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Marfan's syndrome is the commonest autosomal dominant inherited disorder of connective tissue, with a prevalence of 1/5000 to 1/10 000 individuals. 1, 2 There is complete penetrance but great variability in phenotype, the latter varying from florid abnormalities to just outside normal limits. 3, 4
The diagnostic criteria have been established in two workshops as major features in the ocular, cardiovascular, and skeletal systems associated with involvement of the lungs and integument. 5, 6 Dural ectasia may be the most sensitive clinical diagnostic marker but its specificity remains to be established. 7 If a mutation in the FBN1 fibrillin gene is detected, then a major criterion in an organ system and the involvement of another is diagnostic; for relatives, a positive family history, one major criterion, and involvement of a second organ system meet the criteria. 5 The skeletal anomalies which raise the possibility of Marfan's syndrome are quite common in the general population and have necessitated the establishment of rigid guidelines.
Poor muscle development was commented on by Marfan in his original description of an affected five year old child. 8 Although then considered part of the symptom complex, 9- 11 it was poorly characterised and myopathy is not mentioned in the most widely quoted review article 3 or in the two international workshops. 5, 6
Fibrillin-1, the 350 kDa glycoprotein involved in Marfan's syndrome, is present in the endomysium and perimysium of skeletal muscles. 12- 14 It is widely distributed in the body, where it forms a major component of the microfibrillar system and contributes to the mechanical properties of elastic fibres. 12, 13, 15 Mutations in the FBN1 gene on chromosome 15q21 which encodes fibrillin-1 are associated with cases of Marfan's syndrome. 16 Mutations in the FBN2 gene give rise to clinical syndromes (fibrillinopathies) which show phenotypic overlap with Marfan's syndrome, 1, 12 while on the other hand one family with Marfan's syndrome has been linked to a locus on chromosome 3p. 17 Thus the diagnosis of Marfan's syndrome has remained a clinical one.
We report a family fulfilling the diagnostic criteria but also having muscle weakness associated with respiratory failure and abnormal fibrillin immunoreactivity in the endomysium and perimysium.
METHODS
Needle muscle biopsy specimens were obtained from the vastus lateralis muscle...