Is Adrenal Cortical Carcinoma (ACC) hereditary?

Adrenal Cortical Carcinoma (ACC) is primarily a sporadic condition, meaning it occurs by chance in most individuals without a family history; however, a minority of cases are hereditary and linked to specific genetic syndromes. While most cases are not inherited, individuals with a family history of endocrine tumors or certain cancers should consider clinical genetic evaluation to assess their specific risk.

Is Adrenal Cortical Carcinoma (ACC) hereditary?

Most cases of Adrenal Cortical Carcinoma (ACC) are sporadic, arising from somatic mutations that occur during a person's lifetime rather than being passed down through generations. However, approximately 10% to 15% of Adrenal Cortical Carcinoma (ACC) cases are associated with underlying hereditary cancer predisposition syndromes. In these instances, the condition follows an autosomal dominant inheritance pattern, meaning a child of an affected parent has a 50% chance of inheriting the pathogenic variant.

What genetic syndromes are linked to Adrenal Cortical Carcinoma (ACC)?

Several rare genetic conditions increase the risk of developing Adrenal Cortical Carcinoma (ACC). These syndromes often involve germline mutations that are present in every cell of the body. Key associations include:

• Li-Fraumeni Syndrome (LFS): Caused by germline mutations in the TP53 gene.


• Beckwith-Wiedemann Syndrome (BWS): Involving epigenetic or genetic changes on chromosome 11p15.


• Multiple Endocrine Neoplasia Type 1 (MEN1): Less common, but sometimes associated with adrenal tumors.


• Lynch Syndrome: Occasionally linked to an increased spectrum of rare cancers.

When is genetic testing recommended?

Genetic testing for Adrenal Cortical Carcinoma (ACC) is generally recommended for patients who are diagnosed at a young age, those with a significant family history of cancer, or those with clinical features suggestive of a syndromic condition. Because Adrenal Cortical Carcinoma (ACC) is rare, testing is often coordinated by specialized oncology centers. Genetic counseling is essential both before and after testing to interpret results accurately and discuss implications for family members, including reproductive options like preimplantation genetic testing (PGT).

Next steps

• Consult a board-certified genetic counselor to review your personal and family medical history.


• Speak with an oncologist specializing in endocrine tumors regarding the necessity of germline genetic testing.


• Connect with the 265 members of the Adrenal Cortical Carcinoma (ACC) community at DiseaseMaps.org to share experiences and resources.

Medical disclaimer: This content is for informational purposes only and does not constitute medical advice, diagnosis, or treatment; always consult with your primary healthcare provider regarding your specific health situation.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Adrenal Cortical Carcinoma


• Orphanet: Adrenocortical carcinoma


• OMIM (Online Mendelian Inheritance in Man): Adrenal Cortical Carcinoma


• American Association of Endocrine Surgeons (AAES) Patient Education