BACKGROUND: Literature data suggest high inter-study variability in mitral valve prolapse (MVP) prevalence among individuals with thoracic skeletal abnormalities (TSA). This systematic review aimed at estimating the overall prevalence of MVP in individuals with the most common TSA, including not only the oldest studies (before the year 2000) but also the most recent ones (after the year 2000).
METHODS: PubMed and EMBASE databases were systematically reviewed in November 2023. Studies assessing the relationship between MVP and TSA and estimating the MVP prevalence in pectus excavatum (PE), pectus carinatum (PC), scoliosis, straight back syndrome (SBS) and Marfan syndrome (MS) were included. There was no limitation on time periods.
RESULTS: Twenty-five studies with a total of 2800 patients (27.9 ± 13.9 years, 48.2% females) were analyzed. The highest prevalence of MVP was observed among MS patients (47.3%), while the lowest was detected in PC individuals (23%). Prevalence of MVP was similar among PE (30.8%), scoliosis (26.3%) and SBS (25.5%) patients. When dividing the studies on the basis of temporal period, the average MVP prevalence was approximately two-fold higher in all studies conducted before the year 2000 in comparison with the most recent ones, regardless of TSA type. This discrepancy might be primarily ascribed to relevant differences in the echocardiographic criteria employed for MVP diagnosis before (less specific) and after (more specific) the year 2000, respectively.
CONCLUSIONS: The estimated MVP prevalence in TSA individuals is significantly higher than that observed in the general population. Individuals with TSA should be screened for MVP presence on transthoracic echocardiography.

Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the I2 statistics whilst funnel plots and Egger\'s test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.

Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue structural integrity. These disorders significantly elevate the risk of aortic dissection, a life-threatening condition. This comprehensive review delves into the intricate interplay between connective tissue disorders and aortic dissection, shedding light on the clinical features, pathophysiology, genetic underpinnings, diagnostic approaches, clinical management, associated comorbidities, and prognosis, mainly focusing on MS and EDS, while also exploring rare connective tissue disorders and forms of cutis laxa contributing to aortic pathology.

This study aims to fill this gap by assessing the application of 4D flow CMR in MFS through a systematic review and meta-analysis. We conducted a comprehensive search of databases from their inception to May 1, 2023. Eligibility criteria were established based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), with studies scoring above five deemed high quality. Meta-analyses were performed using Stata 15.1 software. Nine studies were analyzed. Findings indicate MFS patients had increased vortex flow in the descending aorta (DAo), larger aortic root diameter (ARD) and Z-scores, lower inner wall shear stress (WSS) in the proximal descending aorta (pDAo), reduced in-plane rotational flow (IRF) in the aortic arch and proximal descending aorta (pDAo), and increased pulse wave velocity (PWV) in the ascending aorta (AAo) and DAo compared to healthy subjects. No significant difference in systolic flow reversal ratio was observed. Sensitivity analysis showed no heterogeneity and Egger\'s test revealed no publication bias. This meta-analysis underscores the effectiveness of 4D flow CMR in detecting MFS, particularly through indicators such as vortex flow, WSS, IRF, ARD, and PWV. The findings provide insights into diagnosing cardiovascular diseases and predicting cardiovascular events in MFS patients. Further case-control studies are needed to establish measurement standards and explore potential indicators for improved diagnosis and treatment of MFS.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder due to pathogenic variants in Fibrillin-1 (FBN1) affecting nearly one in every 10,000 individuals. We report a 16-month-old female with early-onset MFS heterozygous for an 11.2 kb de novo duplication within the FBN1 gene. Tandem location of the duplication was further confirmed by optical genome mapping in addition to genetic sequencing and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. As the vast majority of pathogenic variants associated with MFS are point mutations, this expands the landscape of known FBN1 pathogenic variants and supports consistent use of genetic testing strategies that can detect large, indel-type variants.

