Variant ataxia-telangiectasia in a child presenting with laryngeal dystonia

Arıcan, Pınar; Dündar, Nihal Olgaç; Kırbıyık, Özgür; Çavuşoğlu, Dilek; Yılmaz, Sema Bozkaya; Gençpınar, Pınar

doi:10.24953/turkjped.2020.03.019

Cited by 3 publications

(4 citation statements)

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“…Of the 18246 cases, family history of A-T was reported in 1274 cases ( Table 2 ) and 142 cases (53 studies) had 199 illnesses or symptoms other than A-T in a relative ( Fig 3A ). 1279 cases (109 studies [ 15 , 53 , 65 , 71 , 72 , 78 , 87 , 88 , 95 , 99 – 101 , 109 , 110 , 115 , 118 – 221 ]) were the children of consanguineous relationships, and 186 cases (86 studies [ 23 , 33 , 41 , 50 , 54 , 62 , 63 , 65 , 71 , 74 , 84 , 88 , 95 , 111 , 116 , 142 , 146 , 151 – 153 , 188 , 208 – 210 , 212 , 214 , 216 , 218 , 219 , 221 – 277 ]) were reported as being born of non-consanguineous relationships.…”

Section: Resultsmentioning

confidence: 99%

“… Absence of family history of A-T was documented in at least 60 cases (54 studies [ 21 , 50 , 65 , 80 , 86 , 95 , 98 , 111 , 122 , 134 , 135 , 150 , 155 , 181 , 188 , 190 , 197 , 202 , 203 , 222 , 224 , 236 , 238 , 239 , 242 , 252 , 254 , 255 , 267 , 272 – 274 , 276 , 366 , 379 – 398 ]). …”

Section: Resultsmentioning

confidence: 99%

“…1219 cases (177 studies [ 18 , 28 , 31 , 33 , 36 , 38 , 41 , 42 , 47 – 49 , 52 , 57 , 59 , 62 , 63 , 65 , 66 , 72 , 73 , 75 , 76 , 80 , 84 , 87 , 95 , 99 , 100 , 103 , 106 , 108 , 109 , 111 , 116 , 118 – 120 , 122 , 123 , 126 , 129 , 131 , 138 – 141 , 143 , 147 , 159 , 165 , 166 , 174 – 176 , 179 , 181 , 190 , 191 , 202 , 206 ,…”

Section: Resultsunclassified

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The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

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Background Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition. Objectives Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature. Search methods 107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 –present, Web of Science core collection, Elsevier Scopus, and Cochrane Library. Selection criteria All human studies that report any aspect of A-T. Data collection and analysis Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest. Main results 1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months). Conclusions This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsunclassified

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The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

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“…On history and physical examination, dopa-responsive dystonia, primary torsion dystonia, and myoclonic dystonia were ruled out [9][10]. Concerning this case report, we got written permission from the patient's parents to share his information and image.…”

Section: Case Presentationmentioning

confidence: 99%

Ataxia Telangiectasia Presenting as Cervical Dystonia

LNU¹,

Sehgal²,

Kapila³

et al. 2022

Cureus

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The ataxia telangiectasia mutant (ATM) protein is a sensor and signal transducer that amplifies and communicates signals of DNA damage further to the mediators of cell cycle arrest, apoptosis, and senescence (p16, p19, p21, BAX etc.) which is modified by the strength of the cellular stress. They are able to act as recognition and signaling proteins because of their kinase activity. Classic ataxia telangiectasia is associated with homozygous mutations of the ATM gene, the complete absence of its kinase activity and/or deleterious ATM gene mutations such as truncation/nonsense mutations, loss of function mutation, nonconservative substitutions, frameshift, and deletions. On the other hand, variant ataxia-telangiectasia (A-T) is associated with the presence of residual kinase activity. We report a six-year-old male patient who presented to us with abnormal neck movements as his initial complaint. ATM gene analysis showed a rare pathogenic variant of the ATM gene. The variant was a homozygous nonsense mutation in exon 2 of the ATM gene that resulted in the formation of a stop codon and premature truncation of the protein at codon 23 in exon 2 (p.Arg23Ter). In conclusion, we report a case of an unusual presentation of classic A-T. We should pursue a long-term follow-up and maintain a low threshold for performing pedigree analysis and genetic testing in pediatric patients with movement disorders. In resource-limited settings where kinase enzyme assays are not universally available to patients, web-based mutation prediction tools may be beneficial to predict the deleterious effects of the mutation.

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