Microspherophakia

Abstract: Microspherophakia is an autosomal-recessive congenital disorder characterized by small spherical lens. It may be isolated or occur as part of a hereditary systemic disorder, such as Marfan syndrome, autosomal dominant and recessive forms of Weill-Marchesani syndrome, autosomal dominant glaucoma-lens ectopia-microspherophakia-stiffness-shortness syndrome, autosomal dominant microspherophakia with hernia, and microspherophakia-metaphyseal dysplasia. The purpose of this study was to map and identify the gene for isolated microspherophakia in two consanguineous Indian families. Using a whole-genome linkage scan in one family, we identified a likely locus for microspherophakia (MSP1) on chromosome 14q24.1-q32.12 between markers D14S588 and D14S1050 in a physical distance of 22.76 Mb. The maximum multi-point lod score was 2.91 between markers D14S1020 and D14S606. The MSP1 candidate region harbors 110 reference genes. DNA sequence analysis of one of the genes, LTBP2, detected a homozygous duplication (insertion) mutation, c.5446dupC, in the last exon (exon 36) in affected family members. This homozygous mutation is predicted to elongate the LTBP2 protein by replacing the last 6 amino acids with 27 novel amino acids. Microspherophakia in the second family did not map to this locus, suggesting genetic heterogeneity. The present study suggests a role for LTBP2 in the structural stability of ciliary zonules, and growth and development of lens.

Abstract: Muscular dystrophy, brain changes, severe visual failure, myopia and eye changes consisting of congenital glaucoma, cataract, optic and renal changes, have not previously been grouped together in any known syndrome. A series of nine children (8 boys and 1 girl) aged 12 months to 10 years, one of whom had died at the age of 6 years, and one adult male patient aged 40 years, are described. The general signs, laboratory findings and genetic aspects have been presented in detail in a previous paper. Severe visual handicap, nystagmus and uncontrolled eyemovements were present in 9/10 patients. Myopia of > 2 D was found in 8/10 and severe myopia (> 10 D) in 6/10 patients. Congenital glaucoma was diagnosed and treated in five children and infantile glaucoma in three children. Glaucoma was caused by defective cleavage of the chamber angle as evidenced by membranes and synechiae of the chamber angle on gonioscopy and by histology. Mature cataract was operated in two patients aged 10 and 23 years, respectively. Microspherophakia was present in two boys. The ERG and VER showed non-specific changes in the four patients examined. Tapetoretinal dystrophy was not present. A sequence of muscular dystrophy, brain changes, severe visual failure and eye changes consisting of congenital glaucoma, cataract, optic and retinal changes, has not been found within the range of any hitherto known syndrome.

Abstract: Purpose To report the clinical features, management, and treatment outcomes of glaucoma in microspherophakia. Methods Medical records of 159 eyes of 80 subjects with microspherophakia were reviewed. The clinical features at presentation, presence of glaucoma, methods of treatment, and their outcomes were noted. Glaucoma was diagnosed based on intraocular pressure (IOP)≥22 mm Hg on 2 different occasions and/or glaucomatous optic disc damage. Angle closure was defined as occludable angles >270 degrees with or without presence of peripheral anterior synechiae. Results Glaucoma was diagnosed in 81 eyes (51%). The mean age of subjects was 20±13 years, mean refractive error was -13.5±5.5, the mean IOP was 27.7±11.1 mm Hg. IOP≥22 mm Hg was present in 84% of eyes, disc damage in 59% of the eyes, 75% eyes had angle closure, and 25% had open angle on gonioscopy. Subluxation of crystalline lens was seen in 53 eyes and 14 eyes had dislocation of the lens; systemic associations were present in 21 subjects (3 Marfan syndrome, 18 Weill-Marchesani syndrome). Nine eyes out of 51 and 2 out of 16 eyes responded to medical treatment and laser iridotomy, respectively. Of the 48 eyes that required surgical intervention, 24 eyes underwent trabeculectomy. Complete success probability of trabeculectomy was 86% [95% confidence interval (CI), 63%-95%] at 6 months, 77% (95% CI, 53%-90%) at 1 year, which was maintained till 7 years, and reduced to 61% (95% CI, 26%-84%) at 8 years. Nearly 20% of eyes at presentation and 30% of the eyes at last follow-up were blind due to glaucoma. Conclusions More than half of the eyes with microspherophakia in this series presented with glaucoma; angle closure was the predominant form of glaucoma. Blindness due to glaucoma in microspherophakia was 20% to 30%.