CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Familial Multiple Fetal Cerebral Arteriovenous Malformations: A Case Report of Maternal Genetic Susceptibility and Fetal Manifestation
Provisionally accepted
- Chongqing Health Center for Women and Children, Chongqing, China
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Introduction: Cerebral arteriovenous malformations (AVMs) are rare vascular anomalies that can 6 present significant clinical challenges, especially when occurring in multiple sites. Hereditary 7 hemorrhagic telangiectasia (HHT), a genetic disorder may be caused by mutations in genes such as 8 ENG (encoding endoglin) or ACVRL1 (ALK1), and less commonly SMAD4, is one condition that 9 3 predisposes individuals to multiple AVMs. This case report investigates the role of maternal genetic 10 susceptibility in the fetal manifestation of multiple cerebral AVMs. 11 12 Case Presentation: A multiparous woman with embolized pulmonary AVMs underwent high-13 resolution fetal neurosonography at 29+4 weeks for maternal HHT risk and third-trimester screening 14 flags (prominent venous structures). Targeted ultrasound revealed multiple cerebral AVMs with a 15 dilated superior sagittal sinus. Trio-exome identified a heterozygous ENG variant in the mother, 16 Sanger-confirmed and present in the fetus, consistent with direct genetic predisposition. Limb/ear 17 minor anomalies (polydactyly, accessory auricle) prompted syndromic re-analysis (CM-AVM, JP-18 HHT overlap, PI3K-pathway, GLI3), which was negative for additional diagnostic variants. 19 20 Conclusion: This case strengthens the link between familial ENG-mediated HHT and fetal cerebral 21 AVMs, underscores the value of targeted third-trimester neurosonography in at-risk pregnancies, and 22 clarifies variant-level evidence supporting causality.
Keywords: Fetal multiple cerebral, Multiple cerebral arteriovenous, whole exome sequencing, maternal genetic susceptibility, ENG gene variant
Received: 07 Feb 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Wang, Jiang, Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gongli Chen
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