Facial dysmorphism in congenital rubella syndrome.

PURPOSE: To investigate the dysmorphic facial features in congenital rubella syndrome (CRS) and describe their associations with ocular and systemic features. METHODS: The medical records of children diagnosed with CRS between 2016 and 2021 were retrospectively reviewed for ocular and systemic features. CRS was diagnosed either on the basis of positive serology for rubella antibodies or with the classic triad of congenital cataract, sensorineural hearing loss, and congenital heart defect. Children with photographic documentation of the face were analyzed independently by three experienced investigators for facial dysmorphic features (triangular face, microcephaly, broad forehead, low anterior hairline, whorl on the anterior hairline, prominent nose, micrognathia). The dysmorphic feature was recorded as present only when at least two of the three examiners confirmed its existence. RESULTS: CRS was diagnosed in 237 children: mean age at presentation, 5.45 ± 4.5 years; 126 males (53%); bilateral cataract, 176 (75%). Positive serology for rubella antibodies was noted in 153 children (65%). Photographic record of facial features was documented in 127 (54%). The most common dysmorphic facial feature was wide forehead (82 [65%]), followed by low anterior hairline with whorl (41 [32%]). However, microcornea (P = 0.9801), cataract (P = 0.8342), pupillary sphincter atrophy (P = 0.7421), and salt and pepper retinopathy (P = 0.8803) were not significantly associated with the presence of facial dysmorphism. Congenital heart disease was significantly associated with facial dysmorphism (P = 0.0308). Sensorineural hearing loss was not associated with the presence of facial dysmorphism (P = 0.8463). CONCLUSIONS: Facial dysmorphism is common in children with CRS, but it was not predictive of the presence of ocular manifestations of CRS in this cohort.

Phylogenetic analysis of congenital rubella virus from Indonesia: a case report.

BACKGROUND: Rubella is a common inherited infection resulting in congenital cataracts and a significant cause of permanent vision loss in developing countries. In 2016, Indonesia had the highest number of congenital rubella syndrome (CRS) cases globally. Here, we report the first genotype of the rubella virus extracted from the eye lens from a child with congenital cataracts due to CRS. CASE PRESENTATION: A female neonate was delivered by an elective caesarean delivery with normal birth weight at term from a 24-year-old mother in the rural setting. The baby presented with bilateral congenital cataracts, small-moderate secundum atrial septal defect, severe supravalvular pulmonary stenosis, and profound bilateral hearing loss. She also had microcephaly and splenomegaly. The patient's serology showed persistent positive IgG for rubella virus at the age of four years and four months. Following extraction during cataract surgery, viral detection of the lenses identified the presence of rubella. Phylogenetic analysis confirmed that the virus was grouped into genotype 1E. CONCLUSIONS: Our study reports the first phylogenetic analysis of the rubella virus extracted from the eye lens of a child with CRS in Indonesia. The detection of the rubella virus from eye lenses is remarkably promising. Our findings also emphasize the importance of molecular epidemiology in tracking the origin of rubella infection toward achieving virus eradication.

Epidemiology, etiology and clinical associations of congenital heart disease identified during congenital rubella syndrome surveillance.

BACKGROUND: Congenital heart disease (CHD) is a common congenital malformation. Antenatal rubella infection in the mother and genetic defects are important causes to which CHD are attributed. Exact contribution of antenatal rubella infection or genetic causes to CHD is still unknown. OBJECTIVE: To study the epidemiology, etiology and clinical associations of echocardiographically confirmed congenital heart disease in infants in Western Rajasthan enrolled in the congenital rubella syndrome (CRS) surveillance project. To study the utility of clinical diagnostic criteria in identifying congenital rubella infection. METHOD: This was a prospective observational study, in which 251 patients with echocardiographically confirmed CHD were enrolled. Detailed clinical evaluation was done in all patients. Rubella serology was done in all patients. Genetic and other testing was done as appropriate. RESULT: The hospital-based prevalence of CHD in infants was 1% at our center. Fifty-seven percent of the babies had acyanotic septal heart defects of which ventricular septal defect (VSD) was the most common (35%). Anti-rubella immunoglobulin M (IgM) antibodies were positive in 8.5% of the CHD patients. A clinically identifiable genetic cause was present in 3.6% of the cases. In patients who tested positive for anti-rubella IgM antibodies also, VSD was the most common (33%) CHD followed by Tetralogy of Fallot (13.2%). CONCLUSION: CRS contributes to 8.5% of CHD. CRS is associated with a wide spectrum of CHD. The etiology of a large number of CHD remains elusive. Detailed studies on the cause and mechanism of development of CHD need to be undertaken.

