A novel deep intronic variant in LAMA2 identified by RNA sequencing.

LAMA2-related muscular dystrophy is caused by pathogenic variants of the alpha2 subunit of Laminin. This common form of muscular dystrophy is characterized by elevated CK >1000IU/L, dystrophic changes on muscle biopsy, complete or partial absence of merosin staining, and both central and peripheral nervous system involvement. Advancements in genomic testing using NGS and wider application of RNA sequencing has expanded our knowledge of novel non-coding pathogenic variants in LAMA2. RNA sequencing is an increasingly utilized technique to directly analyze the transcriptome, through creation of a complementary DNA (cDNA) from the transcript within a tissue sample. Here we describe a homozygous deep intronic variant that produces a novel splice junction in LAMA2 identified by RNA sequencing analysis in a patient with a clinical phenotype in keeping with LAMA2-related muscular dystrophy. Furthermore, in this case merosin staining was retained suggestive of a functional deficit.

Expanding the spectrum of LAMB2: Pierson syndrome associated with neuromuscular junction disorder in two patients.

LAMB2 gene disorders present with different phenotypes. Pierson syndrome (PS) is a common phenotype associated with LAMB2 variants. Neuromuscular phenotype has been reported including hypotonia and developmental delay. However, neuromuscular junction abnormalities represented as congenital myasthenic syndrome (CMS) was reported in one adult patient only. Here, in this paper, we present two pediatric cases with a severe presentation of PS and have CMS so expanding the knowledge of LAMB2 related phenotypes. The first patient had hypotonia and global developmental delay. Targeted genetic testing panel demonstrated homozygous pathogenic variant in the LAMB2 gene (c.5182C>T, pGln1728*) which was reported by Maselli et al. 2009. Repetitive nerve stimulation (RNS) showed a decremental response at low frequency of 3 Hz. On the other hand, the second patient had profound weakness since birth. Tri-Whole exome sequencing showed homozygous pathogenic variant in the LAMB2 gene c.2890C>T, pArg964*. A trial of salbutamol did not improve the symptoms. Both patients passed away from sequala of PS. The spectrum of phenotypic changes associated with LAMB2 mutations is still expanding, and further investigation into the various clinical and morphologic presentations associated with these mutations is important to better identify and manage affected individuals.

Titin related myopathy with ophthalmoplegia. A novel phenotype.

Titin-related myopathy is an emerging genetic neuromuscular disorder with a wide spectrum of clinical phenotypes. To date, there have not been reports of patients with this disease that presented with extraocular muscle involvement. Here we discuss a 19-year-old male with congenital weakness, complete ophthalmoplegia, thoracolumbar scoliosis, and obstructive sleep apnea. Muscle magnetic resonance imaging revealed severe involvement of the gluteal and anterior compartment muscles, and clear adductor sparing, while muscle biopsy of the right vastus lateralis showed distinctive cap-like structures. Trio Whole Exome Sequencing (WES) showed compound heterozygous likely pathologic variants in the TTN gene. (c.82541_82544dup (p.Arg27515Serfs*2) in exon 327 (NM_001267550.2) and c.31846+1G>A (p.?) in exon 123 (NM_001267550.2). To our knowledge, this is the first report of a TTN-related disorder associated with ophthalmoplegia.

Muscle MRI patterns for limb girdle muscle dystrophies: systematic review.

Limb girdle muscle dystrophies (LGMDs) are a group of inherited neuromuscular disorders comprising more than 20 genes. There have been increasing efforts to characterize this group with Muscle MRI. However, due to the complexity and similarities, the interpretation of the MRI patterns is usually done by experts in the field. Here, we proposed a step-by-step image interpretation of Muscle MRI in LGDM by evaluating the variability of muscle pattern involvement reported in the literature. A systematic review with an open start date to November 2022 was conducted to describe all LGMDs' muscle MRI patterns. Eighty-eight studies were included in the final review. Data were found to describe muscle MRI patterns for 15 out of 17 LGMDs types. Although the diagnosis of LGMDs is challenging despite the advanced genetic testing and other diagnostic modalities, muscle MRI is shown to help in the diagnosis of LGMDs. To further increase the yield for muscle MRI in the neuromuscular field, larger cohorts of patients need to be conducted.

Role of plasma homocysteine levels and other associated factors with coronary artery disease among Palestinian patients in North Palestine: a case control study.

Introduction: coronary artery disease (CAD) is one of the leading causes of death worldwide, only two thirds of cases can be explained by CAD´s classical risk factors. There is an increase in attention to homocysteine as a causal of CAD. In Palestine, CAD is more common than that in regional surrounding areas. Coronary artery disease is considered the leading cause of death in the West Bank, according to Palestinian Ministry of health annual reports. The study was conducted to determine the level of homocysteine in individuals with no history of CAD and to determine the relationship between CAD and total homocysteine levels and classical risk factors of CAD. Methods: our study is a hospital-based case-control study. A sample size of 84 cases and 81 controls were included in the study. Results: there is a statistically significant increase in plasma total homocysteine level in cases compared to controls (P=0.04) with Odds ratio= 2. There is also a statistically significant association between plasma total homocysteine levels and age of 50 years and above and male gender among both study groups (P= 0.002 and 0.007, respectively). The study showed no significant association between plasma total homocysteine level and the CAD´s classical risk factors among the case group measured in the study, which are diabetes mellitus, hypertension, and smoking (P=0.5, 0.1, and 0.5, respectively). Conclusion: there is a significant difference in homocysteine levels between case and control groups. Coronary artery disease patients have double homocysteine levels compared to those healthy individuals with OR= 2. Healthy Palestinian individuals have a homocysteine level that is lower than that of regional communities. Homocysteine levels increase with advanced age and male gender. There is no significant relation between hyperhomocysteinemia and diabetes mellitus, hypertension, and smoking.

