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The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ systems. These pathologies share many common features, nonetheless compared to Marfan syndrome, LDS' cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis. The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection.

PURPOSE The purpose of this study is to use a genotype-first approach to explore highly penetrant, autosomal dominant cardiovascular diseases with external features, the RASopathies and Marfan syndrome (MFS), using biobank data. METHODS This study uses exome sequencing and corresponding phenotypic data from Mount Sinai's BioMe (n = 32,344) and the United Kingdom Biobank (UKBB; n = 49,960). Variant curation identified pathogenic/likely pathogenic (P/LP) variants in RASopathy genes and FBN1. RESULTS Twenty-one subjects harbored P/LP RASopathy variants; three (14%) were diagnosed, and another 46% had ≥1 classic Noonan syndrome (NS) feature. Major NS features (short stature [9.5% p = 7e-5] and heart anomalies [19%, p

PURPOSE: A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs).METHODS: Two hundred one unrelated children (0-5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011-2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing.RESULTS: The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism).CONCLUSION: Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

PurposeTo report a case of congenital ciliary body cysts causing microspherophakia, ectopia lentis, and secondary angle closure glaucoma in an infant.ObservationsA 16-month-old male was found to have bilateral ciliary body cysts associated with zonular laxity or absence causing microspherophakia and ectopia lentis as demonstrated on multimodal imaging. Additionally, the patient had secondary angle closure glaucoma which was likely multi-factorial related to both lens abnormalities and anterior displacement of the iris from the cysts themselves. The patient underwent lensectomy and cyst removal which resulted in intraocular pressure stabilization and visual rehabilitation.Conclusions and importanceCongenital ciliary body cysts are a rare cause of lens abnormalities and secondary angle closure glaucoma in children. Information regarding genetic underpinnings or systemic associations is limited.

We report a case series of 12 eyes that underwent retinal detachment (RD) repair after secondary implantation of Akreos AO60 intraocular lens (IOL) with a subset experiencing the complication of IOL opacification. Major predisposing risk factors for retinal detachment included trauma (42%), prior vitrectomy (33%), and ectopia lentis (17%). Opacification developed in two eyes with gas tamponade and three with silicone oil tamponade. Two eyes required explantation of the IOL. Permanent visually significant Akreos AO60 lens opacification is a possible complication weeks after retinal detachment repair and can occur regardless of tamponade agent.

Purpose To identify the spectrum and frequency of mutations in congenital ectopia lentis (CEL) and to investigate the correlations between genotype and clinical phenotype in Chinese CEL patients. Methods Ninety-three participants with CEL were enrolled from March 2017 to April 2020. Ocular and systemic examinations were performed for each included patient. Genomic DNA from the included patients was analysed by whole-exome sequencing to detect mutations. Clinical manifestations were compared for different mutation subgroups. Results Gene mutations were detected in 79 patients. Sixty-five were FBN1-associated, and most were related to Marfan syndrome (MFS). The FBN1 mutations mainly consisted of missense mutations (49/65) and were concentrated in the 5′ region. Probands with missense mutations tend to show high corneal astigmatism (χ2 = 3.98, P = 0.046) and severe lens dislocation (t = 2.90, P = 0.006) compared to premature termination codon (PTC) mutations. Conclusions Most Chinese CEL patients were identified as having FBN1 mutations. Those with missense mutations commonly showed severe ocular phenotypes; therefore, reinforced follow-up and long-term observation are required. These correlations implicated the crucial role of missense and cysteine-involving mutations in ocular phenotypes, which might be explained by dominant-negative and nonsense-mediated mRNA decay (NMD).

We present a male infant with alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and macrosomia/macrocephaly at birth. Whole-exome sequencing revealed a homozygous 2bp-insertion in the latent transforming growth factor-beta binding protein 2 (LTBP2) (c.278_279dup, p.(Ser94Glyfs*187)). So far, LTBP2-variants have been frequently reported with an eye-restricted phenotype including primary congenital glaucoma and megalocornea/microspherphakia and ectopia lentis with/without secondary glaucoma. Hitherto reported systemic phenotypes showed, among others, features as tall stature, finger anomalies, high-arched palate and cardiovascular anomalies. The main pathophysiological finding of our patient was an alveolar capillary dysplasia (with pulmonary arterial hypertension and right ventricular impairment but without misalignment of pulmonary veins) resulting in almost continuous oxygen demand and prolonged dependence on mechanical ventilation. He died of respiratory failure at the age of seven months. This patient may extend the LTBP2-related phenotype with resulting diagnostic implications.

