New approach to genetic diagnosis in autism

A practical, stepwise approach to diagnosing genetic causes of autism and related disorders is proposed in the January issue of Genetics in Medicine, official journal of the American College of Medical Genetics (ACMG), published by Lippincott Williams & Wilkins.

The three-tiered approach will yield a specific genetic diagnosis in approximately 40 percent of patients with autism-spectrum disorders, according to the report. The new approach was developed, based on the best available research evidence, by Drs. G. Bradley Schafer of University of Nebraska and Nancy J. Mendelsohn of Children's Hospitals and Clinics of Minnesota.

The number of patients diagnosed with autism-spectrum disorders - including "classic" autism as well as related disorders such as Asperger's syndrome and Rett syndrome - has increased dramatically in recent years. Despite strong evidence that autism is primarily a genetic disorder, diagnosis is still based mainly on behavioral factors. Clinical geneticists are challenged to provide the best possible genetic diagnosis and counseling services for patients and families affected by autism, even as research knowledge of the causes of autism - genetic and otherwise - continues to increase.

"For many practical reasons, a stepwise (tiered) evaluation is the preferred approach - rather than performing a 'shotgun' evaluation in which dozens of tests are ordered as a matter of routine," Drs. Schafer and Mendelsohn write. "In our experience, this approach has a high level of acceptance with third-party payers and with families."

The essential first step - before any genetic tests are done - is pre-evaluation by a professional trained in autism diagnosis, including strict criteria and objective assessments. The examination should also include hearing tests, as children with hearing loss are sometimes mistakenly diagnosed with autism. Tests of cognitive (intellectual) function are recommended as well. While reduced cognitive ability can be part of autism, it is also true patients with severe cognitive impairment can have autistic-like symptoms.

The first tier of genetic evaluation includes tests that should be performed in nearly all children with no obvious cause of autism. For example, chromosome tests may identify fragile X syndrome[COMMENT] - a common cause of inherited mental impairment that may be accompanied by autistic symptoms. Testing for certain metabolic disorders or for rubella infection may pinpoint a specific cause of autism. If one of these causes is identified, no further genetic testing is needed, and patient/family counseling can begin.

If not, testing enters the second tier, including tests for specific gene mutations known to cause autism. The choice of tests may be guided by certain clinical characteristics. For example, autism in girls has been linked to mutations of a gene called MECP, while autism accompanied by abnormal head size may be related to mutations of the PTEN gene.

If necessary, testing proceeds to the third tier, possibly including a magnetic resonance imagine (MRI) scan of the brain. (Some doctors may recommend MRI scanning earlier in the testing process.) Even if the MRI scan doesn't show any specific cause of autism, it may still provide useful information for doctors and parents. Tests for other possible genetic causes may also be done, although the value of these tests is so far unclear.

Drs. Schaefer and Mendelsohn estimate that their structured approach would lead to a diagnosis in approximately 40 percent of patients with autism. This is substantially higher than the current 15 percent diagnosis rate, based on clinical genetic evaluation.

Insurers and others might question the cost-effectiveness of genetic testing for autism - especially since, in many cases, identifying a specific cause won't have a major impact on patient management. However, Drs. Schaefer and Mendelsohn believe their approach to genetic diagnosis will have major benefits for families affected by autism. For some families, the results will provide important information on the risk of autism in future children.

For others, there is a clear benefit to knowing the cause of their child's condition. Discovering the correct diagnosis allows families to stop the 'diagnostic odyssey,' in which the child continues to go to multiple doctors getting un-needed and expensive tests. "It is our contention that all patients with autism should be offered a thorough diagnostic evaluation," Drs. Schaefer and Mendelsohn conclude.

About the American College of Medical Genetics
Founded in 1991, the ACMG ( provides education, resources and a voice for the medical genetics profession. To make genetic services available to and improve the health of the public, the ACMG promotes the development and implementation of methods to diagnose, treat and prevent genetic disease. Members include biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors, and other health care professionals committed to the practice of medical genetics. Genetics in Medicine, now published monthly, is the official journal of the ACMG.

About Lippincott Williams & Wilkins
Wolters Kluwer Health (Conshohocken, PA), a division of Wolters Kluwer, is a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry. Major brands include traditional publishers of medical and drug reference tools and textbooks, such as Lippincott Williams & Wilkins and Facts & Comparisons; electronic information providers, such as Ovid Technologies, Medi-Span and ProVation; and pharmaceutical information providers Adis International and Source®. For more information, visit


On Feb 7, 2008 your column "New Approaches to genetic diagnosis in autism" summarizes an article from the January 2008 issue of "Genetics in Medicine" titled "Genetic evaluation for the etiologic diagnosis of autism spectrum disorders". We are pleased that genetic diagnosis in autism is receiving much attention. However, it is very important that the correct genetic tests are ordered in the evaluation of autism.

In paragraph 5. line 2 of your column, you state "for example, chromosomal tests may identify fragile X syndrome …". Fragile X syndrome is diagnosed by a specific DNA test, the FMR1 test, and not by chromosome analysis. In fact, individuals with fragile X are occasionally not diagnosed because a chromosome test, not a DNA test was ordered. If you note in table 4 of the original article the recommendation is for "DNA for fragile X", not chromosomal studies. These are different tests, which require different tubes, technology and are often performed at different labs.

Liane J. Abrams, M.S. C.G.C - [[email protected]]
Board Certified Genetic Counselor
Genetic Specialist
National Fragile X Foundation
PO Box 190488
San Francisco, CA 94119


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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