Autism Update

title="Proceedings of the National Academy of Sciences">PNAS
has an open-access article describing the current state of knowledge of
the genetics of rel="tag">autism.  The authors looked at
information from the Autism
Genetic Resource Exchange and two other databases; one from
the University of Michigan, the other from the href="http://www.iancommunity.org/">Interactive Autism
Network (IAN) Research Database.  Their findings
indicated that most cases of autism can be explained by one of two
mechanisms.  The concluded that most cases arise from
spontaneous mutations, with a minority occurring due to a dominant
gene.  

href="http://www.pnas.org/cgi/content/full/104/31/12831">A
unified genetic theory for sporadic and inherited autism

Published
online before print July 25, 2007, 10.1073/pnas.0705803104

PNAS | July
31, 2007 | vol. 104 | no. 31 | 12831-12836

Xiaoyue Zhao*,
Anthony Leotta*, Vlad Kustanovich{dagger}, Clara Lajonchere{dagger},
Daniel H. Geschwind{ddagger}, Kiely Law§, Paul Law§, Shanping Qiu¶,
Catherine Lord¶, Jonathan Sebat*, Kenny Ye||,**, and Michael Wigler*,**

Autism
is among the most clearly genetically determined of all
cognitive-developmental disorders, with males affected more often than
females. We have analyzed autism risk in multiplex families from the
Autism Genetic Resource Exchange (AGRE) and find strong evidence for
dominant transmission to male offspring. By incorporating generally
accepted rates of autism and sibling recurrence, we find good fit for a
simple genetic model in which most families fall into two types: a
small minority for whom the risk of autism in male offspring is near
50%, and the vast majority for whom male offspring have a low risk. We
propose an explanation that links these two types of families: sporadic
autism in the low-risk families is mainly caused by spontaneous
mutation with high penetrance in males and relatively poor penetrance
in females; and high-risk families are from those offspring, most often
females, who carry a new causative mutation but are unaffected and in
turn transmit the mutation in dominant fashion to their offspring.

At first it might seem counterintuitive that most cases would occur in
low-risk families.  The explanation is that there are a lot
more low-risk families than there are high-risk families.  



They note that the mutations occur first in germ-line cells (ova and
sperm).  This is consistent with the observation that older
parents are at higher risk for having children with autism.  



In contrast to the highly technical discussion in the PNAS, there is a
nice plain-language account of some of the same ideas.  It
will be published in the New York Times Magazine
this coming weekend.  It is available now to title="free access with University affiliation"
href="http://scienceblogs.com/scientificactivist/2007/06/free_nytimes_select_for_univer.php">Times
Select members; others have to wait for the weekend, for full
text.

href="http://select.nytimes.com/preview/2007/08/05/magazine/1154683896788.html?8tpw&emc=tpw">

What are Austistic Girls Made Of

By EMILY BAZELON

Published: August 5, 2007



The Times article focuses on differences between
girls with autism and boys with autism.

...But
he agrees with Lainhart that it is easier for Asperger's boys to find
other boys -- either on or off the autistic spectrum -- who want to spend
hours on their Game Boys or in a realm of Internet fantasy. Klin and
Lainhart also say they think that the world is a more forgiving place
for boys with the quirks of Asperger's because, like it or not,
awkwardness is a more acceptable male trait.



This
gender dynamic doesn't necessarily affect girls with Asperger's when
they are very young; if anything, they often fare better than boys at
an early age because they tend to be less disruptive. In 1993,
Catherine Lord, a veteran autism researcher, published a study of 21
boys and 21 girls. She found that when the children were between the
ages of 3 and 5, parents more frequently described the girls as
imitating typical kids and seeking out social contacts. Yet by age 10,
none of the girls had reciprocal friendships while some of the boys
did...



...And
so girls with autism and normal intelligence may end up at a particular
disadvantage...

Bazelon also learned that it is possible that some females with
high-functioning href="http://www.nimh.nih.gov/publicat/autism.cfm">autism
spectrum disorders have better social skills, thus they may
not be recognized as readily:

...But
based on their clinical experience, Lainhart and also Skuse see autism
as a heterogeneous disorder. Its profile may change and expand as more
is understood about girls, whose autism, they worry, often goes
undiagnosed. That is partly, Skuse posits, because girls' general
aptitude for communication and their social competence helps some
Asperger's girls "pass" -- they pick up on their difference and
carefully mask it by mimicking other girls' speech and manner and
dress. In a sense, their femaleness allows some girls to seem less
autistic. It is as if they start off with a social advantage -- Skuse
sees this as a 20-point bonus on a scale of 100 -- that helps counter
the disorder. This idea isn't necessarily at odds with the findings
that show girls to be more seriously affected by autism, Skuse says,
because the girls who succeed in masking their deficit wouldn't be
included in studies. And so they are missing from the picture. "There
is no doubt in my mind that the way we have defined autism currently
biases our assessments strongly in the direction of identifying a male
stereotype," he says. The C.D.C. agrees and says that as a result the
estimate for the number of girls with autism and normal intelligence
may be low.

One of the main points in the Times article is that
there is a relative lack of research on autism in girls.  This
is changing, with positive results:

By
isolating sex as a variable, scientists are seeing potential genetic
hot spots for autism. "By comparing males and females, we will have a
much better chance of discovering the causes of autism," says Geraldine
Dawson, a psychology professor and director of the University of
Washington Autism Center, who was a co-author of one of the studies.

The Times article has some inspiring stories about
kids with autism.  This is a nice touch.  It is
something that tends to be lacking in modern academic articles.



UPDATE: the New York Times magazine article now has a permanent link, here.