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Genes May 2024When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is... (Review)
Review
When stroke occurs in pediatric age, it might be mistakenly interpreted as non-accidental head injury (NAHI). In these situations, a multidisciplinary approach is fundamental, including a thorough personal and familial history, along with accurate physical examination and additional investigations. Especially when the clinical picture is uncertain, it is important to remember that certain genetic conditions can cause bleeding inside the brain, which may resemble NAHI. Pediatric strokes occurring around the time of birth can also be an initial sign of undiagnosed genetic disorders. Hence, it is crucial to conduct a thorough evaluation, including genetic testing, when there is a suspicion of NAHI but the symptoms are unclear. In these cases, a characteristic set of symptoms is often observed. This study aims to summarize some of the genetic causes of hemorrhagic stroke in the pediatric population, thus mimicking non-accidental head injury, considering elements that can be useful in characterizing pathologies. A systematic review of genetic disorders that may cause ICH in children was carried out according to the Preferred Reporting Item for Systematic Review (PRISMA) standards. We selected 10 articles regarding the main genetic diseases in stroke; we additionally selected 11 papers concerning patients with pediatric stroke and genetic diseases, or studies outlining the characteristics of stroke in these patients. The disorders we identified were Moyamoya disease (MMD), , pathogenic variant, Ehlers-Danlos syndrome (E-D), neurofibromatosis type 1 (Nf1), sickle cell disease (SCD), cerebral cavernous malformations (CCM), hereditary hemorrhagic telangiectasia (HHT) and Marfan syndrome. In conclusion, this paper provides a comprehensive overview of the genetic disorders that could be tested in children when there is a suspicion of NAHI but an unclear picture.
Topics: Humans; Hemorrhagic Stroke; Child, Preschool; Genetic Testing; Craniocerebral Trauma; Infant; Diagnosis, Differential
PubMed: 38790247
DOI: 10.3390/genes15050618 -
Cureus Feb 2024Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural... (Review)
Review
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 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.
PubMed: 38487153
DOI: 10.7759/cureus.54141 -
Tijdschrift Voor Psychiatrie 2023Hereditary connective tissue disorders are a broad group of congenital disorders that are characterized by a pathological weakness of the connective tissue as a result...
Hereditary connective tissue disorders are a broad group of congenital disorders that are characterized by a pathological weakness of the connective tissue as a result of an incorrect genesis, leading to multisystem complaints. We describe a 14-year-old patient with the hereditary connective tissue disorder Loeys-Dietz syndrome who was admitted to a child psychiatric crisis unit because of depressive and anxiety symptoms. A systematic literature search was carried out to analyze the prevalence of depressive and anxiety symptoms in individuals with hereditary connective tissue disorders Loeys-Dietz syndrome, Ehlers-Danlos syndrome and Marfan syndrome, to identify a possible association between these disorders and explanations for this. We conclude that there is an increased incidence of depression and anxiety symptoms in which pain, fatigue, social support and functioning, quality of life and functional limitations seem to play a role. There is a need for further research to determine exactly which factors contribute and how these can be targeted in prevention and treatment.
Topics: Adolescent; Humans; Anxiety; Connective Tissue; Connective Tissue Diseases; Ehlers-Danlos Syndrome; Loeys-Dietz Syndrome; Quality of Life
PubMed: 37947469
DOI: No ID Found -
Orphanet Journal of Rare Diseases May 2023The purpose of this study was to explore the literature on fatigue in patients with syndromic heritable thoracic aortic disease (sHTAD), including Marfan syndrome (MFS),... (Review)
Review
Fatigue in patients with syndromic heritable thoracic aortic disease: a systematic review of the literature and a qualitative study of patients' experiences and perceptions.
INTRODUCTION
The purpose of this study was to explore the literature on fatigue in patients with syndromic heritable thoracic aortic disease (sHTAD), including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers Danlos syndrome (vEDS) and other sHTADs, critically appraise and synthesize the relevant literature. We also aimed to investigate how adults with sHTAD experience and perceive fatigue, and to discuss clinical implications and direction for further research.
