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Título

SPINOCEREBELLAR ATAXIA TYPE 29 IN A 7- YEAR-OLD GIRL CAUSED BY MUTATIONS IN ITPR1 GENE: CASE REPORT OF A RARE CONGENITAL ATAXIA

Apresentação do caso único

Patient R.V.R.S, female, with a history of delayed neuropsychomotor development: started crawling at 3 years old, walking only at 5 years old and first words at 3 years old. Mother with a history of ataxia and apraxia since infancy, with no defined diagnosis. Regarding perinatal history, the patient was born with a gestational age of 42 weeks, cesarean section, uneventful. The physical examination at admission revealed dysarthria, difficulty recognizing letters of the alphabet and dysgraphia. Convergent strabismus of the left eye was noted, with slow saccadic movements also to the left. Cerebellar tests with predominantly right dysmetria, presence of dysdiadochokinesia. Ataxic gait, with a tendency to fall bilaterally. Magnetic Resonance Imaging showed cerebellar vermis of slightly reduced dimensions with discreet accentuation of the foliae; discreet volumetric reduction of the bridge; EEG and screening tests for inborn errors of metabolism without changes. Throughout follow-up, found possible associated intellectual disability. At the age of 7, an Ataxia and Epilepsy panel was carried out through next generation sequencing (NGS) and a pathogenic variant (chr3:4.645621 T>A) was found to be heterozygous in the ITPR1 gene that causes Ataxia Spinocerebellar Type 29 (SCA29) of autosomal dominant inheritance.

Discussão

SCA29 is an autosomal dominant, very slowly progressive or nonprogressive cerebellar ataxia caused by mutations in ITPR1. Is characterized by infantile-onset hypotonia, gross motor delay and cognitive impairment. Affected individuals exhibit cerebellar dysfunction and often have cerebellar atrophy on neuroimaging. Mutation of the ITPR1 gene is associated with three distinct ataxic phenotypes, a progressive adult-onset form characterized primarily by gait and limb ataxia, termed Spinocerebellar Ataxia Type 15 (SCA15), an early onset form that presents as a hypotonic baby with fixed dilated pupils with progressive cerebellar hypoplasia and ataxia (Gillespie Syndrome), and a congenital non-progressive form associated with intellectual disability (SCA29) as in the case of the patient report. Most cases are describe as de novo ITPR1 missense mutation, but there are reports of disorders family and a carrier parentes with mild ataxia.

Comentários finais

This case is a rare case in the literature, given the majority of autosomal dominant spinocerebellar ataxias usually begin in adult life and a mutation is often de novo, in the case reported, maternal inheritance is suggested.

Referências

- Huang L, et al. Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar
ataxia. Orphanet J Rare Dis. 2012 Sep 17;7:67. PMID: 22986007
- Zambonin JL, et al. Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this
emerging congenital ataxia. Orphanet J Rare Dis. 2017 Jun 28;12(1):121. PMID: 28659154
- Synofzik M, et al. Spinocerebellar ataxia type 15: diagnostic assessment, frequency, and phenotypic features. J Med
Genet. 2011;48(6):407-12. PMID: 21367767.
- McEntagart M, et al. A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence
for Dominant-Negative Effect. Am J Hum Genet. 2016 ;98(5):981-992. PMID: 27108798
- van Dijk T, et al. A de novo missense mutation in the inositol 1,4,5-triphosphate receptor type 1 gene causing severe
pontine and cerebellar hypoplasia: Expanding the phenotype of ITPR1-related spinocerebellar ataxias. Am J MedGenet A. 2017;173(1):207-212. PMID: 27862915

Palavras Chave

Cerebellar Ataxia; Spinocerebellar Ataxia; SCA29