The purpose of medical investigations is to identify the underlying conditions that may be associated with autism/ASD, in particular those that are treatable or have genetic implications. The paediatrician therefore needs an understanding of the evidence base for which physical investigations are appropriate. However, reported rates of children with autism with a recognised medical condition vary between studies depending on diagnostic criteria, the population studied and how extensively the children were investigated. Rates range between 8% and 37%, with the consistent finding that the yield of investigations is higher in those with lower IQ.22,23
Associated conditions include fragile X, tuberous sclerosis, cerebral palsy, untreated phenylketonuria, neurofibromatosis and congenital rubella. Hearing and visual impairments should also be considered.
The NAPC and other recently published reviews recommend a minimum of routine investigations and indicate that it is helpful for parents to be given an explanation about why a particular test is or, more often, is not indicated for their child.
Evidence supports the recommendation of a general physical examination, including Wood's light, identification of dysmorphic features, and routine hearing and vision testing. Chromosomal analysis and specific DNA testing for fragile X is indicated in case of evidence of significant language or learning difficulty, phenotypic features or family history. Further investigations should be guided by clinical presentation. Cass et al
support this recommendation in their recent paper considering the evidence and rationale for medical investigation of children with ASD. They conclude that the yield from investigations is generally low, but factors modifying the pretest probability, such as family history or phenotypic features, of each condition should be evaluated for the child in question.24
Epilepsy is known to be significantly associated with autism. Fombonne reviewed 11 studies that reported rates of epilepsy.6
The median rate was 16.8% (range 0–26.4), with the likelihood of epilepsy increasing with increased severity of mental retardation and with two peaks in the preschool period and adolescence.
Ten per cent of children with autism have an abnormal EEG in the absence of clinical seizures,25
yet there is no conclusive evidence that epileptiform discharges “cause” autism, or that it can be improved with anticonvulsant drugs.26
Use of anticonvulsants should therefore be restricted to the treatment of clinical epilepsy.
Parents or care givers may enquire about neuroimaging. Routine MRI brain scan and EEG are not indicated unless there are seizures or evidence of a focal abnormality on examination.27,28
An EEG may be indicated in children with a fluctuating clinical picture or other unusual features.
Rates of regression, or a period of developmental stasis in children with ASD, vary between 10% and 50%, most often occurring between 18 and 24 months of age.29
Loss of speech before or within the 10‐word stage is the most common loss of skill and does not warrant routine EEG. Developmental regression with onset of autism after normal development to
24 months is less frequent and would warrant more extensive neurological investigation. Indications pointing to inborn errors of metabolism are mental retardation, encephalopathy, recurrent vomiting and dysmorphic features.30
Recently, Challman et al
undertook a retrospective case note study of 182 children diagnosed with either autism or PDD‐NOS, as defined in the Diagnostic and Statistical Manual of Mental DisordersIV
PDD‐NOS, although not directly transferable, can be considered to represent those disorders on the autism spectrum excluding core autism. Aetiologically relevant conditions were found in 5.1% of the PDD‐NOS group and in 3.1% of the autism group; these figures did not differ statistically. Abnormalities on MRI brain scanning showed abnormalities in both groups but rarely yielded clinically useful information. This study suggests that overall the yield of medical investigations is low but is similar for autism and ASD, suggesting that medical investigation should not be limited to only those children with “core autism”. These findings, however, need replication in a UK sample. Although much progress has been made in understanding the role of genetics in the aetiology of autism, the picture is far from clear. Genetic factors are important for both core autism (heritability of approximately 90%) and for the broader ASD phenotype. This means that, for a family with a child with autism, an approximately 6% risk of autism for siblings and an increased risk for a broader autism phenotype of 20% are observed. These rates are significantly greater than the risk in the general population of 0.5%.32
It is likely that multiple genes contribute to autism and ASD susceptibility. Susceptibility loci on chromosomes 2, 7 and 16 have been the most consistently replicated findings to date.33
However, no specific candidate genes have as yet been identified. Further, how particular genes interact to produce the clinically heterogeneous spectrum of ASD remains unclear (see Shastry34
for a recent review).