Seizures are a big concern for families with children with Phelan-McDermid syndrome, but it’s not always clear when or why they happen. A recent study by Dr. Tess Levy from the Seaver Autism Center at Mt. Sinai and with support from the Developmental Synaptopathies Consortium (DSC) looked at 98 people ages 3 to 21 with Phelan-McDermid syndrome to learn more about seizures.
What Did the Study Do?
Researchers asked caregivers about their child’s seizure history and looked at medical records. Caregivers also completed an assessment of adaptive behavior, and the participants with Phelan-McDermid syndrome completed a test to best estimate IQ. They wanted to understand when seizures happen, what kind they are, and if they affect skills like talking or daily tasks.
The study included 26 participants with Class 1 deletions (smaller), 53 with Class 2 deletions (larger), and 19 with sequence variants.
What Did the Study Find?
- Types of Seizure: About 42% of participants had reported history of any type of seizures. The most common types were generalized seizures (27%) and focal seizures (20%). Among individuals with focal seizures, roughly half loss consciousness. Of the motor subtypes, tonic-clonic was the most commonly reported (13/98, or 13%). Only 2% reported having febrile seizures.Â
- Impact on Skills: People with seizures (any type) usually had lower scores on tests of adaptive and cognitive skills compared to those without seizures. However, the type of seizure did not make a big difference. In contrast, individuals with generalized seizures (69%) were more likely to have a reported history of developmental regression, or loss of skills. Of note, age of regression usually occurred prior to age of seizure onset.Â
- Other Factors: The study didn’t find that things like age, sex, or medical problems were linked to seizures. Genetic subgroup (Class 1 deletion, Class 2 deletion, or SHANK3 variant) was not linked to presence of seizures, seizure type, or age of onset. But, participants who had more genes deleted in the 22q13 region were more likely to have seizures, especially generalized seizures. In addition, it is worth noting that the majority of participants with generalized seizures (75%) had an age of onset prior to 10 years old.
- Seizure Management: Most people with seizures used one medicine to control them. A variety of anti-seizure medications were used to control seizures. The most common were levetiracetam, valproic acid, and lamotrigine.
What Does This Mean?
The study confirms that seizures are relatively common in Phelan-McDermid syndrome and may impact skills like communication, cognition, and daily living skills. However, the study was not able to identify any clear risk factors of age, sex, or medical factors on seizures, making it harder to predict WHO will have seizures and WHEN seizures may first occur. Yet, researchers remain cautious in saying these associations do not exist and instead suggest additional studies with a larger patient sample are needed to confirm these findings.Â
For individuals with generalized seizures, the article did offer some new insights. For example, individuals with more genes deleted in the 22q13 region were more likely to have generalized seizures. It also showed that those with generalized seizures were more likely to have developmental regression of skills before the seizures started. However, it’s still unclear if losing skills causes seizures or if both are linked to similar underlying factors.
For the data nerds out there, individuals with seizures are estimated to have adaptive and IQ scores approximately a half a standard deviation lower compared with individuals without seizures. But clinically, these differences are likely to be a bit more subtle. For example, it may be the difference between holding a spoon versus holding a spoon without spilling food, being able to take off clothes unassisted but not yet putting clothes on unassisted, using 10 words consistently versus 50 words consistently. It is important to note that we still do not know whether the underlying features or risk factors for seizures are the same/similar as those for lower adaptive/cognitive functioning OR whether there is a causal relationship. Longitudinal studies that follow individuals with and without seizures across many years would need to be done to better understand.
So What Can You Do?
If your child has seizures, keep tracking them. If your child has lost skills but does not have seizures yet, it’s still important to stay alert, as they may be at higher risk. It may be helpful to talk to your medical and school teams about this article and asking them about increasing services that promote daily living, communication, and/or cognitive skills.
We know that seizures (and the concerns about potential future seizures) are a heavy burden for families of individuals with Phelan-McDermid syndrome. We know you are already doing so much to monitor seizures or seizure risk factors–keep doing what you are doing! Last, consider taking part of studies like the Natural History Study so our researchers continue to collect such good data!
Resources
- Publication: https://link.springer.com/article/10.1186/s11689-024-09541-0
- Epilepsy 101 Video: https://youtu.be/h9XBvdiblUw?feature=shared
- Create Your Seizure Action Plan: https://www.epilepsy.com/preparedness-safety/action-plans
- 24/7 Epilepsy Helpline: https://www.epilepsy.com/247-helpline
- Participate in registry through Rare Epilepsy Network: https://pmsf.org/new-seizure-registry-now-available-for-phelan-mcdermid-syndrome-families/
Full article citation: Levy, T., Gluckman, J., Siper, P. M., Halpern, D., Zweifach, J., Filip-Dhima, R., … & Developmental Synaptopathies Consortium. (2024). Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome. Journal of Neurodevelopmental Disorders, 16(1), 25.