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BACKGROUND: Ophthalmic complications are profound in Marfan syndrome (MFS). However, the overall burden is not well described. Our purpose was to evaluate the ocular morbidity in a nationwide perspective. METHODS: We identified the ocular morbidity in patients with MFS (n=407) by use of Danish national healthcare registers, using number and timing of hospital contacts related to ophthalmic diagnoses, to ophthalmic surgery and to prescriptions for ophthalmic medication. An age-matched and gender-matched background population (n=40 700) was used as comparator. RESULTS: Among MFS, 56% (226/407) of the patients had at least one registration of an ophthalmic diagnosis as inpatient or outpatient during the study period (HR of 8.0 (95% CI 7.0 to 9.2)). Seven out of 11 main groups of diagnoses were affected, including 'Lens', 'Choroid and retina', 'Ocular muscles, binocular movement, accommodation and refraction', 'Glaucoma', Visual disturbances and blindness', 'Vitreous body and globe', and 'Sclera, cornea, iris and ciliary body'. The number of surgical procedures as well as the use of ophthalmic medication in patients with MFS was significantly increased. CONCLUSION: This nationwide epidemiological study of ocular morbidity in MFS demonstrates a profound burden and emphasises the need for thorough and experienced ophthalmological surveillance.
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Síndrome de Marfan , Humanos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/epidemiología , Síndrome de Marfan/diagnóstico , Córnea , Refracción Ocular , Estudios Epidemiológicos , MorbilidadRESUMEN
PURPOSE: To describe the causes of ectopia lentis (EL) and the outcomes after surgery in a Danish population. SETTING: The Eye Clinic Rigshospitalet and Kennedy Center in Copenhagen. DESIGN: Retrospective cohort study. METHODS: Medical records of patients with nontraumatic EL born after 1980 and seen at the Eye Clinic Rigshospitalet and Kennedy Center from 1983 to 2019 were reviewed. Clinical information regarding family history, comorbidities, genetic workup, ophthalmological examinations, and surgical history was retrieved. RESULTS: 72 patients (38 males), of whom 68 had bilateral EL (94.4%) were identified. Marfan syndrome (MFS) was found in 34 (47.2%) and biallelic variants in ADAMTSL4 in 4 (5.6%). Surgery was performed in 38 (52.8%) patients, 66 eyes, with a median age at the time of first eye surgery of 8.4 years (range 0.8 to 39.0 years) and a follow-up of 2.3 years (range 0 to 25.7 years). Intraocular lenses were implanted in 9 (23.7%) (11 eyes). Corrected distance visual acuity improved from 0.7 to 0.2 logMAR (median) in right eyes and from 0.7 to 0.3 logMAR in left eyes postoperatively. 21 patients (56.8%), 42 eyes, did not experience any surgery-related complications. 3 patients (3 eyes) experienced a perioperative tear in the posterior capsule. Temporary postoperative ocular hypertension was reported in 3 patients (7.9%) (3 eyes), and 2 patients (5.4%) (2 eyes) developed persistent ocular hypertension. There were no cases of postoperative retinal detachment. CONCLUSIONS: The main reason for EL was MFS. Surgery improved visual acuity, and postoperative ocular hypertension was the most common complication, whereas retinal detachment was not observed.
