This is a case of a four-month-old female infant who presented with clinical manifestations of congenital rubella syndrome (CRS) — bilateral cataracts, poorly-dilating pupils, microcorneas, salt and pepper retinopathies seen after cataract extractions, bilateral sensorineural hearing loss, patent ductus arteriosus, microcephaly, history of blueberry spots and low birth weight, and positive serum IgM and IgG tests for rubella. The patient’s mother also had prenatal rubella infection. However, the patient also presented with additional set of clinical findings not seen in recent patients with CRS and not commonly reported in literature: visual acuities of poor to no dazzle, bilateral choroidal thickening on ocular ultrasound that spontaneously resolved, optic nerve inflammation that became atrophic, vessel tortuosities seen after cataract extractions, bilateral subependymal cysts with lenticulostriate vasculopathy in basal ganglia, basal ganglia hyperintensity suggestive of calcification, and jaundice. These findings plus the overlapping clinical manifestations with CRS and the positive IgM and IgG for cytomegalovirus (CMV) made us consider a congenital CMV co-infection. CRS already causes significant childhood morbidity. Getting co-infected with CMV in utero worsens morbidity and makes management more difficult. This case presented a congenital co-infection of rubella and CMV and discussed the added challenges in their diagnosis and management.
Rubella Syndrome, Congenital ; Cytomegalovirus Infections ; Coinfection

Congenital cytomegalovirus (CMV) infection (cCMV) is challenging to differentiate from congenital rubella syndrome (CRS) clinically. Virus detection and serological tests are needed. However, they are often not readily available or are expensive. This is a case of a five-month-old male with bilateral cataracts. He was jaundiced at birth and started having seizure episodes at one month of age. He was also diagnosed with right inguinal hernia and had abnormal bilateral hearing tests. Both eyes were noted to have leukocoria at two months of age. There was dazzle on both eyes and sclerae were anicteric. Examination revealed dense cataracts on both eyes, but their ocular ultrasound results were essentially normal. Due to the bilateral hearing loss and bilateral cataracts, CRS was initially considered despite the absence of heart abnormality since there were reported CRS cases without the complete triad. However, possible coinfection or another disease was considered due to the presence of jaundice, seizures, and hernia, which were never seen in our previous CRS patients nor were reported in the literature. The patient underwent cataract extraction on both eyes without intraocular lens implantation (IOL) as recommended for CRS cataracts to prevent severe inflammation. TORCH (TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex) test was negative for rubella but positive for CMV. As such, the patient would have benefitted from early IOL implantation. The patient was then referred to a national medical center for possible treatment. However, since the patient already tested negative for CMV polymerase chain reaction (PCR) there, systemic antiviral therapy was no longer initiated. This case presented the challenge of clinically differentiating cCMV and CRS.
Cytomegalovirus Infections ; Rubella Syndrome, Congenital ; Hearing Loss ; Jaundice

We report three autopsy cases of congenital cytomegalovirus (CMV) infection in fetuses with a review of literature. The clinical manifestations in these cases of congenital CMV infection include intrauterine fetal death, hydrops fetalis, and CMV pneumonia associated with cardiovascular defect. The pathological characteristics were as follows: 1) the kidney was the most frequently involved organ, followed by lung and liver, 2) CMV inclusions were found predominantly in epithelial cells and to a lesser degree in endothelial cells, 3) intrahepatic bile duct epithelial cells were frequently involved, and 4) inflammatory reaction around CMV inclusions was not prominent in the early stage of pregnancy. Diagnostic confirmation was obtained by in situ hybridization (ISH) using a biotinylated CMV-DNA probe, which demonstrated intranuclear inclusions and sometimes recognized cells that did not show intranuclear inclusion.
Autopsy ; Case Report ; Cytomegalovirus Infections/virology ; Cytomegalovirus Infections/pathology* ; Cytomegalovirus Infections/congenital* ; Female ; Fetal Diseases ; Human ; Male ; Pregnancy ; Pregnancy Complications, Infectious

We report three autopsy cases of congenital cytomegalovirus (CMV) infection in fetuses with a review of literature. The clinical manifestations in these cases of congenital CMV infection include intrauterine fetal death, hydrops fetalis, and CMV pneumonia associated with cardiovascular defect. The pathological characteristics were as follows: 1) the kidney was the most frequently involved organ, followed by lung and liver, 2) CMV inclusions were found predominantly in epithelial cells and to a lesser degree in endothelial cells, 3) intrahepatic bile duct epithelial cells were frequently involved, and 4) inflammatory reaction around CMV inclusions was not prominent in the early stage of pregnancy. Diagnostic confirmation was obtained by in situ hybridization (ISH) using a biotinylated CMV-DNA probe, which demonstrated intranuclear inclusions and sometimes recognized cells that did not show intranuclear inclusion.
Autopsy ; Case Report ; Cytomegalovirus Infections/virology ; Cytomegalovirus Infections/pathology* ; Cytomegalovirus Infections/congenital* ; Female ; Fetal Diseases ; Human ; Male ; Pregnancy ; Pregnancy Complications, Infectious

OBJECTIVETo investigate human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes and clinical features in neonates with congenital infections.