Purpose Fibrillin-1 and -2 are major components of tissue microfibrils that compose the ciliary zonule and cornea. While mutations in human fibrillin-1 lead to ectopia lentis, a major manifestation of Marfan syndrome (MFS), in mice fibrillin-2 can compensate for reduced/lack of fibrillin-1 and maintain the integrity of ocular structures. Here we examine the consequences of a heterozygous dominant-negative mutation in the Fbn1 gene in the ocular system of the mgΔlpn mouse model for MFS. Methods Eyes from mgΔlpn and wild-type mice at 3 and 6 months of age were analyzed by histology. The ciliary zonule was analyzed by scanning electron microscopy (SEM) and immunofluorescence. Results Mutant mice presented a significantly larger distance of the ciliary body to the lens at 3 and 6 months of age when compared to wild-type, and ectopia lentis. Immunofluorescence and SEM corroborated those findings in MFS mice, revealing a disorganized mesh of microfibrils on the floor of the ciliary body. Moreover, mutant mice also had a larger volume of the anterior chamber, possibly due to excess aqueous humor. Finally, losartan treatment had limited efficacy in improving ocular phenotypes. Conclusions In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔlpn mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease.

Purpose To describe the long-term incidence of retinal detachment, intra- and postoperative complications, and visual and refractive outcomes of children with Marfan syndrome following lensectomy for ectopia lentis, with or without subsequent correction of aphakia using the Artisan aphakic iris-fixated anterior chamber intraocular lens. Methods The medical records of children treated at the Department of Ophthalmology, Children's University Hospital, Dublin, Ireland, from January 1, 1991, to December 31, 2011, were retrospectively reviewed. The primary outcome measure was rate of retinal detachment at final follow-up. Secondary outcomes included postoperative complications, endothelial cell count, visual acuity, refractive error, and postoperative refraction prediction error. Results A total of 30 eyes of 15 patients underwent lensectomy. Of these, 16 eyes of 8 patients subsequently underwent Artisan implantation. Mean follow-up was 13.8 ± 5.9 years after lensectomy and 4.1 ± 2.8 years after Artisan implantation. There were no cases of retinal detachment. Best-corrected visual acuity was 0.11 ± 0.14 (logMAR) post-lensectomy and 0.12 ± 0.19 post-Artisan implantation. Endothelial cell count of the pseudophakic group was 3109 ± 458 preoperatively and 2632 ± 592 postoperatively. Mean cell loss was 15.4%. One eye required repeat surgical peripheral iridectomy for pseudophakic pupillary block. One eye required re-enclavation of a dislocated Artisan IOL haptic; the same eye required anterior vitrectomy for removal of retained lens fragment from the original lensectomy. Conclusions In this study cohort, there was no increased incidence of retinal detachment in children with Marfan syndrome and ectopia lentis in the setting of one or more prior intraocular procedures. A moderate rate of endothelial cell loss was observed.

Objective To analyze ocular involvement in patients diagnosed with Marfan syndrome (MFS), study their clinical findings and prognosis based on the type of FBN1 mutation, and evaluate possible genotype–phenotype correlations. Design Observational single-centre case series. Participants Eleven patients diagnosed with MFS were included. All subjects met the Ghent criteria of MFS, the diagnosis was confirmed by genetic testing. Methods All subjects underwent a complete ophthalmologic examination. We evaluated clinical data, the incidence of ectopia lentis (EL), and other eye disorders. The association of ocular signs with the type of mutation was analyzed. Results Four of the 11 patients had EL, of which 3 developed secondary glaucoma, and 62.5% of the phakic patients had myopia. Other ocular abnormalities included strabismus, retinal tears, retinal detachment, and amblyopia. The encountered types of mutations were premature termination codon (PTC) in 7 patients, missense in 2 cases, 1 aberration of splicing, and 1 indel mutation. Two novel mutations were found. Of the patients with EL, 2 had a missense, 1 an indel, and 1 a nonsense mutation. Conclusions Myopia was the most frequent ocular involvement. Patients with a PTC mutation revealed to have a smaller risk of EL; however, more studies are required to indicate the mechanism of the correlation.

The term isolated ectopia lentis (EL; subluxation or dislocation of the human crystalline lens) is applied to patients with EL, without skeletal features and in the absence of aortic root dilatation. To date, the only gene shown to cause autosomal-recessive isolated EL is ADAMTSL4. Here we report a novel founder mutation in ADAMTSL4 gene in children of Bukharian Jewish origin presenting with early-onset bilateral EL. A carrier frequency of 1:48 was determined among unrelated healthy Bukharian Jews. Given the complications associated with disease and the allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, pre-implantation or early postnatal diagnosis.

