Bilateral Congenital Cataracts Research Articles

A Case Report of a New Variant Associated with Vici Syndrome in a Turkish Infant; EPG5 Frameshift Variant

Introduction: Vici syndrome is a congenital multisystem disorder characterized primarily by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency, and oculocutaneous hypopigmentation, along with additional newly recognized findings. Autosomal recessive variants in the EPG5 gene, which encodes ectopic P-granules autophagy protein 5 (EPG5), a key regulator of autophagy, are known genetic causes of this syndrome. The aim of this case report is to present a novel disease-causing variant identified through EPG5 gene sequence analysis. Case Presentation: We report on a 2-month-old Turkish girl who presented with developmental delay, bilateral congenital cataracts, microcephaly, hypotonia, hypertrophic cardiomyopathy, hypopigmented skin lesions, and agenesis of the corpus callosum. Genetic analysis revealed a homozygous c.7504delC (p.Gln2502Argfs*4) frameshift variant in the EPG5 gene, which has not been previously documented. Conclusions: Adding a new variant to the literature is crucial, as it highlights the feasibility of reaching an accurate diagnosis through well-conducted physical examination findings in patients with early developmental delay. This case also raises awareness about such rare diseases. Moreover, recognizing new mutations is critical for understanding atypical findings, prognosis, treatment responses, and the genetic risks for other family members.

Development of a prognostic model for predicting long-term visual acuity after cataract surgery in children with bilateral congenital cataracts: a single centre retrospective, observational study

BackgroundTo evaluate factors influencing best corrected visual acuity (BCVA) in paediatric patients with bilateral congenital cataracts (CC) after cataract extraction and intraocular lens (IOL) implantation, as well as develop a robust model for predicting long-term visual acuity.MethodsThis retrospective study followed 194 paediatric patients with bilateral CC from January 2008 to December 2021. The endpoint event was defined as a final BCVA < 0.22 Log MAR at the last follow-up, which indicated good outcome. The probability of reaching this endpoint event was modelled using Cox proportional hazards regression analysis and internally validated through 200 iteration of 5-fold cross-validation.ResultsA prognostic model for long-term visual acuity in bilateral CC after surgical treatment was established as follows: ln h(t) = −0.009 × “age at cataract extraction” − 0.015 × “age at IOL implantation” − 2.934 × “without nystagmus at last follow − up” + ln h0(0), in which h0(t) represents the baseline risk equation that can be any non-negative equation for time (t); h(t) represents the probability of the endpoint event occurring at time (t) without any endpoint event occurring before it. The model was visualized using a nomogram and contour plot to facilitate clinical practice. The model demonstrated reasonably accurate discrimination with an area under the receiver operating characteristic curve of 0.712 (95% confidence interval [CI]: 0.589–0.835) and a C-index of 0.797 (95% CI: 0.683–0.911). According to the model, children with bilateral CC had a higher likelihood of achieving a good outcome (BCVA < 0.22 Log MAR) if they underwent cataract extraction before the age of six months (hazard ratio [HR] 1.80, 95% CI: 0.92–3.70), received IOL implantation before the age of thirty-one months (HR 3.70, 95% CI: 1.77–7.80), and presented without nystagmus during their last follow-up visit (HR 11.20, 95% CI: 3.96–31.80).ConclusionsThis long-term visual acuity prognostic model demonstrates adequate performance for individualized prediction and assists in clinical decision-making. The risk stratification index guides optimal timing for surgery.

