Spinocerebellar ataxia type 14: refining clinicogenetic diagnosis in a rare adult-onset disorder.
Ann Clin Transl Neurol
; 8(4): 774-789, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33739604
ABSTRACT
OBJECTIVES:
Genetic variant classification is a challenge in rare adult-onset disorders as in SCA-PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA-PRKCG a comprehensive phenotype description from a German multi-center cohort, including standardized 3D MR imaging.METHODS:
This cross-sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS).RESULTS:
Our sample included 25 cases confirmed as SCA-PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA-PRKCG included slowly progressive ataxia (onset at 4-50 years), preceded in some by early-onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive-affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA-PRKCG cases but in none of the controls.INTERPRETATION:
In this largest cohort to date, SCA-PRKCG was characterized as a slowly progressive cerebellar syndrome with some clinical and imaging features suggestive of a developmental disorder. The observed non-ataxia movement disorders and cognitive-affective disturbance may well be attributed to cerebellar pathology. Protein modeling emerged as a valuable diagnostic tool for variant classification and the newly described T2 hyperintense dentate sign could serve as a supportive diagnostic marker of SCA-PRKCG.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
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Ataxias Espinocerebelosas
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Ann Clin Transl Neurol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania