Spectrum of Fetal Intraparenchymal Hemorrhage in COL4A1/A2-Related Disorders

Pediatr Neurol. 2023 Oct:147:63-67. doi: 10.1016/j.pediatrneurol.2023.07.008. Epub 2023 Jul 18.

Abstract

Background: COL4A1/A2 variants affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a cause of fetal and neonatal intracranial hemorrhage, porencephaly, and schizencephaly. Fetal magnetic resonance imaging (MRI) findings in COL4A1/A2-related disorders are not well characterized.

Methods: This is a retrospective case series of fetal MRI findings in eight patients with intraparenchymal hemorrhage (IPH) and COL4A1/A2 variants, five of whom have postnatal imaging and clinical follow-up.

Results: IPH was multifocal and bilateral in four of eight patients. IPH involved the frontal lobes in all cases and basal ganglia in six of eight. The median maximum diameter of IPH was 16 mm (range 6 to 65 mm). All patients had ventriculomegaly, and four of eight had intraventricular hemorrhage. Prenatal IPH size correlated clinically with motor outcomes, and none had clinically symptomatic recurrent hemorrhage.

Conclusion: COL4A1/A2 variants can present with a spectrum of IPH prenatally, including small and/or unifocal IPH, as well as multifocal and bilateral IPH, involving the frontal lobes and basal ganglia. Given the wide spectrum of IPH severity seen on fetal brain MRI, genetic testing for COL4A1/A2 variants should be considered in all cases of fetal IPH.

Keywords: COL4A1/2; Fetal MRI; Genetic; Intracranial hemorrhage; Vasculopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / genetics
  • Collagen Type IV / genetics
  • Female
  • Fetal Diseases* / diagnostic imaging
  • Fetal Diseases* / genetics
  • Humans
  • Infant, Newborn
  • Intracranial Hemorrhages* / diagnostic imaging
  • Intracranial Hemorrhages* / genetics
  • Magnetic Resonance Imaging / methods
  • Pregnancy
  • Retrospective Studies

Substances

  • Collagen Type IV
  • COL4A1 protein, human