We present an unusual case of microcornea, bilateral spontaneous dislocation of lenses, and anomalous optic disks in a 7-week-old girl in whom a systemic diagnosis of Marfan syndrome had not yet been confirmed at presentation. The causes and differential diagnoses of this condition are discussed, and the literature on ocular manifestations of neonatal Marfan syndrome is reviewed.

The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs) protein superfamily includes 19 secreted metalloproteases and 7 secreted ADAMTS-like (ADAMTSL) glycoproteins. The possibility of functional linkage between ADAMTS proteins and fibrillin microfibrils was first revealed by a human genetic consilience, in which mutations in ADAMTS10, ADAMTS17, ADAMTSL2 and ADAMTSL4 were found to phenocopy rare genetic disorders caused by mutations affecting fibrillin-1 (FBN1), the major microfibril component in adults. The manifestations of these ADAMTS gene disorders in humans and animals suggested that they participated in the structural and regulatory roles of microfibrils. Whereas two such disorders, Weill-Marchesani syndrome 1 and Weill-Marchesani-like syndrome involve proteases (ADAMTS10 and ADAMTS17, respectively), geleophysic dysplasia and isolated ectopia lentis in humans involve ADAMTSL2 and ADAMTSL4, respectively, which are not proteases. In addition to broadly similar dysmorphology, individuals affected by Weill-Marchesani syndrome 1, Weill-Marchesani-like syndrome or geleophysic dysplasia each show characteristic anomalies suggesting molecule-, tissue-, or context-specific functions for the respective ADAMTS proteins. Ectopia lentis occurs in each of these conditions except geleophysic dysplasia, and is due to a defect in the ciliary zonule, which is predominantly composed of FBN1 microfibrils. Together, this strongly suggests that ADAMTS proteins are involved either in microfibril assembly, stability, and anchorage, or the formation of function-specific supramolecular networks having microfibrils as their foundation. Here, the genetics and molecular biology of this subset of ADAMTS proteins is discussed from the perspective of how they might contribute to fully functional or function-specific microfibrils.

Case report A case is presented of an acute onset lens particle glaucoma originating from a crystalline lens spontaneously dislocated into the vitreous for more than 20 years in a patient diagnosed with Marfan syndrome. Discussion Marfan syndrome is a connective tissue disorder with autosomal dominant inheritance caused by fibrillin gene mutation. Ectopia lentis is the predominant ocular abnormality and a major diagnostic criterion. An association between Marfan syndrome and glaucoma has also been demonstrated. The reported case is unusual in that a complete spontaneous lens dislocation to vitreous was present and progressed to secondary lens particle open angle glaucoma.

Molybdenum cofactor deficiency (MCD) is a rare and ultimately fatal metabolic disease that results in extensive neurodegeneration in early infancy. The causal association of MCD with sulfite oxidase deficiency, a known cause of subluxed lenses (ectopia lentis), has only been recently defined. We report a 16-month-old Saudi Arabian male product of a consanguineous union, who presented as a neonate with intractable seizures and a failure to thrive. Subsequent examinations revealed hypotonia, laryngomalacia, global developmental delay, progressive neurodegeneration and ectopia lentis. Urine analysis revealed elevated sulfocystiene, xanthine and hypoxanthine, which suggested MCD. This diagnosis was confirmed by subsequent genetic analysis, which disclosed a homozygous MOCS1 mutation. A significant family history of sibling death, prior to diagnosis, from intractable seizures and respiratory distress at three months of age, most likely represents the same affliction and suggests an underestimation of MCD worldwide. This case underscores the need to consider and investigate MCD in all cases of intractable infantile seizures. Thus, early diagnosis and confirmatory gene analysis before permanent neurodegeneration is imperative for potential therapeutic intervention.

Because diagnosis of Marfan syndrome is difficult during infancy, we used a large cohort of children to describe the evolution of the Marfan syndrome phenotype with age.Two hundred and fifty-nine children carrying an FBN1 gene mutation and fulfilling Ghent criteria were compared with 474 non-Marfan syndrome children.Prevalence of skeletal features changed with aging: prevalence of pectus deformity increased from 43% at 0-6 years to 62% at 15-17 years, wrist signs increased from 28 to 67%, and scoliosis increased from 16 to 59%. Hypermobility decreased from 67 to 47% and pes planus decreased from 73 to 65%. Striae increased from 2 to 84%. Prevalence of ectopia lentis remained stable, varying from 66 to 72%, similar to aortic root dilatation (varying from 75 to 80%). Aortic root dilatation remained stable during follow-up in this population receiving β-blocker therapy. When comparing Marfan syndrome children with non-Marfan syndrome children, height appeared to be a simple and discriminant criterion when it was3.3 SD above the mean. Ectopia lentis and aortic dilatation were both similarly discriminating.Ectopia lentis and aortic dilatation are the best-discriminating features, but height remains a simple discriminating variable for general practitioners when3.3 SD above the mean. Mean aortic dilatation remains stable in infancy when children receive a β-blocker.

