Overview
Senior-Løken syndrome is a rare autosomal recessive ciliopathy combining nephronophthisis (juvenile-onset renal failure) with retinal dystrophy (Leber congenital amaurosis-like or RP-like). It is caused by mutations in multiple nephronophthisis-related genes (NPHP genes) encoding proteins of the primary cilium. Renal failure typically requires dialysis or transplantation in the 2nd–3rd decade. The retinal component may precede, coincide with, or follow the renal diagnosis.
Genetics
Multiple causative genes, all encoding nephrocystin proteins of the primary cilium. NPHP5 (IQCB1) and NPHP6 (CEP290) are most commonly associated with retinal involvement.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| NPHP5 (IQCB1) | 3q13.33 | AR | Nephrocystin-5; most common cause of SLS with retinal dystrophy |
| NPHP6 (CEP290) | 12q21.32 | AR | Centrosomal protein 290; allelic with LCA10 and Joubert |
| NPHP1 | 2q13 | AR | Nephrocystin-1; most common NPHP gene overall |
| NPHP4 | 1p36.31 | AR | Nephrocystin-4 |
Clinical Presentation
Childhood
- Retinal dystrophy (LCA-like or RP-like)
- Polyuria and polydipsia (renal)
- Anemia
Adolescence
- Progressive renal failure
- Progressive visual loss
- Growth retardation
Young adulthood
- End-stage renal disease requiring transplant
- Severe visual impairment or blindness
Diagnosis
- Renal biopsy: Tubulo-interstitial nephritis with fibrosis
- Renal ultrasound: Small echogenic kidneys
- ERG: Rod-cone or cone-rod dystrophy
- Genetic testing: NPHP gene panel
- Renal function: Creatinine, GFR monitoring
Current Research & Treatment
No disease-modifying treatments for the retinal or renal components. Renal transplantation is standard of care for end-stage renal disease. CEP290-targeted therapies in development for LCA10 may benefit SLS patients with CEP290 mutations.
Active Clinical Trials
The following active clinical trials are investigating treatments for Senior-Løken Syndrome. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.