Hyperekplexia : Adaptative Skills and Neurodevelopmental Trajectory

NCT ID: NCT05652101

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-04-24
• Study Completion Date: 2027-06-01

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients suffering from hereditary hyperekplexia, above 2 years of age

40 patients suffering from hereditary hyperekplexia will be included. The investigators study patients suffering from hereditary hyperekplexia. The diagnostic is clinical, based on the following symptoms, appearing shortly after birth: stiffness, exaggerating response startles to unexpected stimuli, generalized stiffness after the startles.

Children above 2 years old and adults are included, so the neurodevelopment can be evaluated.

collection of medical data

Intervention Type: OTHER

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

Vineland Adaptive Behaviour Scales (VABS2) questionnaire

Intervention Type: OTHER

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.

Interventions

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

Intervention Type: 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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinical diagnostic criteria for hyperekplexia (see Thomas et al. BRAIN, 2013):

• The presence of hypertonia (either hypertonia on examination, axial or segmental, or access of stiffness)
• Exaggerated reflex startles, to auditory, tactile or visual stimuli
• The presence of reflex bursts on percussion of the midline
• Children >2 years and adults
• No opposition of one of the two parents (or legal representative) or of the adult patient

Exclusion Criteria

• The presence of a cause secondary to the hyperekplexia (traumatic, autoimmune, etc.)
• The presence of another cause for a delay in psychomotor development (other neurological pathology, serious head trauma, etc.)
• Pregnant or breastfeeding women
• Person deprived of liberty by judicial or administrative decision

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hopital Femme Mère Enfant

Bron, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Laurence LION FRANCOIS, MD,PhD

Role: CONTACT

laurence.lion-francois@chu-lyon.fr

04 27 85 53 77 ext. +33

Diane PINA

Role: CONTACT

diane.pina@chu-lyon.fr

0633493731 ext. +33

Facility Contacts

Laurence LION FRANCOIS, MD,PhD

Role: primary

laurence.lion-francois@chu-lyon.fr

04 27 85 53 77 ext. +33

Diane PINA

Role: backup

diane.pina@chu-lyon.fr

0633493731 ext. +33

Other Identifiers

2022-A02107-36

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL22_0568

Identifier Type: -

Identifier Source: org_study_id