Bannayan Riley Ruvalcaba Syndrome

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Bannayan Riley Ruvalcaba Syndrome

Bannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. The signs and symptoms of Bannayan-Riley-Ruvalcaba syndrome are present from birth or become apparent in early childhood.

At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size (macrosomia). Growth usually slows during childhood, so affected adults are of normal height and body size. About half of all children with Bannayan-Riley-Ruvalcaba syndrome have intellectual disability or delayed development, particularly the development of speech and of motor skills such as sitting, crawling, and walking. These delays may improve with age.

About half of all people with Bannayan-Riley-Ruvalcaba syndrome develop hamartomas in their intestines, known as hamartomatous polyps. Other noncancerous growths often associated with Bannayan-Riley-Ruvalcaba syndrome include fatty tumors called lipomas and angiolipomas that develop under the skin. Some affected individuals also develop hemangiomas, which are red or purplish growths that consist of tangles of abnormal blood vessels. People with Bannayan-Riley-Ruvalcaba syndrome may also have an increased risk of developing certain cancers, although researchers are still working to determine the cancer risks associated with this condition.

Other signs and symptoms that have been reported in people with Bannayan-Riley-Ruvalcaba syndrome include weak muscle tone (hypotonia) and other muscle abnormalities, thyroid problems, and seizures. Skeletal abnormalities have also been described with this condition, including an unusually large range of joint movement (hyperextensibility), abnormal side-to-side curvature of the spine (scoliosis), and a sunken chest (pectus excavatum).

The features of Bannayan-Riley-Ruvalcaba syndrome overlap with those of another disorder called Cowden syndrome. People with Cowden syndrome develop hamartomas and other noncancerous growths; they also have an increased risk of developing certain types of cancer. Both conditions can be caused by mutations in the PTEN gene. Some people with Bannayan-Riley-Ruvalcaba syndrome have had relatives diagnosed with Cowden syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is one of the PTEN hamartoma tumor syndromes (PHTS). This is a group of disorders caused by mutations in a gene called PTEN. BRRS is present from birth includes large head size, benign polyps in the intestines, benign tumors below the skin called lipomas, and pigmented skin spots on the penis. Treatment is based on the symptoms present. Because of the increased risk of developing cancer in people with the PHTS, cancer surveillance is recommended.

Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas. The disease is inherited in an autosomal dominant manner.[3] The disease belongs to a family of hamartomatous polyposis syndromes, which also includes Peutz–Jeghers syndrome, juvenile polyposis and Cowden syndrome. Mutation of the PTEN gene underlies this syndrome, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, these four syndromes are referred to as PTEN Hamartoma-Tumor Syndromes.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.

Bannayan-Riley-Ruvalcaba syndrome is a congenital disorder characterized by macrocephaly, intestinal polyposis, lipomas, and pigmented macules of the penis. There is limited published radiologic literature on the syndrome. The purpose of this study was to review the brain MR imaging findings in Bannayan-Riley-Ruvalcaba syndrome as well as to compare and contrast the findings with other brain disorders that also have brain cysts and white matter lesions.

All brain MR imaging studies were reviewed in patients with a diagnosis of Bannayan-Riley-Ruvalcaba syndrome from our hospital. All 7 patients were evaluated with brain MR imaging. MR imaging results showed white matter cysts in the parietal lobe (7/7), frontal lobe (3/7), and temporal lobe (1/7).

These were predominantly surrounded by white matter T2 hyperintensities associated with macrocephaly. Cystic lesions on MR imaging in Bannayan-Riley-Ruvalcaba syndrome are prevalent, and knowledge of this differential diagnosis can allow the radiologist to suggest a diagnosis of this condition in a child with macrocephaly.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare condition with hamartomatous polyps of the small and large intestines. It is associated with:

  • macrocephaly (larger head size)
  • lipomas (benign fatty tumors)
  • blood vessel changes (hemangiomas)
  • thyroid problems

Some children may be hypotonic (decreased muscle tone), have learning difficulties, and developmental delays.  Also, the hemangiomas (raised red birthmarks) associated with this condition may be present on internal organs and the skin.

Not all patients diagnosed with BRRS have the same features. Only 50% have developmental and learning delays and only 45% develop intestinal polyps.

In addition, patients may display eye abnormalities such as strabismus (crossed eye), widely spaced eyes, and exotropia (deviation of one eye away from the other). Also, skin abnormalities may include areas of “marbled” pigmentation (cutis marmorata) and freckle-like spots on the genital region of both male and female patients.

Close follow-up with specialists specific to associated symptoms is a vital part of managing this condition.

Symptoms

The features of BRRS are large head size, benign polyps in the intestines, lipomas under the skin, and pigmented skin spots (macules) on the glans penis. Other common features of BRRS include high birth weight, developmental delay, and intellectual disability. People with this syndrome can also have problems with the tone and contraction of skeletal muscles. This myopathy includes the muscles in the limbs that are closest to the middle of the body (proximal muscles). People can also have an unusually large range of joint movement, pectus excavatum (sunken chest), and scoliosis.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) .

The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign mesodermal hamartomas (multiple hemangiomas, and intestinal polyps). Dysmorphy as well as delayed neuropsychomotor development can also be present. The head enlargement does not cause widening of the ventricles or raised intracranial pressure; these individuals have a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue.[medical citation needed.

Some individuals have thyroid issues consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer, most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression.

Cause

BRRS is caused by specific mutations in the PTEN gene. The PTEN gene provides instructions for making a protein that is found in almost all tissues in the human body. The protein acts as a tumor suppressor, which means that it plays a role in preventing cells from growing and dividing too rapidly or in an uncontrolled way.

Diagnosis

Diagnostic criteria have not been established for BRRS; however, BRRS may be suspected based on the presence of signs and symptoms. Although genetic testing is available for the PTEN gene, it is  estimated that only about 65 percent of individuals with a clinical diagnosis of BRRS have a detectable PTEN gene mutation.

In terms of diagnosing Bannayan–Riley–Ruvalcaba syndrome there is no current method outside the physical characteristics that may be present as signs/symptoms. There are, however, multiple molecular genetics tests (and cytogenetic test) to determine Bannayan–Riley–Ruvalcaba syndrome.

There are no specific criteria for diagnosis of BRRS but it is usually determined by the clinical presentation. The pediatric criteria of the PTEN Scoring System can be used and are heavily based on the presence or absence of macrocephaly and the presence of one of four sub-criteria (autism spectrum disorder, dermatologic features, vascular malformations and/or gastrointestinal polyposis). A PTEN mutation confirms that the BRRS patient belongs to the PHTS group.

Treatment

Treatment is based on the specific signs and symptoms present in the individual. Screening recommendations for BRRS have not been established; however, recent studies have suggested that people with BRRS, especially those with a known mutation in their PTEN gene, should undergo increased surveillance of cancer affecting the breast, thyroid, endometrial, and kidney.

In terms of treatment/management one should observe what signs or symptoms are present and therefore treat those as there is no other current guideline. The affected individual should be monitored for cancer of:

  • Thyroid
  • Breast
  • Renal
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