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Cureus Apr 2024Marfan syndrome, a hereditary disorder of connective tissue marked by FBN1 gene mutations, presents a clinical tapestry requiring a multidisciplinary approach for...
Marfan syndrome, a hereditary disorder of connective tissue marked by FBN1 gene mutations, presents a clinical tapestry requiring a multidisciplinary approach for optimal management. This case report details the presentation of an 11-year-old male exhibiting musculoskeletal deformities, notably an abnormally curved spine and congenital hip dysplasia, indicative of Marfan syndrome. The absence of cardiovascular abnormalities and family history challenges the diagnostic process. Clinical evaluation revealed classical signs, including positive wrist and thumb signs, pectus carinatum, a loose skin fold, and scapular winging. Laboratory investigations, including imaging studies, confirmed the diagnosis. The patient's management involves a multifaceted strategy, addressing cardiovascular risks through beta-blockers and potential surgical interventions, orthopedic measures for musculoskeletal complications, and ophthalmologic interventions for ocular manifestations. Genetic counseling facilitates informed decision-making, and psychosocial support ensures holistic care. This case underscores the necessity of recognizing atypical presentations and employing a holistic, collaborative approach for early diagnosis and effective management of Marfan syndrome, thereby emphasizing the importance of ongoing research and heightened clinical awareness in enhancing outcomes for individuals living with this intricate genetic disorder.
PubMed: 38707097
DOI: 10.7759/cureus.57569 -
European Journal of Pediatrics May 2024The cardinal phenotypic hallmarks of Marfan syndrome (MFS) include cardiac, ocular, and skeletal abnormalities. Since the clinical phenotype of MFS is highly...
The cardinal phenotypic hallmarks of Marfan syndrome (MFS) include cardiac, ocular, and skeletal abnormalities. Since the clinical phenotype of MFS is highly heterogeneous, with certain symptoms appearing as children age, the diagnostic process and establishing a genotype-phenotype association in childhood MFS can be challenging. The lack of sufficient childhood studies also makes it difficult to interpret the subject. This study aims to evaluate the relationship between clinical symptoms used as diagnostic criteria and FBN1 variations in children with MFS. This study investigated the relationships between genotypes and phenotypes in 131 children suspected of having Marfan syndrome (MFS). Diagnosis of MFS was made according to the revised Ghent nosology. FBN1 variants were categorized based on exon regions, type of variant, and pathogenicity classes. These FBN1 variants were then correlated with the clinical manifestations including cardiovascular, ocular, facial, and skeletal abnormalities. Out of the children, 43 were diagnosed with MFS. FBN1 variant was identified in 32 (74.4%) of the MFS children. MFS diagnosis could not be made in five (15.6%) FBN1 variant-positive children. The most common cardinal finding is cardiac anomalies n = 38 (88.3%). The most common FBN1 pathogenic variant was c.1786 T > C/p.Cys596Arg n = 4 (12.5%). The distribution of pathogenic variants was as follows: 29 (90.6%) missense, 2 (6.3%) frameshift, and 1 (3.1%) nonsense. The numbers of AD and EL of the variant-positive children were 16 (50%) and 14 (43.7%), respectively. Ocular abnormalities were more common in children with FBN1-positive MFS (p = 0.009). There was no difference in the number of cardiac abnormalities between FBN1-positive and FBN1-negative MFS patients (p = 0.139). Conclusion: This study examines the relationship between FBN1 variants and clinical features used as diagnostic criteria in MFS children. The findings emphasize the importance of long-term monitoring of heterogeneous clinical phenotypes and bioinformatic reanalysis in determining the genotype-phenotype relationship in children, as MFS symptoms can vary with age. What is Known: • Marfan syndrome has highly variable phenotypic heterogeneity. • The genotype-phenotype relationship in childhood Marfan syndrome is not clear enough due to the variation in the time of onset of the findings. What is New: • This article provides regional data for the field of research on genotype-phenotype relationships in childhood Marfan syndrome. • Long-term follow-up of clinical findings and bioinformatics reanalysis is an important requirement for a well-established genotype-phenotype relationship in childhood Marfan syndrome.
PubMed: 38700693
DOI: 10.1007/s00431-024-05579-3 -
Orphanet Journal of Rare Diseases Apr 2024This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome...
