A SECOND CASE WITH SMITH-MAGENIS SYNDROME
TREATED PRIMARILY WITH ANTISTRESS DRUG THERAPY
LASTING FIVE MONTHS
Renato
COCCHI, neurologist and medical psychologist
Summary.
A
8;2-years girl with microdeletion of the chromosome 17 ( p11.2 ) had drug
antistress therapy. The chromosomal anomaly with facial characteristics not
particularly evident, mental retardation, behavioural troubles, hyperactivity,
autistic traits and language problems drew to the diagnosis of the
Smith-Magenis syndrome.
Following
a modulation trial by drugs of body reactions to stress, lasting five months,
she showed language improvement, reduction to respiratory infections easiness,
better behaviour at school and improved learning, and reduced the sameness. Symptoms linked to serotonin and noradrenaline got
worse according perhaps to the seasonal change and precocious summer heat, for
which after early improvements they came back to the state preceding the antistress
drug therapy.
The modulation of stress answers, even
lasting only five months, and with low doses of drugs, appears a practicable
way to reduce the phenotypical expressions of this chromosomal anomaly too.
Key words: chromosomal anomaly, del17(11.p2),
syndrome of Smith-Magenis, girl, stress, antistress drug therapy.
Drug modulation of stress reactions
Other genetic and chromosomal anomalies
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A second case of Smith-Magenis syndrome in a
girl of a few more than eight years occurred to my observation. Since it was
much similar, but different for some details to the previously reported case
(Cocchi, 2001) still in treatment with drugs, I started to do the case history.
The case history.
20.01.2003: Girl, 8;2 years old at the first
visit, with clumsiness, mental and language retardation, and autistic traits,
for which she had the diagnosis of Smith-Magenis syndrome. She is left-handed
and walking about.
Born from regular pregnancy with delivery in
the 40th week, her weigh to the birth was 2720 grams, and Apgar scoring 10/10
to the first minute. No respiratory distress, nor cyanosis, nor pathological
jaundice.
During her first year life she did not
suffer from sleep or feeding problems, upper respiratory tract infections, any
weeping for no reason, but spastic constipation and pallor.
In early childhood she has a convulsive fit
from high fever, and an EEG made four days after recorded the presence of
modest irritating elements. IQ (Griffith method ) at three years scored 78.8.
The girl shows only light dismorphic traits,
with palpebral clefts swerved towards the high, hypotelorism, modest lower part
installs and strong forward versions of the auricular tents ( probable fatherly
heredity ), the superior lip arched, slightly high palate, slightly sharped
jaw, little hands with short fingers. The US heart examination has pointed out
normal findings, but there is a tendinous little rope in the left ventricle.
Two NMRs showed the brain within the normal limits. The caryotype examination
permitted to underline a deletion of the chromosome 17( p11.2), subsequently
confirmed by the FISH method.
She has respiratory infections' easiness, is
a little aggressive against her sister. Her speech is childish and telegraphic.
Now she shows fingers stereotypes, toe walking, self-aggression when
frustrated, introduction of objects in the mouth or in the nose, sameness. She
suffers from the cold, with cool hands and feet. There is no liking for sweet
foods, except chocolate, while there is normal taste for the meat broth.
When it is time to eat she does dramatic
plays, says that she has bellyache, or that she is falling asleep. Her bowel
function runs well.
To maintain the sleep is difficult but she
has always bedwetting. She is daily taking 3mg melatonin and 0.8mg haloperidol.
Her autonomy is very poor (zero, as the mother says).
Not behavioural differences between mornings
and afternoon, nor seasonal differences were reported, but she is more
irritable if the wind blows.
There are present bruxism, repeated
scratching, and masturbation by rubbing. First the mother doesn't admit
opposite behaviour, but she confirms it lately, during the visit.
The girl attends the third class at primary
school, with attention problems and hyperactivity, and fits of spitefulness,
even if then she is cheerful. She reads with difficulty, eating the words, and
she doesn't maintain the line of reading.
In the writing she succeeds to copy, but she
has scarce ability when she writes under dictation, and no ability in
sentences' invention. Being very disgraphic, with the computer she writes
better. As for arithmetic, she knows the digit sequence till 100, not can
always do simple additions by helping herself with the fingers, she is unable
to do subtractions.
Initial therapy, daily doses, by the oral
via: glutamine 125mg; pyridoxine 75mg; amantadine 100mg; amitriptyline 4mg;
oxazepam 3mg. Haloperidol stopped.
