Ruvalcaba-Myhre-Smith syndrome (RMSS) is caused by an autosomal dominant hereditary mutation in the PTEN gene and is associated with intestinal polyps and skin lesions. Patients of the syndrome often suffer from other PTEN-associated syndromes with a diverse clinical picture. The focus of the treatment is on control examinations, which counteract the increased cancer risk of patients.

What is Ruvalcaba-Myhre-Smith Syndrome?

Most benign mucosal evaginations within body cavities are referred to as polyps. Polyp diseases are mainly related to the gastrointestinal tract known and are subject in this context, often family disposition. A subgroup of polyp syndromes forms the group of benign polyp syndromes, including Ruvalcaba-Myhre-Smith syndrome.

The disease is characterized by benign small bowel polyps and is also known as Bannayan-Riley-Ruvalcaba syndrome. The disease is often referred to in the literature as multiple hemangioma, macrocephaly, or pseudopapillaema. Also common are names such as Cowden-Riley-Ruvalcaba overlapping syndrome and Ruvalcaba-Myhre syndrome and Bannayan-Zonana syndrome.

Although no exact prevalence is known, the syndrome is considered a rare disease. Ruvalcaba-Myhre-Smith syndrome is counted among the PTEN hamartoma tumor syndromes that overlap in their phenotype. The basis of all PTEN hamartoma tumor syndromes are genetic defects with autosomal dominant inheritance. Due to the age-dependent penetrance and the different gene expression, there is a great variety of symptoms for the individual clinical pictures.

causes

As with all PTEN-associated syndromes, Ruvalcaba-Myhre-Smith syndrome has a mutation in the PTEN gene that codes for a multifunctional enzyme. In Ruvalcaba-Myhre-Smith syndrome, this mutation is a point mutation on the long arm of chromosome 10.

The PTEN gene and its encoded enzyme function as a tumor suppressor in a healthy body and accordingly prevent the uncontrolled division of certain cell types. The PTEN-encoded lipid phosphatase regulates other proteins by cleaving phosphate groups as an enzyme. Dephosphorylation deactivates proteins. The resulting intervention in the cell cycle has tumor suppressive effects.

Due to the disease-associated mutation in the PTEN gene, the enzyme only partially fulfills its functions. The tumor suppressive protection mechanism thus loses its effectiveness. An uncontrolled proliferation of tissues is the result. Familial clustering was observed for Ruvalcaba-Myhre-Smith syndrome. Inheritance is independent of gender by Autosome. An autosomal dominant inheritance was documented. Heterozygous carriers of the causative mutation also develop Ruvalcaba-Myhre-Smith syndrome.

Symptoms, complaints & signs

Patients with Ruvalcaba-Myhre-Smith syndrome may experience multiple PTEN-associated disorders in some circumstances. The symptoms of the patients differ depending on how many and which PTEN-associated syndromes are present. In addition to scoliosis, hemangiomas can be symptomatic.

In addition, pigmentation disorders often occur in the genital area. Complex movements, such as running, are often difficult to learn due to decreased flexibility, muscle weakness, or general developmental dysfunction. In addition, numerous lipomas usually form on the patient's body.

In addition to macrocephaly, Hashimoto's goiter and vascular malformations, patchy lentiginosis in the area of ​​the penis or vulva is conceivable. Hamartic polyps of the gastrointestinal tract with preferential localization within the small intestine are considered to be the leading symptom of the disease. So far, it has not been conclusively clarified whether observed anomalies such as an increased birth weight of the patients were actually due to the syndrome.

Also, scoliosis and observed hyperextensibility of the joints in the past could theoretically be present as independent phenomena and are therefore negligible as diagnostic-relevant symptoms.

Diagnosis & disease course

So far, no specific diagnostic criteria exist for the diagnosis of RMSS. Mostly the clinical picture leads to a suspected diagnosis. Pediatric criteria of the PTEN score are available for the first suspected diagnosis. To confirm the diagnosis, a molecular genetic analysis is performed which confirms the presence of a PTEN mutation.

If PTEN mutations within the family are already known, prenatal diagnosis is often performed. Although this molecular genetic proof of a PTEN mutation ensures the existence of a PTEN-associated disease, it does not clearly distinguish between individual PTEN syndromes. In terms of differential diagnosis, Ruvalcaba-Myhre-Smith syndrome is to be distinguished in the diagnosis of syndromes such as Lhermitte-Duclos, juvenile polyposis and Peutz-Jeghers syndrome.

Also relevant is a differentiation from Birt-Hogg-Dube syndrome, Proteus syndrome, Cowden syndrome and Gorlin syndrome. Neurofibromatosis type 1 may also confound Ruvalcaba-Myhre-Smith syndrome. The prognosis for patients with Ruvalcaba-Myhre-Smith syndrome depends mainly on the initial symptoms and the possible genotype of the disease.

complications

The symptoms of Ruvalcaba-Myhre-Smith syndrome can be very different, so that no general prognosis of this disease can be given. As a rule, patients suffer from severe pigmentation disorders. Although this does not affect the health, it has a very negative effect on the aesthetics and self-esteem of the person concerned.

In many cases, patients suffer from inferiority complexes or from depression and other mental health problems. Muscle weakness also sets in frequently and there is a slower development. Furthermore, those affected suffer from malformations of the vessels and the small intestine, so it can cause discomfort in the digestive system. The joints and fingers are hyperextendable and can easily be dislocated.

