Boglarka Bansagi, MD, Helen Griffin, PhD, Roger G. Whittaker, MD, PhD, Thalia Antoniadi, PhD, Teresinha Evangelista, MD, James Miller, MD, PhD, Mark Greenslade, PhD, Natalie Forester, PhD, Jennifer Duff, PhD, Anna Bradshaw, Stephanie Kleinle, PhD, Veronika Boczonadi, PhD, Hannah Steele, MD, Venkateswaran Ramesh, MD, Edit Franko, MD, PhD, Angela Pyle, PhD, Hanns Lochmüller, MD, PhD, Patrick F. Chinnery, MD, FRCP, FMedSci and Rita Horvath, MD, PhD
Objective: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England.
Methods: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients).
Results: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62–2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy.
Conclusions: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies.