Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare

overgrowth syndrome Overgrowth syndromes in children constitute a group of rare disorders that are characterised by tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the gene ...

and hamartomatous disorder with occurrence of multiple subcutaneous

lipoma A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than in size. Common locations include upper back, ...

macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...

and

hemangioma A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the ski ...

s. The disease is inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner. The disease belongs to a family of hamartomatous polyposis syndromes, which also includes

Peutz–Jeghers syndrome Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanos ...

juvenile polyposis Juvenile polyposis syndrome is an autosomal dominant genetic condition characterized by the appearance of multiple juvenile polyps in the gastrointestinal tract. Polyps are abnormal growths arising from a mucous membrane. These usually begin appe ...

and

Cowden syndrome Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, ...

. Mutation of the PTEN gene underlies this syndrome, as well as

Proteus syndrome Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development.Freedberg, et al. ...

, and

Proteus-like syndrome Proteus-like syndrome (PLS) is a condition similar to Proteus syndrome, but with an uncertain cause.It's characterized by skeletal and hamartous overgrowth of multiple tissues, nevi in cerebriform connective tissue, blood vessel malformations and l ...

, these four syndromes are referred to as PTEN Hamartoma-Tumor Syndromes.

Signs and symptoms

Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

hamartoma A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...

s (multiple

s, and

intestinal polyp A colorectal polyp is a polyp (fleshy growth) occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer. Colorectal polyps are often classified by their behaviour (i.e. benign vs. malignant) o ...

s).

Dysmorphy A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...

as well as delayed neuropsychomotor development can also be present.update 2016 The head enlargement does not cause widening of the ventricles or raised

intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...

; these individuals have a higher risk of developing

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s, as the gene involved in BRRs is phosphatase and tensin homologue. Some individuals have thyroid issues consistent with

multinodular goiter A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...

thyroid adenoma A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active (functioning autonomously) as a toxic adenoma. Signs and symptoms A thyroid adenoma may be clinically silent ("cold" adenoma), or it may be a functional tumo ...

, differentiated non-medullary

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

, most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression

Genetics

The genetics of the Bannayan–Riley–Ruvalcaba syndrome is determined, in the majority of cases, via the

PTEN gene Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the ''PTEN'' gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate ca ...

which presents about 30

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in this condition. This gene which regulates

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

, when ''not'' working properly can lead to hamartomas. PTEN

chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

location is 10q23.31, while the

molecular A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

location is 87,863,438 to 87,971,930 There are many syndromes that are linked to PTEN aside from Bannayan–Riley–Ruvalcaba Syndrome. The syndrome combines Bannayan–Zonana syndrome, Riley–Smith syndrome, and Ruvalcaba–Myhre–Smith syndrome. Bannayan–Zonana syndrome is named for George A. Bannayan and Jonathan Zonana

Diagnosis

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 Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...

tests (and

cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

test) to determine Bannayan–Riley–Ruvalcaba syndrome.

Differential diagnosis

The differential diagnosis for BRRS consists of the following:

Treatment

In terms of 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

of: *

Thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

Breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

Renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

References

External links

{{DEFAULTSORT:Bannayan-Riley-Ruvalcaba Syndrome Deficiencies of intracellular signaling peptides and proteins Soft tissue disorders Melanocytic nevi and neoplasms Syndromes affecting head size Syndromes affecting the nervous system Syndromes affecting the gastrointestinal tract Syndromes with tumors Rare syndromes