Severe upper airway dysfunction in GNAO1-related disorders.
Por:
Bernardi, K, Ortigoza-Escobar JD, Domínguez-Carral J, Espinoza-Quinteros, I, Mendo, LD, Koy, A and Thiel, M
Publicada:
28 oct 2025
Ahead of Print:
28 oct 2025
Resumen:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Filiaciones:
Bernardi, K:
Univ Cologne, Fac Med, Dept Pediat, Cologne, Germany
Univ Cologne, Univ Hosp Cologne, Cologne, Germany
Sapienza Univ, Dept Human Neurosci, Rome, Italy
Ortigoza-Escobar JD:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
European Reference Network Rare Neurol Dis ERN RND, Barcelona, Spain
Inst Recerca St Joan Deu, Dept Child Neurol, Movement Disorders Unit, Barcelona, Spain
Domínguez-Carral J:
Inst Recerca St Joan Deu, Dept Child Neurol, Epilepsy Unit, Barcelona, Spain
Espinoza-Quinteros, I:
Univ Peruana Cayetano Heredia, Dept Pediat, Pediat Neurol Unit, Lima, Peru
Mendo, LD:
Univ Peruana Cayetano Heredia, Dept Pediat, Pediat Neurol Unit, Lima, Peru
Koy, A:
Univ Cologne, Fac Med, Dept Pediat, Cologne, Germany
Univ Cologne, Univ Hosp Cologne, Cologne, Germany
Univ Cologne, Fac Med, Ctr Rare Dis, Cologne, Germany
Thiel, M:
Univ Cologne, Fac Med, Dept Pediat, Cologne, Germany
Univ Cologne, Univ Hosp Cologne, Cologne, Germany
Green Submitted, gold
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