Objective: This clinical case intends to highlight the in expansion genotypic base of the genetically undefined benign hereditary chorea, where de adenylate cyclase 5 gene (ADCY5) mutation appears to have an in crescendo place.

Background: The clinical syndrome of chorea and generalized dystonia with an autosomal dominant transmission pattern has been object of a clinical expansion that further extrapolates the one encompassed by Huntington’s Disease. The ADCY5 mutation has recently been proposed as cause of part of this undefined syndrome, and its phenotypic profile is under expansion.

Methods: We obtained retrospective data from clinical history, neurological examination, magnetic resonance imaging, and genetic testing.

Results: We report a case of 12 yo boy with a previously uncharacterized movement and gait disorder beginning early in childhood at the age of 12 months in association with frequent falls and diurnal fluctuation (early morning aggravation) determining delayed motor (major), social and cognitive milestones acquisition (mild). Normal pregnancy, delivery and neonatal period. Without history of parental consanguinity. Mother with history of undiagnosed hyperkinetic disorder apparently mimicked by other direct ancestries, namely aunt, and grandfather. The neurological examination revealed a mild dysarthria and a generalized choreo-dystonic posture affecting different segments, manly face, arms, and trunk. The remaining exam was unmeaningful for telangiectasias, tremor, pyramidal or apraxic signs. The ancillary investigation with brain MRI, wide metabolic workup, copper kinetic study and neurotransmitters dosing (5-HIAA, HVA) was unrevealing. The patient didn’t respond to the levodopa trial. Next-generation sequencing dystonia panel including a by demand ADCY5 gene study revealed a heterozygous variant in the later (c.2866G>A;p.Asp956Asn) probably pathogenic according to bioinformatic analysis. Segregation analysis in course.

Conclusions: To our knowledge, this is one of the firstly described ADCY5 mutation cases reported in our country, further emphasizing the role of ADCY5 mutation study in the setting of an undefined benign hereditary chorea or even more complex syndrome. Its clinical spectrum is in active expansion.

References: Mencacci, N. E., Erro, R., Wiethoff, S., Hersheson, J., Ryten, M., Balint, B., … Bhatia, K. P. (2015). ADCY5 mutations are another cause of benign hereditary chorea. Neurology, 85(1), 80–88. https://doi.org/10.1212/WNL.0000000000001720. Carecchio, M., Mencacci, N. E., Iodice, A., Pons, R., Panteghini, C., Zorzi, G., … Nardocci, N. (2017). ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients. Parkinsonism and Related Disorders, 41, 37–43. https://doi.org/10.1016/j.parkreldis.2017.05.004.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/generalized-dystonia-and-chorea-with-family-history-clinical-case/