PMSF Research

RSC History

Recognizing the need to strongly advocate for research to support the small population of PMS affected individuals, in 2006 the foundation chartered a Research Support Committee to reach out the research community and find ways to generate, support, and sustain the advancement of research in areas of genetics, neurology, biology, and other disciplines that would benefit those affected by the syndrome.  Initially, efforts were limited to sponsorship/endorsement of grant proposals to other organizations and provision of family contacts to facilitate research initiatives.  As the Foundation continued to grow the Stapleton Mini-grant program was established in 2007, offering supplements to establish interest and enable research in critical areas.  In 2010 a recognition program was established for research activities which advance the state-of-the-art in areas that affect individuals affected by the syndrome.  As the Foundation continues to grow, the scope of these efforts will be expanded and new initiatives will be adopted to further promote our mission.

RSC Mission

The mission of the Phelan-McDermid Syndrome Foundation’s Research Support Committee (RSC) is to improve the quality of life for individuals and families affected by Phelan-McDermid syndrome by fostering sound genetic, biological and medical research related to the causes, effects, diagnosis and effective treatments of  Phelan McDermid syndrome.

Primary RSC Goals

  • Support the development of effective therapeutic treatments through scientific research
  • Improve the quality of clinical care available to families

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What you need to know about

seizures and a PMS diagnosis


An important paper on epilepsy and EEG findings in those with Phelan-McDermid Syndrome was published recently in Epilepsia. It’s release comes on the heals of our PMS Epilepsy Awareness Week.

You can view the abstract here and we encourage you to share this link with your child’s doctors, who should be able to access it.

Here are some key major points from the paper:


Seizures occur in more than 30% of children with SHANK3 mutations. The most common seizure type is atypical absence. A subset of patients with SHANK3 mutations have medically intractable epilepsy. There are no characteristic abnormalities on EEG in people with PMS. EEG abnormalities are seen in people with PMS with and without history of seizures.


Twenty-four participants, 20 with deletions of 22q13 and 4 with mutations of SHANK3. Eleven of 24 subjects had a history of at least one lifetime seizure (46%), including 2 of the 4 individuals with point mutations.


Of the patients who have had seizures: 90% had absence seizures, 54% had tonic, 18% atonic, 9% tonic-clonic and 9% myoclonic. Of the 11 patients with a history of seizures, 54% had more than one seizure type, and 2 were diagnosed with Lennox Gastaut Syndrome, based on the combination of multiple seizure types (including tonic seizures), intractability of their seizures and characteristic EEG finding of generalized bursts of 1.5–2 Hz spike and slow wave activity.


Five (20%) of 24 subjects had a history of status epilepticus requiring emergency intravenous medication for cessation of seizure activity.


The onset of first seizure ranged from 14 months to 14 years, with a mean age of onset of 5.2 years.


The frequency of seizures similarly varied from a single lifetime seizure to hundreds of seizures per day.


EEG abnormalities were identified in 14 (67%) of 21 participants. EEG findings were varied: Slowing or absence of the occipital dominant rhythm (42%), focal spike and slow wave discharges (38%) and generalized spike and slow wave discharges (19%).

Five of 21 had abnormal EEG findings, but no history of clinical seizures. Most individuals with multiple seizure types had an abnormally slow occipital dominant rhythm (83%), whereas the majority of individuals with a single seizure type were found to have an age-appropriate occipital dominant rhythm (60%). The spectrum of EEG abnormalities was wide. Several patients had combinations of the above-mentioned abnormalities.


Of 24 subjects, 21 had an anatomic brain magnetic resonance imaging (MRI) study available for review (88%). Findings varied. The most common abnormalities were dysmorphisms of the corpus callosum (29%) and T2 hyperintensities of the deep white matter (24%). Anatomic brain abnormalities were detected in both individuals with history of seizures (33%) and without (38%).


The type and number of anticonvulsant medications prescribed varied greatly among subjects. Although under-powered to evaluate for efficacy in this study, no medication was clearly superior for seizure prophylaxis. There was a trend for those with one seizure type to respond to fewer medications than those with multiple seizure types.

Patients with only one type were maintained on less than two anticonvulsant medications, whereas three of five individuals with multiple seizure types required two or more maintenance anticonvulsant medications. Two individuals were found to have pharmacoresistant epilepsy and had implantation of vagus nerve stimulators with mild improvement in seizure frequency (less than 50% reduction in seizures).


The paper provides longitudinal outcomes for 5 of 11 patients who were evaluated at least twice in clinic.


Epilepsy is present in a substantial number of individuals with PMS with a pooled prevalence of 32% in unique studies available from the literature including this one.

