Ruvalcaba-Myhre-Smith Syndrome

By | June 8, 2022

Ruvalcaba -Myhre-Smith syndrome (RMSS) is caused by an autosomal dominant mutation in the PTEN gene and is associated with intestinal polyps and skin changes. Patients of the syndrome often suffer from other PTEN-associated syndromes with a diverse clinical picture. The treatment focuses on check-ups that counteract the patient’s increased risk of cancer.

What is Ruvalcaba-Myhre-Smith Syndrome?

Mostly benign mucosal protuberances within body cavities are referred to as polyps. Polyp diseases are mainly known in relation to the gastrointestinal tract and are often subject to family disposition in this context. A subgroup of the polyp syndromes is the group of harmless polyp syndromes, which includes the Ruvalcaba-Myhre-Smith syndrome. For everything about anthrax, please visit

The disease is characterized by harmless polyps in the small intestine and is also known as Bannayan-Riley-Ruvalcaba syndrome. The disease is also often referred to in the literature as multiple hemangiomata, macrocephaly or pseudopapilledema. Also common are terms such as Cowden-Riley-Ruvalcaba overlapping syndrome, as well as Ruvalcaba-Myhre syndrome and Bannayan-Zonana syndrome.

Although no exact prevalence is known, the syndrome is considered to be a rather rare disease. Ruvalcaba-Myhre-Smith syndrome is one of the PTEN hamartoma tumor syndromes that overlap in their phenotypes. All PTEN hamartoma tumor syndromes are based on genetic defects with autosomal dominant inheritance. Due to the age-dependent penetrance and the different gene expression, there is a large variety of symptoms for the individual clinical pictures.


As is the case for all PTEN-associated syndromes, there is also a mutation in the PTEN gene for Ruvalcaba-Myhre-Smith syndrome, which 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 the enzyme it encodes act 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 intervention in the cell cycle achieved in this way has a tumor-suppressive effect.

Due to the disease-associated mutation in the PTEN gene, the enzyme only partially fulfills its functions. The tumor suppressive protective mechanism thus loses its effectiveness. The result is an uncontrolled proliferation of tissues. Familial aggregation has been observed for Ruvalcaba-Myhre-Smith syndrome. Inheritance occurs through autosomes, regardless of sex. An autosomal dominant inheritance has been documented. Heterozygous carriers of the causative mutation also develop Ruvalcaba-Myhre-Smith syndrome.

Symptoms, Ailments & Signs

Under certain circumstances, patients with Ruvalcaba-Myhre-Smith syndrome suffer from several PTEN-associated diseases at the same time. Patient symptoms differ depending on how many and which PTEN-associated syndromes are present. In addition to scoliosis, hemangiomas can be symptomatic.

In addition, pigment disorders often occur in the genital area. Complex movement sequences such as running are often difficult to learn due to reduced flexibility, muscle weakness or general developmental disorders. 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. Hamartous polyps of the gastrointestinal tract with a preferred localization within the small intestine are considered the main symptom of the disease. So far, it has not been conclusively clarified whether observed anomalies such as increased birth weight in the patients were actually due to the syndrome.

Theoretically, scoliosis and observed hyperextensibility of the joints can also be present as independent phenomena in the past and are therefore to be neglected as diagnostically relevant symptoms.

Diagnosis & course of disease

To date, there are no specific diagnostic criteria for diagnosing RMSS. The clinical picture usually 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 carried out, which confirms the presence of a PTEN mutation.

If PTEN mutations are already known in the family, prenatal diagnosis is often carried out. Although this molecular genetic proof of a PTEN mutation confirms the presence of a PTEN-associated disease, it does not provide a clear distinction between individual PTEN syndromes. In terms of differential diagnosis, the Ruvalcaba-Myhre-Smith syndrome must be distinguished from syndromes such as the Lhermitte-Duclos, juvenile polyposis and Peutz-Jeghers syndromes.

Equally relevant is a differentiation from Birt-Hogg-Dube syndrome, Proteus syndrome, Cowden syndrome and Gorlin syndrome. The Ruvalcaba-Myhre-Smith syndrome can also be confused with neurofibromatosis type 1. The prognosis for patients with Ruvalcaba-Myhre-Smith syndrome depends primarily on the initial symptoms and the possible genotype of the disease.


The symptoms of the Ruvalcaba-Myhre-Smith syndrome can be very different, so that no general prognosis can be given for this disease. As a rule, the patients suffer from severe pigment disorders. Although these do not affect health, they do have a very negative effect on the aesthetics and self-esteem of those affected.

In many cases, patients suffer from inferiority complexes or from depression and other psychological problems. Muscle weakness is also common and development is slowed down. Furthermore, those affected suffer from malformations in the vessels and also in the small intestine, so that there can be problems with digestion. The joints and fingers are hyperextensible and easily dislocated.