Marfan syndrome (MFS) is a systemic connective tissue disease that commonly and most severely affects the ocular, skeletal, and cardiovascular systems. The aim of the manuscript is to review the aortic involvement and complications in MFS, including aortal dissection, thoracic aortic aneurysm, abdominal aortic aneurysm, and acute aortic syndrome. Dissecting thoracic aortic aneurysm and progressing aortic root enlargement are the major causes of MFS morbidity and mortality. Guidelines on aortic disease endorsed by the American College of Cardiology, and the American Heart Association recommend the measurement of the external and internal aortic diameters perpendicular to the axis of blood flow when Computed Tomography, or Magnetic Resonance Imaging, or Cardiac Echography are performed. The pathophysiology, diagnosis, prevention, and medical and surgical treatments of MFS associated with aortic complications are reported in this narrative review. Development and strengthening of centers specialized in cardiovascular diseases and MFS, together with an improvement in the knowledge of its pathogenesis through genetics and proteomics investigations, can ameliorate the prognosis of this disease.

BACKGROUND: Spinal deformities are common in Marfan syndrome (MFS). They usually involve the thoraco-lumbar spine but rarely involves the cervical spine. Kyphosis is the common spine deformity of the cervical spine and mandates surgical correction as they are at risk of neurological deterioration since they are refractory to conservative management. Few studies of surgical correction of spine deformity included cervical deformity.
OBJECTIVE: To analyze the challenges faced during surgery, clinical and radiological outcome, and complications following surgical correction for cervical kyphosis in Marfan syndrome.
METHODS: We identified that 5 patients with a diagnosis of MFS with cervical kyphosis who underwent fusion surgery between the years 2010 and 2022 were reviewed, retrospectively. We analyzed the demographic details, radiological parameters, operative variables (blood loss and nuances), perioperative complications, length of stay, clinical and radiological outcome, and complications following fusion surgery for cervical kyphosis in MFS.
RESULTS: The mean age of patients was 16.6 ± 4.72 years (range, 12-23 years). The average kyphotic vertebra involved is 3 ± 0.7 bodies (range 2-4) with 2 patients with thoracic deformity. All patients underwent surgical deformity correction. All patients improved clinically with Nurick grade (pre vs. post: 3.4 vs. 2.2) and mJOA (pre vs. post: 8.2 vs. 12.6). There was significant deformity correction from 37.48° to 9.1°. Mean blood loss encountered was 900 ± 173.2 ml. Perioperative complications: wound complication with CSF leak (1). Late complications: ventilator dependence (1) and junctional kyphosis (1). Mean length of hospital stay was 103 ± 178.9 days. All patients were doing symptomatically better after mean follow-up of 58 ± 28.32 months. One patient is bedridden and hospitalized.
CONCLUSIONS: Cervical kyphosis is a rare spine deformity in patients with MFS, and they usually present with neurological deterioration mandating surgical correction. Multidisciplinary approach (pediatrics, genetics and cardiology) is required for systematic evaluation of these patients. They should be evaluated with necessary imaging to rule out associated spinal deformity (atlanto-axial subluxation, scoliosis, and intraspinal pathology like ductal ectasia). Our results suggest better surgical outcome in terms of low operative complications with neurologic improvement in MFS patients. These patients require regular follow-up to identify late complications (instrument failure, non-union, and pseudarthrosis).

