A full-term female infant was admitted at 5 hours after birth due to heart malformations found during the fetal period and cyanosis once after birth. Mmultiple malformations of eyes, face, limbs, and heart were noted. The whole-exome sequencing revealed a pathogenic heterozygous mutation, c.2428C>T(p.Arg810^*), in the BCOR gene. The infant was then diagnosed with oculo-facio-cardio-dental syndrome. He received assisted ventilation to improve oxygenation and nutritional support during hospitalization. Right ventricular double outlet correction was performed 1 month after birth. Ocular lesions were followed up and scheduled for elective surgery. The possibility of oculo-facio-cardio-dental syndrome should be considered for neonates with multiple malformations of eyes, face, and heart, and genetic testing should be performed as early as possible to confirm the diagnosis; meanwhile, active ophthalmic and cardiovascular symptomatic treatment should be given to improve the prognosis.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Abnormalities, Multiple/therapy* ; Cataract/genetics* ; Cyanosis ; Proto-Oncogene Proteins ; Repressor Proteins/genetics* ; Heart Defects, Congenital/genetics*

Background: Infants with congenital rubella syndrome (CRS) often require multiple diagnostic procedures and interventions that include cataract surgery and procedures for congenital heart abnormalities. CRS is a vaccine preventable disease. Objective: This study aimed to determine the costs incurred by the parents, Philippine Health Insurance Corporation (PHIC), hospital's medical social service (MSS), and non-governmental organization (NGO) in the management of CRS. Methods: This is a costing study of five children diagnosed with probable CRS who were managed in a tertiary government hospital in Northern Luzon, Philippines. The parents or guardians of the patients were interviewed on the cost incurred particularly on non-medical related expenses during their outpatient department consultations and admissions. Hospital bills from our institutions and those from the previous institutions, if available, were retrieved. Expenses incurred from procedures or medical supplies relating to known complications of CRS were included in the computation. Results: All five patients diagnosed with CRS had cardiac, ear, and eye manifestations. Two patients had postnatal complications. The average cost spent by the five patients' early years of life (mean age of patients was 16 ± 14 months) was ₱409,740.84. A quarter of the cost was out-of-pocket expenses while a third was covered by the hospital's MSS where the patients were seen. Another third was shouldered by an NGO. Most expenses were from the treatment of cardiac complications at 42% of the cost and had the highest average cost at ₱116,586.59. Case 1 had the highest financial cost at ₱833,514.24 mainly from the cardiac complications of CRS. Conclusion The cost of CRS in the early years of life is high. This is a significant financial burden to parents, PHIC, hospital's MSS, and NGO.
Congenital rubella syndrome ; cataract

OBJECTIVE: To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS). METHODS: Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel. CONCLUSION The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.
Cataract ; China ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics* ; Humans ; Hypogonadism/congenital* ; Intellectual Disability/genetics* ; Mutation ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for child with congenital cataract. METHODS: The child was subjected to next-generation sequencing. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The proband was found to harbor novel heterozygous variants of c.855del and c.872dup of the GJA8 gene, which were inherited from his father and mother, respectively. Neither of these two variants has been reported. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.855del and c.872dup variants were classified as likely pathogenic (PVS1_S+PM2+PP4) and pathogenic (PVS1_S+PM2+PM3+PP4), respectively. CONCLUSION The c.855del and c.872dup variants of the GJA8 gene probably underlay the congenital cataract in this patient.
Child ; Humans ; Cataract/congenital* ; Family ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Mutation ; Pedigree

Congenital rubella syndrome (CRS) cases being seen in a tertiary hospital in Baguio rose in 2020 during the COVID-19 pandemic. Its communicability presented logistical challenges to the hospital as additional contact and droplet precautions, including COVID-19 RT-PCR testing, were needed to be observed to prevent rubella transmission. The operations of the institute have also been disrupted and compromised since its space and resources were diverted to the pandemic response. A probable rubella transmission occurred when a patient with CRS was admitted for cataract surgery but was delayed due to the COVID-19 RT-PCR test requirement. Another patient admitted from the Outpatient Department on the same day developed maculopapular rashes for three days during admission but with no febrile episodes and lymphadenopathy. These cases showed how managing CRS cataracts got complicated by the current COVID-19 pandemic which resulted in the review and proposal to revise current hospital policies to minimize the exposure of vulnerable individuals and prevent future transmission.
Rubella Syndrome, Congenital ; Cataract ; COVID-19

