Homozygous TNNI3 frameshift variant in a consanguineous family with lethal infantile dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases. FAMILY DESCRIPTION: Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency. RESULTS: Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG. CONCLUSION: Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.

Delayed Graft Function in Pediatric Kidney Transplant: Risk Factors and Outcomes.

OBJECTIVES: We aimed to identify risk factors and outcomes of delayed graft function in pediatric kidney transplant. MATERIALS AND METHODS: This retrospective study included all kidney transplant recipients ≤19 years old followed up in our department for a period of 34 years, from January 1989 to December 2022. RESULTS: We included 113 kidney transplant recipients. Delayed graft function occurred in 17 cases (15%). Posttransplant red blood cell transfusion was strongly associated with delayed graft function (adjusted odds ratio = 23.91; 95% CI, 2.889-197.915). Use of allografts with multiple arteries and cold ischemia time >20 hours were risk factors for delayed graft function (adjusted odds ratio = 52.51 and 49.4; 95% CI, 2.576-1070.407 and 1.833-1334.204, respectively). Sex-matched transplants and living donors were protective factors for delayed graft function (adjusted odds ratio = 0.043 and 0.027; 95% CI, 0.005-0.344 and 0.003-0.247, respectively). Total HLA mismatches <3 played a protective role for delayed graft function (adjusted odds ratio = 0.114; 95% CI, 0.020-0.662), whereas transplant within compatible but different blood types increased the risk of delayed graft function (adjusted odds ratio = 20.54; 95% CI, 1.960- 215.263). No significant correlation was shown between delayed graft function and allograft survival (P = .190). Our study suggested delayed graft function as a key factor in allograft rejection-free survival (adjusted odds ratio = 3.832; 95% CI, 1.186-12.377). Delayed graft function was a negative factor for early graft function; patients with delayed graft function had a lower estimated glomerular filtration rate at discharge (P = .024) and at 3 (P = .034), 6 (P = .019), and 12 months (P = .011) posttransplant. CONCLUSIONS: Delayed graft function is a major determinant of early graft function and allograft rejection-free survival. Further research is required to establish proper preventive measures.

Spontaneous hemothorax in a 10-year-old boy with COVID-19.

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic causes. Etiologies of spontaneous hemothorax in children include connective tissue disease, neoplasia and coagulopathy, which is associated with thromboembolic events. We present the case of a 10-year-old chronic hemodialysis patient with spontaneous hemothorax with a concurrent COVID-19 infection.

Monogenic urinary lithiasis in Tunisian children: 25 years' experience of a referral center.

OBJECTIVE: To describe the clinical, biochemical and evolutive profile of monogenic urinary lithiasis in Tunisian children followed up in a reference service, during a 25 years period. METHODS: This was a single-center retrospective observational study of children with urolithiasis, conducted in the pediatric nephrology department in Charles Nicolle Hospital, Tunis, Tunisia over 25 years (January 1st, 1996 to December 31, 2020). Children≤18 of age with urolithiasis with or without nephrocalcinosis related to a monogenic disease were included in our study. RESULTS: A total of 66 children were included in our study. Patients were 5.92±3.48 years of age at the time of urolithiasis diagnosis, and 5.33±3.66 years of age at the time of the underlying pathology diagnosis. The inherited urolithiasis disorders found in our series were: primary hyperoxaluria in 44 cases, cystinuria in 9 cases, Lesch Nyhan syndrome in 5 cases. Renal tubular acidosis was found in 3 cases, and hereditary xanthinuria in 2 cases. Bartter syndrome, adenine phosphoribosyltransferase deficiency and Hereditary hypophosphatemic rickets with hypercalciuria were found in 1 case each. After an average follow-up of 6.45±3.79 years, six patients were in end-stage renal disease. Three patients had died, all of them being followed for primary hyperoxaluria type 1. CONCLUSIONS: Monogenic urinary lithiasis, although rare, are most likely under-diagnosed in countries with high consanguinity such as Tunisia. The screening of these diseases seems to be of primary importance because of their significant morbidity.