The Prevalence of Uncontrolled Hypertension among Patients Taking Antihypertensive Medications and the Associated Risk Factors in North Palestine: A Cross-Sectional Study.

Background: Uncontrolled hypertension (HTN) is a challenge for public health professionals all over the world. It is the leading and most important modifiable risk factor for coronary artery disease, congestive heart failure, stroke, renal diseases, and retinopathy. The aim of the present study was to estimate the prevalence of uncontrolled HTN among Palestinian hypertensive patients on treatment. In addition, the study aimed to explore the relationship between socio-demographic and clinical factors with HTN control as well as establish a comprehensive literature review for similar studies. Methods: A cross-sectional study was conducted. 218 hypertensive patients who met the inclusion criteria were included in the study. Results: HTN is not adequately controlled in over 60% of treated patients. Factors that were linked to uncontrolled HTN and were statistically significant as per this study were diabetes (p=0.010), high BMI (p=0.009), smoking (p < 0.0001), lower educational level (p=0.002), and monotherapy (p=0.004). Conclusion: The results suggest that effective efforts on improving HTN control are strongly needed. The efforts need to target hypertensive patients who are also smokers, diabetics, having a low education level, and have a higher-than-normal BMI.

Endovascular Therapy for Childhood Ischemic Stroke.

BACKGROUND Ischemic stroke can have a tremendously negative impact on the fitness and well-being of a child. Because endovascular interventions may be of benefit in the adult stroke population, many investigators have recently evaluated the safety and benefits of pharmacological and non-pharmacological options in the pediatric stroke population and compared pediatric patients to their adult counterparts. Some of these trials have had promising results, showing the positive effects of endovascular treatment in children with arterial acute ischemic stroke due to large-vessel occlusion (LVO). The 2015 American Heart Association/American Stroke Association guidelines suggest that mechanical thrombectomy with stent retrievers may be a consideration in some patients who are younger than 18 years and have severe LVO, when treatment (groin puncture) is initiated within 6 h of symptom onset. However, the method remains under-studied in this age group. CASE REPORT A 7-year-old girl presented with migraine-like headache, right arm and facial weakness, and expressive aphasia 9.5 h after symptom onset. Her PEDS-NIH stroke scale score was 4. Upon further investigations, she was found to have a left middle cerebral artery cryptogenic stroke with a distal left M1 clot, which was successfully treated with mechanical thrombectomy. Huge improvement was noticed during her subsequent physical examination. CONCLUSIONS Endovascular therapy offers an exciting treatment option for the management of pediatric stroke. The extent of safety of mechanical thrombectomy among children who present with large-vessel occlusion over an extended time window remains unknown and warrants further investigations.

Vaccines Attitudes, Concerns, and Information Sources Reported by Parents of Young Children among North Palestinian Parents.

Parental acceptance of routine childhood immunization is critical to protecting children's health, as high vaccination-coverage rates lead to decreased rates of vaccine-preventable diseases. However, to communicate effectively with parents about vaccines and vaccine-preventable diseases, it is necessary to assess their vaccine-related attitudes and concerns continually. Recently the Palestine Ministry of Health has recorded epidemics of measles and mumps. Poor compliance with vaccination has been attributed to multiple factors including physician inadequacy advocating for vaccination and public mistrust of vaccinations. As a result, this study was conducted to describe the vaccine-related attitudes, concerns, and information sources of North Palestinian parents of young children. A cross-sectional survey was conducted involving parents visiting emergency departments and primary health care centers from different North Palestinian hospitals and centers. 480 surveys were eligible and analyzed. The surveys revealed that although parental confidence in vaccine safety is high, several vaccine-related concerns, such as pain from vaccine administration and the number of vaccines given at once, were common among parents of young children. To maintain and improve the success of childhood vaccines in preventing disease, a holistic approach is needed to address parents' concerns in an ongoing manner. Listening and responding in ways and with resources that address specific questions and concerns could help parents make more informed vaccination decisions.

Fanconi-Bickel syndrome in two Palestinian children: marked phenotypic variability with identical mutation.

BACKGROUND: Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare autosomal recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a member of the facilitative glucose transporter family (Santer et al. J Inherit Metab Dis 21:191-194, 1998). The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal renal tubular dysfunction, rickets and severe short stature. CASE PRESENTATION: We report 2 Palestinian patients from 2 families who were homozygous for the mutation p.R301X (C>T) in exon 7of GLUT2 gene. Patient 1 showed clinical and laboratory improvement with age characterized by normal growth and resolution of rickets. Patient 2 had severe phenotype characterized by progressive weight loss, persistent metabolic acidosis, marked polyuria and clinical and laboratory findings of rickets progressing to death at age 10 months. CONCLUSION: This report further expands the clinical spectrum of FBS even with identical mutations. Other yet unknown genetic, environmental or stochastic factors may be responsible for phenotypic variability.