Hereditary and Non-hereditary Cerebellar Ataxias in Latvia: Six Years of Experience at the National Reference Centre (ERN-RND Affiliated Partner)

Abstract

Cerebellar ataxias are rare but disabling disorders, with marked regional differences in genetic subtypes. Data from Eastern Europe, especially the Baltic region, remain scarce. To describe the aetiological spectrum and diagnostic challenges of cerebellar ataxia in Latvia over a six-year period. A retrospective descriptive single centre study was conducted at the national reference centre for rare neurological disorders in Latvia. Patients diagnosed with cerebellar ataxia between 2019 and 2025 were reviewed. Clinical data, laboratory, imaging, and genetic testing were analysed. Of 116 patients, 37 underwent local repeat-expansion analysis (ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, CACNA1A/SCA6); 14 underwent NGS-based broad panels; and 9 were referred for RFC1 repeat-expansion analysis at an external European reference laboratory. Of 116 patients, 70 (60.3%) received a confirmed aetiological diagnosis. Non-hereditary ataxias were the largest subgroup (65.7% of confirmed), with immune-mediated ataxias (21.4%) and sporadic neurodegenerative MSA-C (20.0%) among the most frequent diagnoses. The genetic diagnostic yield was 20.7% (24/116). Among hereditary cases, autosomal dominant ataxias predominated with SCA2 as the most frequent subtype - contrasting with the SCA3 predominance reported in most European cohorts. Autosomal recessive ataxias accounted for 8.6%, with RFC1-related CANVAS identified in 5.7% of confirmed cases; notably, all four RFC1-CANVAS patients presented with focal cervical dystonia (p = 0.020). No cases of Friedreich’s ataxia were confirmed, partly reflecting the absence of routine GAA repeat-expansion testing. The remaining 46 patients were classified as cerebellar ataxia of undetermined aetiology, largely due to limited access to comprehensive genetic testing. This is the first systematic study of cerebellar ataxia in Latvia. Regional variation in genetic subtypes, frequent RFC1-related dystonia, and limited access to comprehensive genetic testing highlight the need for expanded diagnostic capacity. These findings have implications for diagnosis, counselling, and emerging targeted therapies.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1007/s12311-026-02084-1.

Introduction

Ataxia is a neurological syndrome defined by impaired coordination, balance, and gait. Clinically, it is categorised into vestibular ataxia, caused by dysfunction of the vestibular system; sensory ataxia, resulting from impaired proprioceptive pathways; and cerebellar ataxia, arising from intrinsic cerebellar pathology [1].

The onset of cerebellar ataxia varies according to aetiology. Acute presentations are most often related to stroke, trauma, or infection; subacute forms are typically associated with immune-mediated or paraneoplastic mechanisms; and chronic ataxias are predominantly of genetic origin. Despite diagnostic advances, cerebellar ataxias remain rare yet highly disabling disorders, leading to progressive loss of independence, reduced quality of life, and a considerable socioeconomic burden [1, 2].

Although curative options remain unavailable for the majority of cerebellar ataxias, molecular genetic testing has become a cornerstone of clinical evaluation, especially in chronic and progressive cases [3]. Importantly, certain hereditary forms are now amenable to targeted therapy, exemplified by the recent approval of omaveloxolone for Friedreich’s ataxia [4]. The identification of pathogenic variants improves diagnostic accuracy, refines prognostic assessment, and facilitates genetic counselling. Furthermore, elucidating the molecular aetiology contributes to a broader understanding of disease mechanisms and their clinical implications [2, 5].

Despite recent advances, no systematic analyses of cerebellar ataxias have been conducted in Latvia, and data from Eastern Europe remain scarce [6]. The Baltic countries are particularly underrepresented in epidemiological studies, and diagnostic pathways remain challenging due to limited access to genetic testing and expertise. These gaps underscore the need for systematic research. To address this, we conducted the first retrospective study in Latvia to delineate the aetiological spectrum and clinical features of cerebellar ataxias.

Methods

We conducted a retrospective descriptive single-centre study at Pauls Stradiņš Clinical University Hospital. All patients diagnosed with cerebellar ataxia during the period 2019–2025 were identified through medical record review using the ICD-10 codes R27 (ataxia, unspecified), G33.8 (other specified degenerative diseases of the nervous system), and G11 (hereditary ataxias).

