Neurogenetics

Is a neurological condition genetic?

Sometimes. Many neurological conditions have a genetic component, but the relationship between genes and neurological disease is often complex. Some conditions are caused by a single gene variant that is inherited and that significantly increases risk — these are called monogenic or hereditary neurological conditions. Others involve many genes acting together with environmental factors, and may run in families without a clear single-gene explanation. And some neurological conditions that appear in families turn out to be largely coincidental.

The answer matters because it affects whether genetic testing would be useful, what kind of testing makes sense, and what any results would mean for you and your biological family members. A genetic counselor can help you think through these questions before you pursue testing.

When might genetic testing be helpful?

Genetic evaluation may be worth considering if any of the following apply to you or a close family member:

• A neurological condition diagnosed at an earlier age than typical (especially before age 50)
• Multiple family members across generations with the same or related neurological condition
• A neurological condition with a known hereditary form, such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ALS, hereditary ataxia, or Charcot-Marie-Tooth disease
• A diagnosis that is unexplained or atypical after standard clinical workup
• A known pathogenic variant in a neurological gene identified in a close relative
• A direct-to-consumer genetic test that flagged a variant in a neurological gene
• Interest in clinical trial eligibility that requires knowledge of a genetic status

The absence of a family history does not rule out a genetic cause. Many inherited neurological conditions can appear in families without a previously recognized pattern, particularly if the condition presents differently in different generations or if earlier generations went undiagnosed.

Hereditary neurological conditions

Parkinson’s Disease

Most Parkinson’s disease (PD) is not hereditary — the majority of cases are considered idiopathic, meaning no single cause has been identified. However, 10–15% of PD cases have a genetic basis, and several genes have been identified as causes or risk factors. LRRK2 mutations are among the most common genetic causes of both familial and apparently sporadic PD. GBA variants (associated with Gaucher disease) are a common genetic risk factor for PD. SNCA, PRKN, PINK1, and VPS35 are among other genes that can be involved.

Knowing your genetic status can have implications for understanding your PD, making decisions about treatment, family planning considerations, and eligibility for genetic-specific clinical trials. The Parkinson’s Foundation’s PD GENEration program offers free genetic testing and counseling to people with a PD diagnosis.

Huntington’s Disease

Huntington’s disease (HD) is one of the clearest examples of a hereditary neurological condition: it is caused by a specific expansion in the HTT gene and is inherited in an autosomal dominant pattern, meaning a person with one copy of the expanded gene has a 50% chance of passing it to each of their children. HD causes progressive changes in movement, cognition, and behavior, typically appearing in midlife.

Genetic testing for HD is available to at-risk individuals before symptoms appear (predictive testing), but it is approached with particular care because of the significant psychological and life-planning implications of a positive result. The Huntington’s Disease Society of America’s protocol for predictive testing — which involves multiple counseling sessions and psychological support — is considered the gold standard for this type of testing and has informed how other neurological predictive testing is approached.

Alzheimer’s Disease

The genetics of Alzheimer’s disease (AD) are more complex than HD. A small percentage of AD cases — particularly those with onset before age 65 — are caused by pathogenic variants in the APP, PSEN1, or PSEN2 genes. These are rare but highly penetrant. A much more common scenario is late-onset Alzheimer’s disease, for which the APOE gene is a significant risk factor — specifically, the APOE ε4 allele increases risk in a dose-dependent way, but is neither necessary nor sufficient to cause the disease. Having one or two copies of APOE ε4 does not mean a person will develop Alzheimer’s, and many people without it will.

Because of this complexity, the decision to pursue genetic testing for AD is particularly nuanced. The ACMG and NSGC have issued joint guidance on genetic counseling and testing for Alzheimer’s disease, emphasizing the importance of informed decision-making and psychological support both before and after testing.

Other Hereditary Neurological Conditions

Several other neurological conditions have well-established hereditary forms, including ALS (amyotrophic lateral sclerosis), hereditary ataxias, Charcot-Marie-Tooth disease (a hereditary peripheral neuropathy), myotonic dystrophy, and hereditary spastic paraplegia. Research into the genetic basis of many neurological conditions is actively ongoing, and testing options and clinical guidelines continue to evolve.

The state of guidelines in neurogenetics

Clinical guidelines for genetic testing in neurological conditions are less developed than in some other areas of genetics — particularly hereditary cancer, where robust evidence-based guidelines from NCCN, ACMG, and others have been in place for years. For neurological conditions, formal guidelines exist for a small number of conditions (most notably HD and early-onset AD). For others, the research is still at an earlier and actively evolving stage, and many clinical decisions are guided by emerging evidence and expert consensus rather than established protocols.

This is also an area where patient participation in research studies can contribute meaningfully. Several studies currently enrolling have a specific genetic focus, including programs offering free genetic testing and counseling for people with Parkinson’s disease and clinical trials targeting specific genetic subtypes of PD.

What does a neurogenetics consultation involve?

A neurogenetics consultation typically begins with a detailed review of your personal and family medical history, with a focus on neurological diagnoses, age at onset, symptom progression, and any prior testing. Your genetic counselor will discuss whether a genetic contribution is likely, what testing might be informative, and what different results would mean for you and your family.

Predictive genetic testing — testing before symptoms appear in someone who may have inherited a gene variant — deserves particular thought and preparation, especially for conditions like HD and early-onset AD where a positive result carries significant psychological weight and few or no medical interventions are currently available. A genetic counselor can help you think through these considerations at your own pace, without pressure.

If you have already had genetic testing — through a neurologist, a research study, or a direct-to-consumer kit — a genetic counselor can review your results and help you understand what they do and don’t mean for your health and your family’s health.