Early childhood onset progressive myoclonic epilepsy phenotype caused by KCTD7 mutations

Case study: The progressive myoclonic epilepsies (PMEs) are a heterogenous group of disorders characterized by the trias: myoclonus, epilepsy, and progressive neurological. They mostly manifest in late, rarely early, childhood and adolescence. In 2007, KCTD 7 mutations were first described to cause PME.¹ We report three patients with PME and proven KCTD 7 mutation.

The patients were two siblings of a consanguine Pakistani family and a child from a nonconsanguine Greek family. Psychomotor development was normal before the onset of symptoms at the age of 16 to 18 months. The presenting symptoms were mainly myoclonic, atonic, and generalized tonic-clonic seizures. The EEG showed rhythmic high amplitude delta waves with superimposed multifocal spikes predominant in posterior regions. The photic stimulation was normal. There were episodes of myoclonic status epilepticus. These episodes were accompanied by regression affecting language and motor skills.

Metabolic workup was normal. No storage material was detected in ultrastructural analysis of a skin biopsy in two patients. Brain MRI of one patient showed discrete nonspecific subcortical white matter lesions and a progressive brain atrophy, and another patient showed a cortical dysplasia as an incidental finding. Fundoscopy of all children was normal.

A homocygote mutation of the KCTD7 gene was found via high-throughput sequencing (CeGaT GmbH) in the siblings of the consanguine parents. The other patient showed a compound heterocygote mutation.

KCTD7 mutations are increasingly found as a cause of early childhood PME.² Because of its early manifestation within the second year, KCTD7 has to be distinguished from infantile NCL. Symptoms of PME and lack of retinopathy and the characteristic storage material should lead to an analysis of KCTD7.

References

1. Van Bogaert P, Azizieh R, Désir J, et al. Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. Ann Neurol 2007;61(6):579 – 586

2. Kousi M, Anttila V, Schulz A, et al. Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. J Med Genet 2012;49:391 – 399