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Desplazamiento del Cristalino , Síndrome de Marfan , Hipertensión Ocular , Desprendimiento de Retina , Masculino , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Desplazamiento del Cristalino/epidemiología , Desplazamiento del Cristalino/genética , Desplazamiento del Cristalino/cirugía , Estudios Retrospectivos , Ojo , Dinamarca/epidemiologíaRESUMEN
BACKGROUND: Marfan syndrome is associated with abnormalities in the musculoskeletal system including scoliosis, pectus deformities, protrusio acetabuli, and foot deformities. Over a life span, many patients with Marfan syndrome will need treatment; however, the musculoskeletal morbidity over a life span is not well described. The aim of the present study was to assess the overall burden of musculoskeletal disease in patients with Marfan syndrome. MATERIALS AND METHODS: A registry-based, nationwide epidemiological study of patients with a Ghent II verified Marfan syndrome diagnosis from 1977 to 2014. Each patient was matched on age, and sex with up to 100 controls from the background population. RESULTS: We identified 407 patients with Marfan syndrome and 40,700 controls and compared their musculoskeletal diagnoses and surgical treatments using Cox proportional hazards ratio (HR). The risk of a registration of a musculoskeletal diagnosis in patients with Marfan syndrome was significantly increased compared to controls (HR: 1.94 (1.69-2.24). One out of six with Marfan syndrome was registered with scoliosis (HR: 36.7 (27.5-48.9). Scoliosis was more common in women with Marfan syndrome compared to men (HR: 4.30 (1.73-1.08)). One out of 11 were registered with a pectus deformity HR: 40.8 (28.1-59.3), and one out of six with a deformity of the foot. Primarily pes planus (HR: 26.0 (15.2-44.3). The proportion of patients with Marfan syndrome (94/407) that underwent musculoskeletal surgery was also significantly higher (HR: 1.76 (1.43-2.16)). The major areas of surgery were the spine, pectups correction, and surgery of the foot/ankle. Ten patients with Marfan syndrome had elective orthopedic surgery without being recognized and diagnosed with Marfan syndrome until later in life. None of these had scoliosis, pectus deformity or a foot deformity. Among patients with an aortic dissection, the age at dissection was 34.3 years in those with at least one major musculoskeletal abnormality. In patients without a major abnormality the age at dissection was 45.1 years (p < 0.01). CONCLUSIONS: The extent of musculoskeletal disease is quite significant in Marfan syndrome, and many will need corrective surgery during their life span. Surgeons should be aware of undiagnosed patients with Marfan syndrome when treating patients with a Marfan syndrome like-phenotype.
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Síndrome de Marfan , Escoliosis , Femenino , Humanos , Síndrome de Marfan/epidemiología , Modelos de Riesgos Proporcionales , Sistema de RegistrosRESUMEN
OBJECTIVES: Studies indicate that other cardiovascular problems than aortic disease are a burden for patients with Marfan syndrome (MFS). The aim of the study was to assess the extent of this issue. METHODS: A registry-based population study of patients with a Ghent II verified MFS diagnosis. Each patient was matched with up to 100 controls on age and sex. From the Danish healthcare system, we identified 407 MFS patients (from 1977 to 2014) and their cardiovascular events and compared them with those in 40,700 controls. Total follow-up time was 16,439 person years. RESULTS: Mitral valve disease was significantly more common in MFS [HR: 58.9 (CI 38.1-91.1)] and happened earlier and more often in women than men with MFS [age at first registration: 22 vs. 38 years, HR: 2.1 (CI 1.0-4.4)]. Heart failure/cardiomyopathy was also more common in MFS [HR: 8.7 (CI 5.7-13.4)] and men were more affected than women, and at younger age [39 vs. 64 years, HR: 0.18 (CI 0.06-0.55)]. In all cases, atrioventricular block [HR: 4.9 (1.5-15.6)] was related to heart surgery. Supraventricular [HR: 9.7 (CI 7.5-12.7)] and ventricular tachycardia [HR: 7.7 (CI 4.2-14.3)] also occurred more often than in the control group. The risk of sudden cardiac death was increased [HR: 8.3 (CI 3.8-18.0)] but the etiology was unclear due to lack of autopsies. CONCLUSION: Non-aortic cardiovascular disease in patients with MFS is exceptionally prevalent and the range of diseases varies between women and men. Physicians caring for MFS patients must be aware of this large spectrum of cardiovascular diseases.
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Enfermedades Cardiovasculares/epidemiología , Síndrome de Marfan/complicaciones , Vigilancia de la Población , Sistema de Registros , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Causas de Muerte/tendencias , Dinamarca/epidemiología , Ecocardiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Síndrome de Marfan/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Adulto JovenRESUMEN
In Marfan syndrome (MFS), pregnancy is considered as high risk due to the deficiency of fibrillin in the connective tissue and increased risk of aortic dissection. The objective was to demonstrate the consequences on maternal health, in women with diagnosed and undiagnosed MFS at the time of pregnancy and childbirth. By using national health care registries, we identified all pregnancy related outcomes, from women with MFS (n = 183) and an age-matched background population (n = 18,300). We found 91 pregnancies during follow-up. Significantly fewer women with MFS gave birth, compared to the background population. No women with known MFS had a pregnancy related aortic dissection but complications related to the cervix were increased (HR:19.8 [95% CI:2.2-177.5]). Fifty women with MFS were undiagnosed at the time of their first pregnancy and/or childbirth. Among these, there were more birth canal related complications HR:27.2 (95% CI: 2.3-315.0), preeclampsia (HR:2.25 [95% CI: 1.11-4.60]), fetal deaths (HR:12.3 [95% CI: 1.51-99.8]), and all delivery-related dissections came from this subgroup. In conclusion, undiagnosed women with MFS experienced more pregnancy and childbirth related complications including fetal death, birth canal issues, preeclampsia, and aortic disease, which emphasizes the need for an early MFS diagnosis and special care during pregnancy and childbirth.
