263P Updated genetic testing in heart-transplant recipients in Norway between 1983-2022 uncovering genes relevant to neuromuscular disorders

• Published in: Neuromuscular disorders : NMD Vol. 43; p. 104441
• Main Authors: Benterud, A., Popperud, T. Haug, Broch, K., Hasselberg, N., Bogsrud, M. Prøven, Berge, K., Haugaa, K., Ørstavik, K.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2024
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.480

The first heart transplantation in Norway was performed in 1983. Since then, over 1050 patients have received a heart transplant (HTx). About 400 patients had a diagnosis of non-ischemic cardiomyopathy (CM). Over the last 15 years, new genes have been found to be associated with an increased risk of developing CM and neuromuscular disease (NMD). This particularly applies to mutations in the LMNA, TTN and MYH7 genes. Well-known NMDs such as Myotonic dystrophy (MD) type 1 and 2, Duchenne`s and Beckers MD may be dominated by and diagnosed after, cardiac manifestations of the disorder. The aims of the study were to explore to what extent HTx recipients with non-ischemic CM have mutations in genes that may cause NMD. We identified patients using a national HTx registry. Family history, subtype of CM and results from genetic testing were recorded from medical records. Patients not previously tested were offered a genetic test, and previously tested patients with negative results were offered a new test with an updated panel (hereditary CM including genes for NMD). 279 living HTx recipients fulfilled the criteria and 181 patients (112 men) have so far given informed consent. Of these, 108 (60%) were previously genetically tested. An underlying mutation causing CM was identified in 65 (60 %). The mutations were identified in both genes associated with NMD (TTN, LMNA, MYBPC3, MYH7, DMD, BAG3, FKRP, DES) as well as in genes associated with CM only (TNNT2, DSP, PKP2, TNNI3, RBM20). Among the 73 patients (43%) who had not previously been tested, an underlying mutation causing CM was identified in 20 patients (27%) all in genes associated with NMD (TTN, LMNA, MYH7, BAG3, MYBPC3, TNNT2 and DES). 24 patients tested negative, and 29 test results are still pending. Further studies will include neurologic clinical examination and standardized functional tests as well as more elaborate genetic testing in patients with an obvious NMD.