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Chapter 309: Polycystic Kidney Disease and Other Inherited Disorders of Tubule Growth and Development

Jing Zhou; Martin R. Pollak

INTRODUCTION

The polycystic kidney diseases are a group of genetically heterogeneous disorders and a leading cause of kidney failure. The autosomal dominant form of polycystic kidney disease (ADPKD) is the most common life-threatening monogenic disease, affecting 12 million people worldwide. The autosomal recessive form of polycystic kidney disease (ARPKD) is rarer but affects the pediatric population. Kidney cysts are often seen in a wide range of syndromic diseases. Recent studies have shown that defects in the structure or function of the primary cilia may underline this group of genetic diseases collectively termed ciliopathies (Table 309-1).

TABLE 309-1Inherited Diseases Commonly Associated with a Cystic Phenotype
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TABLE 309-1 Inherited Diseases Commonly Associated with a Cystic Phenotype
Disease Mode of Inheritance Renal Abnormalities Other Clinical Features Genes
Autosomal dominant polycystic kidney disease AD Cortical and medullary cysts Liver, pancreatic cysts, hypertension, subarachnoid hemorrhage PKD1, PKD2
Autosomal recessive polycystic kidney disease AR Distal and collecting duct cysts Oligohydramnios if severe, hypertension, ascending cholangitis, liver fibrosis PKHD1
Medullary cystic kidney (Autosomal dominant tubulointerstital kidney disease) AD Small fibrotic kidneys; medullary cysts In adults, gout

UMOD

MUC1

REN
Nephronophthisis AR Small fibrotic kidneys; medullary cysts Growth retardation, anemia, (visual loss, liver fibrosis, cerebellar ataxia if associated with another syndrome) NPHP1-20, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, SDCCAG8, TMEM67, TTC21B
Senior-Loken syndrome AR Renal cysts Juvenile nephronophthisis, Leber amaurosis NPHP1-6, SDCCAG8
Leber congenital amaurosis AR Renal cysts Visual impairment in first year of life; pigmentary retinopathy GUCY2D, RPE65, LCA3-14 (including LCA10, CEP290)
Meckel-Gruber syndrome AR Cortical and medullary cysts CNS anomalies, polydactyly, congenital heart defects MKS1, TMEM216, TMEM67, CEP290, RPGRIP1L, CC2D2A, TCTN2, B9D1, B9D2, NPHP3
Bardet-Biedl syndrome AR Renal cysts Obesity, polydactyly, retinitis pigmentosa, anosmia, congenital heart defects, mental retardation BBS1, 2, ARL6, BBS4,5, MKKS, BBS7, TTC8, BBS9, 10, TRIM32, BBS12, MKS1, CEP290, C2ORF86; modifiers MKS1, MKS3, CCDC28B
Oral-facial-digital syndrome type I AR Renal cysts

Oral cavity, face, and digit anomalies; CNS abnormalities; cystic kidney disease; X-linked with male lethality, primary ciliary dyskinesia

 OFD1
Cranioectodermal dysplasia (Sensenbrenner syndrome) AR Renal cysts Skeletal dysplasia; thoracic deformities; polydactyly; renal cysts; retinitis pigmentosa IFT80
Tuberous sclerosis AD Renal cysts

Angiomyolipomas; renal cell carcinoma

Facial angiofibromas; CNS hamartomas

 TSC1, TSC2
Von Hippel-Lindau disease AD Renal cysts Renal cell carcinoma, retinal angiomas; CNS hemangioblastomas; pheochromocytomas VHL

Abbreviations: AD, autosomal dominant; AR, autosomal recessive; CNS, central nervous system.

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Etiology and Pathogenesis

ADPDK is characterized by progressive formation of epithelial lined cysts in the kidney (Fig. 309-1). Although cysts only occur in 5% of the tubules in the kidney, the enormous growth of these cysts ultimately leads to the loss of normal surrounding tissues and loss of renal function. The cellular defects in ADPKD that have been known for a long time are increased cell proliferation and ...

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