Abstract TMP23: Fetal Intraparenchymal Hemorrhage In Col4a1/2-related Disorders

Abstract

Introduction: COL4A1/A2 mutations affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a potential cause of intracranial hemorrhage across the lifespan. We aim to describe fetal MRI findings and clinical outcomes in seven cases of fetal intraparenchymal hemorrhage (IPH) associated with COL4A1/A2 mutations. Methods: Subjects with COL4A1/A2 mutations were identified from a retrospective single-center cohort study of fetal IPH identified on fetal brain MRI between 1998-2021. Imaging findings were reviewed by two pediatric neuroradiologists, and clinical data were collected from electronic medical records. Results: Among the seven subjects with fetal IPH and COL4A1/A2 mutations, fetal MRI was performed at median gestational age (GA) 29 weeks (range 22-36 weeks) and demonstrated supratentorial IPH in 7/7 with variable size of hemorrhage, including 4/7 with multifocal hemorrhage (Figure 1). Four fetuses were liveborn at median GA 39 weeks (range 33-42 weeks); three pregnancies were terminated. Postnatal imaging revealed recurrent IPH in 1/4 cases, but no cases had recurrent IPH after the neonatal period. None of the seven cases had known family history of COL4A1/A2 or IPH; genetic testing revealed 5/7 with COL4A1 mutation, 1/7 with COL4A2 mutation, and 1/7 with 13q34 deletion with associated loss of COL4A1 and COL4A2 genes. Clinical follow-up data was available for the four liveborn cases through ≥12 months; three had mild hemiplegic cerebral palsy and one had severe spastic quadriplegia. None required CSF diversion, none had epilepsy, and one had visual impairment. Conclusions: Our series suggests that COL4A1/A2 mutations can present as fetal IPH with a wide range of phenotypes ranging from unifocal to multifocal IPH without additional systemic involvement, and that prenatal imaging severity may be associated with early clinical outcomes. COL4A1/A2 testing should be considered in all cases of prenatal IPH, regardless of severity.