An intronic GAA repeat expansion in the FGF14 gene was recently identified as a common cause of autosomal dominant GAA-FGF14 ataxia (SCA27B). We aimed to characterize in detail the clinical and video-oculographic features in our cohort of SCA27B patients. We genotyped the FGF14 GAA repeat expansion in 52 patients with unsolved late-onset cerebellar ataxia. Brain MRI and nerve conduction study, as well as video-oculographic (VOG) assessment, were performed. Eight patients (15.4%) with pathogenic GAA repeat expansion in the FGF14 gene were found. The median age at onset was 51 years (range—23–63 years). Sensory axonal neuropathy was found in 5/8 patients. Cerebellar atrophy was observed in 5/8 patients, and in one case, pontocerebellar atrophy was found. All tested patients had impaired smooth pursuit, 5/6 patients had impaired vestibulo-ocular reflex suppression, nystagmus, and an increased number of square wave jerks, 4/6 patients had horizontal gaze-evoked nystagmus, 3/6 had spontaneous downbeat nystagmus, and 1/6 had an upbeat one. Video head impulse test gain was lower than 0.8 on both sides in 2/4 patients, along with the presence of overt saccades. Further studies in different cohorts are needed to complete the phenotype of the FGF14-related disorders.

Spinocerebellar ataxia type 27B (SCA27B) is a newly identifi ed hereditary ataxia discovered in 2023, characterized by pathological GAA repeat expansions in the FGF14 gene. Current research indicates it as one of the most prevalent forms of adult-onset ataxia, particularly among previously undiagnosed cases. We describe a 64-year-old female patient with SCA27B exhibiting: recurrent dysarthria, downbeat nystagmus and unremarkable neuroimaging fi ndings. This case illustrates a comprehensive diagnostic approach for progressive cerebellar ataxia of unclear etiology (videooculography, Halmagyi video head impulse test, cerebellar MRspectroscopy and genetic testing). We discussed diffi culties of diff erential diagnosis of SCA27B with acquired (including gluten) ataxia.

Introduction. Young-onset amyotrophic lateral sclerosis (yALS) is a rare neurodegenerative disease characterized by the onset of clinical manifestations before the age of 45. The global prevalence, incidence, and genetic structure of yALS remain largely unknown, and the diagnosis is based primarily on clinical presentation, neurophysiologic findings, and molecular genetic analysis. Aim. The aim of this study was to analyze cases of yALS in the Russian Center of Neurology and Neurosciences. Materials and methods. A total of 365 ALS cases were analyzed, of which 47 (12.8%) patients met the criteria for yALS based on the age of onset and were included in this study. All patients underwent the necessary diagnostic procedures to exclude or establish a diagnosis. The coding sequence of the SOD1 gene was analyzed, and the size of the tandem hexanucleotide repeats (GGGGCC)n in the C9orf72 gene was evaluated. In some cases, massive parallel sequencing was performed. Results. Mutations in causative ALS genes were detected in 15 (32%) patients: in 15% of cases, variants were found in the coding sequence of the SOD1 gene and 3’ untranslated region, and in 8.7%, hexanucleotide repeat expansions (GGGGCC)n were found in the C9orf72 gene. In addition, in four (8.5%) yALS cases, mutations in the FUS, UBQLN2, and FIG4 genes were identified using massive parallel sequencing. Conclusion. Early identification of both sporadic and familial forms of yALS and determination of their molecular genetic patterns is critical for timely genetic counseling and identification of potentially treatable etiologies.

Objective. To analyze clinical and genetic characteristics of patients with the verified rare forms of autosomal recessive spinocerebellar ataxias, ATX-ANO10 and ATX-SYNE1. Material and methods. Six unrelated patients with established diagnoses were examined: 4 patients with ATX-ANO10 and 2 patients with ATX-SYNE1. Brain MRI and nerve conduction study were performed. To screen for cognitive impairment, the scale for the Assessment and Rating of Ataxia (SARA), and the Montreal Cognitive Assessment Scale (MoCA) were used. Mutation screening included panel sequencing on the Illumina MiSeq platform. Results. Six variants were found in the ANO10 gene: the previously described pathogenic nonsense mutations c.G1025A (p.W342X) and c.C1244G (p.S415X), as well as novel probably pathogenic variants c.1477-2A>G and c.G101T (p.W34L) and missense mutations c.A110C (p.N37T) and c.T104C (p.L35P) of undetermined significance. A novel nonsense mutation c.C8911T (p.Q2971X) and a previously described pathogenic variant c.C4939T (p.Q1647X) were found in the SYNE1 gene. The clinical presentation of the ATX-ANO10 and ATX-SYNE1 was typical presenting with slowly progressive cerebellar ataxia with pyramidal signs, with young onset and cerebellar atrophy according to brain MRI study. Conclusion. We provided first-ever data on clinical features and mutation spectrum In Russian patients with ATX-ANO10 and ATX-SYNE1. The phenotype of these ataxias is nonspecific, so the method of choice for molecular diagnostics is massive parallel sequencing.

In 2019, it was established that biallelic expansion of pentanucleotide AAGGG repeats in intron 2 of the RFC1 gene is the cause of CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome). In addition to the classic triad of symptoms (cerebellar ataxia, sensory neuropathy, vestibular areflexia), the condition may be accompanied by extrapyramidal and autonomic disturbances, which complicates the differential diagnosis with atypical forms of parkinsonism. This article presents the clinical case of a 69-year-old patient with biallelic RFC1 expansion, whose clinical presentation was dominated by asymmetric parkinsonism, sensory-cerebellar ataxia and autonomic dysfunction. Instrumental studies revealed sensory axonal polyneuropathy, bilateral vestibulopathy and oculomotor disturbances characteristic of cerebellar involvement. Multiple system atrophy and corticobasal degeneration were considered in the differential diagnosis. The combination of sensory neuropathy, cerebellar ataxia and vestibular areflexia formed the basis for molecular genetic testing, which confirmed a biallelic RFC1 expansion. This case highlights the multisystem nature of RFC1-associated disorders and demonstrates that parkinsonism and early autonomic dysfunction may form part of the clinical spectrum of this condition. The findings also raise the possibility of RFC1-associated disease co-occurring with neurodegenerative processes from the group of α-synucleinopathies.