NPH phenotypically presents either as isolated renal disease or as a complex syndrome with manifestation in multiple organs. Most often affected organs are the eyes, liver, skeleton or the central nervous system:
The eyes are most frequently affected in NPH. A rough distinction in two different ways of affection is made: the impairment of ocular movements (oculomotor apraxia e.g. Cogan) and disorders of the retina (retinitis pigmentosa e.g. Senior – Løken Syndrome). The severe congenital form of retinitis pigmentosa (Leber’s congenital amaurosis) is associated with congenital blindness, nystagmus and pupils unresponsive to light. Retinitis pigmentosa has a later onset, first manifests with night blindness and has a slow progress of visual impairment.
Central nervous system:
Different neurological abnormalities can be associated with NPH including oculomotor apraxia, cerebellar hypoplasia, muscular hypotension, seizures, encephalocele, delay of speech development and cognitive impairment.
Polydactyly, short finger and thoracic deformation are for instance common in Jeune asphyxiating thoracic dysplasia. Cone shaped epiphysis are characteristic for Mainzer – Saldino syndrome. Different other skeletal abnormalities can be associated with NPH and are summarized as ciliary chondrodysplasic syndromes.
Congenital liver fibrosis can be found in different ciliopathies (e.g. Boichis syndrome, Arima syndrome, Meckel – Gruber syndrome) and can be isolated or associated with NPH and abnormalities in other organs.
Situs inversus and congenital heart defects:
Situs inversus and congenital heart defects (especially atrial septal defect) are most common in infantile NPH but can also be found in other ciliopathies.
NPH can appear as a renal manifestation of clearly defined syndromes summarized as NPH related ciliopathies (NPH – RC). The following picture shows the most important syndromes:
Nephronophthisis and extrarenal symptoms - summary
|Eyes||retinitis pigmentosa||Senior-Løken syndrome|
|Arima syndrome (cerebro-oculo-hepato-renal syndrome)|
|oculomotor apraxia||Cogan syndrome|
|nystagmus||Joubert syndrome and associated disease|
|CNS||encephalocele||Meckel – Gruber syndrome|
|aplasia of the vermis||Joubert syndrome and associated diseases|
|Liver||hepatic fibrosis||Boichis syndrome|
|Meckel – Gruber syndrome|
|Joubert syndrome and associated diseases|
|Skeleton||short ribs||Jeune asphyxiatign thoracic dysplasia|
|cone shaped epiphyses||Mainzer – Saldino syndrome|
|polydaktyly||Joubert syndrome and associated diseases|
|Bardet – Biedl syndrome|
|other skeletal abnormalities||Cranioectodermale dysplasia/ Sensenbrenner syndrome|
|other defects: situs inversus, congenital heart defect|
- Wolf M. Nephronophthisis and related syndromes. Curr Opin Pediatr. 2015 Apr; 27(2): 201–211.
- Huber C, Cormier-Daire V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012;160C:165–74.
- Otto EA, Schermer B, Obara T, et al. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet. 2003;34:413–420.