biostudies-literatureHelman GNIDA NIH HHSNINDS NIH HHSNational Health and Medical Research CouncilNational Institutes of HealthAustralian Research Council11-19https://www.ebi.ac.uk/biostudies/studies/S-EPMC8327280biostudies-literatureUnknown121<h4>Background</h4>A recurrent homozygous missense variant, c.160G>C;p.(Val54Leu) in HIKESHI, was found to cause a hypomyelinating leukodystrophy with high frequency in the Ashkenazi Jewish population. We provide extended phenotypic classification of this disorder based on clinical history of a further seven affected individuals, assess carrier frequency in the Ashkenazi Jewish population, and provide a neuropathological study.<h4>Methods</h4>Clinical information, neuroimaging, and biosamples were collected. Brain autopsy was performed for one case.<h4>Results</h4>Individuals with HIKESHI-related disease share common clinical features: early axial hypotonia evolving to dystonia or with progressive spasticity, hyperreflexia and clonus, feeding difficulties with poor growth, and nystagmus. SPediatric neurologyFurther Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy.PMC832728075N95019C00048U54 NS1150521068278Hacker JLEkstein JStutterd CAVanderver AAlmad AHarding BHirsch YZerem AJohansson MMHelman GPizzino AViaene ANSchmidt JLGrinspan JBWoidill SLeFevre ANTaft RJFattal-Valevski ASase SSimons CfalseFurther Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy.<h4>Background</h4>A recurrent homozygous missense variant, c.160G>C;p.(Val54Leu) in HIKESHI, was found to cause a hypomyelinating leukodystrophy with high frequency in the Ashkenazi Jewish population. We provide extended phenotypic classification of this disorder based on clinical history of a further seven affected individuals, assess carrier frequency in the Ashkenazi Jewish population, and provide a neuropathological study.<h4>Methods</h4>Clinical information, neuroimaging, and biosamples were collected. Brain autopsy was performed for one case.<h4>Results</h4>Individuals with HIKESHI-related disease share common clinical features: early axial hypotonia evolving to dystonia or with progressive spasticity, hyperreflexia and clonus, feeding difficulties with poor growth, and nystagmus. S2021-01-01T00:00:00Z2021 Aug2026-05-08T02:01:21.132Z2025-02-19T01:31:26.467ZS-EPMC83272803411161910.1016/j.pediatrneurol.2021.04.014