2016 SMS Research Symposium Logo

On February 4-5, 2016, PRISMS hosted our 8th SMS Research Symposium, bringing together over 40 of the world's leading experts, researchers, and professionals together for the only event of its kind focused on Smith-Magenis syndrome. This over $20,000 investment in advancing research for the SMS community was a great success!

Below are some of the responses PRISMS received from attendees following our research event:

"The symposium gave the perfect opportunity to gain so much in one place"

"I found it [the symposium] to be a wonderful place to network and engage more about SMS"

"I liked the variety of presentations and demonstrations of commitment to SMS and related work"

"I felt privileged to participate [in the symposium]"

 

As part of our commitment to supporting research and advancements for the SMS community and sharing that progress with our families, PRISMS funded the creation of abstract summaries to share the latest research findings with you! Please see below for summaries of research presented at PRISMS 8th SMS Research Symposium event.

 

PMP22-RAI1 contiguous gene syndromes:  molecular mechanism and clinical profiling
Presenter: Bo Yuan, PhD, Baylor College of Medicine

There has been a good amount of research focused on identifying the importance of the genes and regions that are involved in Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS). In the same region on chromosome 17, there is also a disorder known as Charcot-Marie-Tooth disease type 1A (CMT1A) that is associated with the PMP22 gene. This research looked at the clinical features and molecular overlap in the genes involved in these disorders. Some individuals with PTLS have larger duplications that include both RAI1 and PMP22, while only a few individuals with SMS also have larger deletions that include the PMP22 gene. The data presented here suggested that these larger deletions and duplications that include both regions should be considered different genomic disorders that include additional clinical features with different molecular mechanisms leading to each.

Integration of functional 'omics' data uncovers unique mitochondrial deficiency in Smith-Magenis syndrome
Presenter: Joseph Alaimo, PhD, Baylor College of Medicine

Through a multiple tier approach, this research looked at the specific function of the RAI1 gene to determine if there were different pathways or patterns that were affecting the expression of the gene in individuals with Smith-Magenis syndrome. They found that in the cells of individuals with Smith-Magenis syndrome, a decrease in the normal function of RAI1 resulted an increase of certain metabolites that can be linked to mitochondrial activity. This is promising because it can identify a future target at treating some of the secondary complications that individuals with Smith-Magenis syndrome experience by targeting the mitochondrial function.

Network analysis postulates a function for RAI1 in epigenetic regulation
Presenter: Murray Robinson, PhD, Molquant, Inc.

Next-generation sequencing has opened doors for researchers to access vast amounts of information regarding individuals with Smith-Magenis syndrome. Because many syndromes have a very distinct molecular pathway defect, the importance of this information along the development of network analysis methods, it has been found that RAI1, the gene in Smith-Magenis syndrome, is linked to ~15% of other known intellectual disability genes. Through more methods, researchers have been about to link many pathways and genes together that are all acting together to produce the typical features associated with Smith-Magenis syndrome, including the sleep (circadian rhythm) disturbances.

Identification of two novel DEAF1 variants in patients with intellectual disability (ID) and demonstration that DEAF1 regulates the expression of RAI1, a causative gene for SmithMagenis Syndrome
Presenter: Li Chen, Fudan University

The symptoms and features that are identified in individuals with changes in the DEAF1 gene are very distinct. Changes in this gene are also linked to an intellectual disability syndrome. DEAF1 was found to bind to a region of the RAI1 gene, possibly impacting its regulation. These two genes function in the same pathway and interact with other genes that are important in neuropsychiatric disorders, regulating the expression of many other genes. Because of this connection, it has been found that there could be a much broader connection for intellectual disability through many different genetic syndromes.

POGZ is mutated in individuals with behavioral abnormalities, microcephaly, intellectual disability, and developmental delay
Presenter: Janson White, Baylor College of Medicine

Because of the newest development of whole exome sequencing, individuals with new gene mutations, or changes, have been identified. By linking six unrelated individuals with a similar clinical picture, this research group identified mutations in the POGZ gene, describing a new intellectual disability syndrome, termed White-Sutton syndrome.

Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo pathogenic variants
Presenter: Marjan Huizing, PhD, NHGRI, NIH

Improvements in genetic testing have allowed researchers to assess individuals who display similar symptoms and features as those with Smith-Magenis syndrome but do not have the typical chromosome 17p11.2 deletion or RAI1 gene change. The group identified 6 individuals who fit this description and performed whole exome sequencing on their DNA. They found changes in other genes that were linked to intellectual disability. Individuals who do not have a previous explanation for their Smith-Magenis-like clinical features should be considered for whole exome sequencing as a part of their diagnostic workup.

Integration of exome sequencing and genomic analysis reveals Smith-Magenis-like causative genes
Presenter: Christine Beck, PhD, Baylor College of Medicine

The introduction of whole exome sequencing has opened new doors for diagnosis of individuals with Smith-Magenis syndrome-like clinical features who do not have the typical 17p11.2 deletion or change in RAI1. This group looked at 15 individuals and found that 9 of these individuals had a potentially damaging change in genes associated with intellectual disability and developmental delay. They are looking at these individuals, as well as others in a database, and seeing if they can link the changes they have found together to explain the clinical picture of these individuals to find out if there are multiple factors and interactions occurring in those individuals with Smith-Magenis syndrome and other disorders that have intellectual disability, developmental delay, and behavioral abnormalities.

