Ultrabiomicroscopic-Histopathologic Correlations in Individuals with Autosomal Dominant Congenital Microcoria: Three-Generation Family Report

Abstract

Background: Congenital microcoria (CMC) is due to a maldevelopment of the dilator pupillae muscle of the iris, with a pupil diameter of less than 2 mm. It is associated with juvenile open angle glaucoma and myopia. We report on a three-generation Mexican-Mestizo family with CMC. The eldest member’s iris biopsy proved muscle anomalies. Further, we analyzed novel ultrasound biomicroscopy findings in the family members who did not require surgery. Patients and Methods: A 62-year-old woman, her 41-year-old son and her 9-year-old grandson affected with microcoria since birth, documented by clinical examination and ultrasound biomicroscopy. The eldest member underwent phacoemulsification, and a biopsy of the iris and the anterior capsule of the lens was taken. Results: Ultrasound biomicroscopy confirmed the CMC diagnosis showing iris thinning and a pupil diameter of less than 2 mm. Histopathology of the iris showed a significant reduction of smooth muscle cells, but no alterations of the anterior lens capsule. Discussion: Although CMC is a rare disorder, which is due to a maldevelopment of the dilator pupillae muscle of the iris, it could be associated with juvenile open angle glaucoma and myopia; therefore, precise diagnosis is required. Ultrasound biomicroscopy could be a great option to confirm the disorder.

Congenital Microcoria: Clinical Features and Molecular Genetics

“…This was substantiated in 1923 by a Norwegian ophthalmologist and pathologist, who provided a detailed clinical description of the ocular phenotype in three siblings combined with a post mortem anatomical analysis of the eyes of two of them who had died of apoplexia cerebri [ 33 ]. This study, along with subsequent post mortem analyses of irises and iridectomy specimens from 25- to 72-year-old individuals, revealed significant iris thinning with atrophy of the stroma, displaying a normal ultrastructure and abundant collagen fibrils but greater numbers of fibroblasts and melanocytes in the ground substance [ 11 , 28 , 32 , 34 , 35 , 36 , 37 ]. Consistent with the observation of partial or total dilation inability among affected individuals, varying dilator muscle anomalies have also been described—from peripheral to generalized dearth or absence of stromal contractile processes of the anterior iris epithelium [ 8 , 9 , 10 , 11 , 21 , 34 , 35 , 38 , 39 ].…”

“…To the best of our knowledge, a total of 160 affected individuals from 49 families have to date been reported with a bilateral disease characterized by partial or total absence of pupil dilation, even after mydriatic treatment [ 8 , 9 ]. A featureless surface with poorly developed collarette and crypts, reduced iris pigmentation, iris stroma thinning, and visible transillumination are typical of the disease [ 9 , 28 , 29 , 30 , 31 , 32 ].…”

Absence of Goniodysgenesis in Patients with Chromosome 13Q Microdeletion-Related Microcoria

“…Interestingly, a 2-generation family with unique heterozygous GPR180 nonsense mutations associated with iridocorneal angle dysgenesis but normal pupillary response and absence of iris transillumination was described. 1 The cases presented herein add to the phenotypic spectrum associated with TGDS or GPR180 gene deletions, ranging from isolated goniodysgenesis, to microcoria with iris hypoplasia but without goniodysgenesis, 7 to the full MCOR phenotype with glaucoma. A goniodysgenetic chamber angle is the result of abnormal migration or differentiation of the neural crest-derived mesenchymal cells.…”

Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria

“…In addition to abnormal dilator pupillae muscle, the miotic iris is thin and displays abnormal stroma and iridocorneal angle. [1][2][3][4] Iris thinning is consistent with transillumination of miotic irises and high sensitivity to light. High myopia and glaucoma are frequently associated with this condition.…”

“…We obtained DNA samples of affected and unaffected members of six MCOR-affected families originating from France, Japan, and Mexico (FR1 and FR2, JP1 and JP2, MX1 and MX2, respectively). Three of these families were previously reported (FR1, the original family that allowed mapping of the MCOR locus on chromosome 13q31-q32; 9,10 JP1, 6 and MX1 4 ). The pedigrees of the families are presented in Figure 1.…”