Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND)

Vera G, Sorlin A, Delplancq G, Lecoquierre F, Brasseur-Daudruy M, Petit F, Smol T, Ziegler A, Bonneau D, Colin E, Mercier S, Cogné B, Bézieau S, Edery P, Lesca G, Chatron N, Sabatier I, Duban-Bedu B, Colson C, Piton A, Durand B, Capri Y, Perrin L, Wiesener A, Zweier C, Maroofian R, Carroll CJ, Galehdari H, Mazaheri N, Callewaert B, Giulianno F, Zaafrane-Khachnaoui K, Buchert-Lo R, Haack T, Magg J, Rieß A, Blandfort M, Waldmüller S, Horber V, Leonardi E, Polli R, Turolla L, Murgia A, Frebourg T, Lebre AS, Nicolas G, Saugier-Veber P, Guerrot AM (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 63

Article Number: 104004

Journal Issue: 10

DOI: 10.1016/j.ejmg.2020.104004

Abstract

De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions. All individuals presented developmental delay with a median age of 2.5 years for independent walking and of 3 years for first spoken words. GATAD2B variant carriers showed very little subsequent speech progress, two patients over 30 years of age remaining non-verbal. ID was mostly moderate to severe, with one profound and one mild case, which shows a wider spectrum of disease severity than previously reported. We confirm macrocephaly as a major feature in GAND (53%). Most common dysmorphic features included broad forehead, deeply set eyes, hypertelorism, wide nasal base, and pointed chin. Conversely, prenatal abnormalities, non-cerebral malformations, epilepsy, and autistic behavior were uncommon. Other features included feeding difficulties, behavioral abnormalities, and unspecific abnormalities on brain MRI. Improving our knowledge of the clinical phenotype is essential for correct interpretation of the molecular results and accurate patient management.

Authors with CRIS profile

Involved external institutions

Hospices Civils de Lyon (CHU) France (FR) Centre hospitalier universitaire (CHU) d'Angers France (FR) Hôpital Universitaire Robert-Debré France (FR) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) France (FR) University of Rouen / Université de Rouen France (FR) CHU de Caen Normandie France (FR) Hôpital Saint Vincent de Paul France (FR) University Hospital Ghent Belgium (BE) Hospital Center University Rouen / Centre hospitalier universitaire de Rouen (CHU) France (FR) Eberhard Karls Universität Tübingen Germany (DE) Universitätsklinikum Tübingen Germany (DE) University of Padua / Universita degli Studi di Padova Italy (IT) Université de Lyon (UDL) France (FR) Centre Hospitalier Universitaire de Nice / CHU de Nice France (FR) Université Bourgogne Franche-Comté France (FR) National Hospital For Neurology and Neurosurgery United Kingdom (GB) Fondazione Istituto di Ricerca Pediatrica Città della Speranza (IRP) Italy (IT) Shahid Chamran University of Ahvaz / دانشگاه شهید چمران اهواز Iran, Islamic Republic of (IR) Centre hospitalier universitaire de Reims (CHU de Reims) France (FR) St George's, University of London (SGUL) / St George's Hospital Medical School United Kingdom (GB) LILLE 1 University - Science and Technology France (FR) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg France (FR)

How to cite

APA:

Vera, G., Sorlin, A., Delplancq, G., Lecoquierre, F., Brasseur-Daudruy, M., Petit, F.,... Guerrot, A.M. (2020). Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND). European Journal of Medical Genetics, 63(10). https://doi.org/10.1016/j.ejmg.2020.104004

MLA:

Vera, Gabriella, et al. "Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND)." European Journal of Medical Genetics 63.10 (2020).

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