Table 1

Summary of the clinical details of monogenic fibrocystic syndromes, listing hepatic, renal, and other associated anomalies

Inherited disorderGene(s) or loci, (protein product); mode of inheritanceRenal abnormalities: imaging and histopathologyHepatic abnormalitiesOther associated featuresPrognosisDifferential diagnosis
AR, autosomal recessive; MCKD, medullary cystic kidney disease; MCDK, multicystic dysplastic kidney; SLS, Senior-Løken syndrome; ESRF, end stage renal failure.
(AR or juvenile) polycystic kidney disease, congenital hepatic fibrosisPKHD1 (fibrocystin); ARAntenatally diagnosed by ultrasonography with grossly enlarged bilaterally echogenic kidneys, absent urine, oligohydramnios and pulmonary hypoplasia. Cysts less than 3 mm in diameter extend from papillary tips to the surface of the cortex; lined by flattened epithelium representing dilated collecting tubules. Adjacent parenchyma develops interstitial fibrosis and glomerulosclerosisCongenital hepatic fibrosis, Caroli’s disease, and biliary dysgenesis. Hepatic disease more prominent if patients present as older children, and results in cirrhosis and portal hypertensionNeonatal presentation often with pulmonary hypoplasiaMajority of neonatally presenting patients die within 6 weeks of pulmonary disease and renal failure; 80% of survivors live until 15 years of age. All will develop ESRF by 20 yearsCaroli’s disease
NephronophthisisNPHP1 (nephrocystin), loci NPHP2-4; ARUltrasound will detect small kidneys, uniformly increased echogenicity and cysts at the corticomedullary junction. Histology shows cortical atrophy with variable numbers of cysts at the corticomedullary junction (up to 1 cm in size). Histology shows tubular atrophy, interstitial fibrosis, and chronic inflammation; progression to glomerulosclerosis with markedly thickened basement membraneCongenital hepatic fibrosisCone shaped epiphyses, retinal degeneration (Senior-Loken syndrome)Patients develop ESRF within 5–10 years after presentationMCKD
Renal-hepatic-pancreatic dysplasia (Ivemark syndrome)Autosomal recessiveMay be detected on antenatal ultrasound showing bilaterally enlarged polycystic kidneys. Histology usually reveals cystic dysplasiaCongenital hepatic fibrosis and Caroli’s diseaseDilated pancreatic ducts, short ribs, polydactyly, polyslpenia, cardiac anomalies, situs inversus, CNS abnormalitiesPrognosis depends on the severity of renal diseaseARPKD, isolated MCDK
Joubert syndromeLoci at 9q34, 17p11; ARRenal changes of nephronophthisis often present in the subset of patients with retinal degeneration. Also associated with multicystic dysplastic kidneyCongenital hepatic fibrosisAgenesis or dysgenesis of cerebellar vermis with or without Dandy-Walker malformation, hypotonia, developmental delay and hyperpnoea/apnoeaSome patients die in infancy from breathing abnormalities; survivors have developmental delay with 25% developing renal insufficiencySLS (NPHP)
Meckel-Gruber syndromeLoci at 13q13, 17q21–24; ARAntenatal ultrasound diagnosis: bilateral gross renal enlargement, variable size cysts. In the peripheral cortex the cysts are very small, thin walled, with a thin zone of normal glomeruli, more centrally the cysts are larger. The largest cysts are in the medulla, up to several millimetres with thick fibromuscular walls separating them from collagenous stromaDuctal plate malformation with periportal fibrosis and biliary dysgenesisOccipital encephalocele, other CNS malformations, polydactyly, cardiac malformationsLethal in the neonatal period from respiratory and renal insufficiencyGoldston syndrome, ARPKD, Joubert syndrome
Bardet-Biedl syndromeGenes BBS2, BBS4, BBS6; loci at 11q13, 3p13, 2q31; AR or possible triallelic inheritancePersistent fetal lobulation, small kidneys with clubbed calyces, cystic dysplasia; may be diagnosed on antenatal ultrasound scanning. Histology changes of nephronophthisisCongenital hepatic fibrosisRetinal degeneration, obesity, polydactyly and other limb deformities, hypogenitalismRenal disease leads to a need for dialysis and transplantation during adolescence and early adulthoodPrader-Willi syndrome
Jeune asphyxiating thoracic dysplasiaPossible locus at 12p; ARHistology may show cystic renal tubular dysplasia, with or without glomerular sclerosis; could also have similar findings to nephronophthisisMay have neonatal cholestasis, Caroli’s disease, and congenital hepatic fibrosisShort stature, narrow, long thorax with short ribs, micromelia, other skeletal malformations, lung hypoplasia, retinal degeneration, pancreatic cysts and insufficiencySeverity of thoracic involvement variable and improves with age; patients who survive beyond infancy may develop renal involvement and ESRF, which determines prognosisEllis-van Creveld syndrome, short rib-polydactyly syndrome (SRPS) types I, II, III