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Abstract

Heritable neuromuscular disorders (NMDs) encompassing congenital muscular dystrophies (CMDs) and myopathies are a group of primary muscular diseases in which independent walking, breathing and feeding/swallowing abilities are variably compromised together with associated extramuscular manifestations. The next generation sequencing (NGS) technologies have played a significant role in uncovering the genes of such genetically heterogeneous group of monogenetic diseases. The clinical features of CMDs/NMDs largely overlap; therefore, a battery of clinical investigations involving muscle magnetic resonance imaging (MRI) and electrophysiology are very helpful in clinical diagnostics. Muscle biopsy despite an invasive procedure can be very informative in diagnosing metabolic myopathies. Gene testing remains mandatory to reach the molecular diagnosis and enables accurate genetic and premarital counseling in high-risk families.

NMDs are broadly classified into AHC, neurogenic, NMJ, myofibrils and metabolic related diseases. Phenotypic classification entails the distribution of muscular involvement that describes the groups of limb girdle muscular dystrophies (LGMDs), which define variable involvements of shoulder and pelvic girdles, distal dystrophies that affect mainly the distal extremities or facial dystrophy labelled facial muscle weakness and wasting. Recent NMDs nomenclature shifted to name the disease-phenotype linked to the specific altered protein.

Congenital forms of muscular diseases (congenital dystrophies and myopathies) are of particular interest since its at-birth or infantile-onset manifestations of generalized hypotonia, respiratory failure, or failure to thrive mandates the urgent and timely NICU (neonatal intensive care unit) incubation. Intensive care accommodation of certain CMDs like SMA-type 1 in the Qatar healthcare system can be extendable for several years. When patients with congenital myopathies/dystrophies grow in childhood, adolescence or become adults, the medical care at the intermittently visited PICU (Pediatric- ICU), complex care facilities, intervention pulmonary and oral feeding clinics and the outpatient clinics of rehabilitation, orthopedics, neurology and cardiology became frequently busy for a long period with these patients.

The huge medical care expense is worth being considered when discussing the value of a tailored newborn screening program in high-risk NMD families. The notion of rare diseases may stand against such screening plans. However, the economy, community and family burdens as well as the high rate diseases from the concept of being “rare” genetic disorders strongly support the need for tailored screening programs, whenever possible.

This CMDs/NMDs Precision Medicine Conference, organized by Weill Cornell Medicine Qatar (WCMQ), sponsored by the Qatar National Research Fund (QNRF)-Conference & Workshop Sponsorship Program (CWSP) and held at the National Convention Center on 11-13 January 2020 was the first in Qatar to gather a team of distinguished international and national physicians and scientists to speak about their experiences and the most up to date information concerning CMD/NMD research, diagnostics, and evolving therapeutics. The interactive meeting’s discussion was truly valuable in underlying what we do need to introduce or improve in our daily practice. The ten questions highlighted in the presentation of the director of the Public Health Department, Ministry of Public Health in Qatar, proposed an actionable plan that can be taken forward. The discussion input by the director of Clinical Research and Affairs, Primary Health Care Corporation (PHCC) in Qatar, highlighted the obvious interest to maximize their role in supporting the early detection of candidate patients. The senior Pediatric Neurologist and conference Co-Chair, Dr. Mahmoud Elsaid, emphasized the importance of establishing a multidisciplinary clinic dedicated to NMDs at Sidra Medicine, Qatar. The unique complex care facilities and the prevention program at Hamad Medical Corporation (HMC) were brought up as being ones of the prominently qualified services in Qatar.

We are truly interested in extending the dimensions of our contribution to the field of myology and having an impactful outcome. At the forefront of translational research, the QNRF grant’s program “Path Towards Precision Medicine (PPM)” has funded in its first cycle, a study at WCMQ, the first to address the clinical, genomic and proteomic characteristics of NMDs in Qatar. The study identified the prevalence of LAMA2-congenital muscular dystrophy in Qatar, which was higher than that reported in the UK and Italy. The high rate of consanguineous marriages and a specific founder mutation are the likely contributors. The study highlighted the unique characteristics of NMDs in Qatari patients: The nonexistence, at most, of the group of myotonic dystrophies among our patients, particular lower incidence of X-linked DMD in Qatari patients compared to that reported worldwide, presence of collagen IV- related muscular dystrophy only in patients of non-Qatari ethnic background and presence of specific founder mutations are examples of such population-specific features. These outcomes, largely uncover the molecular defects of NMDs in national patients. PPM1 study pointed out the urgent need to introduce muscle imaging as routine NMD diagnostics and to carefully investigate candidate genes for mitochondrial and yet uncharacterized myopathies.

Population data of the national programs of Qatar Biobank and Qatar Genome Programme established a good opportunity to further grow and evolve in uncovering new elements of the molecular circuit of muscle diseases.

In order to drive our seat in the field of myology in Qatar, we believe we need to advance our workforce further in all levels of specialization and data sharing. Planning additional NMD-related educational events in Qatar, inviting graduates, postgraduates, healthcare providers and pharmaceutical companies to participate from all over the world will promote our regional and international integration and recognition. Summer school and master classes on NMD’s topics are such educational examples that are globally well perceived. Initiatives for patients’ representative groups will highly impose our community profile and support informative decision making that benefits NMD-patients in various aspects.

Establishing a Qatar Muscle Society and Qatar Institute of Myology or Neuromyology are our ambitious plans that we look forward to accomplishing. A nationally designated body in myology will empower international collaboration and put Qatar on the landscape of evolving clinical trials for the treatment of CMDs and NMDs

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/content/papers/10.5339/qproc.2020.NMD.1
2020-09-15
2020-09-21
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