Infantile Onset of Spinocerebellar Ataxia Type 5 (SCA-5) in a 6 Month Old with Ataxic Cerebral Palsy

Rea, Gillian; Tirupathi, Sandya; Williams, Jonathan; Clouston, Penny; Morrison, Patrick J.

doi:10.1007/s12311-019-01085-7

Cited by 9 publications

(16 citation statements)

References 6 publications

(9 reference statements)

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“…These new cases extend the β-III spectrin-associated phenotypes, and establish that heterozygous SPTBN2 mutations can lead to NPCA with evidence of neurodegeneration on neuroimaging. Our hypothesis is supported by a comprehensive review of 11 cases that show a compatible SCAR14-like phenotype [ 4 , 11 , 12 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionsupporting

confidence: 60%

“…A descriptive analysis of the known NPCA patients carrying heterozygous de novo SPTBN2 mutations (including the two cases here described) is summarized in Table S1 [ 4 , 11 , 12 , 15 , 16 , 17 , 18 , 19 ]. All patients, including seven girls and six boys, presented with hypotonia and/or developmental delay before 12 months of age.…”

Section: Resultsmentioning

confidence: 99%

“…In this report, we describe two unrelated probands manifesting an NPCA phenotype, characterized by novel de novo SPTBN2 mutations. Together with the 11 cases identified in our literature search, all 13 individuals represent a homogenous clinical syndrome consisting of infantile-onset hypotonia and/or developmental delay [ 4 , 11 , 12 , 15 , 16 , 17 , 18 , 19 ]. All patients developed a pure cerebellar syndrome with ataxic gait, dysmetria, slurred speech, abnormal ocular movements, and cognitive deficits [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…We also performed a systematic review of patients diagnosed with NPCA as defined in [ 26 ], and heterozygous de novo SPTBN2 mutations by searching MEDLINE through PubMed (accessed on 13 October 2020), using the following keywords: #1 SPTBN2 , #2 non-progressive congenital ataxia, #3 congenital cerebellar ataxia, or #4 infantile-onset cerebellar ataxia. We selected eight articles that provided detailed clinical, neuroimaging, and genetic findings of 11 patients with NPCA and de novo SPTBN2 mutations ( Table S1 ), with the first case being reported in 2013 [ 4 , 11 , 12 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…As is usually the case with Mendelian disorders, AR inheritance is associated with more severe disease than AD inheritance. SCA5 is characterized by a slowly progressive pure cerebellar ataxia, and marked global cerebellar atrophy on magnetic resonance imaging (MRI) in adulthood, although early onset has also been reported [ 9 , 10 , 11 , 12 ]. Most patients may show ataxic gait, disabling action and postural tremor, pyramidal signs, dorsal column involvement, and gaze palsy.…”

Section: Introductionmentioning

confidence: 99%

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Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Sancho

Andrés-Bordería

Gorría-Redondo

et al. 2021

IJMS

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(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by b-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.

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Section: Introductionsupporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Sancho

Andrés-Bordería

Gorría-Redondo

et al. 2021

IJMS

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Novel SPTBN2 gene mutation and first intragenic deletion in early onset spinocerebellar ataxia type 5

Romaniello

Citterio

Panzeri

et al. 2021

Ann Clin Transl Neurol

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In the present study, we describe two novel cases of SCA5 with early onset. The first one, carrying a novel heterozygous de novo missense mutation in SPTBN2 gene, showed a striking very severe cerebellar atrophy and reduction of volume of the pons at a very young age (16 months). The latter, carrying the first de novo intragenic deletion so far reported in SPTBN2 gene, showed a mild cerebellar atrophy involving the hemispheres and a later onset. In both cases, for the first time, a hyperintense signal of the dentate nuclei was observed.

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Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5

et al. 2021

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Introduction Spinocerebellar ataxias (SCAs) are a heterozygous group of neurodegenerative disorders. Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal-dominant ataxia with pure cerebellum involvement. The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abnormal eye movement, dysarthria, and hyperactive tendon reflexes. Spectrin beta nonerythrocytic 2 gene (SPTBN2), coding β-III spectrin protein, was identified to be associated with SCA5. To date, more than 19 variants of SPTBN2 have been reported. Methods A family and an apparently sporadic patient with ataxia and cerebellar atrophy were recruited from Shandong Province (China). To discover the disease-causing variants, capillary electrophoresis and targeted next-generation sequencing were performed in the proband of the family and the sporadic patient. The candidate variants were verified by Sanger sequencing and analyzed by bioinformatics software. Results In our study, we verified two novel heterozygous variants in SPTBN2 in a SCA pedigree and a sporadic patient. The proband of the pedigree and her mother presented with walking instability and progressively getting worse. The sporadic patient suffered from slurred speech, walking instability, and drinking water choking cough. MRI examination of the proband and sporadic patient both displayed moderate cerebellar atrophy. The variants identified were traditionally conserved and predicted probably damaging and disease-causing by bioinformatics analysis. Conclusion We identified two novel heterozygous variants of SPTBN2 resulting in severe ataxia which further delineated the correlation between the genotype and phenotype of SCA5, and pathogenesis of variants in SPTBN2 should be further researched.

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Infantile Onset of Spinocerebellar Ataxia Type 5 (SCA-5) in a 6 Month Old with Ataxic Cerebral Palsy

Cited by 9 publications

References 6 publications

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Novel SPTBN2 gene mutation and first intragenic deletion in early onset spinocerebellar ataxia type 5

Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5

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