METHODSUrine samples were obtained from 67 neonates with HCMV infection confirmed by polymerase chain reaction (PCR). The gB gene fragment was amplified by nested PCR. HCMV gB genotyping was detected by restriction fragment length polymorphism.

RESULTSIn all these cases, the most prevalent genotype was gBl (50.7%), followed by gB3 (23.9%), gB2 (17.9%), and gBl/gB3 coinfection (7.5%); gB4 was not found. Moreover, gB1 was more prevalent in infants with liver damage (27/37, 73.0%) than in other symptomatic infants without liver damage (13/30, 43.3%; P < 0.05).

CONCLUSIONThe gBI genotype is the most prevalent in infants with congenital symptomatic HCMV disease, especially in those with liver damage, followed by genotypes gB3, gB2, and gB4.

Cytomegalovirus ; genetics ; isolation & purification ; Cytomegalovirus Infections ; congenital ; urine ; virology ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; virology ; Male ; Viral Envelope Proteins ; genetics ; urine

OBJECTIVEHuman cytomegalovirus (HCMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection worldwide. Although 90% of the congenitally infected infants are clinically asymptomatic at birth, evidences show that these infants are at risk for audiologic, neurologic, and developmental sequelae. The aim of this study was to evaluate the outcome of children with asymptomatic congenital human cytomegalovirus infection identified from a cohort of newborn infants screened for congenital HCMV infection compared with matched uninfected control subjects.

METHODSBetween July 2003 and July 2005, eligible hospitalized infants were recruited into the cohort. Serum was collected within two weeks of birth and transported to the laboratory within 24 hours, and stored at -20 degrees C. Then Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) for the presence of HCMV DNA was used as a screening tool for the detection of congenital cytomegalovirus infection. Asymptomatic congenital HCMV infection (ACCMV) was defined as detection of HCMV during the first 2 weeks of life in the absence of any abnormal signs, symptoms, or laboratory findings. The study enrolled 41 siblings with asymptomatic congenital HCMV infection and 21 children whose neonatal screening for congenital HCMV infection showed negative results. Then they were followed up prospectively for the first years of life. A pediatric assessment, including neonatal behavioral neurological assessment (NBNA) was performed at neonatal period by a qualified pediatrician, at which time the CMV status of the infants was not yet known. At one year of age other standardised clinical evaluations were performed by the pediatrician. The Bayley scale of infant development were used to determine the intellectual and neurological development deficits, and the age-adequate neurological examinations based on the criteria by Amiel-Tison to evaluate the general movements for neurological development. Hearing screening were completed for all children to determine their hearing status. Auditory brain-stem response (ABR) and distortion product otoacoustic emission (DPOAE) have been used to accurately diagnose moderate to profound congenital sensorineural hearing loss.

RESULTThere was no significant difference between the mean NBNA score of HCMV group (38.8 +/- 2.75) and the control group (38.5 +/- 2.29) (t = 0.98, P > 0.05). Significant difference was found between the occurrence of hearing loss in infants born with asymptomatic congenital HCMV infection compared with the control group. Audiologic abnormalities (sensorineural hearing loss, SNHL) were present in 5 of 23 congenitally infected children, however, no hearing abnormalities were detected in uninfected children (chi2 = 6.94, P < 0.01). The mean Bayley score of HCMV group (MDI 106.86 +/- 10.24 and PDI 108.45 +/- 18.25) and the control group (MDI 107.49 +/- 19.31 and PDI 107.19 +/- 10.98) did not differ significantly (t = 0.33, P > 0.05, t = 0.35, P > 0.05). Otherwise, there was no significant difference in 52 Amiel-Tison neurological scale between the two groups.

CONCLUSIONThese data suggest that asymptomatic congenital cytomegalovirus infection may be associated with a broad range of audiologic differences in early infancy. Continued monitoring of their hearing status in the first years of life is necessary in these children because further progression of hearing loss is possible. However, asymptomatic congenital HCMV infection is not associated with abnormalities in growth, or neurodevelopmental deficits.

Case-Control Studies ; Child Development ; Cytomegalovirus ; Cytomegalovirus Infections ; congenital ; virology ; Evoked Potentials, Auditory, Brain Stem ; Female ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; Male ; Neonatal Screening

OBJECTIVETo investigate the variability of human cytomegalovirus (HCMV) UL138 open reading frame (ORF) in clinical strains.