Patients were included if they had neurologist-documented cerebellar involvement, defined by the presence of at least two of the following clinical signs, based on neurological examination: gait or truncal ataxia, limb dysmetria or intention tremor, cerebellar dysarthria, or cerebellar oculomotor signs (e.g., gaze-evoked nystagmus, saccadic intrusions, or impaired vestibulo-ocular reflex [VOR]).

Cases were excluded if the clinical picture was consistent with pure vestibular or sensory ataxia without evidence of cerebellar signs. As this was a retrospective study, all data were obtained from existing medical records. Documented nerve conduction studies (NCS) were available in 64 of the 116 included patients (55.2%); in the remaining patients, the presence or absence of a sensory component was determined on clinical grounds based on the documented neurological examination, including assessment of proprioception, vibration sense, and Romberg testing. Patients with sensory polyneuropathy who also exhibited cerebellar ataxia were included, as a sensory component may form part of the clinical phenotype. Patients with pure sensory ataxia, without cerebellar involvement, were excluded; in routine clinical practice such cases are most often coded under a polyneuropathy diagnosis rather than ataxia. Vestibular ataxia was excluded by the presence of cerebellar signs and/or a negative head impulse test in cases presenting with vertigo or imbalance. Cases with functional gait disorders, insufficient documentation, or duplicate records were also excluded.

For each case, demographic, epidemiological, and clinical information was collected from medical records. Diagnostic confirmation was based on clinical evaluation, radiological findings, and, where available, molecular genetic testing. Patients were subsequently classified according to aetiology, laboratory and genetic testing results.

Diagnosis of MSA-C was established according to the 2022 MDS consensus criteria, with cases classified as clinically established or clinically probable MSA-C.

In Latvia, first-line molecular testing was performed at an accredited national laboratory (GenEra) and consisted of targeted sizing of CAG trinucleotide repeats in four genes: ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3) and CACNA1A (SCA6) using PCR followed by capillary electrophoresis–based fragment analysis. Alleles were interpreted against established locus-specific thresholds, with normal alleles defined as < 36 CAG repeats for ATXN1 (in the presence of a CAT interruption), < 31 for ATXN2, < 40 for ATXN3, < 18 for CACNA1A. This assay detects only CAG-type expansions at these four loci and does not identify point mutations, copy-number variants, or non-CAG repeat expansions; consequently, repeat disorders such as SCA8 (ATXN8OS/ATXN8 CTG·CAG), SCA10, SCA12, SCA17, SCA36, FGF14/SCA27B, and the intronic FXN GAA expansion of Friedreich’s ataxia are not covered by local testing. Patients requiring broader investigation were referred to medical genetics for further testing. In addition to the standardised repeat-expansion panel (SCA1, SCA2, SCA3, SCA6) and external NGS/RFC1 testing, a subset of patients underwent targeted single-locus testing outside this algorithm when clinically indicated (e.g., a specific suspected diagnosis based on phenotype or family history). This included Sanger sequencing/repeat-primed PCR analysis of the ATXN8OS/ATXN8 CTG·CAG locus, which was not part of the routine panel and is not detectable by the NGS panel or short-read WES/WGS methods used elsewhere in the cohort. Genetic testing was performed either at an external European reference laboratory or in the in-house genetic laboratory at Children’s Clinical university hospital (CCUH), depending on the clinical indication and test availability.

For patients tested externally, a next-generation sequencing (NGS) panel for ataxia-related genes and RFC1 repeat-expansion analysis for CANVAS were performed.

For in-house testing, whole-exome sequencing (WES) was performed using the Twist Comprehensive Exome panel with mtDNA enrichment reagents. Library preparation and sequencing were performed externally at CeGaT GmbH using NovaSeq 100PE sequencing, while bioinformatic analysis was carried out locally at CCUH. WES data were processed in a secure DNAnexus environment. Reads were aligned to the GRCh38 reference genome using BWA-MEM. Single nucleotide variants and small insertions/deletions within coding regions and ± 150 bp from exon–intron boundaries were called using DeepVariant. Mitochondrial DNA variants were analysed using Strelka2. Additional analyses included short tandem repeat detection using ExpansionHunter and REViewer, regions of homozygosity detection using BCFtools roh and Karyoploter, variant annotation using VEP, and copy number variant detection using ExomeDepth.

