Medical and Dental Consultantsí Association of Nigeria
Home - About us - Editorial board - Search - Ahead of print - Current issue - Archives - Submit article - Instructions - Subscribe - Advertise - Contacts - Login 
  Users Online: 265   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
 

  Table of Contents 
CASE REPORT
Year : 2022  |  Volume : 25  |  Issue : 2  |  Page : 205-210

Marfan Syndrome with Aortic Root Disease, Severe Heart Failure and Aortic Dissection- Two Case Reports


1 Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
2 Department of Medicine, Alex Ekwueme Federal Teaching Hospital, w, Nigeria

Date of Submission05-Dec-2020
Date of Acceptance23-Nov-2021
Date of Web Publication16-Feb-2022

Correspondence Address:
Dr. P O Njoku
Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_675_20

Rights and Permissions
   Abstract 


Marfan syndrome is an uncommon inheritable connective tissue disease which affects the cardiovascular system. This paper presents two cases of Marfan Syndrome with predominant aortic root disease that were seen at the Cardiology Clinic of University of Nigeria Teaching Hospital, Enugu, Nigeria. Their biography, clinical features and echocardiography parameters were captured using structured questionnaire. Both were young males in their 4th decade of life, and had advanced aortic root diseases which were complicated by left ventricular failure in both, while one of them had aortic dissection and ischemic stroke. Young adult Nigerians with Marfan syndrome presented with advanced aortic root diseases, heart failure, aortic dissection and stroke.

Keywords: Aortic root disease, cardiac failure, clinical features, dissection, Marfan syndrome, stroke


How to cite this article:
Njoku P O, Mbadiwe N C, Onwubere B J, Ejim E C, Anisiuba B C, Iyidobi T C, Onyema C T. Marfan Syndrome with Aortic Root Disease, Severe Heart Failure and Aortic Dissection- Two Case Reports. Niger J Clin Pract 2022;25:205-10

How to cite this URL:
Njoku P O, Mbadiwe N C, Onwubere B J, Ejim E C, Anisiuba B C, Iyidobi T C, Onyema C T. Marfan Syndrome with Aortic Root Disease, Severe Heart Failure and Aortic Dissection- Two Case Reports. Niger J Clin Pract [serial online] 2022 [cited 2022 Dec 2];25:205-10. Available from: https://www.njcponline.com/text.asp?2022/25/2/205/337769




   Introduction Top


Marfan Syndrome (MFS) is amongst the most common autosomal dominant inheritable disorders which affect the connective tissue.[1],[2] This disease results from mutation and abnormal functioning of Marfan syndrome gene (MFS1) that codes for connective tissue protein fibrillin. This defective gene has been isolated in Chromosome 15q21 in affected individuals. About two-third of cases are familial with autosomal dominant mode of inheritance, while the remaining one-third are due to sporadic mutations.[3],[4] The reported incidence vary from one region of the world to another as available data show incidence of 1 in 10,000 to 20,000 people in the western world,[5] 1 in 3000 to 5000 individuals in South Africa[6] but data on incidence in Nigeria is rare. Characteristic clinical features involve cardiovascular, ocular and musculo-skeletal systems. The course of the disease is usually progressive and the prognosis is determined by the cardiovascular manifestations, early identification and line of management. Progressive aortic dilatation, usually maximal at the sinus of Valsalva, associated with aortic valve incompetence leads to aortic dissection or rupture and is the principal cause of mortality, but mitral valve prolapse with incompetence may be significant while lens dislocation, myopia, and arthritis associated with chronic joint laxity can cause substantial morbidity.[7],[8] Although family history may be helpful, typical clinical features include a young adult who is tall and has thin body habitus as well as long limbs. Others are arachnodactyly, pectus deformities, scoliosis, high arched palate with dental crowding, skin striae, recurrent hernia and recurrent pneumothorax from ruptured pleural blebs.[7] The Berlin diagnostic criteria of 1988 are of more prognostic value and have shown more consistency in the diagnosis of Marfan syndrome while the Ghent nosology[9] of 1996 is the revised Berlin diagnostic criteria with codified clinical features.

Because of late presentation in most developing countries, many adults with MFS have advanced cardiac diseases.[3],[6],[10] In these case reports, two young adult males with MFS presented with severe aortic aneurysm and biventricular failure while one of them had aortic dissection and stroke. Ethical approval was obtained from the ethics committee of the hospital and consent from the cases repoted.