METHODSHCMV UL138 ORF was amplified by polymerase chain reaction (PCR) and PCR amplification products were sequenced directly, and the data were analyzed in 19 clinical strains.

RESULTSUL138 ORF in all 30 clinical strains was amplified successfully. Compared with that of Toledo strain, the nucleotide and amino acid sequence identities of UL138 ORF in all strains were 97.41% to 99.41% and 98.24% to 99.42%, respectively. All of the nucleotide mutations were substitutions. The spatial structure and post-translational modification sites of UL138 encoded proteins were conserved. The result of phylogenetic tree showed that HCMV UL138 sequence variations were not definitely related with different clinical symptoms.

CONCLUSIONHCMV UL138 ORF in clinical strains is high conservation, which might be helpful for UL138 encoded protein to play a role in latent infection of HCMV.

Amino Acid Sequence ; Cytomegalovirus ; classification ; genetics ; Cytomegalovirus Infections ; congenital ; genetics ; Humans ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Protein Structure, Secondary ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

Cytomegalovirus infection is extremely common in the population, especially for newborns. Congenital CMV infection may cause central nervous system damage and other related diseases, thus potentially harmful. At home and abroad, some related research had been carried out on the incidence of disease, and a variety of detection methods had been developed. In this paper, the current situation of congenital cytomegalovirus infection and detection method is reviewed.
Antibodies, Viral ; blood ; Cytomegalovirus ; isolation & purification ; Cytomegalovirus Infections ; congenital ; diagnosis ; DNA, Viral ; blood ; Female ; Humans ; Infant, Newborn ; Polymerase Chain Reaction ; Pregnancy

PURPOSE: To observe changes in audiology, intellectual development, behavior development, and physical growth during systematic follow-up of infants with asymptomatic congenital human cytomegalovirus (HCMV) infection. MATERIALS AND METHODS: Fifty-two infants diagnosed with asymptomatic congenital HCMV infection from July 2003 to July 2007 served as the infection group, and 21 healthy infants served as the control group. All infants were confirmed to have HCMV infection by Fluorescent Quantative polymerase chain reaction (FQ-PCR). In both the infection and control groups, the neonates and infants at 3 months, 6 months, and 1 year of age underwent examinations. RESULTS: 1) 20 items of National Black Nurses Association (NBNA) scores of neonates 12-14 days after birth in 2 groups were 38.3 +/- 1.95 and 38.5 +/- 2.29, without significant differences. 2) Auditory test: 50 ears of 25 cases in the infection group showed abnormal auditory thresholds in V waves with an abnormal rate of 14%, while no abnormalities were found in 21 cases in the control group. 3) Mental and psychomotor development index scores in the control group (107.49 +/- 11.31 and 107.19 +/- 10.98) were compared with those in 41 asymptomatically infected infants at 1 year of age (107.21 +/- 9.96 and 108.31 +/- 11.25), and no statistically significant difference was noted. CONCLUSION: 1) An elevated threshold in the V wave was present in asymptomatically infected infants, but could not be detected through otoacoustic emission (OAE) screening. 2) Either in the neonatal or infant periods, asymptomatic congenital HCMV infection did not have a significant influence on nervous behavior or on physical and intellectual development.
Auditory Threshold ; *Child Development ; Cytomegalovirus Infections/*complications/congenital ; Female ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Male ; Neuropsychological Tests ; Psychomotor Performance

Infantile osteopetrosis is a rare congenital disorder caused by abnormal bone resorption. Patients with osteopetrosis can have severe anemia, thrombocytopenia, hepatosplenomegaly, rickets, visual impairment, and deafness. Cytomegalovirus also can cause a congenital infection with anemia, thrombocytopenia, hepatosplenomegaly, and calcifications in the brain. We report a 38-day-old infant with severe hepatosplenomegaly, thrombocytopenia, hypocalcemia, and growth failure. Real time polymerase chain reaction detected cytomegalovirus in the plasma. Skeletal radiography revealed generalized bone sclerosis. He was diagnosed with osteopetrosis along with cytomegalovirus infection. Only the test for mutation of the CLCN7 gene, representing the most common and heterogeneous form of osteopetrosis, was available, and the result was negative. With supportive care and antiviral treatment, severe thrombocytopenia due to the cytomegalovirus infection almost normalized despite the possible immunosuppression caused by osteopetrosis. We present the first report of an infant who suffered from osteopetrosis and CMV infection which was successfully treated by long term antiviral agent therapy.
Anemia ; Bone Resorption ; Brain ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Deafness ; Humans ; Hypocalcemia ; Immunosuppression ; Infant ; Infant, Newborn* ; Osteopetrosis* ; Plasma ; Radiography ; Real-Time Polymerase Chain Reaction ; Rickets ; Sclerosis ; Thrombocytopenia ; Vision Disorders