Molecular Genetics & Genomic Medicine (Sep 2021)
Phenotypes and genotypes in non‐consanguineous and consanguineous primary microcephaly: High incidence of epilepsy
- Sarah Duerinckx,
- Julie Désir,
- Camille Perazzolo,
- Cindy Badoer,
- Valérie Jacquemin,
- Julie Soblet,
- Isabelle Maystadt,
- Yusuf Tunca,
- Bettina Blaumeiser,
- Berten Ceulemans,
- Winnie Courtens,
- François‐Guillaume Debray,
- Anne Destree,
- Koenraad Devriendt,
- Anna Jansen,
- Kathelijn Keymolen,
- Damien Lederer,
- Bart Loeys,
- Marije Meuwissen,
- Stéphanie Moortgat,
- Geert Mortier,
- Marie‐Cécile Nassogne,
- Tayeb Sekhara,
- Rudy Van Coster,
- Jenny Van Den Ende,
- Nathalie Van der Aa,
- Hilde Van Esch,
- Olivier Vanakker,
- Helene Verhelst,
- Catheline Vilain,
- Sarah Weckhuysen,
- Sandrine Passemard,
- Alain Verloes,
- Alec Aeby,
- Nicolas Deconinck,
- Patrick Van Bogaert,
- Isabelle Pirson,
- Marc Abramowicz
Affiliations
- Sarah Duerinckx
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire Université Libre de Bruxelles Brussels Belgium
- Julie Désir
- Centre de Génétique Humaine Institut de Pathologie et de Génétique Gosselies Belgium
- Camille Perazzolo
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire Université Libre de Bruxelles Brussels Belgium
- Cindy Badoer
- Department of Genetics Hôpital Erasme ULB Center of Human GeneticsUniversité Libre de Bruxelles Brussels Belgium
- Valérie Jacquemin
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire Université Libre de Bruxelles Brussels Belgium
- Julie Soblet
- Department of Genetics Hôpital Erasme ULB Center of Human GeneticsUniversité Libre de Bruxelles Brussels Belgium
- Isabelle Maystadt
- Centre de Génétique Humaine Institut de Pathologie et de Génétique Gosselies Belgium
- Yusuf Tunca
- Department of Medical Genetics Gülhane Faculty of Medicine & Gülhane Training and Research Hospital University of Health Sciences Turkey Ankara Turkey
- Bettina Blaumeiser
- University and University Hospital of Antwerp Antwerp Belgium
- Berten Ceulemans
- University and University Hospital of Antwerp Antwerp Belgium
- Winnie Courtens
- Centre Hospitalier Universitaire de Liège Liège Belgium
- François‐Guillaume Debray
- Centre Hospitalier Universitaire de Liège Liège Belgium
- Anne Destree
- Centre de Génétique Humaine Institut de Pathologie et de Génétique Gosselies Belgium
- Koenraad Devriendt
- Center for Human Genetics University Hospitals Leuven Leuven Belgium
- Anna Jansen
- Universitair Ziekenhuis Brussel (UZ Brussel) Centrum Medische Genetica Universiteit Brussel (VUB) Brussels Belgium
- Kathelijn Keymolen
- Universitair Ziekenhuis Brussel (UZ Brussel) Centrum Medische Genetica Universiteit Brussel (VUB) Brussels Belgium
- Damien Lederer
- Centre de Génétique Humaine Institut de Pathologie et de Génétique Gosselies Belgium
- Bart Loeys
- University and University Hospital of Antwerp Antwerp Belgium
- Marije Meuwissen
- University and University Hospital of Antwerp Antwerp Belgium
- Stéphanie Moortgat
- Centre de Génétique Humaine Institut de Pathologie et de Génétique Gosselies Belgium
- Geert Mortier
- University and University Hospital of Antwerp Antwerp Belgium
- Marie‐Cécile Nassogne
- Cliniques Universitaires Saint‐Luc Université Catholique de Louvain Brussels Belgium
- Tayeb Sekhara
- Centre Hospitalier CHIREC Brussels Belgium
- Rudy Van Coster
- Universitair Ziekenhuis Gent Ghent Belgium
- Jenny Van Den Ende
- University and University Hospital of Antwerp Antwerp Belgium
- Nathalie Van der Aa
- University and University Hospital of Antwerp Antwerp Belgium
- Hilde Van Esch
- Center for Human Genetics University Hospitals Leuven Leuven Belgium
- Olivier Vanakker
- Universitair Ziekenhuis Gent Ghent Belgium
- Helene Verhelst
- Universitair Ziekenhuis Gent Ghent Belgium
- Catheline Vilain
- Department of Genetics Hôpital Erasme ULB Center of Human GeneticsUniversité Libre de Bruxelles Brussels Belgium
- Sarah Weckhuysen
- University and University Hospital of Antwerp Antwerp Belgium
- Sandrine Passemard
- Department of Genetics APHP Robert Debré University Hospital Paris France
- Alain Verloes
- Department of Genetics APHP Robert Debré University Hospital Paris France
- Alec Aeby
- Hôpital Universitaire des Enfants Reine Fabiola (HUDERF) Université Libre de Bruxelles Brussels Belgium
- Nicolas Deconinck
- Hôpital Universitaire des Enfants Reine Fabiola (HUDERF) Université Libre de Bruxelles Brussels Belgium
- Patrick Van Bogaert
- Department of Pediatrics Centre Hospitalier Universitaire d’Angers France
- Isabelle Pirson
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire Université Libre de Bruxelles Brussels Belgium
- Marc Abramowicz
- Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire Université Libre de Bruxelles Brussels Belgium
- DOI
- https://doi.org/10.1002/mgg3.1768
- Journal volume & issue
-
Vol. 9,
no. 9
pp. n/a – n/a
Abstract
Abstract Background Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results Pathogenic variants in ASPM and WDR62 were the most frequent causes in non‐consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non‐consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.
Keywords