BACKGROUND
This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson's or Spearman's coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group.
RESULTS
Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VOmax) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy.
CONCLUSIONS
This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.
Topics: Humans; Quality of Life; Marfan Syndrome; Male; Female; Cross-Sectional Studies; Child; Adolescent; Surveys and Questionnaires
PubMed: 38685042
DOI: 10.1186/s13023-024-03191-0 -
Journal of AAPOS : the Official... Jun 2024To report the long-term clinical and endothelial cell count (ECC) results of lensectomy with primary anterior chamber iris claw lens implantation in the eyes of patients...
PURPOSE
To report the long-term clinical and endothelial cell count (ECC) results of lensectomy with primary anterior chamber iris claw lens implantation in the eyes of patients ≤18-year-old with ectopia lentis due to Marfan syndrome.
METHODS
The medical records of Marfan patients operated on at a single institution from September 2007 to August 2020, with minimum follow-up of 2 years, were reviewed retrospectively. The following data were analyzed: sex, age at surgery, indication for surgery, the position of the lens in relation to the undilated and dilated pupil, corneal endothelial cell counts (ECC), peri- and postoperative complications, pre- and postoperative best-corrected visual acuity.
RESULTS
A total of forty-two eyes of 23 patients (12 girls and 11 boys) were included. At least two or more postoperative ECCs were collected from 33 eyes (17 patients). Median age at IOL implantation was 6.1 years (range, 1.8-18). Median overall follow-up time was 6.2 years (range, 2-13.5). Median ECC follow-up time was 6.2 years (range, 2-10). Mean best-corrected visual acuity was 0.71 ± 0.38 logMAR before surgery and 0.02 ± 0.25 logMAR at final follow-up. The mean annual ECC decline was 0.71% ± 2.24. Total cell loss from first to last postoperative measurement was 150 cells ± 394 cells/mm (4.81%). Pre- and first postoperative data were available for 17 eyes of 10 patients, with a mean cell loss before and directly after surgery of 269 ± 268 cells (7.94%). Surgery related complications were iris bombé due to blockage of peripheral iridectomy in 3 eyes and claw dislocation due to direct impact trauma in 3 eyes.
CONCLUSIONS
In our large, pediatric study cohort, anterior chamber iris claw IOL implantation resulted in an excellent visual outcome and normal endothelial cell loss compared with normative data. Safety measures are recommended to avoid traumatic dislocation of IOLs.
Topics: Humans; Ectopia Lentis; Marfan Syndrome; Female; Male; Child; Lens Implantation, Intraocular; Retrospective Studies; Visual Acuity; Child, Preschool; Adolescent; Iris; Anterior Chamber; Follow-Up Studies; Infant; Lenses, Intraocular; Postoperative Complications; Endothelium, Corneal; Cell Count
PubMed: 38679138
DOI: 10.1016/j.jaapos.2024.103922 -
Ophthalmology. Retina Apr 2024
PubMed: 38678477
DOI: 10.1016/j.oret.2024.04.001 -
The Journal of Thoracic and... Apr 2024To review the pathology of the mitral valve (MV) and long-term outcomes of surgery in patients with Marfan syndrome (MFS).
OBJECTIVE
To review the pathology of the mitral valve (MV) and long-term outcomes of surgery in patients with Marfan syndrome (MFS).
PATIENTS AND METHODS
From 1988 through 2020, 60 patients with MFS had surgery to correct mitral regurgitation (MR): 19 had isolated MV surgery, 32 had combined MV and aortic root surgery, and 9 had MV surgery after aortic root surgery. Follow-up was complete for a median of 16.1 years.
RESULTS
MV pathology was myxomatous degeneration in all patients and of advanced degree in 78.6% with bileaflet prolapse in 65.5%, mitral annulus disjunction in 57.5%, and mitral annulus calcification in 8.2% of patients. The MV was repaired in 47 patients and replaced in 13. Kaplan-Meier estimates of cumulative mortality at 20 years 21.3% for all patients, 6.7% after MV repair, and 57.8% after replacement (P < .001). MV reoperations were performed in 5 patients: 2 after repair and 3 after replacement. The cumulative incidence rate of reoperations on the MV was 3.8% at 10 years and 11.0% at 20 years in the entire cohort. Among 47 patients who had MV repair, moderate MR developed in 11 patients and severe in 2. Both patients with severe MR underwent MV reoperation. The cumulative incidence rate of recurrent moderate or severe MR after MV repair was 20.4% at 10 years, and 36.5% at 20 years.
