Congenital Zika Syndrome: Genetic Avenues for Diagnosis and Therapy, Possible Management and Long-Term Outcomes

Abstract

Zika virus (ZIKV) was discovered in Uganda in 1947 and was originally isolated only in Africa and Asia. After a spike of microcephaly cases in Brazil, research has closely focused on different aspects of congenital ZIKV infection. In this review, we evaluated many aspects of the disease in order to build its natural history, with a focus on the long-term clinical and neuro-radiological outcomes in children. The authors have conducted a wide-ranging search spanning the 2012–2021 period from databases PubMed, PubMed Central, Web of Science, Medline, Scopus. Different sections reflect different points of congenital ZIKV infection syndrome: pathogenesis, prenatal diagnosis, clinical signs, neuroimaging and long-term developmental outcomes. It emerged that pathogenesis has not been fully clarified and that the clinical signs are not only limited to microcephaly. Given the current absence of treatments, we proposed schemes to optimize diagnostic protocols in endemic countries. It is essential to know the key aspects of this disease to guarantee early diagnosis, even in less severe cases, and an adequate management of the main chronic problems. Considering the relatively recent discovery of this congenital infectious syndrome, further studies and updated long-term follow-up are needed to further improve management strategies for this disease.

Neurodevelopmental outcomes in a cohort of children with congenital Zika syndrome at 12 and 24 months of age

“…( Indicators of ZIKV involvement in neurodevelopmental disorders have been already determined. These are prenatal screening, clinical syndromes and neuroradiological markers (Gullo et al, 2022).…”

“…Indicators of ZIKV involvement in neurodevelopmental disorders have been already determined. These are prenatal screening, clinical syndromes and neuroradiological markers (Gullo et al, 2022). However, they may present later during advanced stages of ZIKV‐related pathology and clinical manifestations, or may be even absent, leading to delays in diagnostics.…”

“…Finally, genotype–phenotype correlations will likely increase the identification of protective and risk factors on the severity of the clinical neurological presentation of CZS. The same could be applicable to the prognostication of developmental trajectories (Gullo et al, 2022).…”

SUMOylation and Viral Infections of the Brain

“…GBS is an autoimmune disease that attacks the peripheral nerves, and hydrocephalus is a well-documented, but rare, complication in individuals with the disorder [ 69 , 70 ]. Hydrocephalus has also been associated with congenital Zika syndrome, a group of birth defects associated with prenatal exposure to ZIKV [ 71 ]. ZIKV has also been shown to infect and replicate in mature neurons and glial cells, induce neuroinflammatory processes, and has been linked to myelitis, peripheral neuropathy, and reduced gray matter volume in motor-associated cortical regions [ 72 , 73 ].…”

Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence

“…Similarly, microcephaly itself comprises complex features linked to multiple causes. Before the Zika-related clusters, the rare cases of microcephaly in Brazil [ 20 ] were explained by complex genetic syndromes, environmental teratogens, low birth weight [ 21 ], and congenital toxoplasmosis and cytomegalovirus [ 22 , 23 ]. In Brazil’s Zika-related microcephaly clusters, multiple factors may have converged to shape the observed heterogeneity of the cases of mother-to-offspring transmission that arises from Zika’s mosquito inoculation and sexual transmission.…”