Introduction:

COL4A1 mutations hereditary vasculopathies are rarely diagnosed in neonates. Mechanisms for variable expressivity are poorly understood. Main phenotypes include familial porencephaly, retinal haemorrhages and hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome (HANAC). We describe unusual combination of fetal IVH, retinal bleeds and cataracts due to a novel mutation.

Case:

A 38 year old Primi delivered a 38+4 weeks gestation, 3.24 kg male (HC 35.3 cm) newborn by emergency caesarean for sub-optimal CTG. Pregnancy was uneventful with normal 20 week anomaly scan. No history of maternal trauma, illness, substance use or early strokes. Ultrasound scan at 30 weeks showed ventriculomegaly. Fetal MRI at 35 weeks showed ventriculomegaly due to IVH.

Baby needed resuscitation (APGARs 2 at 1 & 9 at 5 minutes) and fluid bolus. Bilateral retinal haemorrhages and posterior lenticonus were noted.

The clotting screen, platelets, infective and metabolic work up were normal. Postnatal MRI brain (day 5) showed bilateral porencephaly, abnormal internal capsule posterior limb, atrophy of basal ganglia and thalami, most likely due to fetal IVH.

Chromosomal analysis showed a novel COL4A1 missense heterozygous disease causing variant c.2546G>A [p.(Gly849Glu)] on Exon 32.

He has developmental delay at 1 year. He had bilateral lensectomy and vitrectomy for cataracts and posterior lenticonus. Family had genetic counselling.

Conclusion:

Combination of fetal IVH and porencephaly with eye disease due to COL4A1 mutation is rarely diagnosed. COL4A1 mutation should be done in all cases of fetal IVH.