The Cowden syndrome: a clinical and genetic study in 21 patients.
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.
Starink
T M
TM
van der Veen
J P
JP
Arwert
F
F
de Waal
L P
LP
de Lange
G G
GG
Gille
J J
JJ
Eriksson
A W
AW
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005147:Facial Bones / Q000002:abnormalities; D005148:Facial Dermatoses / Q000235:genetics / Q000473:pathology; D005260:Female; D005350:Fibroma / Q000235:genetics / Q000473:pathology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis; D007223:Infant; D007642:Keratosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010375:Pedigree; D012867:Skin / Q000473:pathology; D012886:Skull / Q000002:abnormalities; D013577:Syndrome
D006680:HLA Antigens; D007126:Immunoglobulin Allotypes