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








Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Saturday, January 3, 2015 12:18 pm