Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous

lipoma A lipoma is a benign tumor made of adipose tissue, 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 inc ...

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 Heredity, familial genetic characteristic. People diagnosed with macrocephaly will receive further medical ...

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 sk ...

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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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 dominance (genetics), autosomal dominant genetic disorder characterized by the development of benign hamartomatous Polyp (medicine), polyps in the human gastrointestinal tract, gastrointestinal ...

, juvenile polyposis and

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

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

Proteus syndrome Proteus syndrome is a rare genetic disorder that can cause tissue overgrowth involving all three Germ layer, embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development.Freedberg, et al. (2003). ...

, and Proteus-like syndrome, 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 ...

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 polyps).

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 Some individuals have thyroid issues consistent with

multinodular goiter A goitre (British English), or goiter (American English), 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 ca ...

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, ...

, 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 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, mitosi ...

in this condition. This gene which regulates

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

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

chromosomal A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...

location is 10q23.31, while the

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

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 branch 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 st ...

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 Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

of: *

Thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

Breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

Renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

References

External links

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