Improving renal phenotype and evolving extra-renal features of 17q12 deletion encompassing the HNF1B gene.

ABSTRACT

BACKGROUND: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT) suggested by fetal ultrasound findings such as parenchymal hyperechogenicity, overt cystic changes or gross morphological urinary system (UT) abnormalities. The postnatal evolution of these 17q12 deletions encompassing the HNF1B gene-associated findings has not been assessed in depth. METHODS: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017. RESULTS: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletion-associated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases. CONCLUSIONS: Fetal-onset HNF1B deletion-associated kidneys' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.