10.
BackgroundThe collagen type IV alpha 1 chain (COL4A1) is an essential component of the basement membrane in small vessels. Pathogenic variants in
COL4A1 cause perinatal cerebral hemorrhages in an autosomal-dominant fashion. However, little is known about the long-term outcomes of patients with mildly affecting
COL4A1 mutations.
Case reportWe report a 17-year-old boy, who presented with recurrent intracranial hemorrhages in the periventricular white matter. He had been followed-up as a child with cerebral palsy bearing intracranial calcifications, developmental delay and epilepsy. Screening tests in infancy provided negative results for intrauterine infections. Severe motor and cognitive deficits persisted after admission. Carbazochrome was introduced on day 19 of admission, which appeared to prevent extension and reactivation of cerebral hemorrhages for over 6 months after discharge.
ResultsTargeted sequencing of
NOTCH3 and TREX1 excluded causal mutations in these genes. The whole-exome sequencing revealed that he carried a
de novo mutation in
COL4A1 (p.Gly696Ser). An overview of the literature for 345 cases with
COL4A1 mutations supported evidence that p.Gly696Ser is associated with the unique phenotype of late-onset hemorrhage among patients with
COL4A1-associated cerebral angiopathy.
ConclusionsThis case first demonstrates that infants with
COL4A1-associated leukoencephalopathy and calcifications have a risk for developing the rupture of small vessels in the cerebral white matter after 10 years of age.
相似文献