Genetic and metabolic investigations for individuals with neurodevelopmental disorders: A survey of Canadian geneticists' practices

Abstract

Neurodevelopmental disorders (NDDs) are genetically heterogeneous. There are many possible etiological investigations for NDDs, and a lack of clear and current guidelines for such testing. Here we characterize the practices of genetic and metabolic physicians in Canada as it pertains to etiological investigation of patients with NDDs, by means of an online questionnaire. The survey response rate was 30% (n = 46). The most commonly ordered first‐line tests for patients with non‐syndromic NDDs are chromosomal microarray (98%) and Fragile X testing (85%). The most commonly ordered second‐line test for non‐syndromic NDDs is a multi‐gene panel (78%) or exome sequencing (29%). Biochemical screening is ordered as a first line test by 33% of respondents, second line by 31%, and rarely or never by 36% of respondents. Those respondents with metabolics fellowship training were more likely to order biochemical screening than those without. The number of years of clinical experience generally did not affect the types of tests ordered. For patients with NDDs, test‐ordering practice among Canadian clinical geneticists is highly variable, in particular with respect to biochemical screening and use of next‐generation sequencing technologies. Evidence‐based guidelines should be developed to facilitate best practices in Canada.

Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)

“…Indeed, there is wide variability in Canadian clinical practice. 36 Both the Canadian Pediatric Society 27 and the American Academy of Pediatrics 28 reference a systematic literature review 80 as the rationale to screen for treatable IMDs in all children presenting with GDD/ID; however, the diagnostic yield of this approach was unknown at the time. The protocol suggested by the Treatable Intellectual Disability Endeavor (TIDE) (www.…”

“…There is also a lack of consensus among experts as to which metabolic investigations comprise a comprehensive screen for IMDs. Indeed, there is wide variability in Canadian clinical practice 36…”

“…Recommendations vary considerably for metabolic testing,25–28 32–35 while the use of gene panels and ES is relatively new and typically not included in recommendations aimed at non-geneticists. Not surprisingly, a recent survey of Canadian genetic and metabolic physicians found that CMA and fragile X testing are the most often used tests for patients with NDDs, while the use of metabolic tests, gene panels and ES was highly variable 36. Therefore, Canadian recommendations for genetic investigation of NDDs are urgently needed.…”

“…Not surprisingly, a recent survey of Canadian genetic and metabolic physicians found that CMA and fragile X testing are the most often used tests for patients with NDDs, while the use of metabolic tests, gene panels and ES was highly variable. 36 Therefore, Canadian recommendations for genetic investigation of NDDs are urgently needed.…”