ADCY5 ‐Mosaic Variants: A Diagnosis Not to Be Missed

BACKGROUND: An increasing number of ADCY5-mosaic patients, seemingly with a milder phenotype, are being identified. However, an in-depth assessment of their clinical characteristics is lacking. CASES: We collected and analyzed data from 12 consecutive ADCY5-mosaic patients diagnosed at our center and 7 cases from the literature; 63% of the patients presented with a baseline hyperkinetic motor disorder with paroxysmal motor exacerbations; 30% had isolated paroxysmal dyskinesias (PxD). Caffeine treatment was highly effective. Developmental delay was observed in 5 patients and especially in those with persistent motor symptoms. PxD were the initial motor symptom in 70% of cases. CONCLUSIONS: ADCY5-mosaic carriers may have the same phenotypic spectrum as non-mosaic carriers but with a milder clinical presentation. Isolated PxD with onset in infancy are a red flag for ADCY5-mosaic variants. Particular attention should be paid when genetic analysis of patients with this phenotype is conducted as mosaicism can be easily missed.