Rare Pediatrics News

Disease Profile

Bannayan-Riley-Ruvalcaba syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

BRRS; Riley-Smith syndrome; Macrocephaly multiple lipomas and hemangiomata;

Categories

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases;

Summary

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] 

Symptoms

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]

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.

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

Cause

Bannayan-Riley-Ruvalcaba syndrome is caused by genetic changes (DNA variants) in the PTEN gene.[1][5]

Diagnosis

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]

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.

    Treatment

    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)

    Organizations

    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

        Learn more

        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.

            References

            1. Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). GeneReviews. Updated June 2, 2016; https://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.

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