   Case Reports Top


Case 1

A 34 year old Mason presented to the Out-patient Clinic on January 22nd, 2018 with complaints of dyspnea on exertion and diurnal bilateral leg swelling of 9 months duration. There were also complaints of recurrent palpitation, orthopnea and cough that was productive of frothy sputum. He was not known to have hypertension or diabetes and there was no family history of similar illness. He participated in acrobatics in school because of his very flexible joints. He also had 13 years history of myopia.

Physical examination showed a young man who was mildly tachypnoeic. He had Marfan Syndrome facie, with high arched palate, crowded dentition and Muller's signs, without leg edema. Cardiovascular examination showed collapsing radial pulse of 78 per minute. The BP was 110/70 mmHg in the right arm and in sitting position. There was Corrigan sign and the apex beat was displaced to the 6th left intercostal space, anterior axillary line and heaving. First, second and 4th heart sounds were heard. Grade 2/6 early diastolic murmur at 3rd left intercostal space as well as grade 2/6 apical pan- systolic murmur were heard. Musculo-skeletal system showed height of 180 cm, with arm span to height ratio of 1:1 and upper to lower segment of the body ratio of 0.79. Other findings were thoraco-lumbar scoliosis, long slender fingers and toes, positive wrist and thumb sign (Steinberg sign), hyper-extension of elbows, fingers, knees and excessive flexion of the trunk, pes planus and valgus deformity. Findings on examination of the eyes included bilateral superior temporal lens subluxation, bilateral immature cataract and myopia. Chest examination showed versicular breath sound and fine bibasal crepitations, while the rest of the examination was unremarkable. A working diagnosis of biventricular failure from severe aortic regurgitation in the background of Marfan Syndrome and aortic aneurysm was made. Investigations were requested and he was commenced on Tab Bisoprolol 2.5 mg once daily (OD), Tab Lorsatan 12.5 mg OD, Tab Frusemide 40 mg OD, Tab Spironolactone 25 mg OD and Tab Rosuvastatin 10 mg nocte.

Electrocardiogram (ECG) showed normal sinus rhythm with heart rate of 78/m, P-mitrale, left axis deviation, inferior myocardial strain and left ventricular hypertrophy. Trans-thoracic echocardiogram done according to American Society of Echocardiography guideline[11] showed grossly dilated aortic root (80 mm), Aortic Z- score[9]: 16.81, severe aortic regurgitation (pressure half time 328 ms), dilated left ventricle (LVIDd: 91 mm, LVIDs: 79 mm), left ventricular (LV) ejection fraction of 30%, mild mitral regurgitation, tricuspid regurgitation (RVSP 40 mmHg) and left ventricular diastolic dysfunction. Patient was considered of low risk for coronary artery disease and coronary angiography was not done.

Although there was no family history, diagnosis of Marfan syndrome was sustained based on clinical and echocardiography findings which met the Ghents criteria. Subsequently, he had open heart surgery and Bentall procedure was done. His post-operative condition was satisfactory and he was discharged home to be followed up on out-patient basis. Take home medications were Tabs Spironolactone 25 mg OD, Tabs Frusemide 40 mg OD, Tabs Losartan 12.5 mg OD, Tabs Bisoprolol 2.5 mg OD and Tabs Warfarin at dose determined by International Normalized Ratio (INR) result.

Case 2

A 38 year old male Aviation Engineer, who presented to the out-patient clinic on 12th March 2019 with complaints of progressive exertional dyspnea and cough of 6 months duration. Dyspnoea progressed from moderate to severe exertion to occur at rest while cough was occasionally productive of frothy sputum. There was recurrent palpitation, paroxysmal nocturnal dyspnea and orthopnea. He was not known to have hypertension or diabetes and there was no history of similar symptoms in the family. He had difficulty in reading and was diagnosed of ectopia lentis and myopia at 18 years by an ophthalmologist who also prescribed reading glasses.