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Síndrome de Marfan/fisiopatología , Salud Materna , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Adulto , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/fisiopatología , Femenino , Muerte Fetal , Humanos , Síndrome de Marfan/epidemiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Resultado del Embarazo , Sistema de RegistrosRESUMEN
Marfan syndrome (MFS), a rare genetic disease, has a prevalence of 6.5 in 100,000. Studies show that patients with MFS have reduced areal bone mineral density (BMD) compared with non-MFS individuals. We have previously shown that patients with MFS have reduced volumetric BMD and compromised trabecular and cortical bone microarchitecture. The present study was a registry-based, nationwide, population-based, cohort study using register data, aimed to evaluate fracture risk and fracture rates in MFS. We included 406 (196 women) patients with MFS through the Danish National Patient Register and 40,724 (19,327 women) persons, randomly selected and matched from the Civil Registry System. A total of 21.9% of the MFS and 18.9% of the reference population had experienced at least one fracture from 1995 to 2018. The fracture incidence rate was 27.5 per 1000 person-years in the MFS cohort (highest in young men and old women with MFS), and 20.3 per 1000 person-years in the reference population. The overall incidence rate ratio between the MFS and the reference population was 1.35 (95% confidence interval [CI ] 1.18-1.55) for all fractures. When evaluating the risk of being registered with an osteoporosis diagnosis in the Danish National Patient Register, starting relevant treatment for osteoporosis or experiencing a hip or spine fracture, 10.3% of the MFS cohort and 3.3% of the reference population could be classified as being osteoporotic. The between-group subhazard ratio was 3.97 (95% CI 2.56-6.25). Patients with MFS started treatment with an antiosteoporotic drug at a younger age than the reference population (57 [interquartile range 55-67] versus 71 [63-73]) years. The life expectancy in MFS is increasing, resulting in more patients facing diseases that are related to old age, such as age-related bone loss and increased risk of fractures. Our data suggest that bone health and fracture prevention needs to be part of the standard care for patients with MFS. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Fracturas Óseas , Síndrome de Marfan , Osteoporosis , Anciano , Densidad Ósea , Estudios de Cohortes , Femenino , Fracturas Óseas/epidemiología , Humanos , Masculino , Síndrome de Marfan/complicaciones , Síndrome de Marfan/epidemiología , Persona de Mediana EdadRESUMEN
Marfan syndrome (MFS) is a hereditary disorder of connective tissue caused by mutations in the fibrillin-1 gene. Studies have shown that patients with MFS have lower bone mass, but little is known about the other constituents of bone strength. We hypothesize that patients with MFS will have larger bone area and compromised cortical microarchitecture compared with non-MFS individuals. A total of 74 adult patients with MFS and 145 age- and sex-matched non-MFS reference individuals were included in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and dual-energy X-ray absorptiometry of total hip and the lumbar spine were performed, and bone turnover and sex hormones were measured. Patients with MFS had significantly lower areal bone mineral density (BMD) at the total spine (-13%) and total hip (-7%) when compared with the reference group. Patients with MFS had significantly larger total bone area at both the radius (+27%) and tibia (+34%). Volumetric BMD at both measured sites showed significantly reduced total, trabecular, and cortical volumetric BMD in patients with MFS compared with the reference group. The microarchitectural parameters at the radius and tibia were compromised in patients with MFS with significantly reduced trabecular number and thickness, leading to a higher trabecular separation and significantly reduced cortical thickness and increased cortical porosity compared with the reference group. The differences in bone density, geometry, or microarchitecture were not explained by increased bone turnover markers or circulating levels of sex hormones. We conclude patients with MFS have altered bone geometry, altered bone microstructure, and lower bone mass (lower areal BMD and volumetric BMD at all sites) compared with healthy reference individuals. Future studies should focus on fracture rates and fracture risk in adult and aging patients with MFS. © 2020 American Society for Bone and Mineral Research (ASBMR).
