The Clinicians Approach to Genetic Testing for Autistic Children

Bruce Buehler, MD, Pediatrics, General, 07:43PM Jul 25, 2010

The incidence of Autism is estimated at 1/100 children by the CDC. Often, families with children who are speech delayed, inattentive, or motorically delayed will search the internet or ask teachers about what might be wrong. Autism is often considered. The family usually seeks a diagnosis from their clinician, asking whether it is Autism.

The broad criteria are:
1. qualitative impairment in social interaction
2. qualitative impairments in communication
3. restricted repetitive and stereotyped patterns of behavior,interests, and activities ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). Washington DC: American Psychiatric Association; 2000:75.)

If the clinician feels the child fits criteria for Autism Spectrum Disorder (ASD), or the child has had psychological testing suggesting Autism, should there be further work up before referral to the schools for interventions? This is an individual decision by the clinician. If testing is indicated, a basic guideline for laboratory studies was proposed by Mendelsohn and Schaefer, Genetic Evaluation of Autism, Seminars in Pediatric Neurology, Volume 15, Issue 1, March 2008, Pages 27-31, Advances in Clinical Genetics (Part III).

In our clinic we have developed a limited approach for initial screening of children with ASD that can be used by the clinician prior to referral for a more extensive developmental or genetic evaluation.
It is our experience that this approach will identify a specific genetic syndrome or abnormality in a percentage of patients brought in by the family for Autism. After initial examination, the child with dysmorphic features or neurologic findings who meets the criteria for Autism Spectrum Disorder will yield the highest percentage, approximately 20% positive tests. Whereas the child without any physical anomalies or neurologic findings will rarely show positive results on this screen.

The tests recommended are Microarray, Fragile X, methylation of Chromosome 15, and MECP2 in females. Microarray will identify small deletions or duplications including Chromosome 16 that cause a condition with Autistic behavior. Fragile X accounts for approximately 10% of males and females with Autistic behavior. Methylation of Chromosome 15 will identify Angelman's Syndrome. MECP2 will diagnose approximately 50% of girls with Retts Syndrome. MRI can be considered if there are significant neurologic findings, including a history of unexplained seizures. If these tests are negative then it is appropriate to refer to a Developmental Pediatrician or Geneticist for further evaluation. Metabolic testing and specific gene tests are very complicated and have a lower yield. Having a specific syndrome or laboratory diagnosis aids in intervention and type of treatment for that child. It also provides information necessary to families for support, prognosis, and risk to future children.

If the evaluation suggests Autism Spectrum Disorder or Autistic behaviors, referral to the schools should be initiated for further educational testing and services. School referral should be made even if the laboratory testing is negative. Early intervention and treatment programs for Autism are most successful when initiated before 2 years of age. .