Genotype-Phenotype Correlations in Children with HHT.

Area of Science:

• Genetics
• Pediatrics
• Vascular Biology

Background:

• Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant disorder.
• HHT is characterized by vascular malformations (VMs) and mutations in ENG, ACVRL1, and SMAD4 genes.
• Genotype-phenotype correlations are established in adults but less understood in children.

Purpose of the Study:

• To investigate genotype-phenotype correlations in pediatric HHT patients.
• To identify specific genetic mutations associated with distinct clinical presentations in children.
• To compare pediatric findings with established adult HHT correlations.

Main Methods:

• Analysis of demographic, clinical, and genetic data from 205 pediatric HHT patients.
• Utilized a chi-square test to assess associations between genotypes and phenotypes.
• Data collected through the multicenter Brain Vascular Malformation Consortium HHT Project.

Main Results:

• ENG mutations were significantly associated with pulmonary AVMs (p < 0.001) and brain VMs (p < 0.001).
• A combined phenotype of pulmonary and brain VMs was also linked to ENG mutations.
• Gastrointestinal bleeding, though rare (4.4%), was associated with SMAD4 genotype (p < 0.001).

Conclusions:

• Genotype-phenotype correlations in pediatric HHT patients mirror those in adults.
• Pediatric patients with ENG mutations exhibit a higher prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.
• These findings aid in understanding HHT heterogeneity and guiding clinical management in children.