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Clin Genet. 2016 Nov;90(5):437-444. doi: 10.1111/cge.12813. Epub 2016 Jul 4.

Characterization of SPATA5-related encephalopathy in early childhood.

Author information

1
Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan. kurata0708@gmail.com.
2
Division of Neurology, National Center for Child Health and Development, Tokyo, Japan. terashima-h@ncchd.go.jp.
3
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
4
Division of Child Neurology, Department of Brain, and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
5
Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
6
Division of Functional Genomics, Research Center for Bioscience, and Technology, Tottori University, Yonago, Japan.
7
Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
8
Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.

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.

KEYWORDS:

SPATA5; giant VEP; hearing loss; hypercupremia; hypomyelination; infantile spasm

PMID:
27246907
DOI:
10.1111/cge.12813
[Indexed for MEDLINE]

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