Dysmorphology

David W. Smith, a pediatrician and clinical geneticist, coined the term dysmorphology in the 1960s and played a major role in the development of this specialized area of study, which is devoted to discovering the pathogenesis of human birth defects. His work in the field of dysmorphology was instrumental in sorting out the many different causes of cognitive disability.

Because physical anomalies are indicators of errors that occur during embryologic development, their study enhances understanding of both genetic and teratogenic insults to human morphogenesis. The recognition of new syndromes, based on their specific physical features, led to the identification of the causative genes, discoveries of the mechanisms by which those genes cause the disorders, and the role they play in normal embryogenesis.

The role of dysmorphology in characterizing hundreds of syndromes associated with cognitive disability suggests that it may also be a useful tool to help clarify the heterogeneity (single disorder with many causes) within autism.

Physical anomalies or malformations are classified as major or minor. Major malformations occur infrequently, affect a medically important structure such as the heart, kidneys or palate, and inflict a significant medical burden. Minor malformations, on the other hand, occur frequently in populations and have no serious medical consequence. But taken together, minor malformations can serve as indicators of altered morphogenesis that occurred early in gestation.

Common examples of minor anomalies include flat philtrum, thin upper lip, abnormal nails and single palmar crease. A dysmorphology examination consists of a careful examination by an individual trained in the recognition of alterations in physical structures and their interpretation including conclusions on their cause, timing, embryologic basis, medical and diagnostic significance.

Relevance to autism:

A number of studies in the 1970s and 80s reported that children with autism have physical features outside the norm^{1,2,3,4,5,6,7}. More recent studies have also found that children with autism are more likely to have minor anomalies than normal or sibling controls⁸,⁹. Although it has been concluded from these reports that children with autism often have minor anomalies, similar findings in children with psychiatric disorders and learning disabilities indicate that the presence of minor physical anomalies is neither specific nor sensitive to the autism diagnosis.

Recently there has been a renewed interest in physical features in autism, with the expectation that they might function as biomarkers with which to subdivide individuals with the disorder into groups for genetic studies. A 2000 study noted that about 20 percent of children with autism have a significant number of physical anomalies consistent with abnormal embryologic development¹⁰. Subsequently, the same researchers described the natural subdivision of the autism spectrum disorders into two groups, complex and essential autism¹¹.

Complex autism is defined by the presence of a significant number of physical anomalies or microcephaly (head circumference less than two standard deviations from the mean), whereas in the essential autism group there is no evidence of abnormal morphogenesis. The essential and complex subgroups appear to be etiologically distinct and differ in their outcomes, recurrence risks, sex ratios and family histories.

The distinction between complex and essential autism is recommended as a necessary first step when working to subdivide autism into causally homogeneous subgroups. Definition of homogeneous subgroups within the autism diagnosis is useful in both clinical care and to advance autism research. Clinically, defining homogeneous autism subgroups is the key to more accurate prognosis, genetic counseling and the development of more effective subgroup-specific treatments. Researchers need ways of selecting homogeneous subsets of autism for study, in order to successfully identify specific causes, biomarkers for early identification and, eventually, cures.

Autism dysmorphology measure:

The Autism Dysmorphology Measure is a measure of generalized dysmorphology developed by Judith Miles, a pediatrician, medical geneticist and dysmorphologist. The ADM, which is used to classify individuals with autism as non-dysmorphic or dysmorphic, assesses the physical structure of 12 body parts¹². It was created in response to a need for a dysmorphology measure that could be completed by clinicians not extensively trained in dysmorphology that would still retain a high level of sensitivity and specificity.

The measure is intended to complement general medical examination and enhance the detection of known causes of autism, such as chromosome disorders, Timothy syndrome, Cornelia de Lange syndrome and other autism disorders associated with abnormal embryogenesis.

Computerized dysmorphology:

A recent adjunct to the standard dysmorphology examination is the computerized assessment of the size and shapes of physical features. Three-dimensional (3D) facial pictures, taken in less than a second with a commercially available 3D imaging system are digitally presented for analysis. Facial landmarks are accurately placed and hundreds of precise facial measurements are generated for analysis using dedicated computer software.

The 3D imaging is used primarily in autism research, where it has provided quantitative facial analysis suggesting the presence of a number of facial phenotypes with specific clinical and behavioral correlates¹³. The 3dMD system is routinely available for clinical use in surgical suites, indicating that this research tool may soon be added to the clinical dysmorphology toolbox.