Year: 2018
Type: article
Study design: Observational Study
Abstract: 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.
Source: Human Mutation
DOI: 10.1002/humu.23563
Authors: Manuela Priolo, Denny Schanze, Katrin Tatton-Brown, Paul A. Mulder, Jair Tenorio, Kreepa Kooblall, Inés Hernández Acero, Fowzan S. Alkuraya, Pedro Arias, Laura Bernardini, Emilia K. Bijlsma, Trevor Cole, Christine Coubes, Irene Dapia, Sally Davies, Nataliya Di Donato, Nursel H. Elcioglu, Jill A. Fahrner, Alison Foster, Noelia García González, Ilka Huber, Maria Iascone, Ann-Sophie Kaiser, Arveen Kamath, Jan Liebelt, Sally Ann Lynch, Saskia M. Maas, Corrado Mammì, Inge B. Mathijssen, Shane McKee, Leonie A. Menke, Ghayda M. Mirzaa, Tara Montgomery, Dorothee Neubauer, Thomas E. Neumann, Letizia Pintomalli, Maria Antonietta Pisanti, Astrid S. Plomp, Sue Price, Claire Salter, Fernando Santos-Simarro, Pierre Sarda, Mabel Segovia, Charles Shaw-Smith, Sarah Smithson, Mohnish Suri, Rita Maria Valdez, Arie Van Haeringen, Johanna M. Van Hagen, Marcela Zollino, Pablo Lapunzina, Rajesh V. Thakker, Martin Zenker, Raoul C. Hennekam
Institutions: Azienda ospedaliera "Bianchi-Melacrino-Morelli", University Hospital Magdeburg, St George's Hospital, Institute of Cancer Research, St George’s University Hospitals NHS Foundation Trust, Lentis, Hospital Universitario La Paz, Centre for Biomedical Network Research on Rare Diseases, Universidad Autónoma de Madrid, University of Oxford, Hospital Universitario Central de Asturias, King Abdulaziz City for Science and Technology, King Faisal Specialist Hospital & Research Centre, Casa Sollievo della Sofferenza, Leiden University, Leiden University Medical Center, Birmingham Women’s and Children’s NHS Foundation Trust, Hôpital Arnaud de Villeneuve, University Hospital of Wales, Technische Universität Dresden, Eastern Mediterranean University, Marmara University, Johns Hopkins University, Johns Hopkins Medicine, University of Birmingham, Sørlandet Sykehus, Ospedale Papa Giovanni XXIII, Heidelberg University, South Australia Pathology, SA Health, University College Dublin, Temple Street Children's University Hospital, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, University of Washington, Seattle Children's Research Institute, Newcastle upon Tyne Hospitals NHS Foundation Trust, Ospedale Antonio Cardarelli, Northampton General Hospital, Northampton General Hospital NHS Trust, Princess Anne Hospital, Royal Devon & Exeter NHS Foundation Trust, Royal Devon University Healthcare NHS Foundation Trust, University Hospitals Bristol NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Argerich Hospital, Amsterdam UMC Location Vrije Universiteit Amsterdam, Università Cattolica del Sacro Cuore
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,740
OpenAlex ID: W2808057155