Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2014 Sep;150(9):990-3.
doi: 10.1001/jamadermatol.2013.10368.

A limited form of proteus syndrome with bilateral plantar cerebriform collagenomas and varicose veins secondary to a mosaic AKT1 mutation

Jamie S Wee  1 , Peter S Mortimer  1 , Marjorie J Lindhurst  2 , Heung Chong  3 , Leslie G Biesecker  2 , Colin A Holden  4
Affiliations
Case Reports

A limited form of proteus syndrome with bilateral plantar cerebriform collagenomas and varicose veins secondary to a mosaic AKT1 mutation

Jamie S Wee et al. JAMA Dermatol. 2014 Sep.

Abstract

Importance: Proteus syndrome is an extremely rare disorder of mosaic postnatal overgrowth affecting multiple tissues including bone, soft tissue, and skin. It typically manifests in early childhood with asymmetric and progressive skeletal overgrowth that leads to severe distortion of the skeleton and disability. The genetic basis has recently been identified as a somatic activating mutation in the AKT1 gene, which encodes an enzyme mediating cell proliferation and apoptosis.

Observations: We present a 33-year-old man who developed plantar cerebriform collagenomas on the soles of both feet and varicose veins in early childhood, in the absence of any skeletal or other connective tissue abnormality. Although the patient did not meet the diagnostic criteria for Proteus syndrome, he was found to have the c.49G>A, p.Glu17Lys AKT1 mutation in lesional skin but not in his blood.

Conclusions and relevance: To our knowledge, this is the mildest molecularly confirmed case of Proteus syndrome, occurring in the absence of the characteristic skeletal overgrowth. These findings extend the spectrum of Proteus syndrome pathological characteristics and suggest that somatic mutations late in development and restricted in distribution cause subtle clinical presentations that do not meet the published clinical criteria.

PubMed Disclaimer

Conflict of interest statement

All Financial Interests (including pharmaceutical and device product(s):

  1. Employment

  2. Consultancies:

  3. Honoraria: Dr. Biesecker receives honoraria from Wiley-Blackwell for editorial duties, which has no relationship to this manuscript.

  4. Speakers bureau

  5. Stock ownership or options

  6. Expert testimony

  7. Grants

  8. Patents filed, received, pending, or in preparation

  9. Royalties: As above for Lindhurst and Biesecker

  10. Donation of medical equipment

Figures

Figure 1
Figure 1
Plantar cerebriform tumors. A, Bilateral plantar involvement. B, Prominent gyriform-like sulci.
Figure 1
Figure 1
Plantar cerebriform tumors. A, Bilateral plantar involvement. B, Prominent gyriform-like sulci.
Figure 2
Figure 2
Histopathological findings of skin biopsy. A, Markedly thickened dermis consisting of thick collagen fibres arranged in a haphazard orientation (hematoxylin and eosin stain). B, Large calibre, irregular thick-walled veins at the interface of the deep dermis and subcutaneous tissue (EVG stain).
Figure 2
Figure 2
Histopathological findings of skin biopsy. A, Markedly thickened dermis consisting of thick collagen fibres arranged in a haphazard orientation (hematoxylin and eosin stain). B, Large calibre, irregular thick-walled veins at the interface of the deep dermis and subcutaneous tissue (EVG stain).
Figure 3
Figure 3
PI3K-AKT-mTOR signalling pathway and associated hamartoma/overgrowth syndromes (PI3K subsumes PIK3CA and PIK3R2, AKT subsumes AKT1-3).
See this image and copyright information in PMC

References

    1. Lindhurst MJ, Sapp JC, Teer JK, et al. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med. 2011;365(7):611–9. - PMC - PubMed
    1. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol. 1987;16(4):899–906. - PubMed
    1. Nguyen D, Turner JT, Olsen C, Biesecker LG, Darling TN. Cutaneous manifestations of proteus syndrome: correlations with general clinical severity. Arch Dermatol. 2004;140(8):947–53. - PubMed
    1. Twede JV, Turner JT, Biesecker LG, Darling TN. Evolution of skin lesions in Proteus syndrome. J Am Acad Dermatol. 2005;52(5):834–8. - PubMed
    1. Biesecker LG, Happle R, Mulliken JB, et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet. 1999;84(5):389–95. - PubMed

Publication types

Substances

Supplementary concepts