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Further delineation of Malan syndrome
Author(s) -
Priolo Manuela,
Schanze Denny,
TattonBrown Katrin,
Mulder Paul A.,
Tenorio Jair,
Kooblall Kreepa,
Acero Inés Hernández,
Alkuraya Fowzan S.,
Arias Pedro,
Bernardini Laura,
Bijlsma Emilia K.,
Cole Trevor,
Coubes Christine,
Dapia Irene,
Davies Sally,
Di Donato Nataliya,
Elcioglu Nursel H.,
Fahrner Jill A.,
Foster Alison,
González Noelia García,
Huber Ilka,
Iascone Maria,
Kaiser AnnSophie,
Kamath Arveen,
Liebelt Jan,
Lynch Sally Ann,
Maas Saskia M.,
Mammì Corrado,
Mathijssen Inge B.,
McKee Shane,
Menke Leonie A.,
Mirzaa Ghayda M.,
Montgomery Tara,
Neubauer Dorothee,
Neumann Thomas E.,
Pintomalli Letizia,
Pisanti Maria Antonietta,
Plomp Astrid S.,
Price Sue,
Salter Claire,
SantosSimarro Fernando,
Sarda Pierre,
Segovia Mabel,
ShawSmith Charles,
Smithson Sarah,
Suri Mohnish,
Valdez Rita Maria,
Haeringen Arie,
Hagen Johanna M.,
Zollino Marcela,
Lapunzina Pablo,
Thakker Rajesh V.,
Zenker Martin,
Hennekam Raoul C.
Publication year - 2018
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23563
Subject(s) - macrocephaly , sotos syndrome , biology , genotype phenotype distinction , phenotype , genetics , exon , point mutation , epilepsy , intellectual disability , mutation , gene , neuroscience
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.