Download PDF
Neuropediatrics
DOI: 10.1055/a-2749-5951
Videos and Images in Neuropediatrics

Compulsive Respiratory Stereotypies in a Patient with SYNGAP1 Mutation

Authors

  • Till Hartlieb 

    1   Center for Pediatric Neurology, Neurorehabilitation and Epileptology, Schön Klinik Vogtareuth, Vogtareuth, Germany
    2   Institute for Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria

  • Celina von Stülpnagel

    2   Institute for Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria
    3   Department for Neuropediatrics, Developmental Neurology and Social Pediatrics, Dr. von Haunersches Children's Hospital, Ludwig-Maximilian-University Munich, Munich, Germany

  • Kirsten Eschermann

    2   Institute for Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria
    4   Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria

  • Lorenz Kiwull 

    2   Institute for Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria
    4   Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria
    5   Institute of Human Genetics, Medical Faculty Otto von Guericke University Magdeburg, Germany

  • Daniel Weghuber

    4   Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria

  • Gerhard Kluger

    1   Center for Pediatric Neurology, Neurorehabilitation and Epileptology, Schön Klinik Vogtareuth, Vogtareuth, Germany
    6   Department of Pediatrics, Institute of Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria; Member of the ERN Epicare

  • Milka Pringsheim

    1   Center for Pediatric Neurology, Neurorehabilitation and Epileptology, Schön Klinik Vogtareuth, Vogtareuth, Germany
    2   Institute for Rehabilitation, Transition and Palliation of Neurologically Ill Children, Paracelsus Medical University, Salzburg, Austria
    7   German Heart Centre Munich, TUM-Klinikum, TU-München, Munich, Germany
Further Information
Also available at
   Permissions and Reprints

Compulsive respiratory stereotypies (CRS) are characterized by non-epileptic syncopal attacks (± convulsions) triggered by self-induced Valsalva maneuvers, mainly observed in patients with autism spectrum disorder (ASD). First described clinically by Aicardi et al (1988) and Gastaut et al (1987), CRS were successfully treated with high-dose fenfluramine (FFA).[1] [2]

A 19-year-old patient with refractory epilepsy and ASD due to a pathogenic de novo splice site SYNGAP1 mutation (c.3408 + 1 G > A) experienced several hundred self-induced CRS daily (see [Video 1]) with loss of tone, eyelid myoclonia, occasionally with convulsions or drops. CRS mostly occurred during periods of inactivity or boredom and seemed to have pleased the patient. Pathophysiologically, diaphragmatic contraction with forced expiration against the closed glottis during the Valsalva maneuver leads to an increased intrathoracic pressure with deviation of the cardiac axis and reduced cardiac output, resulting in cerebral hypoperfusion. In addition, cardiac axis deviation causes an amplitude reduction in ECG (see [Video 1]). EEG during episodes showed high amplitude theta activity without a seizure pattern as a result of cerebral hypoperfusion with intermittent cellular hypoxia. Similar EEG changes based on the same mechanism are seen in the more common affective respiratory convulsions in younger children.

Video 1 CRS episodes in Syngap1 (video only and video plus EEG).

Off-label application of FFA within the framework of an N of 1 trial was well-tolerated (maximum dose 0.42 mg/kg/d [27 mg/d]). CRS decreased significantly in frequency (−50%) and duration (−75%) with no change regarding epileptic seizures. Remarkable increases in vigilance, learning capabilities, and communication skills were observed under FFA. Restlessness and aggressive behavior were reported at maximum dosage, which improved after dose reduction (0.26 mg/kg/d), while maintaining the positive effects described above.



Publication History

Received: 26 August 2025

Accepted: 16 November 2025

Article published online:
26 November 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany