Syndrome: A New Understanding of Neurological Disorders
by Jennifer Wider, MD
While the gene responsible for Rett Syndrome was discovered in 1999, only recently
have researchers realized the potential for the finding to shed light on this
and other neurological disorders. This pivotal research, along with lobbying
efforts by actress Julia Roberts, has brought this once obscure disease to the
political and scientific forefront. Since the discovery of the gene by Huda
Zoghbi, M.D. and colleagues at Baylor College of Medicine, researchers have
been working towards potential therapies and screening techniques.
Rett Syndrome occurs predominantly in females, affecting one in every 15,000
girls worldwide. Children with the disease will develop normally for the first
6 to 18 months, achieving anticipated developmental milestones, and then will
begin to regress as their motor and cognitive skills cease to mature.
The mutation responsible for Rett Syndrome occurs on the tip of the X chromosome
in a gene that researchers have named the MECP2. A child with the disease experiences
marked neurological deterioration because components of the gene are responsible
for normal brain development.
The disorder affects males and females differently because the mutation is
located on the X chromosome, causing an uneven gender distribution as girls
have two X chromosomes and boys have one X and one Y. The effects of the faulty
gene can be offset in girls, to some extent, because the normal X will compensate.
Thus, affected girls have the symptoms of the disease, but can survive the mutation.
The Y chromosome in boys cannot compensate for the X chromosomal mutation and
the defect is usually lethal. The disease is seen almost exclusively in girls
because male pregnancies generally self-abort.
Those affected appear normal at birth and into the first year of life because,
"The protein product of the gene is not needed by the nervous system until
the neurons mature," explains Carolyn Schanen, MD, Ph.D., Head of Human
Genetics Research Programs at the Alfred I. duPont Hospital for Children in
Wilmington, DE. In other words, symptoms will only become apparent when the
brain cells are mature.
Once neurons or brain cells begin to mature, sufferers will experience emotional
withdrawal, loss of previously acquired speech and motor skills, delayed head
growth, and, as the child ages, characteristic hand gestures, breathing abnormalities
and walking problems. Ultimately, Rett Syndrome leaves affected girls dependent
upon wheelchairs and only able to use eye gestures to communicate.
"It is important to note that the gene discovery has revealed that a subset
of patients with several other disorders, such as mild mental retardation and
psycho-affective disorders, have mutations in MECP2," said Dr. Zoghbi.
The association with more common diseases like schizophrenia and bipolar disorder
has led to a better understanding of the function and development of the human
brain. Now, researchers can look for ways to normalize the defect at the cellular
Before the gene discovery, Rett Syndrome was often a clinical diagnosis made
at the age of 7 or 8. Children would pass from one office to the next, misdiagnosed
by doctors who failed to recognize the perplexing symptoms. Now, they can be
treated earlier and taught to retain skills before they lose them.
Rett Syndrome occurs spontaneously in most girls and the risk of a family having
a second child with the disease is very low. "Many families want a prenatal
diagnosis," according to Dr. Schanen. In the past, "Some families
even terminated pregnancies because of female gender. This is no longer an issue
because genetic testing is a major assurance." A genetic counselor can
be consulted for families who already have one daughter with Rett Syndrome,
but routine screening is not recommended because there is currently no effective
Doctors are looking forward to a wide array of treatment alternatives for Rett
Syndrome and the associated diseases. According to Dr. Zoghbi, "When effective
therapeutic options become available, newborn screens can be put in place to
identify affected individuals so that therapy can be started before most symptoms
appear. Such early intervention holds the promise of better outcomes for at
least some of the features of this class of disorders."
In working towards early intervention options, researchers have also begun
to understand the significant role sex plays in varied congenital genetic disorders.
Experts discussed Rett Syndrome and other disorders at the March 2002 scientific
advisory meeting "Sex Begins in the Womb", hosted by the Society for
Women's Health Research and Stanford University School of Medicine.
to receive more information about the Society for Women's Health Research scientific
advisory meeting "Sex Begins in the Womb."
For more information, visit the International Rett Syndrome Association at
The Society for Women's
Health Research is the nation's only not-for-profit organization
whose sole mission is to improve the health of women through research. Founded
in 1990, the Society brought to national attention the need for the appropriate
inclusion of women in major medical research studies and the resulting need
for more information about conditions affecting women. The Society advocates
increased funding for research on women's health, encourages the study of sex
differences that may affect the prevention, diagnosis and treatment of disease,
and promotes the inclusion of women in medical research studies. Dr. Donnica
Moore has been a member of the Society since 1990 and is a past member of its
Board of Directors.
Created: 1/9/2003  - Donnica Moore, M.D.