So What? Does the Test Lead to Improved Health Outcomes?

Abstract

We, the authors of the evidence report on the diagnostic evaluation of children with global developmental delay (GDD) and intellectual disability (ID),1 take issue with the editorial by Dr. Trevathan2 critiquing our recommendations for genetic testing. In his editorial, Dr. Trevathan rejects out of hand the medical and financial utility of genetic testing, particularly chromosomal microarray analysis (CMA), without offering convincing evidence to buttress his claims. Whereas typically we would not respond to empty assertions, we believe that the issue is too important to leave unanswered. We therefore delineate herein the many well-established utilities of genetic testing for children with GDD/ID and provide a rationale for continued and robust use of these diagnostic tools to improve the health outcomes of our patients. Diagnostic genetic testing for this patient cohort may influence patient management. Examples include anticonvulsant selection for patients with SCN1A mutations3 and patients with Angelman syndrome4 or the decision whether to use the ketogenic diet for patients with glucose transporter defects5 or other specialized diets for other conditions. Diagnosis can result in increased surveillance for cancer, as in patients with macrocephaly and autism who have certain PTEN mutations.6 A genetic diagnosis may inform orders for tests and referrals to other specialists, including enzyme replacement therapies.7,8,9,–,13 CMA is currently the most comprehensive and cost-efficient way to interrogate this range of genetic etiologies. Examples include dietary treatments for phenylketonuria and enzyme replacement therapies for Pompe disease and Hurler syndrome.9,–,13 A critical set of assumptions underlies genetic testing: that greater understanding and treatments are derived from knowledge of diagnoses and pathophysiology. The genetic etiology of fragile X syndrome was identified in 1991; only …