Marfan Syndrome: an uncommon cause of heart failure with late presentation and management challenges in a Nigerian patient(case report)

¹Cardiac Care Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria, ²Rheumatology Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria

^&Corresponding author
Busayo Onafowoke Oguntola, Cardiac Care Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria

Introduction    

Marfan syndrome is an autosomal dominant connective tissue disorder with prominent cardiovascular, musculoskeletal and ocular manifestations. It is not a commonly diagnosed aetiology of heart failure amongst adults in this environment.

Patient and observation     

Patient information: a 56-year-old African man who was referred to cardiology clinic on account of recurrent easy fatiguability, palpitations, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea of 3 months. He had no chest pain, bilateral leg swelling, abdominal pain or swelling. He first presented to referral center 2 years prior with history of exertional dyspnea. He was managed as a case of heart failure secondary to hypertensive heart disease. He was thereafter lost to follow-up. He was previously diagnosed with hypertension. He had associated musculoskeletal abnormalities and reduced vision since childhood. He had no known family history of Marfan syndrome.

Clinical findings: he had head bobbing, was not dyspneic, no finger clubbing, no pedal edema. He had a regular, large volume, collapsing pulse of 84 beats/minute. The blood pressure was 130/40mmHg (wide pulse pressure). Corrigan and Duroziez and Traube´s sign were present. The jugular venous pressure was not raised. The precordium was hyperactive, apex beat was displaced at 7^th left intercostal space anterior axillary line, heaving. There was no left parasternal heave. A grade 3/4 diastolic murmur was heard maximally at right parasternal area. A grade 4/6 apical systolic murmur was heard. Musculoskeletal examination findings were an arm span of 191 cm and a height of 184 cm with an arm span height ratio of 1.04. kyphosis, arachnodactyly, positive thumb and wrist signs and wind-swept deformity of the knees (Figure 1). Ocular examination revealed a visual acuity of counting finger, early lens opacity superonasally dislocated lens on the right and a visual acuity of 6/24, superonasally subluxated lens in the left eye.

Diagnostic assessment: the resting 12-lead ECG showed sinus rhythm, normal axis (+60), left atrial abnormalities, left ventricular hypertrophy with strain pattern. The chest X-ray revealed cardiomegaly with left ventricular preponderance (transverse cardiac diameter = 19.5cm). There is associated unfolding of the aorta. There is reduced left lung volume. Thoracic spine scoliosis with convexity to the right (Figure 2). Transthoracic echocardiography revealed - aneurysmal dilatation of aortic root (aortic diameter at the annulus= 4.9cm, sinus of valsalva = 6.9cm) (Figure 3). The aortic valve was trileaflet with poor coaptation. The left ventricle was dilated (left ventricular internal diameter in diastole - 9.6cm) with reduced ejection fraction (ejection fraction = 35%). Severe aortic regurgitation. The CT aortogram revealed aortic root aneurysm, tortuous abdominal aorta, thoracolumbar scoliosis and pectus excavatum. The ocular ultrasound confirmed bilateral ectopia lentis (Figure 4). The laboratory parameters were: packed cell volume - 39%, total white cell count -6,500 cells/mm³, neutrophils- 64%, lymphocytes - 36%, platelets - 308,000 cells/mm³. Serum electrolytes - (sodium - 136mmol/l, potassium - 4.5mml/l, bicarbonate - 22mmol/l), urea - 5.0mmol/l, creatinine - 80 micromol/l. Fasting blood glucose - 4.4mol/l. Fasting lipid profile - (total cholesterol - 4.7mmol/l, triglyceride - 1.2mmol/l, HDL - 2.1mmol/l, LDL- 2.0mmol/l).

Diagnosis: a diagnosis of Marfan syndrome (using revised Ghent´s criteria) in heart failure was made.

Therapeutic interventions: management was multidisciplinary. He was commenced on tab carvedilol 3.125mg b d, tab lasix 40mg daily, tab aldactone 25mg daily, tab losartan 50mg daily. He was referred to the cardiothoracic surgical unit with plans for aortic root replacement. He was counselled on the need for family and genetic screening.

Follow-up and outcomes of intervention: he had symptomatic relief after commencement of beta blocker and angiotensin receptor blocker. He reportedly died at home after sudden onset tiredness. Autopsy was not done.

Discussion     

Marfan syndrome is a connective tissue disorder characterised by disorders of the cardiovascular, ocular and musculoskeletal system [1]. The index case has an aortic aneurysm and heart failure from chronic aortic regurgitation. He also has bilateral ectopia lentis and musculoskeletal involvement. Although these were detected late after complications had set in. The prevalence of Marfan syndrome in Nigeria is not known. However, worldwide it has been estimated to be 1 in 5000 to 2-3 in 10,000 persons [1]. Ekure et al. reported a nuclear family with Marfan syndrome [2] and that Marfan Syndrome accounted for 0.7% of syndromic aetiology of congenital heart disease amongst 767 children studied at Lagos University Teaching Hospital over a 5-year period [3]. Also, Nwokoha et al. reported a 7-year old boy with Marfan syndrome [4].

The mode of inheritance is autosomal dominant [4]. The mutation of the fibrillin-1 (FBN) gene has been implicated in the aetiology of Marfan syndrome [4] in 90% of cases [5]. Abnormality of the fibrillin gene interferes with local TGF-β signalling and impairment of tissue integrity. There is phenotypic and age dependent variations among family members with Marfan syndrome [1]. Although no family history of Marfan syndrome was identified in this case. Diagnosis of Marfan syndrome was made using the revised Ghent's criteria [6]. Aortic root aneurysm (aortic root dilatation Z score of 2 or greater) and ectopia lentis in the absence of family history of Marfan syndrome were used to make the diagnosis in this case.

The management of Marfan syndrome is multidisciplinary. Early identification and institution of prophylactic measures are key. It had been associated with better prognosis and longevity in this group of individuals. However, in our environment the epidemiology is not well known. Also, patients present late with complications as seen in this patient who was initially lost to follow-up and later presented with aortic root aneurysm and heart failure from chronic aortic regurgitation [5]. The management of chronic severe aortic regurgitation includes aortic root replacement which is costly and requires expertise. Healthcare is largely self-funded in our environment which could have contributed to delay in surgical intervention in this case and eventual demise of this case.

Conclusion     

Marfan syndrome is an uncommon cause of heart failure in a middle-aged African man. Early identification and institution of prophylactic measures could have improved the outcome. Management was hampered by lack of funds and difficulty in assessing surgery.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Figures     

Figure 1: wrists and thumb signs

Figure 2: plain chest radiograph, posteroanterior view showing cardiomegaly with left ventricular preponderance and unfolding of the aorta

Figure 3: transthoracic echocardiography, parasternal long axis view showing dilated aortic root

Figure 4: (A, B) ocular ultrasound showing displaced lenses

References