Exploring the role of Islam on the lived experience of patients with Long QT Syndrome in Saudi Arabia.

Genetic services are rapidly growing in the Arab world leading to increasing number of patients being diagnosed with genetic disorders. Islam is the only/major religion of the local population in these countries. Muslim patients integrate religion in virtually every aspect of their lives, and it is vital to understand the role of Islam on their coping and decision-making in the context of genetic counseling. This will help provide patients with the most appropriate services aligned to their religious beliefs and will improve outcomes. Increasing numbers of patients are being diagnosed with Long QT syndrome in Saudi Arabia. Using semi-structured interviews, this study explored the role of Islam on the lived experience of 13 Saudi participants diagnosed with autosomal dominant Long QT syndrome (3/13) or who are carriers of Jervell and Lange-Nielsen syndrome (10/13). The interviews investigated how they made sense of living with the condition in light of their religion/spirituality. The data were analyzed using interpretative phenomenological analysis and produced four superordinate themes: 1) Common belief and idiosyncratic interpretation; 2) Using religion to justify positive reframing of current illnesses; 3) Interplay between belief in medicine and in religion; and 4) Complex impact of diagnosis on religiosity. The results show that the participants' idiosyncratic interpretations of the religious principles, not the principles themselves, had an important influence on their coping, medical decision-making, perceptions regarding the cause of their disease, and compliance with medical advice. A novel insight of the current study is that the personal understanding and interpretation of medical information played the greatest role in the decision-making process, and not the religious beliefs. Thus, it is important for health professionals to give patients' information in a manner that is clear and detailed in order for them to facilitate an informed decision, and to ensure that they fully understand the implications.

The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private mutations (only 32.5% of the recessive mutations are founder), as well as the first instances of recessive inheritance of previously assumed strictly dominant disorders (involving ITPR1, VAMP1, MCTP2, and TBP). Surprisingly, however, dual molecular diagnosis was only observed in 1.5% of cases. Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT1, GRIK4, GRSF1, GTRP1, HID1, IFNL1, KCNC4, LRRC52, MAP7D3, MCTP2, MED26, MPP7, MRPS35, MTDH, MTMR9, NECAP2, NPAT, NRAP, PAX7, PCNX, PLCH2, PLEKHF1, PTPN12, QKI, RILPL2, RIMKLA, RIMS2, RNF213, ROBO1, SEC16A, SIAH1, SIRT2, SLAIN2, SLC22A20, SMDT1, SRRT, SSTR1, ST20, SYT9, TSPAN6, UBR4, VAMP4, VPS36, WDR59, WDYHV1, and WHSC1) not previously linked to human phenotypes and these are presented to accelerate post-publication matchmaking. Two of these genes were independently mutated in more than one family with similar phenotypes, which substantiates their link to human disease (AKAP6 in intellectual disability and UBR4 in early dementia). If the novel candidate disease genes in this cohort are independently confirmed, the yield of WES will have increased to 83%, which suggests that most "negative" clinical exome tests are unsolved due to interpretation rather than technical limitations.

The Impact of Integration of a Genetic Clinic Into a Pediatric Cardiac Unit.

BACKGROUND: Previously published studies suggest that genetic or environmental causes can be observed in 20-30% of congenital heart disease (CHD) patients, which include aneuploidy, single gene defects, pathological copy number variations, and de novo autosomal dominant and recessive inheritance. Moreover, the genetic background of childhood cardiomyopathies (CMs) has not been elucidated well. OBJECTIVE: The study highlights the value of genetic assessment in diagnosing and family counseling for CHD and pediatric CM patients referred to the genetic clinic in a pediatric cardiology department. METHODS: The study involved patients less than 18 years of age attending the cardiogenetic clinic in the pediatric cardiology department between December 2010 and February 2019. The following patient categories who had genetic evaluation were included: CHD in the presence of a syndromic phenotype, patients with CHD having extracardiac congenital anomalies or delayed development, hypertrophic and dilated CM patients, patients with dilated aortic root and ascending aorta, significant CHD in siblings or first-degree relatives, suspected channelopathies; and interrupted aortic arch abnormalities. RESULTS: A total of 285 patients were evaluated in the cardiogenetic clinic. The mean age was 20.2 months, with a range of 0-168. Females and males constituted 153 (53.7%) and 132 (46.3%), respectively. The most common cause of referral to the genetic clinic was the presence of CM (N=134 (46.3%)): hypertrophic CM in 24% and dilated CM in 20% of cases. Seventy-six patients (26.7%) had positive genetic results. The most common genetic abnormality was familial infantile hypertrophic CM-causing gene ELAC2 in 19 (23.5%) cases. CONCLUSION: It may be beneficial for any pediatric cardiology unit to provide an established genetic clinic. Using a genetic clinic will enhance understanding of CHD pathophysiology, family education, and genetic counseling. Agreement on a well-written protocol and the way forward to specify what congenital heart conditions require genetic investigation should be clarified.

