Examining Minor Physical Anomalies in Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD): A Twin Study

Background:  Minor physical anomalies (MPAs) represent subtle anatomical deviations in one’s appearance such as low-set ears, widely spaced eyes, and a short neck. MPAs may suggest some type of abnormal development that occurred in the early embryogenic or fetal periods. MPAs have been shown to be more common in individuals with ASD and ADHD. Further studies are needed, especially with a well-controlled genetic background, to examine this relationship in children and young adults with ASD and ADHD.

Objectives: To describe the findings from clinical morphology exams on monozygotic (MZ) and dizygotic (DZ) twins to identify MPAs in children and young adults with ASD and ADHD, with a special focus on differences in the number of MPAs based on the presence of a diagnosis, the most common MPAs in participants with ASD or ADHD, differences in MPAs in highly discordant pairs, and the relationship between MPAs in twin pairs based on zygosity.

Methods: Clinical morphology exams to identify the presence of MPAs were conducted on 120 individuals representing 51 MZ pairs, 7 DZ pairs, 1 trio of triplets (MZ sisters and DZ brother), and 1 DZ twin. Two clinical geneticists utilized a checklist covering all major body systems to uniformly identify MPAs. All participants also received detailed clinical assessments, including determination of ASD and ADHD through gold standard assessments (e.g., ADOS, ADI-R, SRS, Connors-3, K-SADS, etc.). Roughly 24% of participants had a diagnosis of ASD, 28.3% had a diagnosis of ADHD, and 42.5% were typically developing (42.5%). Descriptive and correlational statistics were performed to summarize the findings from the clinical exams.

Results: The clinical exams revealed the presence of more physical anomalies in participants with ASD (median=9) and ADHD (median=7) compared to those with typical development (median=5). The most common physical anomalies in participants with ASD (n=29) and ADHD (n=34) included hypermobility (37.9% with ASD and 32.4% with ADHD) and being overweight (37.9% with ASD and 26.5% with ADHD). Comparing highly discordant pairs for ASD (i.e., MZ pairs where only one twin has ASD; n=7 pairs), scoliosis was present in the twin with ASD in two pairs. Using a correlation plot, twins who were MZ, regardless of the presence of a diagnosis, demonstrated a positive linear relationship (r_s=.883, p<.001) between the number of MPAs within each twin pair, compared to DZ twins who demonstrated a non-linear relationship (r_s=.209, p=.653), thereby, suggesting a strong genetic basis to MPAs.

Conclusions: Minor physical anomalies were present in children and young adults with ASD and ADHD in greater amounts compared to those without either disorder and appear to have a strong genetic basis when looking at the relationship in the number of MPAs within MZ and DZ twin pairs. Examination of minor physical anomalies in children and young adults with ASD and ADHD may serve as a biomarker to identify individuals with a genetic cause to ASD or ADHD and thereby, help identify potential subtypes of each disorder and/or individuals who would benefit from further testing (i.e., genetic testing).