Variant analysis and interpretation were performed using phenotype-driven virtual gene panels selected according to the patient’s clinical presentation. For in-house analyses, the applied panels included ataxia, hereditary spastic paraplegia, movement disorder, muscle disease and neuromuscular disease gene panels, as appropriate. Variants were interpreted in Congenica CE-IVD and classified according to ACMG/AMP guidelines. Variant interpretation was performed using a phenotype-driven virtual gene panel selected according to the patient’s clinical presentation. For the in-house analysis, the CCUH movement disorders superpanel was applied. The panel name, version/date, number of genes, overall sequencing coverage at different depth thresholds, and complete gene list are provided in Supplementary Table S3. Individual gene-level coverage is available upon request.

Of the 70 patients with suspected genetic ataxia, 37 underwent the GenEra repeat-expansion panel covering four genes, 14 were referred to external laboratories for next-generation sequencing (NGS) of ataxia-associated genes, and 9 were tested for RFC1-related CANVAS.

Data analysis was mainly descriptive. Continuous variables are presented as medians with interquartile ranges (IQR), and categorical variables as absolute counts and percentages. Group comparisons of continuous variables were conducted using the Mann–Whitney U test, while categorical variables were compared with Fisher’s exact test. For 2 × 2 comparisons, exact conditional 95% confidence intervals for the odds ratio were derived from the noncentral hypergeometric distribution; where a cell count was zero, the odds ratio was reported as not estimable, with a one-sided (open) confidence bound. A two-tailed p-value < 0.05 was considered statistically significant.

Ethics

This study was approved by the Ethics Committee of Riga Stradiņš University (approval number: 2-PĒK-4/703/2025). All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.

Results

A total of 116 patients meeting the inclusion and exclusion criteria were identified during the study period, of whom 65 (56.0%) were women. The cohort comprised 112 unrelated probands and two mother-daughter pairs, one with SCA2 and one with a variant of uncertain significance in the SCN8A gene, ascertained independently through the clinic and included as separate patients; the potential marginal inflation of SCA2 and SCN8A frequencies is acknowledged. Among all, 70 patients (60.3%) received a confirmed diagnosis based on clinical evaluation supported by laboratory, radiological, or genetic testing (local and/or external laboratory tests). The remaining 46 patients (39.7%) were classified as idiopathic cerebellar ataxia without a more specific confirmed diagnosis, due to insufficient diagnostic work-up or negative genetic results, often reflecting the limited scope of the routine local SCA panel and the absence of systematic repeat-expansion analysis (Fig. 1).

Fig. 1.

Study design: Identification and categorisation of cerebellar ataxia patients

Within the confirmed cohort, non-hereditary ataxias constituted the largest subgroup (n = 46; 65.7%), followed by autosomal dominant cerebellar ataxias (ADCAs) (n = 17; 24.3%), autosomal recessive cerebellar ataxias (ARCAs) (n = 6; 8.6%), and mitochondrial ataxia (n = 1; 1.4%). Two additional cases carried a variant of uncertain significance (VUS) in the SCN8A gene. Median age at onset was significantly earlier in genetically confirmed cases compared with non-hereditary ataxias (32 years, IQR 22–41 vs. 54 years, IQR 47–61; p < 0.05). The genetic diagnostic yield using the entire cohort (n = 116) as denominator was 20.7% (24/116 confirmed hereditary cases). The aetiological distribution is summarised in Table 1.

Table 1.

Aetiological spectrum of diagnosed cerebellar ataxia cases (n = 70)

Aetiological group	Diagnosis	N	% of total (n = 70)
Non-hereditary ataxias (n = 46, 65.7%)	Immune-mediated cerebellar ataxia*	15	21.4%
	Multiple system atrophy - C (MSA)	14	20.0%
	Alcohol-related toxic cerebellar degeneration	8	11.4%
	Stroke	5	7.1%
	Chiari malformation type I	1	1.4%
	Dandy-Walker syndrome	1	1.4%
	Ataxia-myoclonus-epilepsy syndrome	1	1.4%
	Cerebellar astrocytoma	1	1.4%
Autosomal dominant ataxias (n = 17, 24.3%)	SCA2	9	12.9%
	SCA8	2	2.9%
	SCA6	2	2.9%
	SCA1	1	1.4%
	SCA4	1	1.4%
	SCA14	1	1.4%
	SCA28	1	1.4%
Autosomal recessive ataxias (n = 6, 8.6%)	RFC1-related CANVAS	4	5.7%
	Ataxia-telangiectasia	1	1.4%
	PNPLA6 ataxia-hypogonadism syndrome	1	1.4%
Mitochondrial ataxia (n = 1, 1.4%)	Leigh syndrome	1	1.4%

*Immune-mediated cerebellar ataxia included paraneoplastic antibody–associated ataxias (anti-Yo, anti-Hu, anti-Ri, anti-Tr), anti-NMDA, anti-GAD65–associated ataxia, and gluten-related ataxia, as well as seronegative encephalitis fulfilling clinical criteria

The two SCN8A variants of uncertain significance are additional, non-confirmed cases and are not included among the 70 confirmed diagnoses. Multiple system atrophy (MSA-C) is a sporadic neurodegenerative disorder grouped here, together with the acquired causes, under non-hereditary ataxias. The aetiology of the ataxia-myoclonus-epilepsy case may be genetic.

