Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Childhood-Onset Choreo-Dystonia Due to a Recurrent Novel Homozygous Nonsense Hpca Variant: Case Series and Literature Review Publisher



Magrinelli F1 ; Bhatia KP1 ; Beiraghi Toosi M2, 3 ; Arab F4 ; Karimiani EG5, 6 ; Sedighzadeh S7, 8 ; Ansari B9 ; Neshatdoust M10 ; Rocca C11 ; Houlden H11 ; Maroofian R11
Authors

Source: Movement Disorders Clinical Practice Published:2023


Abstract

Background: Biallelic variants in HPCA were linked to isolated dystonia (formerly DYT2) in 2015. Since then, the clinical spectrum of HPCA-related disorder has expanded up to including a complex syndrome encompassing neurodevelopmental delay, generalized dystonia with bulbar involvement, and infantile seizures. Cases: We report four individuals with a new phenotype of childhood-onset choreo-dystonia belonging to two unrelated Iranian pedigrees and harboring a novel homozygous nonsense pathogenic variant NM_002143.3:c.49C>T p.(Arg17*) in HPCA. Although the families are both Iranian, haplotype analysis of the exome data did not reveal a founder effect of the variant. Literature Review: A systematic review of articles on HPCA and dystonia published since the disease gene discovery (PubMed; search on July 09, 2022; search strategy “HPCA AND dystonia”, “HPCA AND movement disorder”, “hippocalcin AND dystonia”, and “hippocalcin AND movement disorder”; no language restriction) resulted in 18 references reporting 10 cases from six families. HPCA-related dystonia was isolated or in various combinations with neurodevelopmental delay, intellectual disability, seizures, cognitive decline, and psychiatric comorbidity. Onset of dystonia ranged from infancy to early adulthood. Dystonia started in the limbs or neck and became generalized in most cases. Brain MRI was unremarkable in nearly all cases where performed. There was poor or no response to common antidystonic medications in most cases. Conclusions: Our case series expands the pheno-genotypic spectrum of HPCA-related disorder by describing childhood-onset choreo-dystonia as a new phenotype, reporting on a recurrent novel pathogenic nonsense variant in HPCA, and suggesting that exon 2 of HPCA might be a mutational hotspot. © 2022 International Parkinson and Movement Disorder Society.
Other Related Docs
4. A Novel Mutation in Hld-5 With a Comprehensive Literature Review, Basic and Clinical Neuroscience (2025)
14. Genetic Analysis of Mecp2 Gene in Iranian Patients With Rett Syndrome, Iranian Journal of Child Neurology (2019)