Figure 2 Presenting clinical features of probands. All childhood probands presented with motor delay, macrocephaly and learning difficulties. The first bar represents those children who presented with minimal signs of macrocephaly and motor delay/learning difficulties. Two male patients included in this bar had penile freckling noted at diagnosis, but had no lipomata or hamangiomata. For one participant, seen as an adult, the major diagnostic clue was his presentation aged 15 with a thyroid follicular cancer. Only two adults had learning problems and a history of early motor delay; one with Lhermitte–Duclos disease and the other with haemangiomas and lipomas. Three adults presented to a genetics service following a tumour diagnosis: one with a bowel adenocarcinoma in situ in a bowel polyp, who had previous severe fibrocystic disease of the breasts, necessitating bilateral mastectomy; one with a breast cancer, with a history of benign thyroid disease; and the third was a woman who presented with a respiratory arrest, secondary to a polyp obstructing her airway. The diagnosis in the third case was made on the basis of dermatological signs, and she subsequently developed breast cancer and benign thyroid disease. Only one adult (in whom the diagnosis was made by a dermatologist) had facial lesions biopsied to confirm the presence of trichilemmomas, which demonstrates the difficulty of using the Cowden Consortium guidelines to aid diagnosis in a clinical setting.