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Bannayan-Riley-Ruvalcaba syndrome

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Other Names:
BRRS; Riley-Smith syndrome; Macrocephaly multiple lipomas and hemangiomata; BRRS; Riley-Smith syndrome; Macrocephaly multiple lipomas and hemangiomata; Ruvalcaba -Myhre-Smith syndrome; RMSS; Bannayan-Zonana syndrome; BZS; Macrocephaly pseudopapilledema and multiple hemangiomas See More
Categories:
This disease is grouped under:
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a genetic condition that leads to the growth of both non-cancerous and cancerous tumors. Symptoms of BRRS may include large head size, increased birth weight, developmental delay, and intellectual disability. Other symptoms include the appearance of non-cancerous tumors in the digestive system, fatty tumors under the skin, and freckles on the penis. People with BRRS have an increased risk of developing breast, thyroid, and uterine cancer. This condition is part of a group of conditions known as the PTEN hamartoma tumor syndromes, which all share similar features and are caused by genetic changes (DNA variants) in the PTEN gene. BRRS is inherited in an autosomal dominant pattern. Diagnosis is based on clinical exam, the symptoms, and genetic testing. Treatment is aimed at managing the symptoms and careful monitoring for signs of cancer.[1][2][3] 
Last updated: 5/13/2020
The following list includes the most common signs and symptoms in people with Bannayan-Riley-Ruvalcaba syndrome (BRRS). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in BRRS.

Symptoms may include:[1][2][3]
  • Large head size (macrocephaly)
  • Increased birth weight,
  • Intellectual disability
  • Autism spectrum disorder
  • Benign skin tumors:
    • Hair follicle tumors (trichilemmomas)
    • Raised bumps on tongue and gums (oral papillomas)
    • Fatty tumors (lipomas)
  • Growths in the colon (colon polyps)
  • Dark colored freckles on the penis (macular pigmentation)
  • Increased risk for cancer, especially thyroid, breast, uterine, and kidney
People with BRRS may be born with a large head and increased birth weight. Childhood symptoms may include developmental delay, intellectual disability, and/or autism spectrum disorder. As they get older, people with BRRS often develop non-cancerous (benign) growths under the skin and in internal organs. These growths may include fatty tumors, hair follicle tumors and bumps on the tongue and gums.  As adults, people with BRRS are at increased risk to develop breast, thyroid, colon, uterine, and kidney cancers.[4]
Last updated: 5/13/2020

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.

