Information on the following diseases can be found in the Related Disorders section of this report:

• Leber’s Congenital Amaurosis
• Juvenile Nephronophthisis-Medullary Cystic Kidney Disease
• Polycystic Kidney Diseases
• Retinitis Pigmentosa
• Brachymorphism-onychondysplasia-dysphalangism syndrome
• Nephronophthisis 1
• Rhyn’s syndrome
• Mainzer-Saldino syndrome
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Loken-Senior Syndrome is a rare inherited disorder characterized by progressive kidney and eye problems.

The nephronophthisis with or without medullary cystic renal disease appears in the first year of life. The kidney problems are present at birth in some families, but develop very gradually and take a long time before symptoms become apparent in other families. Progressive failure of kidney function occurs as a result of degeneration or loss of function of the small collecting tubes (tubules) in the kidney. This can cause uremia and chronic interstitial nephritis.

Chronic interstitial nephritis is a kidney syndrome in which the spaces between the tissue of the kidney (interstitial) become inflamed and structural changes occur. Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure.

Uremia is a condition that is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood, causing a severe toxic condition. Normally, these by-products of protein breakdown would be passed in the urine.

The progressive atrophy of the retina of the eye may be like Leber's Amaurosis with an absence of light gathering cells (cones and rods) of the retina at birth. A decrease in visual responsiveness at birth is the first sign of this disorder with roving eye movements (nystagmus) being apparent in the first two months of life.

In other cases of Loken-Senior Syndrome the progressive atrophy of the retina of the eye may take a course similar to Retinitis Pigmentosa. This condition typically becomes apparent later in life with the earliest symptom being difficulty seeing in dimly lit places (night blindness). This is slowly followed by tunnel vision. The rate of progression can vary.

Other symptoms have been noted in particular families such as diabetes insipidus, neurosensory hearing loss, muscular incoordination caused by disease of the cerebellum in the brain (cerebellar ataxia), abnormal formation of fibrous tissue in the liver (hepatic fibrosis) and skeletal abnormalities.
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Loken-Senior Syndrome is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

The variability between families affected by Loken-Senior syndrome may be explained by different gene mutations in more than one gene (genetic heterogeneity). Several different gene abnormalities have been noted in individuals with Loken-Senior syndrome including a deletion of both copies of one of the genes for nephronophthisis (NPHP1), an abnormal gene near the NPHP3 locus on chromosome 3 and an abnormal gene overlapping the NPHP4 locus on chromosome 1.
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Loken-Senior Syndrome is a very rare disorder affects males and females in equal numbers. There have been over one hundred and fifty cases of this disorder reported in the medical literature.
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Symptoms of the following disorders can be similar to those of Loken-Senior Syndrome. Comparisons may be useful for a differential diagnosis:

Leber's Congenital Amaurosis is a retinal hereditary disorder of the eye. It is characterized by blindness at birth, roving eye movements, pupils that react poorly to light and dilate widely in the dark. However this disorder does not affect the kidney's. (For more information on this disorder, choose "Leber" as your search term in the Rare Disease Database.)

Juvenile Nephronophthisis-Medullary Cystic Disease is a diffuse kidney disease, either genetic or congenital in origin, which usually appears in children or young adults (juvenile nephronophthisis). It is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood (uremia) due to progressive failure of kidney function. (For more information on this disorder, choose "Medullary Cystic Disease" as your search term in the Rare Disease Database.)

Polycystic Kidney Diseases are inherited disorders that are characterized by many cysts in both kidneys. This causes enlargement of the total kidney size, while reducing the functional kidney tissue by compression. (For more information on this disorder, choose "Polycystic Kidney Diseases" as your search term in the Rare Disease Database.)

Retinitis Pigmentosa is one of a group of inherited eye diseases causing degeneration of the retina. When the retina degenerates, the vision decreases from night blindness to tunnel vision, and vision may eventually be lost. Retinitis Pigmentosa may occur in association with other disorders such as deafness (Usher's Syndrome), central nervous system disorders, metabolic disorders and chromosomal abnormalities such as Turner Syndrome. (For more information on this disorder, choose "Retinitis Pigmentosa" as your search term in the Rare Disease Database.)