Visual and surgical outcomes of childhood glaucoma following cataract surgery

PurposeTo evaluate frequency of surgery and post-treatment outcomes in glaucoma following cataract surgery (GFCS). MethodsThe medical records of patients with GFCS were reviewed retrospectively. Lensectomy and glaucoma surgery details and final examination findings were collected. Inclusion criteria included history of lensectomy at <1 year of age, diagnosis of glaucoma, and at least 1 year of follow-up. ResultsOf 169 eyes of 127 GFCS patients (66 male, 58 bilateral cases), 88 eyes (52%) of 73 (57%) patients underwent glaucoma surgery (median, 3.5 years of age at first glaucoma surgery; median of two glaucoma surgeries). At final follow-up (mean, 13.6 ± 7.0 years), eyes requiring glaucoma surgery had worse visual acuity (P = 0.01) and greater cup:disk ratio (P < 0.01). GFCS patients with history of bilateral congenital cataracts had better visual acuity in affected eyes than those with history of unilateral congenital cataract (P < 0.01). Angle surgery (n = 56), Baerveldt devices (n = 38), Ahmed valves (n = 19), and cycloablation (n = 21) showed 1-year survival rates between 64% and 75%. Baerveldt implants showed the highest 5- and 10-year survival rates, at 65% and 43%, respectively. ConclusionsMore than 50% of eyes with GFCS in our study cohort required at least one glaucoma surgery. Glaucoma surgery and history of unilateral cataract were associated with worse visual acuity outcomes.

Management of Bilateral Congenital and Juvenile Cataracts in a Low-Income Country: Patient Identification, Treatment Outcomes, and Follow Up.

Childhood blindness remains a neglected issue in eye care within low-income countries, with congenital and juvenile cataracts being the most common treatable causes. This study aims to investigate the factors influencing the management of congenital and juvenile bilateral cataracts, provide data on general outcomes and postoperative findings, and discuss treatment in a low-income country context. In this prospective study, data from clinical care were continuously entered into a database, and one follow-up examination of a cohort of 91 patients with congenital and juvenile bilateral cataracts in Kinshasa, Democratic Republic of the Congo, was conducted. Multiple factors that affect the first clinical presentation, the clinical management, and outcome were investigated. Most patients (88.5%) who received medical treatment were identified by cataract finders. A patient's presentation time was independent of the parent's education, social status, income, and sex of the child. The median age at first presentation was 5.8 years (ranging from 0 days to 17.3 years). The best visual acuity outcomes were achieved by patients who underwent surgery during early childhood. According to WHO grades and on an eye level basis, 51.1% (93 out of 182 eyes) showed improvement, while 34.6% (63 eyes) had unchanged results post-surgery. Among the cases without improvement, 76.2% were blind prior to surgery. Postoperative findings were observed in 56% of the patients, with secondary cataracts being the most common, affecting 26.37% of the operated eyes. Optimal management of childhood cataracts involves early identification, efficient hospital infrastructure, high-quality medical care, and long-term follow up. In sub-Saharan Africa, this approach must be adapted to the context of available resources, which differs significantly from those in high- and middle-income countries.

Bilateral developmental cataracts in a child with familial lipodystrophy

Bilateral developmental cataracts are usually caused due to hereditary metabolic disorder or intrauterine infections. Familial lipodystrophy type 7 has variable phenotypes with early-onset cataracts and lower limb spasticity, with most reports showing the onset of cataracts in the second decade of life. We report a rare case of bilateral congenital cataract in a child aged 3 years and 9 months with genetically proven familial partial lipodystrophy type 7. Bilateral developmental cataracts need complete physical examination and genetic analysis to detect unusual and rare causes like familial partial lipodystrophy.

A novel base substitution mutation of the CRYBA2 gene is associated with autosomal dominant congenital cataract

Congenital cataract is one of the leading causes of vision loss in children, and a large proportion of cases are related to genetics. In a Chinese family, we reported a new missense mutation in CRYBA2 (c.223T>C: p.Tyr75His), which can cause autosomal dominant congenital bilateral cataract. We collected blood samples from family members (mother and two sons) and extracted DNA. Through whole-exome sequencing, we discovered a novel unreported mutation. According to relevant ACMG guidelines, this mutation was determined to be a variant of unknown clinical significance. This article further expands the site information on the CRYBA2 mutations.

Postoperative complications and axial length growth after bilateral congenital cataract surgery: eyes with microphthalmos compared to a comparison group.