METHODS
First, a systematic review was performed by searching the published literature in all relevant databases and other sources until 20th October 2022. Second, a qualitative focus group interview study was conducted of 36 adults with sHTADs (LDS n = 11, MFS n = 14, vEDS n = 11).
RESULTS
In the systematic review, 33 articles satisfied the eligibility criteria (3 reviews and 30 primary studies). Of the primary studies: 25 dealt with adults (MFS n = 17, MFS/EDS n = 1, EDS n = 2, LDS/vEDS n = 3, different sHTADs n = 2), 5 with children (MFS n = 4, different sHTADs n = 1). Twenty-two were cross-sectional quantitative studies, 4 prospective and 4 qualitative studies. The quality of the included studies was mostly good, but many had small sample sizes, low response rates and/or participants without verified diagnosis. Despite these limitations, studies indicated high prevalence of fatigue (ranging from 37 to 89%), and fatigue was associated with both health and psychosocial aspects. Few studies found that fatigue was associated with disease-related symptoms. In the qualitative focus groups most of the participants reported that they had experienced fatigue which influenced several aspects of life. Four themes related to fatigue were elucidated: (1) different diagnoses-different fatigue?, (2) the nature of fatigue, (3) searches for causes of fatigue, (4) dealing with fatigue in daily life. The four themes seemed mutually interrelated in terms of barriers, strategies and facilitators for dealing with fatigue. The participants experienced fatigue as a consistent dilemma between self-assertion and inadequacy. Fatigue seems to influence several aspects of daily life and may be one of the most debilitating symptoms of having a sHTAD.
CONCLUSION
Fatigue seems to negatively impact the lives of people with sHTADs and should be recognized as an important aspect in the lifelong follow-up of these patients. The life-threatening complications of sHTADs may result in emotional stress, including fatigue and the risk of developing a sedentary lifestyle. Research and clinical initiatives should consider rehabilitation interventions aiming at postponing the onset or reducing symptoms of fatigue.
Topics: Adult; Child; Humans; Prospective Studies; Marfan Syndrome; Loeys-Dietz Syndrome; Qualitative Research; Ehlers-Danlos Syndrome, Type IV; Fatigue
PubMed: 37208760
DOI: 10.1186/s13023-023-02709-2 -
Medicina (Kaunas, Lithuania) Nov 2022: Marfan syndrome (MS) is a genetic disorder with autosomal dominant inheritance that affects the connective tissue and consequently many organ systems. The... (Review)
Review
: Marfan syndrome (MS) is a genetic disorder with autosomal dominant inheritance that affects the connective tissue and consequently many organ systems. The cardiovascular manifestations of MS are notorious and include aortic root dilatation or acute aortic dissection, which can cause morbidity and early mortality. However, surgical treatment of aortic pathology may be complicated by musculoskeletal deformity of the chest wall, as in pectus excavatum. In this regard, single-stage combined Bentall and Ravitch surgery is an extreme rarity that has also been scarcely reported in the literature. : We present the medical history and single-stage Bentall and modified Ravitch surgical treatment of an 18-year-old male MS patient with symptomatic and severe pectus excavatum (PEX) in conjunction with a pear-shaped aortic root aneurysm. To discuss our case in the context of a synopsis of similar published cases, we present a systematic review of combined Bentall surgical aortic aneurysm repair and Ravitch correction of PEX. : A total of four studies (one case series and three case reports) and a case from our institution describing a single-stage combined Bentall and Ravitch operation were included. Patients were 22 ± 5.9 years of age (median = 22.5 years) and predominantly male (60%). All cases reported a midline vertical skin incision over the sternum. The most common surgical approach was midsternotomy (80%). In all cases metal struts were used to reinforce the corrected chest wall. Postoperative mortality was zero. : Single-stage combined Bentall and Ravitch surgery is an underutilized surgical approach. Its use in MS patients with concomitant PEX and ascending aortic aneurysm that require surgical treatment warrants further investigation. Midsternotomy seems to be a viable access route that provides sufficient exposure in the single-stage surgical setting. Although operative time is long, the intraoperative and postoperative risks appear to be low and manageable.
