Neonatal Aneurysm Rupture in a Child with a De Novo Variant to ANKRD17

Abstract

Ankyrin repeat domain 17 (ANKRD17) is postulated to play a role in the integrity of blood vessels and has been reported to be associated with developmental delays, epilepsy, and growth restriction. Whereas ANKRD17-deficient mice have been demonstrated to experience catastrophic hemorrhages, vascular malformations have not been reported in human patients with pathogenic variants to ANKRD17. We report a term male neonate with a heterozygous de novo variant to ANKRD17 (ANKRD17; c6988 C > G, P.[P2330a]) who experienced subarachnoid hemorrhage from a ruptured aneurysm involving the left middle cerebral artery. He experienced acute symptomatic seizures and required clipping of his aneurysm at 35 days of life, later progressing to developing multifocal drug-resistant epilepsy. To our knowledge, this case represents the first report of a cerebrovascular malformation from a patient with ANKRD17. Further work is needed to investigate whether pathogenic variants to ANKRD17 can lead to cerebral aneurysms or other cerebrovascular malformations in children.

A case of Chopra-Amiel-Gordon syndrome with a novel heterozygous variant in the ANKRD17 gene: A case report

“…Majority of cases represent de novo mutations; however several instances of familial inheritance has been also described. 1,2 Here, we report an additional case of CAGS in a patient with previously unreported heterozygous missense variant in ANKRD17 gene. Detailed description of clinical manifestations and diagnosis are presented.…”

“… 4 ANKRD17-deficient mice models demonstrated abnormalities of embryonic development and hemorrhages with lethality. 4 Silverstein et al 2 reported a male neonate with a heterozygous missense de novo variant in ANKRD17 who experienced subarachnoid hemorrhage from a ruptured aneurysm. However, further functional analyses are needed to confirm its role in causation of cerebrovascular malformations and hemorrhages.…”

“… 1 A single case of ruptured cerebrovascular aneurysm occurring during the neonatal period has been also reported in CAGS. 2 CAGS is caused by heterozygous loss-of-function pathogenic variants in the ANKRD17 (NM_032217.4) located on chromosome 4q13. ANKRD17 encodes ankyrin repeat domain-containing protein 17 (ANKRD17).…”