Newborn Glaucoma: A Neglected Manifestation of Congenital Rubella Syndrome.

PURPOSE: To study the frequency of intrauterine rubella infection in a cohort of neonatal-onset glaucoma (NOG) and its effect on the treatment outcomes. DESIGN: Prospective cohort study. PARTICIPANTS: Infants with NOG presenting to the pediatric glaucoma service at a tertiary care center in northern India at Chandigarh between January 1, and September 30, 2018, with a minimum postoperative follow-up of 1 year were included in this study. METHODS: Rubella immunoglobulin-M (IgM) antibodies were tested in all patients. Surgery for intraocular pressure (IOP) control comprised combined trabeculotomy with trabeculectomy or goniotomy. Presenting features and treatment outcomes at 1 year were compared among infants with and without rubella-IgM antibodies. RESULTS: Of 27 eligible infants, 7 (25.9%) were rubella-IgM positive, and all had bilateral glaucoma. One eye in a rubella-positive baby was an unsightly blind eye and required a prosthesis. A total of 13 eyes of 7 patients were compared with 34 eyes of 20 rubella-negative patients. There was no significant difference in mean age and IOP at presentation. Rubella-positive infants had significantly more opaque corneas (P < 0.001), shorter eyes (P < 0.001), and smaller corneal diameters (P = 0.007) at presentation. Two patients in the rubella group had bilateral cataracts, 3 patients had heart disease, and 1 patient had sensorineural deafness. Salt-and-pepper retinopathy was noted in both rubella-positive infants where fundus evaluation was possible. Despite comparable IOP control (P = 0.51), the corneal clarity remained significantly worse in the rubella-positive patients (P = 0.02). CONCLUSIONS: Twenty-five percent of those with newborn glaucoma had underlying intrauterine rubella infection, thus making them susceptible for development of congenital rubella syndrome (CRS). Neonatal-onset glaucoma is an important component of CRS, which may present without buphthalmos and persistent corneal clouding despite good IOP control.

Is 20/20 visual outcome a reality in rubella cataract? - Prognostic factors in children with cataract associated with congenital rubella syndrome.

Purpose: The aim of this study ws to evaluate prognostic factors associated with final visual outcome in patients with congenital cataract associated with congenital rubella syndrome. Methods: A prospective interventional analysis of preoperative systemic and ocular features of 56 eyes of 28 seropositive infants of less than 12 months presenting to us with bilateral cataract was performed. All infants were surgically treated with cataract extraction, posterior capsulorhexis, and anterior vitrectomy followed by visual rehabilitation. Intraocular lens implantation was done in children after 2 years of age. Outcome data were collected till children reached the fifth chronological age. Chi-square test was used as a test of significance for qualitative data. Results: Of the 56 eyes, 44.6% eyes had vision better than 20/60. Important preoperative factors related to poor visual prognosis were morphology of cataract (P = 0.004), microphthalmos (P < 0.001), features suggestive of iris hypoplasia (P < 0.001), optic atrophy (P < 0.001), nystagmus (P = 0.02), and associated neurological anomalies (P = 0.0023). We found no significant statistical association between postoperative visual outcome and isolated rubella retinopathy, cloudy cornea, cardiological, and ontological abnormalities. Conclusion: Cataract associated with rubella is a common cause of congenital cataract in developing countries. Determining prognostic factors helps us in parent counseling and planning treatment protocols. Nevertheless, early detection and treatment with adequate multidisciplinary approach remains priority for improving long-term visual outcomes.

Etiology of Childhood Bilateral Sensorineural Hearing Loss in Shandong Province, China.

Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for those children who were identified as having hearing loss to identify the potential cause. Results The etiology of bilateral SNHL in our sample was genetic in 874 (39.3%), acquired in 650 (29.3%), and unknown in 697 (31.4%) children. Among children with acquired SNHL, the cause was maternal viral infection in 75 (11.5%); perinatal factors in 238 (36.6%); meningitis, measles, and mumps in 146 (22.5%); and ototoxic exposure in 117 (18%) children. Among the children with genetic SNHL, only 44 (4.9%) were identified as having syndromic hearing loss, and the remainder (95.1%) were classified as nonsyndromic hearing loss. Conclusion The findings indicated that nearly 30% of bilateral SNHL in Shandong province could be preventable through immunization, early prenatal diagnosis, proper treatment of infections, and avoidance of prescription of ototoxic drugs. This finding emphasizes the need for programs aimed at improving the health services at primary and secondary levels of health care, which will in turn prevent childhood hearing loss.

Effectiveness of Combined Direct and Indirect Revascularization for Moyamoya Disease with Concurrent Congenital Rubella Syndrome.

