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Risk Management and Healthcare Policy 2021Weill-Marchesani syndrome (WMS) is an autosomal inherited connective tissue disease. Clinical manifestations include microspherophakia (MSP), high myopia, ectopia...
BACKGROUND
Weill-Marchesani syndrome (WMS) is an autosomal inherited connective tissue disease. Clinical manifestations include microspherophakia (MSP), high myopia, ectopia lentis, open-angle glaucoma, short stature, short fingers, joint stiffness, and (occasionally) cardiovascular defects. At present, a total of four pathogenic gene loci related to WMS have been found: ADAMTS10, ADAMTS17, FBN1, and LTBP2.
CASE REPORT
The patient was a five-year-old girl whose eyesight had become progressively worse for three years before her parents brought her to the hospital. Computer optometry showed high myopia in both eyes, while a slit lamp examination found that the anterior chamber of both eyes was shallow, and the lens was in a state of dislocation (ectopia lentis). An IOLMaster examination revealed that the lens was spherical (MSP), and the lens thickness (LT) was 5.36 mm. Corneal topography showed that the angle kappa was 0.18 mm in the right eye (OD) and 0.30 mm in the left eye (OS). An intraocular pressure (IOP) (OD: 26.5 mmHg, OS: 30.6 mmHg) examination showed that the fundus cup to disc ratio was normal, but secondary glaucoma caused by lens dislocation could be considered. The IOP was maintained within a normal range using antihypertensive drugs. The patient's younger sister also had a dislocation of MSP. Gene detection showed a heterozygous mutation in the LTBP2 gene [c.3672delC:p.Thr1225fs and c.3542delT:p.Met1181fs], and a diagnosis of WMS-like syndrome was confirmed.
CONCLUSION
WMS syndrome is rare, and the mutation of the LTBP2 gene has not been previously recorded in the GnomAD (Genome Aggregation Database) of East Asia. This case report provides some reference for studying the mechanism of WMS and WMS-like syndrome caused by an LTBP2 gene mutation.
PubMed: 33958902
DOI: 10.2147/RMHP.S307290 -
Matrix Biology : Journal of the... Jan 2021Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular...
Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular fibers that centers and suspends the lens in the eye. LTBP-2 has been implicated previously in the development of extracellular microfibrils, although its exact role remains unclear. Here, we analyzed the three-dimensional structure of the ciliary zonule in wild type mice and used a knockout model to test the contribution of LTBP-2 to zonule structure and mechanical properties. In wild types, zonular fibers had diameters of 0.5-1.0 micrometers, with an outer layer of fibrillin-1-rich microfibrils and a core of fibrillin-2-rich microfibrils. LTBP-2 was present in both layers. The absence of LTBP-2 did not affect the number of fibers, their diameters, nor their coaxial organization. However, by two months of age, LTBP-2-depleted fibers began to rupture, and by six months, a fully penetrant ectopia lentis phenotype was present, as confirmed by in vivo imaging. To determine whether the seemingly normal fibers of young mice were compromised mechanically, we compared zonule stress/strain relationships of wild type and LTBP-2-deficient mice and developed a quasi-linear viscoelastic engineering model to analyze the resulting data. In the absence of LTBP-2, the ultimate tensile strength of the zonule was reduced by about 50%, and the viscoelastic behavior of the fibers was altered significantly. We developed a harmonic oscillator model to calculate the forces generated during saccadic eye movement. Model simulations suggested that mutant fibers are prone to failure during rapid rotation of the eyeball. Together, these data indicate that LTBP-2 is necessary for the strength and longevity of zonular fibers, but not necessarily for their formation.
Topics: Animals; Cilia; Ectopia Lentis; Eye; Fibroblasts; Humans; Latent TGF-beta Binding Proteins; Longevity; Mice; Mice, Knockout; Microfibrils; Ocular Physiological Phenomena; Saccades; Tensile Strength; Viscoelastic Substances
PubMed: 33039488
DOI: 10.1016/j.matbio.2020.10.002 -
American Journal of Ophthalmology Case... Dec 2020To report a case of bilateral spontaneous filtering bleb, scleral thinning, microspherophakia, and mild craniofacial dysmorphism.
