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Syndrome of the Month J Med Genet: First Published As 10.1136/Jmg.33.5.403 on 1 May 1996

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Syndrome of the Month J Med Genet: First Published As 10.1136/Jmg.33.5.403 on 1 May 1996 _t Med Genet 1996;33:403-408 403 Syndrome of the month J Med Genet: first published as 10.1136/jmg.33.5.403 on 1 May 1996. Downloaded from Marfan syndrome Jonathon R Gray, Sarah J Davies It is almost a century since Dr Antoine Bernard Clinical features of Marfan syndrome Marfan (1858-1942) presented Gabrielle P to SKELETAL SYSTEM the Medical Society of Paris in 1896' and the Various analyses of affected patients have em- understanding of the condition which carries phasised the presence of dolichocephaly and his name continues to expand. Various de- elongation of the extremities (fig 1), most scriptions of similar syndromes predate that of marked in the fingers and toes (fig 2).7-9 Height Marfan. Williams2 and Conan-Doyle in his A and span have been measured by various work- study in scarlet3 may, in fact, have recognised ers,6 0 concluding that simple assessment of the disorder before Marfan. With the advantage span being greater than height is of no value, of retrospect, various figures including Paga- as this can be observed in approximately 59% nini4 and more recently Abraham Lincoln5 have ofnormal males and 21 % offemales."l Ofmore been proposed to have suffered from Marfan value is the observation that a span exceeding syndrome. McKusick6 gave a classic account height by greater than 8 cm is only observed in of the clinical features of the disorder in the 5-6% of normal patients."1 first edition of Heritable disorders of connective It is currently suggested by some workers tissue. that in the absence of confounding factors, (J Med Genet 1996;33:403-408) such as vertebral deformity causing a loss of height, a span to height ratio of greater than Key words: Marfan syndrome. 1-03 can be considered significant.'2 http://jmg.bmj.com/ jr on September 25, 2021 by guest. Protected copyright. JI... ..I Institute of Medical Genetics, University Hospital of Wales, I...k ."'. Heath Park, Cardiff .::'i CF4 4XN, UK .. J R Gray ..:eg A S J Davies Figure 1 Clinical phenotype: dolichostenomelia, Correspondence to: abnormal upperllower segment ratio, and span greater Dr Davies. than height. Figure 2 Arachnodactyly of the hands and feet. 404 Gray, Davies J Med Genet: first published as 10.1136/jmg.33.5.403 on 1 May 1996. Downloaded from ..AX Figure 3 Typical facial features: dolichocephaly and malar hypoplasia. Figure 4 Kyphoscoliosis. Abnormal limb length is often estimated in terms of an upper segment to lower segment ratio, lower segment being measured from the top of the symphysis pubis to the floor, the crucial as subsequent amblyopia is a common upper segment being defined as total height cause of poor vision. Blindness may also be minus the lower segment. The upper segment caused by varying degrees of retinal de- to lower segment ratio typically in the normal tachment. Approximately 60% of Marfan syn- http://jmg.bmj.com/ adult population is approximately 0 93 while drome patients'7 show lens dislocation to in an adult Marfan syndrome patient it would varying degrees and in the majority of cases approximate to 0.85. This ratio varies with age, this is bilateral. The lens may dislocate into the but for Marfan syndrome patients it is typically anterior chamber causing acute glaucoma in a at least two standard deviations below the mean minority of cases. for age, sex, and race.'3 The mean height is greater than unaffected on September 25, 2021 by guest. Protected copyright. sibs or the population average for sex, age, and CARDIOVASCULAR FEATURES race and tends to run slightly above and parallel Maximum stress is applied to the first part of to the 97th centile.'4 The skull is often ab- the ascending aorta. The first large increase in normally shaped, being long and narrow volume, and hence decrease in stress, beyond (dolichocephaly) (fig 3). A prominent brow, this point is at the innominate artery. As a retrognathic or hypognathic mandible, and a consequence of these haemodynamic factors hypoplastic malar region all may contribute to this is the area at which dissection and dilatation the lugubrious appearance described by McKu- usually occurs. Dilatation usually precedes the sick.'3 The palate is usually high arched and development of an aneurysm. Some degree of narrow leading to dental overcrowding often dilatation can be seen in approximately 50% necessitating orthodontic intervention. Ver- ofchildren and 70 to 80% ofadults with Marfan tebral and pectus deformities are a common syndrome. 8 The pattern of dilatation is of cause ofskeletal morbidity (fig 4) with scoliosis/ some value in predicting prognosis. 