Hyperekplexia : Adaptative Skills and Neurodevelopmental Trajectory

Summary

Hereditary hyperekplexia is a rare neuronal disorder, caused by genetic defects leading to dysfunction of glycinergic neurotransmission.

The clinical presentation is characterized by stiffness and exaggerated startle responses to unexpected stimuli, that appear shortly after birth.

The generalised stiffness can lead to apnea and sudden infant death syndrome.

Several genes are known to be associated with hereditary hyperekplexia. The most frequent are Glycine Receptor Alpha 1 (GLRA1), Glycine Receptor Beta (GLRB) and Solute Carrier Family 6 Member 5 (SLC6A5). They encode for the postsynaptic glycine receptor (GLRA1, GLRB) and the presynaptic glycine transport (SLC6A5). Genetic mutations in these genes lead to dysfunction in the glycinergic inhibitory neurotransmission.

The neurodevelopment was initially described as normal, or as delayed due to the motor difficulties. Global development delay and intellectual disability are reported as well, in the most recent studies.

Nevertheless, the degree of severity of the learning difficulties and the adaptive faculties of the patients is not specified.

Similarly, the efficacy of clonazepam in hyperekplexia is well known, but the evolution of dosage over time and the frequency of complete withdrawal have never been studied.

The primary endpoint of this study is to describe adaptive skills using a standardized questionnaire, Vineland Adaptive Behavior Scale (VABS2).

Secondary endpoints are:

* Neurodevelopmental course study
* Description of the evolution of the clinical manifestations over the years
* Evaluation of the efficacity of the treatment CLONAZEPAM, initially and over time, and evolution of the dosage
* Comparison of clinical and therapeutical characteristics according to the genotype

Conditions

• Hyperekplexia

Interventions

OTHER

collection of medical data

The data collected concerns: * Sex * Age * Socio-professional category of patients or parents / level of education of the parents * Family history * Neonatal patient data (pregnancy, childbirth) * Clinical data (age of onset of symptoms, evolution of these symptoms over the years, psychomotor development, schooling, learning difficulties, rehabilitation) * Therapeutic data (treatments tried, their dosage and effectiveness, changes in dosage over the years) * Paraclinical examinations (Magnetic Resonance Imaging (MRI), scanner, Electroencephalography (EEG)) * Genetic data if available

OTHER

Vineland Adaptive Behaviour Scales (VABS2) questionnaire

This is a standardized semi structured interview that measures adaptative skills in 4 areas, in the fields of communication, socialization, daily living, and motricity (for children under 7 years). It can be used for children and adults. Rating: 2 = yes, usually, 1 = sometimes or partly, 0 = no, never, N = not applicable (when a child is not yet of sufficient age, for example), NS = don't know. The results by domain and by sub-domain are given in raw scores which are then transformed into equivalent ages using a grid provided for this purpose.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Eligibility

Min Age

2 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-04-24

Primary Completion

2027-06-01

Completion

2027-06-01

Countries

• France

Study Locations