BACKGROUND: For several variants of quasi-moyamoya disease, cerebral revascularization treatment is as effective as it is for the more typical cases of moyamoya disease. Here, we examined a case of moyamoya disease with concurrent congenital rubella syndrome (CRS). On the basis of concurrent underlying disease, the patient was considered to have quasi-moyamoya disease and was treated with cerebral revascularization. CASE DESCRIPTION: A 36-year-old female presented with a large cerebral infarction. She was diagnosed with quasi-moyamoya disease on the basis of clinical and imaging features. The ischemic symptoms and cognitive dysfunction improved after combined direct and indirect revascularization. CONCLUSIONS: To our knowledge, this is the first known report of moyamoya disease with concurrent CRS. We treated this patient with revascularization as typical for other quasi-moyamoya conditions including Down syndrome. This case emphasizes the effectiveness of revascularization treatment for moyamoya disease with concurrent CRS for the prevention of ischemic stroke and improvement of cognitive function, despite existing cerebral infarction.

Clinical features and aetiology of cerebral palsy in children from Cross River State, Nigeria.

OBJECTIVE: There are few studies on cerebral palsy (CP) in African children and our study aimed to describe the aetiology, characteristics and severity of CP in children from Nigeria. DESIGN: A population-based study using key informant methodology (KIM) was conducted as part of a clinical research trial. Children aged 4-15 years were clinically assessed for CP. RESULTS: The estimated prevalence of CP using KIM was 2.3/1000 children (95% CI 2.0 to 2.5/1000). 388 children were diagnosed with CP, with Gross Motor Function Classification System level 1 in 70 (18.1%), II in 156 (40.2%), III in 54 (13.9%), IV in 54 (13.9%), V in 54 (13.9%). 300/388 (77.3%) had Manual Ability Classification Scale of level 1-3 and 88 (22.7%) of level 4-5. CP types were spastic in 271 (70%), with 60% of these bilateral and 40% unilateral, ataxic 38 (9.8%), dystonic 18 (4.6%), choreoathetoid 29 (7.5%) and unclassifiable 32 (8.3%). Postneonatal risk factors for CP were seen in 140 (36.1%) children including malaria with seizures 101/140 (72.1%), malaria with coma 21/140 (15.0%), meningitis 12/140 (8.6%), tuberculosis 2/140 (1.4%), sickle cell disease 3/140 (2.2%), HIV 1/221 (0.7%). Prenatal/perinatal risk factors were seen in 248 (63.9%%), birth asphyxia 118 (47.6%) and clinical congenital rubella syndrome 8 (3.3%) and hyperbilirubinaemia 59 (23.8%) were identified as preventable risk factors for CP. CONCLUSION: The profile of CP in this population is similar to that found in other low-income and middle-income countries (LMIC). Some risk factors identified were preventable. Prevention and management strategies for CP designed for LMIC are needed.

Severe Pulmonary Arteriopathy in a Neonate with Congenital Rubella Syndrome and Patent Ductus Arteriosus.

Neonates with congenital rubella syndrome (CRS) are known to have associated congenital cardiac malformations. Patent ductus arteriosus (PDA) is one the most common cardiac anomalies associated with CRS. PDA refractory to medical management and associated with ventilatory dependence is considered for surgical ligation. However, the management of PDA can be challenging in the presence of underlying lung disease or pulmonary vascular disease. Outcomes after closure in neonates are dependent upon age, weight, nutritional status, pre-operative pulmonary arterial hypertension and presence of chronic lung disease. We present a neonate with CRS who required surgical PDA closure. The neonate developed severe pulmonary arterial hypertension which led to fatal outcome. The clinical course is corroborated with histo-pathological changes observed on the autopsy of this neonate.

Diabetic ketoacidosis in a child with congenital rubella syndrome: A case report and review of literature.

Congenital rubella syndrome (CRS) usually occurs in a developing fetus of a pregnant woman who has contracted rubella, usually in the first trimester. With universal rubella vaccination, the incidence of CRS in developed countries has drastically reduced. However, in developing countries, CRS continues to be a public health menace in children. Sensorineural deafness, cataract, micropthalamia, patent ductus arteriosus and pulmonary stenosis are common clinical manifestations in a child affected with CRS. Other relatively rare manifestations are hepatosplenomegaly, thrombocytopenia and blueberry muffin spots. Although it is well known that CRS predisposes towards development of diabetes mellitus usually in adults, but in children only anecdotal case reports are available. Latent viral infection, immune mediated mechanism and HLA allele predisposition are various possible pathogenic mechanisms. Majority of affected persons require insulin therapy. Hereby we are demonstrating a case of seven year old boy with CRS, who presented with diabetic ketoacidosis and was successfully managed with insulin therapy. This report intends to aware clinicians regarding predisposition of children with CRS for developing diabetes, as timely diagnosing and instituting insulin therapy will help in avoiding complications and improving their quality of life.