Introduction: Sulfite oxidase deficiency (SOD) is an autosomal recessive inherited disease usually presenting in the neonatal period with severe neurological symptoms including seizures, often refractory to anticonvulsant therapy, and a rapidly progressive encephalopathy resembling neonatal hypoxic ischemia, with premature death. Most patients develop dislocated ocular lenses. Later or milder presentations of SOD are being reported with increasing frequency. These presentations include neurological regression with loss of previously acquired milestones or movement disorders. Case report: We report a four years old girl presenting with intermittent ataxia and uncoordinated limb movements. A similar episode of ataxia had occurred previously, one year before, with complete neurologic recovery and normal developmental milestones. Bilateral lens dislocation had been recently diagnosed. Cranial MRI demonstrated bilateral globus pallidus enhancement. Low homocysteine was found in plasma and Sulfitest R was positive. Further investigations led to confirmation of isolated sulfite oxidase deficiency with no enzyme activity detected on skin fibroblasts culture. Discussion: This case illustrates the clinical variability of SOD and it is not only atypical but also seems to be the mildest form described so far. The association of ectopia lentis with a movement disorder, even without psychomotor regression, should prompt us to look for this diagnosis.

Background Ocular trauma and acute loss of vision are high-yield patient presentations that may benefit from the use of bedside ultrasound to aid in the diagnosis of a variety of vision-threatening problems. Case Report We present a case of bilateral lens dislocation in which the diagnosis of lens dislocation was missed on initial computed tomography of the orbits but detected on bedside ultrasound. Why Should an Emergency Physician Be Aware of This? Point-of-care ultrasound can rapidly identify ocular pathology and expedite specialist consultation, and if necessary, transfer to a specialty center for further management.

Marfan syndrome is a multi-system connective tissue disorder, with primary involvement of the cardiovascular, ocular and skeletal systems. This autosomal heritable disease is mainly attributable to a defect in the FBN1 gene. Until 2010, the clinical diagnosis of Marfan syndrome was based on the Ghent criteria of 1996. Recently, the Ghent criteria have been revised. The revised guidelines of 2010 place more emphasis on aortic root dilatation, ectopia lentis and FBN1 mutation testing in the diagnostic assessment of Marfan syndrome. Although the revised Ghent criteria of 2010 are easier to apply, they do raise some issues that need to be addressed. In addition to adjustments in the diagnosis of Marfan syndrome, there is progress in the understanding of the pathophysiology in Marfan syndrome, leading to new treatment strategies. Losartan, an angiotensin II receptor type 1 blocker, has been shown to inhibit transforming growth factor beta signal transduction and thereby prevent aortic root aneurysms in a mouse model of Marfan syndrome. This article will provide a critical appraisal of the revised Ghent nosology in 2010 and will highlight future perspectives regarding the treatment of Marfan syndrome.

PurposeTo report a small series of pediatric patients with ectopia lentis that underwent limbal-approach lensectomy and vitrectomy and scleral-fixated intraocular lens implantation and to review the literature on the topic of surgical management of ectopia lentis.MethodA retrospective review of 13 eyes of seven patients that underwent lensectomy, vitrectomy, and scleral-fixated intraocular lens implantation and a review of the ophthalmic literature.ResultsIn our series, the average age at surgery was 70.3±13.8months and the average length of follow-up was 23.8±5.9months. The mean pre-operative visual acuity was 0.86±0.17 which improved to 0.23±0.09 post-operatively (p

There has been a great interest in the last decades about the clinical significance of elevated total plasma homocysteine (tHcy), and especially its possible association with an increased cardiovascular risk. Measurement of tHcy is clearly indicated when homocystinuria is suspected in young or adult patients (in the presence of a severe, atypical or progressive miopia with ectopia lentis and/or venous thromboembolism and/or severe, premature or atypical atherosclerotic vascular disease) and in the evaluation of vitamin B12 and/or folic acid deficiencies. The current evidence does not support either the screening measurement of tHcy or the treatment with vitamin B12 and/or folic acid supplementation in patients with cardiovascular disease. It is important to remember that it remains to be proved whether the long-term administration of folic acid at pharmacological doses is safe.

