Seizure Disorder in Prader-Willi Syndrome

Although it's rarely mentioned in clinical descriptions of PWS, anyone who hangs around families with PWS knows that seizures seem to occur much more frequently in those with PWS than typical individuals. Even in cases where a seizure disorder is never formally diagnosed, many parents have, at one time or another, had their child with PWS evaluated because they appear to be having seizures or unusual movements.

There have been a smattering of papers in the medical literature about seizures in PWS, and a new one [Characteristics and Frequency of Seizures Disorder in 56 Patients with Prader-Willi Syndrome] adds to the growing evidence that seizures are common in this population. Dr. Fan and colleagues at the University of North Carolina had also noticed that a number of the PWS patients in their practice developed seizures, so they decided to review their records over a six year period (2000-2006) to better understand seizures in PWS.  In this study, the authors defined seizure disorder as encompassing "generalized epilepsy, generalized febrile seizure and absence epilepsy".  

Of 56 patients with PWS, one had a diagnosis of seizures that was likely related to complications from a premature birth, while nine other PWS patients had been diagnosed with a seizure disorder.  An additional 6 children had been evaluated for seizures based on staring, tremor or collapsing spells, but were not given a diagnosis of seizure disorder after an EEG test. Thus, the authors conservatively estimate a frequency of seizures in their patients of 16%, more than 3x what is expected in the general population [note: the estimate of seizures in the general population includes febrile seizures, which occur in 2-5% of children].

The authors then go on to review what has previously been published in the medical literature. Combining their patients with those reported in six prior studies, 119 children out of a total of 455 were diagnosed with seizures, for a substantial 26%. Notably, seizures seem to be much more likely to occur in those with PWS by deletion than those with PWS by UPD (uniparental disomy). Although additional studies will be needed to sort this out, the genes for several receptors of the GABA neurotransmitter are in the region deleted in PWS. It may be that deletion of one set of these genes, as occurs in PWS by deletion but not PWS by UPD, underlies the susceptibility to seizure disorder.

The authors conclude that healthcare providers need to be aware that there is likely at least a 3 to 4 fold increased risk of seizure disorder in those with PWS by deletion, compared to the general population. Finally, their call for a multicenter prospective study of seizure phenotype (characteristics), management and outcome is welcomed and should be acted upon quckly. 

Topics: Research

Theresa Strong

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Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.

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