DHDDS-related disease; biallelic missense novel variant causing major severity with an early-onset epilepsy and...

Dehydrodolichyl diphosphate synthase complex is encoded by DHDDS. De novo mutations in this gene are associated with epilepsy, movement disorders, intellectual and motor disabilities. The clinical picture is commonly identified in children and shows variations in terms of age of onset, severity, seizure types, and types of dyskinesia.

we present a case with a infantile- onset epilepsy and severe global developmental delay, caused by a novel, de novo homozygous variant (c.425C > T, p.Thr142Met) in DHDDS. Clinical improvement was achieved with valproate and tetrabenazine treatments in the 2-year-old male patient with drug-resistant epilepsy, hyperkinetic movement disorder and myoclonus.

Despite being rare, DHDDS-related diseases should be considered in patients with movement disorders, seizures and global developmental delay in infancy in differential diagnosis of patients resembling neuronal ceroid lipofuscinosis or progressive myoclonic epilepsies.