Cyclopia in a newborn rhesus macaque born to a dam infected with SIV and receiving antiretroviral therapy during pregnancy.

Abstract

Cyclopia, a rare genetic anomaly and birth defect, was recently observed in our nonhuman primate study. A newborn rhesus macaque, delivered via cesarean section, exhibited facial abnormalities, including a single eye in the middle of the forehead. This macaque was born to a dam who had been inoculated with SIV in the first trimester and received antiretroviral therapy (ART) in the early third trimester of pregnancy. Prenatal ultrasound detected fetal defects, including the fusion of the thalami and absence of third ventricle during the third trimester of fetal development. Remarkably, the newborn macaque was diagnosed with severe alobar holoprosencephaly, characterized by a single eye located on the facial midline and proboscises positioned above and below the eye. This condition was accompanied by the absence of a nose, mouth, mandible, maxilla, nasal and oral cavities, tongue, as well as the esophagus. Subsequent genetic screening identified a significant down-regulation of craniofacial development-associated genes, although genetic mutations in the sonic hedgehog gene (SHH) were not present. As the fetal defects were identified prior to the initiation of antiretroviral therapy, it is possible that other environmental factors may have contributed to the development of cyclopia in this rhesus case. However, the etiology of this congenital HPE case remains essentially unknown.