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Treatment of pervasive aggression in a patient with 47 XYY karyotype

Alina R.Rais MD , Assistant Professor of Psychiatry, Psychiatry Department University of Toledo Medical Center , Toledo, OH.

Introduction

The XYY syndrome is a trisomy of the sex chromosomes where a human male individual presents with 2 Y chromosomes. It is claimed the phenotype of this condition is normal and an estimated 97 % of the United Kingdom’s 47 XYY karyotype males may not know about their karyotype difference from the regular males (1).
In the past it was thought an excess of testosterone may be responsible of these patients aggressive behaviors .However more recent work claims these patients testosterone levels are generally normal(2).
The patients with 47 XYY karyotype have in general an increased risk of learning difficulties and delayed speech and language skills (1)(3).
We want to present the case of young man with 47 XYY karyotype who was admitted into our ward due to aggressive behaviors endangering self and others. His level of aggression was high and rather unresponsive to several medications constituting a very serious treatment challenge.A review of the last 30 years relevant literature is also presented together with the case discussion and some directions of treatment.

Case Presentation

The patient, an 8 year old male, was admitted due to increasing aggressive behavior, increased hyperactivity, and property damage that occurred over the course of the previous week. He presented to the emergency department in a belligerent state as a well developed , well nourished boy appearing large for his age . Mental status examination revealed un uncooperative young boy with poor eye contact , minimal verbal communication and violent behavior. He appeared agitated and irritable , though his motoric behavior seemed appropriate for his age and his gate was normal with no irregular movements. During his interview he was anxious with labile affect , becoming tearful when separated from his mother. His speech was of normal rate though , though characterized by slurring and stuttering . He presented with no hallucinations or delusions and both his thought process and content were in general intact .He was oriented to time only and was easily distracted. Both his judgement and insight of his condition were impaired. Despite his potential for violence toward others , he presented no thoughts to intentionally hurt others or to hurt himself. Based on his past psychiatric history and his present clinical condition the following DSM IV classification diagnoses were made : Mood Disorder NOS , Mild Mental Retardation (by records), Attention Deficit Hyperactivity Disorder NOS and rule out Oppositional Defiant Disorder.

The history revealed that a diagnosis of 47 XYY Syndrome had been made at the age of 6 because of defiant and aggressive behaviors , frequent temper tantrums , larger body size learning difficulties and delayed speech development . Diagnostic studies were performed in which a complete metabolic profile was within normal limits , DNA studies for Fragile X were negative , and chromosome studies revealed a karyotype 47 XYY. An EEG displayed intermittent rhythmic delta waves in the left temporal lobe
induced by hyperventilation and an MRI illustrated sequela from a prior injury to the right temporal area .(The origin of the injury can not be established .No evidence of any past history of head trauma was evident during our investigation). At that time information regarding the 47XYY syndrome was reviewed with the family and the patient was instructed to follow up pediatric psychiatrist.

Over time a medication regime of long acting Methylphenidate (Concerta) up to 54 mg oral daily , Olanzapine 5 mg oral three times a day , Valproate 500 mg oral daily , and Oxacarbamazepam 300 mg oral twice a day was established to address mood lability , aggressive behavior and mild self mutilation.The patient was admitted for psychiatric inpatient treatment on a few different occasions .One week prior to the present admission he was emergently taken to a local community mental health center for assessment due to worsening in his hostile behavior and aggression toward the caregivers . He was added Lithium 300 mg oral twice a day to his medications and discharged home . However his hostility toward authoritative figures , his presence as a threat to his academic peers , and his lack of remorse for his actions continued to escalate following this addition.

Regarding his medical history the patient presented with no pain currently or in the recent past . His eating habits are normal and his appetite unaffected. He suffers from enuresis , encompresis , constipation , and frequent upper respiratory tract infections .
Other than previously mentioned inpatient psychiatric treatment and an appendectomy , he has had no prior hospitalizations and surgeries . From the ages of three to eight hea has experienced tantrums , head banging , property destruction , problems with separation , aggression to self and others , poor attention and concentration , depressive thoughts and suicidal ideation . there is no evidence of any complications during his mother pregnancy and delivery , though there is an unconfirmed possibility of drug and alcohol exposure in the utero.

The patient has a positive family history for Major Depressive disorder (paternal grandmother , mother and brother) and substance abuse ( father and brother). He was a victim of physical and emotional abuse by his parents between the ages 2 and 4 . Consequently he was removed from his home and placed with some of his relatives.
He presented a continous pattern of problematic social interactions with siblings adults and peers.He was schooled in a special program for handicapped children.

