GENPHENACL: Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families.

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT02970266

Collaborator

(none)

659

Enrollment

Location

Duration (Months)

8.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objectives of this study are:

Improve genetic counseling by establishment of prevalences of each of genetic subtypes within a expanded population of patients with LCA taking into account ethnicity of families.
Confirm, refine or modify the genotype-phenotype correlations.
Edit important recommendations for:

The clinical and paraclinical exploration of a new patient based on genotype, especially for extraocular explorations, to book at certain genetic subtypes
Prenatal care of a couple.
Directing families to a therapeutic protocol in progress or in development.

Individualize a panel of families without a mutation in the known genes and identify new genes responsible.

Condition or Disease	Intervention/Treatment	Phase
Leber Congenital Amaurosis

Detailed Description

This study characterize the clinical history of the disease (age and start mode of visual disturbances, rate and mode of progress of disease), careful assessment of retina function and finally, in search of the mutations responsible for this condition.

A full ophthalmic check-up, one at the inclusion and 24 months :

- A genetic consultation taking account of family history and establishment of family tree with precision of geographical origin of birth of ascendants.
- A thorough ophthalmologic examination by a referring medical ophthalmologist, including:

2.1 - An interrogation on the development of the visual awakening since the birth and its possible disturbances.

2.2 - The search for abnormal movements of the eyeballs, and difficulties with regard to different lighting.

2.3 - Visual field evaluation Survey.

2.4 - The study of color vision.

2.5 - The search for a refractive disorder with the automatic refractometer.

2.6 - Measurement of Visual acuity for near and distance.

2.7 - Examination of the eyeball as a whole, examination of the anterior chamber of the eye by the slit lamp.

2.8 - Taking pictures of the fundus of the eye after pupillary dilation.

2.9 - An autofluorescence search using a Scanning Laser Ophthalmoscopy (SLO).

2.10 - Optical Coherence Tomography (OCT) which used to assess the thickness of each of retinal layers.

2.11 - Electrophysiological examination, Electroretinogram (ERG) that allows to record the functional value of the retina.

These two latter examinations last on average 10 minutes after dilation of the pupil.

- A blood sample of 10 milliliters to carry out genetic studies to identify the gene responsible for this condition and genetic counseling refined by taking account the results of this study.

Intermediate visit M12: only for patients younger than 6 years of age on inclusion.

Study Design

Study Type:

Observational

Actual Enrollment :

659 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families: Establishment of Genotype-phenotype Correlations and Updating the Clinical Definition of This Retinal Dystrophy

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Nov 1, 2016

Outcome Measures

Primary Outcome Measures

Improve genetic counseling by establishment of prevalences of each of genetic subtypes within a expanded population of patients with LCA. [24 MONTHS]

Secondary Outcome Measures

Measurement of visual acuity using the logarithmic scale for children under 5 [24 MONTHS]
Measurement of visual acuity using Early Treatment Diabetic Retinopathy Study scale (ETDRS) for far vision [24 MONTHS]
The "Parinaud Scale" for near vision (After the age of 6) [24 MONTHS]
Visual field evaluation Survey [24 MONTHS]
Measurement of refraction by portable automatic refractometer. [24 MONTHS]
Screening for color vision abnormalities using "children's boards" of "Ishihara Test" from the age of 3-4. [24 MONTHS]
Screening for color vision abnormalities using "regular boards" as soon as learning to read figures from the age of five. [24 MONTHS]
Test the color vision deficiency using the " Farnsworth test" in adults and children after the age of 6. [24 MONTHS]
The visual field test using the Goldman dome in adults and children aged 6 to 7. [24 MONTHS]
Electrophysiological examination using Electroretinogram. [24 MONTHS]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients:

Patients of all ages
Patients with symptoms the day of the first consultation allowing to ask the diagnosis of leber congenital amaurosis.
Are affiliated to a social health care.
Written informed consent must be given by patients or holders parental authority for minors.

patients and siblings: