Genetics play an important role in autism. Twin studies suggest that the heritability of autism falls in the range of 36 to 95%. Similarly striking is the fact that the risk of having a child with autism increases significantly if there is already an affected child in the family. It is therefore not surprising that approximately 10-20% of autistic children may have an identifiable genetic defect. In only a minority of these individuals, about 3%, the abnormality follows a Mendelian inheritance, i.e., a single gene is affected like in Rett syndrome or Tuberous Sclerosis Complex. In the vast majority of cases (80-85%) the genetic landscape follows a complex or multifactorial inheritance that involves both genes and environmental factors (see Figure). The question therefore arises as to when is it appropriate to refer an autistic patient for genetic evaluation?
According to a study by Schaefer and Mendelsohn, 2008) “The rationale for a clinical genetics evaluation for persons with ASDs has been questioned by some. Concerns have been expressed over the high cost of such an evaluation coupled with the fact that the information obtained typically will not change interventions for the patient. The rationale for performing a clinical genetics consultation for a patient with an ASD is clear to the clinical geneticist. Clinical geneticists can contribute to the process by examining and evaluating the patient, the parents, and siblings in order to establish an etiology. A definitive diagnosis helps the patient acquire needed services, and is helpful in many other ways for the family. Many families are greatly empowered by knowledge of the underlying cause of a relative’s disorder. Depending on the etiology, associated medical risks may be identified that lead to screening and the potential for prevention of morbidity. Specific recurrence risk counseling—beyond general multifactorial information—can be provided, and targeted testing of at risk family members can be offered. In a limited number of cases (e.g., metabolic disorders) targeted therapies may be or become available.”
I believe that all patients with medically diagnosed (as opposed to self-diagnosed) autism spectrum disorders should have a consultation with a medical geneticist, more so, if any of the following red flags are present:
Presentation of the condition: Is there an earlier age of onset or happens in the less-often affected sex (female)? Is there evidence of neurodevelopmental delay including; global speech and language, cognition, social, motor, or activities of daily living?
Family problems: Are there concerns about disease in the family? Any early disease, death or disability in the family? Are there multiple affected family members? Is there a close biological relationship between the parents (consanguinity)? Have there been problems with reproduction? Are there other risk genes or nonmedical conditions that run in the family?
Physical Examination: Is there a disorder of growth, a trend over time for short stature, somatic overgrowth, or excessive growth velocity? Are there abnormalities in the form/structure of body parts (3 or more of these may point towards a syndrome)?
Suggestive evidence of a disorder of metabolism: Does the patient complains of altered consciousness, early onset of symptoms, unusual odors, recurrent pain, unusual muscle tone, movement disorder, areflexia, decreased muscle mass, cataracts, coarse facial features, joint abnormalities, or skin/hair abnormalities?
A properly conducted genetic evaluation, usually collected from checklists, will provide valuable information to the patient and his/her family. The clinical history will be extensive including prenatal, perinatal, neonatal, infancy, childhood, and aspects of motor and social development. It will also cover the history of first, second and third degree relatives, and graphic depiction of pedigree including specific disorders relevant to presenting symptoms throughout multiple generations. For more information on the family history and pedigree aspect of genetic testing please see Saul et al., 2017.
Approximately 20% of infant deaths are due to genetic causes and 71% of pediatric-in-patients present with a significant genetic component. These conditions are extremely common, primarily so in autism where proper evaluation yield significant findings over 50% of the time. The information gained is of value for proper diagnosis, specific management, anticipatory guidance and as a means to expand our knowledge of risk factors. The high prevalence of genetic disorders in autism is an argument against neurodiversity proponents claiming autism as the result of “normal” variability in the human genome. For those interested in more information related to this subject I have written several blogs on autism-related syndromes caused by genetic defects:
Dravet Syndrome: Lessons in Regressive Autism http://bit.ly/2lurRrP
The Smith-Leml-Opitz Syndrome and Autism http://bit.ly/2m2B7Gy
Tuberous Sclerosis and Autism http://bit.ly/2lk3TP0
Ehlers-Danlos Syndrome and Autism http://bit.ly/2j5sSop
The Rare Urbach-Wiethe Disease and Autism http://bit.ly/2lPtPW6
Saul RA, Trotter T, Sease K, Tarini B. Survey of family history taking and genetic testing in pediatric practice. J Community Genet, 2017 (Epub ahead of print) doi: 10.117/s12687-016-0291-3.
Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med 10(4):301-305, 2008.