Novel mutation in ENG causes autosomal dominant isolated cerebral arteriovenous malformation at young age

Background/Objectives: Cerebral arteriovenous malformation (CAVM) constitute abnormal vessels shunting blood from the arterial to the venous circulation, resulting in high flow lesions prone to rupture. CAVMs account for ~2% of all haemorrhagic strokes. Most CAVM cases are sporadic, although few are due to autosomal dominant inheritance of a genetic mutation, most commonly in the context of Hereditary Hemorrhagic Telangiectasia (HHT), an autosomal dominant genetic disorder characterized by epistaxis, telangiectasias, and multiorgan vascular dysplasia. We studied a case of father and daughter with isolated CAVM ruptures at young age, aiming to identify mutations that cause CAVM.
Methods: Magnetic resonance angiography, whole exome sequencing and validation through PCR and Sanger sequencing.

Results: A father and daughter presented with isolated CAVM, with ruptures at an early age. Both were examined clinically and did not present telangiectasias. A frameshift mutation in ENG (endoglin) chr9:127816006 AG>A HET. (hg38) was found in both affected father and daughter.
Conclusion: Mutations in ENG have been reported to cause HHT1, a subtype of HHT with higher risk for developing CAVM than other subtypes of the disease. This new mutation is unique in causing CAVM at a very young age and without skin presentation of telangiectasias. Thus, genetic testing is important for diagnosis of HHT in families with history of isolated CAVM ruptures.