Annals of Indian Academy of Neurology
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Year : 2021  |  Volume : 24  |  Issue : 4  |  Page : 630-632

Abnormal saccades differentiate adolescent onset variant ataxia telangiectasia from other myoclonus dystonia

Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Kerala, India

Date of Submission17-Jun-2020
Date of Acceptance21-Sep-2020
Date of Web Publication10-Apr-2021

Correspondence Address:
Dr. K P Divya
Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Kerala – 695011
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_619_20

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How to cite this article:
Cherian A, Chandarana M, Susvirkar AA, Divya K P, Saraf UU, Krishnan S. Abnormal saccades differentiate adolescent onset variant ataxia telangiectasia from other myoclonus dystonia. Ann Indian Acad Neurol 2021;24:630-2

How to cite this URL:
Cherian A, Chandarana M, Susvirkar AA, Divya K P, Saraf UU, Krishnan S. Abnormal saccades differentiate adolescent onset variant ataxia telangiectasia from other myoclonus dystonia. Ann Indian Acad Neurol [serial online] 2021 [cited 2021 Oct 25];24:630-2. Available from:


Ataxia telangiectasia (A-T) is an autosomal recessive disorder caused by inactivating mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes the ATM kinase protein.[1] A-T patients usually present before 2 years of age with ataxia, extrapyramidal (EP) movement disorders, oculomotor apraxia (OMA), and peripheral neuropathy leading to wheelchair dependency before end of first decade of life.[2] This classic A-T presentation is characterized by telangiectasias, immunodeficiency, radiosensitivity, and increased serum α-fetoprotein (AFP) levels along with a predisposition to cancer.[2] Besides this prototype, a milder phenotype with later age of onset, slower progression and prolonged survival exists called variant A-T[3] which is associated with mutations that leave some residual ATM kinase activity, whereas it is fully absent in the classic subtype.[4] Variant A-T may rarely present as myoclonus dystonia (M-D).

   Case Report Top

A 30-year-old gentleman presented with involuntary neck movements since 12 years of age and involuntary movements of both upper limbs since 18 years of age. His neck movements were intermittent, nonrhythmic, and horizontal with rotational jerks to left, which were aggravated with stress and anxiety and reduced with sensory tricks. He had intermittent, brief, jerky, shock-like movements of neck and both hands (right > left) with abnormal posture during writing and holding, affecting his ability to do fine work. These movements were exacerbated by somatosensory and auditory stimuli. There were no diurnal fluctuations or paroxysms. Family history was negative.

On examination, there was no oculocutaneous telangiectasia. He had cervical dystonia in the form of left rotacollis with right laterocollis and neck myoclonus [Video 1]. Upper extremities showed asymmetric dystonic posturing of both hands along with myoclonic jerks. He had slow vertical saccade and hypometric horizontal saccades without OMA. Gait ataxia and cerebellar signs were conspicuously absent. His routine blood investigations (hemogram, biochemistry) were normal. KF ring was absent; serum ceruloplasmin and 24-h urinary copper were normal. Ultrasonogram of abdomen–pelvis and magnetic resonance imaging (MRI) of brain were normal. Genetic studies for DYT 1,11 and SCA 1, 2, 3 were negative. Clinical whole-exome sequencing showed a homozygous missense mutation (c. 9156G > C; p.Trp3052Cys) in exon 63 of ATM gene on chromosome 11q22. His serum AFP levels were high at 317.2 ng/ml (normal <10 ng/ml). The same variant was detected by next-generation sequencing in heterozygous condition in the father of the index patient, which was confirmed by Sanger sequencing.

