FETAL RENAL CYSTIC DISEASES by Cathy Cluver1,2, Sammya Moura3, Fabricio Costa4 and Simon Meagher14 1.Mercy Hospital for Women, Melbourne University, Australia; 2.Stellenbosch University, South Africa; 3.University of Fortaleza, Brazil; 4. Monash Ultrasound for Women, Melbourne, Australia Normal Autosomal recessive polycystic kidney Multicystic kidney disease (MCKD): Potter II Autosomal dominant polycystic Hydronephrosis: Potter IV Hyperechoic kidneys + Genetic Syndromes/ Unexplained disease (ARPKD): Potter I kidney disease (ADPKD): Potter III aneuploidies Hyperechoic kidneys Ultrasound Kidneys Bilateral, hyperechoic enlarged kidneys from Often unilateral (80%) US findings after 14-16 weeks Caliectasis: connections visible between calyces and Echogenic kidneys Unilateral or bilateral Finding 16w Large hyperechoic kidney Bilateral enlarged or grossly enlarged pelvis May be enlarged No other anomalies Diagnosis only made in 50% at mid trimester Multiple and non-communicating cysts of variable shapes kidneys Parenchyma not echogenic Associated with other anomalies Renal length most valuable in diagnosis and sizes Hyperechoic cortex only ‘Eggshell sign’: crescent of increased echogenicity at 1-2 mm non-communicating Loss of reniform shape Exaggerated corticomedullary caliceal/ parenchymal interface Renal cysts, some may have macrocystic Ultrasound findings after 14 weeks differentiation Unilateral or bilateral disease Cysts in pancreas, liver, spleen, and CNS Associated with megaureter and perinephric urinoma Cystic fusiform dilatation of the collecting No cysts seen in kidneys Present if renal pelvis AP diameter >5mm at less than 32 ducts weeks and >10mm after 32 weeks Bladder Absent Normal Normal Absent/normal/ dilated/thick-walled bladder Normal Normal AFI Develop severe oligohydramnios Normal if unilateral, oligohydramnios if bilateral Usually normal Normal or oligohydramnios (dependent on cause) Normal/reduced Normal Vesicoureteric reflux / obstruction http://youtu.be/j74CvWUTtGI http://youtu.be/4sT0BPaZv84 http://youtu.be/TcfuHMNqqPA http://youtu.be/oxoFVXGy0Jk http://youtu.be/qD_QXmCu7Pk http://youtu.be/RSXgvWlAiGQ http://youtu.be/VC6rur0JKBM http://youtu.be/Gc2jP4TT9ag http://youtu.be/N89BGCH4uVA http://youtu.be/ZTF5qOBq--8\ Subtypes 1. Unilateral MCKD 2. Unilateral MCKD in 3. Unilateral MCDK Pelvic-ureteric junction obstruction (PUJ) a small atrophic presenting with kidney simple peripheral http://youtu.be/VNAktIZS0pM st 1 Trimester cysts http://youtu.be/EQg2heIa7g ARPKD http://youtu.be/56x9LmRJVM0 http://youtu.be/4y7OjAq84a0 Case 1 http://youtu.be/I-zLC9nWdD8 Case 1 (third trimester) http://youtu.be/rOxYjO6tu0o nd http://youtu.be/5bLKkZJn8HY Case 1 Meckel Gruber Syndrome 2 Trimester http://youtu.be/NKuoqekmvvg http://youtu.be/gEteOD-8mzI Case 1 Case 2 (second trimester) http://youtu.be/ioUX4zQyL5U Case 2 http://youtu.be/Kz2nTj02hy4 http://youtu.be/VihL-6Z5kXI http://youtu.be/zXd48KpJ9oY http://youtu.be/JJgsOz_hTgE http://youtu.be/3Nco-BASv1Y http://youtu.be/fbVHTNYctf0 http://youtu.be/V8ArP8sGvaA Case 2 http://youtu.be/ytNIeeHXOL0 http://youtu.be/Vae5cb2JP6M http://youtu.be/6d51hTe3k_Y http://youtu.be/5keyegsYj_s