Last modified: 2018-09-09
Abstract
Introduction
The etiology of significant proportion of West Syndrome patients remains unclear. In this first Indian study, an extensive clinical and genetic evaluation of Infantile Spasms (IS) patients without an acquired etiology has been done.
Methods
Patients with IS onset before 18 months age without acquired cause identified, seen between March 2015 - 2018. History, investigations (including Neuroimaging and metabolic testing) and treatment were recorded.
Tuberous sclerosis (TS) patients were tested for TSC1 & TSC2 genes. In non TS group, non dysmorphic patients had Whole Exome Sequencing (WES) trio and if normal CGH Microarray. In dysmorphic patients CGH Microarray was done before WES.
Results
Of total 32 patients (M: F = 1:1.3), 5 had TS. Mean IS onset age was 6.91±3.48 months. Nearly half (48%) of Non TS patients were treatment refractory. Twenty one (65%) later developed other epilepsies, most commonly Lennoux Gasatut Syndrome (LGS) (11/21). All non TS patients were developmentally delayed and 17/32 were autistic. Neuroimaging was abnormal in 13/32 (40%).
In 14/32 (43.7%), a genetic cause could be confirmed (5 TSC, 2 Deletions & 7 point mutations). In non TS patients, 9/27 (33%) had a mutation identified.
Conclusion:
TS was the commonest cause of IS in our study. Non TS patients were more likely to have refractory IS and significant proportion had neurological morbidity and later other Epileptic Encephalopathies. The Genetic testing protocol including Whole Exome trio and CGH microarray had a yield in about one third of unclassified West Syndrome patients.