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Case Reports
. 2025 Nov;12(11):1968-1971.
doi: 10.1002/mdc3.70175. Epub 2025 Jun 12.

ADCY5-Mosaic Variants: A Diagnosis Not to Be Missed

Alice Innocenti  1 , Emmanuel Roze  2   3 , Florence Riant  4 , Marie-Céline François-Heude  5 , Bérénice Lecardonnel  5 , Giacomo Garone  1 , Maxime Colmard  5 , Eline Chauvet-Piat  5 , Anne-Cécile Chaux  6 , Marie-Aude Spitz  7 , Beatrice Desnous  8 , Catherine Sarret  9 , Philippe Damier  10 , Thomas Wirth  11   12   13 , Mathieu Anheim  11   12   13 , Emilie Retailleau  3 , Estelle Conabady  3 , Caroline Dubacq  3 , Oriane Trouillard  3   14 , Aurélie Méneret  2   3 , Agathe Roubertie  5   15
Affiliations
Case Reports

ADCY5-Mosaic Variants: A Diagnosis Not to Be Missed

Alice Innocenti et al. Mov Disord Clin Pract. 2025 Nov.

Abstract

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.

Keywords: ADCY5‐mosaic; mixed movement disorder ADCY5 (MxMD‐ADCY5); paroxysmal dyskinesias (PxD).

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Conflict of interest statement

Ethical Compliance Statement: This study was carried out in accordance with the Declaration of Helsinki and was approved by the local ethics committee (ADYC5MO‐CP‐2024‐08‐112). Written informed consent for scientific publication of the patients' data was obtained from the patients or their legal guardians. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: This study was supported by ADCY5.org. The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: A.I., F.R., M.‐C.F.‐H., B.L., G.G., M.C., A.‐C.C., M.‐A.S., B.D., M.A., E.R., E.C., and C.D. report no financial disclosures for the previous 12 months. E.R. reports honorarium for speech from Orkyn, Aguettant, Elivie, Merz‐Pharma, Janssen, and Teva and for participating in advisory boards from Merz‐Pharma, Elivie, Teva, and Bial. He received research support from Merz‐Pharma, Orkyn, Elivie, Everpharma, Amadys, Aguettant, ADCY5.org, Fonds de dotation Patrick Brou de Laurière, Agence Nationale de la Recherche, Dystonia Medical Research Foundation, Hope for Annabel, Cure Alternating Hemiplegia of Childhood Alternating Hemiplegia of Childhood Foundation, Alternating Hemiplegia of Childhood Association of Iceland, Association française de l'hémiplégie alternante, and Alternating Hemiplegia of Childhood Kids of the Netherlands. E.C.‐P. reports a study grant from the Switzerland‐based Fondation Ancrage for her clinical and research fellowship in abnormal movements in Montpellier, France. C.S. reports honoraria for advisory boards from Egetis, Italfarmaco, Novartis, and Argenx and for speech from Biogen and Lupin. P.D. reports honorarium for speech from AbbVie, Teva, and Novartis and participating in the advisory board for Teva. T.W. reports honoraria from IPSEN, AbbVie, and Edimark; research grants from the Revue Neurologique, the Fondation Planiol, the APTES, and the France Parkinson organizations; prize from the Société Française de Neurologie; and travel funding from LVL Medical, the Movement Disorders Society, Homeperf, and Lündbeck. A.M. reports honoraria for speeches from Merz‐Pharma and travel funding from Elivie and Merz‐Pharma. A.R. reports research support from PTC and travel funding from PTC and Biomarin.

References

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