About Frances High, MD, PhD

Dr. High is a physician-scientist in the field of human genetics with specific interests in developmental biology and birth defects. She is board-certified clinician in the fields of Clinical Genetics (ABMGG) and Pediatrics (ABP). Her clinical interests include general clinical genetics, male sex chromosome aneuploidies, genetics of congenital malformations, and genetics of neurodevelopmental disorders. In addition, she has a background in basic science research in developmental biology, specializing in murine models of birth defects. She has a research interest in the genetics of congenital anomalies, especially congenital diaphragmatic hernia (CDH), and currently serves as the lead clinical geneticist at the Pediatric Surgical Research Laboratories at Massachusetts General Hospital and Boston Children’s Hospital as part of a multi-center collaborative study on the genetics of CDH. Dr. High is also the co-director of the MGH Klinefelter syndrome clinic, which is designed to provide multi-specialty clinical care to patients of all ages with Klinefelter syndrome and related sex chromosome variations.  She is also an investigator for the Undiagnosed Diseases Network, a multi-center initiative to bring premier clinical expertise, the latest in diagnostic techniques, and interface with researchers to diagnose and learn from the most challenging medical cases.

Departments, Centers, & Programs:

Clinical Interests:



Mass General for Children: Genetics Program
55 Fruit St.
Yawkey Center for Outpatient Care
Suite 6C
Boston, MA 02114
Phone: 617-726-1561

Medical Education

  • M.D.; Ph.D., University of Pennsylvania
  • Residency, Boston Children's Hospital
  • Fellowship, Boston Children's Hospital

American Board Certifications

  • Clinical Genetics and Genomics, American Board of Medical Genetics and Genomics
  • Pediatrics, American Board of Pediatrics

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Understanding the genetic basis of congenital diaphragmatic hernia (CDH).

I am serving as the lead clinical geneticist for one of the largest and longest-running studies on the genetics of CDH, a common birth defect with high morbidity and mortality. This work contributes significantly to our understanding of the genetics of CDH, identifying critical genes and pathways with sequence variations and copy number variations, and correlating with disease phenotype and severity. Our long-term goal is to harness our understanding of the genetic basis of CDH to improve diagnostic, prognostic, and therapeutic options for these patients.


    1. Longoni M, Russell MK, High FA, Darvishi K, Maalouf FI, Kashani A, Tracy AA, Coletti CM, Loscertales M, Lage K, Ackerman KG, Woods SA, Ward-Melver C, Andrews D, Lee C, Pober BR and Donahoe PK. Prevalence and Penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia. Genet. 87(4):362-7, 2015.
    2. Longoni M*, High FA*, Russell MK*, Kashani A*, Tracy AA, Coletti CM, Hila R, Shamia A, Wells J, Ackerman KG, Wilson JM, Bult CJ, Lee C, Lage K, Pober BR and Donahoe PK. Molecular pathogenesis of congenital diaphragmatic hernia revealed by integrating exome sequencing, developmental data and bioinformatics. Proc Natl Acad Sci USA, 111(34):12450-5, 2014. *equal contributions
    3. High FA, Bhayani P, Wilson JM, Bult CJ, Donahoe PK, Longoni M. De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia. Am J Med Genet A., 170(9):2457-61, 2016.
    4. Donahoe PK, Longoni M, High FA. Polygenic Causes of Congenital Diaphragmatic Hernia Produce Common Lung Pathologies. Am J Pathol, 186(10):2532-43, 2016.
    5. Longoni M, High FA, Qi H, Joy MP, Hila R, Coletti CM, Wynn J, Loscertales M, Shan L, Bult CJ, Wilson JM, Shen Y, Chung WK, Donahoe PK. Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. Hum Genet. 136(6):679-691, 2017.

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