J Pediatr Genet 2021; 10(03): 236-238
DOI: 10.1055/s-0040-1713159
Case Report

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

Gianluca Piccolo
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Elisabetta Amadori
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Maria Stella Vari
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
2   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
,
Francesca Marchese
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Antonella Riva
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Valentina Ghirotto
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Michele Iacomino
3   Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Vincenzo Salpietro
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
2   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
,
Federico Zara
2   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
3   Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy
,
Pasquale Striano
1   Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
2   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
› Author Affiliations
Funding This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (Legge 232/2016).

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.

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

© 2020. Thieme. All rights reserved.

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