Genetic Diseases of Connective Tissue
Rheumatology · Other Rheumatologic Diseases 🎯 Practice these cards
Marfan syndrome is caused by mutations in the ____ gene, which encodes fibrillin-1, and is inherited in an ____ pattern.
Marfan syndrome is the most common syndromic form of heritable thoracic aortic aneurysm disease. It is caused by mutations in FBN1, which encodes fibrillin-1, and is inherited in an autosomal dominant pattern; about one-fourth of cases are sporadic new mutations. Incidence is ~1 in 3000–5000 births.
Vascular Ehlers-Danlos syndrome is caused by mutations in ____ and has a median survival of only ____ years.
Vascular EDS is the most severe EDS subtype, caused by heterozygous COL3A1 mutations (type III collagen). It is characterized by fragility of medium/large arteries and hollow organs — arterial dissection/rupture, spontaneous sigmoid colon perforation, and third-trimester uterine rupture. Median survival is only 40–50 years; by age 40 ~90% have had a major event.
The 2017 international classification recognizes ____ clinical subtypes of EDS; the most common, ____ EDS, is the only subtype with no identified causative gene.
The 2017 International EDS Consortium classification recognizes 13 clinical EDS subtypes. Hypermobile EDS (hEDS) is the most common (80–90% of cases) and is the ONLY subtype with no identified causative gene — it remains a clinical diagnosis. All other subtypes have defined molecular bases.
Per the 2022 ACC/AHA guideline, prophylactic aortic root replacement in Marfan syndrome is recommended at a root diameter ≥____ cm, or ≥4.5 cm with high-risk features.
The 2022 ACC/AHA aortic disease guideline recommends prophylactic aortic root replacement in Marfan syndrome at a root diameter ≥5.0 cm, or ≥4.5 cm with high-risk features (family history of dissection, rapid growth ≥0.3 cm/yr, diffuse root/ascending dilation, marked vertebral-artery tortuosity). Medical therapy is a beta-blocker or ARB at maximally tolerated dose.
The hallmark features of osteogenesis imperfecta are susceptibility to ____, bone deformity, and growth deficiency; most patients have defects in type ____ collagen.
Osteogenesis imperfecta (OI) hallmarks are increased susceptibility to skeletal fractures, bone deformity, and growth deficiency. Most patients have defects in the structure or quantity of type I collagen (COL1A1/COL1A2). Secondary features include blue sclerae, dentinogenesis imperfecta, hearing loss, and ligamentous laxity.
In patients with osteogenesis imperfecta, the leading cause of death is ____ disease.
In OI, pulmonary disease is the leading cause of death — from restrictive/obstructive physiology due to scoliosis and chest-wall deformity plus intrinsic type I collagen defects of the lung parenchyma. Adults also develop mitral regurgitation and aortic-root dilatation (echo every 3–5 years when asymptomatic).
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