Clinical and Genetic Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy Patients: A Single-Center Experience.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited progressive cardiomyopathy. We aimed to define the long-term clinical outcome and genetic characteristics of patients and family members with positive genetic tests for ARVC in a single tertiary care cardiac center in Saudi Arabia. Methods: We enrolled 46 subjects in the study, including 23 index-patients (probands) with ARVC based on the revised 2010 ARVC Task Force Criteria (TFC) and 23 family members who underwent a genetic test for the ARVC between 2016 and 2020. Results: Of the probands, 17 (73.9%) were males with a mean age at presentation of 24.95 ± 13.9 years (7 to 55 years). Predominant symptoms were palpitations in 14 patients (60.9%), and syncope in 10 patients (43.47%). Sustained ventricular tachycardia (VT) was documented in 12 patients (52.2%). The mean left ventricular ejection fraction (LVEF) by echocardiogram was 52.81±6.311% (30-55%), and the mean right ventricular ejection fraction (RVEF) by cardiac MRI was 41.3±11.37% (23-64%). Implantable cardioverter-defibrillator (ICD) implantation was performed in 17 patients (73.9%), and over a mean follow-up of 13.65 ± 6.83 years, appropriate ICD therapy was noted in 12 patients (52.2%). Genetic variants were identified in 33 subjects (71.7%), 16 patients and 17 family members, with the most common variant of plakophilin 2 (PKP2) in 27 subjects (81.8%). Conclusions: ARVC occurs during early adulthood in Saudi patients. It is associated with a significant arrhythmia burden in these patients. The PKP2 gene is the most common gene defect in Saudi patients, consistent with what is observed in other nations. We reported in this study two novel variants in PKP2 and desmocollin 2 (DSC2) genes. Genetic counseling is needed to include all first-degree family members for early diagnosis and management of the disease in our country.

COVID-19 in Unvaccinated patients with inherited metabolic disorders: A single center experience.

Patients with certain inherited metabolic disorders (IMD) are at high risk for metabolic decompensation with exposure to infections. The COVID-19 pandemic has been particularly challenging for health care providers dealing with IMD patients, in view of its unpredictable consequences in these patients. There is limited data in literature on evaluating the impact and the outcome of COVID-19 infection in these patients. This cross-sectional retrospective study on a large cohort of unvaccinated IMD patients, reviewed the incidence of COVID-19 infection, disease manifestation and outcome during the pandemic between November 2019 and July 2021. In this cohort of 1058 patients, 11.7% (n = 124) were infected with COVID-19. Their median age was 16 years (age range 2-42); 57% (n = 71) were males. Post-exposure positive test was noted in 78% (n = 97) patients, while 19% (n = 24) had symptomatic diagnosis and three patients tested positive during pre-hospital visits screening. Most patients, 68.5% (n = 85) had mild COVID-19 related symptoms such as fever, cough, headache and diarrhea while 13.7% (n = 17) patients had no symptoms. Of twenty-two patients (17.7%) who required hospitalization, 16 were adults with various intoxication and energy metabolism disorders, who developed IMD related complications such as metabolic acidosis, hyperammonemia, acute pancreatitis, hypoglycemia, rhabdomyolysis and thrombosis. Ten patients needed intensive care management. The cohort death rate was 2.4% (3 patients). Overall, the clinical course of COVID-19 infection in these IMD patients was relatively mild except for patients with intoxication and energy metabolism disorders who had high risk of developing acute metabolic decompensation with severe complications.