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January 2001

Picture of the Month

Arch Pediatr Adolesc Med. 2001;155(1):88. doi:10.1001/archpedi.155.1.87

Denouement and Discussion: Bannayan-Ruvalcaba-Riley Syndrome

Figure 1. The skin of the penis is freckled.

Figure 2. A subcutaneous lipoma is present in the lower abdominal wall.

The Bannayan-Ruvalcaba-Riley (BRR) syndrome had been thought to be 3 separate disorders until the overlapping findings were considered to represent one syndrome.1 Bannayan2 described a child with congenital macrocephaly and multiple lipomatosis and angiomatosis involving the skin and visceral tissues in 1971. Riley and Smith3 reported a syndrome consisting of macrocephaly, multiple cutaneous hemangiomata, and pseudopapilledema, with an apparent autosomal dominant pattern of inheritance, in 1960. Ruvalcaba et al4 noted the association of macrocephaly, intestinal polyposis, and pigmented penile lesions in 1980.

Clinical features

Macrocephaly is a prominent feature of BRR syndrome. The head circumference is at least 2.5 SD higher than the mean for age, and the brain has normal ventricular size. Down-slanting palpebral fissures and ocular hypertelorism may be present as well as pseudopapilledema and prominent corneal nerves.

Cutaneous abnormalities include lipomas and hemangiomas, as well as mixed vascular-lymphatic-adipose tumors. Although these tumors are most commonly discrete, intracranial, visceral, and osseous lesions have been described, which sometimes are infiltrative.5 Pigmented macules, resembling freckles, on the skin of the shaft and glans penis are present in most males with this syndrome. Café au lait spots, acanthosis nigricans-like lesions, and wart-like lesions of the face have also been described. Almost 50% of patients with BRR syndrome develop hamartomatous polyps of the intestine, usually limited to the distal ileum and colon.1 The polyps may be associated with rectal bleeding or intussusception.

Although infants with BRR syndrome appear large at birth, the head circumference appears to account for apparent increase in total body mass and length.6 Approximately one half of the patients described have had mild to severe mental deficiency and/or speech delay, and 25% have had seizures.1 Hypotonia is common and is associated with a lipid storage myopathic process of the proximal muscles in approximately 60% of patients.1 Common skeletal system abnormalities include joint hyperextensibility, scoliosis, and pectus excavatum. Autoimmune thyroiditis seems to be part of the clinical spectrum of the disorder.1

Molecular biology

The inheritance of BRR is in an autosomal dominant pattern. Germline mutations in the PTEN (phosphatase and tensin homolog deleted on chromosome 10) locus mapped to chromosome 10q23.3 have been reported in patients with this syndrome.6 It is interesting that the same germline mutation has been described in patients with Cowden disease, a disorder that shares some features of BRR syndrome.6 The BRR syndrome and Cowden disease may represent variable manifestations of mutations of the same gene.7 A proposal has been made to encompass these disorders under the acronym PTEN-MATCHS (macrocephaly and myopathy, thyroid disease, cancer, hamartomata, and skin abnormalities).6

Treatment and prognosis

The treatment of patients with BRR is usually symptomatic. Gastrointestinal polyps may require removal, and surveillance of the gastrointestinal tract should be considered. There is a predisposition to cancer of the breast, prostate, and thyroid in Cowden disease. A similar predisposition for the development of malignant tumors in BRR syndrome during adulthood is possible, suggesting that affected children should have regular medical follow-up.

Accepted for publication March 13, 2000.

Reprints: Vasundhara Tolia, MD, Division of Gastroenterology, Children's Hospital of Michigan, 901 Beaubien Blvd, Detroit, MI 48201.

Gorlin  RJCohen  MM  JrCondon  LMBurke  BA Bannayan-Riley-Ruvalcaba syndrome.  Am J Med Genet. 1992;44307- 314Google ScholarCrossref
Bannayan  GA Lipomatosis, angiomatosis, and macrencephalia: a previously undescribed congenital syndrome.  Arch Pathol. 1971;921- 5Google Scholar
Riley  HDSmith  WR Macrocephaly, pseudopapilledema and multiple hemangiomata: a previously undescribed heredofamilial syndrome.  Pediatrics. 1960;26293- 300Google Scholar
Ruvalcaba  RHAMyhre  SSmith  DW Sotos syndrome with intestinal polyposis and pigmentary changes of the genitalia.  Clin Genet. 1980;18413- 416Google ScholarCrossref
Klein  JABarr  RJ Bannayan-Zonana syndrome associated with lymphangiomyomatous lesions.  Pediatr Dermatol. 1990;748- 53Google ScholarCrossref
DiLiberti  JH Inherited macrocephaly-hamartoma syndromes.  Am J Med Genet. 1998;79284- 290Google ScholarCrossref
Perriard  JSaurat  J-HHarms  M An overlap of Cowden's disease and Bannayan-Riley-Ruvalcaba syndrome in the same family.  J Am Acad Dermatol. 2000;42348- 350Google ScholarCrossref