Congenital Zika Syndrome (CZS) Phenotype Seen in Older Children

BACKGROUND: Zika virus (ZIKV) has been documented in Africa since 1947 and Asia since 1969. However, the association of congenital ZIKV infection with microcephaly and serious brain defects was not recognized until a large ZIKV outbreak began in Brazil in 2015. A similar association was retrospectively identified in a 2013–2014 French Polynesian outbreak. In this report, we describe two children, ages 6 (Case 1) and 7 years (Case 2), who display a phenotype consistent with CZS. In both cases, the mothers were residing in Cambodia during their pregnancies (2011 and 2010, respectively); Cambodia has reported ZIKV infections since 2007. METHODS: We review epidemiologic, clinical and laboratory data, and the neurodevelopmental status of these two children. RESULTS: Both mothers reported low-grade fever and erythematous rash during their early second trimesters. The infants were born with severe microcephaly (>3 SD below the mean) with central hypotonia and peripheral spasticity (Figure 1). Both had normal karyotypes, negative TORCH results, and neuroimaging suggestive of CZS with subcortical calcifications, polymicrogyria, abnormal corpus callosum, ex-vacuo ventriculomegaly, and reduced white matter (Figure 2). Case 1 had overlapping cranial sutures and redundant scalp (Figure 3). In 2016, serology immunofluorescence assay, immunoglobulin G, and plaque reduction neutralization test for the mother of Case 1 was positive for Zika. Serology for the mother of Case 2 is pending. Presently, both children have severe developmental delays; neither can sit or hold up their head, and both are nonverbal. Case 1 has bilateral hip contractures and hearing loss. Both are visually impaired and require gastrostomy-tube feedings. Case 2 is tracheostomy dependent. CONCLUSION: Given the maternal febrile rash illness, residence in a ZIKV region during pregnancy, infant features consistent with CZS, and the lack of other identified etiology, CZS should be considered as a possible diagnosis in these cases. It suggests that CZS may have occurred prior to the Brazil and French Polynesia outbreaks. Investigations into neurodevelopmental status of older children with possible CZS can provide insights into the possible long-term effects of CZS. DISCLOSURES: All authors: No reported disclosures.