eRAM

The primary findings in PHTS include increased risk for certain types of cancer, benign tumors and tumor-like malformations (hamartomas), and neurodevelopmental disorders. The symptoms of PHTS vary greatly from person to person and can develop at any age.Cancer in PHTSPrevious data, which focused only on patients with a clinical diagnosis of Cowden syndrome without understanding whether an underlying PTEN mutation was present estimated lifetime breast cancer risk to be 25-50% and risk for non-medullary thyroid cancer to be 10%. Risks for endometrial (uterine) and renal cell (kidney) cancer were thought to be increased, but an exact risk level was undetermined.Current data focusing on patients known to have PHTS provide the following lifetime risk estimates, with the majority of diagnoses occurring after age 30:·Breast cancer: 85%·Thyroid cancer: 35%·Renal cell cancer: 34%·Endometrial cancer: 28%·Colorectal cancer: 9%·Melanoma: 6%.Benign tumors in PHTSBenign skin or oral lesions are very common and most commonly appear in adulthood. The most common types of benign skin lesions seen in PHTS include:.·Lipomas – benign fatty tumors which can appear just under the skin or elsewhere (breast area, GI tract)·Acral keratosis – rough patches of skin most often seen on the extremities (arms, hands, legs, feet)·Papillomatous skin papules – wart-like lesions which can appear anywhere, with feet and hands commonly being affected·Mucosal papillomas – Benign overgrowth of tissue affecting the tongue, gums, or inside the nose·Trichilemmomas – Benign tumor of the hair follicle·Fibromas – another kind of overgrowth involving the skin and other connective tissue; may also affect tissue covering organs, such as the ovaries.Gastrointestinal polyps are very common in adults with PHTS. Among patients who had undergone endoscopy, 93% were found to have polyps. The kinds of polyps found most often were hyperplastic or hamartomatous, which rarely develop into malignancy; however adenomas, which may develop into a cancer, were also identified. Many polyps were very small and did not cause symptoms to make their presence known such as pain or rectal bleeding.Benign breast, thyroid, and uterine lesions are also common in persons with PHTS. Some women have severe fibrocystic disease or changes which lead to multiple breast biopsies and complications with imaging. Multinodular goiter and Hashimoto’s thyroiditis may develop in children and adults. Uterine fibroids may appear and cause bleeding or discomfort to the extent that hysterectomy is indicated without an underlying cancer diagnosis.Vascular tumors, including hemangiomas, arteriovenous malformations, and developmental venous anomalies, have also been observed in patients with PHTS. Treatment of some lesions has been complicated by tendency for regrowth.A minority of adults develop a rare tumor known as a cerebellar dysplastic gangliocytoma (Lhermitte-Duclos syndrome). Symptoms of Lhermitte-Duclos syndrome include increased intracranial pressure, impaired ability to coordinate voluntary movements (ataxia), and seizures. It is rare when a person with adult-onset Lhermitte-Duclos does not have an underlying PTEN mutation, and observing this tumor type is an automatic indicator of need for PTEN testing.Neurodevelopmental concerns in PHTSMacrocephaly (large head size) is found in 94% measured patients with PHTS and can be a helpful screening tool to identify patients at increased risk for PTEN mutation. In most patients large head size is caused by overgrowth of brain tissue as opposed to hydrocephalus. The head shape also tends to be longer than wide (dolicocephaly).Autism and other developmental disorders, such as mental retardation and developmental delays, have been observed in patients with PHTS. In previous case series, up to 12% of children presenting with macrocephaly and an autism spectrum disorder alone were found to have an underlying PTEN mutation. - NORD
Reference: NORD

pten hamartoma tumor syndrome (disorder)
pten hamartoma tumour syndrome

C1959582

C1306837  |  papillary renal cell carcinoma  |  1
C0024141  |  systemic lupus erythematosus  |  1
C0476089  |  endometrial cancer  |  1
C0476089  |  endometrial ca  |  1
C0007134  |  renal cell carcinoma  |  1
C0409974  |  lupus erythematosus  |  1

5728  |  PTEN  |  CLINVAR

HP:0012740  |  Papilloma
HP:0012480  |  Abnormality of cerebral veins
HP:0005987  |  Multinodular goiter
HP:0045059  |  Hyperkeratotic papule
HP:0001480  |  Freckling
HP:0008046  |  Abnormality of the retinal vasculature
HP:0012032  |  Lipoma
HP:0012846  |  Multiple trichilemmomata
HP:0003005  |  Ganglioneuroma
HP:0012114  |  Endometrial carcinoma
HP:0005584  |  Renal cell carcinoma
HP:0010612  |  Plantar pits
HP:0003003  |  Colon cancer
HP:0001028  |  Hemangioma
HP:0000729  |  Autistic behavior
HP:0002664  |  Neoplasm
HP:0000256  |  Macrocephaly
HP:0000077  |  Abnormality of the kidney
HP:0002597  |  Abnormality of the vasculature
HP:0001249  |  Intellectual disability
HP:0002890  |  Thyroid carcinoma
HP:0200034  |  Papule
HP:0000854  |  Thyroid adenoma
HP:0003002  |  Breast carcinoma

HP:0002725  |  Systemic lupus erythematosus  |  1
HP:0005584  |  Renal cell carcinoma  |  1
HP:0030731  |  Carcinoma  |  1
HP:0006766  |  Papillary renal cell carcinoma  |  1