Connective Issues Spring 2022

registries of health information and samples, like blood plasma, from individuals a ff ected with Marfan syndrome and Loey-Dietz to identify patterns related to these conditions and aid in the development of clinical trials and treatment plans. • Increasing collaboration amongst researchers and making it easier for them to collect and share relevant health information related to Marfan syndrome and Loeys-Dietz. Audiologic and Otologic Clinical Manifestations of Loeys-Dietz Syndrome: A Heritable Connective Tissue Disorder Aortic and vascular complications are often the focus of patient care practices and research related to Loeys Dietz, with some additional attention paid to topics like orthopedic issues, asthma, and food allergies. In this article published in the journal Otolaryngology – Head and Neck Surgery, the authors describe their study of 36 children and adults with Loeys-Dietz types 1-4 and how the condition a ff ected their hearing, ears, and face/head. Researchers found mild to moderate hearing loss in 69% of the study participants. A split uvula (the tissue at the back of the throat), hard cleft palate, and post-tympanos tomy tympanic membrane perforation (when a hole exists between the external and middle ear) were more common in LDS-1 and LDS-2 than LDS-3 and LDS-4. Based on their fi ndings, the study team recommended healthcare professionals pay close attention to the hearing and ear health of individuals with Loeys Dietz to manage existing issues and prevent further complications from developing. phenotypic variability and response to treatment in the largest genotype-phenotype pediatric Marfan syndrome cohort, was recently published in Genetics in Medicine. The lead researchers were Dr. Bart Loeys, a member of the Loeys-Dietz Syndrome Foundation Medical Advisory Council and Dr. Josephine Meester from Belgium as well several members of the Foundation’s Professional Advisory Board: Hal Dietz, MD, Johns Hopkins; Shaine Morris, MD, PhD, Texas Children’s Hospital; and Ron Lacro, MD, Boston Children’s Hospital; and several more. In their research, Dr. Loeys and colleagues found that the more severe cardiovascular phenotype was not restricted to mutations in the neonatal FBN1 region, exon 25-33 but was also seen in exons 26 to 49. They also found that ectopia lentis (lens dislocation) is more prominent in some genetic mutations, and there is no di ff erence in the response to treatment between di ff erent types of mutations. STUDY YIELDS NEW FINDINGS

RESEARCH The Loeys-Dietz Syndrome Foundation, a division of The Marfan Foundation, is proud to support clinical and basic science research on Loeys-Dietz syndrome, and it is an integral part of our mission. There have been several recent research articles, all of which have a signi fi cant impact on LDS education and our community. Here are two recent publications. Toward Precision Medicine In Vascular Connective Tissue Disorders In this review published in the American Journal of Medical Genetics , the authors outlined the history of Marfan syndrome and Loeys-Dietz syndrome. The authors identi fi ed a number of obstacles to overcome to advance research and o ff ered recommendations including: • Getting a better understanding of laboratory-based technologies, such as induced pluripotent stem cells (adult stem cells “reprogrammed” to mimic embryonic stem cells), mouse models, and gene editing technologies (editing DNA) and how they can be used to learn more about Marfan and Loeys-Dietz and improve care. • Expanding imaging beyond traditional echocardiograms and CT scans for individuals with Marfan or Loeys-Dietz to help predict the severity of disease or support diagnosis. • Supporting the development and expansion of large History was made from 2007 to 2014 when the Pediatric Heart Network of the National Heart, Lung, and Blood Institute (NHLBI) conducted a 608-person clinical trial on losartan and beta blockers in treating Marfan syndrome. The Foundation played a critical role in the enrollment of people in the study. Never before had such a large study group on Marfan been conducted by the NHLBI and the Foundation was determined to maximize the research opportunity that having such a large cohort provided. Because of this, the Foundation funded ancillary studies to the original clinical trial to further advance research on Marfan syndrome. While the clinical trial results were announced in 2014, the ancillary studies continue to yield results, most recently with the publication of a study on the most severe cardiovascular features that are associated with neonatal Marfan syndrome. This genetics study, Molecular characterization and investigation of the role of genetic variation in

To view all research studies, visit the research tab at LoeysDietz.org.

PHN ANCILLARY

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Spring 2022