Oral and Maxillofacial Pathology
Variable expressivity and novel PTEN mutations in Cowden syndrome

https://doi.org/10.1016/j.oooo.2018.08.016Get rights and content

Cowden syndrome (CS) is a phosphatase and tensin homolog gene (PTEN)–associated condition characterized by multiple mucocutaneous hamartomas and an increased risk of malignancies. We reported an isolated case and another of several individuals in one family affected by CS. The isolated case showed typical features, including fibrocystic breast disease, benign thyroid nodules, and multiple papillomatous lesions in the face and oral cavity, and the cause was a novel nonsense mutation—guanine (G) to thymine (T) transition at position 940 (c.940 G>T)—in PTEN. In the family, the proband showed erythema nodosum, duodenal ulcer, intestinal polyps, cervical lipoma, renal cysts, and glaucoma, whereas multiple members of her family were found to have intestinal polyps, and a sister had been diagnosed with breast cancer at early age. An intronic mutation—T>G transition at the +32 position of intron 8 (c.1026+32 T>G)—was found in this family, with in silico analysis revealing the creation of a new donor splice site. This study confirmed the involvement of PTEN in CS and the variable clinical expressivity of disease.

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Materials and Methods

Written informed consent was obtained in compliance with the tenets of the Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects.

Isolated case

A 34-year-old female was referred with a chief complaint of a 1-year history of oral lesions. During anamnesis, the patient reported fibrocystic breast disease and an intracystic papilloma in the right breast, multiple benign thyroid nodules, gallbladder calculi, pulmonary centrolobular nodules with formation of air cysts, and previously removed epidermoid cysts on her back. Physical examination revealed multiple facial skin papules compatible with trichilemmomas, conjunctival papules, acral

Discussion

CS is characterized by phenotypic variability, so affected individuals often undergo numerous medical evaluations before a conclusive diagnosis can be made. Although several minimal clinical criteria for definitive diagnosis of CS were proposed,2 PTEN genetic testing is still required in individuals with typical clinical features. In the current isolated case, the patient demonstrated typical mucocutaneous lesions, including trichilemmomas, palm keratoses, multiple cutaneous facial papules, and

Conclusions

This study found novel mutations in patients with CS, confirming the variable clinical expressivity of signals. Although both mutations have been described in cancer tissues,13, 14 germline PTEN mutations are rare, and additional phenotypic features are almost always identified in CS cases. Patients with CS should, therefore, be educated about the need for cancer surveillance.

References (14)

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Cited by (2)

This work was supported by grants from The State of São Paulo Research Foundation-FAPESP, São Paulo, Brazil (2016/02667-0).

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