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Array CGH Analysis and Developmental Delay: A Diagnostic Tool for Neurologists

Published online by Cambridge University Press:  23 September 2014

F. Cameron ,
J. Xu ,
J. Jung  and
C. Prasad
F. Cameron
Affiliation:
Western University, London Health Sciences Centre and Western University Ontario, London, Ontario
J. Xu
Affiliation:
Cytogenetics, London Health Sciences Centre and Western University Ontario, London, Ontario Cytogenetics, Alberta Genetics Services, Alberta Health Services, Edmonton, Alberta, Canada
J. Jung
Affiliation:
Western University, London Health Sciences Centre and Western University Ontario, London, Ontario Paediatrics, London Health Sciences Centre and Western University Ontario, London, Ontario
C. Prasad*
Affiliation:
Western University, London Health Sciences Centre and Western University Ontario, London, Ontario Paediatrics, London Health Sciences Centre and Western University Ontario, London, Ontario Children's Health Research Institute, London Health Sciences Centre and Western University Ontario, London, Ontario
*
Genetics, Metabolism and Paediatrics, 800 Commissioners Road East, London, Ontario, N6C 2V5, Canada. Email: [email protected].
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Abstract

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Developmental delay occurs in 1–3% of the population, with unknown etiology in approximately 50% of cases. Initial genetic work up for developmental delay previously included chromosome analysis and subtelomeric FISH (fluorescent in situ hybridization). Array Comparative Genomic Hybridization (aCGH) has emerged as a tool to detect genetic copy number changes and uniparental disomy and is the most sensitive test in providing etiological diagnosis in developmental delay. aCGH allows for the provision of prognosis and recurrence risks, improves access to resources, helps limit further investigations and may alter medical management in many cases. aCGH has led to the delineation of novel genetic syndromes associated with developmental delay. An illustrative case of a 31-year-old man with long standing global developmental delay and recently diagnosed 4q21 deletion syndrome with a deletion of 20.8 Mb genomic interval is provided. aCGH is now recommended as a first line test in children and adults with undiagnosed developmental delay and congenital anomalies.

Résumé

RÉSUMÉ

Le retard de développement survient chez 1 à 3% de la population et son étiologie est inconnue chez à peu près 50% des cas. L'évaluation génétique initiale pour un retard de développement incluait antérieurement une analyse chromosomique et une analyse par FISH (hybridation in situ en fluorescence) de régions subtélomériques. La puce d'hybridation génomique comparative (CGHa) est devenue un outil de détection des changements du nombre de copies géniques ainsi que de la disomie uniparentale et elle est le test le plus sensible pour fournir un diagnostic étiologique dans le retard de développement. Le CGHa permet d'offrir un pronostic et un risque de récurrence, améliore l'accès aux ressources, aide à limiter les évaluations et peut modifier le traitement médical dans bien des cas. Le CGHa a mené à la définition de nouveaux syndromes génétiques associés à un retard de développement. À titre d'exemple, nous décrivons le cas d'un homme âgé de 31 ans qui présentait un retard de développement global depuis longtemps et chez qui un syndrome associé à une délétion 4q21 a été diagnostiqué récemment, soit une délétion de 20,8 Mb. Le CGHa est maintenant recommandé comme test de première ligne chez les enfants et les adultes présentant un retard de développement et des anomalies congénitales.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 40 , Issue 6 , November 2013 , pp. 777 - 782
Copyright
Copyright © The Canadian Journal of Neurological 2013

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