Dep. of Pediatrics
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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.
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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Allen WP, Phelan MC, Stevenson RE (1991): Smith-Magenis syndrome: Report of five patients. Proc Greenwood Genet Ctr 10:18-22.
Amman MG, Singh NN, Stewart AW, Field CJ.(1985): Psychometric characteristics of the Aberrant Behavior Checklist. Am J Ment Def, 99:492-502.
Barnicoat AJ, Moller HU, Palmer RW, Russell-Eggitt I, Winter RM (1996): An unusual presentation of Smith.Magenis syndrome with iris dysgenesis. Clin Dysmorph 5:153-158.
Behjati F, Mullarkey M, Bergbaum A, Berry AC, Docherty Z (1997): Chromosome deletion 17p11.2 (Smith-Magenis syndome) in seven new patients, four of whom had heen referred for fragile-X investigation. Clin Genet 51:71-74.
Chen RM, Lupski
JR, Greenberg F, and Lewis RA (1996>: Ophthalmic manifestations of Smith-Magenis
Colley AF, Leversha
MA, Voullaire LE, Rogers JG (1990): Five cases demonstrating the distinctive
behavioral features of chromosome deletion
17(pll.2p11.2) <Smith-Magenis syndrome>. J Paediatr Child Health 26:17-21.
Fan YS, Farrell
SA (1994): Prenatal diagnosis of interstitual deletion of 17 (Pl 1.2p121.2)
(Smith-Magenis syndrome). J Paediatr Child Health 26:
Finucane BM, Jaeger ER, Kurtz MB, Weinstein M, Scott CI (1993a): Eye abnomalities in the Smith-Magenis contiguous gene deletion syndrome.Am J Med Genet 45:443-6.
Finucane BM. Kurtz M, Babu VR, Scott CI (1993b): Mosaicism for deletion 17p11.2 in 5 boy with the Smith-Magenis syndrome. Am J Med Genet 45:447-9.
Finucane, BM, Konar D, Givler BH, Kurtz MB, and Scott, LI (1994) The spasmodic upper body squeeze: A characteristic behavior in SmithMagenis syndrome. Dev Med Child Neurol 36:70433.
Fischer H, Oswald HP, Duba HD, Doczy L. Simma B, Utermann G, Hass OA (1993): Constitutional interstitial deletion of 17(pll.2) (SmithMagenis syndrome): A clinically recognizable microdeletion syndrome: Report of two csses and review of the literature. Klin Paediatr 205:162-166.
Greenberg F. Guzzetta
V, De Oca-Luna RM, Magenis RE, Smith ACM, Richter SF. Kondo I, Dobyns WB, Pate
PI, Lupski J (1991): Molecular
analysis of the Smith.Magenis syndrome: A possible contiguous.gene syndrome associated with del(17)(pll.2). Am J Hum Genet 49:1207-1218.
Greenberg R. Lewis
RA, Potocki L, Glaze D. Parke J. Killian J, Murpha MA, Williamson D, Brown F,
Dutton R, McCluggage C, Friedman E,
Sulek M, Lupski JR (1996): Multi-discipIinary clinical study of Smith Magenis syndrome (deletion 17p11.2). Am J Med Genet 62:247-254.
Hamill MA, Roberts SH, Maguire MJ, Laurence KM (1990): Interstitial deletion of 17p11.2: Case report and review. Ann Genet 31:3688.
Jan JE and H Espezel (1995): Melatonin treatment of chronic sleep disorders. Dev Med Child Neurol 37:279-281.
Jan JE, Esperzel H, Appieton RE (1994): The treatment of sleep disorders with melatonin. Dev Med Child Neurol 36:97-107.
Lockwood D, Hecht F, Dowman C, Hecht BK, Rizkallah TH, Goodwin TM, Allanson J (1988): Chromosome sub-band 17p11.2 deletion: A minute deletion syndrome. J Med Genet 25:732-737.
Masuno M, Asano J, Arai M, Kuwahara T, Orii T (1992): Interstitial deletion of 17p11.2 with brain abnormalities. Clin Genet 41:278-280.
Meinecke P (1993): Confirmation of a particular but non specific metacarpophalangeal pattern profile in patients with the Smith-Magenis -syndrome due to interstitial deletion of 17p. Am J Med Genet 45:441-42.
Moncla A, Livet MO, Auger M, Mattei JF, Mattei MG, Firaud F (1991): Smith.Magenis syndome: A new contiguous gene syndrome. Report of three new cases. J Med Genet 28:627-632.
Patel SR, Bartley JA (1984): Interstitial deletion of the short arm of chromsome 17. Hum Genet 67:237-238.
Popp DW, Johnson CP, Stratton RF (1987): An additional case of deletion 17p11.2. Am J Med Genet 26:493-495.
Potacki L, Reiter RJ. Glaze D, Lupski JR (1997): Twenty-four hour urinary excretion of 6-suiphatoxymelstonin in Smith-Magenis Syndrome. American College of Medical Genetics Conference, A31.
Smith ACM, Mc Gavran L, Waldstein G (1982): Deletion of the 17 short arm in two patients with facial clefts. Am J Hum Genet 34 (Suppl):A410.
Smith ACM, McGavran L, Robinson J, Waldstein G, Macfarlane J, Zonona J, Reiss J, Lahr M. Allen L, Magenis E (1986): Interstitial deletion of (17)(pll.2p11.2) in nine patients. Am J Med Genet 24:393-414.
Stratton RF, Dobyns WB, Greenberg F, De Sana JR Moore C, Fidone G, Runge GH. et 51- (1986): Interstitial deletion of(17)(p1 1.2p11.2): Report of six additional patients with a new Chromosome deletion syndrome. Am J Med Genet 24:421-432.
Zori RT, Lupski
JR. Heju Z, Greenberg F, Killian JM, Gray BA, Driscoll DJ, Patel Pl, Zackowski
JL (1993): Clinical, cytogenetic, and molecular
evidence for an infant with Smith-Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion. Am J Med Genet 47:504-511.
First Published 10th December 2003