(I-2A.1) 23 years old female with Marfan Syndrome and deformity of the spine Hanna Dziedzic-Oleksy MD, Lidia Tomkiewicz-Pająk MD, Prof. Piotr Podolec MD, PhD

Keywords: Marfan’s Syndrome, spine deformity, aortic aneurysm, pregnancy

Background
Marfan’s Syndrome is an autosomal dominant disorder of a connective tissue. It affects many organs causing abnormalities of the cardiovascular, musculoskeletal and central nervous systems, eyes, lung, skin and the dura. The classical cardiovascular manifestations of Marfan’s Syndrome are mitral valve prolapse and aortic root dilation, leading to aneurysm and dissection.

Case presentation
A 23 y.o. Caucasian female (hight-169cm, arachnodactyly with wrist and thumb sign, severe chest deformity due to thoracic scoliosis, mild aortic valve insufficiency, mitral valve prolaps with moderate mitral regurgitation, aneurysm of the bulb of the aorta, with the familial history of Marfan syndrome) came for the control visit in May 2012.
In 2007, at the age of 18 y.o. she was referred to the cardiologic outpatient department from pediatric department, in order to continue observation and treatment. In 2000 and 2003 the procedures of insertion of corrective rods were performed due to severe thoracic scoliosis.
The CT-scan performed in 2008 showed widen aortic bulb alt the level of coronary sinuses (40mm) and normal width at the level of sino-tubular junction (32mm), ascending aorta (26mm) and descending aorta (18mm). The control CT-scan performed in January 2012 showed enlargement of the bulb of the aorta (48mm) and mild enlargement at the level of sino-tubular junction (35mm), ascending aorta (27mm). At that time she remained under observation.
In May 2012 the patient requested the control visit due to her 7 weeks pregnancy. She was aware of the risk and considerd termination of the pregnancy.

Guidelines
According to the 2010 ESC Guidelines on the management of grown-up congenital heart disease [1], the indication for the aortic surgery in Marfan syndrome patients consider aortic dilation between 46 and 50mm if there is a desire of pregnancy.
According to the 2011 ESC guidelines on the management of the cardiovascular diseases during pregnancy [3] the conditions, in which the risk of pregnancy is in WHO class IV, namely the pregnancy is contraindicated, consider Marfan syndrome with the dilation of the aorta greater than 45 mm.

Expert’s comments:(Written authorization required from each expert)

1.Roland Hetzer, MD, PhD²
The severe chest deformity is not contraindication for operation of the aorta. The operation of the aorta – preferably the Bental procedure should be performed as soon as possible.

2.Bogusław Kapelak, MD, PhD⁴
The severe chest deformity is not contraindication for operation of the aorta. During the operation also mitral valve should be replaced

3.Wojciech Płazak, MD, PhD¹
Chest deformity is not a contraindication for operation of the aorta. The Bental procedure should be performed as soon as possible. Mitral regugitation should be diagnosed more precisely, and probably replaced.

4.Krzysztof Bederski, MD¹
Pulmonary involvement in Marfan syndrome and deformity of spine.
Marfan syndrome is a disorder of connective tissue,inherited as an autosomal dominant of variable expression, and in its classical form comprises abnormalities in the skeleton,cardiovascular system,and eye. Disorders of the respiratory system have been noted in some patients with the syndrome in published reports. As no confirmatory biochemical test yet exists, the diagnosis must be made on the clinical features alone. Some of the clinical features are not specific to Marfan syndrome and are found in other
clinical entities-for example, Ehlers-Danlos syndrome.[1] A study and metaanalysis conducted in the Brompton Hospital and the Paediatric Research Unit, Guy’s Hospital, London and described by Wood et al. shows main pulmonary problems in patients suffering from this disorder.[1]
Spontaneous pneumothorax was the commonest respiratory abnormality detected in this patients, being present at some time in 11%. A patient with Marfan syndrome is probably several hundred times more likely to sustain spontaneous pneumothorax than a normal individual. The possibility that Marfan syndrome may be common in patients presenting with spontaneous pneumothorax has been investigated in a study of patients presenting with this condition, in whom metacarpal index and height-arm span difference were determined and ophthalmological examinations performed.[2]
Spontaneous pneumothorax has been reported in association with other inherited disorders of connective tissue, including Ehlers-Danlos syndrome and the Marfanoid hypermobility syndrome, which has features of both Marfan and Ehlers-Danlos syndromes.[3]
Recurrent pneumothorax, bullae, and emphysema in Marfan syndrome are likely to be due to the generalised connective tissue defect to which cardiac valve abnormalities, aneurysms, ectopia lentis, and bone changes have been attributed. Several studies have documented abnormal elastic tissue in Marfan lungs.[4-7] Whether the changes in elastic tissue in the lung are secondary to a collagen defect or represent an additional abnormality remains to be determined. The suggestion that elastic fibre changes result from cyclical tissue stresses in tissue lacking adequate mechanical support owing to defective collagen seems reasonable. Several reports suggest an increased susceptibility to pulmonary infection in patients with Marfan syndrome. It is possible that this may be related to bronchiectasis resulting from connective tissue weakness.[8]

