Congenital Rubella Syndrome from First Trimester Maternal Infection
The constellation of microcephaly, microphthalmia, cataract, sensorineural deafness, patent ductus arteriosus, and hepatomegaly is pathognomonic for congenital rubella syndrome (CRS) resulting from maternal rubella infection in the first trimester of pregnancy (answer c). 1, 2
Classic Clinical Triad and Extended Manifestations
The infant presents with the classic triad of CRS plus additional characteristic findings:
- Ophthalmic defects: Cataracts and microphthalmia are among the most common manifestations, occurring in up to 78% and 40% of cases respectively 2, 3
- Cardiac defects: Patent ductus arteriosus is the most frequently reported cardiac malformation in CRS, along with peripheral pulmonary artery stenosis 1
- Auditory defects: Sensorineural deafness is a hallmark finding 1, 2
- Neurologic defects: Microcephaly, meningoencephalitis, and mental retardation are characteristic 1, 2
- Hepatosplenomegaly: Present in up to 93% of cases, often accompanied by thrombocytopenia and purpuric skin lesions 1, 2, 4
Critical Timing: First Trimester Infection
The risk of congenital defects is highest when maternal rubella infection occurs during the first 8 weeks of gestation, with up to 85% of exposed infants affected. 1, 2 The CDC guidelines emphasize that infection during the first trimester carries the greatest teratogenic risk, with the likelihood of any defect declining to approximately 52% for infections occurring between weeks 9-12, and becoming rare after the 20th week 1
Why Other Options Are Incorrect
CMV infection (option a): While CMV can cause microcephaly, sensorineural hearing loss, and hepatosplenomegaly, it typically presents with intracranial calcifications and polymicrogyria rather than the classic eye findings (cataracts, microphthalmia) and cardiac defects seen here 1, 5
Varicella in third trimester (option b): Late pregnancy varicella infection does not cause the constellation of defects described; congenital varicella syndrome occurs with first or second trimester infection and presents differently 1
Radiation exposure (option d): First trimester radiation causes microcephaly and growth retardation but does not produce the specific pattern of cataracts, cardiac defects, and hepatosplenomegaly characteristic of CRS 1
Thalidomide (option e): Causes limb reduction defects (phocomelia), ear abnormalities, and cardiac defects, but not the specific triad of cataracts, deafness, and the pattern described 1
Clinical Pearls for Recognition
The combination of the "3 C's" (cataracts, cardiac defects, cochlear deafness) plus microcephaly and hepatosplenomegaly should immediately trigger suspicion for first trimester rubella exposure. 1, 6
Additional diagnostic considerations:
- Maternal history may reveal subclinical infection, as 25-50% of rubella infections are asymptomatic 1, 2
- Laboratory confirmation requires demonstration of rubella-specific IgM antibody in the infant or persistent rubella IgG titers beyond expected passive maternal antibody transfer 1
- The classic "blueberry muffin" appearance (purpuric skin lesions) may be present due to extramedullary hematopoiesis 1, 2
Memory Aid for TORCH Timing
For rubella specifically: First trimester infection = highest risk and most severe manifestations (up to 85% affected), with risk declining substantially after 12 weeks and becoming minimal after 20 weeks 1, 2. This contrasts with CMV, which can cause significant damage throughout pregnancy but has different clinical features 5.