View source for Congenital rubella syndrome

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{{Infobox medical condition (new)
| name            = Congenital rubella syndrome
| image           = Cataracts due to Congenital Rubella Syndrome (CRS) PHIL 4284 lores.jpg
| caption         = White pupils due to [[congenital cataract]]s in a child with congenital rubella syndrome
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| field           = [[Teratology]]
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'''Congenital rubella syndrome''' (CRS) occurs when a human [[fetus]] is infected with the [[rubella virus]] (German measles) via maternal-fetal transmission and develops [[birth defects]].<ref name=Vesikari2021>{{cite book |last1=Vesikari |first1=Timo|last2=Usonis |first2=Vytautas |editor1-last=Vesikari |editor1-first=Timo |editor2-last=Damme |editor2-first=Pierre Van |title=Pediatric Vaccines and Vaccinations: A European Textbook |date=2021 |publisher=Springer |edition=Second|location=Switzerland |isbn=978-3-030-77172-0 |pages=82–83 |chapter= 9. Measles-Mumps-Rubella vaccine|chapter-url=https://books.google.com/books?id=LLg-EAAAQBAJ&pg=PA82|language=en}}</ref> The most common congenital defects affect the ophthalmologic, cardiac, auditory, and neurologic systems.<ref name=Jong2022>{{cite book |last1=Rochester |first1=Caitlin K. |last2=Adams |first2=Daniel J. |editor1-last=Jong |editor1-first=Elaine C. |editor2-last=Stevens |editor2-first=Dennis L. |title=Netter's Infectious Diseases |date=2022 |publisher=Elsevier |location=Philadelphia |isbn=978-0-323-71159-3 |page=53 |edition=2nd |chapter-url=https://books.google.com/books?id=l8skEAAAQBAJ&pg=PA53 |language=en |chapter=12. Rubella }}</ref>

Rubella infection in pregnancy can result in various outcomes ranging from asymptomatic infection to [[Birth defect|congenital defects]] to [[miscarriage]] and fetal death.<ref name=":12">{{Cite journal |date=2001-07-13 |title=Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome |journal=  MMWR. Recommendations and Reports |volume=50 |issue=RR-12 |pages=1–23 |issn=1057-5987 |pmid=11475328}}</ref><ref name=":2">{{Cite web |last=Arrieta |first=Antonio C. |title=Congenital rubella |url=https://www.uptodate.com/contents/congenital-rubella |access-date=2023-02-09 |website=www.uptodate.com}}</ref> If infection occurs 0–11 weeks after conception, the infant has a 90% risk of being affected.<ref name=Vesikari2021/> If the infection occurs 12–20 weeks after conception, the risk is 20%. Infants are not generally affected if rubella is contracted during the third trimester.<ref name=":12" /> Diagnosis of congenital rubella syndrome is made through a series of clinical and laboratory findings, and management is based on the infant's clinical presentation. Maintaining [[rubella]] outbreak control via vaccination is essential in preventing congenital rubella infection and congenital rubella syndrome.<ref name=":12" />

Congenital rubella syndrome was discovered in 1941 by Australian [[Norman Gregg|Norman McAlister Gregg]].<ref name="CDC2012Pink2">{{cite book |last1=Atkinson |first1=William |url=https://www.cdc.gov/vaccines/pubs/pinkbook/rubella.html |title=Epidemiology and Prevention of Vaccine-Preventable Diseases |date=2011 |publisher=Public Health Foundation |isbn=9780983263135 |edition=12th |pages=301–323 |access-date=30 March 2015}}</ref>

