Williams Syndrome CPCP by Medical Student Rob Brown

See Johan’s story at Johan Coetzee.

Here’s a very nice presentation by a senior medical student, Rob Brown on psychiatric medications used to treat psychiatric syndromes frequently seen in patients with a rare genetic disorder, Williams Syndrome. Rob is planning to do his residency in Urology and appreciates what he’s learning during his rotation on the psychiatry consultation service. Rob had a nice outline for his presentation based on a recent review article by Martens and colleagues [1]. The survey was apparently completed by the parents of Williams Syndromes and it was a convenience sample because the survey was distributed to the attendees of the National Williams Syndrome Conference (see link Williams Syndrome Association).

There are differing prevalence rates in the literature on the epidemiology of Williams Syndrome with prevalence rates varying from 1 in 7500 to 1 in 20,000.  It is a neurodevelopmental genetic disorder caused by micro is deletion on the seventh chromosome.  Several genes are deleted, one of them the Elastin gene.  The absent expression of the elastin protein likely contributes to some of the clinical features.

Clinical Features

Cardiovascular disorders include stenosis of medium and large vessels most typically at the aortic valve.  Hypertension often develops in childhood and continues throughout life.  Cardiovascular disorders cause 25-100 times greater mortality than among controls.

Among the endocrine disorders, episodic hypercalciuria occurs between 5 and 50% of patients.  There can be impaired glucose tolerance and frank diabetes mellitus.  There is also a decreased annual height velocity with an early attenuated growth spurt.

Neurodevelopmental disorders include problems with developmental delay in language and motor skills as well as mild to moderate intellectual disability [2].  Interestingly persons with Williams syndrome or often described as friendly, and perhaps overly social leading to the descriptor “cocktail party” personality.  They are also described as highly empathetic, a quality which makes them very likable.

Psychopathology

Attention deficit hyperactivity disorder (ADHD) was estimated in one study to occur in 64% of patients with Williams Syndrome who were between 4 and 16 years of age.  The occurrence rates of behavioral emotional and thought regulation disorders tends to be higher than in the general population, and this is thought to be a result of executive dysfunction.

However, the most studied area for psychopathology in Williams Syndrome persons are the anxiety disorders.  Generalized anxiety disorder (GAD) occurs at a rate of up to 11.3% and the rate for specific phobias tends to be as high as 53%.  About half of Williams Syndrome patients who are adolescents are being treated with an anxiolytic.  Depressive disorders occur in up to 14% of adolescents and 25% of adult patients with Williams Syndrome.

Psychopharmacotherapy

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed psychotropic medications.  The evidence for their efficacy is mostly anecdotal.  Survey results show that 20-50% of the parents’ responded that they are very effective and 2145% say that they are somewhat effective.  The most common side effects are similar to those experienced by neurotypical individuals.  Neurological side effects for the most commonly reported adverse events with SSRIs.  Also reported were dental problems, constipation, scoliosis, and joint problems although these are all more common in all Williams Syndrome patients.  It also appears that Williams Syndrome patients are very sensitive to the disinhibiting effects of SSRIs.

Bupropion was reported to be effective.  Parents gave benzodiazepines high ratings for being effective although there was also a higher rate of side effects reported including aggression, irritability, disinhibition and rebound anxiety.

Behavioral problems have been treated with antipsychotics

In the survey risperidone and quetiapine were reported to be most effective while aripiprazole was least effective.  There was a case report of risperidone causing severe gastrointestinal bleeding and ulcerations into Williams Syndrome patients.  The only side effect of olanzapine mentioned in the survey was weight gain although frank diabetes mellitus can develop with use of this medication. Remember, “first do no harm.”

Conclusion

William Syndrome is a genetic disorder caused by a micro-deletion on chromosome 7.  Cardiovascular, endocrine and neurodevelopmental disorders are common in the disease.  Over half of Williams Syndrome patients have some type of anxiety disorder and many are treated with anxiolytic agents.  There is very little evidence-based research on the effectiveness and side effects of anxiolytic and antipsychotic agents in Williams Syndrome patients.

