Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26322
Title: FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability.
Austin Authors: Schneider, Amy L ;Myers, Candace T;Muir, Alison M;Calvert, Sophie;Basinger, Alice;Perry, M Scott;Rodan, Lance;Helbig, Katherine L;Chambers, Chelsea;Gorman, Kathleen M;King, Mary D;Donkervoort, Sandra;Soldatos, Ariane;Bönnemann, Carsten G;Spataro, Nino;Gabau, Elisabeth;Arellano, Montserrat;Cappuccio, Gerarda;Brunetti-Pierri, Nicola;Rossignol, Elsa;Hamdan, Fadi F;Michaud, Jacques L;Balak, Christopher;Mefford, Heather C;Scheffer, Ingrid E 
Affiliation: Department of Neurology, Queensland Children's Hospital, South Brisbane, Queensland, Australia
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA
Neurogenomics Division, Centre for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute, Phoenix, AZ, USA
Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA
Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, Quebec, Canada
Department of Neurosciences and Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada
Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada
Department of Translational Medicine, Federico II University, Naples, Italy
Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
Department of Neurology and Clinical Neurophysiology, Children's Health Ireland at Temple Street, Dublin, Ireland
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
Epilepsy Research Centre
Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA
Genetics, Cook Children's, Fort Worth, TX, USA
Justin Neurosciences Center, Cook Children's Medical Center, Fort Worth, TX, USA
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
Department of Neurosciences, University of Virginia, Charlottesville, VA, USA
Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Genetics Laboratory, UDIAT-Centre Diagnostic, Parc Taulí University Hospital, Parc Taulí I3PT Research and Innovation Institute, University of Barcelona, Sabadell, Spain
Paediatric Unit, Parc Taulí University Hospital, Parc Taulí I3PT Research and Innovation Institute, University of Barcelona, Sabadell, Spain
Neuropediatrics Unit, Pediatric Service, MutuaTerrassa University Hospital, Terrassa, Spain
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA
Issue Date: Jan-2021
Date: 2020-12-06
Publication information: Epilepsia 2021; 62(1): e13-e21
Abstract: Chromosome 1q41-q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41-q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41-q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41-q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41-q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug-resistant epilepsy, and hyperkinetic movement disorders.
URI: https://ahro.austin.org.au/austinjspui/handle/1/26322
DOI: 10.1111/epi.16784
ORCID: 0000-0001-5260-7187
0000-0002-9420-085X
0000-0002-1825-846X
0000-0002-9304-9385
0000-0002-2311-2174
Journal: Epilepsia
PubMed URL: 33280099
Type: Journal Article
Subjects: FBXO28
developmental and epileptic encephalopathy
movement disorder
profound intellectual disability
Appears in Collections:Journal articles

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