Physical examination showed a young man with Marfan syndrome facie, tachypnoeic with high arched palate but there was no leg edema or digital clubbing. Examination of the musculo-skeletal system showed a slim man of 194 cm in height, weighing 88 kg and arm span to height ratio was 1:1. The upper to lower segment of the body ratio was 0.8. Other findings included long slender fingers and toes, positive wrist and thumb sign (Steinberg sign), hyper-extension of fingers, pes planus and valgus deformity. Cardiovascular examination showed a collapsing radial pulse of 104 per minute. The BP was 120/70 mmHg in the right arm and in sitting position. The jugular venous pulsation was not elevated and the apex beat was located at the 6th left inter-costal space, anterior axillary line and non- heaving. First, 2nd and 3rd heart sounds were heard. Grade 2 pansystolic murmur was heard at the left lower sternal edge while grade 2 early diastolic murmur was heard at the 2nd left inter-costal space. Abdominal examination showed enlarged and tender liver with a span of 14 cm. Findings on examination of the eyes included dislocation of the lens and myopia. Examination of the chest and the neurological systems were unremarkable. A working diagnosis of Marfan Syndrome with aortic aneurysm, severe aortic regurgitation in biventricular failure was made. His ECG showed first degree AV block and left atrial abnormality. Trans-thoracic echocardiogram done according to American Society of Echocardiography guideline[11] showed proximal ascending aortic aneurysm with dissecting flap adjacent to Left coronary cusp with severe aortic regurgitation. All chambers were dilated with global hypokinesia, left ventricular systolic and right ventricular diastolic failure respectively [Table 1]. The diagnosis of Marfan syndrome was sustained based on fulfilment of Ghent's diagnostic criteria. He was commenced on Tab Metoprolol 25 mg OD, Tab Rosuvastatin 10 mg OD. Due to the aortic dissection, vasodilator was not prescribed to avoid hypotension. Few weeks after while awaiting heart surgery in another Specialist Hospital he developed extensive acute cerebral infarct involving the left middle cerebral artery territory. He also developed extensive deep vein thrombosis in the right femoral and popliteo-tibial veins. He was managed conservatively and oral anti-coagulant, medications for the stroke were added while IVC filter was deployed at the level of L2-3 to prevent embolization of the thrombus while waiting for cardiac surgery.
Table 1: Some of the echocardiographic parameters of the patients

Click here to view



   Discussion Top


The different phenotypes in Marfan syndrome are dependent on a wide variety of mutations of fibrillin gene that gives rise to the subtypes of collagen abnormalities.[1] The two patients described above were both males, however no sex predilection has been documented in the case reports in Nigeria and other developing countries.[3],[6],[12],[13] This conforms with large data reviewed in the United States[14] and France.[15] Both patients presented with ocular, musculo-skeletal and cardiovascular features of MFS. Bilateral ectopia lentis was found in both patients and pre-dated onset of cardiac symptoms. Both patients had myopia, which made the second patient use corrective reading glasses early in adulthood. Presence of ectopia lentis is a major criterion for diagnosis of MFS and the most common ocular abnormality in MFS.[8],[16] Some musculo-skeletal features found in both patients included tall and slender habitus, arm span to height ratio >1.05, high arched palate [Figure 1] and crowded dentition, thoraco-lumbar scoliosis, pes planus and valgus deformity of metatarso-phalangeal joint. Others were long slender fingers and toes [Figure 2] and [Figure 3], thumb or Steinberg's sign [Figure 4], wrist or Walker-Murdoch's sign [Figure 5], joint hyper-mobility with Beighton score of 9/9 and stretch marks on the trunk [Figure 6] which were in keeping with findings in MFS.[17] Aortic aneurysm [Figure 7] and [Figure 8] was present in both patients and was complicated by severe aortic regurgitation [Figure 9], markedly dilated left ventricle and left ventricular systolic failure in both patients [Table 1]. Although there was functional aortic and mitral regurgitation in both patients, there was no mitral valve prolapse seen in them on echocardiography. Mitral valve prolapse and dilation of the Sinuses of Valsalva have been identified as the most common cardiovascular features of MFS,[18],[19] due to fibrillin defect believed to cause weakening of the supportive tissues.[20] Aortic root dilation consisting of dilation of the sinuses of Valsalva, expansion of the sino-tubular junction and the aortic annulus may be the initial aortic abnormality. These lead to aortic regurgitation (AR) with a central jet secondary to annular dilatation and/or myxomatous valvular degeneration.[21] Subsequently, large left ventricular end diastolic volume and pressure as well as large left ventricular end diastolic dimension ensue leading to myocardial damage and global hypokinesia[22] as were seen in both cases [Table 1]. The second and older patient was found to have Stanford Type A dissection[18] on transthoracic echocardiography [Figure 10] after he developed worsening dyspnea at rest. Aortic dissection in Marfan syndrome usually arises from intimal tear in the proximal ascending aorta with the dissection involving the sino-tubular junction and aortic sinuses, resulting in prolapse of one or more commissures.[23] Although intramural aortic hematoma was reported in an 11-year-old girl with Marfan Syndrome in northern Nigeria,[3] report of aortic dissection in a Marfan Syndrome patient in Nigeria is rare. In western countries, Type B dissection was documented in the fourth decade of life in male patients despite prior prophylactic aortic root replacement and this was believed to be due to more adverse phenotype or changes in flow dynamics and shear stress due to the rigid proximal conduit.[14] Both patients received beta blockers which reduced the heart rate, blood pressure and further increase in aortic root dimensions.[24],[25] The first patient subsequently received additional low dose angiotensin receptor blocker (Lorsatan), diuretics and oral anticoagulant to mitigate heart failure and complications. The second patient with dissection subsequently developed cerebral infarct involving the left middle cerebral artery territory while waiting for cardiac surgery and was managed conservatively. Reports of similar events in Marfan Syndrome especially in sub-Saharan Africa is rare. However, ischemic stroke or transient ischemic attack (TIA) is known to be common in acute Type A dissection due to extension to the cervico-cerebral arteries or emboli from the site of dissection.[26],[27],[28]
Figure 1: High arched palate