Due to the slower pace of development, patients often rely on the help of parents or other people in their everyday lives and can not master everyday life alone. Whether RuVecaba-Myhre-Smith syndrome reduces life expectancy can not generally be predicted. The victims are dependent on regular examinations. Since the disease can not be treated causally, there are no further complications.

When should you go to the doctor?

Ruvalcaba-Myhre-Smith syndrome, which is known by its diverse names but is extremely rare, is based on a gene mutation. This defect is attributed to the group of hereditary hamartoma polyposis syndromes. The characteristic symptoms of Ruvalcaba-Myhre-Smith syndrome are usually registered at birth. They must then be verified by a genetic test.

The problem with Ruvalcaba-Myhre-Smith syndrome is that the symptoms of this disease are not uniform. They can have different characteristics. However, some of the typical symptoms can be considered as leading symptoms as they are frequent or highly likely to occur.

However, regular visits to the doctor are recommended even after the diagnosis. Those affected by Ruvalcaba-Myhre-Smith syndrome have a higher risk of developing various cancers due to genetic tumor suppression. Especially thyroid cancer or colon cancer are possible. The affected women also increase the risk of breast cancer. Therefore, early onset checkups are indispensable.

The possible medical measures are limited to symptomatic relief. In most cases, interdisciplinary cooperation with specialists from several disciplines makes sense. In addition, in addition to medical support and mental health care can be useful. Because of the variety and the nature of the symptoms, those affected often experience feelings of inferiority or depression.

Indigestion or malformation of the extremities may require treatment. The Ruvalcaba-Myhre-Smith syndrome restricts the quality of life. Most sufferers need life-long support and help.

Treatment & Therapy

A causal therapy is not available for patients with PTEN-associated syndromes as long as gene therapy approaches do not reach the clinical phase. So far, only symptomatic and supportive treatment measures exist for the Ruvalcaba-Myhre-Smith syndrome. The care and treatment of patients takes place in a multidisciplinary team.

The focus is on the monitoring of patients who should prevent complications of polyposis. Severe complications such as bleeding are often detected early enough to intervene through close monitoring. In PTEN germ line mutations, regular monitoring sonographies of the thyroid are also performed.

In addition, underage patients are monitored annually for skin lesions. From the age of 30, annual colonoscopy is recommended. Every two years, kidney imaging is recommended as well. For female patients, a monthly breast control is recommended from the age of 30.

A mammography screening should take place at least annually. Transvaginal ultrasound or endometrial biopsies are also recommended. The same is true for control studies for neurological or vascular anomalies. The increased cancer risk of patients is counteracted by the aforementioned controls. Developmental disorders and muscle weaknesses can be counteracted by physiotherapy.

prevention

So far, only Ruvalcaba-Myhre-Smith syndrome and other PTEN syndromes can be prevented by genetic counseling in the family planning phase. The decision against a own child can be worth considering with appropriate genetics a consideration.

aftercare

The Ruvalcaba-Myhre-Smith syndrome is a genetic mutation and as a result unfortunately no causal follow-up is possible. The focus is thus on the reduction of the various complaints by a symptomatic aftercare. The disease leads to muscle weakness and slowed development, so here physiotherapy should be used supportive.

Because the disease has a negative impact on the overall quality of life of the patient, in some cases psychological treatment is necessary. The lifelong dependence on other people in everyday life, as well as the pigmentation disorders can put a strain on the patients.

After the disease with Ruvalcaba-Myhre-Smith syndrome follow-up examinations are necessary at regular intervals. These focus primarily on the prevention of polyps and possible cancers due to the increased tumor suppression. Thyroid levels are also checked and kidneys examined.

Since it may lead to digestive problems due to the malformations of vessels and small intestine, a periodic inspection by a specialist is also important here. For women, additional gynecological examinations such as mammography, transvaginal ultrasound and endometrial biopsy should be planned. The prognosis of Ruvalcaba-Myhre-Smith syndrome depends on the symptoms and possible genotypes of the disease. Currently, it is unclear whether life expectancy is affected by this disease.

You can do that yourself

Since patients with Ruvalcaba-Myhre-Smith syndrome are at an increased risk of developing cancer, they should minimize known risk factors in everyday life. An unhealthy diet, the consumption of nicotine and alcohol and exposure to other pollutants should be avoided. The focus of self-help measures is on promoting well-being and improving the quality of life.

Stressors can be broken down by cognitive therapies or relaxation techniques. Yoga, autogenic training or meditation have been proven to help strengthen your inner balance and mental balance. A healthy and balanced diet is also recommended, as it supports the immune system and thus reduces the risk of cancer. Disorders of the skin often lead to a reduced self-confidence. Here, too, cognitive training helps to better manage the handling of the pigmentation disorder in everyday life. If tolerability permits, cosmetic products can be used to make it more attractive.

Since it is a genetic disease, relatives and parents should inform the offspring early on the health disorder, the course and the resulting consequences. The discussion of open questions is important so that the child is not exposed to a sudden situation of overburdening in everyday life. Leisure time activities should be geared to the possibilities of the patient and, in addition to the promotion of well-being, should include the creation of a sense of achievement.

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