9 The more kyphoscoliosis occurring in between 30 and generalised, the more serious the probable out- 60% ofMarfan syndrome patients'5 at any time come, and the more generalised pattern tends before skeletal maturity. to occur more in males than in females. The Joint laxity is common but may coexist with advent of echocardiography has made a major normal mobility or even joint contractures. impact on the diagnosis and management of Recurrent joint dislocation may result from the cardiovascular features of Marfan syn- redundant weak joint capsules, ligaments, ten- drome. The diameter ofthe aortic root is meas- dons, and fascia.'6 ured at the level of the sinuses of Valsalva and compared to the body surface area nom- OCULAR FEATURES ograms."0 Approximately 5% of cases are not Myopia is frequent, appears early, and is often adequately assessed by echocardiography be- severe. Monitoring of vision in childhood is cause of pectus deformity. Marfan syndrome 405 Aortic dissection Table 1 A summary of the Marfan syndrome criteria Aortic dissection has been described at aortic according to the Berlin Nosology 1987.29 In the absence of a definitely affected relative there should be skeletal diameters under 5 cm but the usual pattern is involvement plus involvement of two other systems, at of gradual dilatation starting in the aortic root least one of which shows a cardinal feature (*) J Med Genet: first published as 10.1136/jmg.33.5.403 on 1 May 1996. Downloaded from and often extending up into the ascending Cardiovascular Dilatation of the ascending aorta* aorta.'2 There tends then to be a sudden onset Aortic dissection* Mitral regurgitation of aortic dissection with characteristic clinical Calcification of mitral annulus features of acute, anterior chest pain, often Mitral valve prolapse Abdominal aortic aneurysm described as being tearing in character. The Dysrhythmia pain may radiate through to the back or up to Ophthalmological Ectopia lentis* Flat cornea the jaw; very occasionally the dissection may be Elongated globe painless.2' The pattern ofdissection is usually of Retinal detachment Severe myopia distal progression, the minority that extend Neurological Dural ectasia* proximally may interfere with the coronary cir- Learning disability (verbal-performance discrepancy) culation with disastrous results. Respiratory skin/ Pneumothorax integument Striae Hernia Skeletal Chest wall deformity Mitral valve disease Dolichostenomelia not resulting from scoliosis Multivalvular abnormalities are the more fre- Arachnodactyly quent cardiac in children Vertebral column deformity pathology compared Tall stature, especially compared to to aortic complications in adults.22 Mitral valve first degree relatives is often the earliest ofthe cardiovascular High, narrow arched palate disease Protrusio acetabulae manifestations in Marfan syndrome. On echo- Abnormal joint mobility cardiographic assessment, 80% of patients re- gardless ofage or sex show evidence ofprolapse of at least the posterior mitral valve leaflet and often show evidence of valvular redundancy.22 Mitral valve prolapse occurring in Marfan syn- drome is similar to the more commonly found isolated mitral valve prolapse in that they both Diagnostic criteria for Marfan syndrome show increased prevalence in females and an In the absence of an unequivocally affected increased prevalence with age. Differences be- first degree relative there should be involvement tween these two forms of mitral valve prolapse of the skeleton and at least two other systems, include the fact that over one-quarter ofMarfan at least one of those systems showing a major syndrome patients with mitral valve prolapse manifestation. progress to mitral regurgitation by adulthood.23 In the presence of at least one unequivocally affected first degree relative there should be at least two systems involved, preferably one of http://jmg.bmj.com/ those systems showing a major manifestation, Aortic valve but this depending somewhat on the family's Aortic regurgitation is common, progressive, phenotype.29 and found in up to 70% of adult Marfan syn- Table 1 shows the varied manifestations; drome patients.24 those designated "major" manifestations at the conference are indicated by an asterisk. on September 25, 2021 by guest. Protected copyright. OTHER SYSTEM INVOLVEMENT Striae atrophica have been reported in ap- Differential diagnosis of Marfan proximately two-thirds of patients.'2 The syndrome pathology of the striae in Marfan syndrome is It is important to consider both syndromes identical to stretch marks found in non-Marfan sharing a similar multisystem involvement to syndrome patients, the most obvious ab- Marfan syndrome and those which may present normality being elastic fibre fragmentation.25 26 with a single system showing Marfan-like char- Hernias are seen frequently, the most usual acteristics (table 2). being inguinal, either congenital or acquired. A recent population based study of Marfan The value of knowing the patient's diagnosis is syndrome in the UK derived a minimum pre- that reinforcement of a repair with prosthetic valence figure of 1 in 14 217 (7 03 per 100 000 mesh work reduces the significant risk of re- population) and an incidence of 1 in 9802.30 currence after surgery.'2 Marfan syndrome may cause death or severe The major respiratory problem in Marfan handicap through adulthood and it may be syndrome is spontaneous pneumothorax27 anticipated to reduce reproductive fitness.
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