Is PANDAS Hereditary or Genetic?
Research and studies show a strong link between PANDAS/PANS and genetic or hereditary factors. While researchers haven’t found any one specific gene directly linked to the diseases, there are several family factors that may provide insight into an affected child’s symptoms and reactions.
PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) are difficult and debilitating diseases that typically affect children from around the age of three through puberty. They usually occur after a strep infection and cause children to show sudden and intense psychiatric or autoimmune symptoms. An affected child can have an unexpected and dramatic change in personality. They have symptoms that resemble obsessive-compulsive disorder (OCD), anxiety and depression. These personality changes often coincide with the development of tics or other abnormal movements, decline in math and handwriting abilities, sensory sensitivities, restrictive eating and more.
It can be frustrating to get a PANDAS/PANS diagnosis because there is no 100% definitive test for the disease. Typically doctors reach a clinical diagnosis based on a collection of different signs, symptoms, medical history and laboratory findings that cannot be explained by another medical condition. But knowledge is powerful. By researching what PANDAS is and what a typical case looks like, parents can find valuable information to get quick and effective treatment. It can also help to know how certain biological markersand family medical history can aid in a diagnosis.
Knowing what to look for in your family’s medical history can offer a better understanding of the unique symptoms related to PANDAS. A diagnosis can be life-changing for a child. Researchers have found that with an accurate diagnosis, doctors can treat and even reverse PANDAS.
How common is PANDAS?
PANDAS/PANS is estimated to affect 1 in 200 children. However, it is often misdiagnosed or missed entirely. This is because many assume there is no underlying link for the patient’s psychiatric symptoms. It is true there is currently little research on the immune or molecular causes of the disease. But PANDAS Network has built relationships with the leading researchers in the field. This includes Dr. Madeleine Cunningham, immunology and strep expert at the University of Oklahoma; Dr. Dritan Agalliu, neuroscience expert at Columbia University; and Dr. Fabienne Brilot and Dr. Russell Dale, neuroscience experts from the University of Sydney-Australia. These experts have been working for years to find links to a potential genetic predisposition for PANDAS/PANS that environmental stressors may trigger.
Discovering a hereditary link to PANDAS/PANS can offer more relief to families struggling to diagnose and treat this illness.
Current studies on PANDAS/PANS familial genetics
Research has shown that a history of certain medical conditions in family members, specifically mothers and siblings, may indicate a higher risk for PANDAS/PANS.
A Stanford study published in 2015 outlines in detail the neurologic diseases, psychiatric disorders, autoimmune and autoinflammatory diseases, immunodeficiency syndromes and frequent infections (including recurrent streptococcal pharyngitis) that should be considered when tracing family history in relations to PANDAS/PANS.
There is a long list of diseases with potential links to PANDAS/PANS. But there are three main types of conditions that may indicate a predisposition to developing symptoms. You may want to consider the possibility of a PANDAS/PANS diagnosis if your family has a history of:
- Autoimmune diseases
- Immune deficiency (achy joints [EDS] or frequent illnesses as a child)
- Mental health conditions
Autoimmune diseases
A study conducted by Fabienne Brilot found evidence of an autoimmune response attacking the Dopamine-2-receptor (D2R) in one PANDAS patient. When the D2R’s are attacked, the area of the brain that controls motor function and behavior is impacted. Dopamine is a powerful neurotransmitter that regulates mood and movement and it is widely studied in neuropsychiatry. This likely accounts for the decreased writing ability, tics, OCD, extreme anger and other symptoms experienced by children with PANDAS.
Researchers also found evidence of anti-D2R autoantibodies in patients with Sydenham’s chorea (a strep-related neurological disorder), Tourette’s syndrome and other movement disorders. Essentially, the body triggers an autoimmune response, attacking the dopamine receptors required to function normally. The appearance of genetically driven variants of these autoantibodies on the patient’s immune cells suggests that some people have a higher affinity for D2R. This reinforces the idea that PANDAS/PANS has a genetic or hereditary component.