Purpose To report the short-term outcomes and complications of iris-fixated posterior chamber intraocular lenses (PCIOL) in the pediatric population. Design Retrospective, observational case study. Methods Twelve consecutive pediatric patients (17 eyes) underwent placement of foldable iris-sutured PCIOLs between September 1, 2004 and September 30, 2007 by two anterior segment surgeons at a single academic center. Outcome measures included change in visual acuity (VA) and complications. Results In our series, there was a higher rate of dislocation of iris-sutured IOLs in patients with a history of ectopia lentis resulting from Marfan syndrome or hereditary or idiopathic causes than in patients being treated for aphakia resulting from other causes (45% vs 0%). Mean final VA improved by 0.23 logarithm of the minimum angle of resolution units from preoperative baseline. One eye of a Marfan patient sustained a retinal detachment eight months after dislocation of the PCIOL, and one patient experienced iris capture of the IOL after surgery. Conclusions Iris-fixated IOLs are reasonable alternative to transsclerally sutured IOLs to correct aphakia in pediatric patient. Dislocation of the IOLs can occur, however, and there is concern for suture degradation over time. The procedure should be considered with caution in pediatric patients.

Iridodonesis or tremulous iris is a clinical sign of ectopia lentis which is frequently associated with homocystinuria. We present a forty-two-year-old woman victim of a left middle cerebral artery ischemic stroke. The clinical examination found bilateral iridodonesis and laboratory tests showed an increased level of serum homocysteine and homocystinuria. Homocystinuria was caused by a compound heterozygous I278T and D444N mutation of cystathionine beta-synthase (CBS) gene and also a C667T heterozygous polymorphism of methylene-tetrahydrofolate-reductase gene. This case was atypical because of the incomplete phenotype, development of complications in adulthood and the association of a rare compound heterozygous mutation of the CBS gene.

Purpose To review the clinical features of reported cases of Cohen syndrome with a focus on ophthalmic features and report nine new cases. Methods Retrospective case series and literature review. Results Cohen syndrome is a rare autosomal-recessive condition with about 136 reported cases. The typical phenotype of Cohen syndrome is variable and includes mild to severe psychomotor retardation, microcephaly, a cheerful disposition, characteristic facial features, childhood hypotonia and joint laxity, truncal obesity, intermittent neutropenia, along with a progressive retinal dystrophy and refractive myopia. We present nine cases that illustrate the typical clinical features of the disorder at different ages, including a woman with the less common finding of ectopia lentis. Conclusions Cohen syndrome remains underdiagnosed or misdiagnosed by ophthalmologists. Awareness of this condition among ophthalmologists is important because the typical systemic and ophthalmologic findings may lead to an accurate diagnosis and counseling. Although diagnostic criteria exist based on clinical studies of patients with confirmed VPS13B ( COH1 ) gene mutations, no minimal clinical diagnostic criteria are widely accepted at this time.

Marfan syndrome is a widespread disorder of connective tissue. It is characterized by systemic and ocular features due to mutations in the fibrillin gene. Awareness and prompt recognition of the ocular complications of Marfan syndrome may enable improvement and preservation of sight. Studies have been performed in the last few years that enable a better understanding of the genetics of the syndrome, earlier diagnosis, and improvement in the surgical techniques and options.

Purpose: To describe the clinical features of an atypical presentation of ectopia lentis consisting of primary anterior axial lens subluxation in childhood, associated progressive myopia, and complicating angle-closure glaucoma; to facilitate early diagnosis of this triad; and to report the results of lensectomy for treatment. Methods: A retrospective case review of eight patients. Clinical course, visual acuity, gonioscopy, axial length, refraction, fundus examination, associated systemic features, and results of treatment are provided. Results: This subgroup of patients with ectopia lentis is at risk for progressive, synechial, angle-closure glaucoma. Identification of a clinical triad consisting of rapidly increasing myopia, normal axial length, and progressive axial subluxation leads to earlier diagnosis. Prophylactic lensectomy provides a safe and sight-saving treatment that arrests and, at times, reverses the progression of angle-closure glaucoma. Conclusions: Ectopia lentis with anterior axial subluxation and progressive myopia can be a sight-threatening condition when significant forward mobilization of the lens results in synechial angle-closure glaucoma. Recognition of this clinical entity can expedite diagnosis and prevent irreversible loss of vision secondary to glaucoma. Because the primary mechanism of angle closure is angle crowding, peripheral iridotomy does little to control the rise in intraocular pressure. Prophylactic lensectomy has proven to be the most reliable treatment in our experience.

