Developmental and Epileptic encephalopathies (DEE) describe heterogeneous 
epilepsy syndromes, characterized by early-onset, refractory seizures and 
developmental delay (DD). Several DEE associated genes have been reported. With 
increased access to whole exome sequencing (WES), new candidate genes are being 
identified although there are fewer large cohort papers describing the clinical 
phenotype in such patients. We describe 6 unreported individuals and provide 
updated information on an additional previously reported individual with 
heterozygous de novo missense variants in YWHAG. We describe a syndromal 
phenotype, report 5 novel, and a recurrent p.Arg132Cys YWHAG variant and compare 
developmental trajectory and treatment strategies in this cohort. We provide 
further evidence of causality in YWHAG variants. WES was performed in five 
patients via Deciphering Developmental Disorders Study and the remaining two 
were identified via Genematcher and AnnEX databases. De novo variants identified 
from exome data were validated using Sanger sequencing. Seven out of seven 
patients in the cohort have de novo, heterozygous missense variants in YWHAG 
including 2/7 patients with a recurrent c.394C > T, p.Arg132Cys variant; 1/7 has 
a second, pathogenic variant in STAG1. Characteristic features included: 
early-onset seizures, predominantly generalized tonic-clonic and absence type 
(7/7) with good response to standard anti-epileptic medications; moderate DD; 
Intellectual Disability (ID) (5/7) and Autism Spectrum Disorder (3/7). De novo 
YWHAG missense variants cause EE, characterized by early-onset epilepsy, ID and 
DD, supporting the hypothesis that YWHAG loss-of-function causes a neurological 
phenotype. Although the exact mechanism of disease resulting from alterations in 
YWHAG is not fully known, it is possible that haploinsufficiency of YWHAG in 
developing cerebral cortex may lead to abnormal neuronal migration resulting in 
DEE.