Looking for the hidden mutation: Bannayan–Riley–Ruvalcaba syndrome caused by constitutional and mosaic 10q23 microdeletions involving PTEN and BMPR1A
Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a genetic condition characterized by large head size, hamartomas, intestinal polyposis, and genital pigmentation. Intellectual disability is found is around half of BRRS patients as well. This disorder is caused by mutations of the PTEN gene located at 10q23.31 or deletions involving this area of chromosome 10. The PTEN gene is a constitutively active tumor suppressor gene and pathogenic variants predispose patients to a number of cancers including breast cancer, thyroid cancer, endometrial cancer, colorectal cancer, kidney cancer, and melanoma.
The authors report two patients with BRRS. A constitutional 10q23.1q23.3 deletion was found in patient 1 through genetic testing of a buccal mucosa sample. Her clinical features included macrocephaly, hyperpigmented spots, large papillae on her tongue, and dysmorphic facial features. She also had mild intellectual disability.
Patient 2 likewise presented with symptoms of BRRS but genetic confirmation of the diagnosis took many years. Initial genetic testing of the patient’s blood was negative. The diagnosis was genetically confirmed seven years later after testing of the patient’s thyroid gland revealed a high-level mosaicism for 10q23.2q23.3 microdeletion. Chromosomal mosaicism is defined as the presence of two or more chromosomally distinct cell lines in an individual and can present challenges diagnostically. Based on this finding it is important to consider mosaic genetic changes when testing patients who present with clinical BRRS symptoms
Golas MM, Auber B, Ripperger T, et al. Looking for the hidden mutation: Bannayan–Riley–Ruvalcaba syndrome caused by constitutional and mosaic 10q23 microdeletions involving PTEN and BMPR1A. Am J Med Genet Part A 2019, v. 179 (7), 1383-1389.