Valpaços C1,2*, Soares AR3, Baptista R1, Sousa MP1, Madalena C4, Matos P1, Sameiro Faria MD1 and Mota C1
1Department of Child and Adolescent, Pediatric Nephrology Unit, Northern Maternal and Child Center, University Hospital Center, Portugal 2Department of Child and Adolescent, Santa Luzia Hospita, Portugal 3Department of Medical Genetics, Northern Maternal and Child Center, University Hospital Center, Portugal 4Department of Child and Adolescent, Póvoa do Varzim Vila do Conde Hospital Center, PortugalFulltext PDF
Renal cysts often represent a diagnostic challenge in pediatric age, given the range of disorders they may be associated to. They can be either congenital (due to non-hereditary fetal malformations or genetic mutations) or, more rarely, acquired. The Hepatocyte Nuclear Factor-1beta (HNF1β) gene is known to play an essential role in the embryonic development of several organs (such as kidneys, pancreas, liver and parathyroid glands). Molecular genetics has allowed the identification of new mutations occurring in this gene and HNF1β-associated disease is now recognized as a clinical entity of variable and multisystemic phenotype. We present the case of a male child, referred to a pediatric nephrology unit at age 4, after presenting the first signs of nephropathy. Abdominal ultrasonography had shown cortical renal cysts. The patient had a stage 2 Chronic Kidney Disease (CKD). He later presented an insulin-dependent diabetes, at age 7. The combination of early onset diabetes and renal cystic disease was suggestive of an HNF1β-associated condition. Genetic testing of the patient and his parents confirmed a de novo nonsense mutation on heterozygosity at HNF1β (c.301G>T (p.E101*), exon 1). Even though a strictly renal phenotype may occur, the association of renal disease and diabetes at a young age should particularly alert nephrologists and pediatricians to the possibility of an HNF1β- associated disease. Furthermore, the early detection of this genetic mutation will warrant screening of other potential extrarenal disorders or malformations and allow appropriate genetic counseling to patients and their families.
Hepatocyte nuclear factor 1-beta; Cystickidneys; Maturity-onset diabetes of the young; Type 5
Valpaços C, Soares AR, Baptista R, Sousa MP, Madalena C, Matos P, et al. A Renal Cysts and Diabetes (RCAD) Syndrome Associated with a Hepatocyte Nuclear Factor 1β (HNF1β) De Novo Mutation: A Case Report on the Challenges of the Diagnostic during Childhood. Ann Clin Case Rep. 2020; 5: 1794..