24.02.2003: First checkup. She regularly
took the regimen. She sleeps more and better. Less bedwetting as for amount and
frequency and two night she was dry.
Always hyperactiv, as first. She has still
stereotypes of the fingers, toe walking, sameness. Language did not change.
At school perhaps is more calm, less
spiteful and pays more attention. Perhaps she reads better, jumping less the
lines and she writes in more orderly way. Perhaps some new acquisitions to the
computer appeared, like in the reconstruction of plain geomethrical figures.
She tries to do something, but she is
awkward as to dress. Ambidextrous, she tries to use the right hand, but she is
more left-handed. Equally aggressive toward her sister. Autoaggression
unchanged. She is scratching as in pass, but less since she is taken pyridoxine
[??]. Perhaps masturbation by rubbing decreased.
Her appetite is as first, but she plays
always scenes before eating. She always refuses sweet things. In the mornings
she is a little best.
Bruxismo is as first. Perhaps there is less
easiness to upper respiratory tract infections: the last feverish episode had
low temperature and lasted less. Hands and feet are always cool. Surely there
are moments of opposite thought.
Therapeutic variation, daily doses by the
oral via: glutamine 185mg, amitriptyline 6mg; oxazepam 4mg; amantadine 150mg.
16.06.2003, the second checkup. During the
pass period there was behavioural regression, following the house moving, for
which oxazepam, in accord with the family physician, was substituted with
bromazepam, in drops, about 1mg daily.
At the starting of the visit the exasperated
mother reports that all goes wrong, mainly since the last 20-30 days.
She has fit of crying, or tells invented
things (mythomania), and does scenes when she is going to eat. She provokes by
saying that she has bellyache or other troubles, but then she eats.
Hyperacivity came back. The relationship with her grandmother is based on dirty
and derogating words. Now she is scratching more and is tearing her
fingernails. Those symptoms existed even in past, but now are more frequent.
Many waking ups during the night occur, and she goes to the bed of the mother
about to four in the mornings.
Fingers' stereotypes increased, as well as
toe walking, and now she puts little pieces of paper into her nose. The
masturbation has become more frequent. The bruxism is unchanged, the bedwetting
is daily. She provokes the mother to be beaten, and she is amazed if this
doesn't happen. Then, checking other symptoms, I discovered that the mother had
forgotten to report that the daughter speaks better, uses new words, structures
better the sentence, pronounces better. She also read better and holds the
sign. Now she is very skilful at the play-station.
She has always opposite behaviour, mainly at
first time, then she mends. The sameness decreased and at school her behaviour
improved. Always more ambidextrous. As for her health she ran fine, with very
fewer and shorter respiratory infections
Therapeutic variation, daily doses, by the
oral via: Carbamazepine 100mg; clonidine 37.5mg; amantadine 200mg. Bromazepan,
amitriptyline, glutamine and pyridoxine rest unchanged.
Discussion.
The Physician's Guide to Rare Diseases
(1999) summarizes the Smith-Magenis syndrome as a chromosomal anomaly
characterized by unusual facial features, mental retardation, behaviour
abnormalities and speech problems. Its synonym is Chromosome 17, Interstitial
Deletion 17p-. In most affected people the microdeletion 17p- occurs as a
spontaneous event.
The severity of a Smith-Magenis syndrome
depends on the amount of missing genetic material. Children suffering from it
typically have unusual facial features, a raspy or hoarse voice, speech delays,
hearing loss, and hands and feet short and stumpy fingers also occur. But
others are the relevant symptoms.
Growth delay, mental retardation and
hyperactivity usually occur. Self-abuse may include head banging, wrist-biting,
insertion of foreign bodies into body orifices, and pulling out fingernails and
toenails.
Myopia and squint occur frequently, while
the detachment of the retina less often does it. Toenails. The evening falling
asleep is difficult and to stay awake is common.
Some children experienced a high pain
threshold, burning sensation, peripheral neuropathy, amyotrophy, and absent or
decreased reflexes.
Congenital heart defects may also occur.
The symptoms' comparison between this case
and that previously reported (Cocchi, 2001 ), is in the Table 1.