Showing of 93 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal large intestine morphology
Abnormality of the large intestine
0002250
Arteriovenous malformation 0100026
Capillary hemangioma
Strawberry birthmark
0005306
Hamartomatous polyposis 0004390
Intestinal polyposis 0200008
Irregular hyperpigmentation 0007400
Lipoma
Fatty lump
Noncancerous fatty lump
[ more ] 		0012032
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Neoplasm of the breast
Breast tumor
Tumours of the breast
[ more ] 		0100013
Nevus
Mole
0003764
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Visceral angiomatosis 0100761
30%-79% of people have these symptoms
Pectus excavatum
Funnel chest
0000767
Scoliosis 0002650
Subcutaneous hemorrhage
Bleeding below the skin
0001933
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ] 		0001482
5%-29% of people have these symptoms
Abdominal wall muscle weakness 0009023
Abnormality of the optic nerve
Optic nerve issue
0000587
Angina pectoris 0001681
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Broad thumb
Broad thumbs
Wide/broad thumb
[ more ] 		0011304
Cachexia
Wasting syndrome
0004326
Cutis marmorata 0000965
Delayed gross motor development
Delayed motor skills
0002194
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ] 		0002750
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Frontal bossing 0002007
Hashimoto thyroiditis 0000872
Hypoglycemia
Low blood sugar
0001943
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Intracranial hemorrhage
Bleeding within the skull
0002170
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Long philtrum 0000343
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Lymphoma
Cancer of lymphatic system
0002665
Macrotia
Large ears
0000400
Meningioma 0002858
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Multiple cafe-au-lait spots 0007565
Muscular hypotonia
Low or weak muscle tone
0001252
Myopathy
Muscle tissue disease
0003198
Narrow palate
Narrow roof of mouth
0000189
Neoplasm of the adrenal cortex 0100641
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Seizure 0001250
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Tall stature
Increased body height
0000098
Telangiectasia 0001009
Thyroid carcinoma 0002890
Uterine neoplasm
Uterine tumor
0010784
Wide nose
Broad nose
Increased breadth of nose
Increased nasal breadth
Increased nasal width
Increased width of nose
[ more ] 		0000445
1%-4% of people have these symptoms
Decreased circulating antibody level 0004313
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number
[ more ] 		0001888
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection
[ more ] 		0002719
Percent of people who have these symptoms is not available through HPO
Abnormality of the vasculature
Abnormality of blood vessels
Vascular abnormalities
[ more ] 		0002597
Acrokeratosis 0200016
Adult onset
Symptoms begin in adulthood
0003581
Angioid streaks of the fundus 0001102
Autosomal dominant inheritance 0000006
Breast carcinoma
Breast cancer
0003002
Carcinoma 0030731
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Colonic diverticula 0002253
Dysplastic gangliocytoma of the cerebellum 0500009
Fibroadenoma of the breast 0010619
Furrowed tongue
Grooved tongue
0000221
Global developmental delay 0001263
Goiter
Enlarged thyroid gland in neck
0000853
Gynecomastia
Enlarged male breast
0000771
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hemimegalencephaly 0007206
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hydrocele testis 0000034
Hyperthyroidism
Overactive thyroid
0000836
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Hypothyroidism
Underactive thyroid
0000821
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ] 		0001256
Intention tremor 0002080
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Narrow mouth
Small mouth
0000160
Ovarian carcinoma 0025318
Ovarian cyst 0000138
Palmoplantar hyperkeratosis
Thickening of the outer layer of the skin of the palms and soles
0000972
Progressive macrocephaly
Progressively abnormally enlarging cranium
Progressively abnormally enlarging skull
[ more ] 		0004481
Skin tags 0010609
Subcutaneous lipoma 0001031
Thyroid adenoma 0000854
Thyroiditis
Thyroid gland inflammation
0100646
Transitional cell carcinoma of the bladder 0006740
Varicocele 0012871
Showing of 93 |
Last updated: 7/1/2020
Bannayan-Riley-Ruvalcaba syndrome is caused by genetic changes (DNA variants) in the PTEN gene.[1][5]
Last updated: 5/13/2020
Bannayan-Riley-Ruvalcaba syndrome is inherited in an autosomal dominant pattern.[1] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.
Last updated: 5/13/2020
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is diagnosed based on a clinical exam, symptoms, and genetic testing. Diagnostic criteria have been published for the PTEN hamartoma syndromes. BRRS is one of the syndromes.[1][2]
Last updated: 5/13/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
There is no specific treatment for Bannayan-Riley-Ruvalcaba syndrome (BRRS). Treatment is based on management of the specific signs and symptoms. Screening recommendations for people with BRRS include increased surveillance of cancer affecting the breast, thyroid, uterus, and kidney.[1][2][3]

Specialists who may be involved in the care of people with BRRS include:
  • Medical geneticist
  • Neurologist (nerve specialist)
  • Dermatologist (skin specialist)
  • Gastroenterologist (digestion specialist)
  • Urologist (kidney and bladder specialist)
Last updated: 5/13/2020
The prevalence of Bannayan-Riley-Ruvalcaba syndrome is unknown. Cowden syndrome, one of the other syndromes due to PTEN gene variants, is thought to occur in approximately 1 in 200,000 people in the US. Because of the variable and often subtle external characteristics of these conditions, many individuals may remain undiagnosed.[1][2]
Last updated: 5/13/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Lhermitte-Duclos syndrome, Juvenile polyposis syndrome, Peutz-Jeghers syndrome (PJS), Birt-Hogg-Dube syndrome, Proteus syndrome, Cowden syndrome, Gorlin syndrome, and neurofibromatosis type 1 (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Bannayan-Riley-Ruvalcaba syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Bannayan-Riley-Ruvalcaba syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Bannayan-Riley-Ruvalcaba syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). GeneReviews. Updated June 2, 2016; http://www.ncbi.nlm.nih.gov/books/NBK1488/.
  2. Pilarski R. Review: PTEN Hamartoma Tumor Syndrome: A Clinical Overview. Cancers (Basel). Jun 18, 2019; 11(6):pii:E844. https://www.ncbi.nlm.nih.gov/pubmed/31216739.
  3. Macken WL, Tischkowitz M, Lachlan KL. PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature. Am J Med Genet C Semin Med Genet. 2019; 181(4):591-610. https://pubmed.ncbi.nlm.nih.gov/31609537.
  4. Yehia L, Keel E, Eng C. The Clinical Spectrum of PTEN Mutations. Annu Rev Med. 2020; 71:103-116. https://pubmed.ncbi.nlm.nih.gov/31433956.
  5. Lee SH, Ryoo E, Tchah H. Bannayan-Riley-Ruvalcaba Syndrome in a Patient with a PTEN Mutation Identified by Chromosomal Microarray Analysis: A Case Report. Pediatr Gastroenterol Hepatol Nutr. Mar 2017; 20(1):65-70. https://www.ncbi.nlm.nih.gov/pubmed/28401059.