Brain Tissue Low-Level Mosaicism for <i>MTOR</i> Mutation Causes Smith–Kingsmore Phenotype with Recurrent Hypoglycemia—A Novel Phenotype and a Further Proof for Testing of an Affected Tissue
Krzysztof Szczałuba,
Małgorzata Rydzanicz,
Anna Walczak,
Joanna Kosińska,
Agnieszka Koppolu,
Anna Biernacka,
Katarzyna Iwanicka-Pronicka,
Wiesława Grajkowska,
Elżbieta Jurkiewicz,
Paweł Kowalczyk,
Rafał Płoski
Affiliations
Krzysztof Szczałuba
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Małgorzata Rydzanicz
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Anna Walczak
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Joanna Kosińska
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Agnieszka Koppolu
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Anna Biernacka
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
Katarzyna Iwanicka-Pronicka
Department of Audiology and Phoniatrics, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
Wiesława Grajkowska
Department of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
Elżbieta Jurkiewicz
Department of Diagnostic Imaging, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
Paweł Kowalczyk
Department of Neurosurgery, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
Rafał Płoski
Department of Medical Genetics, Medical University of Warsaw, Pawinskiego 3c Str., 02-106 Warsaw, Poland
De novo somatic variants in genes encoding components of the PI3K–AKT3–mTOR pathway, 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 mosaicism. 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.