   Discussion Top

Our case shows that as compared to classic A-T, variant A-T presents predominantly as an EP syndrome (isolated dystonia or M-D with or without choreoathetosis and tremor). Ataxia, telangiectasia, OMA and immunodeficiency can be absent in up to half the variant A-T cases [Table 1]. MRI brain can be normal in 60% of patients while serum AFP elevation is usually mild to moderate. Lesser degrees of supranuclear eye movement abnormalities (slow or hypometric saccades) with modest elevation in serum AFP, as seen in our case, will help to differentiate it from similar presentation of other genetic diseases, namely, dystonia due to epsilon sarcoglycan mutation (DYT-11). Saccadic abnormalities may be seen in M-D due to ADCY5 mutation; however, nocturnal aggravation of movement disorder, facial dyskinesia, axial hypotonia, episodic painful dystonic posturing aggravated by stress or illness, and delayed developmental milestones help in differentiating it from variant A-T [Table 2].[5]
Table 1: Showing key differences between classic and variant A-T

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Table 2: Genes with myoclonus dystonia phenotype and differentiating features

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A unique dominant M-D like syndrome with cardiac arrhythmias, was initially linked to a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels.[6] However, this was refuted by a large European multicentric cohort study.[7] In a study on DYT11-negative patients with M-D phenotype, rare missense variants in RELN were identified. RELN mutations segregate in an autosomal dominant fashion and the product reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures. RELN mutation-positive patients have a higher age at onset and a milder course of disease compared to epsilon sarcoglycan M-D patients though psychiatric abnormalities and response to alcohol were common among both.[8]

Similar M-D like presentation of A-T, with onset in second decade similar to ours, was first reported from India in 2002, however it was not genetically proven.[9] In the largest series of A-T from India consisting of 100 patients, presentation with dystonic crisis was seen in one and 29 subjects had choreoathetosis as initial feature. Neither myoclonus nor M-D phenotype was observed in their cohort.[10]

Our case of genetically proven variant A-T highlights the fact that mild degrees of supranuclear eye movement abnormalities with modest elevation in serum α-fetoprotein will help to differentiate M-D like phenotype from similar presentation of other genetic diseases. Variant A-T needs follow-up due to an increased risk for malignancy compared to others with similar M-D phenotype.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995;268:1749-53.  Back to cited text no. 1
van Os NJH, Hensiek A, van Gaalen J, Taylor AMR, van Deuren M, Weemaes CMR, et al. Trajectories of motor abnormalities in milder phenotypes of ataxia telangiectasia. Neurology 2019;92:e19-29.  Back to cited text no. 2
Verhagen MMM, Abdo WF, Willemsen MAAP, Hogervorst FBL, Smeets DFCM, Hiel JAP, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 2009;73:430-7.  Back to cited text no. 3
Saunders-Pullman RJ, Gatti R. Ataxia-telangiectasia: Without ataxia or telangiectasia? Neurology 2009;73:414-5.  Back to cited text no. 4
Chang FC, Westenberger A, Dale RC, Smith M, Pall HS, Perez-Dueñas B, et al. Phenotypic insights into ADCY5-associated disease. Mov Disord 2016;31:1033-40.  Back to cited text no. 5
Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, et al. CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. Hum Mol Genet 2015;24:987-93.  Back to cited text no. 6
Mencacci NE, R'bibo L, Bandres-Ciga S, Carecchio M, Zorzi G, Nardocci N, et al. The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort. Hum Mol Genet 2015;24:5326-9.  Back to cited text no. 7
Groen JL, Ritz K, Jalalzadeh H, van der Salm SMA, Jongejan A, Mook OR, et al. RELN rare variants in myoclonus-dystonia. Mov Disord 2015;30:415-9.  Back to cited text no. 8
Goyal V, Behari M. Dystonia as presenting manifestation of ataxia telangiectasia: A case report. Neurol India 2002;50:187-9.  Back to cited text no. 9
[PUBMED]  [Full text]  
Mahadevappa M, Kamble N, Santhosh Kumar DV, Yadav R, Netravathi M, Pal PK. A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center. Ann Mov Disord 2020;3:33-8.  Back to cited text no. 10
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  [Table 1], [Table 2]


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