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Neuropediatrics 2022; 53(05): 386-387
DOI: 10.1055/a-1892-1547
Videos and Images in Neuropediatrics

A Novel Homozygous PDE 10A Variant Leading to Infantile-Onset Hyperkinesia

Gesa Trieschmann‡   *
1   Specialist Centre for Paediatric Neurology, Neurorehabilitation and Epileptology, Schoen Clinic Vogtareuth, Vogtareuth, Bayern, Germany
,
Katharina Wach‡   *
1   Specialist Centre for Paediatric Neurology, Neurorehabilitation and Epileptology, Schoen Clinic Vogtareuth, Vogtareuth, Bayern, Germany
2   Department of Paediatrics, University Hospital Goettingen, Goettingen, Germany
,
Maria Abel
3   Specialist Centre for Neurosurgery and Epilepsy Surgery, Vogtareuth, Bayern, Germany
,
Eva Tilgner
4   Social Paediatric Centre, DONAUISAR Klinikum Deggendorf, Deggendorf, Germany
,
Steffen Berweck‡   **
1   Specialist Centre for Paediatric Neurology, Neurorehabilitation and Epileptology, Schoen Clinic Vogtareuth, Vogtareuth, Bayern, Germany
5   LMU Hospital, Department of Pediatrics–Dr. von Hauner Childrens's Hospital, Division of Pediatric Neurology and Developmental Medicine, Ludwig-Maximilians University, Munich, Germany
,
Michael Zech‡   **
6   Institute of Human Genetics, School of Medicine, Technical University of Munich, München, Germany
7   Institute of Neurogenomics, Helmholtz Zentrum München, München, Neuherberg, Germany
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Phosphodiesterase-10A is expressed in medium spiny neurons in the striatum controlling the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) playing a crucial role in movement control.[1] Recently, cases of hyperkinetic disorders with onset in childhood as a result of PDE10A variants have been described.[2] [3] [4]

Our patient is a 9-year-old Iraqi boy presenting with a choreodystonic movement disorder. Pregnancy and perinatal history were unremarkable, first symptoms were noted by the parents at 6 months of age. He has hyperkinetic involuntary movements of the whole body which increase with activity and emotional stress. He is not able to stand or walk and drives a wheelchair. His speech is dysarthric. Cognitive development is estimated as slightly below average but might be confounded by language barrier. Cranial magnetic resonance imaging revealed no abnormalities. The patient was enrolled in an exome-wide sequencing study searching for monogenic causes of cerebral palsy-like syndromes.[5] A novel homozygous variant in PDE10A: NM_001130690.2:c.652C > T, NP_001124162.1:p.Arg218Trp was found leading to substitution of a highly conserved amino acid in the GAF-A of phosphodiesterase-10A; both consanguineous parents were healthy carriers ([Video 1]).

Video 1 A 9-year-old patient with PDE10A variant with a hyperkinetic choreodystonic movement disorder. Treatment with L-Dopa did not change the clinical appearance.


Quality:

As levodopa was shown to reduce involuntary movements in two sisters with PDE10A variants,[3] we undertook a treatment trial of L-Dopa (maximum dose of 5 mg/kg/d) without clear effect and are currently treating with tetrabenazine.

Note

The video was taken at the Specialist Centre for Pediatric Neurology, Neurorehabilitation and Epileptology, Schoen clinic Vogtareuth, Germany.


* Gesa Trieschmann and Katharina Wach contributed equally to the article.


** Steffen Berweck and Michael Zech contributed equally to the article.




Publication History

Received: 19 June 2022

Accepted: 27 June 2022

Accepted Manuscript online:
05 July 2022

Article published online:
28 August 2022

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