Table 1: Comparison between the two treated
cases.
|
Simptom |
First case |
Second case |
Concordance |
|
Chromosomal anomaly |
17(p11.1-p11.2 |
17(p11.2) |
Partial |
|
Gender |
F |
F |
Full |
|
Dismorphic features |
+++ |
+ |
Partial |
|
Hyperactivity |
+++ |
+++ |
Full |
|
Congenital heart anomalies |
- |
-/+ |
Full |
|
Selfaggression |
+++ |
+++ |
Full |
|
Sleep troubles |
++++ |
++++ |
Full |
|
Putting objets into body cavities |
- |
+++ |
Negative |
|
Speech delay |
++ |
+++ |
Partial |
|
Mental retardation |
++ |
+++ |
Partial |
|
Groudless opposition |
++++ |
++++ |
Full |
|
Reverse behaviour |
++++ |
++ |
Partial |
|
Rocking |
+++ |
- |
Negative |
|
Tratti autistici |
+ |
+++ |
Partial |
|
Using derogating or dirty words |
++++ |
+++ |
Partial |
|
Frequent masturbation |
+++ |
+++ |
Full |
|
Clumsiness |
++ |
+++ |
Partial |
|
Short and stumpy fingers |
+++ |
+++ |
Full |
|
Hearing loss |
- |
- |
Full |
|
Growth delay |
+++ |
+++ |
Full |
|
Myopia |
+++ |
- |
Negative |
|
Lever,kidney,spleen, pancreas anomalies |
- |
- |
Full |
|
Bedwetting |
- |
++++ |
Negative |
|
Brain NMR |
++ |
- |
Negative |
Although this is a schematic comparison, we
can see that 19 symptoms out of 24 are concordant, even if sometimes only
partially because the different severity each symptom owns.
That happens because, too having the same
chromosomal anomaly, the phenotype of every person with Smith-Magenis syndrome
may have some differences.
Hyperactivity, self-injurious behaviour, and
sleep disturbance distinguishes Smith-Magenis syndrome from many other genetic
disorders (Di Cicco et al, 2001; Finucane, Dirrigl and Simon, 2001).
Roccella and Parisi, 1999, reported
epileptic crises are quite rare, but an infant with spasms in extension.
The measured IQ ranges between 20-78. Most patients
fall in the moderate range of mental retardation at 40-54, although several
patients scored in the mild or borderline range (Greenberg et al., 1996).
According to Dykens and Smith (1998) sleep
disturbance emerged as the strongest predictor of future maladaptive behaviour.
Medication to help sleep was used by 59% of SMS subjects (Smith, Dykens, and
Greenberg, 1998).
The Smith-Magenis syndrome is probably
under-diagnosed because the facial abnormalities are mild. The behavioural
problems with hyperactivity and self-injuries are dominant, leading to the
diagnosis of psychiatric pathology (Lacombe et al., 1997; Livet et al., 1997).
On a report on three young children,
Willekens, De Cock and Fryns (2000) noted that behaviour problems included very
demanding behaviour, severe temper tantrums, hyperactivity, aggressive
behaviour, self injurious behaviour, sleeping problems and stereotyped
behaviour. Head banging, hand, wrist or finger biting, were also present.
Insertion of objects in the mouth as well as excessive nose picking was very
frequent.
Behaviour troubles and psychomotor delay
represented a major management problem for the parents.
Now I shall go to check better this second
case.
Unusual facial features, mental retardation,
behaviour troubles and language delay are all present. For what concerns the
face, the dismorphic features are however of modest degree.
The mental retardation is evident and at
school there is the need of a support teacher.
Groundless opposition, spitefulness,
selfaggression, and repetitive masturbation are severe behavioural negative
symptoms. The language is childish, telegraphic type, with use of derogating or
dirty words.
Other symptoms found: Sleep disorders, low
growth, short and stumpy fingers, hyperactivity, toe walking and other motor
delays.
The opposition in reply too apparently
neutral order or in demand is a kind of contrary Mary character.
An aspect that requires attention is the
choice of aggressive, derogating or dirty words, with some persons, lately her
grandmother.
As for me, I think that lexical choice of
this girl comes out from that parallel memory where negative words, even
emotionally, or opposite, are stored. I Believe that this file has its site in
the not dominant half-brain or it is under the control of that one.
Moreover, I do not know if this possible
reverse brain dominance is a symptom that not always pertains to the
Smith-Magenis syndrome. I found some incidental reference on the opposition
behaviour, but not as I have tried to describe it. Some opposition behaviour is
usual in mentally retarded persons and it is possible that they are related to
the obstinacy of these persons. Perhaps obstinacy and the reverse half-brain
dominance are two aspects of a unique thing (Cocchi, 1994 ). However this case
showed such characteristic such in a lesser degree than the first described
case (Cocchi, 2001 ).
The drug therapy I prescribed aimed to
modulate stress reactions by acting on GABA, noradrenaline, serotonin and
dopamine.
Five-months therapy, with only one regimen
adjustment, drew to a phenomenon of noticeable interest.
