Developmental and Epileptic Encephalopathy 76

Previous studies have suggested that the ACTL6B monoallelic variant is responsible for an autosomal dominant inherited intellectual developmental disorder with severe speech and ambulation deficits. The clinical phenotype of developmental and epileptic encephalopathy type 76 (DEE76) due to ACTL6B biallelic variants was first reported in 2019, with an autosomal recessive mode of inheritance. In this paper, we report on a child in China with DEE76 caused by a compound heterozygous variant of the ACTL6B gene, and we review the literature on ACTL6B gene variants causing DEE76 with complete clinical information. Including our case 1, the genotype and phenotypic characteristics of 18 children from 14 families are summarized. All 18 cases are autosomal recessive, including 12 with homozygous variants and six with compound heterozygous variants. A total of 17 variants have been reported so far, including 14 variants of the loss function. We summarize the clinical features using Human Phenotype Ontology (HPO) terms. We find that DEE76, caused by the ACTL6B biallelic variant, is an early-onset drug-refractory epilepsy with global developmental delay HP:0001263 , hypertonia HP:0001276 , and microcephaly HP:0000252 , and imaging is characterized by brain delayed myelination HP:0012448 . Our case of DEE76 had not been reported when the patient underwent genetic testing in 2018, and the diagnosis was clarified by the reanalysis of the data 2 years later, being the first reported Chinese patient and the only one in which the application of a ketogenic diet for antiepileptic treatment may have been effective

Biology · Compound heterozygosity · Encephalopathy · Epilepsy · Gene · Genotype-phenotype distinction · Global developmental delay · Intellectual disability · Ketogenic Diet · Phenotype · Psychiatry · Genetics and Neurodevelopmental Disorders · Genomic variations and chromosomal abnormalities · Genomics and Rare Diseases · Medicine · Neuroscience · Genetics

• Standards and guidelines for the interpretation of sequence variants

  Open Access•Sue Richards, Nazneen Aziz et al.•Genetics in Medicine•2015

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