Neurovascular Manifestations in Pediatric Patients With Hereditary Haemorrhagic Telangiectasia

Roxana Azma; Adam A Dmytriw; Asthik Biswas; Mordechai Pollak; Felix Ratjen; Afsaneh Amirabadi; Helen M Branson; Abhaya V Kulkarni; Peter Dirks; Prakash Muthusami

doi:10.1016/j.pediatrneurol.2021.12.004

Neurovascular Manifestations in Pediatric Patients With Hereditary Haemorrhagic Telangiectasia

Pediatr Neurol. 2022 Apr:129:24-30. doi: 10.1016/j.pediatrneurol.2021.12.004. Epub 2021 Dec 30.

Authors

Affiliations

¹ Department of Diagnostic Imaging & Image-Guided Therapy, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
² Department of Diagnostic Imaging & Image-Guided Therapy, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: adam.dmytriw@sickkids.ca.
³ Division Respiratory Medicine, Department of Pediatrics, Translational Medicine, Research Institute, University of Toronto, Toronto, Ontario, Canada.
⁴ Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

PMID: 35176532
DOI: 10.1016/j.pediatrneurol.2021.12.004

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan vascular dysplasia with limited data regarding its neurovascular manifestations and genotype-phenotype correlation in children. The objective of this study was to describe the neurovascular findings in a large cohort of children with HHT and correlate between phenotype and genotype.

Methods: This retrospective study was conducted on 221 children (<18 years) with a definite or possible diagnosis of HHT based on Curacao criteria, or with positive genetics for the mutated genes of ENG, ACVRL-1, and SMAD-4, who also underwent brain MRI and/or conventional angiography. Demographic and clinical information, imaging findings, and follow up information were gathered.

Results: Two hundred twenty-one children with HHT (70.6% genetically confirmed, and 99.5% positive family history) were included, with a median age of 7 years (interquartile range: 3 to 11 years) and 58.8% male predominance. Neurovascular lesions were found in 64 of 221 (28.9%), with 3.1% prevalence of intracranial hemorrhage. The most commonly observed vascular malformations were developmental venous anomalies (48.5%) and brain arteriovenous malformations (AVMs) (31.2%), followed by capillary malformations (14.1%). Multiple AVMs were seen in 10.0% of the cohort. We found no instances of de novo AVM (1281.8 patient-years).A significantly higher proportion of patients with ENG mutations (19.7%) had brain AVM than those with ACVRL-1 (4.9%) and SMAD-4 (0%) mutations (P < 0.01). There was no significant difference in the hemorrhagic risk of shunting lesions associated with ENG (35.3%) or ACVRL-1 (33.3%) positivity (P = 0.9).

Conclusions: We describe the neurovascular imaging and genetic findings from a large pediatric cohort of HHT, to enhance clinical awareness and guide management of patients with HHT.

Keywords: Brain arteriovenous malformations; Genotype-phenotype correlation; Hereditary hemorrhagic telangiectasia; Magnetic resonance imaging.

MeSH terms

Child
Female
Genetic Association Studies
Humans
Intracranial Arteriovenous Malformations* / diagnostic imaging
Intracranial Arteriovenous Malformations* / epidemiology
Intracranial Arteriovenous Malformations* / genetics
Male
Phenotype
Retrospective Studies
Telangiectasia, Hereditary Hemorrhagic* / complications
Telangiectasia, Hereditary Hemorrhagic* / diagnostic imaging
Telangiectasia, Hereditary Hemorrhagic* / epidemiology