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Seattle Children’s geneticists are playing a key role in characterizing the devastating damage to newborns caused by congenital Zika syndrome.

When doctors in Brazil sounded the alarm in 2015 about an outbreak of Zika virus and observed a puzzling spike in newborn brain malformations, neurologists around the world stepped up to help. Dr. William Dobyns, a pediatric neurologist and geneticist at Seattle Children’s, joined an urgent effort by doctors in Brazil and the Centers for Disease Control and Prevention (CDC) to explain the devastating brain deformities and study if they were connected to Zika virus.

Microskull vs SkullEventually, researchers confirmed a link between pregnant women infected with Zika and newborns with troubling symptoms, and they gave the condition a name: congenital Zika syndrome. The first symptom doctors observed was severe microcephaly, in which a baby’s head is significantly smaller than normal. As they assessed affected newborns, doctors learned that the babies could suffer vision and hearing loss, feeding problems, epilepsy, motor disabilities, frozen joints (contractures) and fetal brain disruption sequence, a devastating condition that halts normal brain development well before birth.

“The brain in a fetus is growing and growing and growing,” Dobyns explains. “Then something really bad happens. The brain shrinks and the skull collapses.”

Dobyns adds that some babies born with normal head size have later showed signs of microcephaly or other symptoms.

In December 2016, Dobyns and colleagues published research with the CDC that looked retrospectively at 13 infants with evidence of Zika infection and normal head size at birth. Their head growth had decelerated as early as 5 months of age, and 11 of the babies had microcephaly. Two other babies may also have slower head growth and could eventually show clear signs of microcephaly. The findings offer evidence that the absence of microcephaly at birth among infants with prenatal exposure to Zika virus does not exclude congenital Zika virus infection or the presence of related brain and other abnormalities.

To compound the crisis, many affected babies were born in areas that lacked adequate healthcare. Zika virus has been detected in all of South and Central America and parts of the United States. As of Nov. 30, 2016, the CDC reported more than 2,600 pregnant women with evidence of Zika virus infection in the United States and its territories, with most cases so far in Puerto Rico.

Connecting an old virus to a new syndrome

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According to the World Health Organization, Zika virus was identified in Uganda in 1947. It is spread primarily by the same species of mosquitoes that carry yellow fever, dengue fever and chikungunya.

Scientists confirmed that a woman infected with Zika during pregnancy would have an increased risk of delivering a baby with congenital Zika syndrome. Mothers who were infected in the first or second trimester and experienced symptoms from the virus appear more likely to have babies with severe congenital Zika syndrome.

Dobyns and his colleague Dr. Ghayda Mirzaa reviewed brain scans and photos of affected babies from Brazil and characterized what they observed. As clinicians who treat babies with brain malformations and researchers who study these conditions, they were well-equipped to assess the damage and impacts.

“The severity and spike in cases in Brazil confirmed to us that this condition was something new under the sun,” Dobyns says.

Describing a new diagnosis

As Dobyns and his colleagues reviewed data from Brazil, they were able to characterize congenital Zika syndrome and how it develops, which is crucial to understanding tactics for prevention and treatment.

“Most crucial, perhaps, is that Zika has a debilitating effect on the development of neural stem cells, which double as the scaffolding that helps build the entire human brain,” says Dobyns.

“Zika has a debilitating effect on the development of neural stem cells, which double as the scaffolding that helps build the entire human brain.” – Dr. William Dobyns

Infectious disease specialists at Seattle Children’s Research Institute are also contributing to Zika research. Dr. Lakshmi Rajagopal worked with colleagues at the University of Washington on research showing that a pregnant non-human primate exposed to Zika carried a fetus that experienced abnormal brain development.

That research could provide information about how Zika virus inflicts injury on the fetal brain and offers a model that could be used to test vaccines and treatments.

“We know that congenital Zika syndrome is here to stay,” Dobyns says. “Simply spraying to get rid of mosquitoes is not likely to help much. New treatments such as a vaccine or novel drugs to keep the Zika virus out of neural stem cells are needed, especially for pregnant women.”