# Severe upper airway dysfunction in GNAO1-related disorders

## TL;DR

This study highlights the severe upper airway dysfunction in patients with GNAO1-related disorders, leading to life-threatening complications and poor outcomes despite interventions.

## Contribution

The study emphasizes the critical role of upper airway dysfunction in GNAO1-related disorders and calls for improved therapeutic strategies.

## Key findings

- All four patients exhibited severe hypotonia and hyperkinetic movement disorders, leading to life-threatening respiratory complications.
- Interventions like DBS and tracheostomy did not effectively address airway or swallowing dysfunction.
- All patients died at a young age due to respiratory complications, underscoring the high mortality rate in this condition.

## Abstract

GNAO1-related disorders (GNAO1-RD) encompass a wide phenotypic spectrum, including muscular hypotonia, movement disorders (MD), epilepsy, developmental delay, and intellectual disability. MD often presents with dystonia and choreoathetosis, and dyskinetic crises can lead to life-threatening conditions. Despite increasing reports, limited information exists on the impact of upper airway dysfunction in GNAO1-RD patients. This study examines the implications of muscular hypotonia on upper airway function and subsequent clinical outcomes.

This study includes four patients, three from the GNAO1 registry in Germany, with data collected from medical records including neurological examinations, EEG recordings, genetics, imaging studies, and video documentation of dyskinetic movements and respiratory symptoms. Treatment interventions and clinical outcomes were documented.

The study involved four patients (three males and one female) aged between 15 months and 12 years, all of whom were within the severe spectrum of GNAO1-RD. All patients exhibited severe hypotonia and hyperkinetic MD, leading to recurrent dyskinetic crises. Respiratory complications included an inspiratory stridor and airway obstructions. All patients died at young age (2.4, 2.8, 7.8 and 12 years) due to respiratory complications. Despite interventions such as DBS and tracheostomy, clinical outcomes remained poor.

Upper airway dysfunction significantly contributes to the high morbidity and mortality in GNAO1-RD patients. Current therapeutic options are limited; while DBS can be life-saving during acute crises, it does not address swallowing or airway dysfunction effectively. Multimodal approaches and larger, multicenter trials are needed to improve outcomes for these patients.

The online version contains supplementary material available at 10.1186/s13052-025-02150-0.