The diagnostic strategy of Latin-SEQ uses an algorithm guided by the clinical suspicion of each patient as determined by the referring centre. Patients with hereditary neuromuscular diseases (NMDs) will be evaluated through specific genetic screening using Multiple Ligation Probe Amplification (MLPA) to rule out conditions such as Spinal Muscular Atrophy (SMA), Duchenne/Becker muscular dystrophy, and Charcot-Marie-Tooth neuropathies, or sequencing of recurrent mutations associated with congenital myasthenic syndromes and mitochondrial myopathies. This initial screening is expected to diagnose approximately 20% of cases. Cases not diagnosed through this method will proceed to whole exome sequencing.

In the first stage, exomes will be analysed focusing on a panel of over 600 genes related to neuromuscular diseases (based on http://www.musclegenetable.fr/) which will be updated every 6 months. This approach is expected to resolve 40-60% of cases. For unresolved cases, a more thorough analysis of the whole exome will be conducted, including sequencing of family members when possible. This approach will not only facilitate the diagnosis of rare diseases but also the identification of new genes. In such cases, studies will be conducted to validate the pathogenicity of identified variants and confirm their relevance using various criteria, including in silico analyses and functional studies in cellular or animal models.

In Latin-SEQ, the interpretation and analysis of genetic results follow a meticulous and rigorous process: the obtained data are analysed iteratively, and preliminary results are shared with referring physicians. These results are discussed in regular meetings to evaluate the findings based on the patient’s and family’s clinical presentation. For cases considered resolved, a final genetic report will be issued. For more complex cases, multidisciplinary meetings will be held where genetic results will be discussed alongside other available studies such as MRI or muscle biopsy.

The genetic reports* issued by the coordinating team will provide information on the identified genetic variants and their classification according to the ACMG (American College of Medical Genetics and Genomics) guidelines, detailing each parameter included as well as relevant publications.

In genetic reports, the contact details of available PATIENT REGISTRIES/ASSOCIATIONS will be provided to the referring doctors, preferably within the country of origin or internationally, so they can share them with patients and their families in accordance with their protocols.

Unfortunately, the vast majority of NMDs have no cure or treatment; if any do, this information will also be included in the genetic reports. Clinical follow-up of patients is managed by the referring physicians.

*It is important to note that the results presented in these reports are obtained as part of a research study and therefore do not constitute a diagnostic credential. The interpretation and application of these data are the sole responsibility of the referring physicians. The Latin-SEQ team is not responsible for the use of the information contained in these reports.

The genetic reports will also provide referring physicians of diagnosed patients with contact information for patient registries available preferably in the patient’s country of origin or other international registries. These registries are responsible for sharing information with patients and their families according to their own protocols.

Participation in registries is entirely voluntary and at the discretion of the patient and their family. Patient registries are important tools that systematically archive clinical and genetic data, with the primary aim of locating patients for clinical trials. Registries also serve as a support network for patients, offering additional resources that can assist throughout the course of the disease. The data contained in registries are valuable and contribute to advancing research and knowledge about neuromuscular diseases in the region.

Below, we provide a list of some registries and/or patient associations from various countries that we have compiled and will continue to update. However, this list is not exhaustive, so we recommend further investigation into other registries or associations in your country of residence

The Latin-SEQ project is associated with a subproject called Latin-SEQ+, directed by Dr Lorraine Cowley, a genetic counsellor with extensive experience in counselling patients with rare diseases. Latin-SEQ+ focuses on exploring and improving the experiences of patients and healthcare providers in LATAM concerning the diagnosis of hereditary neuromuscular diseases through whole exome sequencing (WES) and whole genome sequencing (WGS).

This subproject aims to evaluate how genetic diagnoses impact medical care, prenatal testing opportunities, and the communication of genetic information within families. Additionally, it examines the cultural and religious impact on the acceptance of the diagnosis and subsequent measures taken. This study will not only contribute to the growth and improvement of genetic services in Latin America but also provide valuable insights for genetic counselling practice in the UK
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Furthermore, Dr Lorraine Cowley will provide Latin-SEQ+ and Latin-SEQ participating physicians, clinicians, and other healthcare staff in LATAM with resources and training to better understand genetic results and effectively communicate them to patients and their families.