Untitled

Abstract

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is characterised by macrocephaly, intestinal hamartomatous polyps, lipomas, pigmented maculae of the glans penis, developmental delay and mental retardation. The syndrome follows an autosomal dominant pattern of inheritance. In 1997 reports on two BRRS patients with a deletion at 10q23.2-q24.1 were published. In the same year, the first two families with BRRS and a mutation of the PTEN gene were reported. Mutations in the PTEN gene have also been demonstrated in patients with Cowden syndrome (CS), which shows partial clinical overlap with BRRS, and in families with cases both of BRRS and CS. PTEN mutation positive BRRS and CS are likely to be different phenotypic presentations of the same syndrome. If BRRS and CS are one single condition, the question arises whether patients with BRRS should be screened for malignant tumours, since patients with Cowden syndrome have an increased risk of breast, endometrial, thyroid and renal cancer. We present two isolated cases and one family and confirm that BRRS and CS are allelic. Furthermore, we review the PTEN mutation positive BRRS cases, to further delineate the phenotype and to compare the cases with a genomic deletion with the cases with a point mutation. We recommend offering BRRS cases with a mutation in PTEN the same surveillance protocol for (malignant) tumours as is currently recommended for CS. In addition, we propose a yearly haemoglobin test from early infancy for the early detection of intestinal hamartomas, which are likely to give severe complications, especially in BRRS cases.

Thyroid Involvement in Two Patients with Bannayan-Riley-Ruvalcaba Syndrome

“…Neonatal macrosomia (birth weight >97th percentile), increased linear growth, dysmorphic features, joint hyperextensibility, pectus excavatum, scoliosis, and café au lait spots (2,3) are additional characteristics that can be frequently present. Face abnormalities include frontal bossing, hypertelorism, down-slanting palpebral fissures, epicanthus inversus, long philtrum with thin upper lip, and broad mouth with relative micrognathia (2,4). In addition, neuromuscular disorders are often present, encompassing myopaty of proximal muscles (60% of the patients) and delayed neuropsychomotor development of variable degree (20 to 50%) (2).…”

“…In some of patients, arteriovenous malformations have also been reported (5). Intestinal polyps occur in 35-40% (4,6) of patients and they manifest in childhood with chronic anemia, diarrhea or small bowel invagination (4,7,8). The oncologic risk is typically increased with predisposition to develop intestinal, thyroidal, uterine and breast cancer.…”

“…BRRs has an autosomal dominant inheritance (4), with 37% of cases caused by new mutations (10). Germline inactivating mutations of phosphatase and tensin homologue (PTEN) gene are found in approximately 60% of individuals who meet the clinical diagnosis of BRRs (11).…”

“…Germline inactivating mutations of phosphatase and tensin homologue (PTEN) gene are found in approximately 60% of individuals who meet the clinical diagnosis of BRRs (11). PTEN gene is a tumor suppressor gene mapping on chromosome 10q23.3, with relevant role in the pathway of cellular proliferation, migration and apoptosis; somatic mutations have been found in several human solid tumors (4,12), explaining the increased cancer risk in BRRs. PTEN mutations are responsible for the broader definition of the PTEN hamartoma tumor syndromes (PHTS), a group of diseases also including Cowden syndrome (CS), PTEN-related Proteus syndrome, Proteus-like syndrome, and Lhermitte-Duclos syndrome.…”

Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba Syndrome

“…Common facial presentations in BRRS patients include frontal bossing, down-slanting palpebral fissures, strabismus hypertelorism, a depressed nasal bridge, long philtrum, epicanthus inversus, a thin upper lip, a broad mouth and relative micrognathia [4,5]. Hypothonia, delayed psychomotor development, and seizures are also observed in at least half of BRRS patients [2].…”