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Autism - Pervasive Developmental Disorder (PDD)
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Clinical types
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A number of clinical types with different names come under this heading. It appears
that this is a group of disorders whose causes are diverse, but which have not been
adequately characterized. They include:
- Classical (infantile) autism.
- Asperger syndrome.
- A number of other diseases that are characterized by a clinical picture similar
to autism or having autistic traits.
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Clinical signs
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Classical autism (infantile autism):
The characteristics manifested by these children include social and communicational
adjustment disorders, limited, stereotypical fields of interest, and developmental
disorders that appear in the first three years of life. In most cases, the child
behaves abnormally even in infancy (before the age of one year).
Asperger syndrome: The signs
in this condition are similar to those of infantile autism, but milder. The disease
occurs and can be diagnosed in childhood.
There are a number of diseases characterized
by a clinical picture similar to autism or that have autistic traits:
These include fragile X syndrome, a test for which should be carried out in all
such cases, and other syndromes with or without mental retardation. These include chromosome
disorders such as a duplication of an area below the centromere on the long arm
of chromosome 15, etc. Other conditions such as phenylketonuria should be investigated.
However, it must be ascertained that the mother herself does not have phenylketonuria,
since such mothers can give birth to children with both physical and mental problems
unless she adheres strictly to a special diet throughout pregnancy. The mother's
status regarding phenylketonuria can be ascertained by evaluating the phenylalanine/tyrosine
ratio. Psychiatric disorders are also sometimes included in the differential diagnosis.
All these conditions must be considered by the geneticist.
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Inheritance pattern
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The pattern of inheritance is still not clear, and apparently not all cases are
hereditary. According to the results of several studies, it appears that genetic
factors cause around 80% - 90% of all cases of autism.
In addition, there are cases in which environmental factors during pregnancy and/or
birth are associated with abnormal development of the brain center responsible for
autism.
The genetic factors are probably heterogeneous - an analysis of various studies
has shown that more than 12 genes are implicated in autism, to the extent that in
different families the causative gene can be completely different.
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The general opinion is that, at least in some cases, transmission is multifactorial,
i.e. there can be more than 1 gene involved and the environment exerts an influence
as well. In other cases transmission is by autosomal recessive inheritance - in these cases one gene with reduced penetrance
is involved, and this is influenced by different environmental conditions. This
is supported by the occurrence of further cases of autism of different types in
siblings.
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Penetrance
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This is not precisely known and probably differs in different families. The disease
is four times more frequent in males.
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Associated features that can be demonstrated by imagery
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Usually there are no defects that can be identified by ultrasound examination during pregnancy.
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What is the risk of recurrence in a subsequent pregnancy?
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In cases where the affected individual
is the only one in the family: The frequency of childhood autism is 1
in 2,000. Mild autism (based on the severity of the definition used) is of course
more frequent, approaching 1%.
The risk for siblings to be affected is 75 times higher than the regular risk for
the general population. The total risk for siblings is approximately 5% in the case
of autism defined by classical criteria. The percentage is slightly higher if the
fetus in the following pregnancy is a male. Distantly related family members have
no significant additional risk for having an affected child.
If there are two affected siblings:
The risk of having a third affected child is approximately 12% - 25%. More distant
relatives do not have a significant additional risk for having an affected child.
As mentioned, the frequency of this condition in the general population is approximately
1% depending on the definition used.
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Basics: Autism-Symptoms
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Molecular genetic information
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The gene for the disease
The genes that cause autism have yet to be found. According to mathematical/genetic
estimates, there are probably more than 10 different genes that in different combinations
can cause this condition. Different families probably carry different abnormal genes
and different mutations. In addition environmental conditions also affect the expression
of the disease. The complexity of the causes of autism is probably the reason that
the genes have not yet been found.
The key for identifying genetic defects in diseases with genetic heterogeneity such
as autism involves finding families with multiple cases of PDD and autism. Research
groups are therefore concentrating on and are interested in such families at the
present time.
The locations of the possible genes
Studies conducted in recent years have raised the question that genes in a number
of sites in the genome, particularly 2q, 7q, 16p, and 19p, may be implicated. Recently,
evidence has been found in some patients that there is a genetic defect in chromosome
15, in the region 15q11-q13. According to a number of researchers, however, this
is only responsible for approximately 15% of all cases of autism. In these studies
the gene itself has not been identified, and even if it is present and a mutation
in it is associated with autism, it does not cause the condition by itself, but
only together with environmental influences. Therefore, until the picture becomes
clearer, it is not practical to examine families with only one case of autism/PDD.
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Genetic testing
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Diagnostic testing
There are to date no clinical genetic tests for diagnosing this condition. Only
in families with multiple cases is it possible to carry out investigations that
may lead to the possibility of performing practical tests in some families in the
future, initially by indirect tests (linkage analysis), and in the more distant
future, once the gene itself has been found, by identifying the mutation or mutations.
This will be done in cooperation with a genetic institute. See information sheet:
Indirect testing for genetic markers in a family
that has one or several patients - when there are a number of different genes that
can each cause the disease - the gene, or most of the genes not having been located
/ identified / mapped - multifactorial diseases.
Carrier testing
This cannot usually be performed, unless a specific syndrome such as fragile X syndrome, etc. is found. See diagnostic testing above.
Fetal testing
This cannot usually be performed, unless a specific syndrome such as fragile X syndrome,
etc. is found. See diagnostic testing above.
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