Neuromuscular Disorders/Congenital Muscular Dystrophies Present and Future in Qatar: Lessons from PPM1 Research Outcomes
Authors: Abdel Aleem Alice 
Published: September 2020

Editorial

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