The physical and neurological examinations were normal except some minor bruises in the patient’s back. Routine laboratory investigations consisting of a complete blood count with differential , metabolic panel , lipid profile , urinalysis and blood lead levels were within normal limits . Endocrinological laboratory investigations , including thyroid function tests , were also normal . Drug levels reveals a normal lithium level and a valproate level of 65 mcg/ml. An EKG exhibited no abnormalities .

The patient was admitted under suicide and run away precautions . He initially tested limits and needed redirection frequently . He continued to be easily ditracted and demonstrated poor concentration and attention span . In addition , tantrums , a lack of self control with low frustration threshold , attention seeking behavior , and aggression toward staff members were common. During his admission he attended individual ,group
Recreational and academic therapy . This revealed his poor self esteem and poor
3.
expression of his feelings . Furthermore it demonstrated his desire to spend time with his peers but also his difficulties relating to and interacting with them . He had issues with invading others personal space and did not recognize social cues .It was noticed that the addition of Methylphenidate did not clearly improve patient’s attention span and concentration ability . We decided to discontinue the Methylphenidate and the Lithium due to their lack of efficacy . Within days the patient slightly improved .His speech was articulate of low volume , his mood became stabler and less aggressive . he was experiencing no side effects from medications or physical problems , no thoughts or intents to hurt self or others no psychosis , no manic or hypomanic symptoms. The patient was discharged to the outpatient care.

Discussion

The clinical polymorphism of the XYY syndrome is well known (4),(5).There is a wide variation of clinical future of physical and behavioral nature(5).The presence of minimal cerebral dysfunction due to early acquired brain damage and ADHD are thought to be high risk conditions for criminality (4).
Schiavi et al (6) performed a double blind placebo controlled study of XYY and XXY men found in a birth cohort of 4591 tall men who were born in Copenhagen .Information from social records , structural psychological interview and projective tests did not support the notion that men with sex chromosomal anomalies are particularly violent or aggressive. The XYY men had higher concentrations of testosterone and luteinizing hormone(LH) and FSH (follicle stimulating hormone) than matched control groups.It was a high statistic correlation between plasma testosterone level and criminal convictions. However the relations between testosterone level and criminal behavior was not reflected in measures of aggression derived from the psychological interview and projective testing .There was no specific evidence testosterone is a mediating factor in criminal behavior of XYY men.
Hunter(7) studied clinical and psychiatric aspects of XYY males by a survey of 1811 males found in hospitals for mentally handicapped. This survey done in 18 hospitals found 12 males with 47 XYY karyotype . The psychological, physical and social findings were studied in matched groups for IQ and height.The main psychiatric findings were that diminished intelligence , retardation in development of secondary sexual characteristics and poor emotional control were in general leading to inadequate social adaptive patterns. Our case report fits somehow in the last described category .One of the most puzzling characteristics were his non responsivness to a fairly robust combination of mood regulators. One of our hypothesis was that the combination of multiple medications in his case had probably a negative therapeutic effect and fewer medications achieved better results. This case in our opinion clearly teaches that the complexity of interactions between genetic anomalies environmental and individual factors needs to be approached in case by case basis.

References

1. Allanson ,JE , Graham ,GE (2002) “Sex Chromosomes Abnormalities” in Rimoin DL et al – Emery and Rimoin , Principles and Practice of Medical Genetics , 4th ed , London
Churchill – Livingstone , pp 1184 – 1201. ISBN – 0443-06434-2.

2. Ratcliffe SG et al , Prenatal testosterone levels in XXY and XYY males. 1994 Horm Res 42(3):106-9.

3. Milunsky Jeff M . (2004) “ Prenatal Diagnoses of Sex Chromosome Abnormalities”,
in Milunsky , Aubrey (ed), Genetic Disorders and the Fetus : Diagnosis ,Prevention , and Treatment , 5th edition , Baltimore : The John Hopkins University Press , pp 297 – 340.
ISBN 0-8018-7928-0.

4. Knecht T , Bilogical aspects of Delinquency and Aggression – Schweiz Med Wochenschr , 1993 Jun 5 ; 123(22) : 1169-75.

5. Diego Nunez et al , Clinical Polymorphism of the XYY Syndrome , An Esp Pediatr.1992-Aug:37(2):140-4.

6. Schiavi RC , Theilgard A et al , Sex Chromosome anomalies , Hormones and Aggressivity – Arch Gen Psych 1984 Jan ; 41(1): 93-9.

7. Hunter H , XYY males.Some clinical and psychiatric aspects deriving from a survey of 1,811 males in hospitals for mentally handicapped. Br J Psychiatry . 1977 Nov;131:468-77.

Address any correspondence to : Alina R.Rais MD
Ruppert Health Center
3120 Glendale Avenue
Toledo , Ohio 43615
USA

First Published September 2007

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