Birth Order Effects on the Phenotypic Expression of Autism in Multiplex Families

Background:

Autism Spectrum Disorders or ASDs include autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified (PDD-NOS). ASDs are characterized by disturbances in social behavior, impaired communication and the presence of stereotyped behaviors or circumscribed interests. Most cases of ASD remain idiopathic. A few recent studies indicate that some cases may be caused by immunological abnormalities while other studies point to a strong genetic component. Whatever the cause, recent estimates indicate that ASDs are on the rise with the current prevalence reported by the CDC of 1 in every 150 births (Keuhn, 2007). Interestingly, previous studies have found birth order effects on the phenotypic expression of autism in families with more than one affected child (multiplex families; Lord, 1992; Spiker, 2001; Reichenberg, 2007). The rise in ASDs, as well as the presence of birth order effects, suggests that some cases are influenced by environmental factors.

Objectives:

Through this study, we further explore the effects of birth order on phenotypic expression of ASD in multiplex families. The examination of birth order effects on autism symptom severity may provide important clues to the etiology of ASD. For example, the demonstration of increased ASD severity in each subsequently affected birth may point towards a dosage-type effect of either genetic or environmental factors.

Methods:

We utilized pre-existing data from the Autism Genetic Resource Exchange (AGRE) consisting of test scores from children with ASD from multiplex families. ASD was determined by the Autism Diagnostic Interview-Revised (ADI-R) and/or Autism Diagnostic Observation Schedule (ADOS). Mean test scores from the Vineland Adaptive Behavior Scales (VABS), Peabody Picture Vocabulary Test (PPVT) and Ravens Colored Progressive Matrices (RCPM) were compared between first-born and later-born children with ASD. ASD children from multiplex families were also divided into first-born, second-born, and third-born groups for additional analyses. Over 1600 individuals with ASD from nearly 800 multiplex families were included in the study although data from each test was not available for each individual. It was hypothesized that the phenotypic expression of ASD would increase with each subsequently affected child within a family. Therefore, later-born children should be more severely affected and thus perform worse on cognitive tests than first-born children from multiplex families.

Results:

Results showed that there was a significant decline RCPM scores between first-born and later-born children. ANOVA revealed a significant progressive decline in these scores from first-born to third-born children with ASD. Results from the PPVT also demonstrated a significant decline in scores from first-born to later-born children. However, while the means progressively decreased from first-born to third-born children with ASD, the decrease was only significant between first-born and second-born and first-born and third-born children. Results of the VABS comparisons are also reported.

Conclusions:

The results support our hypothesis of an increase in the phenotypic expression of ASD with each subsequently affected child in multiplex families. The significant decline in test scores of cognitive ability supports the idea of a dosage-type effect in utero in some multiplex families. The dosage effect may be due to either environmental or genetic factors.