The very rarely occurring Senior-Løken syndrome ( SLSN ) embodies one of many possible forms of hereditary ciliopathy. The autosomal recessive hereditary syndrome is characterized by the association of nephronophthisis, a special form of interstitial kidney inflammation, and retinal degeneration (retinal dystrophy). Depending on the type of genetic defect, symptoms of retinal degeneration appear during or shortly after birth or later in childhood.
What is Senior Loken Syndrome?
Senior-Løken syndrome ( SLSN ) is one of around 20 known forms of ciliopathy. It is differentiated from other forms of ciliopathy by the simultaneous occurrence of nephronophthisis (interstitial kidney inflammation) and retinal dystrophy with severe to severe impairment of vision. For human immunodeficiency virus in dictionary, please visit dictionaryforall.com.
An exact differentiation of the SLSN from other ciliopathies is not always possible because there are genetic and phenotypic overlaps with other ciliopathies. Cilia play a major role in cell movement and in the extracellular “transportation” of solid and liquid substances, as well as triggering impulses in many sensory processes.
Cilia are protrusions of the cell membrane containing cytoplasm. Ciliopathies, functional disorders of the cilia, therefore have an almost systemic effect on many metabolic processes and on sensory performance. The retinal degeneration associated with Senior-Løken syndrome has two distinct forms.
Leber ‘s amaurosis is the more serious form, which manifests itself during and shortly after birth through restricted visual fields and weakened pupillary reactions as well as through nystagmus.
Causes
Like many other ciliopathies, Senior-Løken syndrome is caused exclusively by oligogenic to polygenic defects. In total, mutants of seven different genes at different loci are in focus as triggers of SLNS. Other genes could be added in the future because research in this area is not yet complete.
The genes that code for proteins in the cilia have a significant influence on the development and thus also on the functionality of the photoreceptors in the retina and on the cells of the tubular epithelium of the kidneys. Since the disease is inherited in an autosomal recessive manner, it can only occur if the gene defects are present on both chromosomes and coincide.
In the combination of a “healthy” gene and a mutated gene, the coding of the non-mutated gene prevails, so that the SLNS does not appear, although the genetic predisposition is latent.
There is not (yet) a complete understanding of the relationships between the genetic defects that lead to the onset of the disease. Epistatic interaction chains of certain genes, i.e. interactions of certain, non-homologous genes with each other, are also under discussion.
Symptoms, Ailments & Signs
Symptoms of SLSN usually appear shortly after birth or during the child’s development phase. Because the kidneys and retina are equally affected, signs and symptoms manifest in parallel in both organ systems, the kidneys and the eyes (retina).
Typically, signs of polyuria, a pathologically increased urination and the associated polydipsia, an increased fluid intake, can already be recognized shortly after birth. Signs of retinal dystrophy usually appear immediately after birth in the form of restricted visual fields and weak pupillary reflexes.
In many cases, nystagma is also observed, which are cascading, jerky movements of the eyes that are usually triggered by impulses from the semicircular canals in the inner ear during acceleration. The symptoms that occur in the kidneys and retina are caused by the progressive degenerative processes of the functional cells of the kidney epithelium and the photoreceptors in the retina of the eyes.
Diagnosis & course of disease
The symptoms that develop in connection with SLSN are not very specific and could also indicate a number of other diseases. Comprehensive examinations such as a kidney function test, laboratory examination of the urine and an ultrasound of the upper abdomen are therefore recommended for clarification.
If the examination takes place in infancy, a liver function test is also recommended in order to rule out liver fibrosis. With regard to the eyes, examinations of the fundus of the eye, visual acuity, field of vision and color vision serve to differentiate it from other diseases. An electroretinogram and measurement of involuntary eye movements complete the investigations.
The course of the SLSN is mainly determined by the progression of the degeneration of the functional kidney tissue. While the degradation processes in the retina ultimately lead to blindness, the prognosis of the overall course of the disease is very unfavorable due to the degradation processes in the kidneys – if left untreated.
Complications
Due to Senior-Løken syndrome, those affected primarily suffer from severe visual problems. These usually appear immediately after birth, so that those affected already suffer from significant limitations in everyday life and thus also from their development in childhood. In the worst case, complete blindness can result.
