Ataxia with oculomotor apraxia type 2: an evolving axonal neuropathy

A 23-year-old woman had presented initially to a podiatrist complaining of poorly fitting shoes during her adolescence. After extensive neurological review, she was diagnosed with ataxia with oculomotor apraxia type 2. This is a progressive autosomal recessive ataxia associated with cerebellar atrophy, peripheral neuropathy and an elevated serum α-fetoprotein. Within Europe, it is the most frequent autosomal recessive ataxia after Friedreich’s ataxia and is due to mutations in the senataxin (SETX) gene. The age of onset is approximately 15 years.The diagnosis of oculomotor apraxia type 2 is often challenging. We provide a framework for assessing a young ataxic patient with or without oculomotor apraxia and review clues that will aid diagnosis. The prognosis, level of disability, cancer and immunosuppression risk all markedly differ between the conditions. Patients and their families need the correct diagnosis for genetic counselling, management and long-term surveillance with appropriate subspecialty services.

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Ataxia with Oculomotor Apraxia Type 2: Novel Mutations in Six Patients with Juvenile Age of Onset and Elevated Serum α-Fetoprotein

Neuropediatrics ◽

10.1055/s-0029-1214424 ◽

2008 ◽

Vol 39 (06) ◽

pp. 347-350 ◽

Cited By ~ 10

Author(s):

V. Bernard ◽

S. Stricker ◽

F. Kreuz ◽

M. Minnerop ◽

G. Gillessen-Kaesbach ◽

...

Keyword(s):

Age Of Onset ◽

Elevated Serum ◽

Novel Mutations ◽

Juvenile Age ◽

Oculomotor Apraxia ◽

Ataxia With Oculomotor Apraxia

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Heterozygous deletion in exon 6 of STEX gene causing ataxia with oculomotor apraxia type 2 (AOA-2) with ovarian failure

BMJ Case Reports ◽

10.1136/bcr-2021-241767 ◽

2021 ◽

Vol 14 (6) ◽

pp. e241767

Author(s):

Jiwan Shriram Kinkar ◽

Patel Zeeshan Jameel ◽

Banshi Lal Kumawat ◽

Priyanka Kalbhor

Keyword(s):

Premature Ovarian Failure ◽

Neurodegenerative Disorder ◽

Elevated Serum ◽

Cerebellar Atrophy ◽

Ovarian Failure ◽

Heterozygous Deletion ◽

Pathogenic Variants ◽

Oculomotor Apraxia ◽

Ataxia With Oculomotor Apraxia

Ataxia with oculomotor apraxia type 2 (AOA2), recently renamed as ATX-SETX, is an autosomal recessive, progressive neurodegenerative disorder belonging to inherited cerebellar ataxias. The pathogenic variants of the SETX gene have been implicated in ATX-SETX. We report the case of a 21-year-old woman presenting with ataxia, oculomotor apraxia and dystonia. She had elevated serum α-fetoprotein (AFP), follicle stimulating hormone (FSH) and luteinising hormone (LH) levels and moderate cerebellar atrophy. On further evaluation, she was found to have premature ovarian failure as well. Multiplex ligation-dependent probe amplification detected a heterozygous deletion in exon 6 of the SETX gene. A combination of cerebellar ataxia, oculomotor apraxia with elevated AFP and cerebellar atrophy are highly suggestive of ATX-SETX. In rare instances, it may be associated with premature ovarian failure with elevated FSH and LH levels, necessitating hormonal survey and fertility evaluation in all patients with ATX-SETX.

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Biallelic Mutation of SETX and Additional Likely “In Cis” SETX Sequence Change in Ataxia with Oculomotor Apraxia Type 2

Journal of Pediatric Genetics ◽

10.1055/s-0040-1713909 ◽

2020 ◽

Author(s):

Michael D. Perry ◽

Martin J. Evans ◽

Philip J. Byrd ◽

Malcolm R. Taylor

Keyword(s):

Autosomal Recessive ◽

Genetic Basis ◽

Autosomal Recessive Disease ◽

Biallelic Mutation ◽

Rna Repair ◽

Oculomotor Apraxia ◽

Repair Protein ◽

Ataxia With Oculomotor Apraxia ◽

In Cis

AbstractAtaxia with oculomotor apraxia type 2 (AOA2) is a slowly progressive, autosomal recessive disease characterized by the triad of ataxia, oculomotor apraxia, and sensorimotor neuropathy. The genetic basis of AOA2 is biallelic mutation of the SETX gene, resulting in reduced or absent senataxin, a DNA/RNA repair protein essential for genomic stability.In this report, we describe a case of AOA2 with two clear pathogenic SETX mutations, one of which is novel. We then discuss two further likely in cis SETX sequence changes, previously reported in the literature as pathogenic, and present the case that they are likely benign polymorphisms.

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CANVAS is a common form of late-onset hereditary ataxia

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.04.51-52 ◽

2020 ◽

pp. 51-52

Author(s):

Е.П. Нужный ◽

Н.Ю. Абрамычева ◽

Е.Г. Воробьева ◽

Е.О. Иванова ◽

Ю.А. Шпилюкова ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Clinical Picture ◽

Autosomal Recessive ◽

Late Onset ◽

Repeat Expansion ◽

Hereditary Ataxia ◽

Recessive Ataxia ◽

Autosomal Recessive Ataxia

Синдром CANVAS (мозжечковая атаксия, невропатия и вестибулярная арефлексия) - аутосомно-рецессивная атаксия с поздним дебютом, обусловленная носительством биаллельной экспансии (AAGGG)n во 2-м интроне гена RFC1. До настоящего момента отсутствуют сведения о распространенности данного заболевания в российских семьях. Нами был проведен поиск биаллельной экспансии AAGGG-повторов у 35 российских пациентов с поздней мозжечковой атаксией. Верифицированы 5 пациентов (14,3%) с синдромом CANVAS и характерной клинической картиной. CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia) is a late-onset autosomal recessive ataxia due to biallelic (AAGGG)n repeat expansion in the 2nd intron of the RFC1 gene. There is no information on the CANVAS prevalence in Russian families. We searched for biallelic expansion of AAGGG repeats in 35 Russian patients with late-onset cerebellar ataxia. Five patients (14.3%) with CANVAS syndrome and a characteristic clinical picture were verified.

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