Topics: Humans; Male; Young Adult; Adult; Adolescent; Female; Funnel Chest; Marfan Syndrome; Sternum; Aortic Dissection; Aorta; Treatment Outcome
PubMed: 36556976
DOI: 10.3390/medicina58121774 -
Frontiers in Cardiovascular Medicine 2022Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common...
Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common cause of heart failure leading to significant morbidity and mortality in both species. Human MVP is usually classified into primary or non-syndromic, including Barlow's Disease (BD), fibro-elastic deficiency (FED) and Filamin-A mutation, and secondary or syndromic forms (typically familial), such as Marfan syndrome (MFS), Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Despite different etiologies the diseased valves share pathological features consistent with myxomatous degeneration. To reflect this common pathology the condition is often called myxomatous mitral valve degeneration (disease) (MMVD) and this term is universally used to describe the analogous condition in the dog. MMVD in both species is characterized by leaflet thickening and deformity, disorganized extracellular matrix, increased transformation of the quiescent valve interstitial cell (qVICs) to an activated state (aVICs), also known as activated myofibroblasts. Significant alterations in these cellular activities contribute to the initiation and progression of MMVD due to the increased expression of transforming growth factor-β (TGF-β) superfamily cytokines and the dysregulation of the TGF-β signaling pathways. Further understanding the molecular mechanisms of MMVD is needed to identify pharmacological manipulation strategies of the signaling pathway that might regulate VIC differentiation and so control the disease onset and development. This review briefly summarizes current understanding of the histopathology, cellular activities, molecular mechanisms and pathogenesis of MMVD in dogs and humans, and in more detail reviews the evidence for the role of TGF-β.
PubMed: 35656405
DOI: 10.3389/fcvm.2022.872288 -
International Journal of Environmental... Apr 2022This meta-analysis aimed to compare Marfan syndrome (MFS) patients with non-MFS populations based on orofacial health status to combine publicly available scientific... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aimed to compare Marfan syndrome (MFS) patients with non-MFS populations based on orofacial health status to combine publicly available scientific information while also improving the validity of primary study findings. A comprehensive search was performed in the following databases: PubMed, Google Scholar, Scopus, Medline, and Web of Science, for articles published between 1 January 2000 and 17 February 2022. PRISMA guidelines were followed to carry out this systematic review. We used the PECO system to classify people with MFS based on whether or not they had distinctive oral health characteristics compared to the non-MFS population. The following are some examples of how PECO is used: P denotes someone who has MFS; E stands for a medical or genetic assessment of MFS; C stands for people who do not have MFS; and O stands for the orofacial characteristics of MFS. Using the Newcastle-Ottawa Quality Assessment Scale, independent reviewers assessed the articles' methodological quality and extracted data. Four case-control studies were analyzed for meta-analysis. Due to the wide range of variability, we were only able to include data from at least three previous studies. There was a statistically significant difference in bleeding on probing and pocket depth between MFS and non-MFS subjects. MFS patients are more prone to periodontal tissue inflammation due to the activity of FBN1 and MMPs. Early orthodontic treatment is beneficial for the correction of a narrow upper jaw and a high palate, as well as a skeletal class II with retrognathism of the lower jaw and crowding of teeth.
Topics: Case-Control Studies; Cleft Palate; Humans; Marfan Syndrome; Oral Health
PubMed: 35564443
DOI: 10.3390/ijerph19095048 -
Journal of Thoracic Disease Aug 2021Aortic aneurysm and dissection are important causes of morbimortality in patients with Marfan syndrome (MFS) and other connective tissue diseases that affect the...
Systematic review and meta-analysis of aortic valve-sparing surgery versus replacement surgery in ascending aortic aneurysms and dissection in patients with Marfan syndrome and other genetic connective tissue disorders.
BACKGROUND
Aortic aneurysm and dissection are important causes of morbimortality in patients with Marfan syndrome (MFS) and other connective tissue diseases that affect the cardiovascular tissues. Timely intervention through different surgical techniques improves the prognosis. Both sparing and replacement-type interventions of the aortic valve are used, but selection depends on the condition of the patient at the time of diagnosis, the patient's emergency condition, surgeon preference and hospital resources. Previous meta-analyses have suggested an advantage with the use of sparing-type interventions, but this finding must be updated and extended to patients with other connective tissue disorders. The objetive of this study is to evaluate the outcomes of valve-sparing root replacement versus aortic root replacement procedures in patients with MFS and similar connective tissue diseases that present with aortic aneurysm or dissection.
