Denys-Drash Syndrome

The Denys-Drash Syndrome is caused by a congenital gene defect that leads to the manifestation of a nephrotic syndrome. With an incidence of 1: 100,000 in newborns, Denys-Drash syndrome is a rare condition.

What is Denys Drash Syndrome?

Denys-Drash syndrome is a rare autosomal recessive inherited disease, usually with the symptom triad progressive kidney disease with manifestation of an early, often bilateral benign Wilms tumor (nephroblastoma), diffuse mesangial sclerosis (proliferating connective tissue cells in the kidney bodies ) and genital anomalies (masculine pseudohermaphroditism).

The Denys-Drash syndrome is counted accordingly to the spectrum of nephrotic syndromes. The genetic defect can initially manifest itself clinically using a Wilms tumor. Postnatally, diffuse mesangial sclerosis develops in combination with a nephrotic syndrome and pronounced proteinuria (increased protein concentration in the urine), with renal failure to be expected within 1 to 4 years.

Incomplete subforms of Denys-Drash syndrome can manifest as diffuse mesangial sclerosis with masculine hermaphroditism or nephroblastoma.

causes

Denys-Drash syndrome is a congenital (congenital) disease that is inherited as an autosomal recessive trait. As a rule (around 90 percent of cases) in Denys-Drash syndrome, a mutation of the WT1 gene (Wilms tumor suppressor gene) on chromosome 11p13 can be identified, which is responsible for the manifestation of Wilms tumor.

In the majority of cases, exon 8 or 9 on the heterozygous germ line in the zinc finger motif is affected. The underlying mutation is a de novo mutation (new mutation) in 90 percent of cases. The corresponding gene regulates the coding of a specific zinc finger protein, which is involved as a transcription factor in the development of the urogenital tract and nephrogenesis.

As a result of the gene defect characteristic of Denys-Drash syndrome, not only do genital anomalies and Wilms tumors manifest, but the kidney tissue increasingly hardens and scarred (sclerosis), so that the functionality of the kidneys is gradually reduced until the kidneys are complete fail.

Symptoms, ailments & signs

Due to Denys-Drash syndrome, patients suffer from a number of different malformations and other ailments. As a rule, the malformations occur primarily on the external genital organs. This can also lead to psychological complaints, as many of those affected no longer feel comfortable with the malformations and suffer from inferiority complexes or from a significantly reduced self-esteem.

Especially in childhood, Denys Drash Syndrome can lead to bullying or teasing, so that the patient develops psychological complaints or depression. As a rule, there is also an increased amount of protein in the urine and the kidneys continue to develop magnesium. As a result, the kidneys are permanently damaged, so that if left untreated, Denys-Drash syndrome leads to complete kidney failure and thus to death of the person concerned.

The patients are therefore also dependent on a transplant or dialysis. Denys-Drash syndrome can also lead to high blood pressure or swelling in the abdomen and kidneys. Renal insufficiency also increases the risk of developing a tumor, which can also lead to patient death. Life expectancy is severely limited by Denys-Drash syndrome if it is not treated.

Diagnosis & course

Denys-Drash syndrome is usually diagnosed two weeks to 1.5 years after birth based on the characteristic symptoms. The malformations of the external genital organs (including the small penis in affected boys, enlarged labia in girls) can in most cases be detected immediately after birth.

Nephrotic syndromes are also associated with abdominal swellings, decreased urine output, proteinuria due to diffuse mesangial sclerosis, and high blood pressure. To rule out or detect a nephroblastoma, the kidneys should be examined sonographically and / or computed tomographically. In addition, malformations of the sexual organs can be visualized using a computer tomography.

In the differential diagnosis, Denys-Drash syndrome should be differentiated from WAGR syndrome, which is also a disease associated with malformations and Wilms' tumor. In addition, hyperechogenic kidneys can also be detected prenatally in cystic kidneys.

As a rule, children affected by Denys-Drash syndrome are diagnosed with kidney insufficiency (kidney failure) before they are three years old and the majority develop a Wilms tumor within the first two years of life. In children with a kidney transplant, however, the prognosis is good.

When should you go to the doctor?

As a rule, Denys-Drash syndrome is already a congenital syndrome, so that no additional diagnosis of this disease by a doctor is necessary. Due to the various malformations and other symptoms, the child is dependent on various examinations and treatments. A doctor should therefore be consulted if the malformations lead to restrictions in everyday life and in the patient's life. These malformations can possibly be corrected through surgical interventions.

