The Cowden syndrome is an autosomal dominant disorder that accompanies the propensity for tumor formation and is due to a mutation in the PTEN gene. Although the neoplasms are mostly benign, the disease nonetheless increases the patient’s risk of cancer. Treatment is purely symptomatic and limited to regular check-ups and tumor resections.

What is Cowden Syndrome?

Phacomatoses are hereditary diseases based on mesenchymal and neuroectodermal dysplasias. Dysplasias correspond to visible malformations of organs or tissues. The so-called Cowden syndrome is assigned to the phacomatoses and is characterized by dysplasias in the sense of tumors of all three embryonic cotyledons.

The syndrome corresponds to an extremely rare disease. Since the first description, only 150 cases have been documented worldwide. The incidence of hereditary disease is estimated to be less than one case in 200,000 people. Both sexes are affected by the hereditary disease with the same frequency. The clinical picture of Cowden’s syndrome is pleomorphic, i.e. multifaceted.

Penetrance is age-dependent and heterogeneous in gene expression. According to current research, syndromes such as Proteus syndrome, Proteus-Like syndrome and Bannayan-Riley-Ruvalcaba syndrome have the same genotypes as Cowden syndrome and therefore only differ in phenotype from the clinical picture.

Causes

Cowden syndrome is genetic. As a hereditary disease, it is passed on in an autosomal dominant mode of inheritance. Researchers identify the cause of the malformations in a mutation in the PTEN gene. This gene codes for the multifunctional enzyme phosphatase and has, among other things, a suppressive effect on tumors.

Due to the mutation of the coding gene, the enzyme partially loses its actual function. This connection explains the tumor-like new tissue formations of the three germ layers that characterize Cowden’s syndrome. For this reason, the syndrome is assigned to the group PTEN hamartoma tumor syndromes, which also includes Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome.

The PTEN gene is located on the long arm of chromosome 10 in the q23 gene locus. The tumor suppressor function of the gene is due to the inhibitory effect on protein kinase Akt. This is a central target molecule in the transduction of antiapoptotic and proliferative stimuli. The mutation-related lack of PTEN inhibition of the gene makes the protein kinase overactive and thus stimulates the formation of tumors.

Symptoms, ailments & signs

Cowden syndrome patients have multiple hamartomas of the skin and mucous membranes. Trichilemmomas of the face, papillomas of the mucous membrane in the mouth, and acral and palmoplantar keratoses are common symptoms. In addition, multiple facial papules can occur. Macular pigmentation in the penis area is also frequently documented.

The same applies to gastrointestinal hamartomas and ganglioneuromas. Other benign tumors in the organs, such as thyroid nodules, fibrocystic breast tumors or lipomas in the connective tissue, are also symptomatic of the syndrome. The majority of all patients also suffer from macrocephaly in the sense of an oversized head circumference.

Intellectual disability and anomalies from the autistic circle have been observed in isolated cases. Basically, Cowden syndrome tumors are mostly benign. Nonetheless, the dysplasias can degenerate, which greatly increases the patient’s risk of cancer. Breast cancer, uterine cancer, and thyroid cancer at a young age are not uncommon.

Diagnosis

The clinical diagnosis of Cowden’s syndrome is based on major and minor criteria from the guidelines of the National Comprehensive Cancer Network. A genetic test reveals a PTEN mutation.

Biopsies and histology are just as often required as part of the diagnosis, as are imaging of internal organs and tissues. The prognosis for patients with Cowden’s syndrome is relatively unfavorable, since the risk of degeneration of the tumors is relatively high. With regular checks, the prognosis improves.

When should you go to the doctor?

If the typical facial papules and other signs of Cowden’s syndrome are noticed, a doctor should be consulted. If tumors and lipomas are suspected, an immediate diagnosis by a specialist is indicated. This is especially true if other symptoms such as skin changes or a decrease in mental performance are noticed. These signs indicate that Cowden’s syndrome is severe and should therefore be examined by a specialist in hereditary diseases and treated directly if necessary.

In addition to the specialist and the family doctor, a specialist in gene therapy can also be called in as part of the treatment. Check-ups and regular biopsies are recommended in any case in order to detect possible degenerations at an early stage. In addition, further therapy may have to be initiated in order to remove larger tumors. The person concerned should speak to the responsible doctor and may then have to go to a clinic. However, only the doctor can answer whether and when complex treatment must be carried out for Cowden syndrome.

Treatment & Therapy

A causal treatment is not yet available for patients with Cowden syndrome. Advances in gene therapy may soon open up causal therapeutic approaches. So far, however, gene therapy approaches have not reached the clinical phase.

For this reason, Cowden syndrome is currently considered an incurable disease that can only be treated symptomatically. The patient’s self-control plays an important role in symptomatic therapy. Ideally, the patients notice any new growths within a very short time and contact a specialist immediately for a check-up.

Check-ups and regular biopsies are strongly recommended to those affected in order to detect possible degeneration early enough. Resection of tumors is a central component of symptomatic therapy. Depending on the location of the tumor, this resection requires a wide variety of procedures.

While some tumors can be removed in a minimally invasive manner, resection of others requires major surgery. During the resection, the preservation of vital structures is essential. If larger parts of the tumor cannot be removed in this context, further therapy takes place. The use of cytostatics, radiation therapy or other therapeutic agents of this type may be necessary in this context.

Outlook & forecast

The prognosis for Cowden syndrome is rather poor. The risk of degeneration of the tumors is relatively high, which means that there is a considerable risk of secondary diseases. However, metastasis can be avoided with regular treatment. The patients still require lifelong drug treatment.

The individual symptoms usually cause serious complaints that can significantly reduce the wellbeing and quality of life of those affected. In addition, some complaints can develop into serious complications. With changes in the skin, there is always the risk of inflammation, ulcers and bleeding. In the long term, these complaints, but also the psychological stress associated with the constant risk of illness, represent a considerable burden for those affected.

Patients who suffer from intellectual disabilities or anomalies from the autistic form as part of Cowden’s syndrome have a poorer prognosis. Affected people are permanently restricted in their quality of life and mostly dependent on outside help. From then on there is always the risk that the dysplasias will develop into cancer. Patients are at increased risk of complications such as breast cancer, thyroid cancer, and uterine cancer, which in Cowden’s syndrome can occur at a young age.

Prevention

Cowden syndrome is a hereditary disease. Since the cause of the syndrome lies in the genes and must therefore be described as an internal factor, there are hardly any preventive measures. In family planning, however, couples can take advantage of genetic counseling. Anyone who suffers from Cowden’s syndrome is most likely to pass it on to their children as an autosomal dominant inheritance.

In order to avoid this scenario, those affected can decide against having their own children. Nonetheless, the option of adoption gives them options for starting a family. Whether such a decision is considered sensible in an individual case depends above all on personal experience with the disease.

Aftercare

In most cases, those affected have only very limited follow-up measures available for Cowden’s syndrome. The further course and thus also the life expectancy of this disease depend very much on the time of diagnosis. Therefore, the person affected should consult a doctor at the first symptoms or signs of this disease in order to prevent further complications or complaints.

Self-healing cannot occur. Since Cowden syndrome is a hereditary disease, genetic counseling should be carried out if you want to have children so that the syndrome does not occur in the descendants. Furthermore, regular examinations and controls of the entire body are necessary in order to detect and treat tumors at an early stage.

Surgical interventions may also be necessary, after which the person concerned must rest and take care of his body. Exertion or other stressful physical activities should definitely be avoided in order not to slow down the healing process. When taking medication, ensure that it is taken regularly and that the dosage is correct. If you have any questions or are unclear, you should always contact a doctor first.

You can do that yourself

Cowden syndrome always requires specialist diagnosis and treatment. Those affected can often take action against the individual symptoms themselves. The typical skin changes on the face can be remedied, for example, through strict body hygiene and the use of suitable care products.

It is best for patients to consult their doctor, who can prescribe a suitable preparation based on the symptoms. In severe cases, the doctor will refer the patient to a specialist who can take further action.

Should mental disabilities develop, therapeutic and physiotherapeutic measures must be taken. The patient is advised to perform memory exercises on a regular basis and, in addition, to take advantage of the medical check-ups.

To make sure that the tumor does not recur after treatment, further examinations by a specialist are necessary. The patient should keep a comprehensive complaint book in which he notes any symptoms and complaints. The notes make it easier for the doctor to set the medication and choose suitable accompanying therapies.

Finally, people who suffer from Cowden’s syndrome depend on the support of family members and friends. The support from family and friends contributes significantly to a speedy recovery.