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. 2025 Sep;12(9):1367-1373.
doi: 10.1002/mdc3.70071. Epub 2025 Apr 7.

STARDEV Study: Neurodevelopmental Trajectory and Long-Term Outcomes of Patients with Startle Disease/Hyperekplexia

Diane Pina  1 , Agathe Roubertie  2 , Marie-Aude Spitz  3 , Claudia Ravelli  4 , Nadia Bahi-Buisson  5 , Farha Gheurbi  1 , Marion Buchy  1 , Thomas Loppinet  6 , Nicole Chemaly-Perin  5 , Marie-Christine Nougues  4 , Benedicte Heron  4 , Regis Lopez  7 , Mathieu Anheim  8 , Mélanie Fradin  9 , Claude Cances  10 , Justine Avez-Couturier  11 , Fabienne Dalmon  12 , Gaëtan Lesca  13   14 , Vincent Des Portes  1   14 , Laurence Lion-François  1
Affiliations

STARDEV Study: Neurodevelopmental Trajectory and Long-Term Outcomes of Patients with Startle Disease/Hyperekplexia

Diane Pina et al. Mov Disord Clin Pract. 2025 Sep.

Abstract

Background: Although initial clinical presentation of hyperekplexia/startle disease is well known, data regarding long-term clinical outcomes is lacking.

Objectives: We provide a long-term evaluation from clinical and pharmacological perspectives, focusing on neurodevelopmental trajectory.

Methods: Twenty-eight patients from nine French hospitals were included based on clinical diagnosis criteria. Adaptive abilities were assessed using VABS-II.

Results: VABS-II showed preserved adaptive abilities, except in motor skills. Early development was marked by neurodevelopmental delay in 53% of patients, with 57% developing neurodevelopmental disorders, primarily specific learning disorders. Intellectual disability and/or autism spectrum disorder were present in five patients. Symptoms were most frequent during the first 3 years of life, with persistence of exaggerated startle reflex and falls. One-quarter of the patients discontinued clonazepam. A genetic variant was found in 85% of patients, involving one of the three main genes GLRA1, SLC6A5, or GLRB.

Conclusions: Our findings highlight preserved adaptive abilities, frequent neurodevelopmental disorders and long-term pharmacodependence.

Keywords: GLRA1; GLRB; SLC6A5; VABS‐II; adaptive abilities; clonazepam; hyperekplexia; neurodevelopment; startle disease.

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Conflict of interest statement

Ethical Compliance Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. The study received approval from the Comité de Protection des Personnes Est III (no. 2022‐A02107‐36). Informed consent was obtained from all the patients included in the study or at least one of the legal representatives if the patient was minor. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Figures

Figure 1
Figure 1
Evolution of symptoms and clonazepam dosages over time. (A–D) Kaplan–Meier curves depicting the probability of presence of each symptom over time. The solid black line represents the estimated symptom presence probability at each time point. The shaded area around the curve indicates the 95% confidence interval for the symptom presence estimate. The x‐axis shows the duration of symptoms in years, while the y‐axis represents the probability of symptom presence. (E) Boxplot illustrating the follow‐up distributions of clonazepam dosage across ages 1–15 The line inside the box indicates the median dosage. The top and bottom of each box represent the upper and lower limits of the interquartile range, respectively. The whiskers extend up to 1.5 times the interquartile range. Data were not available for all 28 patients at each threshold age, therefore data were taken from the patients for whom the data were available at each given age, represented by a black dot.
See this image and copyright information in PMC

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