Genomic Instability, Cancer Predisposition & Overgrowth Disorders

Hereditary cancer predisposition syndromes are genetic disorders in which changes in specific genes can increase an individual’s risk of developing certain types of cancer. Knowledge of these conditions can help inform the possibility of earlier cancer screening and suggest interventions that may prove life-saving, such as prophylactic mastectomy for patients with significantly increased risk for breast cancer due to BRCA1/2 mutations. Many of the other groups of conditions mentioned in greater detail in the categories below are also associated with known increased risk for malignancy.

Genome maintenance and premature aging syndromes are a group of inherited disorders that cause problems with how our cells copy, protect and pass on our genetic material. Though often associated with an increased risk of developing cancer, these conditions are also associated with complex, multi-system clinical concerns with potential to affect many organs. Some of the issues arise at or before birth, while others develop throughout life, particularly those involving the neurological and immune systems. Many of the conditions are also associated with features of premature aging, such as early-onset diabetes and heart and bone disease.

Overgrowth syndromes are a group of genetically driven disorders that result in excessive growth of either one part of the body or the whole body. These syndromes can present before birth, at birth (when newborns are large for their gestational age), or after birth (when individuals show accelerated growth beginning in childhood or adolescence). Some of these disorders may be associated with other significant health concerns such as developmental delay(s), intellectual disability, neurological and immune abnormalities, hormonal imbalances, and predisposition to specific tumors requiring prompt diagnosis and treatment.

Neurocutaneous disorders are genetic conditions predominantly affecting both the nervous system and skin, though other organ systems such as the eyes, heart, blood vessels, lungs, kidneys, endocrine glands and bones, can also be affected. These are also multi-system conditions with a variety of clinical manifestations, from cataracts and hearing loss to seizures, developmental disabilities, skeletal deformities and also risk for certain types of malignancies.

Chromatinopathies, sometimes also known by an overlapping term “epigenetic” disorders, refer to genetic syndromes characterized by mutations in genes that regulate how genes are packaged and used by different cells throughout development. Some of these affect how chromatin—or the packaging of DNA by proteins—is formed, used or maintained. Chromatinopathies are multi-system disorders associated with neurodevelopmental delay(s), intellectual disability, growth and feeding difficulties, neurological, immune, cardiac, craniofacial, and skeletal abnormalities, as well as increased potential for certain types of malignancy. These conditions may have unique “episignatures” with distinctive DNA methylation patterns that may help inform diagnosis in addition to standard genetic testing.

Receiving a diagnosis of genomic instability, cancer predisposition, or overgrowth disorder, or being at risk for or suspected of having one, can feel overwhelming, but learning more about the diagnosis can help you navigate treatment and care. Visit the links below to learn more about some of the different types of rare disorders, their causes, and associated symptoms as well as screening and treatment options. This list includes a selection of genomic instability, cancer predisposition, and overgrowth disorders. Schedule a consultation with us for diagnosis and treatment options for these or any other rare conditions.