Introduction/aims. Currently, there are no straightforward guidelines for the clinical and diagnostic management of neuromuscular disorders. Therefore, I have aimed to describe the diagnostic workflow which is used in my neuromuscular clinic for evaluating patients with this condition. The neuromuscular clinic is situated in IRCCS Policlinico San Martino in Genova and is a neuromuscular university centre in Northwest Italy. Methods. I describe our diagnostic approach to two frequent neuromuscular disorders: hyperCKemia and CMT neuropathy. The first work is an Italian multicentre study evaluating our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening and first-line genetic investigations, followed by successive targeted sequencing panels. Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. The second work includes patients affected by CMT with regular follow-ups in our CMT clinic. I describe the genetic distribution of CMT subtypes in our cohort and report a peculiar phenotype. Moreover, I define our diagnostic experiences as a multidisciplinary outpatient clinic, combining a gene-by-gene approach or targeted gene panels based on clinical presentation. Discussion/conclusion. Taking as a model our experience, I generalise the genetic approach to neuromuscular disorders: the diagnosis strategy should be flexible and tuned to the clinical features of the patient in order to select the best molecular approach for each patient.

Genetic approach to neuromuscular disorders in the NGS era

GEMELLI, CHIARA
2022

Abstract

Introduction/aims. Currently, there are no straightforward guidelines for the clinical and diagnostic management of neuromuscular disorders. Therefore, I have aimed to describe the diagnostic workflow which is used in my neuromuscular clinic for evaluating patients with this condition. The neuromuscular clinic is situated in IRCCS Policlinico San Martino in Genova and is a neuromuscular university centre in Northwest Italy. Methods. I describe our diagnostic approach to two frequent neuromuscular disorders: hyperCKemia and CMT neuropathy. The first work is an Italian multicentre study evaluating our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening and first-line genetic investigations, followed by successive targeted sequencing panels. Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. The second work includes patients affected by CMT with regular follow-ups in our CMT clinic. I describe the genetic distribution of CMT subtypes in our cohort and report a peculiar phenotype. Moreover, I define our diagnostic experiences as a multidisciplinary outpatient clinic, combining a gene-by-gene approach or targeted gene panels based on clinical presentation. Discussion/conclusion. Taking as a model our experience, I generalise the genetic approach to neuromuscular disorders: the diagnosis strategy should be flexible and tuned to the clinical features of the patient in order to select the best molecular approach for each patient.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1089374
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