We describe a case of Bainbridge-Ropers Syndrome with refractory breath holding spells with dystonia and intractable epilepsy. He first presented at two years of age with autistic features, global developmental delay, and intractable epilepsy.  A pathogenic variant of ASXL3 was identified on whole exome sequencing (WES) at age 10-years.

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 choreoathetoid movements have been previously described.

We describe an 11-year old boy who was referred to our clinic at 2-years of age for daily intractable seizures reported since birth, developmental delay, autistic features and feeding difficulties. At age 10-years of age, WES study identified a 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. Spells interrupt his activity and lead to falls. Spells have been refractory to iron supplementation, acetazolamide, and desipramine, and he has been sensitive to adverse side effects. Acetazolamide caused anorexia and encephalopathy requiring hospitalization. Desipramine caused agitation and insomnia. Seizures are events of behavioral arrest with head bobbing/drops and are associated with generalized spikes evolving to high-amplitude delta, lasting for several seconds. He has deteriorating balance, disruptive sleep-wake patterns, and MRI Brain at age 11-years revealed cerebral and cerebellar atrophy.  

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 extremely limited treatment options.