17q12 deletion syndrome causes developmental abnormalities of the kidneys, pancreas, genital tract, and neurodevelopment, and it has a wide range of phenotypes ranging from fetal demise to normal adulthood with minimal renal impairment. Here we describe a rare case of 17q12 deletion diagnosed prenatally, complicated by anhydramnios and Potter sequence. The baby was born but necessitated life-saving interventions due to pulmonary and renal insufficiency and ultimately succumbed to multi-organ failure. We present full autopsy results describing findings linked to 17q12 deletion, including severe bilateral multicystic renal dysplasia, pancreatic hypoplasia, and cysts adjacent to the Fallopian tubes. We also describe pulmonary hypoplasia and Potter facies as consequences of anhydramnios. We correlate these findings to our current understanding of molecular signals altered by 17q12 deletion, notably affecting HNF1B and LHX1 genes, which are known to mediate renal and genitourinary tract development.
MitchelMWMoreno-De-LucaDMyersSM, et al. 17q12 recurrent deletion syndrome. In: AdamMPArdingerHHPagonRA, et al eds. GeneReviews((R)). University of Washington; 1993.
2.
BockenhauerDJaureguiberryG. HNF1B-associated clinical phenotypes: the kidney and beyond. Pediatr Nephrol. 2016;31(5):707-714.
3.
VasileiouGHoyerJThielCT, et al. Prenatal diagnosis of HNF1B-associated renal cysts: is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?Prenat Diagn. 2019;39(12):1136-1147.
4.
JingXYHuangLYZhenLHanJLiDZ. Prenatal diagnosis of 17q12 deletion syndrome: a retrospective case series. J Obstet Gynaecol. 2019;39(3):323-327.
5.
RasmussenMVestergaardEMGraakjaerJ, et al. 17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature. Am J Med Genet A. 2016;170(11):2934-2942.
6.
WuHXLiLZhangH, et al. Accurate diagnosis and heterogeneity analysis of a 17q12 deletion syndrome family with adulthood diabetes onset and complex clinical phenotypes. Endocrine. 2021;73(1):37-46.
7.
NakamuraMKandaSKajihoYMorisadaNIijimaKHaritaY. A case of 17q12 deletion syndrome that presented antenatally with markedly enlarged kidneys and clinically mimicked autosomal recessive polycystic kidney disease. CEN Case Rep. 2021;10(4):543-548.
8.
ZhouCXZhuXYZhuYJ, et al. Prenatal features of 17q12 microdeletion and microduplication syndromes: A retrospective case series. Taiwan J Obstet Gynecol. 2021;60(2):232-237.
9.
LiRFuFZhangYLLiDZLiaoC. Prenatal diagnosis of 17q12 duplication and deletion syndrome in two fetuses with congenital anomalies. Taiwan J Obstet Gynecol. 2014;53(4):579-582.
10.
ChenCPChangSDWangTH, et al. Detection of recurrent transmission of 17q12 microdeletion by array comparative genomic hybridization in a fetus with prenatally diagnosed hydronephrosis, hydroureter, and multicystic kidney, and variable clinical spectrum in the family. Taiwan J Obstet Gynecol. 2013;52(4):551-557.
11.
HendrixNWClemensMCanavanTPSurtiURajkovicA. Prenatally diagnosed 17q12 microdeletion syndrome with a novel association with congenital diaphragmatic hernia. Fetal Diagn Ther. 2012;31(2):129-133.
12.
MadariagaLMoriniereVJeanpierreC, et al. Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin J Am Soc Nephrol. 2013;8(7):1179-1187.
13.
LandingBH. Congenital malformations of the bronchi and lung. In: SaldanaMJ, ed. Pathology of Pulmonary Disease. J. B. Lippincott Company; 1994:71-78.
14.
DesgrangeAHeliotCSkovorodkinI, et al. HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis. Development. 2017;144(24):4704-4719.
15.
HeliotCDesgrangeABuissonI, et al. HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2. Development. 2013;140(4):873-885.
16.
NiborskiLLPaces-FessyMRicciP, et al. Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model. Dis Model Mech. 2021;14(5):dmm047498.
De VasMGKoppJLHeliotCSanderMCereghiniSHaumaitreC. Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors. Development. 2015;142(5):871-882.
19.
QuilichiniEFabreMNordC, et al. Insights into the etiology and physiopathology of MODY5/HNF1B pancreatic phenotype with a mouse model of the human disease. J Pathol. 2021;254(1):31-45.
20.
ClissoldRLShaw-SmithCTurnpennyP, et al. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016;90(1):203-211.
21.
ShawlotWBehringerRR. Requirement for Lim1 in head-organizer function. Nature. 1995;374(6521):425-430.
22.
BernardiniLGimelliSGervasiniC, et al. Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet J Rare Dis. 2009;4:25.
23.
Santana GonzalezLRotaIAArtibaniM, et al. Mechanistic drivers of mullerian duct development and differentiation into the oviduct. Front Cell Dev Biol. 2021;9:605301.
24.
WuGBohnSRyffelGU. The HNF1beta transcription factor has several domains involved in nephrogenesis and partially rescues Pax8/lim1-induced kidney malformations. Eur J Biochem. 2004;271(18):3715-3728.
25.
WildWPogge von StrandmannENastosA, et al. The mutated human gene encoding hepatocyte nuclear factor 1beta inhibits kidney formation in developing Xenopus embryos. Proc Natl Acad Sci USA. 2000;97(9):4695-4700.
26.
KumarMThakurSPuriA, et al. Fetal renal anomaly: factors that predict survival. J Pediatr Urol. 2014;10(6):1001-1007.
