# Cerebrovascular Malformations Associated With Hereditary Hemorrhagic Telangiectasia and HHT‐Like Syndromes: A Comparative Overview

## TL;DR

This paper compares cerebrovascular features of HHT and similar disorders to clarify their distinct risks and diagnostic challenges.

## Contribution

The study provides a detailed comparative overview of cerebrovascular malformations across HHT and HHT-like syndromes, emphasizing diagnostic differentiation.

## Key findings

- Wyburn–Mason syndrome, CM-AVM, and PWS share high-flow AVMs with significant hemorrhagic stroke risk.
- NF1 and PHACE(S) are linked to occlusive arteriopathies and ischemic events rather than hemorrhage.
- KTS, BRBNS, and PHTS show low/mixed-flow anomalies with higher thrombotic risks but lower CNS hemorrhage.

## Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder marked by mucocutaneous telangiectasias, recurrent epistaxis, and visceral arteriovenous malformations (AVMs). Neurologic risks include brain AVMs and hemorrhagic stroke. Several rare genetic and sporadic syndromes (“HHT‐like” syndromes) share overlapping vascular features, complicating diagnosis. Differentiating these conditions is essential for accurate neurovascular risk assessment.

A comprehensive literature review (PubMed, Scopus, Embase, Google Scholar; 1990–2025) targeted cerebrovascular manifestations of HHT and related syndromes. Key entities included Wyburn–Mason syndrome, Cobb syndrome, Klippel–Trénaunay syndrome (KTS), neurofibromatosis type 1 (NF1), PHACE(S) syndrome, capillary malformation–AVM (CM‐AVM), Parkes Weber syndrome (PWS), juvenile polyposis/HHT overlap (JP‐HHT), HHT type 5 (BMP9/GDF2), PTEN hamartoma tumor syndrome (PHTS), and blue rubber bleb nevus syndrome (BRBNS). Data on gene variants, lesion types, neuroimaging, stroke risk, and neurologic outcomes were synthesized.

High‐flow cerebrovascular malformations similar to HHT are prominent in Wyburn–Mason syndrome, CM‐AVM, and PWS, conferring a substantial hemorrhagic stroke risk. NF1 and PHACE(S) primarily feature occlusive arteriopathies linked to ischemic events. KTS, BRBNS, and PHTS predominantly show low‐ or mixed‐flow anomalies with lower CNS hemorrhagic risk but increased thrombotic complications. JP‐HHT carries added gastrointestinal cancer risk via SMAD4 variants, while HHT type 5 often presents incompletely. Genetic testing and tailored neuroimaging are critical for differentiation.

Although many syndromes mimic HHT, few combine mucosal telangiectasias, high‐flow AVMs, and recurrent hemorrhage. Integrating clinical, imaging, and genetic data enables precise diagnosis, risk stratification, and personalized management.

Hereditary hemorrhagic telangiectasia (HHT) and several HHT‐like syndromes, including Wyburn–Mason, Cobb, Klippel–Trénaunay, Parkes Weber, neurofibromatosis type 1, PHACE(S), capillary malformation–AVM (CM‐AVM), Juvenile polyposis/HHT overlap, HHT type 5, PTEN hamartoma tumor syndrome, and blue rubber bleb nevus syndrome, share overlapping cerebrovascular features that complicate diagnosis. This review compares their genetic basis, vascular flow types, and neurologic risks, highlighting distinctions between high‐flow AVMs, occlusive arteriopathies, and low‐ or mixed‐flow malformations.