Prevalence, incidence, and age at diagnosis in Marfan Syndrome

Groth, Kristian A.; Hove, Hanne; Kyhl, Kasper; Folkestad, Lars; Gaustadnes, Mette; Vejlstrup, Niels; Stochholm, Kirstine; Østergaard, John R.; Andersen, Niels Holmark; Gravholt, Claus Højbjerg

doi:10.1186/s13023-015-0369-8

Cited by 150 publications

(129 citation statements)

References 28 publications

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“…One study found EL in 38% of neonates and another study reported that MFS was diagnosed in patients at zero age, but did not specify if EL was present at birth. 2,23 Other studies have not found EL before the age of 18 months. 24,25 Studies in different age groups have reported a frequency of EL in children younger than 10 years from 63% to 75% and younger than 17 years from 15% to 57%.…”

Section: Discussionmentioning

confidence: 92%

“…There is a reason to believe that EL may be present from birth in some MFS patients. One study found EL in 38% of neonates and another study reported that MFS was diagnosed in patients at zero age, but did not specify if EL was present at birth . Other studies have not found EL before the age of 18 months .…”

Section: Discussionmentioning

confidence: 99%

“…Reports on the prevalence of MFS give varying numbers, from 4.6 to 6.5 per 100 000. [1][2][3] MFS is caused by mutations in the gene encoding for the connective tissue protein, Fibrillin-1 (FBN1), but presumed disease-causing variants in FBN1 have been found in a number of different disorders. 4,5 Thus, the diagnosis of MFS is based on diagnostic criteria.…”

Section: Introductionmentioning

confidence: 99%

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Ten‐year reinvestigation of ocular manifestations in Marfan syndrome

Sandvik

Vanem

Rand‐Hendriksen

et al. 2018

Clinical Exper Ophthalmology

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Importance: Long-term follow-up of Marfan syndrome (MFS) patients. Background: Investigate changes in ocular features in MFS patients fulfilling the Ghent-2 criteria following a period of 10 years. Design: Repeated cross-sectional study with two observations. Participants: Eighty-four MFS patients were investigated in 2003-2004 (baseline). Forty-four of these patients (52%) were examined after 10 years. Methods: A comprehensive ocular examination performed at baseline and follow-up. Main Outcome Measures: Development or progression of ectopia lentis (EL).Results: At follow-up, mean age was 50.1 AE 11.9 years (range: 30-80 years), 74% were female and 70% of the patients were diagnosed with EL compared to 66% at baseline. Two patients (3 eyes) had developed EL over the decade, representing a 13% risk. Furthermore, one eye had progressed from a subtle tilt of the lens to dislocation. We found no significant change in the axial length (P = 0.96), the corneal curvature (P = 0.64) or the spherical equivalent (P = 0.23). Best corrected visual acuity was improved at follow-up (P = 0.02). There were 7% and 33% risks for development of retinal detachment and cataract between baseline and follow-up, respectively. Conclusions and Relevance: Our study indicates that even though EL typically occurs at an early stage in most MFS patients, there is still a risk of developing EL in adulthood. The risk of developing vision-threatening complications such as retinal detachment and cataract was much higher than in the normal population, but even so, the visual potential of the MFS patients was relatively good. K E Y W O R D Saxial length, corneal curvature, ectopia lentis, Marfan syndrome, visual acuity

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ten‐year reinvestigation of ocular manifestations in Marfan syndrome

Sandvik

Vanem

Rand‐Hendriksen

et al. 2018

Clinical Exper Ophthalmology

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“…A revision of the cancer penetrance of these disorders is needed. Well-known, highly penetrant genetic disorders with population prevalence frequencies spanning our DICER1 pathogenic variation estimates include sickle cell anemia (1/500 African American births) 33 , Down syndrome (1/700 live births) 34 , velo-cardio-facial syndrome (1/2,000) 35 , cystic fibrosis (1/2,500 white Americans) 36 , neurofibromatosis type 1 (1/3,000) 37 , and Duchenne muscular dystrophy (1/5,000 – 1/7,500 boys) 38 , hemophilia A (factor VIII deficiency; 1/6,500 live male births) 39 , Williams syndrome (1/7,500) 40 and Marfan syndrome (1/7,500 – 1/10,000) 41 . As noted, the penetrance related to the pathogenic DICER1 variants we have reported here needs to be determined.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of DICER1 pathogenic variation in population databases

