Clinical features of the patient
The female subject was the 2nd child of the family born at 38 weeks with a birth body weight of 2990g. There were no remarkable perinatal events or maternal history. Bilateral deafness, hypothyroidism and ventricular septal defects type II were noted in the neonatal period. Episodic dyskinetic movements began at 6 months of age that progressed to general dystonia by 11 months. These dyskinetic/dystonia movements presented as eye deviation and head deviation to the left associated with tongue protrusion, tonic movements of bilateral upper and lower extremities lasting 3 to 60 seconds per episode, with frequency of up to 40 episodes per hour. Brain magnetic resonance imaging (MRI) done on several occasions showed mild cerebral atrophy with bilateral ventricular dilatation, thinning of corpus callosum, decreased subcortical and periventricular white matter and delayed myelination (Figure 1). Electroencephalogram (EEG) done on several occasions were remarkable for global cortical dysfunction and paroxysmal discharges mainly over left hemisphere. Concurrent problems included profound developmental delay, failure to thrive, intractable focal to bilateral tonic-clonic seizures, fluctuating liver function impairment (ALT/AST 227/148 U/L), and recurrent aspiration pneumonia. There was no elevation of creatine kinase (296 U/L) or lactate (1.26 mM). Muscle biopsy only showed neurogenic myopathy with normal electron transfer chain activity. POLG mutation analysis, tandem mass of metabolites, dried blood spot 3-O-methyldopa level were negative. She had progressive deterioration with febrile episodes and passed away at 5 years old. Exome sequencing by an outside group performed previously using a candidate gene panel analysis approach for intellectual disability (that did not include the BCAP31 gene), followed by whole exome analysis based on the phenotypes of intellectual disability, epilepsy, hypotonia, and MRI abnormalities, did not reveal any candidate variants.