Bannayan-Zonana-Ruvalcaba Syndrome

At a glance

An inherited disorder characterized by excessive pre- and postnatal growth manifesting with macro- and scaphocephaly, multiple hamartomas (lipomas, intestinal polyps), and normal or slightly reduced intelligence. As affected infants age, the growth rate slows down and most often results in normal adult height.

Synonyms

Bannayan-Riley-Ruvalcaba Syndrome; Bannayan-Zonana Syndrome; Ruvalcaba-Myhre-Smith Syndrome; Riley-Smith Syndrome. This syndrome is now considered part of the PTEN Hamartoma Tumor Syndrome (PHTS) or PTEN-MATCHS Syndrome (see also “Genetic inheritance”).

History

First described in 1960 by Harris D. Riley and William R. Smith; followed in 1971 by G. A. Bannayan, in 1976 by Jonathan Zonana, David L. Rimoin, and David C. Davis; and finally in 1980 by R. H. A. Ruvalcaba, S. Myhre, and D. W. Smith, all American physicians. According to the history, Riley and Smith’s names should be included in the designation of this disorder, but Bannayan-Zonana or Bannayan-Riley-Ruvalcaba Syndrome seem to be more commonly used today.

Incidence

Unknown, but several case reports exist.

Genetic inheritance

Presumed autosomal dominant inheritance with male predominance (in up to 80% of cases). Some sporadic cases have been reported and seem to have an overall worse prognosis. Variability in the severity of the condition in affected individuals suggests allelic mutations or possible genetic heterogeneity. The gene for Bannayan-Zonana Syndrome has been mapped to chromosome 10q23.31 and encodes the enzyme PTEN (phosphate and tensin) homologue, which is, among other functions, involved in tumor suppression and apoptosis. Some experts have suggested that the Bannayan-Zonana-Ruvalcaba Syndrome should be unified into a single entity with other similar, previously considered separate syndromes, namely, the Riley-Smith Syndrome, Ruvalcaba-Myhre-Smith Syndrome, Cowden Syndrome, and Lhermitte-Duclos Syndrome, which all share the same autosomal dominant inheritance and mutations in the same PTEN gene on chromosome 10q23.31. Clinical and molecular data support the unification with the proposed new nomenclature PTEN-MATCHS Syndrome, which is an acronym that stands for Phosphate, TENsin-homologue Macrocephaly, Autosomal dominant inheritance, Thyroid disease, Cancer Hamartoma, and Skin abnormalities.

Pathophysiology

Multiple hamartomas with various angiomatous, lymphangiomatous, and lipomatous components. Muscle biopsy demonstrates a lipid storage myopathy with increased depositions of lipid droplets in type I fibers. Type II fibers are smaller than normal, but they appear have a higher lipid content than normal type II fibers (but noticeably less than the type I fibers in this disorder). The lipid myopathy may result from a defect in long-chain fatty acid oxidation, which is caused by a deficiency of long-chain L-3-hydroxyacyl-CoA dehydrogenase and seems to respond to carnitine treatment.

Diagnosis

Based on the clinical features and muscle biopsy. Electromyography is consistent with a myopathic condition.

Clinical aspects