http://youtu.be/YA81I1TaYao 2 weeks later: http://youtu.be/jyXabNkN7j0 http://youtu.be/CSY2PH2S6wg rd http://youtu.be/tKGz5bkX6Pc MCKD in superior pole 4 weeks later: http://youtu.be/VOtqpBc_zQ4 3 Trimester http://youtu.be/Ru9Flisd3iA http://youtu.be/5Ui-w8ZIoow http://youtu.be/lWwTHrwPKbI http://youtu.be/aO_NbALLiYs http://youtu.be/s0TbTLOClVk 4. Unilateral MCKD in 5. Unilateral pelvic 6. Unilateral MCKD Case 2 http://youtu.be/L0twMtDa4FM one moeity of a ectopic kidney with reniform shape http://youtu.be/F_KeD27DUY4 duplex system MCKD maintained http://youtu.be/katC_ww7j8Y Posterior urethral valves Trisomy 18 1st trimester http://youtu.be/HnzKlyWmNII http://youtu.be/-dSDKow2JEM http://youtu.be/GIG4zEWHn7M http://youtu.be/mCDMQSM7yWo http://youtu.be/Ia8vY8tSwTU http://youtu.be/uAW9FRMHUus Trisomy 13 http://youtu.be/RgHDugGR-BY http://youtu.be/qumUDlFdawc http://youtu.be/__wBduHKQck http://youtu.be/UTy8rg0O51M http://youtu.be/5iVsuObnXqQ 7. Unilateral MCKD 8. Unilateral MCKD 9. Bilateral MCKD http://youtu.be/29xUFITZcGo with an abnormal with contralateral contralateral kidney renal aplasia) Bardet-Beidl Syndrome http://youtu.be/DOJ8df_tyvY Urethral agenesis http://youtu.be/YDXm59DVe34 http://youtu.be/nIH_qybQQ_A st 1 trimester http://youtu.be/N3gVmSE6JhI http://youtu.be/7WQEpD81YcM 2 weeks later http://youtu.be/PVHAB6OyfoA 2nd trimester http://youtu.be/j7GKPnX91GE http://youtu.be/r8oLEZOiBO8 http://youtu.be/NosvgLPuBDA http://youtu.be/U4RVvdm5NrA 10. Horseshoe MCKD 11. Bilateral MCKD: http://youtu.be/OzVQYjkEJTw Unusual presentation http://youtu.be/uzOMiIcY3pQ http://youtu.be/94bUyDRy1Nc http://youtu.be/TL5vVyfu0lk http://youtu.be/NRNHsp5thc0 Autosomal recessive polycystic kidney Multicystic kidney disease (MCKD): Potter II Autosomal dominant polycystic Hydronephrosis: Potter IV Hyperechoic kidneys + Genetic Syndromes/ Unexplained disease (ARPKD): Potter I kidney disease (ADPKD): Potter III aneuploidies Hyperechoic kidneys Incidence 1:20 000-40 000 Unilateral 1: 3 000-5 000, Bilateral: 1: 10 000 1: 800-1 000 Most common uropathy 1: 100 Sporadic/genetic-linked/family-linked/age-linked 10-21% hyperechoic kidneys Associated Potter sequence develops after 20 weeks In 30–50% the other kidney is dysplastic or affected by Not associated with aneuploidies Aneuploidies: 0,4-1,6% (50% being T21) Extra-renal: None anomalies (oligohydramnios and pulmonary hypoplasia) vesico-ureteric reflux Polycystic disease of liver, spleen and Syndromes: 5-10% (VACTERL, Cerebro-digital syndrome, Cardiac Liver cysts, hepatic fibrosis, portal Unilateral: 26% extra-renal anomalies pancreas rarely seen in the fetus but tuberous sclerosis) Neurological hypertension and biliary duct hypoplasia Bilateral: 67% extra-renal anomalies common in adults Facial (clefts, cataracts, macroglossia) Extra-renal anomalies: cardiac (majority), GIT, CNS, spine, Spinal and limb single umbilical artery, genital anomalies. Diaphragmatic hernia Syndromes: VACTERL, Cerebrodigital, Brachio-oto-renal, GIT: exomphalos Meckel–Gruber, Bardet–Biedl, Fraser, CHARGE Genital and urinary tract anomalies Genetic Autosomal recessive 90% non-genetic- linked Autosomal