To investigate the postoperative clinical outcomes and axial length (AL) growth of infants with congenital cataracts and microphthalmos following first-stage cataract surgery. Retrospective case-control study. Setting: Single centre. Infants with congenital cataract that met the inclusion criteria were classified into two groups: the microphthalmos and comparison groups. All infants underwent a thorough ophthalmologic examination before surgery, and one week, 1 month, 3 months, and every 3 months after surgery. This study enrolled 21 infants (42 eyes) in the microphthalmos group and 29 infants (58 eyes) in the comparison group. More glaucoma-related adverse events were observed in the microphthalmos group (7 eyes, 16.7%) than in the comparison group (0 eyes, 0%) (p < 0.001). At each subsequent follow-up, the comparison group had a greater AL than the microphthalmos group (all p < 0.001), and AL growth was significantly higher in the comparison group than in the microphthalmos group (all p = 0.035). Visual acuity improvement in the microphthalmos group was similar to that of the comparison group. Early surgical intervention improves visual function in infants with congenital cataracts and microphthalmos although with a higher incidence of glaucoma-related adverse events. After cataract removal, the AL growth of microphthalmic eyes is slower than that of normally developed eyes.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy.

Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy and have also been reported in families with only a cataract phenotype. Dilated cardiomyopathy (DCM) is a disorder with a highly heterogeneous genetic etiology involving more than 60 causative genes, hindering genetic diagnosis. In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in NM_001289808.2:c.527A>G of CRYAB in one patient. The mutant alpha-B crystallin protein is predicted to have an extended strand with addition of 19 amino acid residues, p.(Ter176TrpextTer19), which may contribute to aggregation and increased hydrophobicity of alpha-B crystallin. The proband, diagnosed with DCM at age 32, had a history of bilateral congenital cataracts but had no evidence of myopathy or associated symptoms. He also has a 10-year-old child diagnosed with bilateral congenital cataracts with the same CRYAB variant. This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies.

Phenotypic comparison of a novel variant (p.P164R) and A founder mutation (c.748+1G&gt;A) in Warburg Micro syndrome

Warburg Micro syndrome is a rare autosomal recessive disease due to pathogenic variants found most commonly in the RAB3GAP1 gene. It is commonly seen in consanguineous marriages and is characterized by optic, neurologic, endocrinologic and some non-typical findings (cardiomyopathy, peripheral neuropathy). Here, we report two male patients from healthy consanguineous and non- consanguineous carrier parents, with homozygous variants of the RAB3GAP1 gene, presenting with bilateral congenital cataracts, hypogonadism, hypotonia and developmental delay. The first case had a novel variant and had colpocephaly as shown in his MRI brain, which has not been previously reported in the medical literature. The second case was thought to have a founder mutation for Turkey. In conclusion, there was no phenotypical difference between the novel and founder mutations. In Turkish patients suspected to have Warburg Micro syndrome, we recommend molecular testing for the detection of a founder mutation.

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

Hereditary hyperferritinemia cataract syndrome with iron deficiency : a case report

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. HHCS is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. In this case report, we aimed to present a young female patient with a history of cataracts in herself and her family members. Our patient had the dilemma of iron deficiency anemia and hyperferritinemia. As in our patient, patients with HHCS apply to many outpatient clinics and have difficulty in diagnosis. For this reason, we prepared our case to raise awareness.

From Bright to Brightness: Mastering the Management of Bilateral Congenital Cataracts

Congenital cataract is the leading cause of vision loss in newborns and children, and it is caused by an opacity of the eye's lens that occurs at birth or within the first few months of life. Congenital cataracts may develop as unilateral or bilateral. Around 50% of cases of it are considered as idiopathic. A 4-month-old boy was brought by his parents to the Department of Pediatric Ophthalmology and Strabismus in RSUD dr. Zainoel Abidin Banda Aceh with a chief complaint of a white spot on the patient’s right eye. The spot had appeared since birth and became more visible when he was 2 months old. The patient's overall condition was good. Both eyes' visual acuity was blink reflex. The ocular pressure in both eyes was normal. An ophthalmologic examination revealed a fully clouded right eye lens and aphakia in the left eye. The patient had undergone cataract surgery on his left eye on September 6th, 2023. He was diagnosed with Congenital Cataract Oculus Dexter (OD) and Aphakia Oculus Sinister (OS) before surgery. The patient underwent right eye cataract surgery with aspiration irrigation (AI), Primary Posterior Capsulotomy (PPC), and Anterior Vitrectomy (AV) without Intraocular Lens (IOL) implantation within the next two weeks. Following the surgery, the patient's visual function improved to fix and follow the object, the pupils looked round in both eyes, aphakia, and no membrane development. The patient was prescribed glasses for optical rehabilitation.

