Brain tissue low-level mosaicism for mtor mutation causes smith–kingsmore phenotype with recurrent hypoglycemia—a novel phenotype and a further proof for testing of an affected tissue

Abstract

De novo somatic variants in genes encoding components of the PI3K–AKT3–mTOR path-way, including MTOR, have been linked to hemimegalencephaly or focal cortical dysplasia. Similarly to other malformations of cortical development, this condition presents with developmental delay and intractable epilepsy, often necessitating surgical treatment. We describe a first patient with the Smith–Kingsmore syndrome phenotype with recurrent hypoglycemia caused by low-level mosaic MTOR mutation restricted to the brain. We provide discussion on different aspects of somatic mo-saicism. Deep exome sequencing combined with a variant search in multiple tissues and careful phenotyping may constitute a key to the diagnosis of the causes of rare brain anomalies.