It is unclear exactly what distinguishes those individuals who will have a single seizure semiology and infrequent seizures from those who have multiple seizure types. There was no significant difference in deletion size, neuroimaging finding, or other clinical characteristic.

The only parameter that trended with multiple seizure types was slow or absent occipital dominant rhythm (5 of 6) in individuals with multiple seizure types versus those with a single seizure type (2 of 5).

Together, these data demonstrate that medical practitioners must educate families caring for individuals with SHANK3 loss-of-function mutations that epilepsy can become pharmacoresistent and intractable.

Individuals with PMS should be monitored for seizure activity.


PMSF puts focus on epilepsy, seizures

A number of people diagnosed with PMS also experience seizures. It's a growing topic of concern for parents, their doctors and researchers. That's why we're focusing on epilepsy to help parents and caregivers learn more about seizures in PMS and what is happening in research to stop them.

One way to know more about how epilepsy affects those with PMS is to take part in the Rare Epilepsy Network. This registry was created to collect information about rare epilepsy patients to better understand these conditions, develop treatments and improve the lives and quality of care for patients experiencing seizures.

Here's some of the information about seizures that can help to drive research into this debilitating condition:

-- In a study of 32 patients with PMS, 41% of parents reported their child had seizures.

-- Seizures can have a significant effect on quality of life. They can be associated with injury, regression and even death.

-- Your child should have an EEG and a MRI if your child has had an unprovoked (non-febrile) seizure. An EEG should be done if there are signs of behavioral changes or regression, including loss of motor skills.

-- The most common type of seizure in PMS is a staring spell, which can either be an absence seizure (usualy 10-15 seconds) or a complex partial seizure (longer episodes).

-- We don't know what the best treatments are for seizures in those with PMS or if Cannabidiol can control seizures.



PMS families can participate in seizure registry

Twenty-one rare epilepsy organizations have joined forces with the Epilepsy Foundation, Research Triangle Institute, Columbia University and New York University to create the first Rare Epilepsy Network.

REN is a patient registry created to collect information about rare epilepsy patients to better understand these conditions, improve treatments and improve the lives and quality of care of patients living with them. Similar to the Phelan-McDermid Syndrome International Registry (PMSIR), the REN Registry is voluntary, anonymous and data is kept in a secure database.

Participation involves creating an account and completing 12 questionnaires, each only takes between two and 10 minutes at most. Periodically, you may be asked to update your information. The REN Registry has more detailed questions about seizures than the PMSIR does, so not only is it worth participating in both, but you can also choose to have your REN information shared with the PMSIR.

People are eligible for the REN Registry if they meet all of these criteria:

1. Have a diagnosis by a physician of a rare syndrome or disorder that is related to epilepsy or seizures (for example, has PMS)
2. Have had at least one seizure in their lifetime that was not caused by a fever or the direct result of a head injury. We call these types of seizures "unprovoked."
3. Is either at least 18 years old and can consent for themselves or a patient of any age that is not a ward of the state and has a parent or legal guardian that can consent on their behalf.

As a bonus, every Friday in September, the Epilepsy Foundation will be randomly selecting five participants who completed the REN survey since enrollment began to receive a $100 Amazon gift card.

To learn more about this research opportunity and to enroll, click here. If you have questions about how the PMSF or PMSIR are involved with the REN Registry,  This e-mail address is being protected from spambots. You need JavaScript enabled to view it .

Mouse model of autism offers insights

to human patients, potential drug targets

By Duke Medicine News and Communications

DURHAM, N.C. -- A new mouse model of a genetically-linked type of autism reveals more about the role of genes in the disorder and the underlying brain changes associated with autism’s social and learning problems.

Scientists at Duke Health who developed the new model also discovered that targeting a brain receptor in mice with this type of autism could ease repetitive behaviors and improve learning in some animals.

Their report, published May 10 in the journal Nature Communications, suggests that among more than a dozen different lines of mice developed around the world to mirror autism caused by mutations to the SHANK3 gene, Duke researchers are the first to create a mouse in which that gene has been completely eliminated.

The total “knockout” of the gene makes the model more effective for studying SHANK3-related autism and Phelan-McDermid syndrome in humans, many of whom are missing the gene completely, said senior author Yong-hui Jiang, M.D., Ph.D., an associate professor of pediatrics and neurobiology

“This is an important first step in understanding the process of the disorder in humans,” Jiang said. “For many families affected by autism, this is something that could provide hope and potentially lead to a treatment.”

SHANK3 is essential to the function of synapses in the brain and communication between neurons.

