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Helmut Niederhofer
Regional Hospital
of Bolzano
Dep. of Pediatrics
Via L.-Boehler, 5
39100 Bolzano
ITALY
Tel.: +39 0471 466666
Fax: +39 0471 46609
E-Mail: helmut.niederhofer@uibk.ac.at
Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital
anomaly and mental retardation syndrome caused by an interstitial deletion of
chromosome 17 pll.2. Although the physical and molecular genetic features of
SMS are increasingly well understood, work is more limited on SMS's behavioral
phenotype, which includes self-injury, tantrums, aggression, attention deficit,
and sleep disturbance. This case-report describes the lowering of the aggression
level of a 13 year old individual with SMS.
KEY WORDS:
SMS, chromosome del 17 pll.2; behavioural phenotype; mental retardation; Risperidone
Smith Magenis syndrome (SMS)
is a distinct and clinically recognizable multiple congenital anomaly (MCA)
and mental retardation syndrome (most patients between 40 and 54) caused by
an interstitial deletion of chromosome 17 pll.2. First described in two males
reported in 1982 by Smith et al., the syndrome was further delineated in a tandem
series of 15 patients (Smith et al., 1986; Stratton et al., 1986). In all cases,
the 17p11.2 deletion has been associated with a distinct phenotype of physical,
developmental, and behavioral features, now referred to as the Smith-Magenis
syndrome (SMS). More than 100 cases, ranging from 1 month to 72 years of age
have been identified worldwide from a diversity of ethnic groups (Smith et al.,
1982, 1986; Patel and Bartley 1984; Stratton et al., 1986; Popp et al., 1987;
Lockwood et al., 1988; Colley et al., 1990; Hamill et al 1990; Allen et al.,
1991; Greenberg et al., 1991; Moncla et al., 1991; Masuno et al., 1992; Finucane
et al., 1993ab, 1994; Fischer et al., 1993; Meinecke, 1993; Zori et al., 1993;
Fan and Farrell, 1994; Barmcoat et al., 1996; Greenberg et al., 1991, 1996;
Behjati et al 1997).
The largest series of SMS patients (N = 27) was evaluated by Greenberg et al
(1996) as part of a multidisciplinary clinical, cytogenetic, and molecular approach
to SMS. Common features seen in over two thirds of SMS individuals include:
brachycephaly with a characteristic craniofacial features (mid-face hypoplasia,
prominent forehead, upslanting palpebral fissures, epicanthal folds, broad nasal
bridge, downturned mouth with cupid's bow, ear anomalies, and relative prognathism,
and ocular abnormalities); short stature; brachydactyly; a hoarse, deep voice;
historv of infantile hypotonia and failure to thrive; speech delay with/without
associated hearing loss; signs of peripheral neuropathy; behavioral problems
induding sleep disturbance and self-injurious behaviors; and variable degrees
of mental retardation. Several features appear to be age-dependent, including
prominent forehead, prognathism, brachycephaly, hoarse voice, and ophthalmologic
findings, specifically high myopia with/without retinal detachment (Finucane
et al., 1993a,b; Chenet al., 1996). Other less common findings include facial
clefts, congenital heart defects, seizures, and urinary tract anomalies.
The vast majority of persons with SMS have been identified in the last 5 years
as a result of improved cytogenetic techniques for high-resolution banding.
While the number of reported cases remains small, the estimated prevalence of
SMS is 1125,000 births (Green et al., 1991). Virtually all cases of SMS have
been confirmed cytogenetically, with detectable deletions of 17p11.2 ranging
from 2 to 9 megabases. Moderate quality and 450-550 band resolution is generally
adequate for detection of the deletions of 17p11 (Behjati et al.. 1997); however,
clinically suspected cases in which the deletion is not cytogenetically detectable
warrant fluorescence in situ hybridization (FISH) for the SMS region.
In all but one case (Zori et al., 1993), the deletion occurs de novo, suggesting
a low recurrence risk. Random parental origin of the 17p deletion in 15 patients
with SMS was also shown, suggesting the imprinting does not play a role in the
expression of SMS phenotype (Greenberg et al., 1991).
Phenotypically, severe behavior disorders such as autoaggression and automatism of gesticulations are typical for SMS. Patients are quite communicative and follow rules. Furthermore, they are aggressive, explosive, show perseverations as well as attention deficits and hyperactivity.
There are no studies reporting possible efficacy of psychostimulants, antipsychotics, antiepileptics and antidepressants.
For that reason, we describe a case, where risperidone, an atypical antipsychotic, improved aggression and impulsivity significantly.
We report a 12 year old
male patient who suffers from SMS diagnosed 4 years ago. Diagnosis has been
confirmed by genetic examination. The psychomotor agitation, combined with the
attention deficit as well as the aggressive behavior led to a 4 week admission
to a psychiatric hospital. The patient did not suffer from organical diseases,
his IQ was about 67 (HAWIE).
After an EEG, he was medicated with Paroxetine (20mg/die for 2 weeks, then 40mg/die).
He has also been treated psychotherapeutically - until yet.
The Paroxetine serum level was within the therapeutical range. Symptomatology
did not improve sufficiently. So therapy was completed by Carbamazepine (2x300mg/die).
The Carbamazepine serum level was within the therapeutical range, as well as
the simultaneously checked Paroxetine serum level. Symptomatology did not improve
significantly within the following eight weeks. For that reason, the medication
was stopped and the patient was treated psychopharmacolocically with Methylphenidate
(successively up to 30mg/die). Mood stabilizers were not given any longer. Symptomatology
did not improve sufficiently within two months. We suggested switching to Moclobemide,
but the patient and his parents refused.
After a 3 week washout period we started administering Risperidone, with a starting
dose of 1mg daily, 2 mg after one week and after 2 weeks finally 3 mg. We did
not observe any adverse effect. Aggression, measured by the Aberrant Behavior
Checklist (Amman et al, 1985) diminished significantly from a score of 19 to
a score of 10 (p=.0.001, t-test), as well as impulsivity did. The patient finally
attended school regularly.
SMS shows a variety of symptoms
similar to the Attention Deficit Syndrome, including aggression, impulsivity
and attention deficit. Medications such as antidepressants and methylphenidate
or mood stabilizers such as e.g. Carbamazepine do not improve symptomatology
significantly. Antipsychotics show severe collateral effects. For that reason,
their use for adolescents should be handled very restrictively. There are no
systematic studies, reporting possible benefits of antipsychotics for SMS patients.
Risperidon at a dosage less than 4 mg is reported not to have side effects,
even in children and adolescents. For that reason, we used this substance as
"last choice" medication for a child, where antidepressants, methylphenidate
and mood stabilizers were ineffective. Our observation shows, that low dosage
risperidone medication may reduce aggression and impulsivity significantly.
Systematic studies will be necessary to confirm our results and to check possible
benefits of other possible antipsychotics.
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All pages copyright ©Priory Lodge Education Ltd 1994-2004.
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First Published 10th December 2003