Congenital Ocular Abnormalities Research Articles

Care of children with congenital rubella syndrome (CRS) in Indonesia.

Congenital rubella syndrome (CRS) is associated with severe birth defects, that lead to disability in later life. Hence, early detection and intervention are needed to prevent permanent disability and mortality in children with CRS. We evaluated the time to diagnosis or correction intervention related to survival rate using survival analysis. A retrospective cohort study was conducted to evaluate the follow-up of CRS-confirmed cases from 2011-2018 at a national referral hospital in Jakarta, Indonesia. Parents of eligible children who registered in the national CRS registry as laboratory-confirmed CRS cases were contacted through phone calls or home visits and interviewed about the current situation of their child's health. We also obtained clinical data from the medical records. Fifty children, age 4 to 14 years, identified with laboratory-confirmed CRS were included in this study. Half (54%) of these children were female. All were born from mothers with no previous rubella vaccination history. Ophthalmic abnormalities such as congenital cataracts (88%) were the most common birth defect. Multiple congenital abnormalities including congenital heart disease, ocular abnormalities, and auditory defects were identified in 52% of the children. Based on Kaplan-Meier analysis, 50% of children were diagnosed at four months. Ophthalmic corrections such as cataract surgery were performed earlier than heart or auditory correction, with 50% of children undergoing eye correction one month after the diagnosis. There is a vital need to implement CRS surveillance in Indonesia to know the burden of CRS and reinforce the preventive actions, including vaccination against rubella.

Humoral Immunodeficiency in two patients with Alagille Syndrome

IntroductionAlagille syndrome is an autosomal dominant entity caused by mutations that affect the Notch-Jagged1 signaling pathway. It is characterized by cholestasis due to poor bile ducts, congenital heart disease, skeletal abnormalities, ocular abnormalities and characteristic facial phenotype. We present 2 patients diagnosed with Alagille syndrome who presented associated immunodeficiency and required gammaglobulin treatment. Case 117-year-old male patient, who was liver transplanted at 19 months of the age. At 6 years of life, he underwent splenectomy secondary to immune thrombocytopenic purpura. He presented recurrent otitis and severe, large styes on the eyelids. He developed a first episode of pneumonia at 6. He received double kidney transplantation due to end-stage chronic kidney disease at 9. At the age of 10 laboratory results showed: IgG: 374 mg/dl IgM: 43 mg/dl IgE: 3 UI and IgA: 202 mg/dl. Functional responses against protein and polysaccharide antigens were absent. Lymphocytes populations were normal. He started treatment with intravenous gammaglobulin at 10 years of age. Case 27-year-old male patient with liver involvement, portal hypertension and portal vein cavernomas that evolved to hypersplenism with esophageal and gastric varices and gastrointestinal bleeding that required a splenorenal anastomosis and a stent. He presented a ventricular communication with a severe hypoplasia of the left pulmonary branch. He presented multiple infectious events including pneumococcal pneumonia. Laboratory showed pancytopenia secondary to hypersplenism, CD4 T lymphopenia (<250/uL)) with preserved CD4/CD8 ratio with normal lymphocyte proliferations, IgG: 450 mg/dl, IgM: 21 mg/dl, IgA: 136 mg/dl. A humoral response decay against global Pneumococcal capsular polysaccharide was observed. Variable response to protein antigen was present. Daily chemoprophylaxis with trimethoprim sulfamethoxazole was indicated but he repeated infectious episodes, then subcutaneous gammaglobulin was started. ConclusionsWe present2 patients diagnosed with Alagille syndromewith associated immunodeficiency. The NOTCH/Jagged 1 signaling pathway is of profound relevance to the process of somitogenesis and in the development of CD4 and CD8 lymphocytes. The immune compromise of patients with Alagille syndrome should be emphasized and eventually gammaglobulin treatment should be indicated.

