Marfan’s syndrome

A number of rare genetic diseases involve collagen abnormalities, including Marfan s syndrome and the Ehlers-Danlos syndromes, which result in hyperextensible joints and skin. The formation of atheroselerotie plaques, which cause arterial blockages in advanced stages, is due in part to the abnormal formation of collagenous structures in blood vessels. 

Collagen abnormalities, such as Ehlers-Damlos syndrome. Marfan s syndrome, pseudoxanthoma elasticum. and osteogenesis imperfecta... 

The considerably increased (20-40-fold) excretion of acid mucopolysaccharides suggests that Marfan s syndrome also represents a defect in the metabolism of connective tissues (B4). The major mucopolysaccharides excreted were indistinguishable in their electrophoretic mobilities from hyaluronic acid and chondroitin 4- or 6-sulfate. Examination of the levels of mucoproteins and acid mucopolysaccharides in the serum of cases of Marfan s syndrome revealed an increase in the latter, while the former is decreased. Bacchus (B1) considers that this pattern might be of clinical and pathogenetic significance. 

B4. Berenson, G. S., and Serra, M. T., Mucopolysaccharides in urine from patients with Marfan s syndrome. Federation Proc. 18, 190 (1959). 

McKusick, Victor A. The Cardiovascular Aspects of Marfan s Syndrome Circulation 11 (1955) 321-342. 

A 42-year-old woman with Marfan s syndrome, who had previously had an aortic root and valve replacement, presented with fever and polyarthralgia 6 days after receiving acupuncture for back pain (95). Examination of the valve showed no abnormalities, but S. aureus was grown from blood cultures. Extensive investigations did not identify a cause for the infection. Her condition deteriorated despite antibiotic therapy, and emergency aortic root and valve replacement became necessary. She eventually made a full recovery. 

Nambiar P, Ratnatunga C. Prosthetic valve endocarditis in a patient with Marfan s syndrome following acupuncture. J Heart Valve Dis 2001 10(5) 689-90. 

EDS VIII is associated with aggressive periodontal disease. It may be caused by a mutation in one or more genes other than the collagen gene (COL2A1) on chromosome 12. Individuals resemble Marfan s syndrome (Table 6.1), but have normal teeth. They display excessive bleeding around the knees and fragile skin, hallmarks of vascular EDS. 

Fibrillin is encoded by a gene located in the long arm of chromosome 15. Mutations in the fibrillin gene lead to an autosomal dominant trait known as Marfan s syndrome. The incidence of this disorder is 1 10,000, and 15-30% of cases are caused by new mutations in the fibrillin gene. Consistent with the function of fibrillin in the elastic connective tissues, the clinical manifestations present as disorders of cardiovascular, musculoskeletal, and opthalmic systems. For example, dissecting aneurysm of... 

Sjoerdsma, A., Davidson, J. D., Udenfriend, S., and Mitoma, C., Increased excretion of hydroxyproline in Marfan s syndrome. Lancet II, 994r-995 (1958). 

Advanced maternal age is associated with higher risks for chromosomal disorders (e.g., Down s syndrome, trisomy 13), while advanced paternal age is associated with higher risks for new mutations (e.g., those producing achondroplasia or Marfan s syndrome). 

Cystathionine synthetase, a pyridoxal phosphate (vitamin Be) enzyme, catalyzes the condensation of serine and homocysteine to form cystathionine. A deficiency of this enzyme leads to a buildup of homocysteine, which oxidizes to form homocystine. This may result in mental retardation, but sometimes causes dislocated lenses and a tall, asthenic build reminiscent of Marfan s syndrome. Patients with homocystinuria also have a clotting diathesis, requiring care to avoid dehydration during anesthesia. Their cysteine deficiency must be made up from dietary sources. In some cases, dietary intake... 

Marfan s syndrome is caused by which of the following mechanisms ... 

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