Among non-hereditary cases, immune-mediated cerebellar ataxias and multiple system atrophy (MSA-C) were most frequent. MSA-C was diagnosed in accordance with the 2022 MDS consensus criteria, with cases classified as either clinically established (n = 10) or clinically probable (n = 4).

Alcohol-related cerebellar degeneration and stroke were also observed, alongside single cases of Chiari malformation, Dandy–Walker malformation, ataxia–myoclonus–epilepsy syndrome, and cerebellar astrocytoma. Within the immune-mediated subgroup, seronegative encephalitis predominated, while isolated cases were associated with anti-Yo, anti-NMDA receptor, anti-GAD65, and gluten-related antibodies. Four additional patients were classified as post-infectious/self-limited cerebellitis based on acute onset and a non-progressive course.

SCA2 was the most common ADCA (n = 9), including one confirmed mother-daughter pair; SCA6 and SCA8 were confirmed in two cases each; and SCA1, SCA4, SCA14, and SCA28 were each identified in single cases. ARCAs were primarily represented by RFC1-related CANVAS (n = 4), with single cases of ataxia-telangiectasia and PNPLA6-related ataxia-hypogonadism syndrome. The largest genetically confirmed subgroups were therefore SCA2 and CANVAS. Clinical features of SCA2 and CANVAS patients are detailed in Supplementary Tables S1 and S2.

In addition to the classic triad of cerebellar ataxia, sensory polyneuropathy, and vestibulo-ocular reflex impairment, all four patients with RFC1-related CANVAS also presented with focal cervical dystonia, suggesting an expansion of the recognised clinical spectrum of RFC1-related disease. Cervical dystonia was present in all four RFC1-related CANVAS cases (4/4), compared with 30.0% (6/20) of other genetically confirmed ataxias - generalized dystonia in SCA1, ataxia-telangiectasia, and Leigh syndrome; focal cervical dystonia in SCA2; focal voice dystonia in SCA6; and focal hand dystonia in SCA8. The difference was statistically significant (Fisher’s exact p = 0.020; the odds ratio was not estimable owing to a zero cell, and the exact conditional 95% confidence interval for the odds ratio was 1.1–∞). This is a preliminary observation requiring replication in larger cohorts.

Among the 46 undiagnosed patients, the majority (n = 37) were clinically suspected to have a hereditary disorder, including nine with features suggestive of CANVAS but without genetic confirmation. In this cohort, 25 patients underwent targeted local hereditary ataxia testing ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), and CACNA1A (SCA6), none of whom showed a pathogenic variant. An additional six patients underwent NGS-based or other broad panels that did not include repeat-expansion detection.

Discussion

The largest aetiological group comprised non-hereditary ataxias (65.7%), among which immune-mediated ataxia was the most prevalent (21.4%), including paraneoplastic, anti-GAD65, anti-NMDA receptor, and gluten-related forms, with seronegative cases predominating. Notably, as the seronegative patients did not undergo genetic testing, the authors cannot exclude the possibility that a hereditary aetiology may underlie some of these cases.

In most European populations, SCA3 is recognised as the most frequent autosomal dominant cerebellar ataxia, particularly due to well-established founder effects in Portugal, Spain, and several Central European regions [6, 7]. In contrast, our cohort demonstrated a clear predominance of SCA2, accounting for more than half of genetically confirmed ADCA cases. This pattern closely mirrors findings from Italy, where SCA2 has also been reported as the leading subtype [8]. The convergence of Latvian and Italian data underlines the heterogeneity of ADCA distribution across Europe. Such variation emphasises the importance of country-specific epidemiological studies, as extrapolation from broader European data may not accurately reflect local genetic landscapes.

