Genomics’ Red Flag Rule of Too and Two

June 27, 2022

By Patricia (Pat) A. Kelly, DNP, APRN, CNS, AGN-BC, AOCN®

I often use mnemonics, a memory tool, to simplify learning. Mnemonics ( can be any pattern of letters, numbers, words, images, or other relatable associations that help you remember.

My favorite mnemonic for the first steps of when to consider a genetic or genomic condition is called the Rule of Too and Two. I read about this concept several years ago in A Toolkit to Improve Care for Pediatric Patients With Genetic Conditions in Primary Care ( published by the Genetics in Primary Care Institute. Although the institute is no longer active, the pediatric and adult genomic information and toolkit are timeless, and they credit Arthur Grix, MD, as the source for the Too and Two approach in recognizing red flags in family history.

How to Practice

Genetic and genomic conditions should be considered when the descriptors in the sidebar are present. For example:

To be clear, the Rule of Too and Two is not inclusive for hereditary cancer risk assessment. The mnemonic is basic and does not prompt for many phenotypic (physical) characteristics of hereditary cancers or detailed syndromic features. However, it can serve an initial trigger that further assessment ( is needed.

Incorporate Resources in Your Practice

The Too and Two assessment compliments several hereditary cancer resources. ONS’s When to Refer to a Genetics Professional ( guide provides detailed information and a checklist for hereditary risk factors and referral guidelines. ONS’s patient video, Genetic Counseling and You (, reinforces hereditary cancer syndrome red flags and supports the patient with important information on how to prepare for their genetic counseling visit. And the American College of Medical Genetics and Genomics and National Society of Genetic Counselors’ comprehensive practice referral guidelines provides ( a listing of patient or first-degree relative cancer features to consider for a hereditary cancer syndrome differential diagnosis.

All nurses have a responsibility ( to “identify clients who might benefit from referral to genetic specialists or information resources,” including referrals for non-oncology and pediatric genetic conditions. In our busy practices, short prompts can be useful and time conserving. Consider the mnemonic of Too and Two as you examine initial clues for hereditary cancer syndromes.

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