CONCLUSIONS
MV repair was associated with better survival than MV replacement, but recurrent MR after repair occurred in approximately one-third of the patients at 20 years after surgery.
PubMed: 38678476
DOI: 10.1016/j.jtcvs.2024.01.046 -
Ear, Nose, & Throat Journal Apr 2024Epidermoid cysts are rare benign lesions that can derive from abnormally situated ectodermal tissue during embryological development or from implanted epithelium after...
Epidermoid cysts are rare benign lesions that can derive from abnormally situated ectodermal tissue during embryological development or from implanted epithelium after trauma or surgery. In the oral and maxillofacial regions, epidermoid cysts usually develop in the floor of the mouth and rarely in other sites. We describe a rare case of an epidermoid cyst arising in the right maxillary sinus. A 29-year-old man with a known diagnosis of Marfan syndrome presented with progressive swelling and tenderness in the right buccal region, mimicking facial cellulitis, and refractory to medical treatment. Computed tomography scan showed a cystic lesion extending widely into the right maxillary sinus. The cyst was successfully removed with a medial maxillectomy through inferior antrostomy approach under general anesthesia. Histological examination confirmed the diagnosis of an epidermoid cyst, showing a cystic wall lined with a thin layer of keratinizing squamous epithelium and fibroma connective tissue infiltrated with inflammatory cells, with no skin appendages. There has been no evidence of recurrence during the 4 year follow-up. We also conduct a review of the English literature for the reported cases of maxillary epidermoid cyst.
PubMed: 38676551
DOI: 10.1177/01455613241249054 -
Journal of Cardiovascular Development... Apr 2024Marfan syndrome (MIM: # 154700; MFS) is an autosomal dominant disease representing the most common form of heritable connective tissue disorder. The condition presents... (Review)
Review
Marfan syndrome (MIM: # 154700; MFS) is an autosomal dominant disease representing the most common form of heritable connective tissue disorder. The condition presents variable multiorgan expression, typically involving a triad of cardiovascular, eye, and skeletal manifestations. Other multisystemic features are often underdiagnosed. Moreover, the disease is characterized by age related penetrance. Diagnosis and management of MFS in the adult population are well-described in literature. Few studies are focused on MFS in the pediatric population, making the clinical approach (cardiac and multiorgan) to these cases challenging both in terms of diagnosis and serial follow-up. In this review, we provide an overview of MFS manifestations in children, with extensive revision of major organ involvement (cardiovascular ocular and skeletal). We attempt to shed light on minor aspects of MFS that can have a significant progressive impact on the health of affected children. MFS is an example of a syndrome where an early personalized approach to address a dynamic, genetically determined condition can make a difference in outcome. Applying an early multidisciplinary clinical approach to MFS cases can prevent acute and chronic complications, offer tailored management, and improve the quality of life of patients.
PubMed: 38667733
DOI: 10.3390/jcdd11040114 -
Cureus Mar 2024Our purpose is to report a patient with a novel variant in the fibrillin-1 ()gene causing the Marfan syndrome (MFS). The 29-year-old female patient with musculoskeletal,...
Our purpose is to report a patient with a novel variant in the fibrillin-1 ()gene causing the Marfan syndrome (MFS). The 29-year-old female patient with musculoskeletal, cardiovascular, and ocular findings compatible with the MFS had a novel pathogenic mutation on the gene. We report on a patient whose clinical findings are compatible with the MFS. This patient's variant on the gene leading to the syndrome has not been previously described. Additional investigations are needed to determine whether this variant contributes to the development of camptodactyly in patients with the syndrome.
PubMed: 38665719
DOI: 10.7759/cureus.56948 -
Advances in Rheumatology (London,... Apr 2024Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular... (Review)
Review
Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.
Topics: Humans; Arthritis; Collagen; Connective Tissue Diseases; Ehlers-Danlos Syndrome; Hearing Loss, Sensorineural; Joint Instability; Loeys-Dietz Syndrome; Marfan Syndrome; Osteogenesis Imperfecta; Retinal Detachment
PubMed: 38664779
DOI: 10.1186/s42358-024-00373-z