PURPOSE
To report a case of bilateral spontaneous filtering bleb, scleral thinning, microspherophakia, and mild craniofacial dysmorphism.
OBSERVATIONS
An 18-year-old girl was referred to our clinic for evaluation of bilateral spontaneous filtering blebs. Her corrected distance visual acuity (CDVA) was 20/400 in the right eye (RE) and 20/100 in the left eye (LE). She had superior scleral thinning, multicystic filtering bleb, and microspherophakia bilaterally. The IOP was 9 mmHg in the RE and 8 mmHg in the LE. A mild craniofacial dysmorphism including downward slanting of palpebral fissures and malar hypoplasia was present. There was no sign of corneal ectasia in tomography. Anterior segment optical coherence tomography revealed the filtering blebs as subconjunctival low reflective fluid-filled spaces. Due to severe scleral thinning un the RE we performed a tectonic scleral patch graft. 6 months after surgery the depth of the anterior chamber increased and CDVA improved.
CONCLUSION AND IMPORTANCE
This case indicated that the formation of spontaneous filtering blebs may occur in a syndromic condition. In any case with this symptom, special attention should be paid to craniofacial features, sclera, crystalline lens, and IOP. Tectonic scleral patch graft could be a valuable option in selected patients.
PubMed: 33020746
DOI: 10.1016/j.ajoc.2020.100948 -
Medicine Aug 2020Microspherophakia is characterized by a small, spherical crystalline lens with increased sagittal diameter. Because of the uncertainty about the outcome, as well as the...
RATIONALE
Microspherophakia is characterized by a small, spherical crystalline lens with increased sagittal diameter. Because of the uncertainty about the outcome, as well as the complexity of the operation and development of complications, the management and timing of surgical intervention for microspherophakia are still debated. Lens extraction is effective for avoiding the risk of pupillary blockage, but the outcome after operation is controversial. The iTrace (Tracey, USA) report shows the influence of low-order aberrations (LOA) and high-order aberrations (HOA), which may be valuable in predicting postoperative outcome. Our report concerns a child with microspherophakia who underwent lens extraction via the analysis of visual quality by iTrace.
PATIENT CONCERNS
Our report is on the case of a 7-year-old girl whose parents observed she had to bring her papers and books extremely close to her face to read. On examination, the girl was bilaterally diagnosed microspherophakia with a small tremble lens. The objective refraction was -15.0 diopter of spherical power (DS)/-1.00 diopter of cylindrical power (DC) × 180 right eye (OD) and -12.5 DS/-1.50 DC × 20 left eye (OS). The HOA of OD and OS were high up to 0.926 and 0.659, respectively by iTrace. The visual quality remained terrible after correcting LOA (high myopia and astigmatism). According to iTrace report, the patient would get a good visual quality by extracting the clear lens with HOA from cornea after correcting LOA. The girl's parent opted for surgery on the left eye.
DIAGNOSIS
Due to the patient's symptoms, examination results, she was diagnosed with microspherophakia.
INTERVENTIONS
The patient underwent clear lens extraction by ultrasonic phacoemulsification and intraocular lens implantation.
OUTCOMES
The first day after operation, total HOA was decreased to 0.077. Total LOA was 0.713. Corrected distance visual acuity (CDVA) is 20/20. One week after surgery, HOA was 0.110 and LOA was 0.328. CDVA was 20/25. CDVA was still 20/25 one month after surgery. The total HOA was 0.110 and the LOA was 0.334 by iTrace.
LESSONS
ITrace not only plays an important role in analyzing potential reasons of undesirable preoperative visual quality but also can predict postoperative outcomes. All these functions are helpful for determining surgical intervention of microspherophakia cases.
