Clinical trial NCT02881671: Identification of Genetic Basis of Atrioventricular Conduction Defects: From Congenital Forms to Degenerative Forms
Official title: Identification of Genetic Basis of Atrioventricular Conduction Defects: From Congenital Forms to Degenerative Forms
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Congenital Complete Heart Block
Cardiac Conduction Defect Progressive
Keywords: genetic
congenital atrioventricular block
progressive Cardiac Conduction Disease
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2016-08-29
Enrollment: 2600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of both sex with Atrioventricular Conduction Defects and relatives examined during familial screening

Brief summary: Identification of genes involved in congenital atrioventricular block and progressive Cardiac Conduction Disease.

Detailed description: Atrioventricular blocks are a heterogenous group of diseases involving children with congenital atrioventricular block (CAB) and more frequently elderly patients affected by progressive Cardiac Conduction Disease (PCCD).

The aim of the study is to uncover the genetic model, likely more complex than previously appreciated, and characterize the gene expression remodelling leading to high degree of conduction defect.

The recent technological developments in genomics coupled to the availability of large and highly characterized biobanks of patients have now set the stage:

1. To identify rare genetic variants/new genes contributing to CAB and PCCD by exome sequencing on familial form suspected to impact strongly the phenotype
2. To identify common genetic variants modulating the risk of developing (severe) PCCD by GWAS
3. To estimate the prevalence and relevance of genes uncovered by TASK#1, #2 in large patient sets (PCCD and CAB) by NGS.

Eligibility criteria: Congenital atrioventricular block inclusion criteria:

* Patients with idiopathic congenital atrioventricular block diagnosed before the age of 15 years.
* Non-immune congenital atrioventricular block documented by a maternal serology (negative for anti-nuclear antibodies or anti Ro-SSA antibodies and anti La-SSB antibodies)
* Written consent to participate to the study and written consent of both parents.
* Parents of children with idiopathic congenital atrioventricular block.

Congenital atrioventricular block exclusion criteria

* Positive maternal serology
* Patients or parents who are unable to sign or who refuse to sign an informed consent

Progressive Cardiac Conduction Disease inclusion criteria

* Patients with isolated cardiac conduction disorder with a normal morphology of the heart confirmed by echocardiography.
* Relatives of patients with isolated cardiac conduction disorder
* Written consent to participate to the study

Progressive Cardiac Conduction Disease exclusion criteria

* Patients with cardiac conduction disorder associated with a structural cardiopathy or due to an identified cause
* Patients who are unable to sign or who refuse to sign an informed consent

Primary outcomes:
measure: Identification of genetic variations responsible of Atrioventricular Conduction Defects
timeFrame: inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Nantes
country: France
facility: Chu Nantes
city: Rennes
country: France
facility: Chu Rennes
Study officials:
affiliation: Nantes University Hospital
name: vincent PROBST, MD-PHD
role: PRINCIPAL_INVESTIGATOR
References: