Genetic testing in cerebral palsy with clinical and neuroimaging variables

To optimize genetic testing in children with cerebral palsy (CP) by using clinical and magnetic resonance imaging (MRI) variables.

In this mixed methods study, we surveyed current approaches to genetic testing by Australian clinicians involved in the diagnosis of CP. Using an international expert panel we explored 78 variables, to determine which variables were thought to be supportive of monogenic CP. We tested the 78 variables in a retrospective cohort of 100 children with CP, of whom 21 had a genetic cause of CP.

Forty-five clinicians replied to the survey of current practice, 91% agreed that genetic testing has a role in CP, although 47% thought that there was inadequate guidance on which patients to test. The expert panel reached 75% agreement for 30 out of 78 variables for genetic CP, and 14 out of 78 variables against a genetic cause of CP. Retrospective testing in 100 children with CP revealed dysmorphic features (odds ratio [OR] = 7.50; 95% confidence interval [CI] 1.88-29.85) and intellectual disability (OR = 4.86; 95% CI 1.29-18.30) were more common in those with genetic CP, and MRI being compatible with the clinical picture was the feature least common in genetic CP (OR = 0.14; 95% CI 0.05-0.41).

Genetic testing has a role in determining CP aetiology; however, there is no consensus on who should be tested. We used mixed methodology and found that dysmorphic features, intellectual disability, and 'MRI not compatible with the clinical picture' are most supportive of a genetic cause of CP.