title: Characterization of SPATA5-related encephalopathy in early childhood.
abstract: Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole-exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6-12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan. kurata0708@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Kurata
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Tokyo, Japan. terashima-h@ncchd.go.jp.
authors.forename: H
authors.initials: H
authors.lastname: Terashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Matsumura
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maegaki
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Division of Functional Genomics, Research Center for Bioscience, and Technology, Tottori University, Yonago, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Nanba
authors.affiliation: Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D061085:Agenesis of Corpus Callosum; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D004569:Electroencephalography; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010641:Phenotype; D012640:Seizures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D013036:Spasms, Infantile / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology
chemical_list: D018398:Homeodomain Proteins; C000603255:SPATA5 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: SPATA5; giant VEP; hearing loss; hypercupremia; hypomyelination; infantile spasm