Neuropediatrics 2021; 52(05): 377-382
DOI: 10.1055/s-0040-1722686
Original Article

Specific Cognitive Changes due to Hippocalcin Alterations? A Novel Familial Homozygous Hippocalcin Variant Associated with Inherited Dystonia and Altered Cognition

Sandy Siegert
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria
Wolfgang M. Schmidt
2   Neuromuscular Research Department, Medical University of Vienna, Austria
Thomas Pletschko
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria
Reginald E. Bittner
2   Neuromuscular Research Department, Medical University of Vienna, Austria
Sonja Gobara
3   Ambulatorium Sonnenschein, Sozialpädiatrisches Zentrum, St. Pölten, Austria
Michael Freilinger
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria
› Author Affiliations
Funding M.F. reports personal fees from Novartis outside the submitted work. T.P. reports grants from Austrian Childhood Cancer Organization, Austrian Childhood Cancer Organization-Parents' Initiative, Gemeinsame Gesundheitsziele aus dem Rahmen-Pharmavertrag, NF-Kinder, Occursus, and 42virtual outside the submitted work. W.M.S. reports personal fees from AveXis Inc. and PTC Therapeutics Inc. outside the submitted work.


Background Recent research suggested an hippocalcin (HPCA)-related form of DYT2-like autosomal recessive dystonia. Two reports highlight a broad spectrum of the clinical phenotype. Here, we describe a novel HPCA gene variant in a pediatric patient and two affected relatives.

Methods Whole exome sequencing was applied after a thorough clinical and neurological examination of the index patient and her family members. Results of neuropsychological testing were analyzed.

Results Whole exome sequencing revealed a novel homozygous missense variant in the HPCA gene [c.182C>T p.(Ala61Val)] in our pediatric patient and the two affected family members. Clinically, the cases presented with dystonia, dysarthria, and jerky movements. We observed a particular cognitive profile with executive dysfunctions in our patient, which corresponds to the cognitive deficits that have been observed in the patients previously described.

Conclusion We present a novel genetic variant of the HPCA gene associated with autosomal recessive dystonia in a child with childhood-onset dystonia supporting its clinical features. Furthermore, we propose specific HPCA-related cognitive changes in homozygous carriers, underlining the importance of undertaking a systematic assessment of cognition in HPCA-related dystonia.

Publication History

Received: 08 July 2020

Accepted: 23 October 2020

Article published online:
28 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
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