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Ataxia-Telangiectasia: Atypical Presentation and Toxicity of Cancer Treatment

Published online by Cambridge University Press:  02 December 2014

Rochelle A. Yanofsky ,
Sashi S. Seshia ,
Angelika J. Dawson ,
Kent Stobart ,
Cheryl R. Greenberg ,
Frances A. Booth ,
Chitra Prasad ,
Marc R. Del Bigio ,
Jens J. Wrogemann  and
Francesca Fike
...Show all authors
Rochelle A. Yanofsky*
Affiliation:
Section of Pediatric Hematology/Oncology, University of Manitoba & Health Sciences Centre, Winnipeg, MB Department of Pediatrics & Child Health, University of Manitoba & Health Sciences Centre, Winnipeg, MB
Sashi S. Seshia
Affiliation:
Section of Pediatric Neurology, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK
Angelika J. Dawson
Affiliation:
Department of Pediatrics & Child Health, University of Manitoba & Health Sciences Centre, Winnipeg, MB Departments of Biochemistry & Medical Genetics, University of Manitoba & Health Sciences Centre, Winnipeg, MB Division of Laboratory Medicine & Pathology, Section of Genetics and Metabolism, University of Manitoba & Health Sciences Centre, Winnipeg, MB University of Manitoba & Health Sciences Centre, Winnipeg, MB
Kent Stobart
Affiliation:
Section of Pediatric Hematology/Oncology, University of Manitoba & Health Sciences Centre, Winnipeg, MB Department of Pediatrics, Northern Alberta Children's Cancer Program, University of Alberta, Edmonton, AB
Cheryl R. Greenberg
Affiliation:
Department of Pediatrics & Child Health, University of Manitoba & Health Sciences Centre, Winnipeg, MB Departments of Biochemistry & Medical Genetics, University of Manitoba & Health Sciences Centre, Winnipeg, MB
Frances A. Booth
Affiliation:
Department of Pediatrics & Child Health, University of Manitoba & Health Sciences Centre, Winnipeg, MB
Chitra Prasad
Affiliation:
Department of Pediatrics, University of Western Ontario, London, ON, Canada
Marc R. Del Bigio
Affiliation:
University of Manitoba & Health Sciences Centre, Winnipeg, MB Department of Pathology, UCLA/Geffen School of Medicine, Los Angeles, CA, USA
Jens J. Wrogemann
Affiliation:
University of Manitoba & Health Sciences Centre, Winnipeg, MB Diagnostic Imaging, Section of Pediatric Radiology, UCLA/Geffen School of Medicine, Los Angeles, CA, USA
Francesca Fike
Affiliation:
Departments of Pathology & Laboratory Medicine and Human Genetics, UCLA/Geffen School of Medicine, Los Angeles, CA, USA
Richard A. Gatti
Affiliation:
Departments of Pathology & Laboratory Medicine and Human Genetics, UCLA/Geffen School of Medicine, Los Angeles, CA, USA
*
Section of Pediatric Hematology/Oncology, CancerCare Manitoba, 675 McDermot Ave., Winnipeg, Manitoba, R3E 0V9, Canada
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Abstract

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Background:

The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.

Methods:

We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.

Results:

Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were “cured” of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.

Conclusions:

The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.

Résumé:

RÉSUMÉ:Contexte :

L’apparition d’une ataxie cérébelleuse progressive dans la petite enfance est considérée comme une manifestation clé de l’ataxie-télangiectasie (A-T), accompagnée d’apraxie oculaire, de télangiectasies, d’un déficit immunitaire, de susceptibilité au cancer et d’hypersensibilité aux radiations ionisantes.

Méthodes :

Nous décrivons les manifestations cliniques et l’évolution chez trois enfants mennonites chez qui un diagnostic d’A-T a été posé après un traitement pour cancer lymphoïde.

Résultats :

Avant le traitement anticancéreux, tous présentaient des anomalies neurologiques atypiques non évolutives, dont l’âge de début se situait vers 30 mois, soit de la dysarthrie, des dyskinésies, de l’hypotonie et/ou de la dystonie sans télangiectasies. Une ataxie cérébelleuse a été notée chez un seul des enfants et elle est demeurée légère jusqu’à son décès à l’âge de huit ans. Aucun n’a présenté d’infection grave. Les trois enfants ont été « guéris » de leur cancer lymphoïde. Cependant tous ont présenté des effets secondaires du traitement. Les deux enfants qui ont reçu une irradiation crânienne ont présenté des tumeurs cérébrales neuroectodermiques primitives sus-tentorielles, une association jamais décrite auparavant, dont l’issue a été fatale.

Conclusions :

Le mode de présentations neurologiques de l’A-T est vaste. L’ataxie et les télangiectasies peuvent être minimes ou absentes et sans évolution apparente. Le diagnostic d’A-T devrait être envisagé chez tous les enfants qui présentent une dysfonction neuromotrice ou une neuropathie périphérique, surtout chez ceux qui présentent éventuellement un cancer lymphoïde. Si le diagnostic n’est pas posé, les conséquences peuvent être sérieuses. La radiothérapie et les médicaments radiomimétiques devraient être évités chez les individus atteints d’A-T.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 36 , Issue 4 , July 2009 , pp. 462 - 467
Copyright
Copyright © The Canadian Journal of Neurological 2009

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