Two New Families and a Literature Review of ELOVL4-Associated Spinocerebellar Ataxia Type 34.

Autor: Nishide M; Sydney Medical School, University of Sydney, Camperdown, NSW, 2050, Australia., Le Marquand K; Clinical Genetics Service, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia., Davis MR; Department of Diagnostic Genomics, Path West Laboratory Medicine, QEII Medical Centre, Hospital Avenue, Nedlands, WA, Australia., Halmágyi GM; Neurology Department, Royal Prince Alfred Hospital, Camperdown and the University of Sydney, Sydney, NSW, 2050, Australia., Fellner A; Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.; Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, 4941492, Petah Tikva, Israel.; Department of Neurology, Rabin Medical Center, Beilinson Hospital, 4941492, Petah Tikva, Israel., Narayanan RK; Sydney Medical School, University of Sydney, Camperdown, NSW, 2050, Australia.; Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, NSW, 2139, Australia., Kennerson ML; Sydney Medical School, University of Sydney, Camperdown, NSW, 2050, Australia.; Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, NSW, 2139, Australia.; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia., Reddel SW; Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia., Worgan L; Clinical Genetics Service, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia., Panegyres PK; Neurodegenerative Disorders Research Pty Ltd, West Perth, WA, 6005, Australia.; School of Medicine, The University of Western Australia, Nedlands, WA, 6008, Australia., Kumar KR; Sydney Medical School, University of Sydney, Camperdown, NSW, 2050, Australia. kkum4618@uni.sydney.edu.au.; Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia. kkum4618@uni.sydney.edu.au.; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia. kkum4618@uni.sydney.edu.au.; Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, 2139, Australia. kkum4618@uni.sydney.edu.au.
Jazyk: angličtina
Zdroj: Cerebellum (London, England) [Cerebellum] 2024 Feb; Vol. 23 (1), pp. 268-277. Date of Electronic Publication: 2023 Jan 25.
DOI: 10.1007/s12311-023-01522-8
Abstrakt: Autosomal dominant variants in ELOVL4 cause spinocerebellar ataxia type 34 (SCA34; ATX-ELOVL4), classically associated with a skin condition known as erythrokeratoderma. Here, we report a large Italian-Maltese-Australian family with spinocerebellar ataxia. Notably, while there were dermatological manifestations (eczema), erythrokeratoderma was not present. Using a next-generation sequencing panel, we identified a previously reported ELOVL4 variant, NM_022726.4: c.698C > T p.(Thr233Met). The variant was initially classified as a variant of uncertain significance; however, through segregation studies, we reclassified the variant as likely pathogenic. We next identified an individual from another family (Algerian-Maltese-Australian) with the same ELOVL4 variant with spinocerebellar ataxia but without dermatological manifestations. We subsequently performed the first dedicated literature review of ELOVL4-associated ataxia to gain further insights into genotype-phenotype relationships. We identified a total of 60 reported cases of SCA34 to date. The majority had gait ataxia (88.3%), limb ataxia (76.7%), dysarthria (63.3%), and nystagmus (58.3%). Of note, skin lesions related to erythrokeratoderma were seen in a minority of cases (33.3%). Other extracerebellar manifestations included pyramidal tract signs, autonomic disturbances, retinitis pigmentosa, and cognitive impairment. For brain MRI data, cerebellar atrophy was seen in all cases (100%), whereas the hot cross bun sign (typically associated with multiple system atrophy type C) was seen in 32.4% of cases. Our family study and literature review highlight the variable phenotypic spectrum of SCA34. Importantly, it shows that erythrokeratoderma is not found in most cases and that, while a dermatological assessment may be helpful in these patients, SCA34 diagnosis should be considered irrespective of dermatological manifestations.
(© 2023. The Author(s).)
Databáze: MEDLINE
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