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital cataracts. METHODS: Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes. RESULTS: By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing. CONCLUSION The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.
Asian Continental Ancestry Group ; Cataract ; congenital ; genetics ; China ; Heterozygote ; Humans ; Mutation ; Pedigree ; gamma-Crystallins ; genetics

Abnormalities, Multiple ; diagnostic imaging ; genetics ; Cataract ; congenital ; diagnostic imaging ; genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; genetics ; Cornea ; abnormalities ; diagnostic imaging ; Head ; diagnostic imaging ; Humans ; Hypogonadism ; diagnostic imaging ; genetics ; Infant ; Intellectual Disability ; diagnostic imaging ; genetics ; Male ; Microcephaly ; diagnostic imaging ; genetics ; Optic Atrophy ; diagnostic imaging ; genetics ; Phenotype

Adolescent ; Adult ; Cataract ; congenital ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Young Adult

This study was aimed to identify the mutation of the whole coding region of shock transcription factor 4 (HSF4) gene in a Chinese family with autosomal dominant congenital cataract (ADCC). All exons of HSF4 were amplified by PCR. Sequence analysis of PCR products was performed. Restriction fragment length polymorphism (RFLP) analysis was conducted to confirm the pathogenic mutation. The results showed that a C to T substitution occurred at nucleotide 331 in patients of this family, leading to the replacement of the amino acid arginine-111 with cysteine in exon 3. RFLP analysis showed that the amino acid change was co-segregated with all affected individuals. It was concluded that the new mutation of c.331C>T in HSF4 DNA may be responsible for the autosomal dominant congenital cataract in this family.
Amino Acid Sequence ; Animals ; Base Sequence ; Cataract ; congenital ; genetics ; China ; DNA Primers ; DNA-Binding Proteins ; chemistry ; genetics ; Female ; Genes, Dominant ; Heat Shock Transcription Factors ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Sequence Homology, Amino Acid ; Transcription Factors ; chemistry ; genetics

OBJECTIVE: To compare the difference in intraocular pressure (IOP) readings as well as the tolerability between Icare rebound tonometer (Icare RBT) and Goldmann applanation tonometer (GAT), and to evaluate the application of Icare RBT in monitoring the intraocular pressure in children after congenital cataract surgery. METHODS: The IOP was measured with the Icare RBT and GAT respectively in 150 children (262 eyes) after congenital cataract surgery by two experienced ophthalmologists. Correlation and Bland-Altman analysis were used to assess the agreement in IOP readings between the two instruments. The influence of the central corneal thickness (CCT) adjusted for age on IOP readings was analyzed by linear regression analysis. The tolerance of the patients to Icare RBT and GAT measurement were surveyed. RESULTS: The mean age was (44.82 ± 11.56) months in 150 children, including 81 boys and 69 girls. The mean IOP readings by the Icare RBT and GAT were (16.08 ± 5.72) mmHg and (14.17 ± 5.05) mmHg, respectively. The mean difference between the Icare RBT and GAT was (1.91 ± 2.04) mmHg, which was significantly correlated with CCT (r=0.409, P<0.001). The IOP readings by Icare RBT was significantly correlated with that measured by GAT(r= 0.936, P<0.001). The 95% confidence interval of the difference between the two instruments was ?2.10 to 5.91 mmHg. The Icare RBT examination was well tolerated by the children compared to the GAT examination. CONCLUSION The Icare RBT is easy to use and well tolerated by the children after congenital cataract surgery. Compared to GAT, the value measured by the IOPs trends to be overestimated. The difference in readings between the 2 tonometers will magnify with the increase in CCT.
Cataract ; congenital ; Cataract Extraction ; Child, Preschool ; Female ; Humans ; Intraocular Pressure ; Male ; Tonometry, Ocular ; instrumentation