RT Journal Article SR Electronic T1 Delineating FOXG1 syndrome JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e281 DO 10.1212/NXG.0000000000000281 VO 4 IS 6 A1 Vegas, Nancy A1 Cavallin, Mara A1 Maillard, Camille A1 Boddaert, Nathalie A1 Toulouse, Joseph A1 Schaefer, Elise A1 Lerman-Sagie, Tally A1 Lev, Dorit A1 Magalie, Barth A1 Moutton, Sébastien A1 Haan, Eric A1 Isidor, Bertrand A1 Heron, Delphine A1 Milh, Mathieu A1 Rondeau, Stéphane A1 Michot, Caroline A1 Valence, Stephanie A1 Wagner, Sabrina A1 Hully, Marie A1 Mignot, Cyril A1 Masurel, Alice A1 Datta, Alexandre A1 Odent, Sylvie A1 Nizon, Mathilde A1 Lazaro, Leila A1 Vincent, Marie A1 Cogné, Benjamin A1 Guerrot, Anne Marie A1 Arpin, Stéphanie A1 Pedespan, Jean Michel A1 Caubel, Isabelle A1 Pontier, Benedicte A1 Troude, Baptiste A1 Rivier, Francois A1 Philippe, Christophe A1 Bienvenu, Thierry A1 Spitz, Marie-Aude A1 Bery, Amandine A1 Bahi-Buisson, Nadia YR 2018 UL http://ng.neurology.org/content/4/6/e281.abstract AB Objective To provide new insights into the FOXG1-related clinical and imaging phenotypes and refine the phenotype-genotype correlation in FOXG1 syndrome.Methods We analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenic FOXG1 variant and performed phenotype-genotype correlations.Results A total of 37 FOXG1 different heterozygous mutations were identified, of which 18 are novel. We described a broad spectrum of neurodevelopmental phenotypes, characterized by severe postnatal microcephaly and developmental delay accompanied by a hyperkinetic movement disorder, stereotypes and sleep disorders, and epileptic seizures. Our data highlighted 3 patterns of gyration, including frontal pachygyria in younger patients (26.7%), moderate simplified gyration (24.4%) and mildly simplified or normal gyration (48.9%), corpus callosum hypogenesis mostly in its frontal part, combined with moderate-to-severe myelination delay that improved and normalized with age. Frameshift and nonsense mutations in the N-terminus of FOXG1, which are the most common mutation types, show the most severe clinical features and MRI anomalies. However, patients with recurrent frameshift mutations c.460dupG and c.256dupC had variable clinical and imaging presentations.Conclusions These findings have implications for genetic counseling, providing evidence that N-terminal mutations and large deletions lead to more severe FOXG1 syndrome, although genotype-phenotype correlations are not necessarily straightforward in recurrent mutations. Together, these analyses support the view that FOXG1 syndrome is a specific disorder characterized by frontal pachygyria and delayed myelination in its most severe form and hypogenetic corpus callosum in its milder form.FBD=forkhead binding domain