TWENTY-SEVEN MONTHS OF ANTISTRESS DRUG THERAPY
IN A GIRL WITH PARTIAL TRISOMY 22. (Updated
to 97 months of treatment)
Renato Cocchi, neurologist and medical psychologist
Summary.
The case
of a girl with partial trisomy 22 [47, XX+[der] ( 22 )t( 11-22 ) (q24q12)]
treated by an antistress therapy for 97 months is
presented. Symptoms of stress improved were: Mental retardation, anger
outbursts without reason, spastic constipation, self-aggression, recurrent awakenings during the night, day drooling,
rocking, face paleness, cold hands and feet.
Other symptoms improved: Attention, understanding, the mood, irritability,
sociability, self-esteem, the relationship with the object, the play, the
feeding, the weigh-height growth, the autonomy. The
language had poor modification in speaking but some ones in understanding
The antistress drugs used
were glutamine, pyridoxine, a benzodiazepine, carbamazepine,
then clonidine for treating self-aggression, and
finally amantadine for ADHD, on which it had some
improvement.
Key
words: Partial trisomy 22, stress, symptoms, antistress therapy, positive results, attention,
understanding, the mood, irritability, sociability, self-esteem, the
relationship with the object, the play, the feeding, the weigh-height growth,
the autonomy, hyperkinesis.
Other genetic and chromosomal anomalies.
Drug
modulation of stress reactions
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The t(11; 22) is the most common recurrent non-Robertsonian constitutional translocation in humans, having
been reported in more than 160 unrelated families. Balanced carriers are at
risk of having offspring with the derivative 22 syndrome owing to 3:1 meiotic
non-disjunction event. (Hill et al., 2000)
Translocations
of the 11th and 22nd chromosome can develop a disorder known most commonly
known as partial trisomy 11;22.
It is also named as Trisomy 22, Supernumerary der(22)
Syndrome, or unbalanced 11;22 translocation. The children
who suffer from this disorder (which is usually inherited from a carrier
parent) have a marker chromosome, made up of the upper (p section) and part of
the lower
(q section) arms of chromosome 22, and a small portion of the
lower (q section) arm of chromosome 11.
Derivative
22 (der[22])
syndrome is though a rare disorder associated with multiple congenital
anomalies. It can occur in offspring of carriers of the constitutional t(11; 22)(q23; q11) translocation.(Funke
wt al., 1999)
The
t(11;22)(q23;q11) translocation is the only recurrent non-Robertsonian
rearrangement for which there are a large number of unrelated families, apparently
with the same breakpoints (Shaikh et al., 1999).
These families most often have been ascertained through an abnormal child with
the karyotype 47,XX or XY, +der(22) t(11;22)(q23;q11). (Armstrong et
al., 2000).
This
tertiary trisomy can occur resulting in abnormal
progeny of t(11-22( carriers with the der(22) as the supernumary
chromosome. Affected children have a distinct phenotype with multiple anomalies
and severe mental retardation. (Dawson et al., 1996).
Carriers
are phenotypically normal and often go undetected
until diagnosis as a result of infertility investigations or following the
birth of chromosomally unbalanced offspring. Efficient diagnostics of t(11;22) is important for children born to carriers of the
translocation and for prenatal and pre-implantation diagnosis (Tapia-Paez et al., 2001).
There are
a large variety of abnormalities in t(11;22) cases.
Cleft palate, heart defects, mental and physical delays, ear abnormalities,
hearing loss), small chins, undescended testes( known
as criptorchidism), microcephaly,
dislocated hips, long philtrums, broad nose, kidney
abnormalities, and Imperforate anus are among the most common findings.
There are
tumors associated with t(11;
22)(p13; q12) and descriptively designated desmoplastic
small round-cell tumor (DSRCT), as distinctive, rare,
poorly understood member of this family. (Gerald et al., 1998)
Biederman et al., 1980, reported a case of tertiary trisomy (22q11q) 47, XX, +der(22), (22pter = to 22q13
:: 11q25 = to 11qter) in a child with mental retardation, cleft palate, and
congenital heart disease. resulting from 3:1 meiotic nondisjunction in a maternal (11; 22) translocation
carrier.
Kessel and Pfeiffer 1977, report of a case of supernumerary
extra chromosome der(11; 22)(q23; q12) resulting from a balanced translocation
in the mother. The propositus suffers from mental
deficiency, deafness and extreme muscular weakness and exhibits cleft palate, a
labial lymphangioma and an atrial
septum defect.
