# A multidisciplinary approach for identifying and characterizing novel congenital malformation syndromes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $380,363

## Abstract

Over 50% of children with multiple malformations seen in medical genetics clinics for a
suspected genetic syndrome never receive a diagnosis, which leaves unanswered questions
about prognosis and medical/reproductive planning. While individual multiple malformation
syndromes (MMS) are rare diseases (many <1 in 200,000 births), in combination, these
conditions are costly and medically severe. There have been some recent successes in
developing orphan treatments for some of these rare syndromes, but this only represents the
“tip of the iceberg,” and it is thought that there are many more recognized and unrecognized
MMS that will be amenable to new therapies. The next steps toward identifying therapeutic
targets and biomarkers of outcomes for these rare diseases are to 1) identify these MMS, 2)
characterize their clinical profile, and 3) uncover the underlying genetic causes. To accomplish
these goals, we will first identify “new” MMS (i.e., not described in the literature) using
international data from two large networks that represent most of the major birth defects
registries worldwide. By leveraging these population-based data, we will address the limitations
of previous approaches for identifying new MMS (i.e., clinical case reports based on a small
number of cases identified in a single clinic). Second, we will verify the occurrence of
“unconfirmed” MMS (i.e., unconfirmed case reports of only a few cases) using our international
network of birth defects registries to address the possibility that that the malformations patterns
reported in these previous case reports occurred due to chance alone. We will use a network of
medical genetics clinics we have assembled to recruit clinical patients with the new MMS and
the unconfirmed MMS that we validate. We will conduct systematic phenotyping of these cases
to better delineate the clinical profiles of these syndromes. We will also collect DNA samples
from these patients and their families and conduct exome sequencing, which may identify
pathways that could lead to therapeutic targets for these rare but clinically significant conditions.

## Key facts

- **NIH application ID:** 10443745
- **Project number:** 5R01HD093660-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** A.J. Agopian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,363
- **Award type:** 5
- **Project period:** 2018-08-25 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443745

## Citation

> US National Institutes of Health, RePORTER application 10443745, A multidisciplinary approach for identifying and characterizing novel congenital malformation syndromes (5R01HD093660-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10443745. Licensed CC0.

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