Pten hamartoma tumour syndromesQ87.0

The term PTEN-Hamartoma-Tumour Syndrome (PHTS) defines a group of clinically heterogeneous, partially overlapping diseases with autosomal dominant PTEN mutations in the germ line and involvement of descendants of all 3 cotyledons, manifesting as hamartomas, overgrowth and benign as well as malignant neoplasias.

Due to an incomplete and age-dependent penetrance and varying gene expression, the disease patterns show a marked phenotypic heterogeneity. In addition, the mutations known to date are scattered throughout the entire gene, which could also serve as an explanation for the clinical heterogeneity.

PTEN hamartoma tumour syndromes include:

• Cowden syndrome
• Lhermitte-Duclos Syndrome
• Bannayan-Riley-Ruvalcaba syndrome
• Type 2 segmental PTEN hamartoma syndrome
• Familial oligodendroglioma
• SOLAMEN syndrome.

All PHTS are characterized by a germline mutation in the "phosphatase and tensin homologous gene" PTEN. The canonical PTEN signaling chain (canonical= a typical feature) antagonizes phosphoinositide 3-kinase (PI3K), down-regulates P-AKT and thus controls cell cycle, apoptosis, cell migration and stability of the genome.

The timing of the first manifestation of clinical symptoms is determined by the specific disease present in each case. The most important clinical component of PTEN hamartoma tumor syndromes is the premature appearance of malignant tumors. Specifically, the lifetime risks are:

• 85% for female breast carcinoma,
• 35 % for epithelial thyroid carcinoma,
• 28 % for endometrial carcinoma,
• 32 % for renal cell carcinoma,
• 10% for colorectal carcinoma.

The individual components of PHTS present with different clinical symptoms. Furthermore, PTEN mutations promote tumors such as endometrial carcinoma and prostate carcinoma.

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