There was
a case with diaphragmatic hernia and Fryns syndrome
phenotype in partial trisomy22. (de Beaufort et al.,
2000)
A boy
with developmental delay and multiple anomalies consistent with the
supernumerary der(22) syndrome was also described. The
clinical features, including craniofacial dysmorphism,
hypotonia, psychomotor retardation, heart defects,
and urogenital anomalies. (Hou, 2003).
The case
that follows went consultation by passing the word on, the parents having seen
interesting results in a neighbour's girl, with severe mental retardation,
already considered unmanageable.
The
case history.
(January,
2000): A girl with 16 years at the moment of the first visit, suffering from
severe psychomotor delay following chromosomal anomaly 47, XX+[der] ( 22 )t( 11-22 ) (q24q12) went to my outpatient'.
Weigh-high development was absolutely poor as for her age and like to what of a
7-8-old girl. Her face is very unusual and resembles a cat muzzle, and dorsal kyphosis is also present. She did not have menses. In past
she was given open-heart surgery for inter-atrium defect and lack of the
ventricular septum. Moreover, she had even three-times surgery for cleft
palate. She attends a day centre (An Educational-Rehabilitative Centre)
Motility:
She walks about, but she doesn't run, does not climb the staircases, does not
ride the tricycle, does not use the cutlery to eat.
Her hand to take things is the right one.
Speech: Lallation and some single words.
Feeding:
She more appreciates the salty things, and meat broth. In her diet there are
fewer raw vegetables but abundant fruit, and in the morning is soon hungry. She
chews only a few.
Bowel
function: She alternates spastic constipation to diarrhea.
Physical
health: Scarce colds, hands and cool feet, pale.
Sleep:
agitated with some awakenings.
Other
symptoms: Self-aggression, day and night rocking, day bruxism
(from stress), psychomotor agitation. Insistent drooling for which she has
redness around her mouth and her eyes ( She touches
them with her wet hand by the saliva).
Therapy
(daily doses, by the oral via): Glutamine 125mg, pyridoxine 75mg, 100mg carbamazepine, oxazepam 7.5 mg, clonidine 50mcg.
The first
checkup (March 2000) after 45 days of drug therapy:
She slightly improved, with less psychomotor agitation, less self-aggression,
more attention, the bruxism reduced, the rocking
reduced. Now, she is eating a little more either at home and
at the Centre, and her assistants found her improved. Perhaps she is less
drooling. As for speech, she uses better the words she knows. Her hands and
feet are less cold. Her bowel function has fewer episodes of diarrhea. No chewing improvement. Perhaps she sleeps
better. Sometimes she has colic ache (or, now, she more clearly shows it).
As for
her health, she seems to do better.
Therapeutic
variation (daily doses, by the oral via): Oxazepam
15mg, glutamine 180mg, carbamazepine 150mg.
The
second checkup (October 2000): Now she is more calm, with reduced colic aches, but she cries for the
pain when she is defecating. However, her bowel function is improved.
Self-aggression much reduced. She became tall. Now, she is eating more either at home and at the Centre. She is more attentive.
Even in the Centre she looks as improved. The rocking diminished,
and no more nighttime rocking, but sometimes in the
morning it appears. She sleeps better and bruxism
even reduced. Evidently, she slobbers less: She does it more when the weather
is changing, because she feels it and slobbers more. She is using only the
words she knows but she softly sings. Her voice is stronger. Now her feet are
warm, but her hands are cold because she drives them into her mouth, even if a
little less than in past. She listens longer. Her father and her grandmother
tell that now is much more amenable (She is doing well and the same for her
family). Now, she chews some more, mainly fruits. Sometimes, she smiles.
Therapeutic
variation: Carbamazepine 200mg; oxazepam
22.5mg, glutamine 250mg.
The third
checkup (March 2002): She still improved. Now she is
more calm, but not in the afternoon. After lunch she is more irritable and
cries for about one hour. At night she is quiet. She is normally eating,
understands more, and is grown both in weigh and in height, although always
under reference limits. She uses better the words that know, but she did not
get any new one. Bruxism still diminished and
self-aggression greatly reduced. At the Centre assistants found her well, being
more autonomous. Less rocking, less drooling. As for
her health, she is doing well. She puts less her hands in her mouth, so she has
even less redness of the eyes. Usually, she is more attentive to the
surrounding. She chews better, eats more, is more serene and looks for the
companionship. She moves better, but she is always awkward when walking.
Therapeutic
variation (daily doses, by the oral via): Oxazepam
30mg, clonidine 100mcg.
The
fourth checkup (April 2003): Since she was doing
well, the relatives have preferred to postpone the checkup
that happened after 13 months. She always took drug therapy.
