A Case Report of Marfan Syndrome Presenting Initially with Kyphoscoliosis and Multisystem Involvement

One of the most prevalent inherited disorder affecting connective tissue is Marfan syndrome (MFS), an autosomal dominant condition that affects 1 in 3000 to 5000 people. [1] mainly caused by mutations in the FBN1 gene of chromosome 15, which produces fibrillin, a major structural component of the extracellular matrix that supports connective tissues, especially in arteries, the pericondrium, and eye structures. With significant intrafamilial and interfamilial heterogeneity [2]

MFS can have a wide range of clinical severity, from isolated MFS symptoms to neonatal presentations of severe, quickly progressing disease affecting several organ systems. [3] It is an age-related yet highly pervasive disorder that primarily affects the skeletal, ocular, and cardiovascular systems. MFS patients have a variety of skeletal abnormalities, such as thoracolumbar scoliosis, pectus deformities (excavatum and carinatum), arachnodactyly (abnormally long and thin digits), and dolichostenomelia (long limbs relative to the trunk). The most prevalent cardiovascular manifestations are aneurysms, dilatation, and aortic regurgitation. Mitral valve prolapse is another common cardiovascular manifestation. Aortic problems, such as aortic root dilatation and dissection, are the main cause of decreased life expectancy. [2] When skeletal characteristics, ectopia lentis, thoracic aortic disease, or cascade testing for a disease-causing mutation in a family member are present, patients with MFS are usually referred for diagnosis. In order to avoid potentially fatal consequences, early diagnosis is crucial [4]. The diagnosis may be made based on skeletal characteristics, which frequently show up early. In order to monitor the development of aortic root dilatation and vascular anomalies and improve patient prognosis, timely cardiovascular examination and routine echocardiographic follow-up are essential, thereby improving patient prognosis. The Ghent II nosology is used to identify MFS; while genetic testing verifying the existence of an FBN1 pathogenic variation is not usually necessary for diagnosis, it can assist in differentiating MFS from other heritable thoracic aortic disease syndromes that may have skeletal characteristics similar to MFS. [4] Although there is no known cure for MFS, several interventions may help with some features of the illness. The goal of medical treatment using beta-blockers and other afterload-reducing medications is to lessen the strain on the aortic root, mitral valve, and aortic valve. [5] Early detection, medical intervention to stop or slow the progression of aortic dilatation, and prompt elective surgery all enhance outcomes. In this report, we present the case of an 18-year-old male with Marfan syndrome who initially presented with kyphoscoliosis and was later found to have significant cardiovascular and skeletal manifestations. This case highlights the importance of recognizing early skeletal abnormalities for prompt diagnosis and prevention of potentially life-threatening cardiovascular complications.

Case Presentation

An 18- year-old male with a known diagnosis of Marfan syndrome presented with progressive deformity of the spine for 6 months associated with shortness of breath, chest pain, and palpitations for 3 months.

History of present illness

The patient had been diagnosed with Marfan syndrome in 2017 following evaluation for progressive spinal deformity. A cardiovascular assessment performed in 2024 revealed mitral valve prolapse with mild to moderate mitral regurgitation and dilatation of the aortic root. Medication History: The patient was on regular treatment with bisoprolol for the management of cardiovascular manifestations associated with Marfan syndrome.

Family History

Family history was significant for tall stature and cardiovascular illness among paternal relatives. The patient was born out of a consanguineous marriage. The patient’s father reportedly had a tall and slender habitus and died due to a cardiac condition at the age of 39. The paternal grandmother had a tall stature, reportedly expired due to breast cancer at the age of 55, while a paternal uncle was undergoing treatment for cardiovascular disease.

Figure 1. Pedigree chart demonstrating the familial occurrence of Marfan syndrome and cardiovascular manifestations across multiple generations. The proband (P), an 18-year-old male, exhibited Marfan syndrome with pectus excavatum. Shaded symbols indicate affected individuals, the dotted symbol indicates breast cancer, slashed symbols indicate deceased family members, and double horizontal lines represent consanguineous marriage. A deceased 37-year-old female relative had a history of cardiac disease.

Figure 2. CT angiographic reconstruction showing aortic root dilatation and ascending aortic aneurysmal changes in Marfan syndrome.

Diagnosis

Based on clinical features, family history, anthropometric measurements, systemic examination, imaging findings, echocardiographic evaluation, and revised Ghent systemic scoring, the patient was diagnosed with Marfan syndrome associated with kyphoscoliosis, mitral valve prolapse with mitral regurgitation, severe aortic root dilatation, and dural ectasia.

Treatment and Management

The patient was managed conservatively with regular cardiac monitoring and medical therapy, including beta blocker therapy with bisoprolol for control of the cardiovascular manifestations associated with Marfan's syndrome. Serial 2D ECHO was performed for monitoring aortic root dimensions and mitral valve abnormalities. The patient was also referred for orthopaedic evaluation of kyphoscoliosis and associated skeletal deformities. Multidisciplinary management was recommended for systemic involvement associated with Marfan syndrome.

