During continuity clinic, one of the residents shared that he had seen a 17-year-old female in cardiology clinic for follow up of Marfan syndrome. He said that she had some stable aortic root dilatation on echocardiogram, but no problems with the rest of her cardiac anatomy. “We really looked at her mitral valve because if you remember that is commonly affected,” he said. He said that ophthalmology was also treating her for astigmatism, and she had gotten through puberty without her 10 degree scoliosis progressing. Overall, he reported that she was active with walking, bike riding and swimming and she saw the physical therapist intermittently for different joint pain. “She said that usually she just does her exercises and remembers not to be so aggressive with her activity and the pain was manageable,” he said. “They usually pound it into our heads about the aortic dilatation and dissection, but what I learned was with echos, close monitoring and potentially cardiac surgery, these patients have a normal life span which is great for her. She wants to go to college and eventually become a genetic counselor.”
Discussion
Marfan syndrome is an autosomal dominant, highly penetrant condition. Signs and symptoms are highly variable within an affected family and between families. The signs and symptoms also evolve with age. General prevalence is thought to be 4-6:100,000 and the main problem is on chromosome 15 for the gene that encodes for Fibrillin-1. “Fibrillin-1 is a major component of extracellular matrix structures called microfibrils, which are found in tissues alone or closely associated with elastin fibers.”
While it is autosomal dominant, 25% of cases appear to arise de novo. Also there may be mosaicism and therefore different family members may or may not be affected. Sporadic cases tend to have more severe problems, and the neonatal form occurs because of a de novo mutation that is very severe. Diagnosis is based on Ghent criteria but can be more difficult in pediatric age patients as they may not have all of the criteria or not meet specific adult criteria. The criteria are a combination of physical characteristics, family history and genetic testing. Findings of aortic root dilatation and ectopic lentis are important for diagnosis and patient management. Family members should be screened for the gene and physical signs and potential problems based on the pedigree.
Treatment for cardiac issues is monitoring for aortic and other anatomic changes. There are criteria for preventative cardiac surgery if the aortic root becomes a certain size or is increasing too quickly. Beta-blockers are used to help prevent dilatation. Other cardiac problems are managed as they arise. Patients are recommended to have regular low-intensity, low-impact exercise. Routine eye examinations are need to prevent complications. Skeletal and other problems are managed as they arise with an emphasis on function.
Learning Point
Problem associated with Marfan Syndrome include:
- Cardiac
- Cause: weakening of the elastin in the blood vessels which usually stabilizes the expansion and recoil of the vessels
- ***Aortic root dilatation and aneurysms – “Aortic root dilatation is typically present at the first echocardiography in patients who are eventually diagnosed with [Marfan syndrome], even if it is performed in infancy.” Aortic dissections – Type A – ascending aortic dissection with high morbidity and mortality. These were the major cause of death but are less common because of monitoring and preventative surgery for aortic root dilatations. Current life expectancy is that of the general population. Type B dissections occur just distal to the take off of the left subclavian artery. They can also have morbidity and mortality but are less common.
- Pulmonary artery dilatation
- Valve dysfunction – Aortic valve, mitral valve prolapse occurs in up to 90% of patients
- Cardiomyopathy – 5-30%
- Arrhythmias
- Ophthalmological
- Cause: can be found in all parts of the eye but especially around the ciliary body which causes problems with the lens
- ***Ectopia lentis
- Hypoplasia of iris
- Miosis
- Astigmatism
- Myopia
- Skeletal
- Cause: bone formation and function are affected despite the low abundance of microfibrils/elastin in the skeletal matrix
- ***Tall stature with disproportionately long extremities including digits.
- Flexible joints including fallen foot arches
- Spine abnormalities – scoliosis, kyphosis, lordosis
- Sternum abnormalities – pectus carinatum or excavatum
- Indented hip sockets
- Mental health problems
- Overall quality of life is reported as normative but there is a decrease in psychosocial functioning
- Cognitive dysfunction
- Chronic pain
- Anxiety
- Depression
- Schizophrenia
- Other
- Dural ectasia
- Pneumothorax
- Spinal canal enlargement in the lumbar spine
- Striae
- Caries
- Cysts of kidney or liver
- Fatigue
- Headache
- Urogenital problems due to laxity such as incontinence
- Skeletal myopathy
*** – some of the most common problems/physical findings
Questions for Further Discussion
1. How common are aortic aneurysms? A review can be found here
2. What are causes of sudden cardiac death in the pediatric age range? A review can be found here
3. What is in the differential diagnosis of excessive height? A review can be found here
Related Cases
- Disease: Marfan Syndrome
- Symptom/Presentation: Genetic Disorder | Syndromes
- Specialty: Cardiology / Cardiovascular-Thoracic Surgery | Genetics | Ophthalmology | Orthopaedic Surgery and Sports Medicine
- Age: Teenager
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for these topics: Marfan Syndrome and Connective Tissue Disorders.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Lidal IB, Bathen T, Johansen H, Velvin G. A scoping review presenting a wide variety of research on paediatric and adolescent patients with Marfan syndrome. Acta Paediatr. 2020;109(9):1758-1771. doi:10.1111/apa.15186
Magotteaux S, Bulk S, Farhat N, Sakalihasan N, Defraigne JO, Seghaye MC. [Marfan syndrome in childhood and adolescence]. Rev Med Liege. 2016;71(7-8):342-348.
Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. doi:10.1038/s41572-021-00298-7
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa