Marta De Rinaldis1, Roberto Giorda2, Antonio Trabacca3. 1. Scientific Institute IRCCS "E. Medea", Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), Brindisi, Italy. 2. Scientific Institute IRCCS "E. Medea", Molecular Biology Laboratory, Bosisio Parini, LC, Italy. 3. Scientific Institute IRCCS "E. Medea", Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), Brindisi, Italy. Electronic address: antonio.trabacca@lanostrafamiglia.it.
Abstract
BACKGROUND: Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have been recently shown to cause epileptic encephalopathy (MIM # 616409 EIEE33) associated with neurodevelopmental disorders such as intellectual disability, autistic spectrum disorder, hypotonia and dysmorphic facial features. EEF1A2 protein is involved in protein synthesis, suppression of apoptosis, regulation of actin function and cytoskeletal structure. To date, only sixteen patients with EEF1A2 mutations have been reported. CASE REPORT: We described a new case, a boy with severe intellectual disability with absent speech, autistic spectrum disorder, mild dysmorphic facial features, failure to thrive and epilepsy associated to a de novo heterozygous missense mutation in EEF1A2 (c.364G>A; p.Glu122Lys) identified by next generation sequencing; it was already reported in other studies. Most clinical features are shared by all individuals with EEF1A2 mutation, but unlike others reports our patient showed a mild epileptic phenotype: epilepsy developed in late infancy and was well-controlled with antiepileptic drugs. Moreover, at the onset of epilepsy, interictal wake/sleep electroencephalograms showed typical pattern that disappeared with age. CONCLUSION: This report focused that EEF1A2 mutations should be considered not only in patients with epileptic encephalopathy, but also in those with less severe epilepsy. A typical EEG pattern may be a biomarker for EEF1A2 mutation, but further investigations and longitudinal clinical observations are required.
BACKGROUND: Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have been recently shown to cause epilepticencephalopathy (MIM # 616409 EIEE33) associated with neurodevelopmental disorders such as intellectual disability, autistic spectrum disorder, hypotonia and dysmorphic facial features. EEF1A2 protein is involved in protein synthesis, suppression of apoptosis, regulation of actin function and cytoskeletal structure. To date, only sixteen patients with EEF1A2 mutations have been reported. CASE REPORT: We described a new case, a boy with severe intellectual disability with absent speech, autistic spectrum disorder, mild dysmorphic facial features, failure to thrive and epilepsy associated to a de novo heterozygous missense mutation in EEF1A2 (c.364G>A; p.Glu122Lys) identified by next generation sequencing; it was already reported in other studies. Most clinical features are shared by all individuals with EEF1A2 mutation, but unlike others reports our patient showed a mild epileptic phenotype: epilepsy developed in late infancy and was well-controlled with antiepileptic drugs. Moreover, at the onset of epilepsy, interictal wake/sleep electroencephalograms showed typical pattern that disappeared with age. CONCLUSION: This report focused that EEF1A2 mutations should be considered not only in patients with epilepticencephalopathy, but also in those with less severe epilepsy. A typical EEG pattern may be a biomarker for EEF1A2 mutation, but further investigations and longitudinal clinical observations are required.
Authors: Ivan V Pozhidaev; Anastasiia S Boiko; Anton J M Loonen; Diana Z Paderina; Olga Yu Fedorenko; Gennadiy Tenin; Elena G Kornetova; Arkadiy V Semke; Nikolay A Bokhan; Bob Wilffert; Svetlana A Ivanova Journal: Appl Clin Genet Date: 2020-04-22