Phenotype of heterozygous variants of dehydrodolichol diphosphate synthase

Objectives To further identify and broaden the phenotypic characteristics and genotype spectrum of DHDDS. Methods Pathogenic variants of DHDDS were identified by whole exome sequencing; clinical data of the patients were collected and analyzed. Results All cases had seizures and myoclonic seizures could be seen in eight patients (8/10, 80%), with myoclonic status epilepticus in three. The interictal EEG in four patients (4/9, 44%) at seizure onset showed generalized slow waves, slow wave mixed spikes, and spike and waves. Tremor, ataxia, and hypertonia was observed in six, five, and three patients, respectively. The results of short latency somatosensory evoked potential in two patients were normal, and the symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients is a motor abnormality rather than myoclonic seizures. Global DD occurred in all patients, among whom nine patients showed severe ID and one moderate. Five DHDDS variants were identified, three of which had not been reported. Conclusion Myoclonic seizure is the most common seizure type while myoclonic status epilepticus could also occur. The pattern of interictal EEG discharges is characterized by slow waves rather than spike and waves, and generalized discharges is prominent.