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==Signs and symptoms==
[[File:Infant with skin lesions from congenital rubella.jpg|thumb|Infant with skin lesions from congenital rubella]]
[[Image:Congenital Rubella Syndrome, Salt and Pepper Retinopathy.jpg|right|thumb|"Salt-and-pepper" retinopathy is characteristic of congenital rubella.<ref name=Sudharshan>{{cite journal|vauthors=Sudharshan S, Ganesh SK, Biswas J |title=Current approach in the diagnosis and management of posterior uveitis|journal=Indian J Ophthalmol|date=2010|volume=58|issue=1|pages=29–43|pmid=20029144|issn=0301-4738|doi=10.4103/0301-4738.58470|pmc=2841371 |doi-access=free }}</ref><ref>{{cite journal |last1=Khurana |first1=Rahul N. |last2=Sadda |first2=Srinivas R. |title=Salt-and-Pepper Retinopathy of Rubella |journal=[[N Engl J Med]] |date=3 Aug 2006 |volume=355 |issue=5 |page=499 |doi=10.1056/NEJMicm040780 |pmid=16885553 |url=https://www.nejm.org/doi/full/10.1056/NEJMicm040780|url-access=subscription }}</ref>]]

The classic triad for congenital rubella syndrome is:<ref>{{Cite web|title = Congenital rubella syndrome {{!}} Sense|url = http://www.sense.org.uk/content/congenital-rubella-syndrome|website = www.sense.org.uk|access-date = 2015-07-30}}</ref>
* [[Sensorineural hearing loss|Sensorineural deafness]]<ref name=":52">{{Cite book |last1=Zimmerman |first1=LA |title=Harrison's Principles of Internal Medicine |last2=Reef |first2=SE |publisher=McGraw-Hill Education |year=2022 |editor-last=Loscalzo |editor-first=Joseph |edition=21st |publication-date=2022 |chapter=Rubella (German Measles) |editor-last2=Fauci |editor-first2=A |editor-last3=Kasper |editor-first3=D |editor-last4=Hauser |editor-first4=S |editor-last5=Longo |editor-first5=D |editor-last6=Jameson |editor-first6=J}}</ref> (58% of patients)<ref name=":13">{{Cite web |year=2024 |title=Pregnancy and Rubella |url=https://www.cdc.gov/rubella/pregnancy.html |access-date=January 28, 2024 |website=Centers for Disease Control and Prevention |publication-place=Atlanta, Georgia}}</ref>
* Eye abnormalities—especially [[retinopathy]],<ref name=":52" /><ref name=":32">{{Cite journal |last1=Winter |first1=Amy K. |last2=Moss |first2=William J. |date=2022-04-02 |title=Rubella |journal=Lancet |volume=399 |issue=10332 |pages=1336–1346 |doi=10.1016/S0140-6736(21)02691-X |issn=1474-547X |pmid=35367004|s2cid=247846943 }}</ref> [[cataract]],<ref name=":13" /><ref name=":32" /> [[glaucoma]],<ref name=":32" /> and [[microphthalmia]]<ref>{{Cite journal |last=Duszak |first=Robert S. |date=January 2009 |title=Congenital rubella syndrome--major review |journal=Optometry (St. Louis, Mo.) |volume=80 |issue=1 |pages=36–43 |doi=10.1016/j.optm.2008.03.006 |issn=1558-1527 |pmid=19111256}}</ref> (43% of patients)<ref>{{Cite journal |last=Kumar Panda |first=Prateek |date=2019 |title=Diabetic ketoacidosis in a child with congenital rubella syndrome: A case report and review of literature |journal=Diabetes & Metabolic Syndrome |volume=13 |issue=4 |pages=2473–2475 |doi=10.1016/j.dsx.2019.06.026 |issn=1878-0334 |pmid=31405663|s2cid=198296894 }}</ref>
* [[Congenital heart disease]]<ref name=":22">{{Citation |last1=Shukla |first1=Samarth |title=Congenital Rubella |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK507879/ |access-date=2024-01-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29939656 |last2=Maraqa |first2=Nizar F.}}</ref>—especially [[Stenosis of pulmonary artery|pulmonary artery stenosis]] and [[patent ductus arteriosus]] (50% of patients)<ref>{{Cite journal|title = An update on cardiovascular malformations in congenital rubella syndrome.|date = January 2010|pmid = 19697432|journal = Birth Defects Research Part A: Clinical and Molecular Teratology|doi=10.1002/bdra.20621|volume=88|issue=1|vauthors=Oster ME, Riehle-Colarusso T, Correa A |pages=1–8|url = https://zenodo.org/record/1229131}}</ref>

