Senior-Loken syndrome is a very rare autosomal recessive disorder characterized by the combination of two primary features: nephronophthisis (NPH), a chronic kidney disease, and Leber congenital amaurosis (LCA), a retinal dystrophy. This is a deleterious disease which leads to blindness and eventually, to end stage renal failure. Affected patients invariably progress to end stage renal failure, usually before the age of 20-years.
Senior-Loken syndrome has been reported in many cases worldwide, with the prevalence being estimated at around 1 in 1,000,000. To date, no definite treatment is available to prevent progression to visual loss.
Senior-Loken syndrome is a genetically heterogeneous ciliopathy. It can be caused by mutations in seven different genes: NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, and SDCCAG8. These genes encode proteins that play major roles in cell structures called cilia. Cilia are important for the structure and function of several types of cells, including retinal photoreceptor and renal tubular epithelial cells. Mutations in these genes lead to problems with the structure and function of cilia, which disrupt important chemical signaling pathways within cells.
Deletion of the NPHP1 gene is the most common anomaly among Senior-Loken syndrome patients. In some cases, the genetic cause of the disorder is unknown.
Othman et al. (2012) described two sisters with Senior Loken syndrome. The patients were born to first-degree consanguineous parents, and presented in the first year of life with nystagmus and inability to follow light and objects, along with polyuria, polydipsia, and nocturia. They had chronic kidney disease by the age of 12-years. Upon evaluation at the age of 15- and 17-years, they were found to be blind and had nystagmus, with a normal fundus. The younger patient was found to have comorbidity with Sickle Cell Disease. Abdominal US showed undersized hyperechoic kidneys, and a slightly increased echotexture in the liver. Tiny cysts were noted in the renal parenchyma by MRI kidney. Kidney biopsy findings were consistent with an impression of nephropthisis. A diagnosis of SLSN was made, and the patients were started on hemodialysis for 6-months before they had kidney transplants. Both parents and all other siblings were normal. There was negative family history of a similar condition.
AlFadhel and AlAmir (2008) reported an 11-year-old Saudi girl with Senior-Loken syndrome. She was born to first cousin consanguineous parents, and had two blind sisters, and one maternal uncle who was blind and had renal failure. The affected patient was blind and had nystagmus. She had weakness, polyuria, and polydypsia due to on and off vomiting for 2-years. She had renal failure, anemia, and acidosis, in addition to osteopenia and multiple tiny lucencies, consistent with renal osteodystrophy. Abdominal US showed findings consistent with nephropthisis. A diagnosis of Senior Loken Syndrome was made, and renal transplantation was suggested.
Abidi et al. (2014) reported a 28- years-old patient who was diagnosed to have Senior Loken syndrome at the age of 10 years because of renal impairment and tapetoretinal degeneration and was later started on regular hemodialysis. He had no family history of renal disease, hypertriglyceridemia or cholelithiasis. He had abdominal tenderness without guarding. Investigations revealed a lipase level of 3856 I U/l and an abdominal CT scan showed features of acute pancreatitis. The abdominal ultrasound showed no biliary tree malformations or gallstone obstruction. He had no history of recent drug intake or alcohol consumption and his serum triglyceride level was normal. The patient was managed conservatively with good outcome.
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