Auditory phenotype of Smith-Magenis syndrome
Presenter: Megan Brendal, Washington State University

Many individuals with Smith-Magenis syndrome are reported to have hearing loss. Most of this hearing loss is conductive and is mild to moderate. In this study, the specific types of hearing loss were identified and found that hearing loss for individuals with Smith-Magenis syndrome becomes worse throughout life. This information provides important tools to use for medical management and early recognition of the hearing loss for parents and clinicians.

Establishing best practices in clinical care for Smith-Magenis syndrome: the Geisinger specialty clinic model
Presenter: Brenda Finucane, MS, LGC, Geisinger Autism & Developmental Medicine Institute

There are many rare genetic disorders that have previously been identified as needing a specialty center to provide families all the important physicians and therapies in one place. The Geisinger Health System in central Pennsylvania has created such a clinic - or center for excellence - for Smith-Magenis syndrome. The goal was to identify the best practices for individuals with Smith-Magenis syndrome and begin to use them in practice. It also is a hope that there will be more of these centers for excellence being created to support families in all areas of the United States.

Smith-Magenis syndrome displays profound neurodevelopmental behavioral deficiencies and has food behaviors equivalent to Prader-Willi syndrome
Presenter: Sarah Elsea, PhD, Baylor College of Medicine

There are many clinical features of individuals with Smith-Magenis syndrome that are similar to those with Prader-Willi syndrome. This research aimed to look specifically at the features related to behavior and eating habits of those indviduals with Smith-Magenis syndrome on a scale that has previously been used for Prader-Willi syndrome. It was found that there are similar issues in individuals with Smith-Magenis syndrome related to a fixation on food, negative behaviors related to food and an unsatisfied need for food like those with Prader-Willi syndrome. This research can potentially open up the door to providing individuals with Smith-Magenis syndrome a prevention measure similar to that of Prader-Willi syndrome to reduce the risk for obesity.

Experience is the best teacher: Curriculum of Caring impact on health care student as they learn from people who live with developmental disabilities
Presenter: Kerry Boyd, MD, FRCPC, McMaster University, Michael G. DeGroote School of Medicine

It has always been said that experience is the best avenue for learning, and this program is an excellent example. They set up a three step process for first year medical students to gain the experience and training with individuals with developmental delay and intellectual disability. They found that early exposure to these individuals, skills-based training, and clinical application of those skills, greatly improved the quality of care for the patients and a comfort and confidence for the medical students.

Exploring caregiving responsibilities among adolescent and young adult siblings of individuals with Smith-Magenis syndrome
Presenter: Rebecca Foster, PhD, St. Louis Children's Hospital

Most of the research surrounding Smith-Magenis syndrome has been focused on parents and individuals with Smith-Magenis syndrome. This study looked to gain insight from the siblings of these people. It was found that most siblings, 13-25 years of age, were more concerned for their future responsibilities as a caregiver than for financial burdens or handling the difficult behaviors of their siblings. Because of this worry, it is important to find ways to help siblings of individuals with Smith-Magenis syndrome transition from the role as a sibling, with the parent providing the constant care, to the role as the primary caregiver.

An alternative to physical restraint for management of unsafe grounding behavior
Presenter: Willard Hutton, MEd, Life-Skills, Inc.

There is a very common grounding behavior that is used by many individuals with Smith-Magenis syndrome. A constant battle has existed when trying to determine the best way to handle this behavior in the safest way, without injuring anyone. Risk for injury to the person  trying to calm down the individual with Smith-Magenis syndrome, as well as risk for the individual with SMS. This case study of one individual in an adult group home looked at the use of a new way to manage the behavior. They created a 2" x 5" x 8" therapy mat with 4 handles that could be used by staff of the facility to safely transport the individual to a private, safe location. This therapy worked well for this one individual and could potentially be used in future practices for other individuals with Smith-Magenis syndrome.

Recent results of DCCR in Prader-Willi syndrome and therapeutic potential in Smith-Magenis syndrome
Presenter: Neil Cowen, PhD, MBA, Essentialis, Inc.

Very similar traits exist in both Prader-Willi syndrome and Smith-Magenis syndrome. One of the more visible traits is hyperphagia, or the increased and constant desire for food consumption. A new drug has been used in individuals with Prader-Willi syndrome called DCCR and has been found to decrease overall body fat, lean body mass, and the body fat to body mass ratio. They have also found that there is a decrease in the need to ask for more food and even have seen those with Prader-Willi syndrome declining food. Because there are very strong similarities for hyperphagia in individuals with Smith-Magenis syndrome, there is a possibility that this drug could be successful for individuals with SMS as well.

Characterization of the circadian rhythm and sleep aberrations in Smith-Magenis syndrome patients
Presenter: Erica Schreffler, MS, Vanda Pharmaceuticals

Sleep disturbance in Smith-Magenis syndrome is a significant issue every day. The researchers at Vanda Pharmaceuticals have performed an observational study of 8 individuals over a 4-week period of time, specifically looking at the levels of melatonin produced throughout a 24-hour period of time. They found that there was an abnormal pattern of melatonin secretion in each person with SMS and that it was generally stable. This study provided the preliminary information needed to initiate a clinical trial of the melatonin receptor agonist, Hetlioz, toward effective therapy and treatment for individuals with Smith-Magenis syndrome.