News & Events
First Study to Comprehensively Describe Clinical Presentation of Phelan-McDermid Syndrome Will Help Guide Future Research and Clinical Care
(New York – June 11, 2013) In the first prospective study of its kind, Seaver Autism Center researchers at the Icahn School of Medicine at Mount Sinai provide new evidence of the severity of intellectual, motor, and speech impairments in a subtype of autism called Phelan-McDermid Syndrome (PMS). The data are published in the June 11 issue of the journal Molecular Autism.
Mutation or deletion of a gene known as SHANK3 is one of the more common single-gene causes of autism spectrum disorders and is critical to the development of PMS, a severe type of autism. To date, clinicians have relied on case studies and retrospective reviews of medical records to understand the features of this disorder and how the clinical presentation relates to the extent of the genetic changes in the SHANK3 region. In the first systematic and comprehensive prospective trial, researchers led by Alex Kolevzon, MD, Clinical Director of the Seaver Autism Center, under the direction of Joseph Buxbaum, PhD, Director of the Seaver Autism Center, enrolled 32 participants with SHANK3 deletions to comprehensively assess their clinical symptoms and examine how the size of the SHANK3 deletion correlated to those symptoms.
“Previous studies have not utilized prospective assessments to understand Phelan-McDermid Syndrome, and the prevalence of autism spectrum disorder has never been examined using gold-standard instruments” said Dr. Kolevzon. “There is no established standard for assessing this type of autism, and our study provides important guidance in developing such a standard.”
Of the 32 patients enrolled, 84 percent met criteria for an autism spectrum disorder. Seventy-seven percent of patients exhibited severe to profound intellectual disability, with 19 percent using some form of verbal communication. Other common features included low muscle tone, gait disturbance, and seizures. When evaluating the genetic make-up of these patients, the researchers found that the larger the SHANK3 deletion, the more severe the clinical presentation was.
“Our findings provide additional evidence of the significant impairment associated with SHANK3 deficiency,” said Dr. Kolevzon. “Also, knowing how large the deletion of the SHANK3 gene is may have important implications for medical monitoring and individualizing treatment plans. Results also provide much-needed guidance in developing a standardized methodology for evaluating the features of this disorder.”
Many of the patients who participated in this study were next enrolled in a clinical trial at Mount Sinai evaluating Insulin-Like Growth Factor-1 (IGF-1), a commercially available compound for growth deficiency that is known to promote nerve cell survival as well as synaptic maturation and plasticity. The primary aim of the study is to target core features of Phelan McDermid Syndrome, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. The clinical studies with IGF-1 were supported by studies in a genetically modified mouse with a mutation in SHANK3. These studies, carried out by Dr. Ozlem Bozdagi of the Seaver Autism Center, carefully examined brain function in the mice when SHANK3 was mutated, and provided preclinical evidence for a beneficial effect of IGF-1. These studies were reported in the June 11 issue of the journal Molecular Autism.
“The Seaver Autism Center has the unique capacity to evaluate autism spectrum disorders on both the molecular level and the clinical level,” said Dr. Buxbaum. “This capability puts us in a unique position to see the entire picture—the connection between genetics and behavior in these disorders—and to develop new treatments and better tailor existing ones for these children.”
To learn more about the Seaver Autism Center, visit http://icahn.mssm.edu/research/centers/seaver-autism-center.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
For more information, visit http://www.mountsinai.org/.
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Drs. Ozlem Bozdagi Gunal, Teresa Tavassoli, and Joseph D. Buxbaum have recently published a study in Molecular Autism detailing their observation of injections of human insulin-like growth factor-1 (IGF-1) in to a mouse model of ASD and of developmental delay, which they had previously reported in Shank-3 deficient mice. They observed significant beneficial effects, and given the extensive safety data for IGF-1 in children with short stature due to primary IGF-1 deficiency, IGF-1 is an attractive candidate for controlled clinical trials in SHANK3-deficiency and in ASD. Click here to read more.
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On April 30, 2013 in Madrid, Spain, the Hospital La Paz, Instituto de Genética will be hosting a Scientific Meeting on SHANK3 and Phelan-McDermid Syndrome/22q13 Deletion Syndrome. The meeting will be organized by Juan Ramón Rodríguez, Vice President of the Spanish Association of Families with Phelan-McDermid Syndrome.