dominant (90%) Usually not genetic linked Syndromes Normal Karyotype associations/ Significant genetic heterogeneity 10% autosomal dominant 10%: no family history of ADPKD (genetic Meckel Gruber: cleft lip/palate, encephalocele, polydactyly Not associated with Aetiology Single gene disorder: 80% mutation in PKHD1 mutation) Obstructive: and microphthalmia, heart defects and ambiguous syndromes Gene on chr 6P21 Monogenic causes: mutations in individual genes, such as PKD1 mutations (85%): gene on Ureteropelvic junction obstruction (UPJ) 10-30% genitalia, Autosomal recessive 17q21-q24 or 11q13. Aetiology nonspecific Can be associated with other single gene TCF2, PAX2 and uroplakins chromosome 16p13 Ureterovesical obstruction (UVJ)/megaureter 5-10% Beckwidth-Weidermann: overgrowth syndrome, anomalies and aneuploidies Heterozygote mutations in several genes PKD2 mutations (15%): gene on Posterior urethral valves (PUV): only males 1-2% exomphalos, Autosomal dominant 11p15.5 •4 types: prenatal, neonatal, infantile and chromosome 4q21-q23 Urethral agenesis (rare) Simpson-Golabi-Behmel: overgrowth syndrome juvenile Risk of chromosomal anomalies Can be a component of tuberous Ectopic ureter, ureterocoele (5-7%) X-linked /mutations in GPC3 Unilateral dysplasia: 2-4% sclerosis: gene TSC2 on chromosome 16 Bardet Biedl: genital anomalies and polydactyly Bilateral dysplasia: 15-18% Non obstructive Autosomal recessive 2q, 3p,11q,15q and 16q (Trisomy 13 and 18) or inherited conditions (3-10%) Vesicoureteral reflux (VUR) 10-12% Pearlman: Diaphragmatic hernia, macrosomia, cleft palate, Nonrefluxing nonobstructive megaureter dextrocardia, cryptorchidism, Autosomal recessive Risk of non-chromosomal syndromes Prune belly syndrome (rare) Zellweger: hepatomegaly, hypotonia, cataracts • 5-10% Autosomal recessive, multiple genes Physiological: Elejalde- nasal hypoplasia, craniosynostosis, exomphalos, Physiological transient dilation of collecting system (41- short limbs, hydrops 88%): resolves in pregnancy Di George: cardiac anomalies, clefts, absent thymus, 22q deletion VACTERL: vertebral anomalies, anal stenosis or atresia, tracheo-esophageal fistula, radial, renal, cardiac and non- radial limb defects. Sporadic Aneuploidies Trisomy 8,9,13,18 and 21, 45X, Triploidy Antenatal Genetics referral Morphological fetal assessment for other anomalies and Genetic consultation Degree of hydronephrosis is significant: AP diameter Genetic counselling Genetic analysis may be Invasive testing should be offered syndromes Can offer gene sequencing and >4mm in 2nd and 7mm in 3rd trimester. Postnatal risks Offer karyotype with microarray indicated management nd rd Ideally microarray and specifically request Invasive testing is offered if bilateral renal involvement or identification of mutations with greater if >6mm in 2 and >10 in 3 trimester TOP may be indicated Serial ultrasounds to assess PKHD1 gene on chromosome 6P21 (80% cases) if associated non-renal abnormality microarray (DR 50 to 75% for PKD1 and Isolated mild pyelectasis doesn’t incr risk of aneuploidy Serial ultrasounds to assess liquor volume liquor and kidneys Parenteral karyotyping may be