Nocturnal Ballistic Bouts in ADCY5-Related Movement Disorder

TL;DR

A rare genetic movement disorder caused by ADCY5 gene mutations is shown to persist into adulthood with nighttime symptom worsening.

Contribution

Demonstrates that ADCY5-related movement disorder can have persistent nocturnal symptoms into late adulthood, expanding its known clinical spectrum.

Findings

ADCY5-RMD can persist into adulthood with nocturnal ballistic bouts.

Neuroimaging may be normal despite severe clinical symptoms.

Symptomatic treatment with medications can reduce episode frequency and severity.

Abstract

Adenylyl cyclase 5 (ADCY5)-related movement disorder (ADCY5-RMD) is a rare genetic hyperkinetic movement disorder caused by pathogenic variants in the ADCY5 gene, characterized by childhood-onset chorea, dystonia, myoclonus, and distinctive paroxysmal exacerbations, often with nocturnal worsening. The disorder exhibits marked phenotypic variability, minimal disease progression, and frequently normal neuroimaging, leading to frequent misdiagnosis as dyskinetic cerebral palsy or epilepsy.

We report the case of a 60-year-old woman with childhood-onset generalized dystonia, prominent oromandibular and lingual involvement, asymmetric distal choreoathetosis, and recurrent nocturnal ballistic bouts beginning at age 13. Episodes occurred predominantly during sleep-wake transitions and were exacerbated by stress. Neurological examination and brain magnetic resonance imaging (MRI) were unremarkable. Whole-exome sequencing (WES) identified a heterozygous de novo splice-site mutation in ADCY5 (c.2088+1G>A), classified as pathogenic. Symptomatic treatment with trihexyphenidyl, clonazepam, and quetiapine led to a significant reduction in episode frequency and severity.

This case expands the phenotypic spectrum of ADCY5-RMD by demonstrating persistence of sleep-related paroxysmal dyskinesia into late adulthood and highlights the importance of considering ADCY5-RMD in long-standing childhood-onset hyperkinetic movement disorders.

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