Pathogenic Novel Heterozygous Variant c.1076c>T p. (Ser359Phe) chr1: 120512166 in NOTCH2 Gene, Type 2 Alagille Syndrome Causing Neonatal Cholestasis: A Case Report.

BACKGROUND Alagille syndrome (ALGS) is a multisystem hereditary illness with a dominant pattern and partial penetrance. Multiple organ abnormalities can be caused by mutations in the Jagged canonical Notch ligand 1 (JAG1) gene. Notch receptor 2 (NOTCH2) gene mutations are also uncommon. ALGS is also characterized by deformed or narrowed bile ducts and is notoriously difficult to diagnose due to the wide range of symptoms and absence of unambiguous genotype-phenotype connections. Little is known about ALGS patients who have NOTCH2 mutations. We present a patient who developed progressive liver failure due to a unique pathogenic heterozygous variation of the NOTCH2 gene, c.1076c>T p. (Ser359Phe) chr1: 120512166, resulting in type 2 ALGS. CASE REPORT A Saudi Arabian newborn with bilateral hazy eyes, ectropion, dry ichthyic skin, normal male genitalia, and bilateral undescended testes was born at 31 weeks. Previous miscarriages, pregnancy-induced maternal cholestasis, fatty liver, or neonatal jaundice were not reported in the family history. He had developed worsening cholestatic jaundice by the third week of hospitalization. The extensive work-up for metabolic, infectious, and other relevant etiologies was negative. Following gram-negative sepsis, he died of multiorgan failure. A NOTCH2 gene mutation explained the phenotypic difference in our situation. Another intriguing observation was the presence of ichthysis and craniosynostosis in ALGS with a NOTCH2 mutation. CONCLUSIONS Cholestasis in newborns can be difficult to diagnose. Next-generation sequencing detects 112 copy number variants in the cholestasis gene panel blood test. More research is needed to understand why NOTCH2 mutations are relatively rare in ALGS.

An 11-Year-Old Saudi Arabian Girl Who Presented with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection with Coronary Artery Aneurysm and Cardiac Involvement: A Case Report.

BACKGROUND Early in the COVID-19 pandemic, children who were infected with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) with vascular inflammation were described as having a vasculitis similar to Kawasaki's disease. There are now consensus clinical guidelines that have described the presentation and diagnosis of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. This report aims to describe a case of MIS-C in an 11-year-old Saudi Arabian girl who presented with coronary artery aneurysm and cardiac involvement. CASE REPORT We describe an 11-year-old Saudi girl who was asymptomatic for 3 weeks after contracting SARS-CoV-2. Three weeks after suffering a mild flulike illness, she developed a high fever, cough, and severe clinical deterioration within 12 h of admission, including shock, rash, pleural effusion, high inflammatory markers, and a coronary aneurysm. As per current practice, the diagnosis was confirmed as multisystem inflammatory syndrome based on a SARS-CoV-2 test with reverse transcription polymerase chain reaction (RT-PCR) from 2 nasopharyngeal aspirates. Her condition was successfully treated with antibiotics, inotropes, IVIG, aspirin, and Tocilizumab, in addition to high-flow oxygen therapy. Eventually, she was able to return home after fully recovering. CONCLUSIONS The findings in this report suggest that children with MIS-C due to SARS-CoV-2 infection can have a good prognosis, even when they suffer from coronary artery and cardiac involvement. The increasing number of emerging SARS-CoV-2 variants that affect children supports the importance of RT-PCR for the COVID-19 diagnostic test for children with multisystem or cardiovascular inflammation, which may guide the most appropriate clinical management of the variants of MIS-C.