By way of review of the CPCP purpose and structure:

Clinical Problems in Consultation Psychiatry (CPCP):

A weekly case conference held Wednesdays from 8:00 a.m. to approximately 8:45 a.m. Each week, a case is selected from the Daily Review Rounds Records to illustrate a clinical problem for the next week’s meeting. The residents are assigned dates when they rotate. The medical students are welcome and even encouraged to participate as well.

This is a practical way to approach teaching the Practice-Based Learning & Improvement Core Competency. This helps develop the habit of reflecting on and analyzing one’s practice performance; locating and applying scientific evidence to the care of patients; critically appraising the medical literature; using the computer to support learning and patient care; facilitating the education of other health care professionals. This is applying principles of evidence-based medicine (EBM) to clinical practice.

  • Evidence-based medicine is a systematic approach to use up to date information in the practice of medicine
  • Skills are needed to integrate the available evidence with clinical experience and patient concerns
  • Application and evaluation of EBM skills will provide a frame-work for life-long learning.

Self-evaluation is vital to the successful practice of EBM:

  • Am I asking answerable clinical questions?
  • Am I searching the literature?
  • Am I becoming more efficient in my searches?
  • Am I integrating my critical appraisals into my practice?

The assigned resident is responsible for searching the literature and selecting one or two teaching papers for the conference. Presentations will begin with a review of the case, followed by a summary of the references with subsequent round table discussion.

Circulate copies of 2-4 pertinent articles to team members including psychiatric nurses and faculty. A copy machine is available in the departmental administration office. Consult staff can also assist with obtaining copies.

Presentations begin with a 5-minute summary of the case with discussion of both psychiatric and medical aspects of evaluation and management. The remaining time is spent summarizing the pertinent data in the articles. Residents and medical students are encouraged to use the case conference material as preparation for submitting a case report or letter to the editor.

1. Martens, M. A., D. L. Seyfer, et al. (2012). “Parent report of antidepressant, anxiolytic, and antipsychotic medication use in individuals with Williams syndrome: Effectiveness and adverse effects.” Research in Developmental Disabilities 33(6): 2106-2121. Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage regarding their child or adult with WS. Twenty-four percent (24%) of the individuals had been prescribed an SSRI medication, while 12% had been prescribed another type of antidepressant or anxiolytic. Overall, 81% of respondents indicated that SSRI medications were either “Helpful” or “Somewhat Helpful”, with paroxetine reported to be the least helpful. Sixty-four percent (64%) of survey participants reported that non-SSRI antidepressants and anxiolytics were either “Helpful” or “Somewhat Helpful” in treating symptoms of anxiety. Side effects for the antidepressants and anxiolytics were typically neurological in nature. Ten percent (10%) of the survey participants reported taking an antipsychotic medication, with risperidone and quetiapine described as more helpful than aripiprazole. Medication effectiveness may be related to the impact on serotonin levels. These findings call for further studies of medication usage in WS in order to improve their quality of life.

2. Chapman, C. A., A. du Plessis, et al. (1996). “Neurologic findings in children and adults with Williams syndrome.” J Child Neurol 11(1): 63-65.

Twenty-four children with Williams syndrome underwent systematic neurologic evaluations. Abnormalities of mental status, motor coordination, tone, and gait were most prevalent. Tone abnormalities varied as a function of age, with younger children frequently exhibiting decreased tone and older subjects almost exclusively having increased tone. The gait and coordination abnormalities persisted among older subjects, indicating that they were not simply maturational problems. Physicians caring for such youngsters need to be aware that a variety of neurologic abnormalities are common in Williams syndrome and may change or progress over time. Neurologic examinations that reveal findings beyond the typical pattern that we report may raise suspicion for added neurologic insult and warrant further investigation.

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