Type 2 segmental pten hamartoma syndrome

Happle 2007

A clinical picture belonging to the PTEN hamartoma tumour syndromes, characterised by the systematised, unilateral epidermal nevus (PTEN nevus).

The type 2 segmental PTEN hamartoma syndrome was previously misinterpreted as Proteus syndrome. Proteus syndrome, in which activating mutations in AKT1 or PIK3CA are present in mosaic, shows extensive clinical similarity to this syndrome. "In mosaic" means that the mutation affects only certain cell lines. In addition to mutated cells, cell lines exist in which the mutation is not detectable. This phenomenon is particularly evident in the so-called Blaschko lines (see also cutaneous mosaics).

The term PTEN-Hamartoma-Tumour Syndrome (PHTS) defines a group of clinically heterogeneous, partially overlapping diseases with an autosomal dominant PTEN mutation 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.

If a PTEN mutation is present in a clinically suspected Proteus syndrome, then it is a type 2 segmental PTEN hamartoma syndrome.

1. Happle R (2007) Type 2 segmental Cowden disease vs. Proteus syndrome. Br J Dermatol 156: 1089-1090
2. Happle R (2010) The group of epidermal nevus syndromes Part I. Well defined phenotypes.J Am Acad Dermatol 63:1-22; quiz 23-4.
3. Nathan N et al (2017) Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway. Dermatol Clin 35:51-60.