Proteus syndrome: Misdiagnosis with PTEN mutations

  title={Proteus syndrome: Misdiagnosis with PTEN mutations},
  author={Marsha M. Cohen and Joyce T. Turner and Leslie G. Biesecker},
  journal={American Journal of Medical Genetics Part A},
In this editorial, we briefly (1) define Proteus syndrome; (2) analyze reports of PTEN mutations claimed to have ‘‘Proteus syndrome’’ or a ‘‘Proteus-like syndrome’’; (3) demonstrate the high frequency of misdiagnosis of Proteus syndrome by clinicians less familiar with the disorder; and (4) discuss two series of patients who do meet the diagnostic criteria for Proteus syndrome among whom none have been found to have PTENmutations. Proteus syndrome is a highly variable disorder with strikingly… 
Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome
Proteus syndrome is a complex hamartomatous disorder characterized by asymmetrical gigantism, epidermal nevi, vascular malformations, hamartomas, lipomas, and hyperostosis. Since the syndrome was
Proteus syndrome review: molecular, clinical, and pathologic features
Concluding remarks address diagnostic criteria, natural history, management, psychosocial issues, and differential diagnosis ofroteus syndrome.
Diagnosis of Proteus syndrome was correct
The diagnosis was straightforward, and the authors were surprised that it was questioned by Cohen et al.
De Novo PTEN Mutation in a Young Boy with Cutaneous Vasculitis
A case of PHTS syndrome caused by a de novo mutation in PTEN detected using a targeted next generation sequencing (NGS) gene panel which was instigated for workup of cutaneous vasculitis is described.
Genetics of PTEN Hamartoma Tumour Syndrome
The data that are available on risks for malignancy and other features of the syndrome have been almost entirely obtained on cohorts of patients who presented to medical attention and were tested because they demonstrated a significant number of PHTS features, leading to overestimates of the prevalence of these features.
Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity
Data provide a new demonstration of the Happle hypothesis to explain some segmental exacerbation of autosomal-dominant disorders and show that a bi-allelic inactivation of PTEN can lead to developmental anomalies instead of malignant transformation, raising the question of the limitations of the tumor suppressive function in this gene.
PTEN Hamartoma of Soft Tissue: A Distinctive Lesion in PTEN Syndromes
The distinctive histopathology of a predominantly intramuscular lesion in PHTS, often called “arteriovenous malformation,” is delineated, and its identification should prompt a thorough investigation for PHTS.
PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature
The limited understanding of the natural history of childhood‐onset PHTS as a cancer predisposition syndrome is acknowledged and a summary of important management considerations is presented.
Germline PTEN mutations are rare and highly penetrant
PTEN mutations were found in all six families meeting the clinical criteria for Cowden syndrome, and in none of the eight families selected in the computerized medical files to have a combination of breast and thyroid cancers.
The challenges of Proteus syndrome: diagnosis and management
Effective management of Proteus syndrome requires knowledge of the wide array of manifestations and complications of the disorder and a team approach that includes the geneticist, surgeons, and other specialists.


PTEN mutations are uncommon in Proteus syndrome
One of the mandatory diagnostic criteria for Proteus syndrome is a mosaic distribution of lesions and sporadic occurrence, entirely consistent with Happle's hypothesis.
Germline mutation of the tumour suppressor PTEN in Proteus syndrome
Clinical overlap exists between PS and another hamartoma syndrome, Bannayan-Riley-Ruvalcaba syndrome, in which up to 60% of affected subjects are known to carry a germline mutation of the tumour suppressor gene PTEN .6 BRR also shows partial clinical overlap with Cowden syndrome.
Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis.
PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future and postulate that the second hit, R130X, occurred early in embryonic development and may even represent germline mosaicism.
Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia.
It was found that imaging studies are very useful for the characterization of the syndrome and one finding was that splenic hyperplasia can be a manifestation of Proteus syndrome.
Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation.
This is a review of recommendations for diagnostic criteria, differential diagnosis, and guidelines for the evaluation of patients on Proteus syndrome held in March 1998 at the National Institutes of Health.
Proteus syndrome: clinical evidence for somatic mosaicism and selective review.
  • M. Cohen
  • Medicine
    American journal of medical genetics
  • 1993
Selective aspects of Proteus syndrome not previously reviewed are presented including: uncommon neoplasms; pulmonary and renal abnormalities; brain malformations; facial phenotype associated with seizures and severe mental deficiency; and types of abnormal growth in the craniofacial skeleton.
Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin.
  • R. Happle
  • Medicine
    Journal of the American Academy of Dermatology
  • 1987
The proteus syndrome
Four boys are described with partial gigantism of the hands and/or feet, pigmented nevi, hemihypertrophy, subcutaneous hamartomatous tumors and macrocephaly, and/ or other skull anomalies, and the term Proteus syndrome is proposed for this ‘new’ syndrome.
Proteus syndrome.
A girl aged 3 years and 8 months with an epidermal nevus, port-wine stain, macrodactyly with gigantism of the feet, lymphohemagiomas and multiple lipomas is presented.