Chromosomal Abnormalities and Bipolar Affective Disorder: Velo-Cardio-Facial Syndrome

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Medscape Psychiatry & Mental Health eJournal. 1997;2(4) 

In This Article

Five Cases of VCFS and Bipolar Disorder

The patient, a 22-year-old male, was the product of an uncomplicated, full-term pregnancy. With the exception of speech, all developmental milestones were normal. He was first seen at age 5, referred for hypernasality and speech articulation problems. The patient had the classic facial phenotype of VCFS, occult submucous cleft palate, and a small ventricular septal cardiac defect. The diagnosis of VCFS was made on the basis of the clinical findings and by fluorescence in situ hybridization (FISH). The patient had a pharyngeal flap operation at the age of 6 years to correct the speech resonance problems and was followed on a yearly basis.

Described by his parents as quiet, timid, and clumsy, with a feeling of inferiority during his early childhood, the patient had few friends and tried to "hold to himself." At age 15, after being transferred from public school to private school, he "crashed" and began to hide from people, to use foul language, and to have a sleep-wake reversal. He also lost his appetite and lost weight. Over the ensuing months he continued to be depressed, with a diminished appetite. He expressed the feeling that his teachers were spying on him. At this time he was seen by a local psychiatrist who diagnosed him as having "paranoia" and started him on thioridazine 400mg/day. Within the next month, the patient began to have violent outbursts and, on occasion, he would physically assault his father. A year later, the thioridazine dosage was reduced to 100mg/day and he was reported to be less "depressed," although he continued to have difficulty focusing and was easily distracted. During a psychiatric evaluation at age 20 his parents reported that he would periodically express grandiose ideas, initially describing his wish to be a famous athlete and then later espousing many money-making schemes that he expected would make him rich. During these times he was hypertalkative and restless, and had interrupted sleep. Based on information obtained from DICA-R interviews of parents and SCID of patient, as well as a clinical interview, the patient was given the following DSM-IV diagnoses:

  • Axis I: Bipolar I disorder with psychotic (grandiose and paranoid) features

  • Axis II: None

  • Axis III: VCFS (deletion at chromosome 22q11)

This 17-year-old patient was referred at 4 months for treatment of a cleft of the soft palate. She was a product of a pregnancy complicated by toxemia and was delivered by cesarean section. Following surgical repair of the cleft palate, major problems of slow growth, poor weight gain, and social immaturity persisted. Growth hormone intramuscular therapy was instituted at age 3 years, but no improvements resulted.

At the time of psychiatric evaluation, she was living with her mother, father, and siblings. Her mother was diagnosed with cancer, and the illness and ensuing chemotherapy were major stressors for the entire family. The patient had a long history of childhood behavioral problems, including impulsive acts, stealing, truancy, and cursing at authority figures. In the first grade she smacked a teacher in the face because the teacher was shaking her. At age 13, she started to steal items such as lipstick and magazines from stores, and recalled being "obsessed" with lipstick. The patient attended a regular class at a private technical school until she dropped out during midyear of the tenth grade. The patient recalled having trouble attending school because she did not have enough energy and had trouble concentrating in the classroom. In elementary school the patient received group therapy for depression, and is aware of having experienced mood swings since the age of 11, several times a year. Her mother reported that these mood swings occurred every 2 to 3 months. During these episodes she had periods of hypertalkativeness that alternated with sulking withdrawal and avoidance of communication. In addition, she described feeling very excited and full of energy during these periods, and she joked and felt very elated. During these high-energy, elated-mood states, the patient ate carbohydrates excessively, which she described as bingeing. On several occasions she impulsively went on shopping sprees with a credit card and bought clothes that she did not need and never wore. In contrast to these periods of elation, the patient also suffered bouts of irritation, during which she felt easily annoyed or rejected and found it more difficult to get along with others.

The patient experienced her first episode of major depression at age 15. At that time she had suicidal thoughts, stopped eating, and within 2 weeks lost a significant amount of weight. She locked herself in her room for an extended period, overslept day and night, and was anhedonic with no energy. A second episode occurred a year later, which the patient described as more severe than the first. During this episode of 4 to 5 weeks' duration she remembered dressing only in black. While she described having chronic insomnia, typically this became much worse when she was depressed, during which time she ruminated about the day's events and felt useless and worthless. At the time of this evaluation she had been in a continuous state of depression for over a year, interrupted by brief periods of bursts of energy with elation or irritability lasting days to weeks. Based on information obtained from DICA-R interviews of both patient and parents, as well as a clinical interview, the patient was given the following DSM-IV diagnoses:

  • Axis I : Bipolar II disorder; rapid cycling variant

  • Axis II: None

  • Axis III: VCFS (no deletion, by FISH)

This 15-year-old male was first referred at the age of 6 years with speech and language problems. He was born after a pregnancy complicated by polyhydramnios, nausea, vomiting, and signs of early toxemia. He suffered chronic infections throughout infancy and childhood. The diagnosis of VCFS was made on clinical evaluation and confirmed with molecular testing. He had the classic facial phenotype of VCFS, and in addition had learning and emotional problems. Mild pulmonic stenosis was also present.

