GRAPEVINE, TEX. – A tiered diagnostic work-up can double the rate of diagnosis of the syndromes and conditions associated with early-childhood autism, G. Bradley Schaefer, M.D., reported at a meeting sponsored by the American College of Medical Genetics.
The reported incidence of autism has increased fourfold, to 4–5 per 1,000, said Dr. Schaefer, professor of pediatrics at the University of Nebraska, Omaha.
Despite this dramatic increase, only about 20% of patients are now identified with a known syndrome or condition as the underlying cause of the autism, he said.
But that can be increased to 40% of patients if a tiered system of diagnosis is used, he said. His group applied the diagnostic system to all children with autism in University of Nebraska clinics over a 3-year period.
“All patients with autism should see a geneticist,” Dr. Schaefer said. “Families need and want to know why the autism occurred and the risk of recurrence. Diagnosing the condition also has implications for outcome and long-term treatment.”
What is known is that autism is four times more common in males than females, and the likelihood of recurrence within a family depends on the sex of the autistic child. In a family with an autistic girl, there is a 4% chance of autism in a second child. If the affected child is a boy, there is a 7% chance of recurrence. If two children are affected, the recurrence rate is 25%. “There are different genes associated with autism,” he said. “But with some of the newer genetic tests developed in the past 5 years, the diagnosis of the causative syndromes and conditions is increasing.”
The initial evaluation to identify autism should include a dysmorphologic examination, including a Wood's-lamp evaluation and, if autism is suspected, targeted testing. There should be a standard metabolic screening, sensory screening, EEG, and, if clinical indicators are present, a screening for toxoplasmosis, rubella, Cytomegalovirus, and herpes (TORCH) titers, which detects congenital infections–particularly fetal rubella.
If the underlying condition or syndrome is not detected, then testing for prometaphase chromosomes and fragile X syndrome, as well as a brain MRI, should be done.
The third tier comprises MECP2 gene testing; 15-interphase fluorescence in situ hybridization (FISH); 15-methylation/FISH for Prader-Willi, Angelman's, and other syndromes; 17q FISH for Smith-Magenis syndrome; serum and urine uric-acid tests; and a subtelomeric FISH panel if the IQ is below 50.
The fourth tier is less clear and includes metabolic tests that are sometimes unavailable, he said, adding that the tests are of unclear utility but can increase the diagnosis rate.
The final tier includes subtelomeric FISH; comparative genomic hybridization; screening for folate-sensitive fragile sites, 7-dehydrocholesterol, and the UBE3A gene; and an extended metabolic work-up. If testing is done beyond the initial examination, the rate of identification doubles, he said.
“It's exciting to know that we are better at figuring out the causes of autism,” Dr. Schaefer said. “This can have an effect on the long-term outcome of the patient and set the stage for future treatments.”