She
understands more, nearly always simple orders (one-action orders), which she
does. She has become a little spiteful, but it seems that she wants to provoke.
Now, she needs to have psychological support and to receive gratification. Her
motion is better. Now, she learned by herself to open the doors. She doesn't
succeed to eat by herself, she brings the cutlery to the mouth, but then she
throws it away. She has become a little sly dog and the assistants of the
Centre tell the same. Perhaps now she has the more cute face. Finally, she
permits to comb her and want to change, if she is dirty. She doesn't want to
stay so. When the grandmother dresses her, she anticipates the movements. At
night she always sleeps. She eats anything, all the raw vegetables and some
liver also, but she prefers pasta and bread, chews better, slobbers only
sometimes. She sucks her tongue, but the bruxism
fully disappeared. Her smile appears more. She one or two new
words.
She
recognizes more the persons. Hypertonic movements of the arms and of the hands
are present. Now is more quiet even in the afternoon, and she doesn't cry after
lunch. Menses appeared, even if very irregular (three times in a year). Her
face is more rosy. Self-aggression is very rare. The
rocking went down from one hour daily to not more than five minutes. Her health
did well. When she has high fever, she sleeps much. In this time she had much
less her hands in her mouth and nearly missing the redness of the eyes. In the
peers' group she shows her preferences: Usually she stays only with fewer
children. She walks much better, more harmonious in her movements, with her
back more erect. She plays by herself with the teddy bear. Now, she pays more
attention to the television, mainly to music and ballet.
Therapy
variation (daily doses, by the oral via): Oxazepam stopped, delorazepam 0.3mg, amantadine 100mg, clonidine
75mcg.
The fifth checkup (April 2005). The father did
get her to check only after 24 months, because, together, she is going quite
well. According her father and her grandmother, there were some further
improvements.
Motility: Now she is less
clumsy in walking, and less overactive. She does not succeed to use the
staircases by herself. She does swim and horse therapy.
Language: She understands more
but she inclines to obey not. Now, she tries to speak, and she says some words.
Often parents heard her to sing softly by herself.
Behaviour: She became
mischievous: She pays attention if the others look at her, then she does what
she was told to do not. Now she can drink by herself, then
throws down the glass, which sometimes she has broken. She puts less her hands
into her mouth. Rocking much diminished. Self-aggression disappeared. She used
still hair pulling and when told off, she has outbursts. She uses to get out of
the shoes. She searches always to put the hands under the flowing water.
At the
Centre that she attends, she is gladly with the others children who are in
wheelchairs. She uses to play with the hands of other persons. Now, she plays more
by herself, but she did not learn new plays. As for the television, now she
watches it with more attention and she is amused seeing the cartoons.
Mood: Now she is more
serene and smiles more. As the weather is changing, she is a little agitated.
When she is irritated, and somebody caresses her, she becomes calm. Some time
she cries, when she has her nose clogged, and she wants to be cleaned.
Sleep,
feeding and sphincterial control: At night she
sleeps, with rare awakenings, or little walking in the kitchen. When her
grandmother, who sleeps with her, gets up, she does it too. Towards 11am, she
falls into a doze. The bruxism is nearly missing. Now
she is less thin. Now she likes much eating bread, cheeses,
and fruits, but only when she is hungry. She chews better. She has shown
herself more willingly for the dental treatments, and now she has less
drooling, mainly after having her teeth cured. Colic is scarcely present. Bowel
function regulated, but the sphincterial control was
not reached.
Other: She had no
particular problems of health, only some cold. Some time she has some trembling
and some lines of fever. She became a little taller. Her facies
is more beautiful, even if always a typical facies
from a chromosomal anomaly, but more rosy. She understands the danger, but
perhaps only if it involves the sense of the depth.
Therapeutic
variation (daily doses, by the oral via): Delorazepam
0.2mg.
May
2007, the sixth checkup.
She comes back to check only after 25 months, because, altogether, as for her
father and her grandmother, she is doing enough well. The impression of the
current writer could be
of some regressive symptoms.
Motility: Her walking is going well. When there is a
little obstacle that she could easily overcome, she stops. She minds the danger.
Language: Now, she uses the fewer words she knows, and
she did not get new
acquisitions. She listens more and shows
to understand more. She sings softly,
and when there is loud music, she starts dancing. Hyperactivity nearly missed
Behaviour: Rocking did not disappear and she used to pull
her hair. With her front, she touches the edges of the pieces of furniture. Some times she shows
light head banging. She uses scratching eyes and ears. Now, she puts less her
hands in her mouth, and plays with others' hands, and even preferably with
herself hands. The fingers of the feet are scratched in the interstice among
the fingers. Now, she is less calm. She
does not bear the stockings, for which she has needs to hold the shoes' laces
fasten. Currently she feels the changes in the weather. Her habit of throwing
things away did not stop.