Other manifestations of CRS may include:
* [[Spleen]],<ref name=":52" /><ref name=":32" /> [[liver]], or [[bone marrow]] problems (some of which may disappear shortly after birth)
* [[Intellectual disability]]<ref>{{Cite journal |last1=Das |first1=Pratyush Kumar |last2=Kielian |first2=Margaret |date=2021-04-26 |title=Molecular and Structural Insights into the Life Cycle of Rubella Virus |journal=Journal of Virology |volume=95 |issue=10 |pages=e02349–20, JVI.02349–20 |doi=10.1128/JVI.02349-20 |issn=1098-5514 |pmc=8139664 |pmid=33627388}}</ref>
* Small head size ([[microcephaly]])<ref name=":32" />
* [[Low birth weight]]<ref name=":0">{{Cite web|url=http://www.childrenshospital.org/conditions-and-treatments/conditions/c/congenital-rubella/symptoms-and-causes|title=Congenital Rubella Symptoms & Causes {{!}} Boston Children's Hospital|website=www.childrenshospital.org|access-date=2019-03-05}}</ref>
* [[Thrombocytopenic purpura]],<ref name=":52" /><ref name=":1">{{Cite journal |last1=Mawson |first1=Anthony R. |last2=Croft |first2=Ashley M. |date=2019-09-22 |title=Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism |journal=International Journal of Environmental Research and Public Health |volume=16 |issue=19 |pages=3543 |doi=10.3390/ijerph16193543 |doi-access=free |issn=1660-4601 |pmc=6801530 |pmid=31546693}}</ref> leading to easy or excessive bleeding or bruising
* [[Extramedullary hematopoiesis]] (presents as a characteristic [[Blueberry muffin baby|blueberry muffin rash]])<ref name=Jong2022/>
* Enlarged liver ([[hepatomegaly]])<ref name=":5" />
* Small jaw size ([[Micrognathism|micrognathia]])<ref name=":1" />
* Radiolucent bone disease<ref name=":32" />
* Skin lesions <ref name=":0" />

Children who have been exposed to rubella in the womb should also be watched closely as they age for any indication of:
* [[Developmental disability|Developmental delay]]<ref name=":0" />
* [[Autism spectrum|Autism]]<ref name=":22" /><ref name=":1" /><ref name="pmid15121991">{{cite journal|last=Muhle|first=R |author2=Trentacoste, SV |author3=Rapin, I |author3-link=Isabelle Rapin|title=The genetics of autism.|journal=Pediatrics|date=May 2004|volume=113|issue=5|pages=e472–86|pmid=15121991|url=http://pediatrics.aappublications.org/content/113/5/e472.full|doi=10.1542/peds.113.5.e472|s2cid=6077170 |doi-access=|url-access=subscription}}</ref>
* [[Schizophrenia]]<ref name="pmid16469941">{{cite journal|last=Brown|first=A. S|title=Prenatal Infection as a Risk Factor for Schizophrenia|journal=Schizophrenia Bulletin|date=9 February 2006|volume=32|issue=2|pages=200–202|doi=10.1093/schbul/sbj052|pmid=16469941|pmc=2632220}}</ref>
* [[Growth retardation]]<ref>{{Cite journal|title = Pathogenesis of congenital rubella|journal = JAMA|date = 1965-12-20|issn = 0098-7484|pages = 1277–1283|volume = 194|issue = 12|doi = 10.1001/jama.1965.03090250011002|last1 = Naeye|first1 = Richard L.|pmid = 5898080}}</ref>
* [[Learning disability|Learning disabilities]]<ref name=":1" />
* [[Thyroid disorders]]<ref name=":1" /><ref name=":4">{{Cite journal |last1=Terracciano |first1=E |last2=Amadori |first2=F |last3=Pettinicchio |first3=V |last4=Zaratti |first4=L |last5=Franco |first5=E |date=2020-04-02 |title=Strategies for elimination of rubella in pregnancy and of congenital rubella syndrome in high and upper-middle income countries |journal=J Prev Med Hyg |volume=61 |issue=1 |pages=E98–E108 |doi= |issn= |pmc=7225652 |pmid=32490275 |doi-access=}}</ref>
* [[Diabetes mellitus]]<ref name=":4" /><ref>{{Cite journal|doi = 10.1016/S0140-6736(71)90057-2|pmid = 4105044|title = High Frequency of Diabetes Mellitus in Young Adults with Congenital Rubella|journal = The Lancet|volume = 298|issue = 7720|pages = 332–334|date = 1971-08-14|last1 = Forrest|first1 = Jill M.|last2 = Menser|first2 = Margaret A.|last3 = Burgess|first3 = J. A.}}</ref>

