Further delineation of Malan syndrome

被引：53

作者：

Priolo, Manuela ^{[1
]}

Schanze, Denny ^{[2
]}

Tatton-Brown, Katrin ^{[3
,4
]}

Mulder, Paul A. ^{[5
]}

Tenorio, Jair ^{[6
]}

Kooblall, Kreepa ^{[7
]}

Hernandez Acero, Ines ^{[8
]}

Alkuraya, Fowzan S. ^{[9
,10
]}

Arias, Pedro ^{[6
]}

Bernardini, Laura ^{[11
]}

Bijlsma, Emilia K. ^{[12
]}

Cole, Trevor ^{[13
]}

Coubes, Christine ^{[14
]}

Dapia, Irene ^{[6
]}

Davies, Sally ^{[15
]}

Di Donato, Nataliya ^{[16
]}

Elcioglu, Nursel H. ^{[17
,18
]}

Fahrner, Jill A. ^{[19
]}

Foster, Alison ^{[20
]}

Garcia Gonzalez, Noelia ^{[21
]}

Huber, Ilka ^{[22
]}

Iascone, Maria ^{[23
]}

Kaiser, Ann-Sophie ^{[24
]}

Kamath, Arveen ^{[25
]}

Liebelt, Jan ^{[26
]}

Lynch, Sally Ann ^{[27
,28
]}

Maas, Saskia M. ^{[29
]}

Mammi, Corrado ^{[1
]}

Mathijssen, Inge B. ^{[29
]}

McKee, Shane ^{[30
]}

Menke, Leonie A. ^{[31
]}

Mirzaa, Ghayda M. ^{[32
,33
]}

Montgomery, Tara ^{[34
]}

Neubauer, Dorothee ^{[2
]}

Neumann, Thomas E. ^{[35
]}

Pintomalli, Letizia ^{[1
]}

Pisanti, Maria Antonietta ^{[36
]}

Plomp, Astrid S. ^{[29
]}

Price, Sue ^{[37
]}

Salter, Claire ^{[38
]}

Santos-Simarro, Fernando

Sarda, Pierre ^{[14
]}

Segovia, Mabel ^{[39
]}

Shaw-Smith, Charles ^{[40
]}

Smithson, Sarah ^{[41
]}

Suri, Mohnish ^{[42
]}

Maria Valdez, Rita ^{[43
]}

Van Haeringen, Arie ^{[12
]}

Van Hagen, Johanna M. ^{[44
]}

Zollino, Marcela ^{[45
]}

机构：

[1] Grande Osped Metropolitano Bianchi Melacrino More, Unita Operat Genet Med, Reggio Di Calabria, Italy

[2] Univ Hosp Magdeburg, Inst Human Genet, Magdeburg, Germany

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

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

[5] Lentis Psychiat Inst, Jonx Dept Youth Mental Hlth, Autism Team Northern Netherlands, Groningen, Netherlands

[6] Univ Autonoma Madridand, ISCIII, Ctr Invest Biomed Red Enfermedades Raras, Hosp Univ La Paz,IdiPAZ,Inst Med & Mol Genet INGE, Madrid, Spain

[7] Univ Oxford, Radcliffe Dept Med, Acad Endocrine Unit, Oxford, England

[8] Hosp Univ Cent Asturias, Genet Unit, Oviedo, Spain

[9] King Faisal Specialist Hosp & Res Ctr, King Abdulaziz City Sci & Technol, Saudi Human Genome Project, Riyadh, Saudi Arabia

[10] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh, Saudi Arabia

[11] Casa Sollievo Sofferenza Fdn, Cytogenet Unit, San Giovanni Rotondo, Italy

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

[13] Birmingham Womens & Childrens NHS Fdn Trust, Dept Clin Genet, Birmingham, W Midlands, England

[14] CHRU Montpellier, Hop Arnaud Villeneuve, Dept Genet Med, Montpellier, France

[15] Univ Hosp Wales, Inst Med Genet, Cardiff, S Glam, Wales

[16] Tech Univ Dresden, Inst Clin Genet, Dresden, Germany

[17] Marmara Univ Med Sch, Dept Pediat Genet, Istanbul, Turkey

[18] Eastern Mediterranean Univ, Mersin, Turkey

[19] Johns Hopkins Univ, Sch Med, Dept Pediat, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[20] Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham, W Midlands, England

[21] Unit Hosp Univ Cent Asturias, Oviedo, Spain

[22] Sorland Hosp, Kristiansand, Norway

[23] ASST Papa Giovanni XXIII, Lab Genet Med, Bergamo, Italy

[24] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany

[25] Univ Wales Hosp, Inst Med Genet, Cardiff, S Glam, Wales

[26] South Australian Clin Genet Serv, SA Pathol, Adelaide, SA, Australia

[27] Univ Coll Dublin, Sch Med & Med Sci, UCD Acad Ctr Rare Dis, Dublin, Ireland

[28] Temple St Children s Univ Hosp, Clin Genet, Dublin, Ireland

[29] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[30] Northern Ireland Reg Genet Serv, BelfastHSC Trust, Belfast, Antrim, North Ireland

[31] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Amsterdam, Netherlands

[32] Univ Washington, Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA

[33] Univ Washington, Dept Human Genet, Seattle, WA USA

[34] Newcastle upon Tyne NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England

[35] Mitteldeutscher Praxisverbund Humangenet, Halle, Germany

[36] Antonio Cardarelli Hosp, Med Genet & Lab Unit, Naples, Italy

[37] Northampton Gen Hosp NHS Trust, Dept Clin Genet, Northampton, England

[38] Princess Ann Hosp, Wessex Clin Genet Serv, Southampton, Hants, England

[39] CENAGEM, Ctr Nacl Genet, Buenos Aires, DF, Argentina

[40] Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England

[41] Univ Hosp Bristol NHS Trust, Bristol, Avon, England

[42] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England

[43] Hosp Militar Cent Cirujano Mayor Dr Cosme Argeri, Genet Unit, Buenos Aires, DF, Argentina

[44] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[45] Catholic Univ, Inst Med Genet, Dept Lab Med, Rome, Italy

来源：

HUMAN MUTATION | 2018年 / 39卷 / 09期

关键词：

Malan syndrome; Marshall-Smith syndrome; NFIX; phenotype; phenotype-genotype; Sotos syndrome; Weaver syndrome; MARSHALL-SMITH SYNDROME; DNA-BINDING/DIMERIZATION DOMAIN; SOTOS-LIKE OVERGROWTH; MESSENGER-RNA DECAY; INTELLECTUAL DISABILITY; NFIX MUTATIONS; 19P13.13; DELETION; PHENOTYPE; CACNA1A;

D O I：

10.1002/humu.23563

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.

引用

页码：1226 / 1237

页数：12

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