This patient lives with his parents and an older sister and currently attends a special school for learning-disabled students. The patient was described by his parents as a docile and content child until approximately 5 years of age. He would play with toy cars for hours and would isolate himself and play apart from peers in nursery school. Between the ages of 4 and 9 he experienced extreme separation anxiety, and the parents had to sit by his bedside until he fell asleep at night. He would not allow them to leave while awake. In kindergarten he was observed by his teachers to be very restless. At age 7, he became quite distractible and was diagnosed as learning disabled. The school psychologist described him as "emotionally immature and very impulsive," and he was easily provoked to anger, which was sometimes triggered by stressful situations. The parents described him as more volatile at age 7, and that from that age forward, irritability became a consistent feature of his emotional state. The patient becomes easily irritated if someone tries to stop him from doing something that he is interested in, and he will often have temper tantrums that culminate in a destructive act. His parents report that "when he is really angry he is capable of putting a hole in the wall."

When the patient was 10 years old, his parents consulted a child psychiatrist for the learning disability and the behavioral problems. The patient was diagnosed at that time as having ADHD and treated with methylphenidate 15mg in the morning, which resulted in mild improvement in concentration. At age 11-12, the patient began to experience high-energy states that would fluctuate over a period of hours. He would typically get a burst of energy at night and would engage in uncharacteristic activities like cleaning his closet excessively, doing laundry, and making many plans for the next day. He would talk excessively and with great intensity during these periods, so much so that the parents would have to tell him to calm down and to be quiet. Such episodes occurred approximately 2-3 times per month. Based on information obtained from DICA-R interviews of the patient and parents, as well as a clinical interview, the patient was given the following DSM-IV diagnoses:

  • Axis I : Bipolar II disorder, rapid-cycling variant

  • Axis II: Deferred

  • Axis III: VCFS (deletion at chromosome 22q11)

The patient is a 13-year-old female who was reported by her parents to be a shy, timid child who worried a lot. She first came to psychiatric attention at age 6 on entering kindergarten, when she became extremely fearful of separating from her mother and increasingly anxious about going to school and engaging in other activities. She was diagnosed as having separation anxiety disorder with panic attacks and was prescribed alprazolam 0.5mg daily, which alleviated her anxiety and enabled her to return to school. When on the medication, she was noted to be more outgoing and happier at school and continued to do well for many months. In the third grade at age 8, however, she complained of difficulty concentrating, ruminated about death, and again experienced anxiety symptoms in the morning, which resulted in refusal to go to school. Retrospectively, her parents observed that her inattention had more to do with a preoccupation with negative thoughts and a depressed mood. On this occasion, however, she was diagnosed with ADHD and began treatment with methylphenidate. Within 24 hours on this stimulant medication, she became overly exuberant, oppositional, argumentative, and hypertalkative. In addition, she was described as wildly hypersexual and had to be controlled from chasing after her brother and becoming very physical with him. This hypomanic state alternated with downcast, emotionally labile moods, when she would become tearful and ruminate about death. Initially, these cycles alternated within hours and continued for weeks beyond the discontinuation of methylphenidate, ending in a major depression, which was treated with imipramine 40mg daily. Because of side effects she was switched to fluoxetine 20mg daily, to which she had an initial response, but a rapid-cycling pattern developed and she was advised to start on a mood stabilizer. Based on information obtained from DICA-R interviews of both patient and parents, as well as a clinical interview, the patient was given the following DSM-IV diagnoses:

  • Axis I: Bipolar II disorder (rapid cycling variant), initial episode stimulant-induced

  • Axis II: None

  • Axis III: VCFS (deletion on chromosome 22q11)

This patient is a 13-year-old male who lives with his parents and sister. He recently completed the eighth grade in a regular school, where he received speech therapy 3 times per week, had access to a resource teacher, and received psychotherapy once a month.

