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.