Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs) usually from the third decade onward. Approximately 60% of individuals have a recognizable appearance with macrocephaly, frontal bossing, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals respectively. Approximately 5% of all children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor), generally the desmoplastic subtype. The risk of developing medulloblastoma is substantially higher in individuals with an SUFU pathogenic variant (33%) than in those with a PTCH1 pathogenic variant (<2%). Peak incidence is at age one to two years. Life expectancy in NBCCS is not significantly different from average.

Cowden syndrome-1 is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma. Bannayan-Riley-Ruvalcaba syndrome (BRRS), previously thought be distinct, shared clinical characteristics with Cowden syndrome, such as hamartomatous polyps of the gastrointestinal tract, mucocutaneous lesions, and increased risk of developing neoplasms, but had the additional features of developmental delay, macrocephaly, lipomas, hemangiomas, and pigmented speckled macules of the glans penis in males. Because features of BRRS and Cowden syndrome have been found in individuals within the same family with the same PTEN mutation, Cowden syndrome-1 and BRRS are considered to be the same disorder with variable expression and age-related penetrance (summary by Marsh et al., 1999, Lachlan et al., 2007, and Blumenthal and Dennis, 2008). Approximately 80% of patients reported with Cowden syndrome and 60% with BRSS have PTEN mutations (Blumenthal and Dennis, 2008). Some patients with Cowden syndrome may have immune system defects resulting in increased susceptibility to infections (summary by Browning et al., 2015).

Any hereditary breast ovarian cancer syndrome in which the cause of the disease is a mutation in the RAD51C gene.

Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.