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.
It is one of the PTEN hamartoma tumor syndromes (PHTS), a spectrum of disorders caused by mutations in a gene called PTEN. BRRS is a disorder present from birth that is characterized by macrocephaly (larger than normal sized head), intestinal polyposis (multiple benign polyps in the intestines), lipomas (tumors below the skin made up of fatty tissue), and pigmented skin lesion (macule) in the area of the penis called the glans penis. The symptoms of BRRS vary from person to person. Treatment is based on the symptoms present; however, because of the increased risk of developing cancer in people with the PHTS, increased cancer surveillance is recommended.
The characteristic features of this disease is are macrocephaly (larger than normal sized head), intestinal polyposis (multiple benign polyps in the intestines), lipomas (tumors below the skin made up of fatty tissue), and pigmented skin lesion (macule) in the area of the penis called the glans penis. Other common features of BRRS include high birth weight, developmental delay, mental deficiency, myopathy (problems with the tone and contraction of skeletal muscles [muscles that control voluntary movements]) of the proximal muscles (click here to view diagram of the location of proximal muscles), joint hyperextensibility (unusually large range of joint movement), pectus excavatum (sunken chest), and scoliosis.
The list of signs and symptoms mentioned in various sources for Bannayan-Zonana syndrome includes the symptoms listed below:
- High birth weight
- Large birth length
- Reduced muscle tone
- Gross motor delay
- Speech delay
- Mental deficiency
- Large head
- Down-slanting space between eyelids
- Prominent schwalbe lines
- Prominent corneal nerves
- Ileal hamatromatous polyps
- Colonic hamartomatous polyps
- Subcutaneous neoplasms
- Cranial neoplasms
- Osseous neoplasms
- Brownish spots on penis
- Myopathic process in proximal muscles
- Cutaneous angiolipomas
- Hyperextensible joints
- Sunken chest
- Neonatal overgrowth
- Colonic polyps
- Ileal polyps
It 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.
It is inherited in an autosomal dominant pattern, which means an individual needs to only inherit one mutated copy of the PTEN gene in order to have the condition. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
About 60 percent of all cases of Bannayan-Riley-Ruvalcaba syndrome result from mutations in the PTEN gene. Another 10 percent of cases are caused by a large deletion of genetic material that includes part or all of this gene. The protein produced from the PTEN gene is a tumor suppressor, which means that it normally prevents cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. If this protein is missing or defective, cell proliferation is not regulated effectively. Uncontrolled cell division can lead to the formation of hamartomas and other cancerous and noncancerous tumors. The protein produced from the PTEN gene likely has other important functions within cells; however, it is unclear how mutations in this gene can cause the other features of Bannayan-Riley-Ruvalcaba syndrome, such as macrocephaly, developmental delay, and muscle and skeletal abnormalities.
When Bannayan-Riley-Ruvalcaba syndrome is not caused by mutations or deletions of the PTEN gene, the cause of the condition is unknown.
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.
Following tests can be helpful in diagnosing this disease;
- Historyand physical exam provide important clues in diagnosis of macrocephaly.
- Age of child is important because hydrocephalusand anatomic causes of megalencephaly may be present at birth.
- Head circumference percentile shouldbe compared with height and weight percentiles using CDC growthcharts (2001). If weight, height, and head circumference are samepercentile and all are >3 standard deviations above meanfor age and gender, patient most likely is normal. Children whosehead circumference is out of proportion to other growth parametersshould be investigated.
- It is important to remember that inprotein-calorie malnutrition, normal head size may appear largewhen compared with body size.
- Combination of neuroimaging modalitiesis useful in diagnosis.
- Head U/S is usually performed initiallyin neonates and young infants.
- CT is preferred for trauma and acuteneurologic deficits.
- MRI is considered imaging procedureof choice for evaluation of neoplasms, certain vascular and hemorrhagiclesions, and inflammatory processes affecting brain. It is alsomore sensitive and specific than head U/S or CT for evaluationof brain malformations, myelination disorders, and neurodegenerativedisorders.
- Other investigations depend on suspecteddiagnosis from history, physical exam, and imaging findings.
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.
- surgical intervention is necessary
- Ventriculoperitoneal shunt
- Ventriculoatrial shunt
For post-hemorrhagic hydrocephalus, commonly seen in premature infants;
- Serial lumbar punctures to delay shunt placement
- Hydrocephalus resolves spontaneously in the majority
Currently there are no curative treatments;
Management involves addressing the neurologic symptoms
Anticipatory guidance to the caregiver.