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Huesos del Carpo , Síndrome de Marfan , Absorciometría de Fotón , Adulto , Densidad Ósea , Humanos , Vértebras Lumbares/diagnóstico por imagen , Síndrome de Marfan/diagnóstico por imagen , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagenRESUMEN
CONTEXT AND OBJECTIVE: Males with Klinefelter syndrome (KS) are typically hypogonadal with a high incidence of metabolic disease, increased body fat and mortality. Testosterone treatment of hypogonadal patients decrease fat mass, increase lean body mass and improve insulin sensitivity, but whether this extends to patients with KS is presently unknown. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, BMI-matched cross-over study, 13 males with KS (age: 34.8 years; BMI: 26.7 kg/m2) received testosterone (Andriol®) 160 mg per day (testosterone) or placebo treatment for 6 months. Thirteen age- and BMI-matched healthy controls were recruited. DEXA scan, abdominal computed tomography (CT) scan and a hyperinsulinemic-euglycemic clamp, muscle strength and maximal oxygen uptake measurement were performed. RESULTS: Total lean body mass and body fat mass were comparable between testosterone-naïve KS and controls using DEXA, whereas visceral fat mass, total abdominal and intra-abdominal fat by CT was increased (P < 0.05). Testosterone decreased total body fat (P = 0.01) and abdominal fat by CT (P = 0.04). Glucose disposal was similar between testosterone-naïve KS and controls (P = 0.3) and unchanged during testosterone (P = 0.8). Free fatty acid suppression during the clamp was impaired in KS and maximal oxygen uptake was markedly lower in KS, but both were unaffected by treatment. Testosterone increased hemoglobin and IGF-I. CONCLUSION: Testosterone treatment in adult males with KS for 6 months leads to favorable changes in body composition with reductions in fat mass, including abdominal fat mass, but does not change measures of glucose homeostasis.
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A bicuspid aortic valve is not only a common congenital heart defect but also an enigmatic condition that can cause a large spectrum of diseases, such as aortic valve stenosis and severe heart failure in newborns whereas aortic dissection in adults. On the contrary, a bicuspid aortic valve can also occur with normal function throughout life and never need treatment. Numerous genetic mechanisms are involved in the abnormal cellular functions that may cause abnormal development of the aortic valve during early foetal life. As several chromosomal disorders are also associated with a bicuspid valve, there does not appear to be an apparent common trigger to the abnormal development of the aortic valve. The clinical care of the bicuspid aortic valve patient has been changed by a significant body of evidence that has improved the understanding of the natural history of the disease, including when to best intervene with valve replacement and when to provide prophylactic aortic root surgery. Moreover, as bicuspid valve disease is also part of various syndromes, we can identify high-risk patients in whom a bicuspid valve is much more unfavourable than in the normal population. This review provides an overview of all aspects of the bicuspid aortic valve condition and gives an updated perspective on issues from pathophysiology to clinical care of bicuspid aortic valve disease and associated aortic disease in asymptomatic, symptomatic, and pregnant patients, as well as our viewpoint on population screening.
