Drug-resistant epilepsy in an autosomal recessive copper metabolism disorder from SLC33A1 mutation.

UNLABELLED: SLC33A1 mutation (Huppke-Brendel Syndrome) is a rare, autosomal recessive disorder associated with copper metabolism and characterized by global developmental delay, sensorineural hearing loss, congenital cataract and generalized hypotonia. We report two siblings under 6 years with novel SLC33A1 gene mutation, born from heterozygous parents. The first patient developed early onset drug-resistant epilepsy (DRE) secondary to the novel genetic mutation; the second patient did not develop seizures but shared several other phenotypic features of the syndrome, highlighting intrafamilial variation in seizure penetrance. On electroencephalography of the first patient with DRE, independent spike and wave discharges were noted in the temporoparietal region with generalized background slowing. Diffuse electrodecrement with overriding paroxysmal fast activity was correlated with seizure semiology. Neuroimaging revealed generalized cerebral and cerebellar atrophy, ex-vacuo ventriculomegaly, and bilateral chronic subdural collections. We describe a shared genetic mutation in two siblings and highlight their overlapping and distinct clinical features, management challenges, and complications with invasive neuromodulation. These cases expand the differential diagnosis of copper-related metabolic disorders.

PRACTICAL IMPLICATIONS: Variable seizure penetrance in SLC33A1 related disorders could manifest as epileptic phenotypes.