METHODS
A systematic review of cohort studies that evaluated sparing-type (preserving, remodeling, reimplantation, Yacoub, David or Florida Sleeve) or replacement-type (repair, Bentall, Button-Bentall, composite valve graft or Cabrol) procedures in patients with Marfan, Loeys-Dietz, Beals-Hecht or Ehlers-Danlos syndromes was done. Studies were retrieved from the SCOPUS, MEDLINE, CINAHL, EMBASE and LILACS electronic databases up to January 2020 without language restrictions. Only studies that directly compared sparing- versus replacement-type procedures were included in the meta-analysis.
RESULTS
A total of 33 studies (n=1,807 subjects) reported sparing-type surgical interventions and 26 studies (n=2,218 subjects) reported replacement-type surgical interventions. Pooled rates of endocarditis, thromboembolism and aneurysm were higher in replacement-type surgical intervention studies. Sixteen studies were included in the meta-analysis. Sparing-type interventions were associated with a reduced risk of endocarditis (RR =0.13, 95% CI: 0.03-0.61); however, replacement-type interventions favored freedom from valve reoperation (RR =2.39, 95% CI: 1.24-4.60). All studies were at low risk of bias.
CONCLUSIONS
The choice of the best surgical technique is dependent on the type of disease (MFS or other connective tissue diseases) as well as the accompanying aortic and cardiovascular damage, since these key factors are heterogeneous. Although the results of this meta-analysis tend to show some advantages for one type of surgical intervention over the other and viceversa, the surgeon can only make the best decision during the surgical act.
PubMed: 34527322
DOI: 10.21037/jtd-21-789 -
Case Reports in Genetics 2020Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by...
Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by pathogenic variants in the proto-oncogene gene, a known suppressor of TGF- activity, located on chromosome 1p36. There is considerable phenotypic overlap with Marfan and Loeys-Dietz syndromes. Common clinical features of SGS include craniosynostosis, marfanoid habitus, hypotonia, dysmorphic facies, cardiovascular anomalies, and other skeletal and connective tissue abnormalities. Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. We describe a 25-year-old male with the syndrome. Genetic analysis revealed a novel c.350G>A (p.Arg117His) variant, which was predicted to be pathogenic by the CTGT laboratory. The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures. His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia. Ophthalmic manifestations are an integral component of the syndrome; however, they have not been well characterized in the literature. From a systematic review of previously published cases to date, we summarize the eye and ocular adnexa manifestations reported.
PubMed: 33628537
DOI: 10.1155/2020/7353452 -
Asia-Pacific Journal of Ophthalmology... Jan 2021We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and...
PURPOSE
We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome.
DESIGN
Systematic review.
METHODS
We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes.
RESULTS
Our search yielded 217 papers. After removing duplicated and irrelevant reports, we included 57 articles involving 2624 eyes. The mean age at operation was 51.47 ± 25.62 years. Sutured SFIOL was most commonly reported in all subjects with Marfan syndrome and 92.87% of pediatric patients. The pooled intraoperative complication rate was 6.65%. Minor anterior chamber hemorrhage was the most common intraoperative (1.92%) and postoperative complication (13.93%). Optic capture was the top intraocular lens (IOL)-related complication (4.47%). The overall mean endothelial cell loss was 8.95% at 16.77 ± 11.04 months. Overall 11.99% of SFIOLs were decentred with a mean distance of 0.49 ± 0.40 mm and a mean degree of tilt by 4.11 ± 3.03°.
CONCLUSIONS
Glued SFIOL had the fewest IOL-related complications and the lowest endothelial cell loss. Sutured SFIOL carried the highest IOL-related complications, whereas sutureless, glueless SFIOL was associated with the greatest endothelial cell loss.
Topics: Humans; Lens Implantation, Intraocular; Lenses, Intraocular; Postoperative Complications; Retrospective Studies; Sclera; Suture Techniques; Visual Acuity
PubMed: 33481393
DOI: 10.1097/APO.0000000000000369