Click here to view
Figure 2: Arachnodactyly

Click here to view
Figure 3: Thumb or Steinberg's sign

Click here to view
Figure 4: Straie at the shoulder regions

Click here to view
Figure 5: Trans-thoracic parasternal long-axis echocardiography showing aortic aneurysm

Click here to view
Figure 6: Trans-esophageal short axis echocardiogram recorded at the base of the heart showing dilated aorta and severe regurgitation on color

Click here to view
Figure 7: Arachnodactyly in the right hand of the Marfans patient (Right)

Click here to view
Figure 8: Wrist or Walker-Murdoch's sign

Click here to view
Figure 9: Parasternal long-axis transthoracic echocardiogram showing dilated aortic aneurysm

Click here to view
Figure 10: Parasternal long-axis transthoracic echocardiogram showing dilated aortic root, type A acute dissection and the intimal flap (rightward-pointing arrow in the aortic root). The aortic valve is anterior to the dissecting flap

Click here to view



   Conclusion Top


Marfan Syndrome in the young adult commonly presents with advanced aortic root disease that could be complicated by severe left ventricular failure. Type A aortic dissection and acute ischemic stroke could also occur but are preventable if patient is identified early for timely cardiac surgical intervention. Aggressive conservative management by regular monitoring with echocardiography and early commencement of appropriate medications could reduce morbidity and mortality particularly in resource poor countries where cost of surgery is prohibitive and manpower as well as facilities for urgent surgical intervention are limited.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Recommendation

Early presentation of patients with MFS and early interventions is advocated. The older patient in this report developed aortic dissection and stroke while awaiting cardiac surgery. This underscores the need for early identification, appropriate medical management, early profiling and surgical care for those with severe aortic aneurysm.

Acknowledgements

Management and staff of the National Cardiothoracic Centre of Excellence, University of Nigeria Teaching Hospital, Enugu, Nigeria, Save a Heart Nigeria, VOOM Foundation and our foreign collaborators.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Robinson PN, Arteaga-Solis E, Baldock C, Collod-Béroud G, Booms P, De Paepe A, et al. The molecular genetics of Marfan syndrome and related disorders. J Med Genet 2006;43:769-87.  Back to cited text no. 1
    
2.
Judge DP, Dietz HC. Marfan's syndrome. Lancet 2005;366:1965-76.  Back to cited text no. 2
    
3.
Aliyu I, Akhiwu HO. Intramural aortic hematoma in an 11-years-old girl with Marfan's syndrome. Niger J Cardiol 2014;11:139-41.  Back to cited text no. 3
    
4.
Keane MG, Pyeritz RE. Medical management of Marfan's syndrome. Circulation 2008;117:2802-13.  Back to cited text no. 4
    
5.
Baumgartner WA, Cameron DE, Redmond JM, Greene PS, Gott VL. Operative management of Marfan's syndrome: The Johns Hopkins experience. Ann Thorac Surg 1999;67:1859-60.  Back to cited text no. 5
    
6.
Naidoo P, Ranjith N, Zikalala Z, Mahoney S, Ho K. Marfan syndrome: A case report and pictorial essay. Pan Afr Med J 2018;30:171.  Back to cited text no. 6
    
7.
Randhawa AK, Mishra C, Gogineni SB, Shetty S. Marfan syndrome: Report of two cases with review of literature. Niger J Clin Pract 2012;15:364-8.  Back to cited text no. 7
  [Full text]  
8.
Dean JC. Marfan syndrome: Clinical diagnosis and management. Eur J Hum Genet 2007;15:724-33.  Back to cited text no. 8
    
9.
Loeys BL, Dietz HC, Braverman AC, Callewaert BL, Backer JD, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010;47476-855.  Back to cited text no. 9
    
10.
Ekure EN, Onakoya AO, Oke DA. Marfan syndrome: A study of a Nigerian family and review of current cardiovascular management. West Afr J Med 2009;28:48-53.  Back to cited text no. 10
    
