Abstract
Background
ITPR1 gene encodes inositol 1,4,5-trisphosphate-receptor-type 1, a Ca2+ channel highly
expressed in cerebellar Purkinje cells. ITPR1 gene variants, through a loss-of-function mechanism, have been found to be related
with the manifestation of spinocerebellar ataxia (SCA) 15, an adult-onset slow progressive
cerebellar ataxia, SCA 29, a rare non-progressive congenital cerebellar ataxia and
Gillepsie syndrome (SCA 29 phenotype plus aniridia). They share an heterogeneity of
additional phenotypic features while no genotype-phenotype correlation has ever been
found.
Case report
Here we report the case of a boy with cerebellar ataxia who came to our clinic due
to his cervical dystonia in the form of retrocollis. He presented an early-onset,
non-progressive cerebellar ataxia, with cognitive impairment and delayed motor milestones.
Whole exome sequencing (WES) revealed an heterozygous nucleotide variation, c.829A > C
(p.Ser277Arg) in ITPR1 gene (NM_001168272.1), a de novo ITPR1 variant, as his parents came up with negative genetic testing. Due to his clinical
presentation and genetic result, we came up with the diagnosis of SCA 29.
Conclusion
We described cervical dystonia as a phenotypic feature of ITPR1 related SCA 29, found in a new de novo ITPR1-variant.
Keywords
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References
- Spinocerebellar ataxia: an update.J Neurol. 2019; 266: 533-544
- Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias.Neurochem Int. 2016; 94: 1-8
- Spinocerebellar ataxia type 15.Handb Clin Neurol. 2012; 103: 561-565
- A new autosomal dominant pure cerebellar ataxia.Neurology. 2001; 57: 1913-1915
- Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans.PLoS Genet. 2007; 3: e108
- Spinocerebellar ataxia 15: A phenotypic review and expansion.Neurol Neurochir Pol. 2017; 51: 86-91
- Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this emerging congenital ataxia.Orphanet J Rare Dis. 2017; 12: 121
- Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus.Neurology. 2004; 63: 2288-2292
- Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia.Orphanet J Rare Dis. 2012; 7: 67
- De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function.Eur J Hum Genet. 2018; 26: 1623-1634
- Treatment of cervical dystonia with botulinum toxin.Mov Disord. 2004; 19: S109-S115
- Current concepts on the clinical features, aetiology and management of idiopathic cervical dystonia.Brain. 1998; 121: 547-560
- The basal ganglia and cerebellum interact in the expression of dystonic movement.Brain. 2008; 131: 2499-2509
- Cervical dystonia: a neural integrator disorder.Brain. 2016; 139: 2590-2599
- A novel gain-of-function mutation in the ITPR1 suppressor domain causes spinocerebellar ataxia with altered Ca(2+) signal patterns.J Neurol. 2017; 264: 1444-1453
- Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene.J Neurol. 2015; 262: 1278-1284
- The autosomal recessive cerebellar ataxias.N Engl J Med. 2012; 366: 636-646
- Dystonia.Dystonia Nat Rev Dis Primers. 2018; 4: 25
- Phenomenology and classification of dystonia: a consensus update.Mov Disord. 2013; 28: 863-873
- ITPR1 autoimmunity: Frequency, neurologic phenotype, and cancer association.Neurol Neuroimmunol Neuroinflamm. 2018; 5: e418
Article info
Publication history
Published online: February 08, 2022
Accepted:
January 17,
2022
Received in revised form:
January 15,
2022
Received:
October 21,
2021
Identification
Copyright
© 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. All rights reserved.