Marfan's Syndrome*

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MARFAN'S

SYNDROME*

T h e condition originally described b y M a r fan1 a s dolichostenomelia w a s apparently a * Reprinted by permission from The Lancet, May 21, 1955, page 1062. 331

c o n g e n i t a l a b n o r m a l i t y of t h e s k e l e t o n c h a r ­ acterized b y t h e length a n d slender propor­ t i o n s o f t h e l o n g b o n e s . T h e a l t e r n a t i v e title of a r a c h n o d a c t y l y w a s i n t r o d u c e d b y A c h a r d 2 to emphasize t h e " s p i d e r l i k e " appearance of

332

CORRESPONDENCE

the hands. The syndrome is now taken to in­ clude various ocular abnormalities, of which subluxation of the lens is the commonest, and cardiovascular lesions, of which aortic dila­ tation and dissecting aneurysm are probably the most usual and are certainly the most serious. Achard first drew attention to a hereditary and familial tendency, but according to Rados3 the family history was positive in less than 40 percent of cases. McKusick4 has now re-emphasized the importance of heredity in the genesis of the syndrome. An inquiry into the kinships of 50 unequivocal cases revealed a total of 105 affected persons, excluding many doubtful cases. Of the relatives of all the available patients with subluxation of the lens, 70 percent had recognizable stigmas of the syndrome. The genetic data indicate that the disease arises as a result of a single mutant gene which is subsequently trans­ mitted as a dominant. McKusick concludes that about 15 percent of all cases arise from such a mutation and 85 percent by transmis­ sion. The large number of tissues and structures that may be affected in Marian's syndrome suggests that, if a single defect is responsi­ ble, this must be fundamentally important. Its nature is by no means clear ; from the micro­ scopic appearance of cystic medial necrosis, which is the usual finding where the aorta is dilated or has undergone aneurysmal dis­ section, McKusick concludes that the elastica is probably the tissue primarily affected. But it is difficult to see how such involvement can be responsible for the various ocular and skeletal abnormalities "unless one assumes that the presence of this defect during embryogenesis produces an abnormal setting in which these particular anomalies occur with increased incidence."4 In any event the fun­ damental defect is functional rather than structural, at least in so far as it affects the aorta. What is inherited is apparently an inability of the elastic tissues to withstand the normal wear and tear of life. Conse­

quently the patient may in childhood show no evidence of cardiovascular abnormality, but in adult life have severe aortic dilatation, valvular incompetence, and myocardial hyper­ trophy.5 The presence of an underlying biochemical defect is strongly suggested by the production in rats fed on the seeds of Lathyrus odoratus of a syndrome that includes skeletal defects and degeneration of the media of the aorta leading to dissecting aneurysms.0 An active principle recently extracted from the seeds of L. odoratus is ß-amino propionitrile. Lathyrism in rats cannot justifiably be re­ garded as a phenocopy of Marian's syn­ drome. But the striking similarity of many of the features of these two conditions does sup7 port the view that the complex anomalies that make up the syndrome in man are based on a single transmissible biochemical defect. REFERENCES

1. Marian, A. B. : Bull. Soc. méd. Hop. Paris, 13:220, 1896. 2. Achard, C. : Ibid., 19:834, 1902. 3. Rados, A.: Arch. Ophth., 27:477, 1942. 4. McKusick, V. A.: Circulation, 11:321, 1955. 5. Goyette, E. M., and Palmer, P. W. : Ibid., 7 :373 1953. 6. Ponseti, I. V., and Shepard, R. S. : J. Bone & Joint Surg., 36A:1031, 1954.

CORRESPONDENCE "FIRST, DO NO HARM"

Editor, American Journal of Ophthalmology: I should like to comment on the fine sym­ posium in the August, 1955, issue of T H E AMERICAN

JOURNAL OF OPHTHALMOLOGY

regarding retrolental fibroplasia, and on Dr. Reese's accompanying epitaph for the same disease. I cannot let this opportunity pass without perhaps remarking that American medicine and the various people most directly interested have done an extraordinarily good job in fighting an unnecessary fire. Retro­ lental fibroplasia is certainly a man-made dis­ ease. That it has been made by man's thought-