DISCUSSION

Marfan syndrome (MFS) is a genetic disorder, an inherited connective tissue disorder transmitted in an autosomal manner, characterized by a range of systemic symptoms due to mutations in the gene encoding Fibrillin-1 (FBN1). The primary clinical features of MFS vary greatly in severity and typically affect the cardiovascular, ocular, and musculoskeletal systems. These symptoms encompass aneurysms and dissections of the ascending aorta, mitral valve prolapse, dislocation of the lens, and the abnormal growth of elongated limbs. [6] The present case demonstrates typical multisystem involvement of Marfan's syndrome affecting the skeletal and cardiovascular systems. Although the majority of individuals with MFS inherit the condition from an affected parent, 25% of cases arise from a new mutation in the FBN1 gene, which encodes the connective tissue protein fibrillin1. [2] The patient's family history prominently featured tall height and cardiovascular issues among paternal relatives. This positive family history in the current case further underscores the genetic nature of the condition Individuals with MFS exhibit excessive linear growth of their long bones and experience joint laxity. Some patients may exhibit joint laxity, particularly involving the elbows and fingers. Individuals with MFS tend to be taller than average, with limbs that are disproportionately long compared to their trunk, a condition known as dolichostenomelia. They often display arachnodactyly, characterized by a positive thumb sign. Diagnostic indicators for scoliosis in these patients include a vertical rib difference of 1.5 cm between the left and right sides of the chest and a Cobb angle of at least 20 degrees. In the absence of scoliosis, an exaggerated kyphotic curve in the thoracolumbar spine may assist in diagnosing MFS. [8] In this particular case, the patient exhibited kyphoscoliosis, elongated limbs, arachnodactyly, chest wall deformity, and reduced upper-segment to lower-segment ratio, all of which are typical skeletal features linked to MFS. Dural ectasia is a common manifestation of Marfan syndrome, particularly involving the lumbosacral region, and is considered an important feature in the revised Ghent criteria. [7] MRI findings in the present case demonstrated dural ectasia at the lumbosacral level. Cardiovascular characteristics include aortic enlargement at the sinuses of Valsalva, susceptibility to aortic tears and ruptures, mitral and tricuspid valve prolapse, and expansion of the proximal pulmonary artery, which are primary contributors to morbidity in MFS [6]. Aortic aneurysm is a crucial factor in diagnosing Marfan syndrome, with the most significant life-threatening risk being the dissection of such an aneurysm. Patients with MVP and MFS encounter mild regurgitation. In these individuals, the progression of MR is attributed to the spontaneous rupture of the chordae tendineae or infective endocarditis. Heart failure resulting from MVP and MR is a significant cause of morbidity and mortality in young children with rapidly advancing MFS [2]. In the present case, serial 2D echocardiographic evaluation revealed mitral valve prolapse with mild to moderate mitral regurgitation and severe aortic root dilatation, which are important cardiovascular manifestations associated with Marfan syndrome. It was recommended to use serial echocardiography for routine aortic root monitoring to evaluate the course of the disease and reduce the risk of life-threatening complications such as aortic dissection. The criteria for diagnosing MFS were last updated in 2010 and are known as the Ghent II nosology. These updated guidelines highlight the importance of cardiovascular symptoms and include FBN1 sequencing. They stress that individuals showing signs of other syndromes, such as Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome, congenital contractural arachnodactyly, familial thoracic aortic aneurysms and dissection, and vascular Ehlers-Danlos syndrome, should undergo genetic testing to rule out these conditions. It is crucial to recognize that the Ghent II criteria for diagnosing MFS include skeletal overgrowth, such as pectus deformities and scoliosis [9]. In this case, Marfan syndrome was supported by skeletal abnormalities, cardiovascular findings, positive family history, and a revised Ghent systemic score of 8 [Table 1]. Detecting Marfan syndrome at an early stage is crucial, as prompt monitoring and medical intervention can help mitigate severe cardiovascular risks. The primary causes of death in these patients are aortic root enlargement and aortic dissection. Therefore, consistent follow-up using echocardiography and CT angiography is vital to evaluate the progression of aortic expansion and valve issues. Managing Marfan syndrome necessitates a collaborative approach that includes cardiologists, orthopedic specialists, ophthalmologists, and genetic counseling. Singh and Lacro suggest that patients diagnosed with aortic root dilatation should be treated with appropriate doses of either a beta-blocker or an ARB. In more severe cases, a combination of these treatments should be considered [10]. Beta-blockers can help lower the hemodynamic pressure on the aortic wall, which may slow the expansion of the aortic root. For patients experiencing significant progressive aortic root dilatation, surgical interventions such as aortic root replacement, the Bentall procedure, or valve-sparing aortic root surgery might be necessary to mitigate the risk of aortic dissection and rupture. Those with scoliosis and skeletal deformities may need regular orthopedic evaluations and supportive care. Beyond medical treatment, non-pharmacological strategies include regular echocardiographic monitoring, limiting activities to decrease aortic stress, physiotherapy and orthopedic care for skeletal issues, regular ophthalmologic evaluation, and genetic counseling for affected families. This case highlights the significance of thorough clinical evaluations and imaging in identifying the multisystem involvement characteristic of Marfan syndrome. Recognition of skeletal anomalies alongside cardiovascular symptoms and application of the revised Ghent criteria facilitated the early diagnosis and appropriate monitoring and treatment.

CONCLUSION

Marfan syndrome is a multisystem connective tissue disorder with potentially life-threatening cardiovascular complications. Early recognition of characteristic skeletal and cardiovascular manifestations, along with application of the revised Ghent criteria and appropriate imaging studies, is essential for timely diagnosis. Regular cardiovascular surveillance and multidisciplinary management play a crucial role in reducing morbidity and improving long-term outcomes in affected individuals.

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