Cowden disease
Allelic diseases - Autosomal dominant disease allelic with Bannayan-Riley-Ruvalcaba syndrome (PTEN mutations). Cowden syndrome and Bannayan-Ruvalcaba-Riley syndrome (BRRS; MIM.153480) share clinical characteristics such as hamartomatous polyps of the gastrointestinal tract, mucocutaneous lesions, and increased risk of developing neoplasms. Furthermore, both conditions and several other distinctive phenotypes are caused by mutations in the PTEN gene. For this reason, it has been suggested that the spectrum of disorders be referred to as PTEN hamartoma tumor syndrome (PHTS). Approximately 80% of CS patients have PTEN mutations.
Phenocopies - Mutations in the SDHB (MIM.185470) and SDHD (MIM.602690) genes have been identified in a subset of PTEN mutation-negative patients with a Cowden-like syndrome (MIM.612359).
Synopsis
craniofacial anomalies
- progressive macrocephaly
- "birdlike" facies
- hypoplastic mandible
- hypoplastic maxilla
- cataract
- angioid streaks
- myopia
- microstomia
- high-arched palate
- scrotal tongue
- oral papillomas
thyroid aomalies (30%)
- goiter
- thyroid adenoma
- hyperthyroidism
- hypothyroidism
- thyroiditis
- thyroid follicular carcinoma
- thyroid medullary carcinoma (#17603316#)
digestive anomalies
- hamartomatous polyps
- colon diverticula
skeletal anomalies
- scoliosis
- kyphosis
- pectus excavatum
genital anomalies
- virginal hyperplasia
- fibrocystic breast disease
- gynecomastia in males
- breast fibroadenomas
- hydrocele
- varicocele
- vaginal cysts
- vulvar cysts
- ovarian cysts
- uterine leiomyomas
cutaneous anomalies
- multiple facial papules
- acral keratoses
- palmoplantar keratoses
- multiple inverted follicular keratoses
- multiple skin tags
- facial trichilemmomas
- subcutaneous lipomas
neurocerebral anomalies
- Lhermitte-Duclos disease
- cerebellar gangliocytoma (seizure and tremor)
tumors predisposition
- breast cancer
- thyroid follicular carcinoma
- thyroid medullary carcinoma (#17603316#)
- endometrial adenocarcinoma
- ovarian carcinoma
- cervical carcinoma
- transitional cell carcinoma of the bladder
- colon adenocarcinoma
- meningioma
Etiology
germline mutations in PTEN gene (MIM.601728)
germline mutations in Cowden-like syndrome in genes
- SDHB of succinate dehydrogenase (#18678321#)
- SDHD of succinate dehydrogenase (#18678321#)
- BMPR1A gene (MIM.601299)