Clinical and genetic characterization of 5q SMA in Palestine

Description

Spinal muscular atrophy (SMA) is a genetic condition that impacts motor neurons which have the role in muscle movement. The degeneration of these motor neurons results in symptoms of muscle weakness and muscle wasting, which can affect the ability to move, breathe, and swallow. The most common form of SMA is the 5q-SMA in which there are disease-causing changes in both alleles of the SMN1 gene leading to a deficiency of survival motor neuron (SMN1) protein. The SMN2 gene is closely related to the SMN gene and is important for producing small amounts of SMN protein that has a function. Generally, the higher the number of SMN2 gene copies, the lesser the severity of the disease but the correlation is not absolute. There can be two patients with the same copy number of the SMN2 gene who experience symptoms at different times and achieve different motor skills. Studying the differences requires connecting the genetic data with clinical information from the history of the disease with its onset and milestones achieved in motor skills. In particular, treatment history plays an important part in this process, because treatment is able to change the course of the disease and influence the conditions of the patient over time. In Palestine, information about SMA patients is dispersed between the various hospital records and genetic laboratories. Thus, it becomes difficult to gather a clear picture about their clinical and genetic characteristics. The establishment of a multicenter registry will help in the aggregation of these records through the application of standardized procedures and guidelines, ensuring that any missing information could be identified, and an essential baseline established for future research and following up the patients. It can also provide local evidence for advocating the improvement of diagnostic and therapeutic services. Research Questions 1. What are the demographic, clinical, and genetic characteristics of patients with genetically confirmed 5q-SMA at participating Palestinian healthcare institutions? 2. What SMN1 findings and SMN2 copy numbers are documented among these patients? 3. How does SMN2 copy number relate to the age at which symptoms begin, the highest motor milestone achieved, and clinical severity? 4. What clinical differences are seen among patients with the same SMN2 copy number, taking treatment history and other available factors into account? 5. What gaps in existing records need to be addressed to build a reliable Palestinian SMA registry? Study Aim We aim to establish the first published multicenter genetic and clinical characterization of 5q-SMA in Palestine by compiling existing hospital-based genetic testing results (SMN1 and SMN2), performing additional genetic analysis when needed, and correlating genetic findings with clinical severity. The study is being organized by the Palestinian RNA Group at Al-Quds University in collaboration with the pediatric neurologists Dr. Motee Ashhab and Dr. Bassam Abu Libdeh.   Study Design: This is an observational, multicenter study with cross-sectional genetic characterization, retrospective and prospective clinical data collection. Clinical and genetic information will be obtained using a standardized form based on the TREAT-NMD SMA dataset. The information will be gathered from patients’ medical files and genetic reports and verified if necessary with medical professionals of the patients. 80 patients will be recruited during 24-month periods from Al-Makassed Hospital, Caritas Baby Hospital, and other Palestinian Ministry of Health-related facilities in Ramallah and Hebron. Information that will be collected will include age of onset, family history, motor development, respiratory and food support, treatment information, SMN1 results as well as SMN2 copy number results. Future Plans In the next phase, we will assess whether SMA therapies improve prognosis in Palestinian patients by monitoring clinical outcomes in individuals who receive treatment, using clinical trial–based outcome measures.