Molecular characterization using exome sequencing of two probands with the undiagnosed developmental delay from Central Brazil

Noonan syndrome (NS) is a heterogeneous autosomal dominant disorder caused by germline mutations in genes belonging RAS-MAPK pathway. Herein, we described two patients with developmental delay and syndromic features from Central Brazil diagnosed with NS using an exome sequencing target gene panel. Germline mutation in genes that participates in the RAS-MAPK signaling pathway are associated with developmental disorders that share particular clinical features such as craniofacial dysmorphisms, congenital heart defects, musculoskeletal and ocular abnormalities, and neurocognitive impairment. The exome sequencing through the intellectual disability gene panel was an effective approach to identify de novo pathogenic mutations in SOS1 and PTPN11 genes that are responsible for Noonan syndrome and was an efficient method to direct the adequate clinical management and better follow-up of the probands and their families.

Association entre la consanguinité et les anomalies congénitales oculaires au Togo

To investigate the possibility of an association between parental consanguinity and the occurrence of congenital ocular abnormalities. A retrospective cross-sectional study was carried out over 3 years, from January 2016 to December 2018, in the pediatric ophthalmology unit of the University Hospital Campus of Lomé (Togo). It included children with congenital ocular abnormalities. Age, gender, geographic origin (city or urban area, village or rural area), degree of consanguinity of parents and types of congenital ocular abnomalities were the variables of study. Odds Ratio (OR) and logistic regression were used to investigate the correlation between parental consanguinity and the occurrence of congenital ocular abnormalities. A P-value of<0.05 was considered statistically significant. Among the 103 patients with congenital ocular abnormalities, there were 60 (58.2%) males and 43 (41.8%) females. The mean age of the patients was 16 months, range 1 month-5 years. Patients born to consanguineous parents were 26.2% (27) of the total population. Of these 27 patients, 25 (92.6%) were born to second-cousin marriages and 24 (88.89%) came from a rural area. Parental consanguinity was correlated with developmental abnormalities of the globe (OR=37.50; 95% CI: [4.46-314.80]; r=3.62; P=0.00), sclerocornea (OR=13.04; 95% CI: [1.39-122.54]; r=2.57; P=0.02) and corneal dystrophy (OR=9.37; 95% CI: [0.93-94.36]; r=2.24; P=0.02). Our study suggests the existence of a correlation between parental consanguinity and the occurrence of congenital ocular abnormalities.

Pregnancy with seropositive toxoplasmosis: a case report

Introduction: Toxoplasmosis is present in every country and seropositive rates vary between regions from less than 10% to more than 90%. Toxoplasmosis in pregnancy can result in severe sequelae to the fetus. Primary infection in pregnancy may cause spontaneous abortion or fetal death in utero. Congenital ocular and neurological abnormalities may also occur. We present a case involving toxoplasmosis infection in early pregnancy and an overview of the management and the clinical outcomes for both mother and fetus.Case report: A 26-year-old pregnant woman (G1P0A0) showed a high concentration of IgG anti-toxoplasmosis in early pregnancy with a concentration of 1200. Throughout the pregnancy, an increase in the concentration of IgG anti-toxoplasma was found. At 14 weeks gestation, concentration increased four-fold to 9068. During the ultrasound observation no hydrocephalus, ocular, and neurological abnormalities were found. Amniocentesis was performed for PCR examination and the result turned out negative. The patient was given spiramycin 1 gram daily for the remaining of her pregnancy. At 40 weeks gestation, the patient gave birth vaginally to a healthy term 3700 grams baby boy. There were no signs of major anomalies found in the baby.Conclusions: Diagnosis and screening of toxoplasmosis require proper understanding of serological examination, as well as the specificity and sensitivity of the diagnostic tools. Ultrasound monitoring for the detection of congenital toxoplasmosis can also help with diagnosis.

Mutations in LAMB2 are associated with albuminuria and optic nerve hypoplasia with hypopituitarism

CONTEXT Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome). CASE DESCRIPTION This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2-/- mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland. CONCLUSION We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2.

Evaluation of the short- and long-term complications and outcomes of phacoemulsification surgery in alpacas.