Mood: Her face is less relaxed. She laughs a lot.
When she stays alone, some times she looks for the company.
Sleeping, feeding and
sphincteral control:
She sleeps 7-8 hours. Her bowel is more regulated, and now she has
less colic ache. She eats more at home
that in the Centre that she attends.
Chewing improved, mainly for fruits and the bread. Now she eats all the vegetables. She drinks
by herself from the glass, but doesn't know how to properly place
it and would throw it away. The oversalivation reduced, but when she suffers from
gingivitis, it returns as first. Her height did not grow, her weight equals
Other: She did not have any particular health's problems,
and she caught only some cold. A left
under-orbital eczema is visible.
No
therapeutic variation.
The eighth checkup,
on February 2008. As the father and the grandmother
say, she is doing well. The first impression of the writer,
is not at once positive, but he has to change it.
Motility: Deambulation is well, she walks
more harmonious and runs. In front of the television, when there are musical shows, she
usually dances and she respects the rhythm.
She brings well the glass to the mouth, but she
doesn't always put back it on the table in
suitable
way. Hyperkinesis greatly decreased and she can stay
sitting. The steps give her always a feeling of danger, but she faces them with
increased safety.
Behaviour:
More cunning and spiteful. There are always stereotypies
of the arm.
Rocking is a little diminished. She pulls less her hair. With her front face
she touches less the edges of the pieces of furniture. Head banging
disappeared. She scratches less her eyes and her ears, and perhaps little less
she scratches
the fingers of
her feet, in the interstice among the
fingers. Now, she put less her hands in her mouth. She
would want her shoes removed.
The changes in the weather trouble her
lesser. She plays with the hands of the
others and sometimes intentionally scratches them.
Language:
Now, she listens of more. She uses as
many words she knows ( four at all, as with the
grandmother reports) but she has a turn for speaking of more, even if she has not done news
verbal
acquisitions. The parents say her to understand of more. Sometime, she sings
softly.
Mood:
Now, she is lesser irritable, more serene, and she searches for the company.
Sleep,
feeding and sphincteral control:
Sleeping lasts about 7-8 hours. Drooling nearly stopped. She eats of more ( as an adult person, the grandmother says). She likes much
the crumb of the bread and she chews the little pieces of the meat. Now,
she eats even
apples and
oranges.
The mozzarella is her preferred cheese, and she eats it with the fork, but to
times she eats it even in great morsels. Her bowel function runs better,
with rare colic
aches. Growing in height did not happen, her heavy is 30kg.
Other:
She has not had particular problems of health, only some cold. The underorbital eczema of the left side is intermittent.
Therapeutic variation: Amantadine
50mg daily.
Discussion.
It is
reported that the partial trisomy of the chromosome
22 does not have any therapy. That is true, if we think to a some chromosomal
rearrangement. That is not true if we want to act on symptoms of the answer to
stress, those symptoms that do the phenotypical
difference among two same subjects as for the chromosomal anomaly. Such stress
symptoms, to a large extent produced from the illness itself as a metabolic
internal stress, are not specific reactions to the homeostasis perturbation.
This is not the first case with genetic or chromosomal anomalies I treated by
drugs.
Beyond
the syndrome of the Down, on which I am involved since the 1979 (see: <www.stress-cocchi.org/Down's syndrome>), I
prescribed drug therapies in cases of tuberous sclerosis, Cri-du-chat
syndrome, Aicardi-Goutieres syndrome, Smith-Magenis syndrome, Hallervorden-Spatz
disease. My pharmacological action is not then on the cause - and it would not
be this - but on the individual resistance abilities, which can be, in some
degrees, modulated.
This
case, besides the exact chromosomal diagnosis, had physical features among the
more frequent of this syndrome: a cardiac defect (surgically fixed), cleft
palate (surgically fixed), mental retardation, delay of body development, delay
of the speech, face abnormalities.
In the
case here reported the incentive to try a drug therapy was the presence of many
symptoms linked to stress reactions. In other terms, the presence of symptoms
that are not specific of a partial trisomy 22. We can
find them in other mental illnesses, not necessarily genetic or chromosomic ones.
We list
now several of them, with the possible neurochemical
mechanism involved in brackets:
- mental retardation (GABA - glutamate?);
- speech retardation (GABA - grutamate?)