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Válvula Aórtica/anomalías , Válvula Aórtica/fisiopatología , Cardiopatías Congénitas/complicaciones , Enfermedades de las Válvulas Cardíacas/genética , Válvula Mitral/fisiopatología , Disección Aórtica/etiología , Válvula Aórtica/patología , Cardiopatías Congénitas/patología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Válvula Mitral/patologíaAsunto(s)
Enfermedades de la Aorta , Síndrome de Marfan , Progresión de la Enfermedad , Fibrilina-1 , Fibrilinas , HumanosRESUMEN
The Marfan syndrome (MFS) is strongly associated with aortic disease causing a high prevalence of prophylactic aortic surgery, aortic dissection, and sudden death. The aim of the present study was to evaluate mortality in a nationwide Danish MFS population diagnosed by the Ghent II criteria. In a register-based setting, we identified all Danish patients with MFS (nâ¯=â¯412, men nâ¯=â¯215) by assessment of their medical records. We established a gender and age matched control cohort based on 41,000 control patients (men nâ¯=â¯21,500). MFS cases risk time was 6,669 patient years. We applied Cox regression using each case and his/her control as one stratum, adjusting for age and calendar time. We found a significantly decreased lifespan of 50years compared with 60years among controls. The mortality hazard ratio among MFS compared with controls was significantly increased to3.6 (CI 2.8-4.7, p < 0.001); men 4.0 (CI 2.8-5.7, p < 0.001); women 3.2 (CI 2.1-4.8,p < 0.001). Aorta disease represented the main reason for the overall increased mortality with a hazard ratio of 194.6 (CI 67.4-561.7, p < 0.0001); men 208.7 (CI 53.8-809.1, p < 0.001); women 173.4 (CI 31.5-954.5, p < 0.001). In addition, an unexplained mortality due to respiratory illness was not attributed to pneumothorax. Excluding cardiovascular and respiratory causes of death, we found no indication that MFS is associated with increased mortality for other reasons.
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Enfermedades de la Aorta/mortalidad , Síndrome de Marfan/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Aorta/etiología , Niño , Preescolar , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Longevidad , Masculino , Síndrome de Marfan/complicaciones , Persona de Mediana Edad , Sistema de Registros , Factores de RiesgoRESUMEN
BACKGROUND: Genetic FBN1 testing is pivotal for confirming the clinical diagnosis of Marfan syndrome. In an effort to evaluate variant causality, FBN1 databases are often used. We evaluated the current databases regarding FBN1 variants and validated associated phenotype records with a new Marfan syndrome geno-phenotyping tool called the Marfan score. METHODS AND RESULTS: We evaluated four databases (UMD-FBN1, ClinVar, the Human Gene Mutation Database (HGMD), and Uniprot) containing 2,250 FBN1 variants supported by 4,904 records presented in 307 references. The Marfan score calculated for phenotype data from the records quantified variant associations with Marfan syndrome phenotype. We calculated a Marfan score for 1,283 variants, of which we confirmed the database diagnosis of Marfan syndrome in 77.1%. This represented only 35.8% of the total registered variants; 18.5-33.3% (UMD-FBN1 versus HGMD) of variants associated with Marfan syndrome in the databases could not be confirmed by the recorded phenotype. CONCLUSION: FBN1 databases can be imprecise and incomplete. Data should be used with caution when evaluating FBN1 variants. At present, the UMD-FBN1 database seems to be the biggest and best curated; therefore, it is the most comprehensive database. However, the need for better genotype-phenotype curated databases is evident, and we hereby present such a database.Genet Med advance online publication 01 December 2016.
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Fibrilina-1/genética , Estudios de Asociación Genética/métodos , Síndrome de Marfan/diagnóstico , Bases de Datos Factuales , Bases de Datos de Ácidos Nucleicos/normas , Femenino , Fibrilinas , Pruebas Genéticas/métodos , Variación Genética/genética , Genotipo , Humanos , Masculino , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Mutación , FenotipoRESUMEN
BACKGROUND: Marfan syndrome is associated with morbidity and mortality due to aortic dilatation and dissection. Preventive aortic root replacement has been the standard treatment in Marfan syndrome patients with aortic dilatation. In this study, we present aortic event data from a nationwide Marfan syndrome cohort. METHOD: The nationwide cohort of Danish Marfan syndrome patients was established from the Danish National Patient Registry and the Cause of Death Register, where we retrieved information about aortic surgery and dissections. We associated aortic events with age, sex, and Marfan syndrome diagnosis prior or after the first aortic event. RESULTS: From the total cohort of 412 patients, 150 (36.4 %) had an aortic event. Fifty percent were event free at age 49.6. Eighty patients (53.3 %) had prophylactic surgery and seventy patients (46.7 %) a dissection. The yearly event rate was 0.02 events/year/patient in the period 1994-2014. Male patients had a significant higher risk of an aortic event at a younger age with a hazard ratio of 1.75 (CI 1.26-2.42, p = 0.001) compared with women. Fifty-three patients (12.9 %) were diagnosed with MFS after their first aortic event which primarily was aortic dissection [n = 44 (83.0 %)]. CONCLUSION: More than a third of MFS patients experienced an aortic event and male patients had significantly more aortic events than females. More than half of the total number of dissections was in patients undiagnosed with MFS at the time of their event. This emphasizes that diagnosing MFS is lifesaving and improves mortality risk by reducing the risk of aorta dissection.
