Autism spectrum disorders (ASD) are among the most common forms of severe developmental disability with a prevalence of 1 in 150 children. The inheritance pattern of ASD in most families is complex and not compatible with simple Mendelian inheritance. It may also vary according to gender and comorbidities (e.g. seizures, IQ). Recent studies have suggested disparate clinical and genetic settings depending on a simplex autism (only one affected family member) or a multiplex autism (two or more affected family members) definition.
Objectives:
This study aimed to explore whether the phenotype varies depending on the presence or absence of affected siblings.
Methods:
A total of 2,396 children (2,080 males, 316 females) from the Simons Simplex Collection (SSC) and 2,247 children (1,808 males, 439 females) from the Autism Genetic Resource Exchange (AGRE) multiplex database were examined. The SSC includes families with only one child diagnosed with ASD (simplex autism), and probands with mental age below 18 months were excluded. The AGRE includes families with two or more members diagnosed with ASD, Pervasive Developmental Disorder-Not Otherwise Specified or Asperger’s syndrome. The following variables were extracted for comparisons: the Autism Diagnostic-Interview-Revised (ADI-R) sub scores, the Vineland Adaptive Behaviors Scales (VABS), and the presence of epilepsy.
Results:
Mean VABS composite standard scores were found to be significantly lower in multiplex ASD than simplex ASD (OR=0.94; 95% confidence interval (CI):0.93-0.94). Children with multiplex ASD were also found to have more first word delay (OR=1.7, 95%CI:1.5-2.0) and a lower overall level of language (OR=2.2, 95%CI:1.9-2.4). While adjusting for adaptive level, the difference remains significant. Considering ADI-R scores, repetitive and stereotyped behavior scores were found to be significantly lower in multiplex ASD than simplex ASD (OR=0.88, 95%CI:0.85-0.9). Non-verbal communication scores were found to be significantly higher in multiplex ASD than simplex ASD (OR=1.12, 95%CI:1.09-1.15). Finally, epilepsy was more frequent in multiplex ASD than simplex ASD.
Conclusions:
Multiplex and simplex autism may be defined by a difference in phenotype severity with children with multiplex autism found to show more adaptive and language impairment, less repetitive and stereotyped behaviors, and more epilepsy.
See more of: Clinical Phenotype
See more of: Symptoms, Diagnosis & Phenotype