11.
Henry WL, De Maria A, Gramiak R, King DL, Kisslo JA, Popp RL. Report of the American Society of Echocardiography Committee on Nomenclature and Standards in Two-dimensional Echocardiography. Circulation 1980;62:212-217.  Back to cited text no. 11
    
12.
Akinlade OM, Yusuf AM, Akintunde AA, Opadijo OG. Rheumatic heart disease in a patient with Marfan's syndrome. Int J Case Rep Images 2019;10:101020Z01OA2019.  Back to cited text no. 12
    
13.
Omolase CO, Akinwalere AK, Omotayo RS, Omolase BO, Elekwachi G, Majekodunmi MY. Bilateral ectopia lentis in Marfan's syndrome: A case report. Clin Surg 2018;3:2244.  Back to cited text no. 13
    
14.
Roman MR, Devereux RB, Preiss LR, Asch FM, Eagle KA, Holmes KW, et al. Associations of age and sex with Marfan phenotype: The NHLBI GenTAC Registry. Circ Cardiovasc Genet 2017;10:e001647.  Back to cited text no. 14
    
15.
Benoist G, Tubach F, Roy C, Rioux S, Michelon-Jouneaux M, Chevallier B, et al. Skeletal evolution in Marfan syndrome: Growth curves from a French national cohort. Pediatr Res 2018;83:71-7.  Back to cited text no. 15
    
16.
Rubin SE, Nelson LB. Ocular manifestations of autosomal dominant systemic conditions. Duane's Clinical Ophthalmology on CD – Rom. Philadelphia: Lippincott Williams and Wilkins; 2006;3:58.  Back to cited text no. 16
    
17.
Van de Velde S, Fillman R, Yandow S. Protrusio ccetabuli in Marfan síndrome: History, diagnosis, and treatment. J Bone Joint Surg Am 2006;88:639-46.  Back to cited text no. 17
    
18.
Daily PO, Trueblood HW, Stinson EB, Wuerflein RD, Shumway NE. Management of acute aortic dissections. Ann Thorac Surg 1970;10:237-47.  Back to cited text no. 18
    
19.
Marsalese DL, Moodiew DS, Vacante M, Lytle BW, Gill CC, Sterba R, et al. Marfan's syndrome: Natural history and long term follow up of cardiovascular involvement. J Am Coll Cardiol 1989;14:422-8.  Back to cited text no. 19
    
20.
Lee B, Godfrey M, Vitale E, Hori H, Mattei MG, Sarfarazim M, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature 1991;352:337-9.  Back to cited text no. 20
    
21.
Gu X, He Y, Li Z, Han J, Chen J, Nixon JV. Echocardiographic versus histologic findings in Marfan syndrome. Tex Heart Inst J 2015;42:30-4.  Back to cited text no. 21
    
22.
Isekame Y, Gati S, Aragon-Martin JA, Bastiaenen R, Seshasai SR, Child A. Cardiovascular management of adults with Marfan syndrome. Eur Cardiol Rev 2016;11:102-10.  Back to cited text no. 22
    
23.
Maruf MF, Hossain N, Akter T, Chowdhury AA, Hasan K, Karim R, et al. Bentall surgery for aortic root aneurysm in a patient with Marfan syndrome. Cardiovasc J 2015;8:78-81.  Back to cited text no. 23
    
24.
Salim MA, Alpert BS, Ward JC, Pyeritz RE. Effect of betaadrenergic blockade on aortic root rate of dilation in the Marfan syndrome. Am J Cardiol 1994;74:629-33.  Back to cited text no. 24
    
25.
Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med 1994;330:1335-41.  Back to cited text no. 25
    
26.
Koga M, Iguchi Y, Ohara T, Tahara Y, Fukuda T, Noguchi T, et al. Acute ischemic stroke as a complication of Stanford type A acute aortic dissection: A review and proposed clinical recommendations for urgent diagnosis. Gen Thorac Cardiovasc Surg 2018;66:439-45.  Back to cited text no. 26
    
27.
Doroghazi RM, Slater EE, DeSanctis RW, Buckley MJ, Austen WG, Rosenthal S. Long-term survival of patients with treated aortic dissection. J Am Coll Cardiol 1984;3:1026-34.  Back to cited text no. 27
    
28.
Bossone E, Corteville DC, Harris KM, Suzuki T, Fattori R, Hutchison S, et al. Stroke and outcomes in patients with acute type A aortic dissection. Circulation 2013;128 (11 Suppl 1):S175-9.  Back to cited text no. 28
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
 
 
    Tables

  [Table 1]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Case Reports
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1330    
    Printed14    
    Emailed0    
    PDF Downloaded172    
    Comments [Add]    

Recommend this journal