Preferred initial diagnostic and predictive test for PTEN-related disorders.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics of PTEN hamartoma tumor syndrome (PHTS): Clinical findings are highly variable and include Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome (PSL).
CS: Multiple hamartoma syndrome with increased risk for malignant and benign tumors of the breast, thyroid, and endometrium. Other associated findings include macrocephaly and mucocutaneous lesions (facial trichilemmonas, palmoplantar keratoses, and papillomatous papules).
BRRS: Characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, hemangiomas, and pigmented macules of the glans penis.
PS: A progressive disorder demonstrating mosaic distribution of associated lesions. Findings include hamartomatous tissue overgrowth, hyperostoses, connective tissue and epidermal nevi, dysregulated adipose tissue, vascular malformations, and other congenital malformations.
PSL: Describes individuals with significant features of PS who do not meet clinical diagnostic criteria for PS.
Incidence: At least 1 in 200,000 for CS; PS is rare with approximately 120 reported cases; unknown for other PTEN-associated conditions.
Inheritance: Autosomal dominant. All mutations causing PS and 50-90 percent causing CS are de novo.
Penetrance: 99 percent by 30 years of age for CS.
Cause: Pathogenic PTEN gene mutations.
Clinical Sensitivity: 85 percent for CS, 65 percent for BRRS, 50 percent for PSL, and 20 percent for PS.
Methodology: Bidirectional sequencing of the PTEN promoter, coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large PTEN coding region deletions/duplications.
Analytical Sensitivity and Specificity of Sequencing: 99 percent.
Analytical Sensitivity and Specificity of MLPA: 90 and 98 percent, respectively.
Limitations: Diagnostic errors can occur due to rare sequence variations. Some regulatory region mutations, deep intronic mutations and large deletions of exon 3 may not be detected. Breakpoints for large deletions/duplications will not be determined.
|Component Test Code*||Component Chart Name||LOINC|
|2002471||PTEN FGA Specimen|
|2002473||PTEN-Related Disorders, Seq and Del/Dup|
- Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
- PTEN sequencing and deletion/duplication assay