- anger
outbursts without reason (noradrenalin-adrenalin);
- spastic
constipation or diarrhea (peripheral acetylcholine);
- poor
greediness for sweet things (glutamate - GABA);
-
greediness for meat broth (glutamate - GABA)
-
self-aggression (adrenalin)
-
recurrent awakenings during the night (GABA - adrenaline);
- day
drooling (GABA - peripheral acetylcholine);
- hyperkinesis and attention deficit disorder (dopamine -
GABA);
- rocking
(GABA-glutamate?),
- face
paleness (noradrenalin)
- cold
hands and feet (GABA-glutamate?)
These are
the symptoms I used for choosing the drug regimen acting on GABA (diazepam, carbamazepine, pyridoxine and glutamine), on adrenalin (clonidine), and on dopamine (amantadine).
It is
possible that the new balance between the A type, and the B type GABAergic inhibition, indirectly improves serotoninergic and cholinergic pathways besides increasing
the stress threshold. Till now, I did not prescribe specific drugs acting in
these two neurotransmitters, even because I did not find symptoms of deficit.
Here
instead other symptoms modified in better: Attention, understanding, the mood,
irritability, sociability, self-esteem, the relationship with the object, the
play, the feeding, the weigh-height growth, the autonomy, hyperkinesis.
Speech
had poorly improvement in production, but some in understanding.
Of
course, since any antistress therapy needs to be
tailored to the current case, because stress answers are different in each
person, for genetic and acquired factors, the therapy I used here cannot be a
standard one.
Some
health professionals - it is already happening mainly about Down subjects I
treated - maintained that in similar patients this improvement would have
happened anyhow, even without any drug therapy.
This girl
had however sixteen years at the moment of the first drug prescription, and
progresses were fewer till then.
Already
ten months after the starting of the therapy the relatives said that the girl
was much more manageable, or, in other words, they did much less labours to
follow her.
Having in
mind the possibilities and the limits of an antistress
drug therapy in persons who are carriers of genetic or chromosomal anomalies,
even an easy management of this subject by her relatives is always a notable
result too.
References
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J, Goldman AS, Speed RM, Hulten MA. "Meiotic
studies of a human male carrier of the common translocation, t(11;22), suggests
postzygotic selection rather than preferential 3:1 MI
segregation as the cause of liveborn offspring with
an unbalanced translocation." Am J Hum Genet 2000, 67: 601-609.
Biederman BM; Lin CC; Lowry RB; Somerville R. Tertiary trisomy (22q11q),47,+der(22),t(11; 22). Hum Genet 1980, 53:
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Cocchi R. Seven months of palliative therapy in two siblings
with neural-axonal dystrophy of Hallervorden-Spatz
In: www.stress-cocchi.org/Genetics6.htm
Dawson
AJ; Mears AJ; Chudley AE; Bech-Hansen
T; McDermid H. Der(22)t(11;
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Beaufort C; Schneider F; Chafai R; Colette JM; Delneste D; Pierquin G.
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RK; Ferreira J; Merscher S; ohouri
M; Cannizzaro L; Shanske A;
Morrow BE . Der(22) syndrome and velo-cardio-facial
syndrome/DiGeorge syndrome share a 1.5-Mb region of
overlap on chromosome 22q11. Am J Hum Genet 1999, 64:747-758.
Gerald
WL; Ladanyi M; de Alava E; Cuatrecasas M; Kushner BH;
Hill AS;
Foot NJ; Chaplin TL; Young BD. The most frequent constitutional translocation
in humans, the t(11;22)(q23; q11) is due to a highly specific alu-mediated recombination. Hum Mol Genet 2000, 12:
1525-1532.
Hou JW. Supernumerary chromosome marker Der(22)t(11;
22) resulting from a maternal balanced translocation. Chang Gung Med J China
2003, 26:48-52
Kessel E; Pfeiffer RA, 47,XY,+der(11; 22)(q23; q12)
following balanced translocation t(11;22)(q23; q12)mat. Remarks on the problem
of trisomy 22. Hum Genet 1977, 37: 111-116.
Shaikh TH; Budarf ML; Celle L; Zackai EH; Emanuel BS.
Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation
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Tapia-Paez I; Kost-Alimova M; Hu P; Roe BA; Blennow E; Fedorova L; Imreh S; Dumanski JP. The position of t(11; 22)(q23; q11)
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Posted
on Internet on April 2003. Copyright by Renato Cocchi,
2003
For more
information on partial trisomy 22 see: www.c22c.org
Author's address:
Dr Renato COCCHI via Rabbeno,
3
42100 Reggio Emilia (Italy).
renatococchi@libero.it
Italian
translation // traduzione italiana
Other
genetic and chromosomal anomalies
Drug
modulation of stress reactions
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