AUTISM & GENETICS

How Your Child Might Benefit From Testing

Richard G. Boles, M.D.

Below is a summary of an article that was written by Dr. Richard G. Boles and published in AUTISM ADVOCATE Parenting Magazine. Access the full article at AUTISM ADVOCATE Parenting Magazine here.

Autism Spectrum Disorder and Genetics

Autism is a common condition that is defined based on behavioral observation. In essence, the term “autism” is applied when there is substantial impairment in social communication with onset in early childhood.  Intelligence can be low, normal or high, as long as social communication skills fall far below that of other cognitive, or thinking skills. Specific behavioral criteria are used to determine the presence or absence of the diagnosis, regardless of the underlying biology. Thus defined, and given the incredible complexity of the human brain, it is not surprising that hundreds of known factors can result in autism. In this regard, autism is not an exception since many other common brain disorders, including migraine, epilepsy, schizophrenia, intellectual disability and depression, are also defined based on specific diagnostic criteria based primarily on simple observation. Indeed, multiple factors can lead to each of these conditions.

The number of children found to be affected by Autism has been expanding rapidly in recent decades. This is difficult to explain by a genetic cause alone, and there are many different theories to explain the rapid growth of the autistic population. While many believe that the increase in autism is based primarily on environmental factors (e.g., toxins, diet, immunizations), these hypotheses are not reflected in the multiple well-performed studies that demonstrate autism to be predominately genetic in cause. This dichotomy has produced a rift between the scientific community, which points to genetic factors, and the activist parent community, which points to environmental factors. If autism is genetic or “set in stone” at the time of conception and unchangeable thereafter, does that mean that any attempts at treatment are doomed to fail?  This suggestion goes against the direct observations of many families in which autistic behaviors started abruptly with an environmental stimulus, and later improved with specific treatments, which are also environmental factors. Can both the researchers and the families be correct? Yes! The solution to the dichotomy may lie in the fact that both parties underestimate, or fail to communicate, the extent to which genes are under environmental control.

Autism is, by and large, a genetic condition resulting from variants in a very large number of genes. In general, however, environmental factors often act to trigger the development of disease, while genetics determines the predisposed population at risk.

Autism and Genetic Variation

An important minority of individuals with autism appear to have monogenic “cause” of disease related to a single variant (or pair of variants) in a single gene. These disease-causing variants used to be called “mutations,” but this word is now considered pejorative. There are many models to show how a gene can result in autism, and some of the more important ways are summarized here. Most commonly, monogenic autism-related variants are “heterozygous,” meaning that a single variant is sufficient to result in disease. Since it is uncommon that either parent has a full case of autism, these variants are generally not present in either parent, but the result of new genetic changes that only affect that one individual. New genetic variants (referred to as “de novo”) are quite common in autism. They are identified as likely the primary cause of disease in approximately one-third of all cases, in my experience. In order to detect most de novo variants, “trio” sequencing of the patient and both parents is required.

Monogenic autism can also be the result of a single disease-related variant on the X-chromosome in males, who have only one X-chromosome inherited from the mother and one Y-chromosome inherited from the father. This X-chromosome variant can be new, inherited from a mother who is mildly affected or from an asymptomatic mother as females have two X-chromosomes, one from each parent. Another form of monogenic autism is autosomal recessive inheritance, in which the child inherited a disease-causing variant in a gene, which can be the same or different variant(s), from both parents. The parents, with one disease-causing variant each, are generally asymptomatic “carriers.”

The most common model for how genes lead to autism is polygenic, with the child inheriting autism risk variants from both parents. The parents, as well as siblings and other relatives, obviously carry at least some of these genes, and may also be affected with autism, mildly affected with social issues, ADHD or a learning disability, or completely unaffected and neurotypical.

The Benefits of Genetic Testing

The scientific literature reveals that WES, with all of the different testing components discussed above (CMA, mtDNA, TNR), identifies a diagnosis in about 50 percent of cases.8 It is worth noting that the studies that this number is based on are dated. In my informal review of my own patients, the figure is closer to 75 to 80 percent with WGS. Like neurodevelopmental disorders in general, autism is a wide spectrum that can range from isolated mild social awkwardness or ADHD to severe intellectual disability, absent speech and social engagement, and multiple additional features of brain dysfunction, such as epilepsy. As expected, genetic diagnoses are more likely on the severe end of the spectrum.

In addition, monogenic and de novo findings are more common as one moves towards the severe end. However, diagnoses and successful treatment options are not uncommon even on the mild side of the spectrum. In my own practice, I recommend DNA sequencing in all autism cases.

In many cases with autism, multiple genes are involved. Thus, a singular “cause” cannot be identified as one does not exist. Genetic testing in this setting is aimed at identifying risk factors for disease, with the hope that at least one will be treatable.  Learn more about WES and WGS genetic testing, limitations, and costs by clicking here.

Treatment Approaches in Autism

Oftentimes, WES/WGS provides specific genetic information regarding the genetic component(s) in an individual patient that allows for personalized medical therapy.  However, there are pathways leading to disease that are common to many patients with autism that can be utilized while genetic testing is pending, or if such testing is not feasible.

Multiple research studies have demonstrated that there is a component of mitochondrial dysfunction (abnormal energy metabolism) in many, if not most, cases of autism (Frye and Rossignol). Mitochondria are structures within virtually all human cells that produce 90 percent of the energy needed for biological functions. I have found that most people with autism benefit from mitochondrial-targeted therapies. These are aimed at increasing cellular energy and at detoxifying mitochondria that are dysfunctional through measures such as reducing reactive oxygen species.

“Mitochondrial cocktail” refers to a combined nutritional support, including vitamins, minerals and cofactors, to achieve those aims, and generally consists of about 10 to 30 different components. The data supporting nutritional support in autism are strongest for the following nutrients: carnitine, coenzyme Q10, magnesium, pyridoxine (vitamin B6), folate (vitamin B9), cobalamin (vitamin B12), and vitamin D3. These nutrients are common constituents of a mitochondrial cocktail. A positive response to a mitochondrial cocktail appears to be somewhat independent of the genetic findings in an individual patient since mitochondrial dysfunction appears to be a common phenomenon for autism in general.

Conclusion

It is clear that children with autism spectrum disorder often can benefit from genetic testing. Such testing may lead knowledgeable medical professionals to treatment options that improve behavior, social and communication issues, as well as associated problems such as pain, gastrointestinal symptoms and fatigue. As I have indicated, the preferred test is whole genome sequencing (WGS) for a patient with autism and both parents, referred to as a “trio.” Dietary supplements can also have a significant impact on autism. The bottom line is there are steps you can take to help your child and work towards real improvement.

Access the full article at AUTISM ADVOCATE Parenting Magazine here.

Disclosure: Dr. Boles is the Chief Medical & Scientific Officer for NeuroNeeds LLC, the start-up company that makes SpectrumNeeds®, QNeeds®, and CalmNeeds®.  You are under no obligation to purchase this or any products, whether recommended by Dr. Boles or another health care provider. As always, it is recommended that you contact your physician regarding these products and all other changes to disease management.

The Content within this article and NeuroNews Blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this Blog.

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