Validation of the RADIAL Algorithm for Diagnosis of Autosomal Recessive Cerebellar Ataxia

University Hospital, Strasbourg, France400 enrolled

Overview

RADIAL is an algorithm which has been developed following a review of the literature on 67 autosomal recessive cerebellar ataxias (ARCA) and personal clinical experience. Frequency and specificity of each feature were defined for each autosomal recessive cerebellar ataxia, and corresponding prediction scores were assigned. Clinical and paraclinical features of patients are entered into the algorithm, and a patient's total score for each ARCA is calculated, producing a ranking of possible diagnoses. Sensitivity and specificity of the algorithm were assessed by blinded analysis of a multinational cohort of 834 patients with molecularly confirmed autosomal recessive cerebellar ataxia. The performance of the algorithm was assessed versus a blinded panel of autosomal recessive cerebellar ataxia experts. The correct diagnosis was ranked within the top 3 highest-scoring diagnoses at a sensitivity and specificity of \>90% for 84% and 91% of the evaluated genes, respectively. Mean sensitivity and specificity of the top 3 highest-scoring diagnoses were 92% and 95%, respectively. Our aim is now to validate in a prospective cohort of ARCA, the performance of RADIAL to predict the correct genetic diagnosis.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

400

Conditions

Autosomal Recessive Cerebellar Ataxia

Eligibility

Sex: ALLMin age: 5 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: \- For patients: 1. Patient, male or female, over 5 years old (no upper age limit) 2. Patient with cerebellar ataxia who started before the age of 40 3. Patient with a family history compatible with autosomal recessive inheritance (sporadic case, consanguinity, several cases in siblings) 4. Patient in which an acquired cause of cerebellar ataxia has been excluded 5. Patient whose genetic diagnosis is unknown (NB: patients with a known negative result for the Friedreich's disease gene are eligible for inclusion)) 6. For patients over 18 years old: patient speaking and reading French, able to give a signed and dated informed consent to participate in the study. Patients who have reached the age of majority and whose DNA has been banked and who have signed a consent form authorizing the subsequent use of this DNA for research purposes, including genetic analysis of cerebellar ataxias or associated pathologies, and for whom the RADIAL information sheet can be completed in full, are eligible for inclusion. 7. For patient under 18 years old: Tutor or person with parental authority must speak French and be able to give a signed and dated informed consent for the minor patient. Patients who are minors, whose DNA has been banked and for whom the parental authority has signed a consent form authorizing the subsequent use of this DNA for research purposes, including genetic analysis of cerebellar ataxias or associated pathologies, and for whom the RADIAL information sheet can be completed, are eligible. 8. Patient affiliated to the French national health insurance \- For relatives: 9. Male or female, over 18 years old (no upper age limit) 10. Biological father or mother of a patient included in RADIAL-VALID research protocol 11. (for prospective inclusion only) To be available for a visit to the participating center where the child is being followed 12. Speaking and reading French, able to give a signed and dated informed consent to participate in the study 13. Subject affiliated to the French national health insurance Exclusion Criteria: \- For patients: 14. Patient in whom targeted sequencing of a panel of PMDA genes and/or exome/genome sequencing have already been performed. * For patients and related: 15. Subject of a legal protection measure 16. Subject in exclusion period (determined by previous or current study)

Locations (8)

CHU de Besancon- Neurology

Besançon, France

RECRUITING

CHU de Dijon- Neurology

Dijon, France

RECRUITING

CHU Lille- Neurology

Lille, France

NOT_YET_RECRUITING

CHU Marseille- Neurology

Marseille, France

RECRUITING

CHU Montpellier - Neurology

Montpellier, France

RECRUITING

CHU Nancy- Neurology

Nancy, France

RECRUITING

CHRU de Strasbourg - Neurology/Pediatrics

Strasbourg, France

RECRUITING

CHU Toulouse- Neurology

Toulouse, France

RECRUITING

Outcomes

Primary Outcomes

Percentage of patients for whom the final genetic diagnosis is in the top 3 of the diagnoses proposed by the RADIAL algorithm (corresponding to the diseases with the 3 highest score given by the algorithm).

The final diagnosis will be established after a genetic analysis and a medical interpretation of the results by geneticists.