meireles, Ana ^{[4
]}

Bertoli, Marta ^{[5
]}

Dean, John ^{[6
]}

Douglas, Andrew G. L. ^{[7
,8
]}

Ellis, Ian ^{[9
]}

Foster, Alison ^{[10
,11
]}

Graham, John M. ^{[12
,13
]}

Hague, Jennifer ^{[14
]}

Hilhorst-Hofstee, Yvonne ^{[15
]}

Hoffer, Mariette ^{[15
]}

Johnson, Diana ^{[16
]}

Josifova, Dragana ^{[4
]}

Kant, Sarina G. ^{[15
]}

Kini, Usha ^{[17
]}

Lachlan, Katherine ^{[7
]}

Lam, Wayne ^{[18
]}

Lees, Melissa ^{[19
]}

Lynch, Sally ^{[20
]}

Maitz, Silvia ^{[21
]}

McKee, Shane ^{[22
]}

Metcalfe, Kay ^{[23
]}

Nathanson, Katherine ^{[24
]}

Ockeloen, Charlotte W. ^{[25
]}

Parker, Michael J. ^{[16
]}

Pierson, Tyler M. ^{[26
]}

Rahikkala, Elisa ^{[27
]}

Sanchez-Lara, Pedro A. ^{[12
,13
]}

Spano, Alice ^{[21
]}

Van Maldergem, Lionel ^{[28
,29
]}

Cole, Trevor ^{[11
]}

Douzgou, Sofia ^{[30
,31
]}

Tatton-Brown, Katrina ^{[1
,32
]}

机构：

[1] St Georges Univ NHS Fdn Trust, South West Thames Reg Genet Serv, London, England

[2] Inst Canc Res, Div Clin Studies, London, England

[3] Inst Canc Res, Div Genet & Epidemiol, London, England

[4] Guys & St Thomas NHS Trust, Dept Clin Genet, London, England

[5] Newcastle Tyne NHS Fdn Trust, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England

[6] Aberdeen Royal Infirm, North Scotland Med Genet Serv, Aberdeen, Scotland

[7] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England

[8] Human Dev & Hlth, Southampton, Hants, England

[9] Liverpool Womens NHS Fdn Trust, Dept Clin Genet, Liverpool, Merseyside, England

[10] Univ Birmingham, Inst Canc & Genom Sci, Birmingham, W Midlands, England

[11] Birmingham Womens & Childrens NHS Fdn Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England

[12] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA

[13] Dept Pediat, Cedars Sinai Med Ctr, Los Angeles, CA USA

[14] Addenbrookes Hosp, E England Reg Med Genet Serv, Cambridge, England

[15] Leiden Univ Med Ctr, Dept Clin Genet, Leiden, Netherlands

[16] Sheffield Childrens NHS Fdn Trust, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England

[17] Oxford Univ Hosp NHS Fdn Trust, Oxford Ctr Genom Med, Oxford, England

[18] Western Gen Hosp, Dept Clin Genet, Edinburgh, Midlothian, Scotland

[19] Great Ormond St Hosp Sick Children, Clin Genet Unit, London, England

[20] Temple St Childrens Hosp, Dublin, Ireland

[21] South Gerardo Hosp, MBBM Fdn, Pediat Genet Unit, Monza, Italy

[22] Northern Ireland Reg Genet Ctr, Belfast, Antrim, North Ireland

[23] Manchester Ctr Genom Med, Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England

[24] Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA

[25] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands

[26] Board Governors Regenerat Med Inst, Dept Pediat & Neurol, Cedars Sinai Med Ctr, Los Angeles, CA USA

[27] Oulu Univ Hosp & Univ Oulu, Dept Clin Genet, PEDEGO Res Unit & Med Res Ctr Oulu, Oulu, Finland

[28] Univ Franche Comte, Ctr Genet Humaine, Besancon, France

[29] Natl Inst Hlth Med Res INSERM, Clin Investigat Ctr 1431, Besancon, France

[30] Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, St Marys Hosp, Manchester Ctr Genom Med, Manchester, Lancs, England

[31] Univ Manchester, Sch Biol Sci, Div Evolut & Genom Sci, Manchester, Lancs, England

[32] St Georges Univ London, London, England

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS | 2019年 / 181卷 / 04期

基金：

英国惠康基金;

关键词：

CHD8; intellectual disability; macrocephaly; overgrowth; AUTISM; MUTATIONS; 14Q11.2; MICRODELETION; GENES;

D O I：

10.1002/ajmg.c.31749

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes an overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely pathogenic CHD8 variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All patients presented with intellectual disability, with 85% in the mild or moderate range, and 85% had a height and/or head circumference >= 2 standard deviations above the mean, meeting our clinical criteria for overgrowth. Behavioral problems were reported in the majority of patients (78%), with over half (56%) either formally diagnosed with an autistic spectrum disorder or described as having autistic traits. Additional clinical features included neonatal hypotonia (33%), and less frequently seizures, pes planus, scoliosis, fifth finger clinodactyly, umbilical hernia, and glabellar hemangioma (<= 15% each). These results suggest that, in addition to its established link with autism and intellectual disability, CHD8 causes an overgrowth phenotype, and should be considered in the differential diagnosis of patients presenting with increased height and/or head circumference in association with intellectual disability.

引用

页码：557 / 564

页数：8

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