Table 2 Clinical signs in all demonstrated and assumed mutation carriers in the six Cowden syndrome families with PTEN mutation. Families ordered by genetic position of mutations
Phenotype (Age in years at diagnosis) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Mutation(s)! | Family | Patient (sex, year of birth) | Breast | Thyroid | Endometrium | CNS | Gastrointestinal tract ‡ | Skin lesions Histology | Others |
c.50delAA Frameshift | A | Pid* 1 (F, 1970) | Bilateral mastectomy (34) | Goitre (23) | Lhermitte-Duclos disease (24) Macrocephaly | Hyperplastic colon polyps without dysplasia (26, 8) | Cavernous haemangioma (18) | ||
Pid 3 (F, 1999) | Macrocephaly Born with hydrocephalus | Born with neural tube defect | |||||||
Pid 4 (F) Dead, not tested | Cancer (46) | ||||||||
c.68T>A Nonsense | B | Pid 1 (F, 1958) | Cancer (24) | Follicular cancer (13) | Simple hyperplasia (43) | Macrocephaly | Hyperplastis colon polyps (42, 3) | + (35) skin with trichilemmomal hyperplasia | Liver haemangioma (35) |
Pid 4 (F) Dead, not tested | Bilateral cancer (45) | Goitre (35) | Gastric leiomyoma (45) | ||||||
c.328C>T Nonsense | C | Pid 1 (F, 1958) | Cancer (35) Prophylactic contra lateral mastectomy | Atypical hyperplasia (36) | Macrocephaly | +(29) Multiple Trichillemmomas periorally | Cavernous haemangioma (17) Lipoma (36) | ||
c.565A>T Nonsense | D | Pid 1 (F, 1950) | Bilateral cancer (30) (31) | Adenoma (31) | Uterine polyp (52) | Macrocephaly | Multiple non classifiable gastric, duodenal, colon and rectal fibrous polyps (30) | + (44) | Hypersementosis in teeth (32) Osteoma (32) Haemangioma (38) Neurofibroma (45) |
Pid 2 (F, 1972) | Adenoma (29) | Goitre (30) | Macrocephaly | Colon polyps with erosions and teleangiestatic granulation tissue (22, 30) | + (22) Papules on right ankle and squamous cell hyperplasia And Hyperkeratosis | Ethmoidectomy with removal of polyp from maxillary sinus (22) Dysplasia in nevus (22) Von Willebrands disease (30) | |||
Pid 3 (F, 1974) | Bilateral adenoma (21) | Goitre and follicular adenoma (22) | Macrocephaly | ||||||
Pid 18 (F, 2003) | Macrocephaly | ||||||||
c.1008C>G Nonsense | E | Pid 1 (F, 1946) | Cancer (45) | Goitre (21) and papillary cancer (45) | Lhermitte-Duclos disease (51) Macrocephaly | + (52) Squamous cell hyperplasia on hands | Lipoma (5) Parathyroid adenoma (45) Haemangioma (54) | ||
Pid 12 (M, 1975) | Goitre (14) Goitre and thyroiditis (31) Thyroidectomy (31) | Macrocephaly | |||||||
c.1028T>A, c.1039T>C Missense, missense† | F | Pid 1 (F, 1962) | Atypical hyperplasia and adenoma (33) Bilateral mastectomy (44) | Goitre (33) | Cancer (31) | Macrocephaly | Multiple hyperplastic duodenal and colon polyps (30) | ||
Pid 2 (F, 1948) | Adenoma (30) | Goitre (31) Follicular adenoma (40) | Cancer (47) | Macrocephaly | Hyperplastic gastric, small intestine, colon and rectal polyps (37) | + (36) Fibroepithelial polyps in the axilla | |||
Pid 3 (F, 1967) | Adenoma (33) | Follicular cancer (11 | Polyps (29) | Macrocephaly | Not examined | Haemangioma (9 months) Cephalic haematoma (1) Chronic cheilitis (5) Ectopic breast tissue (16) | |||
Pid 4 (F) Dead, not tested | Bilateral cancer (56) | Adenoma (49) | Nodular cystic hyperplasia (50) | Malignant schwannoma in peripheral nerves (33) | |||||
Pid 5 (F, 1965) | Bilateral adenoma (38) | Goitre(38) | Polyp (39) | Macrocephaly | Hyperplastic colon and rectal polyps (39) | + (38) Dermatofibroma and fibroepithelial polyp | Neavi with cell changes (39) | ||
Pid 7 (M, 1950) | Goitre (31) | Pineal gland tumour (42) | Macrocephaly | Multiple colon polyps seeming like ganglioneuroma and Peutz Jeghers polyps (42) Colectomized (42) Gastric, duodenal and small intestine polyps (53) Inflammatory polyp and multiple polyps perianally (53) | Epilepsy (42) | ||||
Pid 8 (F, 1952) | Bilateral cancer (43, 53) | Goitre (28) | Polyp and simple hyperplasia (50) | Macrocephaly | Hyperplastic colon polyp and juvenile hamartomata type colon polyp (49, 2) | Removed epidermal cyst (52) | Liver haemangioma (51) Kidney cancer (52) | ||
Pid 9 (F, 1955) | Small cysts bilaterally (50) | Goitre (25) | Myoma (39) Uterus removed (45) Polyp isthmus uteri (48) | Macrocephaly | Hyperplastic colon and rectal polyps with focal fibrosis (48, 7) | + (48) | Lipoma (36) | ||
Pid 32 (F, 1973) | Macrocephaly | Polydactylia foot (5) | |||||||
Pid 42 (M, 1989) | Macrocephaly | Haemangioma (11) | |||||||