Diseases title

Bannayan-Riley-Ruvalcaba syndrome )

Orpha Number: 109
BRRS, Myhre-Riley-Smith syndrome, Syndrome de Myhre-Rikey-Smith

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.The prevalence is unknown, but BRRS is generally considered as a rare disease.BRRS shares some of the clinical characteristics of Cowden syndrome (CS; see this term) but with differing frequencies. Unlike CS, the classic presentation of BRRS occurs neonatally or shortly thereafter with macrocephaly, Hashimoto struma (see this term), lipomatosis, vascular malformations and speckled lentiginosis of the penis or vulva. Developmental delay and gastrointestinal hamartomatous polyposis occur in a subset of BRRS patients. It is unclear if the case-based signs of myopathic processes in proximal muscles, pectus excavatum, joint hyperextensibility, scoliosis and high birth weight are truly components of BRRS. Although predisposition to cancer was not thought to be a feature of this syndrome, it is now believed that BRRS patients with a PTEN mutation share the same risk of cancer development as CS patients. The earliest age at diagnosis of thyroid cancers in PTEN hamartoma tumor syndrome (PHTS; see this term) is 6 years of age.BRRS is caused (in 60% of cases) by a mutation in the phosphatase and tensin homolog (PTEN) gene (10q23) that encodes PTEN, a dual-specifity phosphatase. When BRRS is accompanied by germline PTEN mutations, it belongs to the PHTS group. Because the non-PTEN CS-related genes (ex. SDHB-D, AKT1, PIK3CA and KLLN) have not been formally studied in BRRS, it is not clear if they are also etiologic for non-PTEN-related BRRS.There are no specific criteria for diagnosis of BRRS but it is usually determined by the clinical presentation. The pediatric criteria of the PTEN Scoring System can be used and are heavily based on the presence or absence of macrocephaly and the presence of one of four sub-criteria (autism spectrum disorder, dermatologic features, vascular malformations and/or gastrointestinal polyposis). A PTEN mutation confirms that the BRRS patient belongs to the PHTS group.Differential diagnoses include Lhermitte-Duclos syndrome, Juvenile polyposis syndrome, Peutz-Jeghers syndrome (PJS), Birt-Hogg-Dube syndrome, Proteus syndrome, Cowden syndrome, Gorlin syndrome, and neurofibromatosis type 1 (see these terms).Antenatal diagnosis is possible for at-risk pregnancies if the disease causing mutation is discovered in an affected family member.BRRS is inherited autosomal dominantly. Genetic counseling can be offered to patients with PTEN mutations and asymptomatic family members should also be tested for the mutation to identify those that need to be monitored before symptom onset.Management and treatment is multidisciplinary. Monitoring for complications of gastrointestinal hamartomatous polyposis is very important as they can be more severe than those seen in CS. Once a germline PTEN mutation is identified, the patient should undergo a screening thyroid ultrasound exam. In patients under the age of 18, a yearly skin check and thyroid ultrasound examination is recommended. A colonoscopy and biennial renal imaging should begin between the ages of 35-40. Women should perform monthly breast self-examinations and yearly breast screenings as well as transvaginal ultrasounds or endometrial biopsies beginning at the age of 30. It is also important to pay attention to neurogical and vascular malformations as well as GI symptoms.The prognosis is unknown and is dependent on initial presentation and likely genotype.
source: Orphanet