The human embryo develops three basic germ layers, which each give rise to various and occasionally overlapping structures. This is known as the Germ Layer Theory, originally proposed by Karl von Baer.
Until more recently, it was believed that the mesodermal layer (see image below) was the only layer from which skeletal and connective tissues arose. It wasn’t until the latter part of the 20th century that it was realized that most of the bones of the skull, including the face, were actually derived from the neural crest, a portion of tissue located in the ectoderm that also gives rise to the nervous system, melanocytes (pigment cells), and some skin cells.
We have known for some time that tight links exist between the development of the brain and the formation of the face and skull. Not only are these two systems derived from similar groups of neural crest progenitor cells, but they also appear to be in constant crosstalk with one another during early development, likely sharing and responding to many of the same gene products due to their shared parentage. Therefore, it’s interesting though unsurprising to find many individuals with various neurodevelopmental conditions who share craniofacial dysmorphism (malformation of the skull/face) as a related feature.
Autism is no exception. Of course, there are many genetic syndromes that have autism as a primary or secondary feature that exhibit facial malformations. Individuals Fragile X, for instance, often have characteristic facial features such as macrocephaly, a large forehead, long face, prominent jaw, and large ears.
A boy with Fragile X Syndrome.
Individuals with Smith-Magenis Syndrome, another condition that often has autism as a secondary feature, likewise have particular facial characteristics, including a broad face, underdevelopment of the midface giving the cheeks and eyes a sunken flat appearance, a broad nasal bridge, and a downturned mouth.
A young man with Smith-Magenis Syndrome.
As a final autism-related example, people with Pitt-Hopkins Syndrome tend to have multiple facial anomalies, including a square forehead, a protruding lower face, broad nasal bridge, flaring nostrils, and a wide open mouth.
Two individuals with Pitt-Hopkins Syndrome, from youth to adulthood.
Each of these are somewhat extreme examples of craniofacial dysmorphism, most likely due to the fact that they’re caused by rare mutations that have serious consequences for tissue development, including the brain, when they do occur. Most of these individuals tend to have varying degrees of intellectual disability alongside their other features.
But what about autism that isn’t due to highly detrimental rare mutations? Do they show facial dysmorphisms as well?
According to Aldridge et al. (2011), some subgroups in idiopathic autism (as it’s currently known) do actually show distinctive facial characteristics that vary from control groups, though the features may be comparatively more subtle requiring the assistance of technology. While a large portion of kids in the Alridge et al. study didn’t appear to differ from controls, two autism subgroups did emerge, which together comprised about 1/3rd of the larger group.
The first autism subgroup (Subgroup 1) shown above, which made up about 19% of the group, exhibited increased distances (in black) between numerous landmarks between the eyes, nose, and mouth, with a decreased distance between landmarks along the mouth itself ranging down to the chin (white). These boys tended to be more severely affected, with fewer instances of Asperger’s Syndrome and macrocephaly in the group.
Meanwhile, boys in Subgroup 2 (~9%) tended to show decreased inter-landmark distances surrounding the orbital and nasal regions and increases in the length of the upper lip. In contrast to the first subgroup, this second subgroup had lower severity scores, more instances of Asperger’s Syndrome, and more occurrences of macrocephaly.
This study suggests that, while not all individuals with autism exhibit measurable facial dysmorphism, significant subgroups do– subgroups which tend to occupy the two extremes of functioning. Since all the boys participating in this study had to be capable of a certain level of self-restraint in order to sit still long enough to have their pictures taken, one can assume that the lower functioning ranges of autism were not well-represented in this study.
However, the fact that two separate subgroups emerged, reflecting not only a divergence in facial features but also levels of functioning, it may suggest different but overlapping causes to their respective autisms, in terms of genetic and environmental factors. These two subgroups may in fact be two different types of autism, etiologically.