Fowler vasculopathy

Fowler vasculopathy, also known as proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome, is an extremely rare and lethal autosomal recessive disorder affecting the developing central nervous system. It is characterized by a distinctive proliferative glomeruloid vasculopathy — an abnormal overgrowth of blood vessel tissue in the brain — that leads to severe destruction of brain tissue during fetal development. The condition results in hydranencephaly (absence of the cerebral hemispheres, replaced by fluid) or severe hydrocephalus, along with other brain malformations. The disease is caused by biallelic pathogenic variants in the FLVCR2 gene (also known as SLC49A2), located on chromosome 14q24.3. This gene encodes a transmembrane transporter protein believed to play a critical role in vascular development in the central nervous system. The hallmark pathological finding is a proliferative vasculopathy with glomeruloid bodies in the leptomeningeal and cortical blood vessels, which distinguishes this condition from other causes of hydranencephaly. Fowler vasculopathy typically presents prenatally or at birth. Affected fetuses may show polyhydramnios, arthrogryposis (joint contractures due to reduced fetal movement), and severe brain abnormalities detectable on prenatal ultrasound. The condition is invariably fatal, with most affected individuals being stillborn or dying shortly after birth. There is no curative treatment available. Management is limited to supportive care and genetic counseling for affected families. Prenatal diagnosis is possible through molecular genetic testing when the familial variants are known.

Common questions about Fowler vasculopathy