Purpose: High refractive errors and optical aberrations reduce vision when the lens edge bisects the pupil. We studied outcomes of eyes with ectopia lentis following lensectomy. Methods: Charts of 11 consecutive patients with bilateral ectopia lentis who underwent lensectomy-anterior vitrectomy in at least one eye from 1985 to 2004 were reviewed. Eighteen eyes were operated. One eye was excluded due to short-term follow-up ( Results: Mean age at surgery was 7.7 years (2 to 17 years). Median follow-up after lensectomy was 10 years (range 2 to 16 years). Six eyes were followed for 6 to 10 years, and another six eyes were followed for 11 to 16 years. Patient diagnoses included Marfan syndrome (nine eyes), ectopia lentis et pupillae (three eyes), simple ectopia lentis (two eyes), homocystinuria (two eyes), and sporadic spherophakia (one eye). Preoperative best-corrected visual acuity (BCVA) ranged from 20/60 to light perception, and postoperative BCVA ranged from 20/20 to 20/100 (14 eyes were at least 20/30). Complications included posterior vitreous detachment (two eyes, 12%), glaucoma (one eye, 6%), transient ocular hypertension (one eye, 6%), wound dehiscence with iris incarceration (one eye, 6%), transient vitreous hemorrhage (one eye, 6%), and peripheral anterior synechiae (one eye, 6%). No retina detached. Conclusions: Our cohort of patients with long-term follow-up shows that pars plana lensectomy can be successful in restoring vision when conservative measures fail.

Background A child with microspherophakia is described who was managed with scleral fixation of the loose capsular bag using Ahmed capsular tension segment and the small capsular bag was expanded using a standard capsular tension ring. Methods The child presented initially with lenticular myopia and concomitant glaucoma for which he was treated with peripheral iridotomy alone. The IOP remained uncontrolled after iridotomy procedure. Therefore, bimanual clear lens aspiration was performed; standard capsular tension ring was implanted ‘in the bag’ and Ahmed capsular tension segment was sutured to the sclera to stabilize the capsular complex. Foldable acrylic IOL was then injected into the bag. Results Postoperatively, the child had an unaided acuity of 20/30 on ETDRS. The IOL was centered well and the capsular bag had expanded due to the effect of CTR. Conclusions This ‘dual support’ technique takes advantage of using both CTR and CTS to overcome the generalized zonulopathy found in cases of microspherophakia. It effectively counteracts lenticular myopia, treats glaucoma, strengthens the capsular bag and does not entail the future risk of IOL-bag dislocation.

Microphthalmos with cyst is a rare condition characterized by a small globe and an inferior uveoretinal coloboma. There is also a defect in the posterior aspect of the eye through which a cyst lined by neuroectodermically derived tissue protrudes into the orbit. A case of isolated bilateral colobomatous and cystic microphthalmos is reported in an otherwise healthy child, showing no evidence of chromosomal abnormalities. Microscopic findings in the enucleated eye consisted of iris and retinal dysgenesis, ectopia lentis, persistent anterior tunica vasculosa lentis and pupillary membrane, intrachoroidal smooth muscle, and optic nerve hypoplasia. In the orbital cyst, a thick membrane reminiscent of the retinal inner limiting membrane lay between the fibroadipose and vascularised outer wall and the inner neuroectodermal lining.

Objective The authors describe two cases of isolated sulfite oxidase deficiency found in one family. This is a rare autosomal-recessive disorder presenting at birth with seizures, severe neurologic disease, and ectopia lentis. It can be easily missed with metabolic screening; however, the finding of lens subluxation stresses the importance of ophthalmic assessment in making the diagnosis. Design Two observational case reports. Intervention/methods Ophthalmic assessment, biochemical assay for specific urinary and plasma metabolites, magnetic resonance imaging, and gene sequencing were used to make the diagnosis of the disease in the proband. The diagnosis was subsequently recognized in a previously affected sibling after the postmortem neuropathology was reviewed. Mutation analysis was performed on cultured fibroblasts from the proband to identify and categorize the specific mutation responsible for the disease in the family. From this, future prenatal detection of sulfite oxidase deficiency is possible. Main outcome measures The diagnosis of sulfite oxidase deficiency was established in this family, enabling appropriate genetic counseling and recurrence risk estimation. Results Point mutations were found in both alleles of the sulfite oxidase gene in the proband. The first is a 623C → A mutation, which predicts an A208D substitution, and the second is a 1109C → A, which predicts an S370Y substitution. Both residues A208D and S370Y are critical for sulfite oxidase activity. Conclusions Isolated sulfite oxidase deficiency is a rare heritable disease for which mutation analysis can allow accurate prenatal screening. It often is difficult to diagnose by clinical presentation alone, but the critical finding of lens subluxation accompanying seizures and diffuse neurologic disease in an infant should alert the physician to the diagnosis.