Topics: Aberrometry; Astigmatism; Child; Corneal Diseases; Corneal Topography; Ectopia Lentis; Female; Glaucoma; Humans; Iris; Lens Implantation, Intraocular; Myopia; Phacoemulsification; Treatment Outcome; Ultrasonics; Visual Acuity
PubMed: 32846863
DOI: 10.1097/MD.0000000000021937 -
The National Medical Journal of India 2019
Topics: Child; Corneal Diseases; Ectopia Lentis; Female; Glaucoma; Humans; Iris; Lens, Crystalline
PubMed: 32769256
DOI: 10.4103/0970-258X.291302 -
Scientific Reports Jul 2020Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and...
Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.
Topics: ADAMTS Proteins; Anthropometry; Bodily Secretions; Brachydactyly; Canada; Female; Fingers; HEK293 Cells; Humans; Male; Mutation, Missense; Phenotype; Weill-Marchesani Syndrome; Exome Sequencing
PubMed: 32616716
DOI: 10.1038/s41598-020-66978-8 -
Indian Journal of Ophthalmology Jun 2020
Topics: Corneal Diseases; Ectopia Lentis; Glaucoma; Humans; Iris; Lens Subluxation; Lens, Crystalline
PubMed: 32461458
DOI: 10.4103/ijo.IJO_1898_19 -
The British Journal of Ophthalmology Mar 2021Ectopia lentis refers to dislocation or subluxation of the crystalline lens. Fibrillin-1, encoded by , is an important microfibrillar structural component that is...
BACKGROUND
Ectopia lentis refers to dislocation or subluxation of the crystalline lens. Fibrillin-1, encoded by , is an important microfibrillar structural component that is specifically required for the suspensory ligament of the lens. mutations may cause abnormal structure of microfibrils and has been associated with a broad spectrum of clinical phenotypes. In this study, we characterised a Chinese dominant family with late-onset isolated ectopia lentis caused by a novel missense mutation.
METHODS
Eight family members, including four patients with suspected isolated ectopia lentis, were recruited from Shanghai. Clinical data and family history of the proband and other affected family members were collected. Ophthalmic examination, systemic examination and echocardiography were performed. Whole exome sequencing and Sanger sequencing were used to detect potential pathogenic variants.
RESULTS
A novel heterozygous missense mutation c.4031 G>A/p.Gly1344Glu in exon 33 of was identified. This mutation was detected in all affected family members and led to specific ocular system phenotypes (ectopia lentis, microspherophakia and secondary glaucoma) with minor skeletal involvement (hallux valgus).
CONCLUSION
The novel c.4031G>A mutation in is a likely pathogenic mutation for isolated ectopia lentis. Our study expands the spectrum of mutations and contributes to better comprehension of genotype-phenotype correlations of ectopia lentis disease.
Topics: DNA; DNA Mutational Analysis; Ectopia Lentis; Female; Fibrillin-1; Genetic Association Studies; Genotype; Humans; Male; Middle Aged; Mutation; Pedigree; Phenotype
PubMed: 32404357
DOI: 10.1136/bjophthalmol-2019-315265 -
Indian Journal of Ophthalmology Apr 2020A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of...
A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of sclerotomies. Filtering blebs were managed by suturing the sclerotomies. Targeted gene sequencing identified a variant of ASPH gene (p.Arg688Gln) which is not known to be associated with Traboulsi syndrome. But considering the paucity of cases with genetic analysis, it would be possible that p.Arg688Gln is a pathogenic variant. This is the first case report of Traboulsi syndrome due to an ASPH variant not reported earlier that can lead to recurrent filtering blebs.
Topics: Female; Humans; Ectopia Lentis; Glaucoma; Retinal Detachment; Retrospective Studies; Vitrectomy
PubMed: 32174599
DOI: 10.4103/ijo.IJO_1249_19