The genetics of Marfan syndrome and related conditions is reviewed in an updated AAP clinical report that aims to help pediatricians recognize the features of the syndrome and care for patients in a medical home.
Marfan syndrome is a heritable connective tissue disorder that affects many organ systems. It is caused by a pathogenic change in FBN1, the gene that codes for fibrillin-1.
While some Marfan cases were thought to be caused by pathogenic variants in other genes, such as TGFBR1and TGFBR2, it now is known that these gene changes cause other conditions, including Loeys-Dietz syndrome and isolated aortopathies.
The clinical report, updated from 2013, reviews the many pathogenic variants that have been described in FBN1 and their relationship to the clinical presentation of patients.
The report, Health Supervision for Children and Adolescents With Marfan Syndrome, from the AAP Council on Genetics, is available at https://doi.org/10.1542/peds.2023-061450 and will be published in the April issue of Pediatrics.
Among the guidance is an expanded section on the cardiovascular system, the major source of morbidity and mortality in patients with this syndrome. The section educates pediatric primary care providers about the cardiac care of their patients but defers to the preferences of the patient’s pediatric cardiologist.
Aortic diameter size now is measured using z-scores, and the recommendations for surveillance have changed somewhat. In addition, the cardiovascular therapies have changed because of extended trials with new medications, specifically angiotensin-receptor blockers. Medications that are contraindicated for children and adolescents with Marfan syndrome also are discussed.
The major addition to the musculoskeletal section is a review of cervical spine anomalies that are seen in a higher prevalence and may need to be monitored.
New sections on pain and quality of life underscore the need for parents and caregivers to recognize the toll of the condition on children and adolescents. The medical home is particularly important for adolescents as they transition to adulthood.
A discussion on what has been described as the severe presentation of Marfan syndrome during infancy emphasizes that this presentation is part of the severity continuum and not a separate condition. Some individuals are diagnosed with Marfan syndrome in infancy due to a family history or other factors but do not have a severe presentation associated with a high mortality.
The report also includes sections on growth and development, ocular issues, pulmonary/airway and sleep issues, dural ectasia, dental concerns, pain and physical activity, and prenatal and psychosocial issues.
Dr. Burke is a lead author of the clinical report and chair of the AAP Council on Genetics Executive Committee.