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Aneurisma de la Aorta/epidemiología , Disección Aórtica/epidemiología , Síndrome de Marfan/epidemiología , Adolescente , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/cirugía , Implantación de Prótesis Vascular , Niño , Preescolar , Dinamarca/epidemiología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/cirugía , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: The diagnostic criteria of Marfan syndrome (MFS) highlight the importance of a FBN1 mutation test in diagnosing MFS. As genetic sequencing becomes better, cheaper, and more accessible, the expected increase in the number of genetic tests will become evident, resulting in numerous genetic variants that need to be evaluated for disease-causing effects based on database information. The aim of this study was to evaluate genetic variants in four databases and review the relevant literature. METHODS: We assessed background data on 23 common variants registered in ESP6500 and classified as causing MFS in the Human Gene Mutation Database (HGMD). We evaluated data in four variant databases (HGMD, UMD-FBN1, ClinVar, and UniProt) according to the diagnostic criteria for MFS and compared the results with the classification of each variant in the four databases. RESULTS: None of the 23 variants was clearly associated with MFS, even though all classifications in the databases stated otherwise. CONCLUSION: A genetic diagnosis of MFS cannot reliably be based on current variant databases because they contain incorrectly interpreted conclusions on variants. Variants must be evaluated by time-consuming review of the background material in the databases and by combining these data with expert knowledge on MFS. This is a major problem because we expect even more genetic test results in the near future as a result of the reduced cost and process time for next-generation sequencing.Genet Med 18 1, 98-102.
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Bases de Datos Genéticas , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Fibrilinas , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Proteínas de Microfilamentos/genética , MutaciónRESUMEN
BACKGROUND: Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome. METHOD: Using unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977-2014). Following, we confirmed or rejected the diagnosis according to the 2010 revised Ghent nosology. RESULTS: We identified a total of 1628 persons with possible Marfan syndrome. We confirmed the diagnosis in 412, whereof 46 were deceased, yielding a maximum prevalence of 6.5/100,000 at the end of 2014. The annual median incidence was 0.19/100,000 (range: 0.0-0.7) which increased significantly with an incidence rate ratio of 1.03 (95% CI: 1.02-1.04, p < 0.001). We found a median age at diagnose of 19.0 years (range: 0.0-74). The age at diagnosis increased during the study period, uninfluenced by the changes in diagnostic criteria. We found no gender differences. CONCLUSION: The increasing prevalence of Marfan syndrome during the study period is possibly due to build-up of a registry. Since early diagnosis is essential in preventing aortic events, diagnosing Marfan syndrome remains a task for both pediatricians and physicians caring for adults.
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Síndrome de Marfan/diagnóstico , Síndrome de Marfan/epidemiología , Sistema de Registros , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Dinamarca/epidemiología , Femenino , Fibrilina-1 , Fibrilinas , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
A 29-year-old woman with Marfan syndrome, a bicuspid aortic valve, and a dilated aortic sinus (5.2 cm) presented herself in clinic 14 weeks pregnant. She was advised to discontinue the pregnancy due to risk of dissection; however, she decided to continue. She was treated with labetalol (300 mg/day) to reduce blood pressure and was admitted for bed rest from week 30. Her aortic diameter was assessed by echocardiography every 2nd week and remained unchanged. She was treated with betamethason at week 26 and the child was born by a caesarean section in week 35. The post-operative course was uneventful.
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Válvula Aórtica/anomalías , Enfermedades de las Válvulas Cardíacas/complicaciones , Síndrome de Marfan/complicaciones , Complicaciones Cardiovasculares del Embarazo/prevención & control , Embarazo de Alto Riesgo , Adulto , Antihipertensivos/uso terapéutico , Válvula Aórtica/diagnóstico por imagen , Enfermedad de la Válvula Aórtica Bicúspide , Cesárea , Dilatación Patológica/prevención & control , Ecocardiografía , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Humanos , Síndrome de Marfan/diagnóstico por imagen , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Seno Aórtico/diagnóstico por imagenRESUMEN
Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.