To describe the complications and determine the visual outcomes associated with phacoemulsification surgery in alpacas. Five alpacas (nine operated eyes). Medical records of alpacas with a clinical diagnosis of cataracts that received elective phacoemulsification surgery at Cornell University over a 15year period were reviewed. The mean (± standard deviation) age of the five operated alpacas was 104days (±64days). The cataracts were suspected to be congenital in all alpacas. Concurrent congenital ocular abnormalities were common in the operated eyes and included microphakia, persistent patent hyaloid arteries, and persistent patent tunica vasculosa lentis. No significant intraoperative complications were identified in any cases. In the immediate postoperative period, uveitis was mild-to-moderate in most operated eyes, ocular hypertension was not detected, and clinically significant corneal edema did not occur in any eyes. The mean (± standard deviation) duration of clinical follow-up after surgery was 32months (±25months). A peri-incisional corneal stromal ulcer associated with fibrinous uveitis was identified in a single eye during recheck examination 4weeks postoperative that resolved with medical therapy. Long-term complications included unilateral glaucoma in two alpacas that resulted in vision loss. On the final recheck ophthalmic examination, 78% (7 of 9) of operated eyes were visual and all operated alpacas had vision in at least one operated eye. In this series, the visual outcomes associated with elective phacoemulsification surgery in alpacas were good. Glaucoma was the most common vision-threatening long-term postoperative complication.

In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy

BackgroundZika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. MethodsPregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. FindingsZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. InterpretationOur results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. FundThis work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University.

Multiple congenital ocular abnormalities including microphthalmia, microphakia and aphakia in a Simmental cross bull

A 20-month-old Simmental cross bull presented to the Scottish Centre for Production Animal Health and Food Safety, University of Glasgow School of Veterinary Medicine, in April 2015 with multiple congenital...

Middle Ear Pressure Changes Over Time in Children with Down Syndrome

Down syndrome is one of the most common genetic conditions affecting approximately 1 in every 1000 live births. There are a multitude of potential clinical manifestations associated with this condition including dysmorphic features, organic disorders such as congenital cardiac defects, gastrointestinal defects, ocular abnormalities, celiac disease and endocrine disorders along with haemato-oncological, immunological and disorders affecting the ears, nose and throat.

Ocular manifestations of PACS1 mutation

Heterozygous mutation in the PACS1 (phosphofurin acidic cluster sorting proteins 1) gene is a known cause of developmental delay, multiple congenital anomalies, dysmorphism, and ocular abnormalities. We present the case of an affected 10-year-old girl, conceived by assisted reproductive technology, who has ocular coloboma and findings characteristic of PACS1 mutation.

Congenital Ocular Abnormalities in Free-Ranging White-Tailed Deer.

Congenital ocular abnormalities in cervids have been previously reported as individual cases from various regions of the United States and include microphthalmia, anophthalmia, congenital cataracts, dermoids, and colobomata. A common underlying cause for these abnormalities, such as nutritional deficiencies, environmental toxin exposures, or genetic mutations, has not been established. This retrospective study summarized and compared cases of suspected congenital ocular abnormalities in free-ranging white-tailed deer ( Odocoileus virginianus) submitted to the Southeastern Cooperative Wildlife Disease Study (SCWDS) in Athens, Georgia, to the preexisting literature. Of 3645 accessions of white-tailed deer submitted to SCWDS, 15 qualifying case records were found. An additional 15 cases were reported previously in the literature. Conditions described in SCWDS cases included microphthalmia (8/15), congenital cataracts (3/15), anophthalmia (2/15), colobomata (1/15), anterior segment dysgenesis (1/15), ectopic lacrimal gland tissue (1/15), and congenital blindness with corneal opacity (1/15). Most (11/15; 73%) of the SCWDS cases were male fawns with an average age of 4 months at presentation, consistent with previously described cases. Most animals had bilateral abnormalities with few extraocular congenital abnormalities, also consistent with existing reports. Cases were variably tested for various infectious agents at the time of submission; 2 cases were seropositive for bluetongue virus. Spatiotemporal clustering of cases was not evident. This study provided a concise and systematic summary of known existing cases of congenital ocular defects in fawns but did not identify a cause.

Skeletal impairment in Pierson syndrome: Is there a role for lamininβ2 in bone physiology?

IntroductionPierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. MethodsWe report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty.This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of “normal low” quantity and quality; major radial and cubital deformations were observed. Stainings of laminin β2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin β2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. ConclusionThis is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3β1, receptor for laminin β2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin β2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin β2 in bone physiology.

