Projects

Establishment of novel genetic causes of ID and CP

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, including certain treatable inborn errors of metabolism. Therefore, understanding the genetic landscape of CP has implications for diagnosis as well as treatment.

Description

In this project, we are using exome and genome sequencing to discover genetic disorders presenting as cerebral palsy, in instances where there are risk factors for CP, as well as those where there are no risk factors for CP.

Funding Sources

1. National Institutes of Health - National Institute of Neurological Disorders and Stroke (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

Circadian Biology of EHMT1 and Sleep-Related Neurodevelopmental Collapse in Kleefstra Syndrome

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 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.