5. Grzegorz Kopeć, MD, PhD¹
Thoracic surgery involvement in Marfan syndrome and deformity of spine.
Marfan syndrome is a disorder of connective tissue,inherited as an autosomal dominant of variable expression, and in its classical form comprises abnormalities in the skeleton,cardiovascular system,and eye. Disorders of the respiratory system have been noted in some patients with the syndrome in published reports. As no confirmatory biochemical test yet exists, the diagnosis must be made on the clinical features alone. Some of the clinical features are not specific to Marfan syndrome and are found in other clinical entities-for example, Ehlers-Danlos syndrome.[1]
Marfan’s syndrome is an hereditary disorder of the connective tissue which in its most classic form includes cardiovascular, ocular and skeletal manifestaions. Scoliosis is frequently present (40-75 per cent); the type of curve is similar to that seen in idiopathic scoliosis, but progression is often much more severe. There’s been reported a case of a woman aged thirty-two who had never been treated, had two 180 degree curves. There is a high incidence (50 per cent) of double curves (right thoracic and left lumbar) and a 23 per cent incidence of triple curves. Vertebral inversion (thoracic lordoscoliosis) is very common and often accompanied by severe respiratory insufficiency, particularly if it is associated with funnel chest. Conservative treatment is almost invariably ineffective and should be reserved only for very slight curves. All curves of 50 degrees or more should be surgically corrected. A 40-50 per cent correction can be achieved without risk. In view of the high incidence of pseudarthrosis, systematic review and, if necessary, revision of the arthrodesis is to be recommended. In the more severe cases of kyphosis it is advisable also to perform an anterior arthrodesis. Surgery is contraindicated in the presence of severe mitral or aortic insufficiency or aortic aneurysm.[2-3]

6. Jakub Podolec, MD, PhD³
Due to the enlargement of the aortic bulb to 48mm in women with Marfan syndrome, the risk of developing an aortic dissection is high. ESC guidelines indicate that these patients should be surgically treated before pregnancy [1]. There was an increase of 8 mm noticed in the 4 years period of time (2 mm per year). Due to the fact that the measurements had been done 5 months ago, an MRI scan without gadolin contrast should be considered before the decision regarding the surgical treatment. In case of the enlargement of the aortic bulb above 48mm, surgery should be performed in the nearest future. If the diameter remains at the level of 48mm, it might be considered to monitor the status of the patient (echocardiography or MRI without gadolin every 2-4 weeks) for the time after which the child is able to live outside mother‘s body. Physical activity should be limited for that period of time. Bentall-de Bono with mitral valve replacement surgery shall be considered right after cesarean section delivery. It should be considered to administrate beta-blockers to slow down aortic enlargement. Factors that will prompt the recommendation for surgery when aorta is 0,5-1cm/year, family history of premature aortic dissection <50mm and presence of geater than mild aortic regurgitation. Surgical replacement of the aortic root does not completely normalize the risk because dissection may occur elsewhere in the aorta [2][3]. In the last 20 years mortality rates after surgical treatment concerning mothers and children decreased signifficantly (from 30% to 0 % and from 50% to 10% respectively) which may favour the decision of early surgery [4]. Gott et al reported 30-day mortality after aortic root surgery was 0% in patients treated electivly and 5.6% for urgent surgery [5].

7.Piotr Musiałek MD, PhD¹
This patient requires surgery of the aortic root — and this should be performed as soon as only feasible due to the on-going (documented) aortic root dilatation. The final decision about the mitral valve will be the decision of the surgeon performing the aorrtic root surgery.

8.Anna Kabłak-Ziembicka, MD, PhD¹
Severe chest deformity is related to the increased risk of cardiothoracic surgery procedures. However, due to the substantial risk of the aortic dissection during pregnancy and childbearing period, the patient should be referred to cardiosurgery department in order to perform the Bental procedure for aortic aneurysm.

Expert’s conclusions:
The patient should undergo operation of the aorta (the Bental procedure) and the replacement of the mitral valve as soon as possible.

Authors:
Hanna Dziedzic-Oleksy MD¹, Lidia Tomkiewicz-Pająk MD¹, Prof. Piotr Podolec MD, PhD¹.

Experts:
Roland Hetzer, MD, PhD²,Bogusław Kapelak, MD, PhD⁴,Wojciech Płazak, MD, PhD¹,Krzysztof Bederski, MD¹,Grzegorz Kopeć, MD, PhD¹,Jakub Podolec, MD, PhD³,Piotr Musiałek MD, PhD¹,Anna Kabłak-Ziembicka, MD, PhD¹

¹Department of Cardiac and Vascular Diseases, Jagiellonian University College of Medicine, John Paul II Hospital, Krakow, Poland
²Medical Director and Chair of the Executive Management Board, Deutsches Herzzentrum, Berlin, Germany
³Department of Hemodynamics and Angiocardiography, John Paul II Hospital, Krakow, Poland
⁴Department of Cardiac, Vessels Surgery and Transplantology, Jagiellonian University College of Medicine, John Paul II Hospital, Krakow, Poland)