Brachymorphism-Onychodysplasia-Dysphalangism Syndrome is a rare disorder characterized by short stature, abnormal fingers and fingernails, facial abnormalities and mild mental retardation.

Nephronophthisis 1 is a rare disorder characterized by anemia, excessive urination (polyuria), excessive thirst (polydipsia) and toxic accumulation of the products of protein breakdown in the blood (uremia).

Rhyns Syndrome is an extremely rare disorder characterized by retinitis pigmentosa, nephronophthisis, low functioning pituitary gland (hypopituitarism), skeletal abnormalities, drooping eyelids and liver disease.

Mainzer-Saldino Syndrome is a rare disorder characterized by chronic kidney failure, skeletal abnormalities of the hands, retinitis pigmentosa and muscular incoordination (ataxia).
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Patients with Medullary Cystic Disease need careful management of uremia when it occurs. Diet must be carefully monitored. An increase of calories in the diet should be coupled with a reduction in the total content of dietary protein. Sufficient carbohydrates and fats should be consumed to provide energy and prevent the body from metabolizing its own proteins.

Kidney failure may need to be managed with hemodialysis. Kidney transplantation is sometimes indicated.

When the retinal atrophy in Loken-Senior Syndrome resembles Retinitis Pigmentosa, the patient may benefit from various visual aids. The aids may be 1) optical aids, such as Corning and NOIR glasses, the Fresnel Prising telescopes, microscopes and night vision aids; 2)non-optical aids, such as the Wide Angle Mobility Light, paper guides, large print typewriters and adjustable stands; and 3) electronic aids such as Apollo Laser and Visualtek closed-circuit TV, reading machines and talking computers.

Genetic counseling may be of benefit for patients and their families.

Researchers at the Cullen Eye Institute of the Baylor College of Medicine in Houston, TX, and the Hospital For Sick Children in Toronto, Canada are studying a group of inherited retinal disorders including Leber's Congenital Amaurosis. Families with at least two affected members whose parents are both living are needed to participate in the program. For information, please contact:

Richard A. Lewis, M.D.
Cullen Eye Institute
Department of Ophthalmology
Baylor College of Medicine
One Baylor Plaza
6501 Fannin St.
Houston, TX 77030
(713) 799-5942

Maria A. Musarella, M.D. F.R.C.C.S. (C)
Hospital For Sick Children Research Institute
555 University Ave.
Toronto, Ontario, Canada
M5G 1X8

At the present time, scientists are working on the effectiveness of the orphan drug Cronnassial as a possible treatment for Retinitis Pigmentosa. Physicians who would like more information on this treatment may contact:

Fidia Pharmaceutical
1775 K St., NW, Suite 800
Washington, D.C. 20006

Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.

Lewis RA. Loken-Senior Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams, and Wilkins, 2003:692-3.

McKusick,VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 266900: Last Edit Date; 12/26/2002.

Buyse ML, Ed. Birth Defects Encyclopedia. Blackwell Scientific Publications, 1990. Pp.1463.

Schuman JS, et al. Senior-Loken syndrome (Familial Renal-Retinal Dystrophy) and Coat’s disease. Am J Opthalmol. 1985:6:822-7.

Fillastre JP, et al. Senior-Loken syndrome (nephronophthisis and tapeto-retinal degeneration. Clin Nephrol. 1976;5(1):14-9.

Omran H, Sasmaz G, Haffner K, et al. Identification of a gene locus for Senior-Loken syndrome in the region of the nephronophthisis type 3 gene. J Am Soc Nephrol. 2002;13:75-79.

Scheuermann MJ, Otto E, Becker A, et al. Mapping of gene loci for nephronophthisis type 4 and Senior-Loken syndrome to chromosome 1p36. Am J Hum Genet. 2002;70:1240-1246.

Senior B, Friedman AI, Braudo JL. Juvenile familial nephropathy with tapetoretinal degeneration: a new oculorenal dystrophy. Am J Opthalmol. 1961;52:625-633.

Warady BA, Cibis G, Alon U, et al. Senior-Loken syndrome:revisited. Pediatrics. 1994;94:111-112.