==Diagnosis==
[[File:Rubella serology.png|thumb|Congenital rubella serology timeline]]
Diagnosis of congenital rubella syndrome is made based on clinical findings and laboratory criteria.<ref name=":12" /> Laboratory criteria include at least one of the following:
* Detection of the rubella virus via [[Reverse transcription polymerase chain reaction|RT-PCR]]<ref name=":5" />
* Detection of rubella-specific [[Immunoglobulin M|IgM antibody]]<ref name=":5" />
* Detection of infant rubella-specific [[Immunoglobulin G|IgG antibody]]<ref name=":5" /> at higher levels (and persists for a longer time) than expected for passive maternal transmission
* Isolation of the rubella virus by nasal, blood, throat, urine, or [[cerebrospinal fluid]] specimens

Findings in the following categories characterize the clinical definition:

# Cataracts/congenital glaucoma, congenital heart disease (most commonly, patent ductus arteriosus or peripheral pulmonary artery stenosis), hearing impairment, pigmentary retinopathy
# Purpura, [[hepatosplenomegaly]], jaundice, microcephaly, developmental delay, [[meningoencephalitis]], radiolucent bone disease

A patient is classified into the following cases depending on their clinical and laboratory findings:<ref name=":12" />
* '''Suspected:''' A patient that has one or more of the clinical findings listed above but does not meet the definition for probable or confirmed classification
* '''Probable:''' A patient that does not have laboratory confirmation of congenital rubella but has either two clinical findings from Group 1 as listed above, OR one clinical finding from Group 1 and one clinical finding from Group 2 as listed above
* '''Confirmed:''' A patient with at least one laboratory finding and one clinical finding (from either group) as listed above
* '''Infection only:''' A patient with no clinical findings as described above, but meeting at least one confirmed laboratory criterion

==Prevention==
Vaccinating the majority of the population is effective at preventing congenital rubella syndrome.<ref name=WHO2011>{{cite journal|title=Rubella vaccines: WHO position paper.|journal=Wkly Epidemiol Rec|date=15 July 2011|volume=86|issue=29|pages=301–16|pmid=21766537|url=https://www.who.int/wer/2011/wer8629.pdf}}</ref> With the introduction of the rubella vaccine in 1969, the number of cases of rubella in the United States has decreased 99%, from 57,686 cases in 1969 to 271 cases in 1999.<ref name=":12" /> For women who plan to become pregnant, the [[MMR vaccine|MMR (measles, mumps, rubella) vaccination]] is highly recommended, at least 28 days before conception.<ref name=":0" /> The vaccine should not be given to women who are already pregnant as it contains live viral particles.<ref name=":0" /> Other preventative actions can include the screening and vaccinations of high-risk personnel, such as medical and child care professionals.<ref>{{Cite web|url=https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/congenital-rubella|title=Congenital Rubella - Pediatrics|website=Merck Manuals Professional Edition|language=en-US|access-date=2019-03-05}}</ref>