Case Report of Cardiac Arrest After Succinylcholine in a Child With Muscle-Eye-Brain Disease.

Muscle-eye-brain disease is a rare autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and brain malformation. We report an intraoperative hyperkalemic cardiac arrest following the administration of succinylcholine in a child with muscle-eye-brain disease. The disease was diagnosed only after this event. Our experience suggests that preoperative determinations of serum concentrations of lactate and creatine kinase may be useful if clinical signs consistent with myopathy are present.

Clinical Features and Outcome of Paediatric Retinal Detachment

Purpose: The aim of this study was to assess the clinical features and outcome of paediatric retinal detachment (RD). Methods: Ninety-five eyes of 87 children under 18 years of age with RD were assessed. The risk factors, morphology of RD, therapeutic approach and functional results were evaluated. Results: Sixty-seven boys and 20 girls with a mean age of 10.4 years (standard deviation 5.5) presented with RD. The following risk factors were identified: myopia (23%), congenital or developmental ocular abnormalities (37%), history of ocular trauma (40%) and previous ocular surgery (27%). Seventy-seven (81%) eyes underwent surgery. The primary reattachment rate was 44%. In 18%, reattachment was achieved after several surgeries. The overall recurrence rate after surgical reattachment was 39%. Conclusions: Paediatric RD is a sight-threatening condition. Often, aggravating factors, such as delayed diagnosis, hereditary ocular abnormalities or strong vitreous adherence, are present. Hopefully, modern surgical techniques may contribute to a better outcome of RD in the future.

Cutting Your Losses: Addressing Nutritional Deficiencies in Pregnancy after Bariatric Surgery

Pregnancy after bariatric surgery in morbid obesity can reduce the risk for gestational diabetes, preeclampsia, and large for gestational age infants. However there is an increased risk for small for gestational age infants, shorter gestation, and a trend to increase in stillbirth and neonatal death. We describe a patient who had an extreme form of bariatric surgery, pancreatico-biliary diversion with duodenal switch (BPD-DS), resulting in numerous vitamin and mineral deficiencies and perinatal demise. A female patient underwent BPD-DS for morbid obesity at age 21 years, resulting in a 215-pound weight loss down to 155 pounds at height of 68 inches. Post-surgery, two pregnancies were complicated by early spontaneous abortion. In a third pregnancy, vitamin A deficiency and night blindness was detected. That pregnancy resulted in delivery of a fetus with numerous congenital anomalies, and neonatal death due to respiratory failure related to a congenital diaphragmatic hernia. The neonate had low risk DNA. At age 28 years, she presented with a 4th pregnancy at 8 weeks gestation. Multiple nutritional deficiencies were detected, including deficiencies in vitamins A, D, E, and K, iron and zinc. These were aggressively replenished. Pancreatic enzyme supplementation was added. Total parenteral nutrition was initiated 3 weeks before delivery for severe intrauterine growth retardation. At 37 weeks, a planned Cesarean section was performed with delivery of a healthy neonate. The infant is doing well 6 months post-partum. Nutritional deficiencies are well-recognized complications of bariatric surgery. BPD-DS is an extreme form of surgery. In addition to a restrictive surgical procedure, there is delayed mixing of bile and pancreatic enzymes until the final 50-100 cm of the ileum. This results in significant fat malabsorption and consequently, a greater risk of fat-soluble vitamin deficiency. Hypovitaminosis A, as in our patient, has been associated with congenital ocular abnormalities, as well as congenital diaphragmatic hernia, a lifethreatening cause of newborn respiratory failure. Our patient's case is instructive as it highlights possible consequences of not aggressively repleting nutritional deficiencies (3rd pregnancy), and contrasts the successful outcome of aggressive nutritional repletion (4th pregnancy). Monitoring and treating nutritional deficiencies during pregnancy after bariatric surgery is important, particularly for the more extreme form, BPD-DS.

Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients

To determine the full spectrum of ocular manifestations in patients with Noonan syndrome (NS). Prospective cross-sectional clinical and genetic study in a tertiary referral center. Twenty-five patients with NS (mean age, 14 years; range, 8 months-25 years) clinically diagnosed by validated criteria. All patients were examined by the same team following a detailed study protocol. Genetic analyses were performed in 23 patients. Ocular abnormalities of vision and refraction, external ocular features, ocular position and motility, anterior segment, posterior segment, and intraocular pressure. Ocular features of vision and refraction were amblyopia (32%), myopia (40%), and astigmatism (52%). External ocular features were epicanthic folds (84%), hypertelorism (68%), ptosis (56%), high upper eyelid crease (64%), lower eyelid retraction (60%), abnormal upward slanting palpebral fissures (36%), downward slanting palpebral fissures (32%), and lagophthalmos (28%). Orthoptic abnormalities included strabismus (40%), abnormal stereopsis (44%), and limited ocular motility (40%). Anterior segment abnormalities included prominent corneal nerves (72%) and posterior embryotoxon (32%). Additional ocular features were found, including nonglaucomatous optic disc excavation (20%), relatively low (<10 mmHg) intraocular pressure (22%), and optic nerve hypoplasia (4%). Mutations were established in 22 patients: 19 PTPN11 mutations (76%), 1 SOS1 mutation, 1 BRAF mutation, and 1 KRAS mutation. The patient with the highest number of prominent corneal nerves had an SOS1 mutation. The patient with the lowest visual acuity, associated with bilateral optic nerve hypoplasia, had a BRAF mutation. Patients with severe ptosis and nearly total absence of levator muscle function had PTPN11 mutations. All patients showed at least 3 ocular features (range, 3-13; mean, 7), including at least 1 external ocular feature in more than 95% of the patients. Noonan syndrome is a clinical diagnosis with multiple genetic bases associated with an extensive variety of congenital ocular abnormalities. Ocular features of NS are characterized by 1 or more developmental anomalies of the eyelids (involving the position, opening, and closure) associated with various other ocular abnormalities in childhood, including amblyopia, myopia, astigmatism, strabismus, limited ocular motility, prominent corneal nerves, and posterior embryotoxon.

Splenic Hamartomas in Alagille Syndrome: Case Report and Literature Review

Alagille syndrome is a rare autosomal dominant disorder with characteristic findings of paucity of intrahepatic bile ducts, congenital heart disease, and vertebral, ocular, and renal abnormalities. We present a unique autopsy case of an 18-year-old female with Alagille syndrome and splenic hamartomas. Autopsy findings included growth restriction, Tetralogy of Fallot, paucity of intrahepatic bile ducts, end-stage renal disease with mesangiolipidosis, and splenomegaly with two well-circumscribed, splenic tumors. Histologic findings of the splenic tumors revealed disorganized vascular channels lined by cells without cytologic atypia. Immunohistochemical analysis demonstrated CD8+CD31+ endothelial cells, consistent with splenic hamartomas. In summary, Alagille syndrome is a rare genetic disorder characterized by JAG1 mutations and disrupted Notch signaling. Review of the literature highlights the importance of Notch signaling in vascular development and disorders. However, to our knowledge this is the first description of splenic hamartomas in Alagille syndrome.

Congenital Trochlear–Oculomotor Synkinesis

Synkinesis of the extraocular muscles forms a subset of congenital ocular motility abnormalities termed congenital cranial dysinnervation disorders. Synkinesis most frequently involves the abducens or oculomotor nerves and rarely the trochlear nerve. Only 3 such patients have been described in the literature. We report an isolated case of trochlear-oculomotor synkinesis in a healthy 6-year-old boy and discuss the proposed pathophysiology of this disorder.

Congenital Lateral Nasal Proboscis with Orbital Mass

ABSTRACT Proboscis lateralis is a rare craniofacial malformation frequently associated with congenital ocular abnormalities. These abnormalities included anophthalmia, microphthalmia, microcornea, lenticular opacities, cyclopean eye, and colobomas of the choroid, retina, iris and eyelids. We report a case of unilateral proboscis lateralis in a newborn infant with an associated solid orbital mass. How to cite this article Kaur B, Bansal S, Saikia UN, Gupta P. Congenital Lateral Nasal Proboscis with Orbital Mass. Clin Rhinol An Int J 2014;7(3):139-141.