Clinical Guidance

FBN1-related Marfan syndrome (Marfan syndrome), a systemic disorder of connective tissue, is part of a broad phenotypic continuum associated with heterozygous FBN1 pathogenic variants that ranges from mild (features of Marfan syndrome in one or a few systems) to severe (rapidly progressive multiorgan disease in neonates). Cardinal manifestations of Marfan syndrome involving the ocular, skeletal, and cardiovascular systems have a high degree of clinical variability. Table 3. FBN1-Related Marfan Syndrome: Frequency of Cardinal Manifestations in Adults by System

Source: GeneReviews — "FBN1-Related Marfan Syndrome"

Penetrance

Although intrafamilial clinical variability can be extensive, FBN1-related Marfan syndrome shows high clinical penetrance.

Source: GeneReviews — "FBN1-Related Marfan Syndrome"

Differential Diagnosis

Loeys-Dietz syndrome (LDS) is an autosomal dominant condition that includes many features of Marfan syndrome (long face, downslanted palpebral fissures, highly arched palate, malar hypoplasia, micrognathia, retrognathia, pectus deformity, scoliosis, arachnodactyly, joint laxity, dural ectasia, and aortic root aneurysm with dissection). Some features of Marfan syndrome are either less common or prominent (dolichostenomelia) or absent (ectopia lentis). Unique features can include widely spaced eyes, broad or bifid uvula, cleft palate, hydrocephalus (rare), Chiari I malformation, blue sclerae, exotropia, craniosynostosis, cervical spine instability, talipes equinovarus, soft and velvety skin, translucent skin, easy bruising, milia, generalized arterial tortuosity, and frequent aneurysms and dissection throughout the arterial tree. Individuals with LDS are at risk for cervical spine malformation and/or instability, food and environmental allergies, asthma, eczema, eosinophilic esophagitis, and inflammatory bowel disease (rare). Aortic aneurysms in LDS behave very differently from those in Marfan syndrome, with frequent dissection and rupture at small dimensions and in early childhood. LDS results from a heterozygous pathogenic variant in SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, or TGFBR2. Shprintzen-Goldberg syndrome (SGS). The phenotype of SGS is distinctive but shows significant overlap with LDS and Marfan syndrome. Major distinctions include the unique and highly penetrant developmental delay in SGS, with less frequent and milder cardiovascular manifestations than in either Marfan syndrome or LDS. Table 5. Comparison of Clinical Features in Marfan Syndrome, Loeys-Dietz Syndrome, and Shprintzen-Goldberg Syndrome

Source: GeneReviews — "FBN1-Related Marfan Syndrome"

Clinical Guidance

The following should be avoided:

• Contact sports, competitive sports, and isometric exercise. Note: Individuals can and should remain active with aerobic activities performed in moderation.

• Activities that cause joint injury or pain

• Agents that stimulate the cardiovascular system including routine use of decongestants. Caffeine can aggravate a tendency for arrhythmia.

• Agents that cause vasoconstriction, including triptans

• LASIK eye surgery to correct refractive errors

• For individuals at risk for recurrent pneumothorax, breathing against resistance (e.g., playing a brass instrument) or positive pressure ventilation (e.g., SCUBA diving)

• Fluoroquinolone antibiotics due to the considerable evidence suggesting exacerbation of predisposition for aneurysm and dissection

• Avoidance of classes of antihypertensive agents (e.g., calcium channel blockers, ACE inhibitors) where there is an absence of direct evidence for their efficacy or safety in individuals with Marfan syndrome

Source: GeneReviews — "FBN1-Related Marfan Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "FBN1-Related Marfan Syndrome"