Despite being the most common autosomal recessive cerebellar ataxia worldwide, with an estimated prevalence of 1–2 per 100,000 individuals in Europe, no cases of FRDA were identified in our Latvian cohort; however, systematic GAA repeat-expansion testing was not part of the routine diagnostic panel, and the apparent absence may reflect diagnostic gaps in addition to genuine low prevalence [9]. This observation is consistent with reports from Finland, where national series have similarly failed to document genetically confirmed FRDA cases [10, 11]. The apparent absence across the Baltic and Nordic region contrasts with data from Central and Southern Europe, where FRDA represents a substantial proportion of recessive ataxias. Several explanations are possible: a true low prevalence in the Northern European gene pool due to founder effects and population history, or underdiagnosis related to the limited availability of molecular testing. In Estonia and Lithuania, published data are scarce, but clinical experience also suggests FRDA is rarely encountered. Whether the absence of FRDA in Latvia reflects genuine epidemiological variation or simply diagnostic gaps remains unresolved, underscoring the importance of broader genetic testing availability and cross-border epidemiological studies in the Baltic region. Given that FRDA remains the most common autosomal recessive ataxia in Europe and that heterozygous carriers are relatively frequent, the routine inclusion of FXN GAA repeat-expansion testing in the national diagnostic pathway is of particular importance and should be prioritised in future protocols.

Since the discovery of biallelic intronic repeat expansions in RFC1 in 2019, this disorder has been recognised as one of the most frequent causes of late-onset ataxia, explaining up to one-fifth of cases previously considered idiopathic in Western European cohorts [12]. In our Latvian series, four cases were genetically confirmed, and an additional nine were clinically suspected, indicating that RFC1-related disease is also a major contributor to late-onset ataxia in the Baltic region. Comparable data from Baltic countries remain scarce. Importantly, all four genetically confirmed cases in our cohort presented with focal cervical dystonia in addition to the classic triad of cerebellar ataxia, sensory polyneuropathy, and vestibulo-ocular reflex impairment. This consistent association has not been highlighted in prior European cohorts, where dystonia is described only sporadically [13]. Our finding, therefore, expands the recognised clinical spectrum of RFC1-related disease and suggests that dystonia may represent an underappreciated, yet clinically relevant feature in affected patients.

In addition to established ataxia subtypes, our cohort revealed two related patients carrying an SCN8A variant of uncertain significance (c.5597G > A, p.Arg1866Gln). Pathogenic variants in SCN8A are best known for their association with epilepsy-related syndromes, yet recent reports have broadened the phenotypic spectrum to include cerebellar ataxia [14, 15]. While the pathogenicity of the variant identified in our patients remains unresolved, its presence in first-degree relatives with progressive cerebellar symptoms raises the possibility of a causal link, warranting further investigation.

Beyond SCN8A, newly recognised repeat-expansion disorders are reshaping the landscape of late-onset ataxia. In particular, expansions in FGF14 (SCA27B) have recently been identified as one of the most frequent causes of adult-onset ataxia in European cohorts [16–20]. These findings highlight the need to integrate testing for novel repeat-expansion loci into standard diagnostic pipelines. Given that such expansions are typically undetectable by conventional exome or genome sequencing, their recognition is relevant for regions like Latvia, where diagnostic access is still restricted and many cases remain unsolved.

To contextualise our findings within Europe, we summarised published data on the prevalence and predominant subtypes of hereditary cerebellar ataxias across different countries (Table 2).

Table 2.

Comparative epidemiology of hereditary cerebellar ataxias in Europe

Country/Region	Prevalence of ADCA (per 100,000)	Predominant ADCA subtype(s)	FRDA prevalence	Notes	Reference
Portugal	4–5	SCA3 (Machado–Joseph disease)	1–2	Strong founder effect	Ruano 2014
Spain	2–4	SCA3, SCA2 (regional variation)	1–2	Higher SCA2 in N. Spain	Ruano 2014
Italy	3–5	SCA2	1–2	Regional founder effect	de Mattei 2024; Brusco 2004
France	2–3	SCA3, SCA7	1–2	SCA7 more frequent than elsewhere	Ruano 2014
Germany	2–3	SCA3, SCA6	1–2	Higher frequency of SCA6	Ruano 2014
UK	1–2	SCA6, SCA7, RFC1 (late-onset)	1–2	RFC1-related CANVAS significant	Yau 2025
Finland	< 1	Rare isolated families	Not reported	No FRDA cases documented	Pajakkala 2000
Latvia (this study)	cohort only	SCA2, RFC1-CANVAS	None detected	First systematic analysis	Current study

As shown in Table 2, our data resemble Italy, where SCA2 is also the most frequent ADCA, but differ from Portugal and Spain, where SCA3 predominates due to founder effects. In contrast, Germany and France show a broader distribution with relatively higher frequencies of SCA6 and SCA7, respectively. The absence of FRDA in Latvia, which may in part be attributable to insufficient testing, mirrors findings from Finland, whereas Central and Southern Europe consistently report prevalence rates of 1–2 per 100,000. Finally, the recognition of RFC1-related CANVAS in the UK and Italy parallels our findings, reinforcing its importance across European cohorts.