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

A X-linked nonsense APOO/MIC26 variant causes a lethal mitochondrial disease with progeria-like phenotypes.

APOO/MIC26 is a subunit of the MICOS complex required for mitochondrial cristae morphology and function. Here, we report a novel variant of the APOO/MIC26 gene that causes a severe mitochondrial disease with overall progeria-like phenotypes in two patients. Both patients developed partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. The patients died at an early age of 12 or 18 months. Exome sequencing revealed a mutation (NM_024122.5): c.532G>T (p.E178*) in the APOO/MIC26 gene that causes a nonsense mutation leading to the loss of 20 C-terminal amino acids. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells. We conclude that the novel mutation found in the APOO/MIC26 gene is a loss-of-function mutation impairing mitochondrial morphology and cristae morphogenesis.

Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing.

The present study aimed to identify the molecular etiology of non-syndromic congenital cataract (CC) using whole-exome sequencing (WES) analysis. In the present study, ophthalmologic results and pedigree analysis of the families of 12 patients with non-syndromic CC were evaluated. WES analysis was conducted after DNA was isolated from peripheral blood samples obtained from the patients. Twelve non-syndromic probands (10 males and 2 females) with bilateral CC were included in the study. Patient age ranged between 1 and 11months. WES analysis showed pathogenic/likely pathogenic variant in 7 (58%) of the 12 families and variant of unknown significance (VUS) in 5 (42%) of them. All the 13 different variants detected in 9 different CC-related genes were co-segregated with the disease. Autosomal dominant inheritance was found in 7 (58%) of the families and autosomal recessive inheritance was found in 5 (42%) of them. To the best of our knowledge, the present research is one of the limited numbers of studies in the Turkish population in which genetically heterogeneous non-syndromic CC was investigated using WES analysis. Novel variants that we identified in DNMBP, LSS, and WFS1 genes, which are rarely associated with the CC phenotype, have contributed to the mutation spectrum of this disease. Identifying the relevant molecular genetic etiology allows accurate genetic counseling to be provided to the families.

Infective Etiologies in Patients with Bilateral Congenital Cataract

Objective: To determine the frequency of positive Toxoplasma, Rubella, Cytomegalovirus, Herpes Simplex virus and Syphilis serology in patients with bilateral congenital cataract and their correlation with different type of cataracts and age groups.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Department of Pediatric Ophthalmology and Strabismus, Armed Forces Institute of Ophthalmology, Rawalpindi Pakistan, from May to Dec 2022.&#x0D; Methodology: Data was collected by a single investigator on Microsoft Excel sheet including patient’s age, gender, mode of delivery, consanguinity of parents, and type of congenital cataract, results of TORCH Screening and Presence or absence of amblyopia. TORCHS screening comprised of serum IgM and IgG levels for Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Simplex virus and Syphilis. &#x0D; Results: A total of 134 patients reported to our institute with bilateral congenital cataract during the study period. Out of them 56 patients had positive results of TORCH screening (41.7%) Out of total 56 patients with bilateral congenital cataract testing positive for TORCH, 30(53.6%) were male while 26(46.4%) were female. Age range was from 1-17 months (9.2±4.2 months).Lamellar cataract was the most common cataract type in our study sample 16(28.6%).&#x0D; Conclusion: In patients with bilateral congenital cataract positive TORCHS serology was most frequent. Serum Rubella IgM followed by Rubella IgG was positive in most cases. Most common age of presentation in our study was from 4-7 months. Furthermore, lamellar cataract followed by nuclear cataract was the commonest cataract type.

Clinical observation of spontaneous brain activity in children with congenital cortical cataract amblyopia

