Capillary Malformation-Arteriovenous Malformation Syndrome Associated with RASA1 and EPHB4 Mutations: Comparative...

Area of Science:

• Vascular biology
• Genetics
• Neonatology

Background:

• Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare vascular disorder.
• Caused by RASA1 and/or EPHB4 gene mutations, it leads to complex vascular malformations.
• Neonatal intracranial arteriovenous shunts are exceptionally rare in CM-AVM.

Purpose of the Study:

• To report three neonates with early-onset high-flow shunts.
• To analyze distinct genetic signatures (RASA1, EPHB4, dual mutations) and their genotype-phenotype spectrum.
• To emphasize early multimodal hemodynamic evaluation for managing life-threatening shunts.

Main Methods:

• Clinical case series of three neonates with CM-AVM.
• Analysis of clinical evolution, Doppler ultrasound, EEG, and MRI data.
• Genetic analysis to identify RASA1 and EPHB4 mutations.

Main Results:

• Three distinct genetic profiles were identified: CM-AVM1 (RASA1), CM-AVM2 (EPHB4), and dual variant (RASA1 + EPHB4).
• Early-onset high-flow shunts were observed in all three neonates.
• Multimodal evaluation facilitated comparison of genotype-phenotype correlations.

Conclusions:

• Early multimodal hemodynamic evaluation is crucial for identifying and managing neonatal shunts in CM-AVM.
• Distinct genetic mutations in RASA1 and EPHB4 contribute to a varied CM-AVM phenotype.
• This study expands understanding of rare neonatal presentations and genetic variations in CM-AVM.