In many cases, the patients are dependent on the help of other people in their everyday life and, especially at a young age, cannot easily carry out many everyday things. This can lead to psychological problems or depression. Furthermore, this syndrome also causes problems in the kidneys, so that the patients can suffer from renal insufficiency. In the worst case, it can even lead to the death of the person concerned.
Patients are then dependent on a kidney transplant or on dialysis . As a rule, Senior-Løken syndrome always leads to a complete loss of vision, which cannot be treated. The kidney problems can be limited with a healthy lifestyle. However, in most cases, the patient’s life expectancy is significantly reduced by the syndrome.
When should you go to the doctor?
Senior-Løken syndrome must always be treated by a doctor. In most cases, this disease cannot heal itself, so that the affected person is always dependent on medical treatment. Since Senior-Løken syndrome is a genetic disease, genetic counseling should also be carried out if you wish to have children in order to prevent the syndrome from being passed on to offspring. A doctor should be consulted if the person concerned suffers from eye problems.
These symptoms appear for no particular reason and do not go away on their own. Furthermore, kidney problems also indicate Senior-Løken syndrome and must also be checked by a doctor if they occur together with the eye problems. If Senior-Løken syndrome is not treated, the worst case scenario can lead to complete blindness of the person affected. Therefore, early detection of the syndrome is very important.
In the case of Senior-Løken syndrome, a general practitioner can be consulted in the first place. Further treatment is then carried out by an internist or an ophthalmologist.
Treatment & Therapy
If the diagnosis is positive for SLSN, it is important that the affected children undergo regular renal function tests in order to be able to recognize the gradual progression of the disease. Since there is currently (still) no drug known to cure juvenile nephronophthisis, all treatment methods are initially aimed at combating symptoms and relieving pain.
A controlled intake of salts is important in order to keep the electrolyte balance in balance, which can shift due to the constant loss of fluids. If the progression of the disease has reached a critical stage, short-term and recurring dialysis can be life-saving. The only long-term treatment is a kidney transplant.
Also for the treatment of the retinal problems that develop parallel to the kidney problems, no drug or other treatment is known that could slow down or even stop the progression of retinal dystrophy. Therefore, only a poor prognosis is possible for the progression of retinal dystrophy. The disease always ends with a total loss of vision, i.e. complete blindness.
Prevention
Senior-Løken syndrome is due solely to genetic causes. Any precautionary measures such as changes in diet or preventive medication would not be effective. In principle, a prenatal diagnosis is possible if the gene defects are known in the family and documented accordingly.
Aftercare
The treatment of Senior-Løken syndrome goes directly into the follow-up phase, in which the sick children have to be examined regularly. Parents are responsible for adhering to the appointments for the kidney function test. They should follow doctor’s recommendations closely to relieve their children’s symptoms and pain.
The disease is hereditary, so a change in diet only improves body awareness, but has no direct effect on the symptoms. Nevertheless, parents should pay attention to a good electrolyte balance and for this purpose supply the salts prescribed by the doctor. In this way, the increased fluid loss can be compensated.
Depending on the severity of the disease, regular appointments for dialysis should be made. The sick children often feel weakened and need appropriate caring support. Genetic counseling makes sense as part of family planning if the genetic defect is known. This point also plays a relevant role in the combined prevention and aftercare.
The involvement of family members and friends helps the affected children with everyday problems. At the same time, safety increases when the social environment is informed about the disease. In connection with the negative impact of the disease on the retina of the eye, psychotherapy can be useful.
You can do that yourself
Children suffering from Senior-Løken Syndrome need special loving support in everyday life. Above all, parents should ensure that the kidneys are regularly checked for their function. This allows the progress of the disease to be reliably identified. If the genetic defect is known, a corresponding test can be carried out as part of prenatal diagnostics.
However, the hereditary disease cannot be prevented or stopped by a healthy diet or by certain medications. In everyday life it is important that patients receive salts in a controlled manner. These ensure a balanced household of the electrolytes and prevent them from being washed out by the continuous loss of liquid. At an advanced stage of the disease, critical situations may arise. Dialysis is then indispensable. Children often get used to recurrent dialysis at a young age. Still, many parents hope to have a kidney transplant to make life easier for their children.
In addition to the kidney problems, the negative development of the retina also plays a role. Unfortunately, no successful drug therapy is known for this so far, so that the retinal dystrophy progresses. Due to the poor prognosis of the disease, psychological support is recommended for the affected families.
