# Craniofacial Microsomia: Genetic Causes and Pathway Discovery

> **NIH NIH U01** · SEATTLE CHILDREN'S HOSPITAL · 2021 · $359,999

## Abstract

PROJECT SUMMARY
Craniofacial microsomia (CFM) is a common congenital condition (1:3,500) that affects the facial skeleton,
ears, and facial nerve among other facial and extracranial malformations. As a result, children with CFM
frequently require multiple interventions to restore their airway, feeding, hearing, and facial symmetry. The
lifelong health care needs associated with CFM substantially impact families, the health care system, and
society. The genetic risk factors for this condition remain largely unknown and large multi-center studies
addressing this fundamental gap in knowledge have not yet been conducted. In this application, we propose to
study the genetic etiology of CFM. Our long term objective is to identify the genetic and non-genetic risk factors
that contribute to CFM and evaluate the affected genetic pathways. We have identified 18 candidate genes for
CFM in our study of 29 trios (affected individual with CFM and non-affected parents). Based on our preliminary
findings and using the FACIAL network, an established network funded by the NIH specifically designed to
study CFM, we propose to conduct the following studies: Aim 1) define genes and gene pathways whose
expression is disrupted in the developing facial tissue that contributes to the CFM phenotype; Aim 2) identify
new candidate genes for CFM by using whole genome sequencing in 170 trios from banked samples (n=70)
and prospective enrollment (n=100); and Aim 3) detect mutations in 50 candidate genes identified in our
previous genetic studies in CFM and in Aims 1 and 2 using targeted capture sequencing on samples from 490
individuals with CFM. The combination of deep high throughput sequencing and gene expression studies in
relevant tissues from human and animal models will facilitate the identification of meaningful genetic causes for
this disorder. Our multidisciplinary FACIAL network has the infrastructure to investigate the genetic complexity
in CFM. Including both national and international sites, which have a higher prevalence of CFM, the FACIAL
network has the ability to collect high-quality data on a large (n=660) and well-characterized population. We
expect that our proposed studies will identify genes that cause CFM and generate insights into the pathways
that regulate craniofacial development, thus providing useful information for the study of CFM and other
craniofacial disorders. This research will positively impact health care for this population by identifying options
for molecular diagnosis, precise family and reproductive counseling, and for tailored clinical management and
primary prevention strategies for high-risk populations. This is of highest relevance to the NIDCR mission to
improve craniofacial health through research.

## Key facts

- **NIH application ID:** 10224167
- **Project number:** 5U01DE025862-05
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Carrie Lyn Heike
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,999
- **Award type:** 5
- **Project period:** 2017-09-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224167

## Citation

> US National Institutes of Health, RePORTER application 10224167, Craniofacial Microsomia: Genetic Causes and Pathway Discovery (5U01DE025862-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10224167. Licensed CC0.

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