Several diagnostic barriers emerged from our study. In Latvia, access to genetic testing remains limited, with neurologists currently able to request only SCA1, SCA2, SCA3, and SCA6 analyses. Broader testing, including FRDA, RFC1 and FGF14 expansions, falls under the responsibility of medical geneticists, which may delay comprehensive genetic evaluation. Importantly, these obstacles are not unique to Latvia. Similar challenges are reported internationally: even in centres with advanced sequencing capacity, the diagnostic yield for hereditary ataxias remains only 30–40% [21]. A substantial proportion of late-onset or apparently sporadic cases remain unresolved, largely due to repeat-expansion disorders such as RFC1-CANVAS and FGF14-SCA27B that are invisible to routine exome/genome analysis [16]. Furthermore, differences in national healthcare systems and referral pathways contribute to variable access to testing across Europe and North America. Collectively, these factors highlight the need for a more standardized and comprehensive diagnostic approach, integrating phenotype-driven selection, targeted repeat-expansion assays, and emerging long-read sequencing technologies.

Our findings underscore the importance of timely genetic confirmation in patients with cerebellar ataxia. Beyond its role in refining prognosis and enabling accurate genetic counselling, molecular diagnosis increasingly determines access to targeted therapies. The recent approval of omaveloxolone for Friedreich’s ataxia illustrates how patients without a confirmed genetic diagnosis may be excluded from disease-modifying treatments and clinical trial opportunities [4]. As additional therapies are developed for specific ataxia subtypes, delayed or incomplete genetic testing risks widening the gap between patients in regions with advanced diagnostic infrastructure and those where access remains restricted. For countries such as Latvia, improving diagnostic pathways is therefore not only a scientific necessity but also an urgent clinical priority to ensure equitable access to emerging therapies.

Limitations

This study has several limitations. First, its retrospective, single-centre design may have introduced referral bias, as our clinic serves as a national reference centre and may receive a disproportionate number of complex or late-onset cases. Second, not all patients with clinically suspected hereditary ataxia underwent genetic testing, primarily due to the limited availability of assays beyond SCA1, SCA2, SCA3, and SCA6 in Latvia. Several important loci — including FRDA, SCA7, SCA 8, SCA10, SCA12, SCA17, SCA36, and FGF14/SCA27B — were not systematically tested, and the true prevalence of these subtypes is likely underestimated. Furthermore, genetic testing strategies were not fully standardised across the cohort: while most patients were evaluated using the routine repeat-expansion panel or external NGS/RFC1 testing, a small number of cases (including the two SCA8 diagnoses) resulted from targeted single-locus testing requested on clinical grounds, which may introduce ascertainment bias not fully captured by the panel-based diagnostic yield reported here. Third, the mostly descriptive nature of our analysis did not allow for systematic phenotypic characterisation or longitudinal follow-up, which could have provided more detailed genotype–phenotype correlations. Finally, our findings are based on a relatively small national cohort, and while they provide the first systematic data from Latvia, larger multicentre studies across the Baltic and Nordic region will be required to confirm whether the observed distribution patterns reflect true epidemiology or local diagnostic practices.

Conclusions

Our study provides the first systematic analysis of cerebellar ataxias in Latvia and highlights notable regional differences in the genetic profile. SCA2 and RFC1-related CANVAS are identified as the main subtypes, while no cases of Friedreich’s ataxia were confirmed; systematic FRDA testing was not routinely available and absence may partly reflect diagnostic gaps. The consistent association between cervical dystonia and RFC1 expansions broadens the recognised phenotype and has direct therapeutic implications. These findings underline the importance of comprehensive and accessible genetic testing, including assays for recently identified repeat-expansion disorders, to improve diagnostic accuracy and facilitate timely access to counselling and emerging targeted therapies in the Baltic region and beyond.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Krista Lazdovska: Conceptualization, Data curation, Formal analysis, Writing – original draft. Alise Baborikina: Data curation. Vladimirs Krutovs: Data curation. Marija Rozevska: Data validation, Investigation (genetic data). Viktorija Ķēniņa: Conceptualization, Supervision.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.