Even with kidney failure, the person concerned is dependent on medical treatment. Swellings or high blood pressure should also be examined by a doctor. Examination of the disease is usually done in a hospital. Further treatment is carried out by a specialist and, for example, with dialysis.A kidney transplant is also possible in order to completely combat kidney failure. Since those affected suffer relatively often from infections and inflammation due to Denys-Drash syndrome, these should also be examined by a doctor.

Doctors & therapists in your area

Treatment & Therapy

A Denys-Drash syndrome cannot be treated causally, as this is attributed to a congenital gene defect. Accordingly, the therapeutic measures aim in particular at the control and regulation of kidney function, the treatment of high blood pressure and proteinuria and the reduction of the symptoms specifically associated with the nephrotic syndrome.

Proteinuria cannot be controlled by conventional drugs. The same applies to the nephrotic syndrome, which cannot be treated with corticosteroids or other immunosuppressants and whose therapy consists primarily of blood dialysis with subsequent unilateral or bilateral nephrectomy (kidney removal) and kidney transplantation.

The primary goal of nephrectomy is to avoid the development of Wilms' tumor. Transplanted kidneys are usually not affected by Denys-Drash syndrome. In most cases, the intersex genital organs are surgically adapted to the external phenotype. In addition, in some cases, surgical removal of the abnormal sexual organs may be indicated in order to minimize the risk of tumor manifestation in these tissue structures.

In the case of Denys-Drash syndrome, adequate nutrition and appropriate prophylaxis with regard to infectious diseases are recommended.

Outlook & forecast

Since Denys-Drash syndrome is a genetic disease, it cannot be treated with causal therapy. Only symptomatic treatment options are therefore available to those affected to alleviate the symptoms.

If there is no treatment for Denys-Drash syndrome, those affected suffer from severe malformations of the genital organs. There is no self-healing, so that those affected cannot engage in sexual acts. Likewise, malformations of the kidneys can occur, which in the further course lead to renal insufficiency. This can be fatal for the person affected and is therefore treated with dialysis or a transplant.

Treatment of the syndrome is always based on the severity of the malformations. These can be corrected through surgical interventions so that patients can participate in sexual intercourse. The symptoms of the kidneys can usually not be stopped or cured, so that those affected are always dependent on a transplant. The life expectancy of the patient is usually limited by Denys-Drash syndrome. An early start of therapy always has a positive effect on the further course of the disease.

prevention

Since Denys-Drash syndrome is a congenital disease, it cannot be prevented.

Aftercare

People with Denys-Drash syndrome usually require lifelong treatment. Therapy and aftercare flow smoothly into one another due to the complex symptoms. Follow-up care can include measures after an operation, such as is necessary in the case of severe genital malformations. The person concerned then has to go to follow-up on a regular basis and also take advantage of therapeutic discussions, since there are usually psychological complaints that have to be dealt with over the long term.

Medical follow-up care and therapy should take place in consultation with the family doctor so that both aspects of the treatment can be coordinated. After a kidney disease, a nephrologist must be seen at regular intervals. The person concerned should first see a doctor once a month. The cycle can be reduced later, always with a view to the course of the disease and any complications.

Denys-Drash syndrome always requires ongoing follow-up care and treatment, because this ensures that the drugs used optimally support the inpatient treatment and the patient can lead a life that corresponds to the state of health. If the disease has caused tumors, follow-up care by a suitable oncologist is also necessary.

You can do that yourself

People who suffer from Denys-Drash syndrome first need medical treatment. The malformation syndrome can, however, also be treated yourself.

After the actual therapy, a healthy diet can help to alleviate the symptoms and support healing. The dermatologist will recommend a diet with sufficient vitamins and nutrients. It is important to avoid substances that could irritate the skin. In addition, no unhealthy foods such as fast food or overly spicy foods should be consumed.

Alcohol and caffeine should also be avoided initially to prevent re-infection. After a kidney transplant, the patient must first take it easy. In any case, strenuous physical activity should be avoided. In addition, we recommend physiotherapy exercises that strengthen the immune system without putting too much strain on the body. Furthermore, the cause of the disease must be determined.

Since the Denys-Drash syndrome can develop very differently and is accompanied by different symptoms, the individual therapy must always be worked out together with the responsible specialist. The patient should contact the doctor for this and, if necessary, also involve a nutritionist, sports doctor and psychologist in the therapy.