Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension

N/ANot Yet RecruitingNCT07314814

Prof. Valérie Mc Lin120 enrolled

Overview

Congenital portosystemic shunt (CPSS) are rare vascular malformations causing blood from the intestines to bypass the liver and directly flow into body's general circulation. Such liver bypass can cause several health problems, one of the most severe being portopulmonary hypertension (PoPH). The goal of this study is to identify pathogenic and potentially pathogenic genetic variants in patients who have both CPSS and PoPH. Future research will assess the contribution of these genetic variants to the development of PoPH. The long-term goal is to use genetic information to identify patients with congenital portosystemic shunts (CPSS) or chronic liver disease who are at risk of developing PoPH to offer anticipatory management. Children and adult patients with both CPSS and PoPH, as well as their close relatives (patient's parents and siblings) can take part in the study. Genetic variations within each family will be studied.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

Portopulmonary Hypertension Pulmonary Arterial Hypertension (PAH)Congenital Portosystemic Shunt

Interventions

Eligibility

Sex: ALLMin age: 1 DayMax age: 99 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Patient is a participant to the IRCPSS with history of PoPH * Trios composed of CPSS PoPH patients and their parents (trios are mandatory) * Brother/sister of an enrolled patient * Trios accept to provide biological samples (blood), sign the inform consent. * Siblings and/or siblings' legal representatives accept to provide biological samples (blood), sign the inform consent. Exclusion Criteria: * Trio condition is not met. * No genuine parent-offspring trios (check for medically assisted procreation with donors, and adoption) * For siblings, half-brothers or half-sisters are excluded, as well as adopted children, or children issued from medically assisted procreation with donors. * Secondary portosystemic shunts * The refusal by the patient or the patient's legal representatives to provide biological samples or agree with the proposed procedure or after voluntary withdrawal from the project. * The refusal of one of the parents to provide biological samples or to agree with the proposed procedure or after voluntary withdrawal from the project.

Outcomes

Primary Outcomes

List of variants from targeted analysis of selected gene panels

presence/absence of pathogenic variants in known genes (pulmonary arterial hypertension ; hereditary hemorrhagic telangiectasia ; congenital heart disease) and potentially pathogenic variants in genes previously associated with PoPH in cirrhosis cohort.

Time frame: From February 2026 to February 2029

List of variants from whole genome analysis

variants identified using family based search for dominant or recessive potentially pathogenic variants

Time frame: Fron February 2026 to August 2029

Central Contacts

Prof. Dr. med Valérie A McLIn, MD

CONTACT

+41223724545 valerie.mclin@hug.ch

Dr. phil. nat Isabelle Schepens, PhD