A case of Bainbridge-Ropers syndrome with breath holding spells and intractable epilepsy: challenges in diagnosis and management

• Authors: Tuba Khan, Emory University; Alison Dolce, University of Texas Southwestern Medical Center; Kimberly Goodspeed, University of Texas MD Anderson Cancer Center
• Journal Title: BMC Neurology
• Volume: Volume 22, Number 1
• Publisher: BMC Publishing | 2022-02-16, Pages 60-60
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s12883-022-02573-w
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; Bainbridge-Ropers syndrome; Breath-holding spells; ASXL3 gene

Abstract

Background Bainbridge-Ropers syndrome is caused by monoallelic ASXL3 variants on chromosome 18. Clinical features include dysmorphic facies, developmental delay, intellectual disability, autistic traits, hypotonia, failure to thrive, seizures and hyperventilation. Breath-holding spells with choreathetoid movements have been previously described. Case presentation We describe an 11-year old boy who has daily intractable seizures reported since birth, developmental delay, autistic features and feeding difficulties. He was eventually found to have de novo, heterozygous pathogenic variant (c.1612G > T, p.E538*) in the ASXL3 gene. He has frequent episodes of breath-holding accompanied by dystonic posturing with right leg extension and head turning without ictal EEG correlate. The breath-holding spells have been refractory to several medication trials including iron supplementation, acetazolamide, and desipramine. Conclusions This case represents a more severe phenotype of Bainbridge-Ropers Syndrome than previously described with refractory breath-holding spells with dystonia, intractable epilepsy, and progressive cerebral/cerebellar atrophy. Breath-holding spells cause significant morbidity, are poorly understood, and have very limited treatment options.