Ten-Year Epidemiological Review of In-Hospital Patients with Marfan Syndrome

Marfan syndrome is a connective tissue disorder with a worldwide prevalence of 1 in 5,000, without any racial predilection. Major cardiovascular manifestations of Marfan disease often require surgical intervention. The aim of this study was to examine the demographics of patients with Marfan syndrome admitted to Hong Kong hospitals over a 10-year period from 1997 to 2006. We retrospectively reviewed the prospectively collected Hong Kong Health Authority's Clinical Data Analysis and Reporting System and Clinical Medical System. Statistical analysis was performed using SPSS, version 15. A total of 525 patients with Marfan syndrome (310 male, 215 female) were included in this study. For males, mean age at first hospital admission was 19.8 years (range 0-78) and for females, 18.7 years (range 0-60). One hundred and twelve (21.3%) patients (56 male, 56 female) had documented aortoiliac aneurysms and/or dissection, with 74 (66.7%) cases involving the thoracic aorta. Forty-nine (9.3%) patients had major cardiac or aortoiliac operations, with an operative mortality of 5/49 (10.2%). Thirty-seven (7.0%) patients (23 male, 14 female) died during this period, with a mean age at death of 41.0 years (range 0-83) for males and 29.9 years (range 0-59) for females. The majority of these patients died of cardiovascular causes, with four aortic dissections, two ruptured aneurysms, seven with sudden collapse and cardiac arrest, and five with heart failure. In addition, there were other causes of mortality: five perioperative, one congenital, and four pulmonary causes, three with malignancy and one of stroke. The cause of death was unknown in five patients. Patients with aortoiliac diseases have a statistically significant higher mortality rate (p < 0.05). This population-based study shows that significant numbers of patients with Marfan syndrome are admitted to hospital per year, with a significant proportion requiring admissions at a young age. Life span in Marfan patients is markedly shortened, and aortoiliac disease is probably underdiagnosed. A standardized diagnostic and therapeutic follow-up program should be offered to these patients and their families.

Introduction

First described by Antoine Marfan in 1896,¹ Marfan syndrome is a connective tissue disorder caused by a mutation in the fibrillin-1 (FBN1) gene on chromosome 15, which determines the structure of fibrillin. More than 550 mutations in the fibrillin-1 gene have been identified worldwide;² the mutation is not always fully penetrant, and patients may not be diagnosed until later in life.3, 4, 5 There is also significant genetic heterogeneity in that some individuals with marfanoid phenotype have mutations in the TGFBR1 (transforming growth factor-ß receptor 1) or TGFBR2 gene.⁶ It has been estimated that approximately 1 in 5,000 in the United States has Marfan syndrome.⁷ Marfan syndrome does not have a particular gender, racial, geographic, or ethnic predilection.8, 9

The life expectancy of patients with Marfan syndrome has increased from a mean age at death of 32 in 1972 to 41 in 1993,⁷ due to better understanding of the disease process, closer follow-up protocols, active medical management, and advances in cardiac and vascular surgical technology.¹⁰ Despite the proven genetic links of Marfan syndrome, there is often a lack of standardized genetic screening and counseling service offered to patients’ families.¹¹ There are studies to show that sudden cardiovascular deaths in first-degree relatives of patients with Marfan syndrome may be avoidable by careful preparticipation screening.12, 13 In a screening of 29,067 children in China, Sun et al.¹⁴ found that the prevalence of Marfan disease was 17.2 per 100,000 of the Chinese population. In a review of 564 patients with Marfan syndrome from 18 provinces and cities in China over a 37-year period, 74.3% of the patients had a strong positive family history. Again, there seems to be a lack of diagnostic and therapeutic follow-up for patients with Marfan syndrome and their families.

The aim of the study was to determine the epidemiology and demographics of patients with Marfan syndrome who were admitted to hospitals in Hong Kong over a 10-year period from 1997 to 2006.