Table 3.

Genetic Disorders with Kidney Cysts in the Differential Diagnosis of 17q12 Recurrent Deletion Syndrome

Gene(s)DisorderMOIKidney PhenotypeExtrarenal Phenotype
DNAJB11
GANAB
PKD1
PKD2 		ADPKD ADNumerous bilateral cysts; kidney enlargement; hypertension; nephrolithiasis; progressive CKD, w/ESKD in mid- to late-adulthood. DNAJB11- & GANAB-assoc disease have milder phenotypes w/normal-sized kidneys, smaller cysts, & less progression to ESKD.Liver cysts; intracranial aneurysms; cardiac valve abnormalities; diverticular disease; hernias
ALG8
GANAB 1
LRP5
PRKCSH
SEC63
SEC61B 2		ADPLD (OMIM PS174050)ADFew cysts occasionally reportedPolycystic liver disease
MUC1 ADTKD-MUC1 (previously known as MCKD1)ADTubulointerstitial disease; few small corticomedullary cysts in 50%; normal or small-sized kidneys; CKD, highly variable progression to ESKDHyperuricemia, gout
REN ADTKD-REN (previously known as FJHN2)ADTubulointerstitial disease, cysts, slowly progressive CKDAnemia, hyperuricemia, gout
SEC61A1 ADTKD-SEC61A1 3 (also referred to as FJHN4)ADBilateral small cysts in 50%; normal or small-sized kidneys; CKDIUGR, congenital anemia
UMOD ADTKD-UMOD (previously known as FJHN1 or MCKD2)ADTubulointerstitial disease; normal or small kidneys; few unilateral or bilateral cysts in 1/3; variable progression of CKD to ESKDHyperuricemia, gout
JAG1
NOTCH2 		Alagille syndrome ADRenal dysplasia, renal tubular acidosis, CAKUTCholestatic liver disease, cardiac anomalies, characteristic facies, skeletal anomalies, ophthalmic anomalies
PKHD1
(DZIP1L) 4		 ARPKD AREnlarged, hyperechogenic kidneys in utero; multiple small bilateral cysts in childhood; ESKD in 1st decade in 50%Congenital hepatic fibrosis, Caroli syndrome, pulmonary hypoplasia, prenatal oligoanhydramnios
EYA1
SIX1
SIX5 		Branchiootorenal spectrum disorder ADRenal agenesis, hypoplasia, or dysplasia; ureteropelvic junction obstruction; calyceal cyst/diverticulum; calyectasis, pelviectasis, hydronephrosis, VUREar abnormalities (deafness, outer ear anomalies, middle ear anomalies, preauriular pits); 2nd branchial arch anomalies (sinus tract, cyst)
BICC1 Cystic renal dysplasia, susceptibility to (OMIM 601331)ADCystic renal dysplasia, VURNone
BMPER Diaphanospondylo-dysostosis (OMIM 608022)ARNephroblastomatosis w/cystic kidneysSkeletal anomalies (small chest, abnormal vertebral segmentation, & posterior rib gaps); craniofacial anomalies (ocular hypertelorism, epicanthal folds, depressed nasal bridge w/short nose, & low-set ears)
PMM2 HIPKD 5ARAntenatal or childhood onset enlarged hyperechogenic kidneys w/multiple cysts; variable progression of CKD to ESKD from infancy to early adulthoodInfantile hyperinsulinemic hypoglycemia; liver cysts
CEP290
INVS
IQCB1
NPHP1
NPHP3
NPHP4
TMEM67
(≥19 genes) 6		 Nephronophthisis ARCorticomedullary cysts; normal or small-sized kidneys (but often moderately enlarged in infantile onset type); urinary concentrating & sodium reabsorption defect; progressive CKDNephronophthisis may be isolated or part of a syndrome, such as Joubert, Bardet-Biedl, Jeune, Meckel-Gruber, Senior-Loken, Leber congenital amaurosis, Cogan, or COACH.
OFD1 Oral-facial-digital syndrome type I XLPolycystic kidneys in women; progressive kidney dysfunction in adulthoodCleft palate, dental anomalies, facial dysmorphology, digital anomalies, ID
PAX2 Renal coloboma syndrome (See PAX2-Related Disorder.)ADHypoplasia, hypodysplasia, multicystic dysplastic kidney, VUR, other CAKUT, FSGS, uric acid nephrolithiasisOptic nerve dysplasia, retinal coloboma, other eye malformations
TSC1
TSC2 		Tuberous sclerosis complex ADMultiple & bilateral cysts & angiomyolipomas, oncocytomas, renal cell carcinomaCortical tubers, astrocytomas; epilepsy, ID; cutaneous angiofibromas, hypopigmented patches; retinal hamartoma; cardiac rhabdomyoma; pulmonary LAM;
VHL von Hippel-Lindau syndrome ADBilateral cysts, renal cell carcinomaretinal hemangiomas; hemangioblastomas of the cerebellum, spine, retina; pheochromocytoma; pancreatic neuroendocrine tumors
CRB2 Ventriculomegaly w/cystic kidney disease (OMIM 219730)ARMicroscopic renal tubular cystsDilated cerebral ventricles, postaxial polydactyly, ventricular septal defect

AD = autosomal dominant; ADPKD = autosomal dominant polycystic kidney disease; ADPLD = autosomal dominant polycystic liver disease; ADTKD = autosomal dominant tubulointerstitial kidney disease; AR = autosomal recessive; ARPKD = autosomal recessive polycystic kidney disease; CAKUT = congenital anomalies of the kidney and urinary tract; CKD = chronic kidney disease; COACH = cerebellar vermis hypo/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis; ESKD = end-stage kidney disease; FJHN = familial juvenile hyperuricemic nephropathy; FSGS = focal segmental glomerulonephritis; HIPKD = hyperinsulinemia with hypoglycemia and polycystic kidney disease; ID = intellectual disability; IUGR = intrauterine growth restriction; LAM = lymphangioleiomyomatosis; MCKD = medullary cystic kidney disease; MOI = mode of inheritance; VUR = vesicoureteric reflux

1.
2.
3.
4.

DZIP1L has not yet been definitively proven to be a second locus for ARPKD (see ARPKD).

5.
6.

Listed genes represent the most common genetic causes of nephronophthisis; for other genes associated with this phenotype, see Nephronophthisis.

From: 17q12 Recurrent Deletion Syndrome

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