Emergence of the Natural History of Myhre Syndrome: 47 Patients Evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016–2023)

    May 2024 in “ American Journal of Medical Genetics Part A ”
    Angela E. Lin, Eleanor R. Scimone, Robyn P. Thom, Duraisamy Balaguru, T. Bernard Kinane, Peter P. Moschovis, Michael S. Cohen, Weizhen Tan, Cole Hague, Katelyn Dannheim, Lynne L. Levitsky, Evelyn Lilly, Daniel DiGiacomo, Kara M. Masse, Sarah Kadzielski, Claire Zar‐Kessler, Leo C. Ginns, Ann M. Neumeyer, Mary K. Colvin, Jack S. Elder, Christopher P. Learn, Hongmei Mou, Kathryn M. Weagle, Karen Buch, William E. Butler, Kenda Alhadid, Patricia L. Musolino, Sadia Sultana, Dhrubajyoti Bandyopadhyay, Otto Rapalino, Zachary S. Peacock, Elizabeth L. Chou, Gena Heidary, Aaron T. Dorfman, Shaine A. Morris, James D. Bergin, Jonathan H. Rayment, Lisa A. Schimmenti, Mark E. Lindsay, MGH Myhre Syndrome Study Group
    TLDR Myhre syndrome symptoms worsen over time, with specific genetic variants affecting severity.
    The study at Massachusetts General Hospital Myhre Syndrome Clinic evaluated 47 patients with Myhre syndrome, a rare condition caused by SMAD4 variants, from 2016 to 2023. Most patients (81%) returned for follow-up, and all showed symptom progression over at least 5 years. The study identified specific SMAD4 variants, with p.Ile500Val being the most common (49%). Patients with the p.Arg496Cys variant had fewer instances of hearing loss, growth restriction, and aortic hypoplasia. The p.Ile500Thr variant was associated with moderate/severe aortic hypoplasia in 60% of cases, though the small sample size (n=5) limited statistical analysis. Two deaths were reported due to cardiovascular disease and airway stenosis. The research highlights the need for evidence-based guidelines and further natural history studies to support future therapies.
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