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Epilepsia. 2016 May;57(5):e97-e102. doi: 10.1111/epi.13358. Epub 2016 Apr 8.

RARS2 mutations in a sibship with infantile spasms.

Author information

1
Molecular Neurosciences, Developmental Neurosciences Programme, UCL-Institute of Child Health, London, United Kingdom.
2
Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
3
Department of Molecular Neuroscience, UCL-Institute of Neurology, London, United Kingdom.
4
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, U.S.A.
5
Department of Paediatric Neurology, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
6
Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
7
Genetics and Genomic Medicine Programme, UCL-Institute of Child Health, London, United Kingdom.
8
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
9
Department of Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
10
Department of Neurophysiology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
11
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.

Abstract

Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl-tRNA synthetase 2 (RARS2). Mutations in this gene have been classically described in pontocerebellar hypoplasia type six (PCH6), a phenotype characterized by early (often intractable) seizures, profound developmental delay, and progressive pontocerebellar atrophy. The electroclinical spectrum of PCH6 is broad and includes a number of seizure types: myoclonic, generalized tonic-clonic, and focal clonic seizures. Our report expands the characterization of the PCH6 disease spectrum and presents infantile spasms as an associated electroclinical phenotype.

KEYWORDS:

Infantile spasms; Pontocerebellar hypoplasia type 6; RARS2; Whole exome sequencing

PMID:
27061686
PMCID:
PMC4864753
DOI:
10.1111/epi.13358
[Indexed for MEDLINE]
Free PMC Article

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