KERMOND R1, MCCARTHY H1,2,3,4, KENNEDY S1,3, MACKIE F1,3, ALEXANDER S2,4, SHALHOUB C1,3
1Department of Nephrology, Sydney Children’s Hospital Randwick, Sydney, Australia, 2Department of Nephrology, The Children’s Hospital at Westmead, Sydney, Australia, 3UNSW School of Women’s and Children’s Health, Sydney, Australia, 4USyd Faculty of Medicine and Health, Sydney, Australia
Aim: To further assess the genotypic and phenotypic variation of the PAX2-related disorder.
Background: PAX2 encodes a transcription factor important for the development of the kidneys, genital tract, eyes and ears. It is also expressed in the pancreas and central nervous system during embryonic development. PAX2-related disorder is an autosomal dominant disease that is classically associated with renal and ophthalmological involvement.
Methods: We identified 18 patients from 5 families with a confirmed pathogenic variation of the PAX2 gene.
Results: Of the 18 patients with genetically proven disease, one had no documented renal involvement. 13/18 had variable congenital anomalies of the kidney and urinary tract (CAKUT) including hypodysplasia (44%), vesicoureteric reflux (with or without dysplasia) (16%), pelviureteric junction obstruction (6%) and multicystic dysplastic kidney (6%). 3/18 had no CAKUT and presented with focal segmental glomerulosclerosis (FSGS). All patients with renal involvement had evidence of proteinuric chronic kidney disease (CKD) and most were hypertensive. The degree of CKD varied within families with nil obvious genotypic-phenotypic correlation. In one family with monozygotic twins, twin one required a renal transplant at age ten while twin two had CKD stage three at age seventeen. 2/15 patients who had a formal review had no ophthalmological manifestations while 13/15 patients had some change ranging from unilateral optic pit to bilateral optic disc coloboma. Other clinical manifestations in this cohort included sensorineural hearing loss, neonatal hypercalcaemia, growth failure, dyslipidaemia and obesity.
Conclusions: Pathogenic variations of the PAX2 gene result in a variable phenotypic expression even within families. This condition should be considered in patients presenting with either ophthalmological or CAKUT/FSGS where there is a family history of coloboma or renal disease.
Dr Rachael Kermond is an Advanced Paediatric Nephrology Trainee currently completing a Nephrology Fellowship at the Children’s Hospital Westmead, Sydney. She is passionate about patient centred care and medical education. Rachael’s current research interests include renal genetics, acute kidney injury and transplantation.