Bannayan-Riley-Ruvalcaba syndrome

Bannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. Its signs are present from birth or become apparent in early childhood. At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size, although growth usually slows during childhood so that affected adults are of normal height and size. About half of affected children have intellectual disability or delayed development, particularly of speech and of motor skills such as sitting, crawling and walking, and these delays may improve with age. About half of people with the condition develop hamartomatous polyps in the intestines, and other noncancerous growths include lipomas and angiolipomas under the skin and hemangiomas made of tangled abnormal blood vessels. Weak muscle tone, seizures, thyroid problems such as multinodular goiter or Hashimoto thyroiditis, and skeletal differences such as joint hyperextensibility, scoliosis and a sunken chest have also been reported, and there may be an increased risk of certain cancers, which researchers are still working to define. About 60 percent of cases result from mutations in the PTEN gene, a tumor suppressor, and another 10 percent from a large deletion that includes part or all of the gene; the cause of the remainder is unknown. The condition is inherited in an autosomal dominant pattern. Its features overlap with those of Cowden syndrome, which can also be caused by PTEN mutations, and researchers have proposed that the two lie on a spectrum called PTEN hamartoma tumor syndrome rather than being distinct conditions. The prevalence is unknown, though it appears rare, with several dozen cases reported in the medical literature and a suspicion that it is underdiagnosed. Other names include Bannayan-Zonana syndrome, Ruvalcaba-Myhre-Smith syndrome and Riley-Smith syndrome.