Mitral valve prolapse (MVP) represents the most frequent cause of primary mitral regurgitation. For several years, biological mechanisms underlying this condition attracted the attention of investigators, trying to identify the pathways responsible for such a peculiar condition. In the last ten years, cardiovascular research has moved from general biological mechanisms to altered molecular pathways activation. Overexpression of TGF-β signaling, for instance, was shown to play a key role in MVP, while angiotensin-II receptor blockade was found to limit MVP progression by acting on the same signaling pathway. Concerning extracellular matrix organization, the increased valvular interstitial cells density and dysregulated production of catalytic enzymes (matrix metalloproteinases above all) altering the homeostasis between collagen, elastin and proteoglycan components, have been shown to possibly provide a mechanistic basis contributing to the myxomatous MVP phenotype. Moreover, it has been observed that high levels of osteoprotegerin may contribute to the pathogenesis of MVP by increasing collagen deposition in degenerated mitral leaflets. Although MVP is believed to represent the result of multiple genetic pathways alterations, it is important to distinguish between syndromic and non-syndromic conditions. In the first case, such as in Marfan syndrome, the role of specific genes has been clearly identified, while in the latter a progressively increasing number of genetic loci have been thoroughly investigated. Moreover, genomics is gaining more interest as potential disease-causing genes and loci possibly associated with MVP progression and severity have been identified. Animal models could be of help in better understanding the molecular basis of MVP, possibly providing sufficient information to tackle specific mechanisms aimed at slowing down MVP progression, therefore developing non-surgical therapies impacting on the natural history of this condition. Although continuous progress has been made in this field, further translational studies are advocated to improve our knowledge of biological mechanisms underlying MVP development and progression.

To support the development of clinical practice guidelines on the management of patients with genetic aortopathies and arteriopathies, a writing committee from the Society for Vascular Surgery has commissioned this systematic review.
We conducted a systematic review and searched multiple databases for studies addressing six questions identified by the Society for Vascular Surgery guideline committee about evaluating and managing patients with genetic aortopathies and arteriopathies. Studies were selected and appraised by pairs of independent reviewers.
We included 12 studies in this systematic review. We did not identify studies about the long-term outcomes of endovascular repair for aortic aneurysm in patients with heritable aortopathy or about new aortic events in pregnant women with a history of aortic dissection (AD) or aneurysm. A small case series demonstrated a 100% survival rate and 100% aortic intervention-free survival at 15 months (range, 7-28 months) after endograft repair for type B AD. A positive genetic diagnosis was discovered in 36% of patients with aortic aneurysms and dissections who had no risk factors for hereditary aortopathies, and these patients had a mortality rate of 11% at a median follow-up duration of 5 months. Black patients had lower 30-day mortality than White patients (5.6% vs 9.0%, respectively), but they had a higher overall aortic reintervention rate at 30 days after AD repair (47% vs 27%, respectively). Aortic reinterventions owing to aneurysmal expansion and endoleak at 30 days were higher in Black patients than White patients. The certainty of evidence was judged to be very low across all the outcomes evaluated in this systematic review.
The available evidence suggests high survival after thoracic endovascular aortic repair for type B AD in young patients with heritable aortopathies, but with limited long-term follow-up. Genetic testing in patients with acute aortic aneurysms and dissections had a high yield. It was positive for most patients with risk factors for hereditary aortopathies and in more than one-third for all other patients, and was associated with new aortic events within 15 years.

Collagen vascular disorders (CVDs), also known as connective tissue diseases (CTDs), are a heterogeneous group of entities that affect the connective tissues and are capable of causing end-organ damage to multiple systems, primarily cardiopulmonary and musculoskeletal. However, the occurrence and severity are highly variable among patients. Ocular involvement occurs in a significant number of these disorders and may precede the onset of other extraocular features, thereby serving as an important marker in the diagnosis of these diseases. A timely and accurate diagnosis enables the management of complications. CTDs are primarily immune-mediated inflammatory diseases; however, classifications have encompassed heritable disorders affecting collagen-containing structures and disorders of vascular development. A review of literature published until 25 January 2022 and collected from various databases using the relevant keywords was conducted. All publications (original articles, review articles, as well as case reports) describing the ocular features in CTDs were studied in detail. The objective of this review is to recognize the common ophthalmic presentations of various autoimmune and heritable CTDs, distinguish them from overlapping diseases, elaborate on the prognosis and management of these varied eye presentations, and deliberate on their impact on other ophthalmic surgeries.