Should Everyone with CP have Genetic Testing?

Summary: 

Some individuals with Cerebral Palsy had both genetic diagnoses and risk factors suggesting that genetic variants might make these individuals more susceptible to acquired brain injuries. Genetic testing may help families answer the question as to why they or their loved one has CP and facilitate early interventions and potential treatment.

Background

Cerebral palsy (CP), one of the most common motor disabilities in children, has long been considered an acquired condition following a brain injury that occurs before or during birth. Risk factors for CP include premature (preterm) birth, infection, and brain bleeds. However, in 10% to 15% of cases, there is no clear cause. There is increasing recognition that genetics plays a part in CP, but no standardized approach to genetic testing in patients with CP exists. 

What happened in the Study?

We asked the question whether both people with and without known risk factors for CP should have genetic testing.

We evaluated 151 unrelated patients with CP cared for at the NewYork-Presbyterian/Columbia University Irving Medical Center. Of these, 81.5% had identified or suspected risk factors for their CP and 18.5% had no identified risk factors. We performed whole exome sequencing (a technique that involves identifying variations in a person's genetic makeup to understand what may be causing symptoms or a disease) and screening for environmental risk factors such as preterm birth, brain-related events, birth asphyxia, and intrauterine infection.

This is what we found:

• Genetic diagnosis in 8.1% of the group with high risk factors.
• Genetic diagnosis in 14.3% of the group without high risk factors.
• Six genes not previously associated with CP were identified, these occurred only in the group with CP risk factors.
• Global developmental delay and intellectual disability were associated with a positive genetic diagnosis across the entire cohort.
• Extreme preterm birth, stroke, brain hemorrhage, and older age were associated with a negative genetic diagnosis.

What what does this mean?

While the rate of genetic diagnoses among individuals without risk factors (14.3%) was higher than those with risk factors (8.1%), the difference was not significant. Some individuals had both genetic diagnoses and risk factors suggesting that genetic variants might make these individuals more susceptible to acquired brain injuries. Genetic testing may help families answer the question as to why they or their loved one has CP and facilitate early interventions and potential treatment.

Authors:

Halie J May, Jennifer A Fasheun, Jennifer M Bain, Evan H Baugh, Louise E Bier, Anya Revah-Politi, New York Presbyterian Hospital/Columbia University Irving Medical Center Genomics Team, David P Roye Jr, David B Goldstein, Jason B Carmel