Objective: To investigate the characteristics of spontaneous brain activity in children with congenital cortical cataract amblyopia. Methods: A cross-sectional study was conducted. Twenty cases of unilateral congenital cortical cataract amblyopia (unilateral amblyopia group) and 14 cases of bilateral congenital cortical cataract amblyopia (bilateral amblyopia group) were enrolled from January 2022 to December 2022 at the First Affiliated Hospital of Zhengzhou University. Seventeen age and gender matched children with normal visual acuity were recruited as the healthy control group. Resting-state functional MRI (fMRI) was performed on all participants, and the amplitude of low-frequency fluctuations (ALFF) technique was used to analyze their spontaneous brain activities. The original ALFF value of each voxel was divided by the average ALFF value of the whole brain to obtain the standardized ALFF value (referred to as ALFF value), which reflected the intensity of spontaneous brain activity in different brain regions. General demographic data were compared using one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Comparison of ALFF values was conducted using one-way analysis of variance. Results: There were no significant differences in age, gender, distribution of amblyopic eye or non-dominant eye, and degree of refractive error among the three groups (all P>0.05). Compared to the healthy control group, the unilateral amblyopia group showed higher ALFF values in the right posterior lobe of the cerebellum (67 voxels, t=3.48) and left posterior lobe of the cerebellum (71 voxels, t=4.09), and lower ALFF values in the right postcentral gyrus (91 voxels, t=-3.91), right inferior parietal lobule (73 voxels, t=-4.88), right inferior frontal gyrus (78 voxels, t=-4.09), left inferior parietal lobule (556 voxels, t=-4.82), and left inferior frontal gyrus (122 voxels, t=-4.27) (all P<0.01). The bilateral amblyopia group showed higher ALFF values in the right insula (60 voxels, t=3.54), right Rolandic operculum (69 voxels, t=3.73), right posterior lobe of the cerebellum (54 voxels, t=3.43), and left posterior lobe of the cerebellum (143 voxels, t=3.69), and lower ALFF values in the left inferior frontal gyrus (99 voxels, t=-4.39), left postcentral gyrus (231 voxels, t=-4.28), and right inferior parietal lobule (54 voxels, t=-3.77) (all P<0.01). Compared to the unilateral amblyopia group, the bilateral amblyopia group showed higher ALFF values in the left middle frontal gyrus (52 voxels, t=3.15, P=0.029), left posterior lobe of the cerebellum (77 voxels, t=3.39, P=0.001), and right Rolandic operculum (53 voxels, t=3.59, P=0.007). Conclusion: Children with congenital cortical cataract amblyopia exhibit altered spontaneous brain activity in multiple brain regions, and there are differences in spontaneous brain activity changes between unilateral and bilateral amblyopia.

A Baby Girl Born with Bilateral Congenital Cataract to A Mother with Unilateral Congenital Cataract Treated in Childhood

We hereby disseminate a case of a baby girl, who at ten months of age received MMR vaccine but was discovered to later have unilateral congenital cataract at eight years of age. At 25 years, she was married giving birth to a baby boy who had normal vision. Unfortunately, the second baby girl was detected to have bilateral cataract for which the baby at four months of age underwent lens aspiration and anterior vitrectomy of both eyes at a gap of one week. A month later a glass with bilateral +21 Diopters were prescribed. She is planned for intraocular lens implant at around four years of age. She is on currently on visual rehabilitation and treatment for amblyopia Learning lesson from this case being the fact that congenital cataract may run in family and may impart vision deprivation in the offspring; therefore, the importance of preconception counseling is important.

Autosomal recessive congenital cataract is associated with a novel 4-bp splicing deletion mutation in a novel C10orf71 human gene

Congenital cataract is one of the most genetically heterogeneous ocular conditions with different genes involved in its etiology. Here, we describe the analysis of a new candidate gene of a congenital bilateral cataract associated with polymalformative syndrome, moderate global developmental delay, microcephaly, axial hypotonia, intrauterine growth restriction and facial dysmorphism for two affected siblings. Molecular analysis included exome sequencing and genome wide homozygosity mapping revealed a region of homozygosity shared by the two affected siblings at 10q11.23. The new C10orf71 gene was included in this interval and direct sequencing of this gene revealed an already described homozygous c. 2123T > G mutation (p. L708R) for the two affected subjects. Interestingly, we revealed in contrast a 4-bp deletion on the 3'-splicing acceptor site of intron 3-exon 4, namely defined as IVS3-5delGCAA. The C10Orf71 gene expression analysis using RT-PCR showed an expression pattern in different fetal organs and tissues as well as in leukocytes and confirmed that the IVS3-5delGCAA deletion of the C10orf71 gene is a splicing mutation responsible for the shortening of the C10orf71 protein in the two related patients. The C10orf71 gene has not been described to date as associated to the autosomal recessive phenotype.