Senior–Løken syndrome

Overview

Senior–Løken syndrome (SLS) is a rare, inherited disorder that primarily affects the kidneys and the eyes. It is classified as a ciliopathy, a group of disorders caused by defects in the structure or function of cilia—microscopic, hair-like structures that play critical roles in various cellular processes. SLS is characterized by the combination of nephronophthisis, a progressive kidney disease that leads to end-stage renal failure, and retinal degeneration resembling Leber congenital amaurosis or retinitis pigmentosa, resulting in progressive vision loss. The condition is typically diagnosed in early childhood, although the severity and progression of symptoms can vary.

Causes

Senior–Løken syndrome is caused by mutations in genes involved in ciliary function. To date, several genes have been linked to the disorder, including NPHP1, NPHP5/IQCB1, NPHP6/CEP290, and others. These genes produce proteins essential for the structure and operation of primary cilia, which are important for signaling pathways in kidney and retinal cells. The syndrome is inherited in an autosomal recessive pattern, meaning that a child must inherit two defective copies of the gene—one from each parent—to develop the condition. Parents who carry one copy of the mutated gene typically show no symptoms.

Symptoms

The hallmark features of Senior–Løken syndrome are kidney dysfunction and progressive vision loss. Symptoms may vary depending on the specific genetic mutation, but common features include:

Renal Symptoms (Nephronophthisis):

• Polyuria (excessive urination)

• Polydipsia (excessive thirst)

• Salt wasting

• Growth retardation in childhood

• Progressive kidney dysfunction, often leading to end-stage renal disease (ESRD) in adolescence

Ocular Symptoms (Retinal Degeneration):

• Night blindness (nyctalopia)

• Loss of peripheral vision progressing to tunnel vision

• Visual acuity loss, eventually leading to legal blindness in many cases

• Fundoscopic exam may show pigmentary retinopathy similar to retinitis pigmentosa or features of Leber congenital amaurosis

Other Possible Symptoms:

• Occasional mild developmental delay

• Rare involvement of other organs such as the liver or cerebellum in complex cases

Diagnosis

Diagnosis of Senior–Løken syndrome typically involves a combination of clinical evaluation, imaging, and genetic testing. Key steps include:

• Clinical history and examination: Assessment of visual symptoms and growth patterns, particularly in children with suspected kidney disease

• Ophthalmologic examination: Electroretinogram (ERG), fundus imaging, and visual field testing to detect retinal degeneration

• Renal imaging and function tests: Ultrasound may show small, echogenic kidneys; blood and urine tests assess renal function

• Genetic testing: Targeted gene panels or whole exome sequencing can confirm mutations in known SLS-associated genes

Early diagnosis is critical for managing the progressive nature of both kidney and eye involvement.

Treatment

There is no cure for Senior–Løken syndrome, and treatment is aimed at managing symptoms and slowing disease progression. A multidisciplinary approach involving nephrologists, ophthalmologists, and genetic counselors is essential. Treatment strategies include:

Renal Management:

• Monitoring kidney function with regular blood and urine tests

• Managing electrolyte imbalances and dehydration with dietary modifications and medications

• Dialysis or kidney transplantation in advanced cases of renal failure

Ophthalmologic Care:

• Regular visual assessments and supportive therapies

• Low vision aids and rehabilitation services

• Protective measures to optimize remaining vision (e.g., sunglasses to reduce light sensitivity)

Additional Support:

• Growth monitoring and nutritional support in children

• Genetic counseling for affected families

• Psychosocial support and educational accommodations

Prognosis

The prognosis of Senior–Løken syndrome depends on the severity and rate of progression of kidney and vision loss. Most individuals develop end-stage renal disease during the first or second decade of life, requiring dialysis or transplantation. Vision loss is also progressive and usually leads to severe visual impairment or blindness in adolescence or early adulthood. While life expectancy can be normal with successful renal transplantation and supportive care, the quality of life may be affected by vision impairment and the demands of chronic kidney disease. Early diagnosis and comprehensive, lifelong management can improve outcomes and help affected individuals lead productive lives.