Fetal intracranial hemorrhage represents a rare event with an estimated prevalence of 1:10 000 pregnancies. We report a patient diagnosed prenatally with intracranial hemorrhage and ventriculomegaly carrying a novel, previously unreported, likely pathogenic variant in COL4A1. At the gestational age of 27 weeks, dilation of lateral ventricles was detected during a routine prenatal ultrasound scan, confirmed by prenatal MRI at 30 + 3 weeks of gestation. Prenatal examinations included amniocentesis with conventional G-band karyotyping and arrayCGH, and maternal testing for TORCH and parvovirus B19 infections. Virtual gene panel based on whole-exome sequencing data was performed postnatally. At the age of 2.5 months, the patient manifested epileptic seizures that remain difficult to control. Postnatal MRI showed partial thalamic fusion and polymicrogyria, in addition to severe enlargement of lateral ventricles, multiple deposits of hemosiderin in cerebral and cerebellar hemispheres, and thin optic nerve and chiasma. Virtual gene panel based on whole-exome sequencing data led to a detection of a de novo previously unreported in-frame deletion NM_001845.5:c.4688_4711del in COL4A1 located in the highly conserved NC1 domain initiating collagen helix assembly. The presented case lies one a more severe end of the COL4A1 mutation-related disease spectrum, manifesting as fetal intracranial bleeding, malformation of cortical development, drug-resistant epilepsy, and developmental delay.

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University and Motol University Hospital Full Member of the ERN EpiCARE Prague Czech Republic

Department of Neonatology Thomayer University Hospital Prague Czech Republic

Department of Neurosurgery 2nd Faculty of Medicine Charles University and Motol University Hospital Full Member of the ERN EpiCARE Prague Czech Republic

Department of Obstetrics and Gynaecology Neonatal Unit 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Paediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Full Member of the ERN EpiCARE Prague Czech Republic

Department of Pathological Physiology 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Radiology 2nd Faculty of Medicine Charles University and Motol University Hospital Full Member of the ERN EpiCARE Prague Czech Republic

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