FaCD Online Syndrome Fact Sheet

Last updated: 18 Sep 2008

Name: Bannayan-Riley-Ruvalcaba syndrome

Synonym: subset of PTEN-Hamartoma Tumor Syndrome; incl.: Ruvalcaba-Myhre-Smith s.

Mode of Inheritance: AD

Genes

PTEN, mapped to 10q23.3

Tumor features

colorectal hamartomatous polyps
facial papules
hamartomatous polyps in small intestine
hemangioma
lipoma
oral papules
trichilemmoma

Tumor features (possible)

breast cancer
meningioma
thyroid adenoma
thyroid cancer

Non-tumor features

cornea, prominent nerves
developmental delay/mental deficiency/mental retardation
gross motor delay
hearing loss
high birth weight
hypotonia
joint laxity
lipid storage myopathy of proximal muscles
macrocephaly
pectus excavatum
pigmented macules on glans and shaft of penis
scoliosis
seizures
vulvar lentigines

Comment

Lipid storage myopathy, pigmented macules on glans and shaft of penis and vulva , intestinal hamartous (juvenile type) polyps and neurodevelopmental delay are the typical features[1-9,16]. A clinical overlap with Cowden disease has been noted and indeed germline mutations in the PTEN gene, involved in Cowden disease have been detected in this disorder. It should therefore be considered as a variant of Cowden syndrome[10-16]. DiLiberti[10] proposed the nomenclature PTEN-MATCHS (Macrocephaly, Autosomal dominant, Thyroid disease, Cancer, Hamartomata, Skin abnormalities) to cover the clinical spectrum associated with germline PTEN mutations. More recently the name PTEN hamartoma tumour syndrome (PHTS) has been coined for the same purpose[16].

Links

A Guide for patients and their families, published on Virtual Children's Hospital's site 18 1 08

References

[1] Gujrati M, Thomas C, Zelby A, Jensen E, Lee JM. Bannayan-Zonana syndrome: a rare autosomal dominant syndrome with multiple lipomas and hemangiomas: a case report and review of literature. Surg Neurol 1998; 50:164-168.
[2] Fargnoli MC, Orlow SJ, Semel-Concepcion J, Bolognia JL. Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome. Arch Dermatol 132[10], 1214-1218. 1996.
[3] Miles JH, Zonana J, Mcfarlane J, Aleck KA, Bawle E. Macrocephaly with hamartomas: Bannayan-Zonana syndrome. Am J Med Genet 1984; 19(2):225-234.
[4] Foster MA, Kilcoyne RF. Ruvalcaba-Myhre-Smith syndrome: a new consideration in the differential diagnosis of intestinal polyposis. Gastrointest Radiol 1986; 11(4):349-350.
[5] Gretzula JC, Hevia O, Schachner LS, DiLiberti JH, Ruvalcaba RH, Schimschock JR, Weleber RG, Halal F, Lipson MH, Blumberg B, et al. Ruvalcaba-Myhre-Smith syndrome. Pediatr Dermatol 1988; 5(1):28-32.
[6] Gorlin RJ, Cohen MM, Jr., Condon LM, Burke BA. Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 1992; 44(3):307-314.
[7] Hayashi Y, Ohi R, Tomita Y, Chiba T, Matsumoto Y. Bannayan-Zonana syndrome associated with lipomas, hemangiomas, and lymphangiomas. J Pediatr Surg 1992; 27(6):722-723.
[8] Higginbottom MC, Schultz P. The Bannayan syndrome: an autosomal dominant disorder consisting of macrocephaly, lipomas, hemangiomas, and risk for intracranial tumors. Pediatrics 1982; 69(5):632-634.
[9] Lowichik A, White FV, Timmons CF, Weinberg AG, Gunasekaran TS, Nathan K, Coffin CM. Bannayan-Riley-Ruvalcaba syndrome: spectrum of intestinal pathology including juvenile polyps. Pediatr Dev Pathol 2000; 3(2):155-161.
[10] DiLiberti JH. Inherited macrocephaly-hamartoma syndromes. Am J Med Genet 79[4], 284-290. 1998.
[11] Marsh DJ, Dahia PLM, Zheng ZM, Liaw D, Parsons R, Gorlin RJ, Eng C. Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16[4], 333-334. 1997.
[12] Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PLM, Zheng ZM, Liaw D, Caron S, Duboue B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, LePrat F, Odent S, Toulouse C, Olopade OI, Sobol H, Tishler S, Woods CG, Robinson BG, Weber HC, Parsons R, Peacocke M, Longy M, Eng C. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 7[3], 507-515. 1998.
[13] Longy M, Coulon V, Duboue B, David A, Larregue M, Eng C, Amati P, Kraimps JL, Bottani A, Lacombe D, Bonneau D. Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype. J Med Genet 1998; 35:886-889.
[14] Lachlan KL, Lucassen AM, Bunyan D, Temple IK. Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. Journal of medical genetics 2007; 44(9):579-85.
[15] Hendriks YM, Verhallen JT, van der Smagt JJ, Kant SG, Hilhorst Y, Hoefsloot L, Hansson KB, van der Straaten PJ, Boutkan H, Breuning MH, Vasen HF, Bröcker-Vriends AH. Bannayan-Riley-Ruvalcaba syndrome: further delineation of the phenotype and management of PTEN mutation-positive cases. Familial cancer 2003; 2(2):79-85.
[16] Orloff MS, Eng C. Genetic and phenotypic heterogeneity in the PTEN hamartoma tumour syndrome. Oncogene 2008; 27(41):5387-97.