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Senior-Loken syndrome

Orpha number ORPHA3156
Synonym(s) Nephronophthisis with retinal dystrophy
Renal dysplasia - retinal aplasia
SLSN
Prevalence 1-9 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Childhood
ICD-10
  • Q61.5
OMIM
UMLS -
MeSH
  • C537580
MedDRA -
SNOMED CT -

Summary

Senior-Loken syndrome (SLSN) is a very rare autosomal recessive oculo-renal disease characterized by the association of nephronophthisis (NPHP), a chronic kidney disease, with retinal dystrophy.

The worldwide prevalence is estimated at around 1/1,000,000.

The disease manifests after birth or during childhood with symptoms of nephronophthisis such as polyuria, polydipsia, secondary eneuresis and anemia. The progression of the disease can lead to acute or chronic renal insufficiency and finally to end-stage kidney disease (ESKD). Ocular features include congenital or early-onset severe visual loss, due to retinal dystrophy. In rare occasions, other additional clinical signs may be observed like liver fibrosis, obesity and neurologic disorders.

SLSN is a genetically heterogeneous ciliopathy. Mutations in 7 different genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, SDCCAG8) have been described. These genes encode for proteins of the primary cilia playing key roles in the development and function of several cell types, including retinal photoreceptor and renal tubular epithelial cells. Epistatic interactions, oligogenic inheritance or modifying alleles have been also suggested to influence the expressivity of the different extrarenal phenotypes.

Complete renal (kidney function, urinary analysis and abdominal ultrasound) and ophthalmologic (funduscopy, visual acuity test, refraction defects, colour vision test, ocular motility and electroretinogram) evaluations are recommended. Hepatic evaluation to exclude liver fibrosis (liver function and abdominal ultrasounds) and neurological examination for infant patients are also highly recommended. Genetic diagnosis of SLSN requires the mutational screening of the implicated genes; deletion of the NPHP1 gene is the most recurrent anomaly.

SLSN presents genetic and clinical overlap with other ciliopathies, in particular with isolated NPHP, Joubert syndrome related diseases (JSRD), mainly Joubert syndrome with oculorenal defect (JS-OR), Bardet-Biedl syndrome (BBS) and Alström syndrome (see these terms). Physical examination should consider the presence of the main clinical signs of JSRD (hypotonia, ataxia and breathing abnormalities in infants) and BBS (polydactyly and obesity). The phenotypic hallmark of JSRD is the presence on MRI of 'molar tooth sign' (a midbrain-hindbrain malformation). Other extrarenal signs to consider are nystagmus, psychomotor and learning delay, diabetes mellitus, deafness, hypogonadism, and/or scoliosis.

Prenatal diagnosis can be made only in families in which the molecular defect had been previously identified in the proband.

Transmission of SLSN is autosomal recessive.

Affected children should be regularly monitored by a pediatric nephrologist. This involves monitoring the weight and height, controlling blood pressure, renal function studies, measuring the urinary concentration and studying urinary elimination of sodium by the kidney. Early management of NPHP may delay the progression toward renal failure and minimize secondary complications. In case of ESKD, patients require dialysis or kidney transplantation. No treatment is currently available to prevent progression to visual loss.

Prognosis depends mostly on renal complications that represent the major cause of death if not timely diagnosed and managed.

Expert reviewer(s)

  • Dr A. AVILA
  • Dr Carmen AYUSO GARCÍA
  • Dr M. CORTON
  • Dr José María MILLÁN SALVADOR

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