Neurofibromatosis type 1 (NF1) is a genetic disorder that is characterized by changes in skin color and growth of tiny nodules along nerves in the skin, brain, eye and other parts of the body.
Scientists have linked mutations in a single gene to autism in people
who have this rare tumor syndrome typically diagnosed in childhood.
‘Mutations in a single gene have been linked to autism in people who have this rare tumor syndrome typically diagnosed in childhood.’
About 100,000 people in the United States have neurofibromatosis type 1. Autism, meanwhile,
affects 1% to 2% of all children in the United States and
is four to five times more common in boys than in girls.
The findings, in patients with NF1, may
lead to a better understanding of the genetic roots of autism in the
wider population. The findings are published in the journal JAMA Psychiatry
Studying 531 patients at six clinical centers in the United States,
Belgium, the United Kingdom and Australia, the researchers found that
mutations in the NF1 gene that cause the disease also contributed to
autistic behaviors in almost half of the patients.
"NF1 is caused by mutations in a single gene - NF1," said first
author Stephanie M. Morris, an instructor in neurology. "Our
research indicates that this single gene also is associated with autism
spectrum disorders in these same patients. That may make it possible to
look downstream from the gene to find common pathways that contribute to
autism in the wider population."
NF1, the disorder caused by NF1 mutations, usually appears during
childhood. Symptoms can vary in severity, but they include café au lait
spots, which are flat, brown spots on the skin. Other symptoms include
tiny nodules on the iris of the eye, nerve tumors, bone deformities such
as a curved spine or a bowed lower leg, and optic gliomas, tumors of
the optic nerve. Kids with NF1 also can have learning disabilities.
"In the 25-plus years that I've taken care of kids with NF1, we've
only recently started to recognize that these children also often have
symptoms of autism," said senior investigator David H. Gutmann, the Donald O. Schnuck Family Professor of Neurology and director of the
Washington University NF Center. "In the past, we didn't really
understand the association between NF1 and autism, but now we have new
insights into the problem, which will allow us to design better
treatments for children with NF1 and autism."
The findings also could help scientists who study the genetics of
autism understand how mutations in a single gene can contribute to
symptoms of autism, such as problems with social and language skills and
"What's unique about our findings is that it's likely mutations in
the NF1 gene are driving most of the symptoms of autism in children with
NF1," said the study's other senior investigator, John N. Constantino,
the Blanche F. Ittleson Professor of Psychiatry and Pediatrics and
director of the William Greenleaf Eliot Division of Child &
Adolescent Psychiatry. "Here, we have a single-gene disorder that
affects a fairly large number of people and is causing autism in a
significant number of those who are affected. This work could provide us
with an opportunity to study a single gene and figure out what it is
doing to cause autistic syndromes."
Constantino said most autism spectrum disorders are influenced by
multiple genes but that isolating this one gene can aid efforts to learn
how other, unrelated genes may interact along that same pathway to
contribute to autism in people who don't have NF1.
Learning how those various genes come together to cause symptoms
eventually could lead to better treatments. But already the findings are
benefiting children and families treated at the Washington University
"We've been able to screen children at our center, identify autism
spectrum disorder, attention-deficit disorder and problems with
executive cognitive function," Morris said. "And when we identify these
deficits in kids, we can tell their parents, inform their schools and
enable these children to get the resources and support they need -
specifically academic and social support - to improve their quality of