Cowden syndrome is an autosomal-dominant inherited disorder associated with a tendency to form tumors and is due to a mutation in the PTEN gene. Although the neoplasms are usually benign, the disease nevertheless increases the risk of cancer in patients. Treatment is purely symptomatic and is limited to regular checkups and tumor resections.
What is Cowden syndrome?
Phakomatoses are inherited disorders based on mesenchymal and neuroectodermal dysplasias. Dysplasias correspond to visible malformations of organs or tissues. The so-called Cowden syndrome is assigned to the phakomatoses and is characterized by dysplasias in the sense of tumors of all three embryonic germ layers. The syndrome corresponds to an extremely rare disease. Since its initial description, only 150 cases have been documented worldwide. The incidence of the hereditary disease is estimated to be less than one case in 200,000 people. Both sexes are affected with equal frequency by the hereditary disease. The clinical picture of Cowden syndrome is pleomorphic, i.e. multiform. Penetrance is age-dependent and heterogeneous in gene expression. Syndromes such as Proteus syndrome, Proteus-Like syndrome, and Bannayan-Riley-Ruvalcaba syndrome share the same genotype as Cowden syndrome, according to recent research, and thus differ from the clinical picture only in phenotype.
Causes
Cowden syndrome has its cause in the genes. As a hereditary disease, it is passed on in the autosomal dominant mode of inheritance. Researchers identify the cause of the malformations as a mutation in the PTEN gene. This gene codes for the multifunctional enzyme phosphatase and has a suppressive effect on tumors, among other things. Due to the mutation of the coding gene, the enzyme partially loses its actual function. This connection explains the tumor-like tissue neoplasms of the three cotyledons that characterize Cowden syndrome. For this reason, the syndrome is assigned to the PTEN hamartoma tumor syndrome group, which also includes Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome. The PTEN gene is located on the long arm of chromosome 10 in gene locus q23. The tumor suppressor function of the gene is due to its inhibitory effect on protein kinase Akt. This is a central target molecule in the transduction of anti-apoptotic and proliferative stimuli. The mutational lack of PTEN inhibition of the gene renders protein kinase overactive and thus stimulates tumor formation.
Symptoms, complaints, and signs
Patients with Cowden syndrome suffer from multiple hamartomas of the skin and mucous membranes. Trichilemmomas of the face, mucosal papillomas of the mouth, and acral and palmoplantar keratoses are common symptoms. In addition, multiple facial papules may occur. Macular pigmentation in the penile region is also frequently documented. The same is true for gastrointestinal hamartomas as well as ganglioneuromas. Symptomatic for the syndrome are also other benign tumors in the organs, such as thyroid nodules, fibrocystic tumors of the breast or lipomas in the connective tissue. The majority of all patients also suffer from macrocephaly in the sense of an oversized head circumference. Mental retardation and anomalies of the autistic form have been observed in isolated cases. In principle, the tumors of Cowden syndrome are usually benign. Nevertheless, the dysplasias can degenerate, greatly increasing the risk of cancer in patients. Breast cancer, uterine cancer, and thyroid cancer at a young age are not uncommon.
Diagnosis
Clinical diagnosis for Cowden syndrome is made using major and minor criteria from the National Comprehensive Cancer Network guidelines. Genetic testing yields evidence of a PTEN mutation. Biopsies and histology are frequently required as part of the diagnostic process, as are imaging of internal organs and tissues. The prognosis for patients with Cowden syndrome is relatively unfavorable, as the risk of tumor degeneration is relatively high. Prognosis improves with regular monitoring.
When should you see a doctor?
When the typical facial papules and other signs of Cowden syndrome are noticed, a physician should be consulted. If tumors and lipomas are suspected, immediate evaluation by a specialist is indicated.This is especially true if further symptoms such as skin changes or a decrease in mental performance are noticed. These signs indicate that Cowden syndrome is taking a severe course and are therefore best examined by a specialist in hereditary diseases and, if necessary, treated directly. As part of the treatment, a specialist in gene therapy may be consulted in addition to the specialist and the family physician. Control examinations 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 to remove larger tumors. The affected person should talk to the responsible physician for this and may then have to visit a clinic. However, only the physician can answer whether and when complex treatment must be performed for Cowden syndrome.
