Complex Neurological Phenotype Associated with a De Novo DHDDS Mutation in a Boy with Intellectual Disability, Refractory Epilepsy, and Movement Disorder

Abstract

Mutations in the DHDDS gene (MIM: 617836), encoding a subunit of dehydrodolichyl diphosphate synthase complex, have been recently implicated in very rare neurodevelopmental diseases. In total, five individuals carrying two de novo mutations in DHDDS have been reported so far, but genotype–phenotype correlations remain elusive. We reported a boy with a de novo mutation in DHDDS (NM_205861.3: c.G632A; p.Arg211Gln) featuring a complex neurological phenotype, including mild intellectual disability, impaired speech, complex hyperkinetic movements, and refractory epilepsy. We defined the electroclinical and movement disorder phenotype associated with the monoallelic form of the DHDDS-related neurodevelopmental disease and possible underlying dominant-negative mechanisms.

Keywords

DHDDS - neurodevelopmental disorder - epilepsy

Authors' Contributions

G.P. performed study design and experimental data acquisition, analysis, and interpretation of data for this study. E.A., M.S.V., and V.G. conceptualized the study, helped acquire clinical data, contributed to the manuscript, analyzed and interpreted phenotype data. M.I. contributed to the manuscript, and helped in analysis and interpretation of genetic data. F.M.V.S. performed critical revision of the manuscript document. P.S. and F.Z. supervised the study and obtained funding.

Consent for Publication

Written consent for recording and publishing photographs and videos of the patient were obtained from his parents.

Publication History

Received: 24 April 2020

Accepted: 08 May 2020

Article published online:
31 July 2020

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