In the case of Sydenham’s chorea (a variant of PANDAS), doctors can find the D2 antibody in a blood test. But only Oxford University in England currently uses this test. PANDAS patients have not received this test, which is why Cunningham created an alternative test. This test is also not widely received at this time, mostly because this is a rare disorder. You can read more about how the Cunningham Panel works and what it tests for.
A 2020 study found that patients with PANS had a high rate of arthritis (38.8%), blood dyscrasias (e.g., leukopenia, lymphopenia), elevated levels of auto-antibodies (10-20%) and other autoimmune diseases like psoriasis, celiac disease and thyroiditis (17.3%). Dr. Jenny Frankovich (Rheumatology, Stanford University) has published several papers that show PANDAS is autoimmune in nature. But there is still no specific test to prove this yet. However, it does explain why and how IVIG and other autoimmune treatments usually help patients.
These studies continue to lead researchers to believe that PANDAS/PANS are autoimmune diseases. Studying genetic links in each patient can continue to confirm this as well as leading to faster diagnoses.
Immune deficiency
Studies also found of the patients who meet PANDAS diagnosis criteria, their siblings and parents reported more immune-mediated diseases than healthy controls. In one report, first-degree relatives of children with PANDAS were noted to have increased rates of OCD, tic disorders and acute rheumatic fever. This suggests that the children inherited a specific vulnerability to nonpyogenic poststreptococcal sequelae. In other words, they are more susceptible non-strep bacteria illnesses. This is why the term PANS exists, because other infections appear to occasionally create this psychiatric onset.
Mental health conditions
Psychiatric family history may provide important clues about genetic susceptibilities to OCD, anxiety or mood disorders, ADHD, and pervasive developmental disorder (PDD) in children diagnosed with PANDAS.
A National Institute for Mental Health (NIMH) study found a 10-fold increase in rates of OCD and tic disorders among first-degree relatives of PANDAS probands (the first person in the family diagnosed with PANDA/PANS). Neuropsychiatric disorders among siblings are also particularly common and important to assess for in children affected by PANDAS/PANS.
Two New Studies: Is there a common genetic link to PANDAS/PANS?
The consensus is that PANDAS/PANS likely has a genetic or hereditary link. But researchers also agree that there is no one gene that causes these diseases. The genes are heterogenous, or largely varied in nature. In a European study of 386 children (133 of which were siblings), researchers found more than 10 heterogeneous genes. This means PANDAS/PANS activates differently in each person’s immune system even though it usually links back to an autoimmune reaction.
This European study suggests the genes were all found to be highly expressed in the enteric (intestines) nervous system and in the choroid plexus (part of the central nervous system) and brain vasculature. These findings suggest that these genes might contribute to a breach in the blood-brain barrier (BBB). The breach essentially allows autoantibodies and other inflammatory agents into the brain. This could be what causes the reactions and symptoms experienced by many PANDAS/PANS patients.
The conclusion of this study finds that PANS is a genetically heterogeneous condition (involving many different genes). Researchers concluded it can either be a stand-alone neuropsychiatric condition or a condition combined with other neurodevelopmental disorders.
A second study of 70 children divided into groups of PANDAS, PANS and Sydenham Chorea found unusual genetic variants in five different genes. These genes regulate t-cell (immune) function and microglia (regulators of the central nervous system). This study, titled The Role of Adaptive Immunity and Genetic Risk Factors in Vascular and Neuronal Dysfunction in Post-Infectious Autoimmune Encephalitis, will be published in 2022 by Columbia University and Children’s Hospital Pennsylvania. Listen to a 10 minute lecture by Dr. Agalliu (at 37 minutes) where he describes this important new work.
Where do you go from here?
Thanks to some of the current and ongoing research above, you may have one more reason to consider PANDAS/PANS as a diagnosis for your child: family history and genetics. Take the time to look into your family’s medical history to find any potential established links to PANDAS/PANS. Also take time to review the common symptoms and potential biological markers for PANDAS. Then use this research and information to discuss a possible PANDAS diagnosis with your child’s physician.
While finally getting a diagnosis can be a huge relief, it is also just the beginning of you and your child’s journey with PANDAS/PANS. PANDAS Network remains dedicated to offering support throughout this process by providing resources and information on how to find the right doctor and what to do after a diagnosis.
