Senior-Løken syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 4, 2016
StartDiseasesSenior-Løken syndrome

Senior-Løken syndrome is a rare genetic disorder characterized by nephronophthisis and Leber congenital amaurosis. Symptoms usually begin in infancy or early childhood. There is no cure for the condition. However, the vision problems caused by Leber congenital amaurosis and the kidney failure caused by nephronophthisis can be delayed. 

Contents

Definition & Facts

Senior-Løken syndrome is a rare genetic condition that is characterized by the combination of two conditions, nephronophthisis and Leber congenital amaurosis. Nephronophthisis is a condition characterized by scarring (fibrosis) and inflammation in the kidneys that impairs the kidney's ability to function. Leber congenital amaurosis is a condition that primarily affects the retina, located at the back of the eye. The retina detects light and color.

Individuals with this condition also develop fluid-filled cysts in the kidneys. These cysts are typically found in the corticomedullary region and usually develop in infancy or early childhood and get progressively worse. Individuals with nephronophthisis experience increased urine production (polyuria), general weakness, extreme tiredness, and excessive thirst (polydipsia). 

Senior-Løken syndrome is estimated to affect one person in one million worldwide. The condition affects males and females in equal numbers. The condition is inherited as an autosomal recessive genetic trait. Recessive genetic disorders occur when a person inherits two abnormal genes for the same trait, one abnormal gene from each parent. 

Symptoms & Complaints

Nephronophthisis eventually leads to end-stage renal disease, which is life-threatening kidney failure. End-stage renal disease will typically occur in late childhood or early adolescence. End-stage renal disease occurs when the kidneys are no longer able to filter waste products and fluids from the body effectively. 

Leber congenital amaurosis causes vision problems, such as photophobia (sensitivity to light), hyperopia (extreme farsightedness), and nystagmus (involuntary eye movement). Some people with Senior-Løken syndrome develop vision problems within the first few years of life while others don't develop vision problems until later in childhood. 

Some individuals with Senior-Løken syndrome also have other symptoms. These symptoms may include skeletal abnormalities, hepatic fibrosis (abnormal formation of the fibrous tissue in the liver), neurosensory hearing loss, cerebellar ataxia (loss of muscle coordination caused by disease in the cerebellum, a part of the brain), and diabetes insipidus.

Causes

Senior-Løken syndrome has been linked to a variety of genetic mutations thus far. Specifically, genetic mutations in the genes IQCB1, CEP290, NPHP1, NPHP4, SDCCAG8, and WDR19 cause Senior-Løken syndrome. The proteins made by these genes play a significant role in cell structures called cilia.

Cilia are tiny hair-like structures that stick out of a cell's surface. They are responsible for transmitting information from one cell to another. Cilia also play an important part in sensory input and are essential for the structure and function of kidney cells. Mutations in any of the genes named above may lead to cilia functioning problems, which causes problems in important signaling within cells. 

Diagnosis & Tests

A physician will ask the parents about a child's symptoms and medical history and conduct a physical examination to begin the diagnostic process for Senior-Løken syndrome. An eye examination will be needed to confirm the presence of Leber congenital amaurosis. The retinas of infants with Leber congenital amaurosis appear normal upon examination. However, an electroretinography will detect little or no activity in the retina. 

Eye drops to dilate and numb the eyes are given in preparation of an electroretinography (ERG). The eyelids are held open with a retractor. A small electrode, approximately the size of a contact lens, is placed on each eye. Another electrode is placed on the skin to function as a ground for the electrical signals created by the retina. The physician flashes a light in the eye, and the electrodes record the retina's activity. The retina's activity is measured in a normal light as well as a darkened room. 

A computerized tomography (CT) scan and an ultrasound can detect the presence of nephronophthisis. In a CT scan, special X-ray equipment is utilized to form detailed pictures of the body's insides. In a renal ultrasound, sound waves are utilized to create images of the kidneys. Physicians can see the presence of kidney cysts utilizing either test. 

Senior-Løken syndrome can be diagnosed using genetic tests as well. A genetic mutation on one of the associated genes linked to the condition yields a diagnosis of Senior-Løken syndrome. 

Treatment & Therapy

The symptoms of nephronophthisis can be managed when a diagnosis is made early. End-stage kidney failure can also be delayed with an early nephronophthisis diagnosis. A pediatric nephrologist should regularly monitor the blood pressure, weight and height, urine concentration, and kidney function of a child with Senior-Løken syndrome.

Medications may be used to control blood pressure. When renal failure occurs, a kidney transplant or dialysis is required. Dialysis removes waste, salt, and excess water from the body so that they do not build up to toxic levels, helps control blood pressure, and keeps a safe level of potassium, bicarbonate, and sodium in the blood. 

For those with Leber congenital amaurosis who have some vision, low-vision aids, such as talking computers, talking watches, and large print reading materials may be helpful. Additionally, glasses may improve vision in some patients. Educational and support program for visually impaired children and their families are also often helpful. 

Prevention & Prophylaxis

There is no way to prevent Senior-Løken syndrome. However, people thinking about becoming parents can undergo genetic counseling to determine if they are genetic carriers for the genetic mutations known to cause the condition.

If both potential parents are carriers of a specific genetic mutation, there is a 50% chance that their child will also be a carrier of the mutation and a 25% chance that their child will have Senior-Løken syndrome. With this information, parents can make informed choices regarding having children.