Siddharth Srivastava Lab

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Projects

Establishment of novel genetic causes of ID and CP

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Gene/Variant Discovery for CP

Status
ongoing
Rationale
Cerebral palsy (CP) is the most common childhood-onset motor disability. A diverse set of risk factors contributes to CP. In approximately 20% of cases, there are no clear perinatal risk factors, suggesting the possibility of an underlying genetic disorder. Understanding the genetic landscape of CP has implications for diagnosis as well as treatment.
Description
In this project, we are using genome sequencing to discover genetic disorders presenting as cerebral palsy, in instances where there are known acquired risk factors for CP, as well as those where there are no acquired risk factors for CP.
Funding Sources
  1. NIH K23
Acknowledgments

This study is part of the Children’s Rare Disease Cohorts (CRDC) Initiative, supporting gene discovery for different disease cohorts.

Characterization of specific neurodevelopmental deficits in genetic NDDs

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Status
ongoing
Rationale
Kleefstra Syndrome (KLEFS1) is a complex neurodevelopmental genetic syndrome characterized by a high prevalence of autism and intellectual disability, as well as severe neuropsychiatric illness. The latter can include severe insomnia, psychosis, catatonia, bipolar disorder, obsessive compulsive disorder, and/or developmental regression. The neuropsychiatric illness in KLEFS1 represents a significant concern for affected families and represents a priority area for intervention. Notably, there is some limited data suggesting that use of certain antipsychotics, including olanzapine, may potentially restore functioning in individuals with KLEFS1 who have experienced insomnia, psychosis, and developmental regression.
Description
In this project, we are studying the relationship between sleep and neurospychiatric illness in individuals with KLEFS1, pairing functional studies of EHMT1 biology using patient-derived fibroblasts with standardized neurodevelopmental assessments, standardized sleep assessments, and Fitbit-based actigrapahy.
Funding Sources
  1. Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center
Acknowledgments

This study is a joint collaboration with the lab of Jonathan Lipton, focused on circadian biology in neurodevelopmental disorders, and the lab of Joe Kossowsky, focused on health information from wearable devices.

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Natural History Study of Kleefstra Syndrome

Status
ongoing
Description
In this project, we are carrying out a longitudinal natural history study of Kleefstra Syndrome using standardized neurodevelopmental assessments, EEG biomarkers, and biometric recordings of sleep.
Funding Sources
  1. IDefine

Clinical practice changes regarding genetic testing for NDDs

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Defining the Role of Genetic Testing in the Diagnostic Workup of Cerebral Palsy

Status
ongoing
Description
We are carrying out a comparative effectiveness study to measure the effectiveness and impact of three testing approaches in CP: (1) brain MRI alone, (2) brain MRI plus ES, and (3) brain MRI plus GS. Our long-term goal is to provide doctors and families with evidence to guide decision-making, reduce confusion, and help update official medical society practice guidelines for diagnostic testing for CP.
Funding Sources
  1. PCORI