Ataxia Telangiectasia Presenting as Cervical Dystonia

LNU, Priyal; Sehgal, Vineet; Kapila, Saniya; Gulati, Nihal; Sehgal, Lucky Bhalla

doi:10.7759/cureus.30723

Cited by 3 publications

(3 citation statements)

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“…After reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia, we found that dystonia-dominant A-T cases may have a significantly different clinical picture compared to the typical A-T. In total, 13 pedigrees including 30 patients with ATM mutations were reviewed ( 7 , 10 – 18 ) ( Table 1 ). The median age of onset was 10.67 years, ranging from 1 to 20 years old.…”

Section: Discussionmentioning

confidence: 99%

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review

Liu

Wang²,

Xu³

2023

Front. Pediatr.

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BackgroundAtaxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, including classic A-T and milder form of AT. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T such as ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifesting isolated generalized or segmental dystonia without any signs of classical A-T.MethodsAn A-T pedigree with predominant dystonia was collected. Genetic testing was performed by targeted panel of genes involved in movement disorders. The candidate variants were further confirmed by Sanger sequencing. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T.ResultsTwo novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. The proband presented isolated segmental dystonia without any signs of ataxia and telangiectasias. We reviewed the literatures and found that the patients with dystonia-dominant A-T tend to have a later-onset and slower progression of the disease.ConclusionTo our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. Early ATM genetic testing should be considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

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Section: Discussionmentioning

confidence: 99%

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review

Liu

Wang²,

Xu³

2023

Front. Pediatr.

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“… Abbreviations: ANO3 —anoctamin 3 [ 31 ]; ATM —ataxia-telangiectasia mutated [ 32 ]; ATP7B —ATPase copper transporting beta [ 33 ]; C19orf12 —chromosome 19 open reading frame 12 [ 34 ]; CACNA1A —calcium channel, voltage-dependent, P/Q type, alpha-1A subunit [ 35 ]; CACNA1B —calcium channel, voltage-dependent, N type, alpha-1B subunit [ 36 ]; CIZ1 —CIP1-interacting zinc finger protein [ 37 ]; COL6A3 —collagen, type VI, alpha-3 [ 38 ]; CP —ceruloplasmin [ 39 ]; DRD5 —dopamine receptor D5 [ 40 ]; FTL —ferritin light chain [ 41 ]; FUS —fused in sarcoma [ 15 ]; GCH1 —GTP cyclohydrolase 1 [ 42 ]; GNAL —guanine nucleotide-binding protein alpha-activating activity polypeptide, olfactory type [ 20 ]; KMT2B —lysine-specific methyltransferase 2B [ 43 ]; LRRK2 —leucine-rich repeat kinase 2 [ 15 ]; PANK2 —pantothenate kinase 2 [ 44 ]; PRKRA —protein kinase, interferon-inducible double-stranded RNA-dependent activator [ 17 ]; RAB12 —RAS-associated protein RAB12 [ 45 ]; REEP4 —receptor expression-enhancing protein 4 [ 16 ]; SGCE —sarcoglycan, epsilon [ 46 ]; SPR —sepiapterin reductase [ 47 ]; SYNE1 —spectrin repeat-containing nuclear envelope protein 1 [ 15 ]; TH —tyrosine hydroxylase [ 48 ]; THAP1 —THAP domain-containing protein 1 [ 49 ]; TOR1A —torsin 1A [ 50 ]; TUBB4A —tubulin, beta-4A [ 51 ]; VPS16 —VPS16 core subunit of corvet and HOPS complexes [ 52 ]; VPS41 —VPS41 subunit of HOPS complex [ 21 ]; WDR45 —WD repeat-containing protein 45 [ 53 ]. …”

Section: Figurementioning

confidence: 99%

Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants

Salamon

Nagy

Pál

et al. 2023

IJMS

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Dystonia is a rare movement disorder which is characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements, postures, or both. The two most common forms of adult-onset focal dystonia are cervical dystonia (CD) and benign essential blepharospasm (BSP). A total of 121 patients (CD, 74; BSP, 47) were included in the study. The average age of the patients was 64 years. For the next-generation sequencing (NGS) approach, 30 genes were selected on the basis of a thorough search of the scientific literature. Assessment of 30 CD- and BSP-associated genes from 121 patients revealed a total of 209 different heterozygous variants in 24 genes. Established clinical and genetic validity was determined for nine heterozygous variations (three likely pathogenic and six variants of uncertain significance). Detailed genetic examination is an important part of the work-up for focal dystonia forms. To our knowledge, our investigation is the first such study to be carried out in the Middle-European region.

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“…J Neurol Neurosurg Psychiatry Res 2023; 5 (1): 109. doi: 10.31531/edwiser.jnnpr.1000109 movement disorders such as dystonia, choreoathetosis, myoclonus, and tremors. General physical appearance is characterized by the presence of short stature, café au lait spots, progeric skin and hair changes, oculocutaneous telangiectasia, horizontal head thrusts due to difficulty in initiating horizontal saccades (both voluntary and reflex saccades are affected), ocular apraxia, diabetes mellitus, and features of glucose intolerance like acanthosis nigricans, hypogonadism, lymphocytopenias, predisposition to malignancy, hypoimmunoglobulinemia, and other immune defects [2].…”

Section: Introductionmentioning

confidence: 99%

A Rare and Unusual Case of Ataxia Telangiectasia with Cervical Dystonia from India

Chamraj

2023

J Neurol Neurosurg Psychiatry Res

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We reported a rare and unusual case ATM gene variant responsible of familial Ataxia-Telangiectasia (A-T) with cervical dystonia rather than ataxia as hall mark clinical manifestations in 18-year-old male patient from India. Patient was presented with clinical indications of neck rotatory movements in the last 2 years. Initially intermittent, slowly become constant with more backwards turning and painful movements with severe disability. Examination findings revealed no conjunctival telangiectasia and neurological examination findings suggestive of cervical dystonia with severe retro collis. The patient has a family history of dystonia, his sister started noticing involuntary neck movement in the last 1.5 years with gradual progression. Her physical examination revealed no evidence of conjunctival lesions and neurological examination suggestive of cervical dystonia with lateral collis. MRI findings of patient were normal. Both the patient and her sister are siblings of a consanguineous product. Patient has been referred for whole exome sequencing. The exome data analysis identified a novel homozygous missense variant c.5751A>T, p.Arg1917Ser (chr11:108307973A>T) in ATM gene responsible for familial A-T with cervical dystonia without chorea as hall mark clinical manifestations. In conclusion, to the best of our literature knowledge this is the rare and unusual case from India wherein we are reporting a novel homozygous missense variant c.5751A>T, p.Arg1917Ser (chr11:108307973A>T) in ATM gene responsible for familial A-T with cervical dystonia rather than ataxia as hall mark clinical manifestations affecting both brother and sister in the same family. Thus, early onset of cervical dystonia should be taken into account as a key characteristic of variant A-T, which can manifest without general ataxia and may cause adults with primary dystonia to receive an incorrect diagnosis.

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Ataxia Telangiectasia Presenting as Cervical Dystonia

Cited by 3 publications

References 16 publications

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review

Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants

A Rare and Unusual Case of Ataxia Telangiectasia with Cervical Dystonia from India

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