Scientific Organizers
Catalina Betancur, PhD (Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie, París)
Joseph D. Buxbaum, PhD (Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York)
Pablo D. Lapunzina Badía, MD, PhD (Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Servicio Madrileño de Salud, Madrid)
Speakers
Catalina Betancur, MD, PhD (INSERM, CNRS, Université Pierre et Marie Curie, Paris)
Joseph D. Buxbaum, PhD (Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York)
Alex Kolevzon, MD (Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York)
Pablo D. Lapunzina Badía, MD, PhD (INGEMM – Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Servicio Madrileño de Salud, Madrid)
Mara Parellada, MD, PhD (Directora del programa AMI-TEA (Atención Médica Integral de los pacientes con Trastorno del Espectro Autista), Hospital Gregorio Marañón, Madrid)
Due to limitations on the size of the conference room, only the first 100 people who register may attend the conference. Please send an email to Juan Ramón Rodríguez (juanramonrh@22q13.org.es). Entry is free.
Where:
INGEMM – Institute of Medical and Molecular Genetics, Hospital Universitario La Paz, Madrid Health Service
Address: Paseo de la Castellana 261, 28046 Madrid
When:
April 30, 2013
Start: 10:00 h (4:00am Eastern)
End: 14:00 h (8:00am Eastern)
(At the end of the conference, families who wish may stay to continue to talk to some of the speakers.)
To view a detailed schedule of the event, please click here.
To view a livestream of this event, please click here.
Seaver Autism Center Seminar Series presents:
“Mapping the neuronal methylome at the epigenetic interface of genetic and environmental risk factors”
Janine LaSalle, PhD (Professor, Medical Microbiology and Immunology, Rowe Program in Human Genetics,
University of California, Davis School of Medicine)
Icahn School of Medicine at Mount Sinai
1425 Madison Avenue at 98th Street (Icahn Medical Institute)
First Floor Seminar Room (#L1-12)
New York, NY 10029
For more information, please contact jessica.brownfeld@mssm.edu.
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Seaver Autism Center Distinguished Lecturer Series presents:
“The Emergence of Brain and Behavior Characteristics in Autism during Infancy”
Joseph Piven, MD
Sarah Graham Kenan Professor of Psychiatry, Pediatrics and Psychology
Director, Carolina Institute for Developmental Disabilities
University of North Carolina
Reception immediately following. Refreshments will be served.
Dr. Piven is a psychiatrist who has conducted clinical research on the pathogenesis of neurodevelopmental disorders including studies of early brain and behavior development, genotype-phenotype relationships and neurological aspects of the variable expression of neurogenetic developmental disorders. He is the Principal Investigator of an NIH-funded Autism Center of Excellence Network and an NICHD-funded intellectual and developmental disabilities research center.
Wednesday, March 6, 2013 at 5:30-6:30pm
Icahn School of Medicine at Mount Sinai
1425 Madison Avenue (Icahn Medical Institute)
First Floor Seminar Room (#L1-12)
New York, NY 10029
For more information or if you would like to attend, please contact jessica.brownfeld@mssm.edu.
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Seaver Autism Center Seminar Series presents:
“A Genetics-First Approach to Autism Research and Treatment”
David Ledbetter, PhD, FACMG (Executive Vice President and Chief Scientific Officer, Geisinger Health System)
Thursday, February 21, 2013 at 2:00-3:00pm
Icahn Medical Institute
First Floor Seminar Room (#L1-12)
Mount Sinai School of Medicine
1425 Madison Avenue at 98th Street
New York, NY 10029
For more information, please contact jessica.brownfeld@mssm.edu.
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The Autism Sequencing Consortium has published a white paper in the journal Neuron, identifying several new potential drug targets for ASD and detailing steps forward for the field of autism research. The paper was first authored by Dr. Joseph D. Buxbaum, Director of the Seaver Autism Center, and research was supported by the National Institute of Mental Health and the Seaver Foundation. The full text of the paper can be found here, and the press release issued by the Icahn School of Medicine at Mount Sinai can be found here.
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Researchers at the University of Chicago have completed a study which “suggests that the 22q13 deletion phenotype includes abnormal posterior fossa structures that are unlikely to be attributed to SHANK3 disruption.” This study also indicates other genes which may be related 22q13.3 deletion phenotypes. To read more, click here.
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Researchers at Stanford University and Ulm University confirmed that autism and the Phelan-McDermid Syndrome-associated Shank3 mutation disrupt the connection between brain cells grown in the laboratory. Click here to read more.
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Our conference is a one-day event held at Mount Sinai School of Medicine. It includes a series of lectures and workshops given by accomplished professionals in the field of autism, including Dr. Simon Baron-Cohen as the keynote speaker. The purpose of the conference is to advance knowledge of the practicing psychiatrist, neurologist, psychologist, geneticist, other health care professional, educator, family member and social worker as to the accurate recognition, diagnosis, and treatment of autism spectrum disorders. The morning session features scientific presentations by renowned autism researchers, and the afternoon workshops are led by Seaver researchers and representatives from community partners such as Federation Employment and Guidance Services-Health and Human Services System, and New York organizations such as the Office for People With Developmental Disabilities.
Visit www.seaverconference.eventbrite.com to register and learn more. To view the full conference brochure click here.
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