Genetic Predisposition in Cerebral Palsy

Study Overview
=================
Brief Summary
-----------------
Cerebral palsy (CP) is a major neurodevelopmental disorder with an estimated prevalence of approximately one in 500 children. It is characterised by permanent developmental disorders of movement and posture, responsible for activity limitations, caused by non-progressive damage to the brain of the fetus, newborn or infant during development. The neurobiological mechanisms involved in CP remain poorly understood, although the interruption of cerebral oxygen supply during pregnancy or at the time of delivery is classically considered to be the main factor causing neurodevelopmental sequelae. CP also occurs in full-term infants without a clearly identifiable etiology. Data from the literature suggest the existence of other pathophysiological processes than only acquired brain lesions related to pregnancy and delivery, such as genetic or epigenetic factors. According to some research teams, nearly one third of CP could have a genetic cause or could be favoured by genetic variants. Preliminary research has made significant progress in revealing unusual copy number variants and/or mutations in single genes in children with CP. Several of the identified genes are involved in neurodevelopment and neuronal connectivity. Nevertheless, the identification of these abnormalities in CP may contribute to a better understanding of the pathophysiology of this complex and multifactorial disorder. It could also shed new light on the analysis of medico-legal files and bring encouraging perspectives by targeting new therapeutic interventions. The main hypothesis is that a certain number of cerebral palsies are related to - or favoured by - genetic abnormalities that we will search for with genetic screening tests.

Official Title
-----------------
Genetic Predisposition in Cerebral Palsy

Conditions
-----------------
Cerebral Palsy

Intervention / Treatment
-----------------
* Genetic: Whole-exome sequencing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Child between 2 and 15 years old with a clinical diagnostic of cerebral paralysis with bilateral somatic involvement Child born from 34 SA Agreement of the legal representatives for the genetic study Both parents available for a parental genetic study (if detection of class 3 variant) Affiliation to the social security system Exclusion Criteria: Genetic syndrome identified or malformative or infectious etiologies identified Neonatal encephalopathy criteria in a clear obstetrical etiological context responsible for major perinatal anoxia with Sarnat 2 or 3 Unilateral motor disorders in the term child (congenital hemiplegia)

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: Patients between 2 and 15 years old, born after 34 weeks' gestation, with a diagnosis of cerebral palsy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: children with cerebral palsy<br>Patients between 2 and 15 years old, born after 34 weeks' gestation, with a diagnosis of cerebral palsy. | Genetic: Whole-exome sequencing<br>* The whole-exome sequencing will be performed via a blood sample from a patient with a diagnosis of cerebral palsy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients for whom a significant genetic variant was identified on the exome by the High-throughput sequencing technique after comparison with the databases of human polymorphisms and pathogenic variants up to date during the analysis. | Are considered positive for a significant genetic variant, patients for whom a or several class 4 or 5 variants have been identified, and explain the phenotype of pc. Genetic variants will be classified according to the recommendations of the American College of Genetics Medical (ACMG: American College of Medical Genetics) from 1 to 5. | Until the end of study, an average of 4.5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cerebral Palsy, Genetic predisposition, Neurodevelopmental disorder