Treatment and therapy
Causal treatment is not yet available for patients with Cowden syndrome. It is possible that advances in gene therapy will soon open up causal therapeutic approaches. To date, however, gene therapy approaches have not reached the clinical phase. For this reason, Cowden syndrome is still considered an incurable disease that can only be treated symptomatically. Patient self-monitoring plays an important role within symptomatic therapy. Ideally, patients notice any neoplasms within a very short time and contact a specialist immediately for control. Control examinations and regular biopsies are strongly recommended to the patients in order to detect possible degenerations early enough. Resection of tumors is a central component of symptomatic therapy. Depending on the localization of the tumor, this resection requires a wide variety of procedures. While some tumors can be removed minimally invasively, major surgery is required to resect others. During resection, it is imperative to preserve vital structures. If larger portions of tumors cannot be removed in this context, further therapy will take place. The use of cytostatics, radiation therapy, or other therapeutics of this type may be required in this context.
Outlook and prognosis
The prognosis is rather poor in Cowden syndrome. The risk of tumor degeneration is relatively high, resulting in a significant risk of sequelae. However, with regular treatment, metastasis can be avoided. Patients nevertheless require lifelong drug treatment. The individual symptoms usually cause serious discomfort, which can significantly reduce the well-being and quality of life of those affected. In addition, serious complications can develop from some complaints. For example, skin changes always carry the risk of inflammation, ulcers and bleeding. In the long term, these complaints, but also the psychological stress associated with the constant risk of disease, represent a considerable burden for those affected. Patients suffering from mental retardation or abnormalities from the autistic spectrum of forms in the context of Cowden syndrome have a worse prognosis. Affected persons are permanently limited in their quality of life and are usually dependent on outside help. In addition, there is always a risk that the dysplasia will develop into cancer. Patients have an increased risk of secondary diseases such as breast cancer, thyroid cancer, and uterine cancer, which can occur at a young age in Cowden syndrome.
Prevention
Cowden syndrome is a hereditary disease. Because the cause of the syndrome lies in the genes and must therefore be called an internal factor, few preventive measures exist. However, couples can take advantage of genetic counseling in family planning. Those who suffer from Cowden syndrome themselves are likely to pass it on to their children in autosomal dominant inheritance. To avoid this scenario, affected individuals can decide against having children of their own. The possibility of adoption nevertheless provides them with options for starting a family. Whether such a decision is considered appropriate in an individual case depends primarily on personal experience with the disease.
Follow-up
In most cases, only very limited aftercare measures are available to the affected person with Cowden syndrome.The further course and thus also the life expectancy of this disease depend very much on the time of diagnosis. Therefore, the affected person should already consult a doctor at the first symptoms or signs of this disease in order to prevent further complications or complaints. A self-cure cannot occur in this case. Since Cowden syndrome is a hereditary disease, genetic counseling should be performed if the patient wishes to have children, so that the syndrome does not appear in the descendants. Furthermore, regular examinations and checks 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 affected person must in any case rest and also take care of his body. Efforts or other stressful and physical activities are to be refrained from in any case, in order not to slow down the healing process. When taking medication, always ensure that it is taken regularly and in the correct dosage. If there are any questions or if anything is unclear, a doctor should always be contacted first.
What you can do yourself
Cowden syndrome always requires a specialist diagnosis and treatment. Those affected can often take action against the individual symptoms themselves. For example, the typical skin changes on the face can be remedied by strict personal hygiene and the use of appropriate skin care products. Patients are best advised to consult their doctor, who can prescribe a suitable product in view of the symptoms. In severe cases, the medical professional will refer the patient to a specialist who can take further action. If mental disabilities develop, therapeutic and physiotherapeutic measures must be taken. For example, the patient is advised to perform regular memory exercises and also to take advantage of the medical check-ups. To ensure 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 down any symptoms and complaints. The notes will help the physician adjust medication and choose appropriate adjunctive therapies. Finally, people suffering from Cowden syndrome depend on the support of relatives and friends. Support from family and acquaintances contributes significantly to a speedy recovery.
