Case ReportClonic seizures, continuous spikes-and-waves during slow sleep, choreoathetosis and response to sulthiame in a child with FRRS1L encephalopathy
Introduction
Developmental and epileptic encephalopathy is a newly coined term to describe patients in whom developmental impairments result from combination of seizures, electroencephalogram (EEG) abnormalities and the underlying disease [1]. They comprise a heterogenous group of conditions, many of which start in infancy and have underlying genetic abnormalities. Ferric chelate reductase 1 like (FRRS1L) encephalopathy (Early Infantile Epileptic Encephalopathy-37) is a rare example of this condition. Only 14 children from five families have been reported with FRRS1L gene mutation. All had epilepsy, movement disorders and severe developmental delay or regression [2], [3].
Seizures in FRRS1L encephalopathy were mostly refractory to anti-epileptic drugs (AEDs). Various seizure types were described by Madeo et al. [2], including clonic, hemi-clonic, generalized tonic-clonic, spasms and ‘multifocal’ seizure types. Detailed EEG findings were reported in two of the patients from Shaheen’s series [3]; one girl displayed a continuous spikes-and-waves during slow sleep (CSWS) pattern and her brother showed stereotyped occipital spike waves with fixation off phenomenon [4].
Herein we report a patient with FRRS1L encephalopathy, describing the seizures and clinical phenotype, EEG evolution and response to AEDs, highlighting the good response to sulthiame.
Section snippets
Case report
This boy was the first born from a non-consanguineous Malay couple. He was born term, weighed 3.14 kg at birth (at 25th centile) with head circumference (COH) of 32 cm (on the 3rd centile). He had uneventful antenatal and neonatal period but at 6 months old was noted to be globally delayed as he could not fix or follow objects, nor could he reach for objects or roll over. He started to have abnormal movement involving the limbs starting at the age of 7 months. These were repetitive movements of
Discussion
Our patient with FRRS1L encephalopathy displayed many clinical features described in the literature, namely the infantile onset refractory seizure, severe developmental delay and evolving movement disorder. In addition, our patient showed severe failure to thrive and microcephaly. Of particular interest, the seizures in our patient responded well to sulthiame, an observation not reported previously.
In the largest case series thus far, Madeo et al. [2] identified four different homozygous
Conclusion
Sulthiame may have a role in the early treatment of seizures in children with refractory epilepsy due FRRS1L mutation. It remains to be seen if sulthiame can also be effective for controlling seizures in other EIEE with CSWS patterns.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The authors would like to acknowledge the patient and his caregivers for their contribution and permission to publish patient’s video. The authors also like to thank Eriko Koshimizu, Satoko Miyatake and Naomichi Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine for performing the whole exome sequencing.
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