title: SPTAN1 encephalopathy: distinct phenotypes and genotypes.
abstract: Recent progress in genetic analysis reveals that a significant proportion of cryptogenic epileptic encephalopathies are single-gene disorders. Mutations in numerous genes for early-onset epileptic encephalopathies have been rapidly identified, including in SPTAN1, which encodes α-II spectrin. The aim of this review is to delineate SPTAN1 encephalopathy as a distinct clinical syndrome. To date, a total of seven epileptic patients with four different in-frame SPTAN1 mutations have been identified. The major clinical features of SPTAN1 mutations include epileptic encephalopathy with hypsarrhythmia, no visual attention, acquired microcephaly, spastic quadriplegia and severe intellectual disability. Brainstem and cerebellar atrophy and cerebral hypomyelination, as observed by magnetic resonance imaging, are specific hallmarks of this condition. A milder variant is characterized by generalized epilepsy with pontocerebellar atrophy. Only in-frame SPTAN1 mutations in the last two spectrin repeats in the C-terminal region lead to dominant negative effects and these specific phenotypes. The last two spectrin repeats are required for α/β spectrin heterodimer associations and the mutations can alter heterodimer formation between the two spectrins. From these data we suggest that SPTAN1 encephalopathy is a distinct clinical syndrome owing to specific SPTAN1 mutations. It is important that this syndrome is recognized by pediatric neurologists to enable proper diagnostic work-up for patients.
authors: 1] Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan [2] Niigata University Medical and Dental Hospital, Niigata, Japan.
authors: Jun
authors: J
authors: Tohyama
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Mitsuko
authors: M
authors: Nakashima
authors: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Shin
authors: S
authors: Nabatame
authors: Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors: Ch'ng
authors: C
authors: Gaik-Siew
authors: Department of Pediatrics, Tokyo Kita-Social Insurance Hospital, Tokyo, Japan.
authors: Rie
authors: R
authors: Miyata
authors: Department of Pediatric Neurology, University Children's Hospital, Ljubljana, Slovenia.
authors: Zvonka
authors: Z
authors: Rener-Primec
authors: Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Mitsuhiro
authors: M
authors: Kato
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Hirotomo
authors: H
authors: Saitsu
mesh_terms: D017668:Age of Onset; D001927:Brain Diseases / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D005799:Genes, Dominant; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D013049:Spectrin / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D013049:Spectrin
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