Genetic testing in cerebral palsy with clinical and neuroimaging variables

Abstract

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

Method: 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.

Results: 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).

Interpretation: 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.

FIGURE 1

Clinician survey of current practice responses about the role of genetic testing in cerebral palsy (CP). In total, 45 clinicians responded to the survey of clinical current practice. (a) Breakdown of specialists who contributed to the survey with just under half of respondents being paediatric neurologists. (b) Most respondents agreed that genetic testing had a role in CP and that it would be beneficial to families. However, most felt that there was inadequate information to determine who should be tested. (c) The benefits of genetic testing according to our survey participants. (d) The perceived barriers to genetic testing as determined by the survey participants. (e) The perceived effect on families caused by a lack of access to genetic testing. (f) The types of genetic testing requested by our survey participants.

FIGURE 2

Expert survey factors likely to predict monogenic cause of cerebral palsy (CP) with greater than 75% agreement from the expert panel. There were 78 factors tested; 34 reached greater than 75% agreement. Factors in blue are thought to be more likely in those with genetic CP (n = 20), whereas factors in red are less likely in genetic CP (n = 14). Abbreviations: CSF, cerebrospinal fluid; HIE, hypoxic–ischaemic encephalopathy; MRI, magnetic resonance imaging.

FIGURE 3

Demographics of retrospective cohort (n = 100). (a) Gestational age: 68% of the cohort were born at term. (b) Motor topography: 40% of our retrospective cohort had cerebral palsy with four‐limb involvement. (c) Motor phenotype: in our retrospective cohort, a mixture of dystonia and spasticity was most common and found in 38% of children. (d) Comorbidities: intellectual disability, visual impairment, congenital anomaly, and epilepsy were the most common findings.