Anti-Jo-1 Antibody-positive Interstitial Pneumonia in an Elderly Patient with Congenital Rubella Syndrome.

A 71-year-old woman with congenital rubella syndrome (CRS) presented with prolonged cough. No physical findings suggested the presence of any connective tissue diseases. Chest computed tomography showed ground-glass opacities and consolidations in the bilateral lower lobes. She had elevated serum Krebs von den Lungen-6, hypoxemia and positive serum anti-Jo-1 antibody. Bronchoalveolar lavage fluid revealed lymphocytosis with a decreased CD4/CD8 ratio. A transbronchial lung biopsy specimen revealed organizing pneumonia. Based on a diagnosis of interstitial pneumonia with autoimmune features (IPAF), systemic corticosteroids were administered, and a good outcome was obtained. A possible relationship between CRS and IPAF is herein discussed.

Aniridia: A Rare Manifestation Of Congenital Rubella Syndrome.

A foetus affected by a congenital rubella infection can develop congenital rubella syndrome (CRS). Aniridia is the absence of iris, rarely been described in literature in association with CRS, can easily be overlooked, leading to complications e.g. glaucoma and blindness later in life. We report a case of a neonate with CRS and aniridia presenting at a tertiary care hospital.

Clinical manifestations of congenital rubella syndrome: A review of our experience in Vietnam.

Rubella vaccination programs have dramatically reduced the incidence of rubella and congenital rubella syndrome (CRS) in developed countries. However, CRS prevalence is still rising in developing countries where rubella-containing vaccines (RCV) are not included in the immunization program and even in some countries where a part of the population lacks immunity to rubella despite the presence of RCV in the regular immunization program. This review aimed to summarize the clinical features of CRS using data from our studies conducted between 2011 and 2015 in Vietnam, wherein we examined clinical manifestations in Vietnamese children with CRS who were born after the large rubella outbreak of 2011; a series of studies dealing with CRS in North America and Europe after the 1960s epidemic; and those from countries before introduction of RCVs. This review shows that children with CRS have a variety of disabilities such as hearing, visual, developmental, behavioral, cardiac, and endocrine impairments, which have variable severity and may appear in different combinations. Some of these impairments can appear or worsen later in the lives of these children. Physicians should thus complete pediatric, cardiac, auditory, ophthalmologic, and neurologic examinations along with laboratory diagnostic testing soon after birth. These assessments should be repeated during follow-up if congenital rubella infection is suspected in a neonate. Timely intervention for cardiac defects can be lifesaving. Early introduction and continuation of speech, occupational, physical, and behavior therapies and training with appropriate medical interventions by a multidisciplinary team approach are required to maximize quality of life.

Clinical profile of congenital rubella syndrome in Yogyakarta, Indonesia.

BACKGROUND: Congenital rubella syndrome (CRS) has many severe neurological manifestations and other systemic consequences. Although various studies have been done in Indonesia, there are no conclusive results on CRS incidence. The aim of this study was therefore to investigate the incidence, clinical manifestations and outcomes of CRS in Yogyakarta, Indonesia. METHODS: A descriptive study involving a review of congenital anomalies associated with CRS was carried out at Dr Sardjito Hospital, Yogyakarta, Indonesia, from July 2008 to June 2013. CRS was categorized according to the World Health Organization (WHO) classification. This study involved children aged <1 year old, and was conducted at the outpatient clinic, pediatric and neonatology wards. RESULTS: A total of 201 children met the criteria for suspected CRS during the 5 year study. Of those patients, 6% were classified as having laboratory-confirmed CRS, 21.4% as having clinically compatible CRS, and 72.6% as having discarded CRS (i.e. a suspected case that does not meet the criteria for CRS). The estimated incidence of laboratory-confirmed CRS and laboratory-confirmed and clinically compatible CRS in Yogyakarta, Indonesia during the study period was 0.05:1,000 and 0.25:1,000 live births, respectively. Of the laboratory-confirmed CRS patients, 83.3% of children had congenital heart disease (CHD), 75% had hearing impairment, 66.7% had congenital cataract and 50% had microcephaly. Furthermore, none of the mothers was vaccinated against rubella. CONCLUSIONS: The incidence of CRS in infants in Yogyakarta Indonesia is considered high, with most clinical manifestations being CHD, hearing impairment and congenital cataract. This emphasizes the necessity for epidemiological study of CRS in other hospitals and the importance of establishing a national rubella vaccination program in Indonesia.