Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria.

[cowden syndrome]

PTEN hamartoma tumor syndrome (PHTS ) refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN ) gene . Diagnostic criteria for Cowden syndrome , the principal PTEN -related disorder , were first established in 1996 before the identification of the PTEN gene and the ability to molecularly confirm a clinical diagnosis . These consortium criteria were based on clinical experience and case reports in the existing literature , with their inherent selection biases . Although it was initially reported that approximately 80 % of patients with Cowden syndrome had an identifiable germline PTEN mutation , more recent work has shown these diagnostic criteria to be far less specific . In addition , increasing evidence has documented the association of a broader spectrum of clinical features with PTEN mutations . Our goal was to develop revised , evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN -related clinical syndromes .We performed a systematic search and review of the medical literature related to clinical features reported in individuals with a PTEN mutation and /or a related clinical diagnosis .We found no sufficient evidence to support inclusion of benign breast disease , uterine fibroids , or genitourinary malformations as diagnostic criteria . There was evidence to include autism spectrum disorders , colon cancer , esophageal glycogenic acanthosis , penile macules , renal cell carcinoma , testicular lipomatosis , and vascular anomalies .We propose revised , evidence-based criteria covering the spectrum of PTEN -related clinical disorders . Additional research on clinical features associated with PTEN mutations is warranted .

Diseases
Validation

Diseases presenting "renal cell carcinoma" symptom

cowden syndrome

dedifferentiated liposarcoma

esophageal adenocarcinoma

esophageal squamous cell carcinoma

liposarcoma

pleomorphic liposarcoma

severe combined immunodeficiency

systemic capillary leak syndrome

von hippel-lindau disease

This symptom has already been validated