Smith magenis syndrome five-year-old beth has smith-ma

1. Smith-Magenis Syndrome
Five-year-old Beth has Smith-Magenis syndrome (SMS). SMS is
caused by a
deletion mutation of chromosome 17. Along with facial and
skull abnormalities,
which her parents first noticed when she was just a baby, Beth
has several
cognitive and behavioral problems, including mental
retardation, tantrums,
hyperactivity, attention deficit, and self-injury. She also has a
severe sleep
disturbance.
Beth’s sleep pattern is very different from that of a typical child
her age. She
awakens at least once every night and then has a hard time
getting back to sleep.
She is usually awake to stay by 4 or 5 a.m. As a result, she feels
extremely sleepy
during the day, and has sudden “sleep attacks.” Beth’s tiredness
contributes to her
cognitive and behavioral difficulties. However, new research
may soon help Beth
and others with SMS get the sleep they need.
Dr. Hélène De Leersnyder of Necker-Enfants Malades Hospital
in Paris became
interested in the sleep disturbance aspect of SMS when she
attended a meeting of

2. parents of children with SMS. She was intrigued by the parents’
unanimous reports
of their children’s sleep troubles. De Leersnyder and some of
her colleagues
decided to see if they could discover the cause of the SMS sleep
disturbance.
The researchers found that individuals with SMS have an
“inverted circadian
rhythm of melatonin.” In other words, the timing of the rise and
fall in their levels
of the hormone melatonin is the opposite of what it should be.
In an individual
with a normal sleep cycle, levels of melatonin fluctuate in a
predictable way—that
is, melatonin peaks at night, causing drowsiness, and then
subsides, reaching its
lowest level in the middle of the day. But in people with SMS,
melatonin levels are
lowest at night and highest during the day. The results of this
study were presented
at the annual meeting of the American Society of Human
Genetics in 1999.
Next De Leersnyder turned her efforts to developing an
effective treatment. With
the goal of normalizing the sleep cycles of children with SMS,
De Leersnyder’s
group gave the children two medications: a drug called
acebutolol in the morning
and a melatonin pill in the evening. Although the potential
benefit of taking
melatonin is easy to understand, the reason for administering
acebutolol is less
obvious. The natural secretion of melatonin in the body is
controlled by the

3. sympathetic division of the autonomic nervous system, which
uses the
neurotransmitter norepinephrine. Acebutolol is a type of drug
called a selective
beta-adrenergic antagonist, meaning that it blocks the
interaction of norepinephrine
with certain of its membrane receptors. Thus, acebutolol
suppresses the secretion
of melatonin.
The results of De Leersnyder’s dual-medication tactic, reported
in 2003, were very
promising. Not only did the combination of drugs help the
children with SMS have
a more normal sleep cycle, but it also lessened the severity of
their behavioral
problems and improved their ability to concentrate. There are
other selective beta-
adrenergic antagonists besides acebutolol, and now De
Leersnyder is testing those
on children with SMS, along with melatonin, to see if any of
them can produce
even greater improvement. Although beta-adrenergic
antagonists and melatonin
can’t cure SMS, they may help reduce some of the symptoms of
children like Beth.
Questions
1. What are the consequences of constantly interrupted sleep for
an individual
who does not have SMS? How might this help explain why
normalizing the

4. sleep cycle helped with some of the cognitive and behavioral
problems of
the children with SMS?
2. Does the sleep disturbance in SMS bear any similarity to
better-known
problems, such as jet lag? Explain.
3. Review the definition of a syndrome. How does the term
apply to Beth’s
condition?