Due to the slowed development, the patients are often dependent on the help of their parents or other people in their everyday life and cannot cope with everyday life on their own. It cannot generally be predicted whether life expectancy will be reduced as a result of Ruvalcaba-Myhre-Smith syndrome. Those affected need regular check-ups. Since the disease cannot be treated causally, no further complications arise.

When should you go to the doctor?

The Ruvalcaba-Myhre-Smith syndrome, which is known under various names but occurs extremely rarely, is based on a gene mutation. This defect is assigned to the group of hereditary hamartoma polyposis syndromes. The characteristic symptoms of the Ruvalcaba-Myhre-Smith syndrome are usually already registered at birth. They must then be verified by genetic testing.

The problem with Ruvalcaba-Myhre-Smith syndrome is that the symptoms of this disease do not occur uniformly. They can have different characteristics. However, some of the typical symptoms can be regarded as key symptoms, since they occur frequently or with a high probability.

However, regular visits to the doctor are also advisable after the diagnosis has been made. Those affected by Ruvalcaba-Myhre-Smith syndrome have a higher risk of developing various forms of cancer due to genetic tumor suppression. Thyroid cancer or colon cancer are the most common. The women affected also have an increased risk of breast cancer. Early check-ups are therefore essential.

The possible medical measures are limited to symptomatic relief. Interdisciplinary cooperation with specialists from several disciplines is usually useful. In addition to medical support, psychological support can also be useful. Because of the variety and type of symptoms, those affected often experience feelings of inferiority or depression.

Digestive problems or deformities in the extremities may require treatment. The Ruvalcaba-Myhre-Smith syndrome limits the quality of life. Most sufferers need lifelong 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. Also for the Ruvalcaba-Myhre-Smith syndrome only symptomatic and supportive treatment measures exist so far. Patients are cared for and treated by a multidisciplinary team.

The focus is on patient monitoring to prevent complications of polyposis. Severe complications such as bleeding are often detected early enough to be able to intervene through close monitoring. In the case of PTEN germline mutations, regular monitoring sonographies of the thyroid gland are also carried out.

In addition, underage patients are checked annually for skin changes. Annual colonoscopies are recommended from the age of 30 . Imaging tests of the kidneys are also recommended every two years. Monthly breast checks are recommended for female patients over the age of 30.

A mammography screening should take place at least once a year. Transvaginal ultrasound examinations or endometrial biopsies are also recommended. The same applies to check-ups for neurological or vascular abnormalities. The increased cancer risk of the patients is counteracted by the mentioned controls. Developmental disorders and muscle weakness can be countered by physiotherapy.


So far, Ruvalcaba-Myhre-Smith syndrome and other PTEN syndromes can only be prevented by genetic counseling during the family planning phase. The decision not to have your own child can be worth considering if you have the right genetics.


The Ruvalcaba-Myhre-Smith syndrome is a genetic mutation and means that causal follow-up care is unfortunately not possible. The focus is therefore on reducing the various complaints through symptomatic aftercare. The disease leads to muscle weakness and slowed development, so physiotherapy should be used to support this.

Since the disease negatively affects the overall quality of life of the patient, psychological treatment is necessary in some cases. The lifelong dependency on other people in everyday life, but also the pigment disorders can put a lot of strain on the sufferer.

After the illness with Ruvalcaba-Myhre-Smith syndrome, check-ups are necessary at regular intervals. These focus primarily on the prevention of polyps and possible cancer through increased tumor suppression. The thyroid levels are also checked and the kidneys examined.

Since malformations of the vessels and small intestine can lead to digestive problems, periodic check-ups by a specialist are also important here. In women affected, additional gynecological check-ups such as mammography, transvaginal ultrasound and endometrial biopsy should be scheduled. The prognosis for Ruvalcaba-Myhre-Smith syndrome depends on the symptoms and the possible genotypes of the disease. It is currently not possible to say whether life expectancy will be affected by this disease.

You can do that yourself

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

Stressors can be reduced through cognitive therapies or relaxation techniques. Yoga, autogenic training or meditation have been proven to help strengthen inner balance and mental balance. A healthy and balanced diet is also advisable, as it supports the immune system and thus reduces the risk of cancer. Skin disorders often lead to reduced self-confidence. Here, too, cognitive training helps to better deal with the pigment disorder in everyday life. If tolerance permits, cosmetic products can be used to make beautification.

Since it is a genetic disease, relatives and parents should inform the offspring at an early stage about the health disorder, the course and the resulting consequences. Discussing open questions is important so that the child is not suddenly exposed to situations of excessive demands in everyday life. Leisure activities are to be geared to the patient’s possibilities and should include the development of a sense of achievement in addition to promoting well-being.

Ruvalcaba-Myhre-Smith Syndrome