Purpose To examine the fibrillin-1 ( FBN1 ) gene for mutations in members of a Chinese family with isolated ectopia lentis. Design Clinically relevant laboratory investigation. Methods Family members underwent clinical examinations. Genomic DNA was extracted from leukocytes of peripheral blood from the available members and 100 controls for mutation analysis. The 65 exons of FBN1 were amplified by polymerase chain reaction and screened for mutations by a combination of denaturing high-performance liquid chromatography analysis and direct DNA sequencing. Results A mutation, c.184C→T in exon 2 of FBN1 , which results in substitution of arginine by cysteine at position 62 of the fibrillin-1 protein (p.R62C) in all affected family members but in none of the unaffected individuals. Conclusions A recurrent mutation of FBN1 gene resulted in an arginine-to-cysteine residue (p.R62C), is responsible for the patients with isolated ectopia lentis in a Chinese family.

Marfan syndrome (MFS) is one of the most common inherited connective tissue disorders that severely affects the cardiovascular system. Mutations in the gene encoding fibrillin-1 (FBN1) have been shown to cause MFS as well as dominant ectopia lentis and neonatal Marfan syndrome. Fibrillin-1 is the major component of elastic fiber microfibrils in the extracellular matrix of connective tissue. Recent molecular studies have brought some light into understanding the pathogenesis of MFS, but the diagnostic problems still prevail, and targeted therapy of MFS must await better dissection of the role of fibrillin-1 in tissue phenotype using different experimental systems. (Trends Cardiovasc Med 1997;7:282-288). © 1997, Elsevier Science Inc.

The Marfan syndrome is defined by a combination of features of defective microfibrillar organization and function in multiple tissues and organs. Most of the features, including the cardinal ones of dis-proportionate tall stature, ectopia lentis, mitral valve prolapse, aortic root dilatation and aortic dissection, are age dependent, which may make diagnosis in a child difficult. Recently revised diagnostic criteria strengthen the requirements for an affected relative and specify how molecular data can be used in both a positive and negative sense. The goal is to identify from among many conditions, both hereditary and acquired, that share features with Marfan syndrome those patients who warrant the label of Marfan syndrome and structured, preventive management.

Purpose: To describe the criteria and techniques for the surgery of hereditary subluxated lens in children and analyze the visual and surgical outcome after an extended period of follow-up. Methods: From 1982 to 1994, 65 children who had subluxation of their lens were followed in the authors' clinic. Thirty-seven children (59 eyes) underwent surgery (27 eyes had Marfan syndrome; 23 eyes had essential dislocation; and 9 eyes had a diagnosis of homocystinuria, aniridia, microphthalmia, or Weill-Marchesani syndrome). The indications for surgery were best-corrected visual acuity of less than 20/70, forward subluxation of the lens to the anterior chamber, monocular diplopia, or rapidly progressing posterior subluxation of the lens. All 54 eyes with subluxation of the crystalline lens behind the iris underwent pars plana lensectomy combined with anterior vitrectomy. In five eyes with total forward dislocation of the lens in the anterior chamber, a limbal approach for removal of the lens and protruding vitreous was used. Results: Postoperative follow-up ranged from 12 to 144 months (average, 55 months). After surgery, 52 eyes (88%) of the entire group achieved an improvement (2 lines or more on the Snellen chart) in best-corrected visual acuity. Seven eyes (12%) did not show improvement and remained with the same visual acuity as before the surgery. Retinal detachment was detected in one eye 2 years after surgery and was the only major postoperative complication observed in these patients. Conclusion: These results and the unique continuous and long-term follow-up on our patients demonstrate that lensectomy of ectopia lentis combined with anterior vitrectomy using a closed-system technique is a beneficial and relatively safe procedure.

