Genetic Testing and Patient Communications

Written by Margaret Anne Rockwood | Last updated April 29th, 2026
Medically reviewed by Doreen Ho, MD and Jennifer Morganroth, MD, MBA

A diagnosis of ALS leads the physician and patient into a highly emotion-laden conversation. Physicians are tasked with sensitively helping the patient balance their need for hope with the need to acknowledge the extremely challenging nature of their disease.

It may be the right time to bring in other supports (counseling, family services), but the trusted physician sets the stage, not only for how the patient and family will proceed, but what mindset they adopt to help them move forward with the best treatment and life-planning decisions.

First Things First: The Universal Offer

The physician should offer newly diagnosed patients a multi-panel gene panel immediately upon a confirmed or strongly suspected diagnosis of ALS, particularly in the setting of the FDA approved medication, Tofersen, for SOD1 ALS.

Genetic counseling is offered both pre-test and post-test to help address the psychological impact and the risk to family members, and is recommended, particularly if testing is positive.

If a clear pathogenic variant is found, the patient can be described as having “genetic ALS,” even if they have no known family history. This can change the prognosis and, in some cases, can provide a clear molecular target for therapy or clinical trials.

In addition to the “Big Four” (C9orf72, SOD1, FUS, and TARDBP), modern guidance emphasizes including several other genes that are “strongly” or “definitively” associated with the disease.

Presenting Results to the Patient

Helping a patient and their family navigate genetic results is one of the most sensitive aspects of ALS care. Suggested touchpoints include:

Reiterating why the test was done

• First, testing may unveil if there is a specific ‘key’ to the patient’s ALS that might warrant use of new, targeted therapies or trials.
• Second, while optional, testing can inform life-planning decisions family members make, such as on reproduction and life insurance. Genetic counseling is required to be part of the testing process, encouraging careful consideration of the clinical, psychological and familial implications.

The 10% Rule: A pathogenic or likely pathogenic variant in a known ALS gene is identified in about 10-15% of ALS cases overall; proportions are higher in familial ALS than in apparently sporadic ALS. However, whenever the panel is negative, the diagnosis remains ‘sporadic ALS’.

Explaining the genetic results

• Positive result (pathogenic variant):
  • Name the gene: Explain that a suspected pathogenic variant in the gene is likely the primary cause of the ALS (e.g., SOD1). Using analogies (such as a critical typo in an instruction manual) when helpful.
  • Family impact: Share that because the gene can be hereditary, the patient’s children and full siblings have a 50% chance of having this same marker. Due to age-dependent and incomplete penetrance of the pathogenic variant, not all of those who have the pathogenic variant will develop ALS.
  • Next steps for the family: Recommend that the patient’s family see a genetic counselor to discuss what this means for each of them.
  • Next step for the patient: If the patient has a pathogenic variant for which there is an FDA-approved treatment (as with SOD1), or open, relevant clinical trials, explain the specific treatments that target this pathogenic variant. Include the potential effects on disease progression, treatment limitations and side effect profile.

• Negative result: 
  • Explanation: Emphasize that a negative panel result is what is seen in about 90% of cases, and that it means their ALS is considered ‘sporadic’. The clinical diagnosis of ALS is still valid, resting on history, examination and electrophysiology testing.
  • Family reassurance: Share that while not having a specific genetic target is the downside of a negative diagnosis, generally this is good news for the family. Depending on the degree of a shared environment and subtle familial clustering, their risk may be just slightly elevated over that of the general population.
  • The Caveat: Remind the patient that the negative result does not exclude a genetic component; it means that no currently recognized pathogenic variant in the tested genes was identified. Reinterpretation in the future may be appropriate as knowledge evolves.

• VUS (Variant of Uncertain Significance) Result:

• • Explanation: Relate that the finding of a ‘variation’ in a gene that may be linked to ALS, but the medical community does not yet know whether it is causal or a harmless ‘quirk’.
  • The Action Plan: Explain that their ALS is treated as a ‘negative’ for now, with the same treatment as for ‘sporadic’ ALS, but assure that the lab report remains on file in case new research reclassifies the role it may play in ALS.

Beyond a ‘warm handoff’

Because ALS and its progressive symptomology are profoundly consequential for patients and families, physicians often feel that a standard “warm hand-off” is insufficient. Yet only a fraction of all outpatient encounters occur with a physician in the ALS clinic, with a large share handled by home care nurses and allied health professionals.​

Despite having the right support team in place, where possible, the diagnosing neurologist or primary physician may want to maintain an ongoing, personal connection with the patient. This can be a lifeline for many patients, as continuity and a sense of non-abandonment are repeatedly identified as important to patients adjusting to serious diagnoses.

Telehealth has become common for ongoing ALS follow-up. This offers the physician an opportunity for ongoing, lower-burden conversations and keeps patients abreast of the latest medical knowledge and drug opportunities, especially as progression limits their ambulation.

Given the complexities of navigating care and resources patients can encounter, this reassurance may be invaluable.

References

1. Evidence-based consensus guidelines for ALS genetic testing and counseling. Roggenbuck, J., et al. (2023). Annals of Clinical and Translational Neurology, 10(11), 2074–2091.
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