Congenital rubella syndrome overview

# Overview
In 1941, congenital rubella syndrome was recognized as a complication of rubella infection among pregnant women who became infected with the virus early in their pregnancy. An Australian ophthalmologist made the connection and reported 78 cases of congenital cataract among infants born to mothers who had a rubella infection early in their pregnancy. The pathogenesis of congenital rubella syndrome is multifactorial. However, pregnant women who are not vaccinated against rubella are at high risk of contracting the infection. If they get infected during pregnancy, the virus can infect the placenta and spread to the fetus, leading to disruption of the normal process of organogenesis. Rubella virus has largely been eradicated in many parts of the developed world. However, in the developing world where MMR vaccine is not available or accessible, infection with rubella and consequently, congenital rubella syndrome is an important health issue. Many of the congenital infections have overlapping features and hence, congenital rubella must be differentiated from the other TORCH infections. Congenital rubella syndrome affects multiple organ systems. The classic triad consists of cataracts, sensorineural hearing loss and patent ductus arteriosus (PDA).

# Historical Perspective
Originally, rubella was referred to as the third disease, because it was thought to branch from measles or Scarlet fever. However, in 1814, it was recognized as a separate entity of disease and became known as German measles. In 1941, congenital rubella syndrome was recognized as a complication of rubella infection among pregnant women who became infected with the virus early in their pregnancy. An Australian ophthalmologist made the connection and reported 78 cases of congenital cataract among infants born to mothers who had a rubella infection early in their pregnancy.

# Classification
There is no classification scheme for congenital rubella syndrome. However, in 2009, the CDC published the case classification of congenital rubella syndrome and divided into suspected cases, probable cases, confirmed cases and infection only, based on symptoms and/or laboratory findings.

# Pathophysiology
The pathogenesis of congenital rubella syndrome is multifactorial. However, pregnant women who are not vaccinated against rubella are at high risk of contracting the infection. If they get infected during pregnancy, the virus can infect the placenta and spread to the fetus, leading to disruption of the normal process of organogenesis. The degree of severity of malformations depends on the gestational age of the onset of infection. The highest risk of fetal anomalies or poor pregnancy outcomes such as spontaneous abortion and stillbirth is highest if a woman becomes infected prior to conception or in the in the first 8-10 weeks of gestation.

# Causes
The cause of congenital rubella syndrome is rubella virus. Rubella virus is a single-stranded, positive-sense RNA virus (ssRNA). It is the only member of the genus Rubivirus and belongs to the family of Togaviridae.

# Differentiating Congenital Rubella Syndrome from other Diseases
The most important congenital infections, which can be transmitted vertically from mother to fetus are the TORCH infections. These infections have overlapping features and hence, must be differentiated from CRS.

# Epidemiology and Demographics
The exact incidence of congenital rubella syndrome is hard to estimate, because in many parts of the developing world rubella has been eliminated. However, very few cases are still reported in the U.S and they are believed to be imported cases. In addition, rubella infection and congenital rubella syndrome are still a challenge in the developing world, with most cases occurring in Africa and Southeast Asia.In countries without rubella immunization, the incidence is estimated to range between 60-220 per 100,000 cases.

# Risk Factors

# Screening
There is no screening test for congenital rubella syndrome.

# Natural History, Complications and Prognosis
Congenital rubella syndrome can cause serious birth defects and the prognosis depends on the severity of the problem. Heart defects can be corrected but neurological damage is permanent.

# History and Symptoms
The symptoms of rubella in the pregnant woman are similar to those seen in any child or adult with rubella infection. Of note, young women are more likely to suffer from sequelae of polyarthritis and polyarthralgia. In the infant, symptoms such as irritability, low birth weight, skin lesions, white appearance to the cornea may be seen and be suggestive of congenital rubella syndrome.

# Physical Examination
Congenital rubella syndrome affects multiple organ systems. The classic triad of congenital rubella syndrome consists of cataracts, sensorineural hearing loss and patent ductus arteriosus (PDA). However, many other findings are evident on physical examination, including low birth weight, skin lesions and hepatosplenomegaly.

# Laboratory Findings
Prenatal testing consists of direct isolation of the virus, viral nucleic acid quantification or detection of antibodies against rubella in fetal blood via various invasive techniques, such as amniocentesis, fetal blood sampling and chorionic villi sampling. Postnatal testing consists of isolation of the virus from throat or urine cultures and detection of serology (IgG or IgM antibodies against rubella). Other laboratory findings in infants with congenital rubella syndrome include thrombocytopenia and elevated levels of PT, PTT and bilirubin.

# Electrocardiogram
Electrocardiogram findings in a child of congenital rubella syndrome depends on the type of heart defect (mostly PDA) and its severity.

# Chest X Ray
The chest radiograph may show increased pulmonary vascularity and cardiomegaly due to ventricular enlargement. The heart size might be normal if the shunt is small. However, CXR findings depend on the size and type of associated heart defect.

# CT Scan
Congenital rubella syndrome is associated with craniofacial abnormalities, most commonly microcephaly or hydrocephaly. Hence, CT scan is able to assess the underlying brain and the forebrain is usually most affected. In addition, a multi-detector CT scan (MDCT) is used to detect the various cardiac anomalies associated with congenital rubella syndrome. Findings such as patent ductus arteriosus, its degree of severity as well as other associated cardiac anomalies may be seen.

# MRI
Congenital rubella syndrome is associated with craniofacial abnormalities, most commonly microcephaly or hydrocephaly. Hence, MRI is able to assess the underlying brain and the forebrain is usually most affected.

# Echocardiography and Ultrasound
On echocardiography, the several cardiac anomalies associated with congenital rubella syndrome may be seen. These include patent ductus arteriosus, pulmonary artery stenosis, coarctation of the aorta, as well as septal defects (VSD or ASD). Prenatal ultrasound, although not sensitive, is highly specific in detecting the various anomalies associated with congenital rubella syndrome. Findings such as IUGR, fetal hydrops, microcephaly, cardiac and ophthalmic defects may be seen on ultrasound.

# Other Imaging Findings
There are no other imaging findings associated with congenital rubella syndrome.

# Other Diagnostic Studies
There are no other diagnostic studies associated with congenital rubella syndrome.

# Medical Therapy
There is no specific medical treatment for congenital rubella syndrome.

# Surgery
The role of surgery in patients with congenital rubella syndrome consists of treating the several cardiac, ophthalmic and hearing complications that arise as a result.

# Primary Prevention
MMR vaccination prior to pregnancy can prevent congenital rubella syndrome.

# Secondary Prevention
Infants with congenital rubella syndrome should be placed in isolation during their hospital stay. In addition, appropriate measures should be taken to ensure that all healthcare workers and caregivers of the infected child are immune to rubella.