What we know: Phenotype

Iker Spozio


According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the core features of autism spectrum disorder (ASD) are:

“Deficits in social cognition and communication,” which manifest as difficulties in reciprocal relationships such as joint attention, eye contact, empathy and understanding the thoughts and intentions of others.

“Restricted interests and repetitive behaviors,” which manifest as inflexible adherence to purposeless routines.

Skilled clinicians can agree on quantitative measures of such behaviors. These measures are the best ‘biomarkers’ we have at present to chart progress over time and the efficacy of treatments. With current instruments, an autism diagnosis is usually made in the third year of life.

What we know

  1. Beyond the core features, individuals on the autism spectrum may exhibit one or more associated deficits that add to the heterogeneity of the clinical picture:
    1. A low nonverbal intelligence quotient (nvIQ), which is significantly correlated with autism severity
    2. Language impairment, which may be evident in acquisition of words, semantic processing, echolalia and prosody
    3. Motor deficits, usually in the form of poor control of skilled movements
    4. Hypo- or hypersensitivities to sensory stimulation
    5. Macrocephaly, evident in about 20 percent of individuals with autism
    6. Epilepsy (recurrent seizures), which occurs at some time between birth and adolescence in about 30 percent of individuals with autism
    7. Abnormal EEG discharges during overnight electroencephalograms, exhibited by more than 70 percent of individuals with autism.
    8. Sleep disorders, including short rapid-eye-movement sleep and short total sleep time
  2. Regression, defined as a loss of previously acquired skills, occurs in approximately 20 percent of individuals with autism.
  3. Nearly 20 percent of Simons Simplex Collection families report reduction in autism-related behaviors when their children experience a fever.

What is next?

  1. We need to stratify the broad autism phenotype by correlating autism traits with the following:
    1. Quantitative measures of social cognition, working memory, attention and language
    2. Autism risk genes, insertion and deletion mutations and copy number variants
    3. Gene expression profiles or epigenetic marks
    4. Anatomical or functional neural correlates
    5. Trajectories of individuals with autism with low and high intelligence quotients
    6. Measures of autonomic functions (such as pupil diameter, pulse rate and blood pressure) and patterns of motor activity
  2. Do sensory abnormalities arise in the periphery or in the central nervous system?
  3. Are the beneficial effects of fever due to a sensitive, temperature-dependent neural process, or are they a different consequence of inflammation?
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