Clinical trial NCT02461420: Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
Official title: Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Phelan-McDermid Syndrome
Autism Spectrum Disorder
Intellectual Disability
Keywords: Phelan-McDermid Syndrome
PMS
Genotype
Phenotype
Natural History
Mapping
22q13 Deletion Syndrome
SHANK3
Autism Spectrum Disorder
ASD
Intellectual Disability
ID
EEG
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institutes of Health (NIH)
name: Office of Rare Diseases (ORD)
name: National Center for Advancing Translational Sciences (NCATS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Phelan-McDermid Syndrome Foundation
First posted: 2015-06-03
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 190 subjects with PMS will be enrolled across the 6 sites for this study

Brief summary: The purpose of this study is to comprehensively characterize PMS using standardized medical, cognitive, and behavioral measures and to track the natural history of the syndrome using repeated longitudinal assessments. In addition, this study will be aiming to identify biomarkers using neuroimaging, including diffusion tensor imaging and identify genetic factors which contribute to diverse phenotypes in patients with PMS.

Detailed description: Phelan-McDermid syndrome (PMS) or 22q13 Deletion syndrome, caused by a loss of one copy of the SHANK3 gene, is characterized by global developmental delay/intellectual disability, motor skills deficits, delayed or absent speech, and autism spectrum disorder. The goal of this study is to understand more about the PMS phenotype and the biological pathways associated with ID and ASD in the disorder, and to establish the foundation for future clinical trials in PMS and in other ID/ASD-associated disorders that share signaling pathways with PMS.

Individuals with PMS will be asked to participate in this study if they are 18 months or older with pathogenic deletions or mutations of the SHANK3 gene at time of enrollment, as well as healthy controls. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. Parents and unaffected siblings may also be asked to consent to have blood drawn for analysis.

The study involves 3 on site visits over 2 years. Study visits involve a physical exam, medical history questions, blood work and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Eligibility criteria: Inclusion Criteria:

* Individuals older than 18 months of age with pathogenic deletions or mutations of the SHANK3 gene
* English speaking individuals

Exclusion Criteria:

* Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
* For subjects involved in imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator
* For subjects involved in EEG/ ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or over age 11 at the time of enrollment.
* Unwilling or unable to comply with study procedures and assessments

Primary outcomes:
measure: Change in global cognitive ability at 12 months
timeFrame: 12 months
measure: Change in adaptive behavior at 12 months
timeFrame: 12 months
measure: Change in language abilities at 12 months
timeFrame: 12 months
measure: Change in motor functioning at 12 months
timeFrame: 12 months
measure: Change in autism symptoms at 12 months
timeFrame: 12 months
measure: Change in global cognitive ability at 24 months
timeFrame: 24 months
measure: Change in adaptive behavior at 24 months
timeFrame: 24 months
measure: Change is language abilities at 24 months
timeFrame: 24 months
measure: Change in motor functioning at 24 months
timeFrame: 24 months
measure: Change in autism symptoms at 24 months
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Alexander Kolevzon, MD
role: STUDY_CHAIR
References:
citation: Bassell J, Srivastava S, Prohl AK, Scherrer B, Kapur K, Filip-Dhima R, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Buxbaum JD, Kolevzon A, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome. Pediatr Neurol. 2020 May;106:24-31. doi: 10.1016/j.pediatrneurol.2020.01.006. Epub 2020 Jan 31.
citation: Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome. Pediatr Neurol. 2019 Jan;90:37-43. doi: 10.1016/j.pediatrneurol.2018.09.008. Epub 2018 Sep 21.