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International Journal of Molecular... Feb 2024Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms... (Review)
Review
Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.
Topics: Humans; Aortic Valve; MicroRNAs; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Bicuspid Aortic Valve Disease; Marfan Syndrome; Calcinosis; Phenotype; Atherosclerosis; Fibrosis
PubMed: 38473887
DOI: 10.3390/ijms25052641 -
European Journal of Pediatrics May 2024Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This... (Observational Study)
Observational Study
Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This observational, cross-sectional, multicenter study explores associations between physical fitness and cardiovascular parameters, systemic manifestations, fatigue, and pain in children with MFS and LDS. Forty-two participants, aged 6-18 years (mean (SD) 11.5(3.7)), diagnosed with MFS (n = 36) or LDS (n = 6), were enrolled. Physical fitness was evaluated using the Fitkids Treadmill Test's time to exhaustion (TTE) outcome measure. Cardiovascular parameters (e.g., echocardiographic parameters, aortic surgery, cardiovascular medication) and systemic manifestations (systemic score of the revised Ghent criteria) were collected. Pain was obtained by visual analog scale. Fatigue was evaluated by PROMIS® Fatigue-10a-Pediatric-v2.0-short-form and PROMIS® Fatigue-10a-Parent-Proxy-v2.0-short-form. Multivariate linear regression analyses explored associations between physical fitness (dependent variable) and independent variables that emerged from the univariate linear regression analyses (criterion p < .05). The total group (MFS and LDS) and the MFS subgroup scored below norms on physical fitness TTE Z-score (mean (SD) -3.1 (2.9); -3.0 (3.0), respectively). Univariate analyses showed associations between TTE Z-score aortic surgery, fatigue, and pain (criterion p < .05). Multivariate analyses showed an association between physical fitness and pediatric self-reported fatigue that explained 48%; 49%, respectively, of TTE Z-score variance (F (1,18) = 18.6, p ≤ .001, r = .48; F (1,15) = 16,3, p = .01, r = .49, respectively). Conclusions: Physical fitness is low in children with MFS or LDS and associated with self-reported fatigue. Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with MFS and LDS. What is Known: • Marfan and Loeys-Dietz syndrome are heritable connective tissue disorders and share cardiovascular and systemic manifestations. • Children with Marfan and Loeys-Dietz syndrome report increased levels of disability, fatigue and pain, as well as reduced levels of physical activity, overall health and health-related quality of life. What is New: • Physical fitness is low in children with Marfan and Loeys-Dietz syndrome and associated with self-reported fatigue. • Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with Marfan and Loeys-Dietz syndrome.
Topics: Humans; Loeys-Dietz Syndrome; Adolescent; Marfan Syndrome; Child; Male; Cross-Sectional Studies; Female; Physical Fitness; Fatigue; Pain; Exercise Test
PubMed: 38466415
DOI: 10.1007/s00431-024-05456-z -
Scientific Reports Mar 2024In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS...
In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (Fbn1) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. It is well established that the MFS mouse model exhibits an accelerated-aging phenotype in elastic organs like the aorta, lung, and skin. However, the impact of Fbn1 mutations on the in vivo function and structure of various artery types with the consideration of sex and age, has not been adequately explored in real-time and a clinically relevant context. In this study, we investigate if Fbn1 mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice. In vivo ultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls. Furthermore, this research is a vital step in understanding MFS's broader implications and sets the stage for more in-depth future analyses, while providing data-driven preclinical justification for re-evaluating diagnostic approaches and therapeutic efficacy.
Topics: Animals; Female; Male; Mice; Aorta; Fibrillin-1; Marfan Syndrome; Mice, Inbred C57BL; Mutation; Phenotype
PubMed: 38461168
DOI: 10.1038/s41598-024-56438-y -
Journal of Medical Genetics Apr 2024Marfan syndrome (MFS) is a multisystem disease with a unique combination of skeletal, cardiovascular and ocular features. Geleophysic/acromicric dysplasias...
