The Cowden syndrome: a clinical and genetic study in 21 patients

Clin Genet. 1986 Mar;29(3):222-33. doi: 10.1111/j.1399-0004.1986.tb00816.x.


An analysis of the findings in 21 patients with the Cowden syndrome or the multiple hamartoma syndrome is presented. The Cowden syndrome is a cancer-associated genodermatosis with characteristic mucocutaneous findings and a wide array of associated abnormalities including a high incidence of breast cancer in female patients. Genetic studies confirmed autosomal dominant inheritance with a high penetrance in both sexes and moderate interfamilial and intrafamilial differences in the expressivity of a number of symptoms. Familial occurrence was present in 4 of the 7 families. There was a strong predominance of female patients (6:1), which may be fortuitous. Mucocutaneous changes were the most constant (100% incidence) and characteristic findings; they almost invariably became manifest in the second decade. Four of our 18 female patients (22%) were treated for breast cancer, a lower incidence than reported previously. No increased incidence of other types of malignancies was found. Craniomegaly (high head circumference) was found to be the most common extracutaneous manifestation (80% incidence); craniomegaly appears to be an important early marker. We also found high incidences of gastrointestinal polyps (approximately 60%) and cutaneous fibromas (76%), while the incidence of thyroid abnormalities, thus far regarded as the most common extracutaneous finding, was similar to that reported previously (62%). G-banded karyotype and preliminary DNA-repair studies revealed no clear abnormalities. No linkage with the loci of HLA, and immunoglobulin haplotypes was found.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / immunology
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Facial Bones / abnormalities
  • Facial Dermatoses / genetics
  • Facial Dermatoses / pathology
  • Female
  • Fibroma / genetics
  • Fibroma / pathology
  • HLA Antigens / analysis
  • Humans
  • Immunoglobulin Allotypes / analysis
  • Infant
  • Keratosis / genetics*
  • Keratosis / pathology
  • Male
  • Middle Aged
  • Mucous Membrane / pathology
  • Neoplasms, Multiple Primary / genetics*
  • Pedigree
  • Skin / pathology
  • Skull / abnormalities
  • Syndrome


  • HLA Antigens
  • Immunoglobulin Allotypes