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.