BACKGROUND
Marfan syndrome (MFS) is a multisystem disease with a unique combination of skeletal, cardiovascular and ocular features. Geleophysic/acromicric dysplasias (GPHYSD/ACMICD), characterised by short stature and extremities, are described as 'the mirror image' of MFS. The numerous pathogenic variants identified in MFS are located all along the gene and lead to the same final pathogenic sequence. Conversely, in GPHYSD/ACMICD, the 28 known heterozygous pathogenic variants all affect exons 41-42 encoding TGFβ-binding protein-like domain 5 (TB5).
METHODS
Since 1996, more than 5000 consecutive probands have been referred nationwide to our laboratory for molecular diagnosis of suspected MFS.
RESULTS
We identified five MFS probands carrying distinct heterozygous pathogenic in-frame variants affecting the TB5 domain of FBN1. The clinical data showed that the probands displayed a classical form of MFS. Strikingly, one missense variant affects an amino acid that was previously involved in GPHYSD.
CONCLUSION
Surprisingly, pathogenic variants in the TB5 domain of FBN1 can lead to two opposite phenotypes: GPHYSD/ACMICD and MFS, suggesting the existence of different pathogenic sequences with the involvement of tissue specificity. Further functional studies are ongoing to determine the precise role of this domain in the physiopathology of each disease.
Topics: Humans; Bone Diseases, Developmental; Fibrillin-1; Limb Deformities, Congenital; Marfan Syndrome; Mutation
PubMed: 38458756
DOI: 10.1136/jmg-2023-109646 -
Frontiers in Genetics 2024Increasing evidence shows that epigenetics also plays a key role in regulating the pathogenetic mechanism of all types of aortic aneurysms. It is well-known that... (Review)
Review
Increasing evidence shows that epigenetics also plays a key role in regulating the pathogenetic mechanism of all types of aortic aneurysms. It is well-known that epigenetic factors modulate gene expression. This mechanism appears to be of interest especially knowing the relevance of genetic susceptibility and genetic factors in the complex pathophysiology of aortic aneurysms, and of sporadic forms; in fact, the latter are the result of a close interaction between genetic and modifiable lifestyle factors (i.e., nutrition, smoking, infections, use of drugs, alcohol, sedentary lifestyle, etc.). Epigenetic factors include DNA methylation, post-translational histone modifications, and non-coding RNA. Here, our attention is focused on the role of miRNA in syndromic and sporadic forms of thoracic aortic aneurysms. They could be both biomarkers and targets of novel therapeutic strategies.
PubMed: 38450200
DOI: 10.3389/fgene.2024.1365711 -
International Journal of Surgery Case... Mar 2024Dural ectasia, which is often idiopathic, is seen both in patients with neurofibromatosis and Marfan's syndrome. In neurofibromatosis, the ectasia is most often seen in...
INTRODUCTION AND IMPORTANCE
Dural ectasia, which is often idiopathic, is seen both in patients with neurofibromatosis and Marfan's syndrome. In neurofibromatosis, the ectasia is most often seen in the thoracic region but can occur at any point along the dura. A complication such as cauda equina syndrome is usually rare.
CLINICAL PRESENTATION
A 48 year old male complaining of recurrent throbbing headache, for 3 years, 2 years ago he developed progressively lower back pain, associated with numbness and tingling sensation of the lower limbs. A year ago he experienced defecation and urinary incontinence. On further questioning the patient reported to have first degree relative with neurofibromatosis. On examination he has multiple café au laite on the trunk, back and left arm, and plexiform on the left palm, mild right deviation on thoracic region on the back. Lower limb muscle power grade 4/5 bilaterally, sensation was intact. Laboratory work up Full blood counts, electrolytes, renal and liver function tests were normal, MRI of the lumbar spine demonstrate L3/L4 and L4/l5 mild disc bulge with no significant narrowing of the primary canal and no evidence of existing nerve root impingement, increase antero-posterior diameter of dura sac involving L5-S1, with a Dural Sac Diameter of S1 increased compared to that of L4 with mild scalloping of lower lumbar vertebra and pronounced at S1 vertebral body. A diagnosis of cauda equina syndrome and dural ectasia secondary to neurofibromatosis was rendered. Lumbar peritoneal shunting, was reached as a surgical treatment for this patient, but due to inadequate and unavailability of the required shunting equipment, the patient was managed conservatively with anti- inflammatory medications, lumbar CSF tapping, genital hygiene and counselling. 3 months of follow up, the patient was able to walk, with power 5/5 to both lower limbs, however fecal and urine incontinence persisted.
