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Introduction: Polycystic kidney disease (PKD) is a genetic disorder with a variable clinical presentation dominantly characterized by cystic expansion of the kidney in addition to various extrarenal manifestations, most commonly cysts and aneurysms. Therefore, when other abonrmalities are present, expanded genetic testing might indicate an additional underlying cause. Patient (N°) 1 2 3 4 5 Age at onset (yrs) 6 5 6 7 6 Genetic findings FBN2 (VUS) KRAS mosaic NF1 NF1 FBN2 Vascular abnormalities (stenosis) Supra-renal aorta, bilateral renal artery (left post-stenotic aneurysm), inferior mesenteric artery Sub-renal aorta, bilateral renal artery ; inferior mesenteric artery Renal aorta, bilateral renal artery, celiac tripod, superior mesenteric artery Renal aorta, bilateral renal artery (right post stenotic aneurysm) Renal aorta, bilateral renal artery ; ectasia of ascending aorta ; bicuspid aortic valve Drugs (N°) 2 3 3 1 4 Follow up (yrs) 3 9 15 8 1 Endovascular/ surgical treatment Percutaneous angioplasty Percutaneous angioplasty - - Percutaneous angioplasty Renal auto-transplant Reduction of anti-HTN treatment - - - - 1 drug stopped, 1 reduced dosage Pediatric Nephrology (2022) 37:2803–2969 2887Material and methods: Case report Results: We present the case of a 16 months old girl with arterial hypertension and polycystic kidney disease. She was born premature with unremarkable gestation. Shortly after birth she developed lower extremities edemas, oligury and hyponatremia. From the second day of her life increased blood pressure was measured. Renal ultrasound revealed large kidneys with many small cysts in parenchyma while echocardiogram indicated hypertrophy of interventricular heart septum. Due to involvement of various organ systems at the age of 11 months comprehensive genetic testing was performed. Sequence analysis using the Blueprint Genetics (BpG) Whole Exome Plus identified a heterozygous nonsense variant PKHD1 c.9319C>T, p. (Arg3107*), a heterozygous missense variant PKHD1 c.4882C>G, p. (Pro1628Ala), and a heterozygous missense variant PTPN11 c.178G>A, p.(Gly60Ser). The two former variants are classified as pathogenic and the latter as likely pathogenic. Conclusions: While mutations in PKHD1 gene are related to defects in cilia-mediated signaling activity resulting in cyst formation and recessive form of PKD, PTPN11 muatations have been associated with dysregulation of the RAS-MAPK signaling pathway recognized as the molecular cause underlying a group of clinically related developmental disorders with features including reduced growth, facial dysmorphism, cardiac defects, ectodermal anomalies, variable cognitive deficits, and susceptibility to certain malignancies. Consequently, there is a wide range of possible genotypic-phenotypic correlations arising from those mutations, previously undescribed in the same patient. |
