# Investigating the Genetic Landscape of Cerebral Palsy

> **NIH NIH K23** · BOSTON CHILDREN'S HOSPITAL · 2021 · $196,020

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cerebral palsy (CP) is the most common childhood-onset motor disability, affecting 764,000 individuals
in the United States alone. The lifetime medical costs for a single individual with CP are estimated at $1.4M,
which represents a substantial healthcare and economic impact. A diverse set of risk factors contributes to CP,
including prematurity, intrauterine infection, and hypoxic ischemic encephalopathy. In approximately 20% of
cases, there are no clear perinatal risk factors (“cryptogenic CP”). There is accumulating evidence from rare
familial cases and a growing number of isolated cases suggesting that cryptogenic CP may result in part from
single gene disorders, including over 50 treatable inborn errors of metabolism. However, these studies have
involved small numbers of participants, with patient populations characterized using administrative data with
limited attention to precise clinical characterization. The full breadth of the genetic landscape of CP is
unknown.
 We hypothesize that a substantial portion of individuals with cryptogenic CP will have a pathogenic or
likely pathogenic variant in a single gene providing an explanation for their symptoms. We propose rigorously
phenotyping a large prospective cohort of individuals with both cryptogenic and non-cryptogenic CP who have
undergone exome sequencing through an institutional genomics pilot study, and then analyzing exome
sequencing data to determine the presence of single gene disorders in each subgroup.
 To accomplish these goals, we will classify patients as cryptogenic CP or non-cryptogenic CP. We will
systematically, rigorously, and longitudinally characterize neurological, motor, communication, and
neuroimaging phenotypes using research measures validated for CP. Next, we will analyze exome data using
an institutional pipeline for variant interpretation. Finally, we will build a statistical model that correlates the
presence of a genetic disorder with phenotypic measures in order to help predict which individuals with CP are
most likely to have a single gene disorder.
 If applied to the population at large, the proposed work could lead to identification of single gene
disorders in thousands of individuals with CP, including treatable conditions where a molecular diagnosis may
positively alter a child's developmental trajectory. Determining etiology represents a first step in understanding
the biological substrates of CP needed for developing rational therapeutics for this highly prevalent condition.

## Key facts

- **NIH application ID:** 10301468
- **Project number:** 1K23NS119666-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Siddharth Srivastava
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,020
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301468

## Citation

> US National Institutes of Health, RePORTER application 10301468, Investigating the Genetic Landscape of Cerebral Palsy (1K23NS119666-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10301468. Licensed CC0.

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