Authors: Christy Kuriakose, A1, Nawab Ali A2, A3, Caoimhe McKenna A3, Sarah Mason A4, Gavin McCluskey A5, John McConville A4,A6, Grace McMacken A2,A4.

Affiliations: A1) School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, BT7 1NN, United Kingdom. A2) Centre for Public Health, Queen’s University Belfast, Belfast, BT12 6BA, United Kingdom. A3) Clinical Genetics Service, Belfast Health and Social Care Trust, Belfast, BT12 6BA, United Kingdom. A4) Regional neuromuscular service, South Eastern Health and Social Care Trust, Dundonald, BT16 1RH, Northern Ireland, United Kingdom. A5) Department of Neurology, Altnagelvin Area Hospital, Western Health and Social Care Trust, Londonderry, BT47 6SB, Northern Ireland, United Kingdom. A6) Wellcome Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast, BT9 7BL, United Kingdom

Background/ Introduction: Background: Charcot–Marie–Tooth disease (CMT) is the most common inherited neuromuscular disorder, affecting approximately 1 in 2,500 individuals 1–3. Accurate identification and molecular diagnosis are increasingly important for genetic counselling, service planning and emerging gene-targeted therapies. We aimed to characterise the adult inherited neuropathy cohort in Northern Ireland and evaluate the current rate of molecular diagnosis.

Material & Methods: We performed a regional observational study of adults with clinically suspected or genetically confirmed inherited neuropathy in Northern Ireland. Cases were identified through the regional neuromuscular service, electronic healthcare records and the regional genetics database. Duplicate records were removed. Molecular diagnoses were considered confirmed when pathogenic or likely pathogenic variants were identified in recognised inherited neuropathy genes according to ACMG/AMP classification criteria.

Results: Preliminary analysis identified 190 adults with clinically suspected or genetically confirmed inherited neuropathy. A confirmed molecular diagnosis was established in 115 patients (61%). The commonest genotype was PMP22 duplication (CMT1A; n=71), with the remaining genetically confirmed cases distributed across multiple inherited neuropathy genes. 75 patients (39%) remained without a confirmed molecular diagnosis, including 19 with one or more variants of uncertain significance (VUS). Ongoing review has identified patients with historical negative genetic testing or incomplete investigation who may be suitable for contemporary genomic testing and reanalysis.

Conclusion: This represents the first regional description of the inherited neuropathy population in Northern Ireland. A substantial proportion of patients remain without a molecular diagnosis despite specialist follow-up, highlighting an important unmet diagnostic need. These findings support systematic genomic re-evaluation, the importance of rare disease registries, and improved readiness for precision medicine and clinical trials.