<scp>ELOVL4</scp> with erythrokeratoderma: A pediatric case and emerging genodermatosis

Croitoru, David; Lu, Justin D.; Lara‐Corrales, Irene; Kannu, Peter; Pope, Elena

doi:10.1002/ajmg.a.62136

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…Importantly, EK-related skin lesions were only seen in a minority of cases (33.3%), which is in contrary to the reported prototypic manifestation of SCA34/ATX- ELOVL4 (OMIM #133190). Whilst the majority of cases with EK skin lesions had EKV [ 3 ], several cases had lesions more consistent with progressive symmetric erythrokeratoderma (PSEK) rather than EKV [ 10 , 12 ]. Of note, one study reported a 16-year-old boy with PSEK skin lesions with no neurological or cerebellar clinical signs who was found to have the c.698C > T ELOVL4 variant [ 12 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…Whilst the majority of cases with EK skin lesions had EKV [ 3 ], several cases had lesions more consistent with progressive symmetric erythrokeratoderma (PSEK) rather than EKV [ 10 , 12 ]. Of note, one study reported a 16-year-old boy with PSEK skin lesions with no neurological or cerebellar clinical signs who was found to have the c.698C > T ELOVL4 variant [ 12 ]. This case highlights the potential clinical phenotypic variability for ELOVL4 -associated disease, though it is plausible that this individual develops ataxia later in his life.…”

Section: Literature Reviewmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Literature Reviewmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

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

et al. 2023

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“…Importantly, EK-related skin lesions were only seen in a minority of cases (33.9%), which is in contrary to the reported prototypic manifestation of SCA34/ATX-ELOVL4 (OMIM #133190). Whilst the majority of cases with EK skin lesions had EKV (3), several cases had lesions more consistent with progressive symmetric erythrokeratoderma (PSEK) rather than EKV (9,10). Of note, one study reported a 16-year-old boy with PSEK skin lesions with no neurological or cerebellar clinical signs who was found to have c.698C > T ELOVL4 variant (10).…”

Section: Literature Reviewmentioning

confidence: 99%

“…Whilst the majority of cases with EK skin lesions had EKV (3), several cases had lesions more consistent with progressive symmetric erythrokeratoderma (PSEK) rather than EKV (9,10). Of note, one study reported a 16-year-old boy with PSEK skin lesions with no neurological or cerebellar clinical signs who was found to have c.698C > T ELOVL4 variant (10). This case highlights the potential clinical phenotypic variability for ELOVL4-associated disease, though it is plausible that this individual develops ataxia later in his life.…”

Section: Literature Reviewmentioning

confidence: 99%

A family study and literature review of ELOVL4-associated spinocerebellar ataxia type 34

Nishide

Marquand

Davis

et al. 2022

Preprint

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Autosomal dominant disease-causing variants in the ELOVL4 gene (Elongation of Very Long Chain Fatty Acids-like 4) cause spinocerebellar ataxia type 34 (SCA34; ATX-ELOVL4), classically associated with a skin condition known as erythrokeratoderma. Here, we report a large Italian-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 subsequently performed the first dedicated literature review of ELOVL4 variants causing ataxia to gain further insights into genotype-phenotype relationships. We identified a total 59 reported cases of SCA34 to date. The majority had gait ataxia (88.1%), limb ataxia (76.3%), dysarthria (62.7%), and nystagmus (57.6%). Of note, skin lesions related to erythrokeratoderma were seen in a minority of cases (33.9%). 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 30.3% 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.

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