ABSTRACT
Basal cell carcinomas (BCC) have been recently included into the spectrum of BAP1-tumor predisposition syndrome (TPDS). Uveal melanoma (UM) is also a tumor often observed in patients with this hereditary tumor syndrome, in particular bilateral UM is highly suspicious for BAP1-TPDS although no patient has been reported yet. Based on our index patient with BAP1-TPDS with bilateral UM (choroid OD, oculus dexter; iris OS, oculus sinister), several BCCs and thyroid cancer as well as a family history for cancer, this paper analyzes hints and pitfalls to diagnose this syndrome clinically and histologically. A previously undescribed germline variant, namely a heterozygous deletion of a single nucleotide on position 2001 (c.2001delG;p.[Thr668Profs*24] in exon 16 of the BAP1 gene), was identified. Structural changes in the C-terminal of the BAP1 protein were observed by in silico analysis. While the excised iris melanoma showed loss of BAP1 nuclear staining by immunohistochemical staining, the BCCs of our patient (and in the control group, n = 13) were BAP1 positive. Genetic analysis of the BCC of the ocular adnexae confirmed a remaining intact BAP1 copy. The constellation of (bilateral) UM in combination with BCC should raise suspicion for a BAP1-TPDS. As our BCCs probably developed independently from the BAP1-TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.
Subject(s)
Carcinoma, Basal Cell/genetics , Melanoma/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Uveal Neoplasms/genetics , Aged , Carcinoma, Basal Cell/pathology , Diagnosis, Differential , Female , Germ-Line Mutation , Humans , Melanoma/pathology , Protein Domains , Tumor Suppressor Proteins/chemistry , Ubiquitin Thiolesterase/chemistry , Uveal Neoplasms/pathologyABSTRACT
PURPOSE: To assess the natural disease progression of high myopia in Caucasians considered at risk for the development of myopic choroidal neovascularization (mCNV). METHODS: Subjects were recruited in 25 clinical sites between June 2014 and June 2016. Main inclusion criteria included axial length of ≥26 mm, best-corrected visual acuity ≥0.05 decimal equivalent and presence of at least one out of five predefined morphological disease risk criteria. These were (1) subfoveal choroidal thinning < 50 µm, (2) enhanced choroidal curvature length > 6,300 µm, (3) lacquer cracks, (4) patchy atrophy > 5 mm2 and (5) preexisting mCNV in the fellow eye (German Clinical Trial Register DRKS00007761). RESULTS: A total of 150 participants (66% females) with a mean age of 57.2 (±12.7) years (range 21.9-86.2 years) were included. The disease criteria most frequently encountered were choroidal thinning (33.3%) and lacquer cracks (32.7%). Enhanced choroidal curvature length was detected in only 8 subjects and always occurred in combination with other disease criteria. Presence of patchy atrophy was found to be more common in older subjects (p = 0.0012) and also associated with a more severe disease manifestation. CONCLUSION: The baseline data of this study indicate that enhanced choroidal curvature might be less common in Caucasians than in Asian populations. Further, disease severity in patients with high myopia is relatively high in the presence of patchy atrophy.
Subject(s)
Choroidal Neovascularization/diagnosis , Myopia, Degenerative/diagnosis , Myopia, Degenerative/ethnology , White People/ethnology , Adult , Aged , Aged, 80 and over , Atrophy , Axial Length, Eye/pathology , Choroid/pathology , Disease Progression , Female , Fluorescein Angiography , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Research Design , Surveys and Questionnaires , Tomography, Optical Coherence , Visual Acuity/physiology , Young AdultABSTRACT
BACKGROUND/OBJECTIVES: The acute and long-term effects of interventional edge-to-edge repair on the mitral valve (MV) geometry are unclear. We sought to assess MV-annular geometry and the association of changes in MV-diameters with functional response one year after MitraClip implantation. METHODS: Consecutive patients (n=84; age 81.2±8.3years, logistic EuroSCORE 21.7±17.9%) with symptomatic moderate-to-severe mitral regurgitation (MR) underwent MitraClip-procedure. MV-annular geometry was assessed with 3D TOE before, immediately and one year after clip implantation. RESULTS: 96.7% of secondary mitral regurgitation (SMR) patients presented with moderate-to-severe MR, 3.3% with severe SMR, respectively. 66.7% of primary MR (PMR) patients had moderate-to-severe MR, and 33.3% severe PMR respectively. When analyzing immediate effects of MitraClipC on mitral geometry, only patients with SMR (n=60, 71.4%) experienced significant reductions of the diastolic MV anterior-posterior diameters (AP: 3.9±0.5cm, 3.5±0.7cm; p<0.001), and annulus-areas (2D: 12.9±3.8cm2, 12.6±3.7cm2; p<0.001; 3D: 13.4±3.8, 13.1±3.2cm2; p<0.001). All measures on MV annular geometry were not significantly altered in patients with PMR (p>0.05). After one year of follow-up, MV annular parameters remained significantly reduced in SMR patients (p<0.05) and remained unchanged in subjects with PMR (p>0.05). Only SMR patients experienced significant increase in 6min walking distances (p=0.004), decrease in pulmonary pressures (p=0.007) and functional NYHA-class (p<0.001); in patients with PMR only NYHA class improved after one year (p<0.001). CONCLUSION: Edge-to-edge repair with the MitraClip-system impacts on MV-geometry in patients with SMR with stable results after 12months. Reduction of MV-annular dimensions was associated with higher rates of persisting MR reduction and better functional status in patients with SMR.