Kim

Field

Schultz

et al. 2017

Intl Journal of Cancer

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The DICER1 syndrome is associated with a variety of rare benign and malignant tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and Sertoli-Leydig cell tumor (SLCT). The prevalence and penetrance of pathogenic DICER1 variation in the general population is unknown. We examined three publicly-available germline whole exome sequence datasets: Exome Aggregation Consortium (ExAC), 1000 Genomes (1000G), and the Exome Sequencing Project (ESP). To avoid over-estimation of pathogenic DICER1 variation from cancer-associated exomes, we excluded The Cancer Genome Atlas (TCGA) variants from ExAC. All datasets were annotated with snpEFF and ANNOVAR and variants were classified into four categories: likely benign (LB), unknown significance (VUS), likely pathogenic (LP), or pathogenic (P). The prevalence of DICER1 P/LP variants was 1:870 to 1:2,529 in ExAC-nonTCGA (53,105 exomes) estimated by metaSVM and REVEL/CADD, respectively. A more stringent prevalence calculation considering only loss-of-function and previously-published pathogenic variants detected in ExAC-nonTCGA, yielded a prevalence of 1:10,600. Despite the rarity of most DICER1 syndrome tumors, pathogenic DICER1 variation is more common than expected. If confirmed, these findings may inform future sequencing-based newborn screening programs for PPB, CN and SLCT, in which early detection improves prognosis.

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“…Lastly, our study was limited to patients with MFS and BAV, so our findings may not necessarily be applicable to other cohorts. However, MFS is a leading etiology of geneticallyassociated TAA, affecting up to 65,000 individuals in the United States and 1,400,000 worldwide (23). Moreover, our findings provide important hypothesis-generating data concerning aortic stiffening as a novel predictor of TAA growth that can be broadly tested in future studies encompassing cohorts with both genetic and sporadicallymediated TAA.…”

Section: Limitationsmentioning

confidence: 95%

Cine-CMR partial voxel segmentation demonstrates increased aortic stiffness among patients with Marfan syndrome

Singh

Almarzooq

Codell³

et al. 2017

J. Thorac. Dis.

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Background: Standard cine-cardiac magnetic resonance (CMR) imaging is commonly used to evaluate cardiac structure, geometry and function. Prior studies have shown that automated segmentation via partial voxel interpolation (PVI) accurately quantifies phantom-based cardiac chamber volumes and necropsy left ventricular myocardial mass. Despite this, the applicability and usefulness of PVI in the determination of physiologic parameters of the aorta such as aortic stiffness has yet to be investigated. Methods: Routine CMR was conducted with a 1.5T (GE) scanner with pulse sequences similar to that of standard CMR (parameters: TR 3.4 msec, TE 1.14 msec, flip angle 60°, temporal resolution ~30-40 msec). Views were obtained in standard cardiac-oriented longitudinal or axial views (2, 3 and 4 chambers). Within non-dilated regions of the descending thoracic aorta, aortic area was quantified via a novel PVI automated process (LV-METRIC), which discerns relative amounts of blood pool in each voxel. Aortic stiffness, as calculated from brachial artery pulse pressure and aortic area at maximal and minimal dimensions, was evaluated in 60 total segments (one segment per patient). All segments were in the descending aorta and were not aneurysmal. Results: Sixty patients in total were studied, including 50 that had genetically-related aortic disorder [35 bicuspid aortic valve (BAV), 15 Marfan syndrome (MFS)]. Ten normal controls without aortic disease were included for comparison purposes. All patients (n=60) had evaluable CMR images for assessment of the descending aorta with use of automated segmentation. Patients with BAV and MFS were similar to controls in age, systolic blood pressure, brachial artery pulse pressure, smoking status or hypercholesterolemia (all P=NS). There were more women (P<0.001), lower body mass index (P=0.008), and greater height (P<0.001) in the MFS cohort compared to BAV and controls. Descending aortic area in either systole (maximal) or diastole (minimal) was similar among all three cohorts. However, change in aortic area (ΔArea) throughout the cardiac cycle was substantially lower in MFS than control subjects (P<0.001). In contrast, change in aortic area throughout the cardiac cycle was not significantly different between BAV vs. controls (P=0.62). Aortic stiffness was increased among MFS patients versus control subjects (P=0.014). When comparing MFS to BAV subjects, a comparable trend was observed (P=0.09). No statistical difference was evident in aortic stiffness in patients with BAV versus control subjects (P=0.29). Conclusions: The application of PVI to standard CMR imaging can assess abnormal descending aorta functional indices in normal caliber segments in MFS subjects. Future prospective studies with larger subject populations are warranted to further determine the overall utility of automated aortic segmentation as a possible early biomarker of aortic dysfunction before overt dilatation.

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Prevalence, incidence, and age at diagnosis in Marfan Syndrome

Cited by 150 publications

References 28 publications

Ten‐year reinvestigation of ocular manifestations in Marfan syndrome

Ten‐year reinvestigation of ocular manifestations in Marfan syndrome

The prevalence of DICER1 pathogenic variation in population databases

Cine-CMR partial voxel segmentation demonstrates increased aortic stiffness among patients with Marfan syndrome

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