Some symptoms have continued to improve like
school behaviour, school learning, language, easiness to the respiratory
infectious, sameness, the use of the right hand.
Others like bruxism, bedwetting and doing
scenes at the moment of going to eat, did not change.
Other ones, after an initial improvement,
came back to the first level, namely hyperactivity, to scratch and to rip the
fingernails, the sleep trouble, the fingers sterereotypies, the toe walking,
the masturbation, to put objects in the mouth or in the nose.
Lately, the weeping, the tendency to
aggressive and offensive language, the provocative behaviour worsened.
This partial regression related to a season
difficult change and to the spring onset of a long period of summer heat. To
which the child seems to have reacted with possible reduction of serotoninergic
and noradrenergic brain mechanisms and compensating accentuation of peripheral
adrenergic incretion.
Conclusions.
This is the case history of an 8;2-years-old
girl with microdeletion of the chromosome 17 ( p11.2 ) had drug antistress
therapy. The chromosomal anomaly with facial characteristics not particularly
evident, mental retardation, behavioural troubles, hyperactivity, autistic
traits and language problems drew to the diagnosis of the Smith-Magenis
syndrome.
Other evident symptoms were marked
opposition, a low frustration threshold with irritability, spitefulness and
selfaggression, use of derogating words, autistic traits.
Following a modulation trial lasting five
months, of body reactions to stress by low doses drugs, she showed language
improvement, reduction to respiratory infections easiness, better behaviour at
school and improved learning, and reduced the sameness. Symptoms linked to
serotonin and noradrenaline got worse according perhaps the seasonal change and
precocious summer heat, for which, after early improvements, they came back to
the state preceding the antistress drug therapy.
Even here, as it occurred in the first case
treated for 30 months now, the modulation of stress answers, even lasting only
five months, and with low doses of drugs, appears a practicable way to reduce
the phenotypical expressions of this chromosomal anomaly too.
The case history will be timely updated, if
the girl will go on with the drug therapy..
References.
AA. VV. : Physician's guide
to rare diseases (Edizione italiana della 2a edizione americana) Hyppocrates,
Milano 1999: 178-179.
Cocchi R. Drug therapy in a
girl aged ten with Smith-Magenis syndrome. Posted on Internet on November 2001
(Genetic4-htm)
Di Cicco M, Padoan R,
Felisati G, Dilani D, Moretti E, Guerneri S, Selicorni A. Otorhinolaringologic
manifestation of Smith-Magenis syndrome. Int J Pediatr Otorhinolaryngol 2001,
59: 147-150.
Dykens EM; Smith AC.
Distinctiveness and correlates of maladaptive behaviour in children and
adolescents with Smith-Magenis syndrome. J Intellect Disabil Res 1998, 42(Pt
6): 481-489.
Finucane B.M. et al.: Eye
abnormalities in the Smith-Magenis contiguous gene deletion syndrome. Am. J.
Med. Genet. 1993, 45: 443-446
Finucane B.M. et al.:
Mosaicism for deletion 17p11.2 in a boy with Smith-Magenis syndrome. Am. J.
Med. Genet. 1993, 45: 447-449
Finucane B; Dirrigl KH;
Simon EW. Characterization of self-injurious behaviors in children and adults
with Smith-Magenis syndrome. Am J Ment Retard 2001, 106: 52-58.
Greenberg F. et al.:
Molecular analysis of the Smith-Magenis syndrome: A possible contiguous-gene
syndrome associated with del(17)(p11) Am. J. Hum. Genet. 1991, 28: 627-632.
Hodapp RM, Fidler DJ; Smith
AC. Stress and coping in families of children with Smith-Magenis syndrome. J
Intellect Disabil Res 1998, 42(Pt 5): 331-340.
Moncla A. et al.:
Smith-Magenis syndrome: A new contiguous gene syndrome: Report of three new
cases. J. Med. Genet. 1991, 28: 627-632.
Smith AC, Dykens E,
Greenberg F. Sleep disturbance in Smith-Magenis syndrome (del 17 p11.2). Am J
Med Genet 1998, 81: 186-191.
Willekens D, De Cock P,
Fryns JP. Three young children with Smith-Magenis syndrome: their distinct,
recognisable behavioural phenotype as the most important clinical symptoms.
Genet Couns 2000, 11: 103-110.
First published on Internet on June, 2003.
Copyright by R. Cocchi, 2003.
Author's address: dr Renato
Cocchi, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Drug modulation of stress reactions
Other genetic and chromosomal anomalies
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