Brain pathology in an infant with PROKR2 microduplication: A case report

Abstract

Overexpression of prokineticins and their receptors is increasingly recognized as a contributing factor in heart failure and often fatal myocyte necrosis. Activation of prokineticin pathways is typically triggered by cerebral hypoxia and ischemia, viral and bacterial infections, inflammatory and immune responses, or energy deprivation leading to cell apoptosis. However, experimental models have demonstrated that prokineticin pathway activation can also occur independently due to aberrant expressions of specific microduplicated/microdeleted genes. Although prokineticins may play a causal role in cardiac death in adults and children with abnormalities of accessory pathways between the atria and ventricles, they have never been reported to cause brain injuries, especially in neonates. This report describes an infant born with facial dysmorphisms and moderate hypoxic distress at birth but without evidence of atrioventricular conduction defects, viral or bacterial infections, or severe metabolic dysfunction. Despite these findings, neuropathologic examination following the infant’s death at 5 months revealed recent necrotic foci in the cerebral cortex and, in particular, older brain lesions with features indicative of metabolic energy failure in subcortical structures. Genetic analysis identified a rare prokineticin receptor 2 (PROKR2) gene microduplication, which, in the absence of other identifiable causes, is strongly implicated as a contributing factor in the observed chronic brain lesions. These findings suggest that PROKR2 gene microduplication may contribute to unexplained neonatal brain injury, warranting further investigation.

Keywords

Prokineticin receptor 2 / Microduplication / Heart failure / Cerebral necrosis / Cardiac injury

Acknowledgments

None.

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

Author contributions

Conceptualization: All authors

Investigation: All authors

Writing - original draft: All authors

Writing - review & editing: All authors

Ethics approval and consent to participate

The manuscript did not need the approval of the Ethical Committee of our University Administration as this is not a requirement for the publication of a single case provided that it is of definite interest to the scientific community (Regulations of the Ethical Committee of “Area Vasta Emilia Nord,” Italy, approved on September 22, 2020).

Consent for publication

Informed consent for publishing his/her data was obtained verbally from the mother, and patient anonymity was maintained.

Availability of data

Data and materials are available from the authors upon reasonable request.

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