The phenotypic spectrum of congenital Zika syndrome

Am J Med Genet A. 2017 Apr;173(4):841-857. doi: 10.1002/ajmg.a.38170.

Abstract

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

Keywords: Zika virus; congenital Zika infection; congenital Zika sequence; congenital Zika syndrome; disruption; disruptive sequence; dysmorphology; fetal brain disruption sequence; teratogen; teratology.

MeSH terms

  • Antibodies, Viral / cerebrospinal fluid
  • Brain / abnormalities
  • Brain / virology
  • Brazil / epidemiology
  • Disease Outbreaks*
  • Female
  • Fetal Diseases / diagnostic imaging
  • Fetal Diseases / epidemiology*
  • Fetal Diseases / pathology
  • Fetus
  • Humans
  • Immunoglobulin G / cerebrospinal fluid
  • Infant
  • Microcephaly / complications
  • Microcephaly / diagnostic imaging
  • Microcephaly / epidemiology*
  • Microcephaly / pathology
  • Neuroimaging
  • Pregnancy
  • Pregnancy Complications, Infectious / diagnosis
  • Pregnancy Complications, Infectious / epidemiology*
  • Pregnancy Complications, Infectious / pathology
  • Syndrome
  • Zika Virus / growth & development
  • Zika Virus / immunology
  • Zika Virus / pathogenicity
  • Zika Virus Infection / complications
  • Zika Virus Infection / diagnostic imaging
  • Zika Virus Infection / epidemiology*
  • Zika Virus Infection / pathology

Substances

  • Antibodies, Viral
  • Immunoglobulin G