A rare syndrome characterized by multiple hamartomas
(small flesh-colored nodules on the skin made up by hair follicles and small
wart-like growths) and a risk of breast, thyroid, and uterine neoplasias.
Multiple Hamartoma Syndrome.
Named after Rachel Cowden, the first patient described.
More than 200 cases have been described in the medical
literature. Males and females are equally affected, however, thyroid cancer
is the most common cancer in males, whereas breast cancer is the most common
in affected women.
Autosomal dominant with interfamilial and
Cowden syndrome results from a mutation in the
PTEN (phosphatase and tensin homologue) tumor suppressor gene. (Synonym: MMAC1 [mutated in
multiple advanced cancers-1] gene), which has been mapped to 10q23. PTEN
encodes a phosphatase involved in regulation of growth, survival, and death
of cells. The lack of PTEN functionality appears to be responsible for the
uncontrolled proliferation of certain cells and the formation of hamartomas (and neoplasias).
Based on the clinical findings. Usually Cowden syndrome
is diagnosed only after the first year of life. Mucocutaneous signs are most
pathognomonic but least obvious. Signs include acral keratosis, facial
trichilemmomas, oral papillomas, and scrotal tongue. The International
Cowden Syndrome Consortium summarized the diagnostic features into major
criteria (macrocephaly, thyroid cancer, breast cancer, and Lhermitte-Duclos
disease [see Other Conditions to Be Considered]) and minor criteria (mental retardation, nonmalignant thyroid
changes, nonmalignant breast tumors, gastrointestinal hamartomas, lipomas,
fibromas, urogenital tumors). Mucocutaneous lesions alone can meet the
criteria under certain circumstances (depending on the number and type of
lesions). The diagnosis is considered very likely when one major and
three minor criteria, two major criteria (but only if either macrocephaly or
Lhermitte-Duclos disease is present), or four minor criteria are met.
Macrocephaly, not secondary to hydrocephalus, may
be present in up to 39% of patients and usually becomes evident only
after the first year of life. It is often accompanied by frontal bossing,
adenoid facies, hypoplastic maxilla and mandible, and high arched palate.
Mild mental retardation with seizures and cerebellar signs (tremor) is
present in 12% of patients. Kyphosis, kyphoscoliosis, and anomalies of
the thyroid gland are reported in approximately two thirds of patients and
may include multinodular goiter, adenomas, and follicular adenocarcinoma.
Patients should undergo regular checkups for signs of thyroid cancer
(especially men). The most serious malignancy in females is (early-onset)
breast cancer, which may affect up to one third of female patients and often
occurs bilaterally. Gastrointestinal adenomas, hamartomatous and
hyperplastic polyps, lymphangiomas, and ganglioneurofibromas may occur in
almost three fourths of patients and can be localized anywhere between the
esophagus and the anus (including gallbladder) but are most common in the
colon. Malignant transformation is a possible risk. Urogenital lesions
include carcinomas of the kidneys, urethra, and uterine cervix, ovarian
cysts, leiomyomas, and teratomas, vaginal and vulvar cysts, and testicular ...