Ruvalcaba Syndrome

What are the other Names for this Condition? (Also known as/Synonyms)

• Bannayan Syndrome
• Ruvalcaba-Myhre Syndrome
• Ruvalcaba-Myhre-Smith Syndrome

What is Ruvalcaba Syndrome? (Definition/Background Information)

• Ruvalcaba Syndrome or Bannayan-Ruvalcaba-Riley Syndrome (BRRS) is a congenital genetic  condition characterized by macrosomia (abnormally large size at birth), macrocephaly (abnormally enlarged head), scaphocephaly (narrow and long head), mild retardation, multiple non-cancerous tumors and tumor-like growths (called hamartomas), short stature, craniofacial abnormalities (abnormalities of brain and face), and freckles on the penis and vulva
• The symptoms can either be present at birth or shows up during early childhood. The incidence of Ruvalcaba Syndrome is very rare. It is inherited in an autosomal dominant pattern (only one copy of mutated gene is required to develop this condition)
• Development of the following conditions are also commonly seen in those with Bannayan-Ruvalcaba-Riley Syndrome:
  • Hamartomas (benign growth) in the intestines
  • Fatty superficial tumors (lipomas and angiolipomas)
  • Hemangiomas (benign blood vessel tumors)
  • Risk of developing certain cancers            
• Often symptomatic treatment and supportive management of the condition is undertaken by a team of medical specialists. The prognosis is dependent upon a variety of factors, but is generally grim

Who gets Ruvalcaba Syndrome? (Age and Sex Distribution)

• Any individual is likely to be affected by Ruvalcaba Syndrome; it is an age non-specific disorder
• Males are most often affected by this syndrome
• No geographical, ethnic, or racial predominance has been observed
• More than 50 cases within multigenerational families have been reported in medical literature

What are the Risk Factors for Ruvalcaba Syndrome? (Predisposing Factors)

The risk factors associated with Ruvalcaba Syndrome includes:

• Gender : Males are most often affected by this syndrome
• Genetic factors: It is an inherited disorder, usually inherited in an autosomal dominant pattern. A positive family history increases the risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Ruvalcaba Syndrome? (Etiology)

Ruvalcaba Syndrome is inherited in an autosomal dominant pattern. About 60% of Ruvalcaba Syndrome cases are caused by mutations in the PTEN gene and another 10% of the cases are caused by a large deletion of genetic material in the PTEN gene that may include a part or the entire gene.

• The protein produced by PTEN genes acts as a tumor suppressor that helps in preventing cells from growing and dividing in an abnormal or uncontrolled way
• When a defect or mutation in this gene occurs, the cell proliferation process is affected, which can lead to formation of hamartomas and other cancerous and non-cancerous tumors
• When Ruvalcaba Syndrome is not caused by mutations of the PTEN gene, the exact cause is not known

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Ruvalcaba Syndrome?

Symptoms generally vary from one patient to another. However the general symptoms exhibited by Ruvalcaba syndrome include:

• Increased birth weight and macrosomia (large body size at birth)
• Slow growth rate
• Ocular or eye abnormalities such as:
  • Strabismus (crossed eyes)
  • Ocular hypertelorism (widely spaced eyes)
  • Downward slanting eyelid folds (downslanting palpebral fissures)
  • Exotropia (deviation of one eye from the other)
  • Amblyopia (visual impairment)         
  • Pseudopapilledema (abnormal elevation of the optic desk so that it appears to be swollen) 
• Hypotonia: Decreased muscle tone especially of the arms and legs
• Weak facial muscles
• Highly arched roof of the mouth (palate)
• Excessive drooling
• Delayed speech development
• Delay in development of motor skills such as sitting, standing, or walking
• Development of hamartomatous polyps in the intestines (intestinal polyps), the back wall of the throat (pharynx), and tonsils
• Development of fatty tumors called lipomas and angiolipomas under the skin
• Development of red or purplish growths, called hemangiomas, consisting of abnormal tangles of blood vessels is also commonly observed
• Abnormal skin coloration or pigmentation  (cutis marmorata)
• Development of freckle-like spots (pigmented macules) on the penis in males and vulva in females
• Appearance of coffee-colored spots on the skin
• Abnormal widening of the small blood vessels resulting in red lesions in the skin called as telangiectasias
• Enlarged penis and testes which may occur in rare cases
• Skeletal abnormalities affecting the muscles (myopathy) may be commonly seen, which includes:
  • Hyperextensibility of the joint movements
  • Scoliosis - abnormal side to side curvature of the spine
  • Sunken chest or pectus excavatum
  • Abnormally long fingers
  • Unusual broad thumbs and great big toes

How is Ruvalcaba Syndrome Diagnosed?

The diagnosis of Ruvalcaba Syndrome may involve:

• Complete evaluation of medical history along with a thorough physical exam
• Imaging studies such as CT and MRI scan of the affected organs
• Ophthalmoscopy and slit lamp methods are used to detect the abnormalities of the inner eye
• Muscle activity is tested through electromyography (administering electrical charges) and microscopic examination of muscle tissue (muscle biopsy)
• Genetic testing of the PTEN gene can help identify individuals who suffer from mutation of the gene causing Ruvalcaba Syndrome
• Between the ages of 35-40 years, a colonoscopic test and a biennial renal imaging test should be undertaken
• A monthly breast examination, yearly breast screenings, transvaginal ultrasounds, and endometrial biopsies are all recommended for women starting from the age of 30 years

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Ruvalcaba Syndrome?

The complications that may arise due to Ruvalcaba Syndrome include:

• Intellectual disability
• Problems of thyroid gland, including thyroid tumor
• Seizures
• Development of certain other tumors and malignancies

How is Ruvalcaba Syndrome Treated?

Treatment for Ruvalcaba Syndrome is aimed at treating each of the symptoms separately. A team effort from specialists involving pediatricians, surgeons, speech pathologists, rheumatologists, ophthalmologists, physical therapists, and other healthcare professionals is generally required to manage the individuals with the condition.

• Early diagnosis and appropriate early treatment is the need of the hour
• Surgical intervention is required to remove hamartomas that can cause serious complications
• Individuals should be carefully monitored for the development of gastrointestinal polyps. The affected individuals are also closely monitored for the risk of developing other tumors and malignancies
• The delay in motor development can be treated through physical therapy
• Speech therapy is needed to improve the speech of affected individuals
• Special remedial education, special social support, physical therapy and other medical, social, and vocational services may be utilized for improving the condition of the affected children
• Genetic counseling may be beneficial to the affected individuals and their families

How can Ruvalcaba Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Ruvalcaba Syndrome, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Asymptomatic family members should also be tested for mutation in the PTEN gene
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Ruvalcaba Syndrome? (Outcomes/Resolutions)

The prognosis of Ruvalcaba Syndrome is poor and unpredictable; it depends on the initial presentation and severity of the symptoms.

Additional and Relevant Useful Information for Ruvalcaba Syndrome:

The symptoms of another disorder, namely Cowden syndrome, are almost similar to that of Ruvalcaba Syndrome except for a few minor differences.