Midline non-ictal rhythmic waveforms as possible electroencephalographic biomarkers of Smith-Klingsmore syndrome in children

TL;DR

This paper suggests that specific EEG patterns could help diagnose Smith-Klingsmore syndrome in children with incomplete symptoms.

Contribution

The study identifies midline rhythmic waveforms as potential EEG biomarkers for Smith-Klingsmore syndrome.

Findings

Two children with the same MTOR mutation showed unique EEG patterns including midline rhythmic waveforms.

These EEG features may help identify Smith-Klingsmore syndrome even when clinical symptoms are incomplete.

The findings suggest EEG traits could serve as endophenotypes for early diagnosis of the syndrome.

Abstract

•The SKS results from heterozygous MTOR mutations yielding dysmorphic traits/macrocephaly, seizures, intellectual disability.•Phenotype is variably expressed hampering an expedite diagnosis.•Specific electroencephalographic traits can represent endophenotypes useful to suspect SKS.

The SKS results from heterozygous MTOR mutations yielding dysmorphic traits/macrocephaly, seizures, intellectual disability.

Phenotype is variably expressed hampering an expedite diagnosis.

Specific electroencephalographic traits can represent endophenotypes useful to suspect SKS.

Pathogenic variants of the MTOR gene result in the Smith-Kingsmore syndrome, whose phenotypical spectrum includes facial dysmorphisms and neurological features. Expressivity is variable, patients exhibit a combination of intellectual disability, macrocephaly and epilepsy. The diagnosis can be missed, failing to detect the causative pathogenic mutation in patients with somatic mosaicism or even skipping to analyze MTOR when the phenotype is not completely expressed.

Herein, we report two children harboring the same MTOR recurring mutation (c.5395G>A/p.Glu1799Lys) whose EEG displayed a peculiar combination of midline rhythmic waveforms and asynchronous spike-and-wave discharges with anterior fast activity in sleep and wake. Conclusion: We suggest these features might be considered as possible hallmarks of the syndrome and could aid to expedite the diagnosis when the phenotype is incomplete.

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