Bannayan–Riley–Ruvalcaba syndrome

Bannayan–Riley–Ruvalcaba syndrome (BRRS) is an uncommon condition marked by excessive tissue growth and the development of hamartomas. Its key features include multiple fatty lumps under the skin (subcutaneous lipomas), an unusually large head (macrocephaly), and clusters of abnormal blood vessels (hemangiomas). The disorder follows an autosomal dominant inheritance pattern and is part of a group of hamartomatous polyposis syndromes, alongside Peutz–Jeghers syndrome, juvenile polyposis, and Cowden syndrome. A mutation in the PTEN gene causes BRRS, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome; these four are together known as PTEN Hamartoma-Tumor Syndromes.

People with BRRS often have a large head and benign mesodermal hamartomas, which can include multiple hemangiomas and intestinal polyps. Some individuals also show facial or body differences (dysmorphy) and delays in neuropsychomotor development. Thyroid problems may occur, such as multinodular goiter, thyroid adenoma, or differentiated non-medullary thyroid cancer. Most lesions grow slowly, but in some cases, they can affect internal organs or the brain, potentially causing bleeding or symptoms from mechanical compression.

Genetically, most cases of BRRS are linked to the PTEN gene, where about 30 different mutations have been found. This gene normally controls cell growth; when it malfunctions, hamartomas can form. The PTEN gene is located on chromosome 10 at position 10q23.31, with a molecular range from 87,863,438 to 87,971,930 base pairs. Besides BRRS, several other syndromes are associated with PTEN mutations. The syndrome itself combines features from three previously described conditions: Bannayan–Zonana syndrome, Riley–Smith syndrome, and Ruvalcaba–Myhre–Smith syndrome. Bannayan–Zonana syndrome was named after George A. Bannayan and Jonathan Zonana.

Diagnosis of BRRS currently relies on recognizing the physical signs and symptoms, as there is no other established method. However, various molecular genetics tests (and cytogenetic testing) can help confirm the diagnosis. The differential diagnosis for BRRS includes other similar conditions.

Treatment focuses on managing the specific signs and symptoms present, since no standard guidelines exist beyond that. Affected individuals should be monitored for cancers of the thyroid, breast, and kidney.