Asunto(s)
Hipogonadismo/etiología , Síndrome de Klinefelter/complicaciones , Composición Corporal , Encéfalo/fisiopatología , Cognición , Fertilidad , Terapia de Reemplazo de Hormonas , Humanos , Hipogonadismo/metabolismo , Hipogonadismo/fisiopatología , Resistencia a la Insulina , Síndrome de Klinefelter/metabolismo , Síndrome de Klinefelter/fisiopatología , Masculino , Osteoporosis/etiología , Osteoporosis/fisiopatología , Testículo/fisiopatología , Testosterona/administración & dosificaciónRESUMEN
Soluble CD163 (sCD163) is a novel marker linked to states of low-grade inflammation such as diabetes, obesity, liver disease, and atherosclerosis, all prevalent in subjects with Turner syndrome (TS) and Klinefelter syndrome (KS). We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards to treatment with sex hormone therapy in males with and without KS and females with and without TS. Males with KS (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study. Females with TS (n=8) and healthy age-matched controls (n=8) participating in a randomized crossover trial. The intervention comprised of treatment with sex steroids. Males with KS had higher levels of sCD163 compared with controls (1.75 (0.47-6.90) and 1.36 (0.77-3.11) respectively, P<0.001) and the levels correlated to plasma testosterone (r=-0.31, P<0.01), BMI (r=0.42, P<0.001), and homeostasis model of assessment insulin resistance (r=0.46, P<0.001). Treatment with testosterone did not significantly lower sCD163. Females with TS not receiving hormone replacement therapy (HRT) had higher levels of sCD163 than those of their age-matched healthy controls (1.38±0.44 vs 0.91±0.40, P=0.04). HRT and oral contraceptive therapy decreased sCD163 in TS by 22% (1.07±0.30) and in controls by 39% (0.55±0.36), with significance in both groups (P=0.01 and P=0.04). We conclude that levels of sCD163 correlate with endogenous testosterone in KS and are higher in KS subjects compared with controls, but treatment did not significantly lower levels. Both endogenous and exogenous estradiol in TS was associated with lower levels of sCD163.
Asunto(s)
Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Arterias Mamarias , Síndrome de Marfan/complicaciones , Adulto , Cateterismo Cardíaco , Ecocardiografía , Humanos , Enfermedad Iatrogénica , Masculino , Tomografía Computarizada por Rayos XRESUMEN
CONTEXT: Recently, new clinically important information regarding Klinefelter syndrome (KS) has been published. We review aspects of epidemiology, endocrinology, metabolism, body composition, and neuropsychology with reference to recent genetic discoveries. EVIDENCE ACQUISITION: PubMed was searched for "Klinefelter," "Klinefelter's," and "XXY" in titles and abstracts. Relevant papers were obtained and reviewed, as well as other articles selected by the authors. EVIDENCE SYNTHESIS: KS is the most common sex chromosome disorder in males, affecting one in 660 men. The genetic background is the extra X-chromosome, which may be inherited from either parent. Most genes from the extra X undergo inactivation, but some escape and serve as the putative genetic cause of the syndrome. KS is severely underdiagnosed or is diagnosed late in life, roughly 25% are diagnosed, and the mean age of diagnosis is in the mid-30s. KS is associated with an increased morbidity resulting in loss of approximately 2 yr in life span with an increased mortality from many different diseases. The key findings in KS are small testes, hypergonadotropic hypogonadism, and cognitive impairment. The hypogonadism may lead to changes in body composition and a risk of developing metabolic syndrome and type 2 diabetes. The cognitive impairment is mainly in the area of language processing. Boys with KS are often in need of speech therapy, and many suffer from learning disability and may benefit from special education. Medical treatment is mainly testosterone replacement therapy to alleviate acute and long-term consequences of hypogonadism as well as treating or preventing the frequent comorbidity. CONCLUSIONS: More emphasis should be placed on increasing the rate of diagnosis and generating evidence for timing and dose of testosterone replacement. Treatment of KS should be a multidisciplinary task including pediatricians, speech therapists, general practitioners, psychologists, infertility specialists, urologists, and endocrinologists.