University of Nebraska Medical Center

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PTEN Hamartoma Tumor Syndrome (10q23.31)

Aliases

PHTS; Cowden syndrome (CS); Cowden disease; Multiple Harmatoma Syndrome; Bannayan-Riley-Ruvalcaba syndrome (BRRS); Proteus syndrome (PS); Proteus-like syndrome

Gene(s) involved

PTEN at 10q23.31

Brief description of disorder

PTEN hamartoma tumor syndrome is inclusive of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes. A diagnosis of PHTS is only conferred in individuals in whom a PTEN mutation has been identified. In contrast to CS, Bannayan-Riley-Ruvalcaba syndrome and Proteus or Proteus-like syndromes are congenital in nature.

Hhamartoma tumor syndrome is inclusive of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes. A diagnosis of PHTS is only conferred in individuals in whom a mutation has been identified. In contrast to CS, Bannayan-Riley-Ruvalcaba syndrome and Proteus or Proteus-like syndromes are congenital in nature.

Cowden syndrome is a syndrome of multiple hamartomas with an exacerbated risk of tumors in the thyroid, endometrium, and breasts. Affected individuals usually present by their late 20s. The risk of developing breast cancer is 25-50% and is usually diagnosed between 38 and 46 years of age. There is a 10% risk of developing thyroid cancer, usually follicular thyroid cancer; and up to 10% risk of endometrial cancer. CS is also characterized by macrocephaly, trichilemmomas, and papillomatous papules.
Characteristics of BRRS are intestinal polyposis, lipomas, pigmented macules on the glans penis, and macrocephaly. Proteus and proteus-like syndromes are characterized by congenital malformations and harmatomatous overgrowths in a variety of tissue types.

The prevalence of PTHS is unknown due the variability of presentation. Many cases of PTHS are thought to go unrecognized. The incidence of Cowden syndrome has been estimated at 1 in every 200,000.

Inheritance pattern

PHTS is transmitted in an autosomal dominant fashion; however de novo mutations are not uncommon. Estimates indicate that Cowden syndrome may be a de novo genetic occurrence at least 40% of the time.

PHTS is transmitted in an autosomal dominant fashion; however mutations are not uncommon. Estimates indicate that Cowden syndrome may be a genetic occurrence at least 40% of the time.

Genetics

It is estimated that individuals meeting the clinical criteria for CS and BRRS have a detectable mutation rate in PTEN 80% and 60% of the time respectively. BRRS is associated with large deletions, while CS is not. Proteus and Proteus-like syndrome are found to have detectable PTEN mutations in 20% of cases.

Reasons for referral

confirmation of a clinical diagnosis
genetic counseling
prenatal diagnosis in at-risk pregnancies
identification of at-risk family members
Test method at this facility

Conventional G-banded cytogenetic analysis, FISH, Array CGH, Molecular studies, DNA sequencing.

Test sensitivity

Cytogenetic analysis detects approximately 25% of deletions that are greater than 5 Mb. FISH and aCGH will detect 98-100% of deletions/ duplications; however deletions/duplications that are smaller than 100 kb will not be detected by aCGH and deletions/duplications that are smaller than the FISH probe will not be detected by FISH. Molecular studies will detect mutations in PTEN >90% of the time.

Specimen requirements

For cytogenetic analysis, FISH, and aCGH:
Blood:

For cytogenetic analysis, FISH, and aCGH:

Adult: 3-5 ml peripheral blood in a sodium-heparin tube. N
ewborn: 1-3 ml blood in a sodium-heparin tube.

For Molecular PTEN sequencing:
Blood:

Adult / Newborn: 1-3 ml peripheral blood in an EDTA (purple top) tube.

Transport at room temperature. Deliver ASAP with a completed Cytogenetics & Molecular Cytogenetics Requisition form. Notify HGL by calling (402) 559-5070 when specimen is being shipped.

Shipping and Handling Information

Turn-around-time

Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array CGH: 5-14 days
Molecular studies/DNA sequencing: 14-28 days

CPT codes

Cytogenetic Analysis - 88285(x3), 88261, 88280(x2), 88291, 88230(x2), 88289
Metaphase/Interphase FISH - 88273, 88275, 88271(x2), 88291
Array CGH - 83892(x2), 88384, 88386, 88230, 88385, 88291
Molecular studies/ Sequencing - 83904(x9), 83912, 83896(x9), 83898(x9), 83894

**Additional costs may apply for DNA extraction and storage**

References
GeneReviews (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=phts)

The information contained on this page is subject to change.

Updated: 8/25/2009

Human Genetics Laboratory