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PTEN Hamartoma Tumor Syndromes (PHTS) comprise a spectrum of rare, autosomal dominant genetic disorders caused by germline mutations in the PTEN gene, which encodes a tumor suppressor protein regulating the PI3K/AKT/mTOR pathway.
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Genetic basis:
| Feature | Description |
|---|---|
| Gene involved | PTEN (Phosphatase and Tensin Homolog) |
| Location | Chromosome 10q23.3 |
| Function | Tumor suppressor; regulates cell cycle, apoptosis, and cellular growth |
| Mutation type | Germline loss-of-function mutations |
| Inheritance | Autosomal dominant |
Schematic representation of the PI3K/Akt/mTOR pathway.
Blumenthal, G., Dennis, P. PTEN hamartoma tumor syndromes. Eur J Hum Genet 16, 1289–1300 (2008). https://doi.org/10.1038/ejhg.2008.162
| Syndrome/Disorder | Key Features |
|---|---|
| Cowden Syndrome (CS) | Multiple hamartomas, breast/thyroid/endometrial cancer, mucocutaneous lesions |
| Bannayan–Riley–Ruvalcaba Syndrome (BRRS) | Macrocephaly, developmental delay, lipomas, penile lentigines, intestinal polyps |
| Proteus Syndrome | Asymmetric overgrowth, cerebriform connective tissue nevi, vascular malformations |
| Proteus-like Syndrome | Partial or atypical features of Proteus syndrome with PTEN mutations |
| Autism spectrum disorder with macrocephaly | Some cases linked to germline PTEN mutations |
Comparison table:
| Feature | Cowden Syndrome | BRRS | Proteus Syndrome |
|---|---|---|---|
| Macrocephaly | + | + | + |
| Hamartomas | Skin, breast, GI, thyroid | GI, lipomas, hemangiomas | Connective tissue, adipose |
| Cancer risk | High | Not well defined | Controversial |
| Mucocutaneous lesions | Trichilemmomas, papillomas | Penile lentigines | Cerebriform nevi |
| Developmental delay | Sometimes | Frequent | Variable |
| PTEN mutation | Yes | Yes | Variable (not always present) |
| Inheritance | Autosomal dominant | Autosomal dominant | Sporadic (mosaic) |
Common Findings: