Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension (Gen-PoPH-CPSS)

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 Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension (PAH); Portopulmonary Hypertension; Congenital Portosystemic Shunt
• Intervention / Treatment: Genetic: targeted gene panels analysis; Genetic: whole genome analysis

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Prof. Dr. med Valérie A McLIn, MD; Phone Number: +41223724545; Email: valerie.mclin@hug.ch
• Study Contact Backup: Name: Dr. phil. nat Isabelle Schepens, PhD; Phone Number: +41223724545; Email: isabelle.schepens@hug.ch

Study Locations

• Switzerland
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1205
      • University Hospitals Geneva / University of Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patient participant in the IRCPSS, with history of CPSS and PoPH ; both parents of the patient participants; possibly patient siblings.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

30 families; patient + parents+ siblings

Genetic: targeted gene panels analysis; The following gene panels will be analyzed : pulmonary arterial hypertension ; hereditary hemorrhagic telangiectasia ; congenital heart disease and potentially pathogenic variants in genes previously associated with PoPH in cirrhosis cohort.; Genetic: whole genome analysis; Family-based identification of dominant or recessive potentially pathogenic variants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Fron February 2026 to August 2029

Collaborators and Investigators

• Sponsor: Prof. Valérie Mc Lin

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: December 18, 2025
• First Posted (Estimated): January 2, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Genetic; Genomic; PAH; CPSS; PoPH; IRCPSS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Vascular Malformations; Hypertension, Pulmonary; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pulmonary Arterial Hypertension; Congenital Portosystemic Shunt; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Public Health; Environment and Public Health; Genetic Techniques; Sequence Analysis; Molecular Epidemiology; Genetic Association Studies; Oligonucleotide Array Sequence Analysis; Genome-Wide Association Study
• Other Study ID Numbers: 2024-01698 (Other Identifier: Commission Cantonale d'Ethique de la Recherche (CCER) , Geneva Switzerland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: to be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No