Infants with birth defects suspected to be caused by congenital rubella infection should be investigated thoroughly. Confirmed cases should be reported to the local or state health department to assess control of the virus, and isolation of the infant should be maintained.<ref name=":3">{{Citation |title=Rubella |date=2021-05-17 |url=http://dx.doi.org/10.1542/9781610025225-part03-ch120 |work=Red Book (2021) |pages=648–655 |publisher=American Academy of Pediatrics |doi=10.1542/9781610025225-part03-ch120 |isbn=978-1-61002-522-5 |access-date=2023-02-09|url-access=subscription }}</ref>

== Management ==
Infants with known rubella exposure during pregnancy or those with a confirmed or suspected infection should receive close follow-up and supportive care. There are no medications or antivirals that will shorten the clinical course of the virus.<ref name=":2" /> Only those with [[Immunity (medical)|immunity]] to rubella should have contact with infected infants, as they can shed viral particles in their respiratory secretions through 1 year of age (unless they test with repeated negative viral cultures at age 3 months).<ref name=":12" /> Many infants can be born with multiple birth defects that require multidisciplinary management and interventions based on clinical manifestations. Often, these infants will require an extended period or lifelong follow-up with medical specialists. Early diagnosis of congenital rubella syndrome is important for planning future medical care and educational placement.<ref name=":5">{{Cite journal |last1=Leung |first1=A. K. C. |last2=Hon |first2=K. L. |last3=Leong |first3=K. F. |date=April 2019 |title=Rubella (German measles) revisited |journal=Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi |volume=25 |issue=2 |pages=134–141 |doi=10.12809/hkmj187785 |issn=1024-2708 |pmid=30967519|doi-access=free }}</ref>

=== Auditory care ===
Many infants with CRS may be born with [[Sensorineural hearing loss|sensorineural deafness]] and thus should undergo a newborn hearing evaluation. Hearing loss may not be apparent at birth and thus requires close auditory follow-up. Infants with confirmed hearing impairment may require hearing aids and may benefit from an early intervention program.<ref name=":2" />

=== Ophthalmologic care ===
Eye abnormalities, including cataracts, infantile glaucoma, and retinopathy, are common in infants born with CRS.<ref name=":3" /> Infants should undergo eye examinations after birth and during early childhood. Those with congenital eye defects require care from a pediatric ophthalmologist for specialized care and follow-up.<ref name=":2" />

=== Cardiac care ===
Congenital cardiac anomalies, including [[Stenosis of pulmonary artery|pulmonary artery stenosis]] and [[patent ductus arteriosus]], can be seen in infants with CRS. Infants should undergo cardiac evaluation soon after birth, and those with confirmed cardiac lesions will require specialized care with a pediatric cardiologist for any interventions and follow-up care.<ref name=":2" />

==See also==

* [[Jay Horwitz]] (born 1945), New York Mets executive born with the syndrome

==References==
{{reflist}}

{{Medical resources
|   DiseasesDB     = 11729
|   ICD10          = {{ICD10|P|35|0|p|35}}
|   ICD9           = {{ICD9|771.0}}
|   ICDO           =
|   OMIM           =
|   MedlinePlus    = 001658
|   eMedicineSubj  = emerg
|   eMedicineTopic = 388
|   MeshID         = D012410
}}
{{Viral cutaneous conditions}}
{{Certain conditions originating in the perinatal period}}
{{Diseases of maternal transmission}}

[[Category:Congenital disorders]]
[[Category:Infections specific to the perinatal period]]
[[Category:Rubella]]
[[Category:Syndromes caused by microbes]]
[[Category:Virus-related cutaneous conditions]]
[[Category:Disability]]
[[Category:Infectious diseases]]
[[Category:Pediatrics]]
[[Category:Hematology]]