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Patient Story

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A 14-year-old girl is brought to her pediatrician for a routine health maintenance visit. The pediatrician notes that she is tall for her age, has long, slender fingers, hypermobile joints, and that her arm span is longer than her body span (Figures 223-1 to 223-3). She also has a high arched palate and a systolic murmur. The pediatrician refers the girl to a cardiologist, who performs an echocardiogram, which reveals mitral valve prolapse without regurgitation, and dilatation of the aortic root. The pediatrician and cardiologist suspect that the child has Marfan syndrome and order a test for fibrillin 1 mutation, which confirms the diagnosis. Her pediatrician plans a multidisciplinary team for the girl, including baseline and follow-up ophthalmology examinations, and close follow-up visits with the cardiologist, orthopedist, and geneticist.

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FIGURE 223-1

Tall stature, reduced upper to lower segment ratio, and increased arm-span-to-height ratio in a 14-year-old girl with Marfan syndrome. (Used with permission from Elumalai Appachi, MD.)

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FIGURE 223-2

Arachnodactyly (long, slender fingers) in the same girl as in Figure 223-1. This is a non-specific feature of Marfan syndrome. (Used with permission from Elumalai Appachi, MD.)

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FIGURE 223-3

Hypermobility of the thumb joint in Marfan syndrome illustrated by the same girl as Figures 223-1 and 223-2. (Used with permission from Elumalai Appachi, MD.)

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Introduction

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Marfan syndrome (MFS) is a heritable disorder of connective tissue resulting from mutations in the gene encoding the extracellular matrix protein fibrillin 1(FBN1). Individuals with MFS manifest variable clinical features, which often involve the skeletal, cardiovascular, and ocular systems.

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Epidemiology

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  • The incidence of this disorder is about 1 per 5,000 to 10,000 births.1

  • MFS is inherited in an autosomal dominant manner; thus, there is a 50 percent chance of an offspring inheriting the condition from the affected parent.

  • Approximately 1/3 of cases are sporadic due to de novo mutations; new mutations are often associated with advanced paternal age.

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Etiology and Pathophysiology

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  • MFS is associated with abnormal biosynthesis of fibrillin-1, which is the major constituent of microfibrils. Mutations in FBN1 are found in about 95 percent of patients who meet the diagnostic criteria for Marfan syndrome.2,3

  • The FBN1 locus resides on the long arm of chromosome 15 (15q21) and the gene is composed of 65 exons. More than 1,000 mutations distributed throughout FBN1 have been identified, many being unique to a given family.4,5

  • The condition results from a structural deficiency of connective tissues. The decreased fibrillin-1 leads to a primary derangement of elastic fiber deposition, ...

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