DISCUSSION
this case was particularly unusual due to the combination of cauda equina syndrome and dural ectasia, Dural ectasia is seen with various conditions including Marfan syndrome, Ehlers-syndrome, neurofibromatosis 1, Ankylosing spondylitis, trauma, scoliosis or tumors it may also have no clear cause. In most cases patients with dural ectasia are asymptomatic few may present with low back pain, radicular pain in the buttocks or legs and headache and rarely caudal equina syndrome. The management of dura ectasia may be conservative for asymptomatic patient and for a symptomatic patient surgery such as stabilization, marsupialization and lumbar peritoneal shunt.
CONCLUSION
Dural ectasia with cauda equina syndrome are rarely complication of neurofibromatosis. Familiarity with its classic imaging and clinical features as described in this case report can help its early detection and management.
PubMed: 38442676
DOI: 10.1016/j.ijscr.2024.109465 -
Journal of Neurosurgery. Case Lessons Mar 2024Marfan syndrome, a connective tissue disorder, poses unique challenges in neurosurgery, given the fragility of vascular structures. Superior cerebellar artery (SCA)...
BACKGROUND
Marfan syndrome, a connective tissue disorder, poses unique challenges in neurosurgery, given the fragility of vascular structures. Superior cerebellar artery (SCA) aneurysms in patients with the syndrome are rare and present distinct surgical difficulties, necessitating innovative approaches.
OBSERVATIONS
A 29-year-old male with Marfan syndrome presented with a subarachnoid hemorrhage from a ruptured SCA aneurysm. Given the lack of a defined aneurysm neck and the small diameter of the SCA, standard clipping and endovascular therapies were unsuitable. A microsurgical approach using microsutures was successfully employed, effectively managing the aneurysm while preserving the parent artery.
LESSONS
This case underscores the efficacy of the microsuture technique in complex neurosurgical scenarios, particularly in patients with connective tissue disorders such as Marfan syndrome. The adaptability of surgical strategies, as demonstrated in this case, is crucial for achieving successful outcomes in patients with unique anatomical challenges.
PubMed: 38437680
DOI: 10.3171/CASE23763 -
Journal of Diabetes Investigation Mar 2024Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP-D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by...
Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP-D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by pathogenetic variants in FBN1. Here, we report a patient with type 2 diabetes mellitus, AVP-D, and Marfan syndrome. Although the coexistence of type 2 diabetes mellitus and AVP-D is rare, for those patients with type 2 diabetes mellitus, the existence of AVP-D should be considered when polyuria is not in accordance with the blood glucose levels, especially for those with a low urine specific gravity. Specific symptoms or signs help to identify Marfan syndrome early, and genetic testing of the FBN1 pathogenetic variant helps to make a definitive diagnosis.
PubMed: 38429969
DOI: 10.1111/jdi.14169 -
BMC Cardiovascular Disorders Feb 2024There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome.
BACKGROUND
There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome.
METHODS
Young adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status.
RESULTS
After PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged.
CONCLUSIONS
The QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease's progression.
Topics: Young Adult; Humans; Middle Aged; Marfan Syndrome; Quality of Life; Aortic Dissection; Pain; China
PubMed: 38424531
DOI: 10.1186/s12872-024-03740-2 -
Cureus Jan 2024Meningoceles refer to the protrusion of meninges filled with cerebrospinal fluid (CSF) through a bone defect. There is scarce literature on the management of multiple...
Meningoceles refer to the protrusion of meninges filled with cerebrospinal fluid (CSF) through a bone defect. There is scarce literature on the management of multiple giant anterior sacral meningoceles (ASMs). We report the case of a patient with Marfan syndrome presenting with gait disturbances and dizziness triggered by posture changes due to multiple giant ASMs. The patient was managed through an anterior approach involving a multidisciplinary team of surgeons. Care was taken to limit the persistence of CSF leak using an omental pedicled flap. This technique has only been mentioned twice in the literature for such cases. A literature review was conducted focusing on the evolution course and surgical strategy of meningoceles.
PubMed: 38384626
DOI: 10.7759/cureus.52724