The parents reported that he had been an impulsive child since approximately the age of 2, with night-time enuresis until age 8, and that it has always been very difficult for him to adjust to minor changes. If a game had been canceled or the restaurant where they wanted to go was closed, he became very angry, and it could take him hours to calm down. The patient was described as very distractible, and the mother stated that he frequently fluctuated between a very low and an inflated self-esteem. He started to have severe temper tantrums 1 to 2 years before evaluation, with a frequency of approximately once per month. The tantrums, which lasted about half an hour, were usually triggered by seemingly minor incidents--for example, something did not go the way he wanted it to, or something had been taken away from him. He would then yell and scream, pound on walls and doors and spit down the stairs, and would often punch his sister and father, or attempt to choke his mother. At the conclusion of such an episode, the patient was contrite and remorseful, stating that it was not really him but that "my brain is telling me to do these things." He would explain that he felt the behaviors to be beyond his control, but he denied hearing voices. He was recently suspended from school for throwing water at another student, and has been swearing with increasing frequency over the past couple of months. Although these impulsive behaviors were severe enough to result in his being suspended from school, his parents believe that these episodes are more severe at home. The patient once stole from his family, but the mother did not consider this very important. He lies quite frequently, especially about his age or about his sister's name. His mother referred to them as "white lies" and "stupid lies," and stated that he never lies about something important. She said that he is making up facts and "thinking he is funny." He sometimes acts mischievously, according to his parents. This was evident during his evaluation, when he stuffed the bathroom sink with paper towels and turned on the water. He fights when other students tease him, but he is not very often involved in physical fights.

When the patient was 12 years old, teachers contacted the parents because they had observed that the patient looked depressed at times. Since then he has received counseling for depression. The parents have observed that over the last year the patient's mood is sometimes "down." According to them, these periods appear to be triggered by some disappointment, or by frustration about having VCFS or by feeling rejected by his peers. He then keeps to himself, wants to be alone, withdraws from the family, does not feel like talking, and sometimes cries. He engages in solitary activities, such as watching TV or playing computer games, and nobody is allowed to enter his room or is able to coax him to come out. The parents reported that during these episodes of being down, sad, and depressed, his behavior is distinctly different from when he is impulsive. These depressive episodes usually last for a few hours but might reoccur for a couple of days and then resolve for a longer time period (ie, weeks). The parents stated, however, that their son has been chronically depressed over the past year ("He is a little bit sad all of the time"), except during the episodes of impulsivity.

Over the past year the patient experienced episodes of exuberance and extreme excitement prior to such special events as going on trips or attending sporting events. At these times he was hypertalkative and his speech was pressured and repetitive. During these periods he stayed on the same subject for days, and it was very difficult, if not impossible, to draw his attention to any other subject. Each of these episodes lasted approximately 1 week. When the parents consulted a child psychiatrist because of the impulsivity and difficult behavior of their son, the patient was diagnosed with ADHD. The psychiatrist prescribed dexamphetamine, initially at a dosage of 10mg/day, which was increased to 20mg/day after 2 weeks. This was reported to have produced a slight improvement in his impulsive behavior and inattention. Since starting dexamphetamine, a diurnal variation in his mood has been reported during which the patient is irritable, restless, impatient, and easily upset in the morning, "bugging" and insulting other family members. He is much calmer when he gets home from school. It is not entirely clear whether this mood change is linked to the dexamphetamine that he takes every morning.

Recently, the patient developed obsessions about germs in food. He is very concerned that people who touch his food might not be clean, and he sometimes refuses to eat the food (eg, fast-food hamburger) that has already been ordered because he is concerned about germs and getting sick. He was extremely afraid of the dark in the past, and is still scared by it, but is now able to go to the basement with all the lights switched on. His parents described his extreme fear at seeing a strange dog, which has made him cross the street to avoid an encounter; his response to a familiar dog is much less intense. He was very scared of heights in the past, but on a recent visit to Manhattan he had no problem walking on the terrace of the Empire State Building. Based on information obtained from DICA-R interviews of both patient and parents, as well as a clinical interview, the patient was given the following DSM-IV diagnoses:

  • Axis I: Cyclothymic disorder (not rapid cycling), with episodes of hypomania, irritability, and impulsivity and episodes of mild depression. The duration is over 1 year.

  • Past diagnosis: Nocturnal enuresis (until age 8); ADHD (he does not meet all the criteria in the present, but met them in the past).

  • Axis II: None

  • Axis III: VCFS (deletion at chromosome 22q11)


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