Marfan syndrome is an autosomal dominant, multisystem disorder characterized by cardiovascular, skeletal, and ocular abnormalities.  One of the major features of Marfan syndrome (MFS) and the majority of Marfan-related disorders is an increased risk for Thoracic Aortic Aneurysms (TAAs), which if left untreated, has a high morbidity and mortality rate.  Identifying individuals at risk for TAAs is complicated by the fact that sudden cardiac death is often the major first clinical signs.

Diagnosis of MFS or Marfan-like syndromes is also often challenged by the extensive phenotypic variability within and between families, phenotypic overlap with clinically related disorders, and age-dependent symptoms that appear over time.  Marfan syndrome is the most common inherited form of syndromic TAAs, aneurysms that occur with a wide range of clinical abnormalities across various body systems.  Other syndromic TAA conditions include Marfan-like Syndrome, Loeys-Dietz Syndrome, Ehlers-Danlos Syndrome (EDS), and Arterial tortuosity syndrome.  Familial nonsyndromic TAAs are characterized by aneurysms without the presence of other clinical manifestations and typically follow an autosomal dominant pattern of inheritance.  Three genes have been associated with familial nonsyndromic TAAs: TGFBR2 in TAA2, ACTA2 in TAA4, MYH11 in familial TAA and patent ductus arteriosus.

Sporadic forms of TAAs have also been reported. To date, ten genes (ACTA2, CBS, FBN1, FBN2, MYH11, COL3A1, SLC2A10, SMAD3, TGFBR1, and TGFBR2) have been associated with various forms of MFS and Marfan-related syndromes.  Establishing the cause of Marfan and Marfan-like syndromes is essential for prognosis, management, and genetic counseling.