Anterior segment alterations in congenital primary aphakia—a clinicopathologic report of five cases

Chaurasia, Sunita; Jakati, Saumya; Ramappa, Muralidhar; Mishra, Dilip Kumar; Edward, Deepak P.

doi:10.4103/ijo.ijo_2078_19

Cited by 10 publications

(1 citation statement)

References 12 publications

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“…Given dense corneal opacities, full clinical assessment of FOXE3 defects requires alternative imaging modalities, such as ultrasound, optical coherence tomography (OCT), or magnetic resonance imaging (MRI) to diagnose; thus, the complete spectrum of FOXE3 ocular defects in many affected individuals may not be fully identified. In prior studies, all individuals with primary aphakia undergoing penetrating keratoplasty were found to have atrophic iris tissue, suggesting that the absence of the lens disrupts iris development; however, since no genetic analysis was performed, the causative variant(s) in these cases may directly affect development of both structures ( 40 ). Indeed, mouse models ( dysgenic lens , Foxe3 dyl ) support a role for Foxe3 in iris development; Foxe3 +/− mice have intact lens epithelia but hypoplastic iris tissue and iridocorneal and iridolenticular adhesions ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive phenotypic and functional analysis of dominant and recessiveFOXE3alleles in ocular developmental disorders

Reis

Сорокина

Ďuďáková

et al. 2021

Human Molecular Genetics

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The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%), and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%), and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia, or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

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Section: Discussionmentioning

confidence: 99%

Comprehensive phenotypic and functional analysis of dominant and recessiveFOXE3alleles in ocular developmental disorders

Reis

Сорокина

Ďuďáková

et al. 2021

Human Molecular Genetics

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Variable phenotype of secondary congenital corneal opacities associated with microphthalmia with linear skin defects syndrome

Franco

Scanga

Nischal

2022

American J of Med Genetics Pt A

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To describe the anterior segment (AS) findings in patients with microphthalmia with linear skin defects syndrome (MLS), also known as microphthalmia, dermal aplasia, and sclerocornea (MIDAS). A retrospective chart review was conducted to identify patients with a diagnosis of MLS syndrome seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, AS optical coherence tomography, and molecular testing were reviewed. Five female patients (10 eyes) were identified. One eye was anophthalmic, one was in a status post penetrating keratoplasty, and eight eyes presented with congenital corneal opacity (CCO).Of these, one showed a normal lens and a very small faint CCO; five showed congenital aphakia and characteristic silvery appearance of the cornea with vascularization; and two showed irido-corneal adhesions in association with normal or abnormal lens and localized avascular CCO. Genetic testing was performed and revealed involvement of HCCS in four patients. In MLS patients, kerato-irido-lenticular dysgenesis can be associated with secondary CCO. It is important to distinguish these CCO from sclerocornea, in order to refine the appropriate management and counseling the parents about the prognosis.congenital corneal opacities, congenital primary aphakia, MIDAS syndrome, MLS syndrome | INTRODUCTIONMicrophthalmia with linear skin defects syndrome (MLS) or microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome is a rare X-linked dominant disorder caused by pathogenic variants or copy number variants in the HCCS, COX7B, or NDUFB11 genes (van Rahden et al., 2015). The proposed diagnostic criteria include microphthalmia and/or anophthalmia as the cardinal ocular features to

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Lens

Yanoff,

Sassani

2025

Ocular Pathology

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Anterior segment alterations in congenital primary aphakia—a clinicopathologic report of five cases

Cited by 10 publications

References 12 publications

Comprehensive phenotypic and functional analysis of dominant and recessiveFOXE3alleles in ocular developmental disorders

Comprehensive phenotypic and functional analysis of dominant and recessiveFOXE3alleles in ocular developmental disorders

Variable phenotype of secondary congenital corneal opacities associated with microphthalmia with linear skin defects syndrome

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