Jiang said autism researchers worldwide could use the mouse model to study ways to compensate for the gene and improve symptoms in people with autism spectrum disorders and Phelan-McDermid Syndrome, a more profound developmental condition caused by mutations to SHANK3 and other genes in chromosome 22.

Over the past five years, researchers observed abnormal brain activity in the SHANK3 knockout mice when compared to controls. The knockout mice would vocalize less, groom obsessively to the point of losing fur, fail to heed the established social hierarchy in groups, and were often unable to locate their own homes, wandering into strangers’ nests.Jiang said autism researchers worldwide could use the mouse model to study ways to compensate for the gene and improve symptoms in people with autism spectrum disorders and Phelan-McDermid Syndrome, a more profound developmental condition caused by mutations to SHANK3 and other genes in chromosome 22.

“Some of the repetitive behaviors, inability to read social cues, and restricted interests copy many of the symptoms we see in people with autism,” said co-lead author Alexandra Bey, an M.D./Ph.D. candidate at the Duke University School of Medicine. Scientists at the University of North Carolina-Chapel Hill and Fudan University in Shanghai also contributed to the report.

In one experiment, mice were placed in a box with numerous holes and paths to explore. Curious control mice roamed while knockout mice often stuck to a small area and repeated the same routes.

“This replicates what see in many children with autism,” Bey said. “In children, perseveration is a behavior such as playing with the same toy over and over again in the same way, and not exploring new ways to interact with it.”

As they studied brain activity in the knockout mice, the researchers also found prominent changes in a receptor in the brain known as mGluR5 and other proteins that support the function of neurons and synapses, said co-lead author Xiaoming Wang, M.D., Ph.D., senior research associate in Duke’s department of pediatrics. The team tested two chemical compounds that target the mGluR5 receptor and found they could actually relieve the animals of some of their repetitive habits or enhance their learning.

“The regulation of this receptor is complex and gives rise to other behavioral challenges, but this is a clue for further research,” Wang said. “In the future, it’s possible that a similar class of drug could be tried on humans. We are interested to see our study help others around the world better understand this gene and how it affects synapses and hope the model can be generalized to other autism genes.”

Watch: "The PMS International Registry:
What are you doing with my data?"

This Webinar will teach you about the types of data collected in the Phelan-McDermid Syndrome International Registry, what it tells us about our community, what opportunities and limitations it offers and more.

Rebecca Davis, the PMS_DN Data Coordinator and Registry Coordinator, provides an overview of the International Registry including summaries of who participates, where they live, age, sex and race.

Rebecca will also review how data is collected, how the data is used, opportunities (including the PMS_DN) and limitations of the registry and how you can make sure your data is up to date.


Watch: PMS_Data Network webinar

Pick up some tips on collecting medical reocrds

You can watch the most recent Phelan-McDermid Syndrome Foundation webinar about the PMS_Data Network and learn tips on collecting your child's medical records. The webinar is just over half an hour long.

To watch the webinar, click here.

Watch: Developmental Synaptopathies

Consortium webinar

Learn about the upcoming clinical research study


Nearly 100 people logged on for the Phelan-McDermid Syndrome Foundation's webinar about the Developmental Synaptopathies Consortium clinical research study.

We would like to thank Dr. Alex Kolevzon of the Icahn School of Medicine at Mt. Sinai and Dr. Mustafa Sahin at Harvard Medical School for their time and insight.

If you weren't able to participate, you can watch it here. It's just over half an hour long.

The study, to be performed at six sites around the country, targets those with PMS who are 3-21 years old and have a deletion or mutation in the SHANK3 gene, which includes rings or mosaics. Assessments will take two-three days for parent reporting and medical testing at Mt. Sinai in New York; Boston Children's; Rush in Chicago; NIMH in Bethesda, Maryland; University of Texas Southwestern; and Stanford.

International families can participate, as well, Kolevzon said: "There's no exclusion." But, Sahin noted, "we can only take English-speaking patients just for the requirements of keeping everything standardized."

Making travel a bit easier will be money from the Foundation to cover some travel costs for families.

Providing funding for travel is "one of the ways the (PMS) Foundation is supporting this project," said Geraldine Bliss, PMSF Research Support Committee Chair. "We ... wanted to make sure that there wouldn't be a huge travel burden on families."

Sahin said the PMS Foundation was key to getting the consortium funded.

"I want to thank the Phelan-McDermid Syndrome Foundation for really making the grant possible for us to be able to apply," he said. "We really wouldn't have been able to get this grant funded, without (PMSF's) help, from the NIH."


GET IN TOUCH: Click here for a list of contacts at the medical

facilities that are part of the consortium.

Last Updated on Sunday, 11 September 2016 22:12
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