Marfan’s Syndrome

Discussion

• older names include dolichostenomelia (Greek for long, narrow limbs) and dystrophia mesodermalis congenital, typus Marfanis;
• inherited as an autosomal dominant trait with variable expressivity.
• characterized by long, thin limbs and by laxity of ligaments;

Pathophysiology

• dz of collagen synthesis (possibly the alpha subunit)
• may have abnormal production of collagen type I (and ? type II);
• gene for this disorder has been located on long arm of chromosome 15 in gene for fibrillin-1 (FBN-1) mapped to 15q2112;
  • fibrillar protein found in eye, aorta, and several connective tissues;
  • different mutations have been found throughout the gene causing marfan's syndrome;
• mutations in transforming growth factor-ß receptor 2 (TGFBR2) can also cause Marfan syndrome;

References

• Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene.
• Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies.
• Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome.
• Heterozygous TGFBR2 mutations in Marfan syndrome.
• Of Marfan's Syndrome, Mice, and Medications

Differential dx

• mitral valve prolapse syndrome
• homocystinuria
  • characterized by tall stature, arachnodactyly, sciolosis, metal retardation, osteoporosis, DVT, and ectopic lens;
  • pts w/ clinical features of Marfan's dz but no family history should have urinalysis for homocystine;
• stickler Syndrome
• hypermobility syndrome
• ehlers-danlos syndrome:

Related problems

• increased length of the limbs as compared with the trunk;
  • arm span-to-height ratio of greater than 1.05;
  • this ratio may be exaggerated by scoliosis;
• eye
• cardiac:
• muscle: hypotonia of muscle
• spinal anomalies:
  • scoliosis: occurs in over 60 percent of patients and is most often thoracic and convex to the right;
• pectus deformities
• aortic regurgitation & AAA;
• joint laxity:
  • joint laxity is treated conservatively;
  • joint laxity is variable.
  • chronic & recurrent subluxation of patella, shoulder, SC joint, and MP joints of the thumb are common;
  • genu valgum and recurvatum also occur.
  • soft-tissue surgery to correct joint laxity is unsuccessful, and best treatment is therapy aimed at strengthening the muscle;
  • pes planovalgus, characterized by long, thin foot w/ esp long great toe, & unstable ankle often make shoe-fitting difficult;
  • these are be treated w/ orthosis &, rarely, arthrodesis;
  • flexion deformities of the fingers and toes
• elbow: congenital joint contractures is an important manifestation of Marfan syndrome
• hand:
  • congenital contractural arachnodactyly (long slender "seida" fingers)
  • thumb sign the thumb projects beyond the ulnar border of the hand, when maximally opposed within the clenched hand,
  • ref: Arachnodactylie. Achard C. Bull Mêm Soc Méd Hôp Paris.1902; 19:834 -43.
• hip joint: protrusio
  • is peculiar finding in many pts & may be progressive, symptomatic, & accompanied by chondrolysis;
  • radiographic findings:
    • center-edge angle of Wiberg of greater than 40 deg;
    • crossing of the teardrop by the ilioischial line;
  • treatment:
    • protrusio acetabuli: treated w/ early triradiate cartilage fusion;
    • closure of triradiate cartilage reportedly corrects abnormality in symptomatic patients.
  • references:
    • Protrusio Acetabuli in Marfan Syndrome: Age-Related Prevalence and Associated Hip Function.
    • Protrusio acetabuli in Marfan's syndrome.
• knee joint: recurrent dislocation of the patella
• feet: flat feet

References

• Un cas de déformation congénitale des quatre membres, plus prononcée aux extrémités, caractérisée par l'allongement des os avec un certain degré d'amincissement. Marfan AB.  Bull Mêm Soc Méd Hôp Paris.1896; 13:220 -7.
• Medical Progress: Heritable Diseases of Collagen.
• Cardiac, skeletal, and ocular abnormalities in patients with Marfan's syndrome and in their relatives. Comparison with the cardiac abnormalities in patients with kyphoscoliosis.
• The Metacarpal Index: A useful aid in the diangosis of the Marfan Syndrome.
• A metatarsal equivalent to the metacarpal index in marfan syndrome.
• Improving clinical recognition of Marfan syndrome