SignatureChip® Detection Rates for PTEN Hamartoma Tumor Syndrome and Allelic Disorders
PTEN Hamartoma Tumor Syndrome is a syndrome that incorporates several disorders with phenotypic overlap caused by mutations in PTEN, including Bannayan-Riley Ruvalcaba syndrome, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome. Although these disorders have specific distinguishing characteristics, they have features in common and recommended management is virtually identical for all.
2-11% of cases of Bannayan-Riley-Ruvalcaba syndrome (BRRS) are caused by deletions of the PTEN gene, the majority of which are detectable by rray CGH technology. Approximately 60% have identifiable PTEN point mutations. Patients with this condition often have autistic features, macrocephaly, hamartomatous intestinal polyps, lipomas and penile freckling.
~1% of cases of Cowden syndrome (CS) are caused by deletions of the PTEN gene, the majority of which are detectable by array CGH technology. Approximately 80% have identifiable PTEN point mutations that are not detectable by array CGH. Patients with this condition may have cancers of the breast, uterus, thyroid, and urogenital tract as well as macrocephaly, Lhermitte-Duclos disease (macrocephaly, seizures, and mental retardation associated with dysplastic gangliocytoma of the cerebellum), specific skin lesions (i.e. trichelemmomas, lipomas), hamartomatous polyps, fibrocystic breasts, and urogenital system malformations and tumors. Autistic-like tendencies have also been reported in some patients.
Large deletions have not been reported in cases of Proteus syndrome or Proteus-like syndrome; however, this disorder has phenotypic overlap with BRRS and CS and is considered part of the PTEN Hamartoma Tumor Syndrome Spectrum. Detection rates for point mutations are not reported consistently, implying a possible second locus for these syndromes. These are disorders of mosaic, progressive overgrowth, including connective tissue nevi, macrocephaly, ovarian and parotid tumors, atypical adipose tissue growth, and vascular malformations.
Although Macrocephaly/autism syndrome is not considered part of the PTEN Hamartoma Tumor Syndrome, it is allelic to these tumor syndromes and has the overlapping phenotype of both macrocephaly and autistic-like features. Approximately 4% of patients with a head circumference >2 standard deviations above the mean and autism spectrum disorder have point mutations in PTEN, that are not detectable by array CGH.
| Condition | OMIM# | Gene/ Locus | Location | Detection rate for deletion/duplication by microarray | Comments | References | |
|---|---|---|---|---|---|---|---|
| ■ Microdeletions or microduplications have been associated with this condition. □ Microdeletions or microduplications are rare or not yet associated with this condition. Information based on UCSC Genome Browser, March 2006 Assembly |
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Bannayan-Riley-Ruvalcaba (BRRS) GeneReviews |
153480 | PTEN | 10q23.31 | ~2-11% have a detectable deletion | ~60% have mutations not detectable by array CGH. | Marsh et al. 1998. Hum Mol Genet 7:507-15. Medline Marsh et al. 1999. Hum Mol Genet 8:1461-72. Medline Zhou et al. 2003. Am J Hum Genet 73:404-11. Medline |
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GeneReviews |
158350 | PTEN | 10q23.31 | ~1% have a detectable deletion | ~80% have mutations not detectable by array CGH. | Marsh et al. 1998. Hum Mol Genet 7:507-15. Medline Zhou et al. 2003. Am J Hum Genet 73:404-11. Medline |
| □ | 605309 | PTEN | 10q23.31 | Unknown | ~4% have mutations not detectable by array CGH. | Butler et al. 2005. J Med Genet 42:318-21. Medline Buxbaum et al. 2007. Am J Med Genet B 144:484-91. Medline |
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| □ | GeneReviews |
176920 | PTEN | 10q23.31 | Unknown | Smith et al. 2002. J Med Genet 39:937-40. Medline Zhou et al. 2000. Hum Molec Genet 9:765-68. Medline |
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