Summary of the clinical details of monogenic fibrocystic syndromes, listing hepatic, renal, and other associated anomalies
| Inherited disorder | Gene(s) or loci, (protein product); mode of inheritance | Renal abnormalities: imaging and histopathology | Hepatic abnormalities | Other associated features | Prognosis | Differential 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 fibrosis | PKHD1 (fibrocystin); AR | Antenatally 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 glomerulosclerosis | Congenital hepatic fibrosis, Caroli’s disease, and biliary dysgenesis. Hepatic disease more prominent if patients present as older children, and results in cirrhosis and portal hypertension | Neonatal presentation often with pulmonary hypoplasia | Majority 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 years | Caroli’s disease |
| Nephronophthisis | NPHP1 (nephrocystin), loci NPHP2-4; AR | Ultrasound 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 membrane | Congenital hepatic fibrosis | Cone shaped epiphyses, retinal degeneration (Senior-Loken syndrome) | Patients develop ESRF within 5–10 years after presentation | MCKD |
| Renal-hepatic-pancreatic dysplasia (Ivemark syndrome) | Autosomal recessive | May be detected on antenatal ultrasound showing bilaterally enlarged polycystic kidneys. Histology usually reveals cystic dysplasia | Congenital hepatic fibrosis and Caroli’s disease | Dilated pancreatic ducts, short ribs, polydactyly, polyslpenia, cardiac anomalies, situs inversus, CNS abnormalities | Prognosis depends on the severity of renal disease | ARPKD, isolated MCDK |
| Joubert syndrome | Loci at 9q34, 17p11; AR | Renal changes of nephronophthisis often present in the subset of patients with retinal degeneration. Also associated with multicystic dysplastic kidney | Congenital hepatic fibrosis | Agenesis or dysgenesis of cerebellar vermis with or without Dandy-Walker malformation, hypotonia, developmental delay and hyperpnoea/apnoea | Some patients die in infancy from breathing abnormalities; survivors have developmental delay with 25% developing renal insufficiency | SLS (NPHP) |
| Meckel-Gruber syndrome | Loci at 13q13, 17q21–24; AR | Antenatal 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 stroma | Ductal plate malformation with periportal fibrosis and biliary dysgenesis | Occipital encephalocele, other CNS malformations, polydactyly, cardiac malformations | Lethal in the neonatal period from respiratory and renal insufficiency | Goldston syndrome, ARPKD, Joubert syndrome |
| Bardet-Biedl syndrome | Genes BBS2, BBS4, BBS6; loci at 11q13, 3p13, 2q31; AR or possible triallelic inheritance | Persistent fetal lobulation, small kidneys with clubbed calyces, cystic dysplasia; may be diagnosed on antenatal ultrasound scanning. Histology changes of nephronophthisis | Congenital hepatic fibrosis | Retinal degeneration, obesity, polydactyly and other limb deformities, hypogenitalism | Renal disease leads to a need for dialysis and transplantation during adolescence and early adulthood | Prader-Willi syndrome |
| Jeune asphyxiating thoracic dysplasia | Possible locus at 12p; AR | Histology may show cystic renal tubular dysplasia, with or without glomerular sclerosis; could also have similar findings to nephronophthisis | May have neonatal cholestasis, Caroli’s disease, and congenital hepatic fibrosis | Short stature, narrow, long thorax with short ribs, micromelia, other skeletal malformations, lung hypoplasia, retinal degeneration, pancreatic cysts and insufficiency | Severity of thoracic involvement variable and improves with age; patients who survive beyond infancy may develop renal involvement and ESRF, which determines prognosis | Ellis-van Creveld syndrome, short rib-polydactyly syndrome (SRPS) types I, II, III |