Weill-Marchesani syndrome is a genetically determined rare systemic connective tissue disorder consisting of brachymorphy, brachydactyly, aortic stenosis, and Ophthalmologic abnormalities, such as ectopia lentis, microspherophakia, and secondary glaucoma. The primary lesion is fibrous tissue hyperplasia. Airway control and intubation may be difficult in patients with WMS because of stiff joints, poorly aligned teeth, and maxillary hypoplasia with a narrow palate. We describe the successful airway management of a patient with WMS and laryngeal stenosis, using an intubating laryngeal mask following failed conventional laryngoscopic intubation. (C) 2003 by Elsevier Science Inc.

Ectopia lentis (EL), a dominantly inherited connective tissue disorder, has been genetically linked to the fibrillin gene on chromosome 15 (FBN1) in earlier studies. Here, we report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but distinct conditions with typical manifestations in the ocular and skeletal systems, the fundamental difference between them being the absence of cardiovascular involvement in EL. We report a point mutation, cosegregating with the disease in the described family, that displays EL over four generations. The mutation changes a conserved glutamic acid residue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mutagenetic studies have demonstrated the necessity of an analogous glutamic acid residue for calcium binding in an EGF-like repeat of human factor IX. This provides a possible explanation for the role of this mutation in the disease pathogenesis.

Common conditions that give rise to dislocated lenses are Marfan's syndrome, primary ectopia lentis and homocystinuria. Children with these conditions frequently have lenticular myopia before surgery and require aphakic corrections postoperatively. Asymmetrical lens dislocation and amblyopia make postoperative optical correction difficult. The optimum way of treating either the resultant anisometropia or bilateral aphakia, is with contact lenses. A retrospective study was carried out on 17 children with dislocated lenses. Patients with both unilateral and bilateral aphakia are included. Their keratometry measurements and contact lens fitting are discussed.

The oculocutaneous features of the heritable disorders of collagen and elastic tissue are highlighted. Although there is an emphasis on the classic ocular stigmata of each entity-angioid streaks of pseudoxanthoma elasticum, blue sclerae of osteogenesis imperfecta, ocular fragility of EhlerDanlos syndrome, ectopia lentis of Marfan syndrome-other significant ocular findings are detailed.

A boy visited an ear-nose and throat clinic for serous rhinorrhea and a tumor-like mass in the nasal cavity. X-ray and computered tomographies showed a bone-like mass with a slightly radiolucent center which seemed to stem from the nasal septum. A supernumerary tooth in the nasal cavity was extirpated under local anesthesia. In some reports, complications of supernumerary tooth were severe and involved areas other than the nose (cleft lip and/or palate, bilateral aniridia and ectopia lentis, familial adenomatous polyposis coli, ventricular septal defect or patent ductus arteriosus). A case had a risk of inducing severe intracranial complication. Therefore we must not overlook a supernumerary tooth.

This is a collective review of 564 patients with Marfan syndrome among 98 pedigrees reported from 18 provinces and cities in China over a 37-year period from 1951 to 1987. A positive family history of Marfan syndrome was found in 74.3% of the patients: the mode of inheritance was dominant in 73.8% and recessive in 0.5%. Sporadic cases occurred in 25.7%. A screening of 29,067 children found five children with Marfan syndrome, giving a prevalence of 17.2 per 100,000 of the population, a gene frequency of 8.61 per 100,000 genes, and a penetrance of 71.69%. Pleiotropy was clear in these cases: arachnodactyly in 77%, ectopia lentis in 86.8%, and dilated aortic root in 80.1%. Chromosome examination showed no regular aberrations except in a family of five in whom a giant-satellited chromosome 14 was found in three afflicted members but not in the two unaffected relatives. The high prevalence of aortic root dilation in Marfan syndrome makes echocardiography the most useful and practical means of diagnosis. Close follow-up and regular echocardiographic evaluation are indicated not only in patients with Marfan syndrome but also in their families, for both diagnostic and therapeutic purposes.

We present a 7 1/2-year-old girl with type I homocystinuria who required anesthetic care during repair of bilateral ectopia lentis. Homocystinuria is an autosomal recessive disorder and represents the second most common error of amino acid metabolism. Defective function of the enzyme cystathionine synthetase results in elevated serum levels of methionine and homocysteine. Physiologic disturbances include an increased risk of thromboembolic events and hypoglycemia. Perioperative measures to prevent thromboembolic events include diet therapy to lower serum methionine and homocysteine levels, adequate preoperative hydration, maintenance of intraoperative cardiac output, and the use of pneumatic stockings to prevent peripheral stagnation of blood. Hypoglycemia is thought to be due to alterations in insulin release associated with high levels of circulating sulfur-containing amino acids such as methionine. Perioperative measures include normalization of serum methionine and administration of exogenous glucose during periods of fasting.