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Adult medical issues

 

The following is a compilation of unique issues concerning adults with Williams syndrome, prepared by BR Pober, MD, Department of Genetics Yale School of Medicine.

Note: This article was originally presented as a PowerPoint presentation and therefore follows more of an outline form.

The topics covered are:

 

Williams syndrome (WS)

  • Several published medical & psychological series on WS adults.
  • Demonstrate a variety of ongoing problems & suggest that WS potentially a "multi-system" disorder throughout the life cycle.
  • For many, emotional & psychiatric problems significantly affect quality of life
  • No studies exist on life expectancy but some 60 year olds with WS are "alive & well".

Potential Areas of Vulnerability for Adults

  • ENT / Audiologic
  • Endocrine
  • Dental
  • Gastrointestinal
  • Anxiety & other emotional problems
  • Accelerated aging - "appears" to be a characteristic (possibly related to elastin deletion)

Yale Study on Adults with WS

  • Recruited 20 WS adults over 30 yrs old (& their families) to spend 2-3 days Yale CCRC
  • Underwent battery of medical, cognitive and MRI tests
  • 10 Males and 10 Females
  • Average age = 38.8 yrs (range 30-51)
  • Average age of clinical diagnosis = 23 yrs
  • Variety of reasons for study participation

ENT / Audiologic

  • Only a few published studies on ENT/Audiologic issues in adults
  • We collected information from parents
  • Performed standard audiologic testing

    Information collected

    • Few patients/parents were aware of hearing loss prior to audiologic testing @ Yale
    • Hyperacusis not ongoing clinical concern
    • Problem with ear wax build-up in majority of patients
      • recurring problem
      • many patients require ENT "clean-out"
      • has negative impact on daily functioning

    Audiogram Results in WS*

    • Normal audiogram
    		 = 4/20 (20%)
    • Mild-moderate
        sensorineural hearing loss
        (SNHL) in hi frequencies
    		 = 13/20 (65%)
    • Atypical SNHL
        &/or mixed hearing loss
    		 = 3/20 (15%)
    • Uncorrected Hearing levels

    Average Excess Hearing Loss in WS Subjects
    after Correcting for Age (left ear)

    1000Hz 2000 3000 4000 6000Hz
    0 10Db 12Db 17Db 25Db

    Conclusions

    • Majority of WS adults >30 yrs old mild to moderate high frequency SNHL
    • This type of HL,"presbycusis", is normal phenomenon of aging but appears to be developing prematurely in WS
    • Suspect that deletion of gene in WS critical region confers susceptibility to early onset SNHL
    • Major limitation is lack of longitudinal followup
      • audiograms on other younger WS children do not show this pattern

    Clinical Implications

    • Need to be vigilant & screen for hearing loss
    • Moderate high frequency loss can negatively impact daily function
    • Some WS adults benefit from hearing aid
    • Recommend adults with WS have audiologic evaluations every 1-2 yrs,
      • sooner if symptoms warrant
      • further apart once stable pattern is documented
      • monitoring for wax build-up

Reported Endocrine Problems in WS

  • Growth failure
  • Early puberty
  • Hypercalcemia
  • Hypothyroidism
  • Diabetes mellitus

    Hypothyroidism

    • We performed chart review of 52 WS patients seen at Yale who had complete thyroid blood work
    • Among children:
      • increased frequency of hypothyroidism (underactive thyroid) that requires Rx;
      • increased frequency of "subclinical" hypothyroidism (thyroid gland produces enough thyroid hormone but in response to a boosted signal from the brain)
    • Among adults:
      • Increased frequency of hypothyroidism (underactive thyroid)
      • Increased frequency "subclinical" hypothyroidism (thyroid gland produces enough thyroid hormone but in response to a boosted signal from the brain)
      • Several adults receiving treatment for subclinical hypothyroidism which may not be needed

    Recommendations re: Thyroid Screening

    • Check thyroid functions (including TSH) upon diagnosis of WS
    • If normal, check every few years
    • If hypothyroidism, perform appropriate diagnostic work-up & treat with thyroid hormone replacement
    • If subclinical hypothyroidism, consult endocrinologist & monitor regularly

    Diabetes & Abnormal Glucose Tolerance

    • Reports of diabetes in adults with WS
    • Became concerned about glucose metabolism based on our own patients & discussions with Dr. Osborne re: molecular genetics of WS
    • To investigate frequency of blood sugar problems, we performed oral glucose tolerance tests

    Oral glucose tolerance test (OGTT)

    • Asymptomatic patients with no known diabetes
    • Overnight fast
    • Ingest 75 grams glucose
    • Glucose & insulin determinations (-15, 0, 30, 60, 90, 120 minutes)
    • Results permit glucose homeostasis classification

    OGTT Results

    Classification of "Glucose" status among 20 adult study subjects*

    • Clinical diabetes
    • Silent diabetes
    • Impaired glucose tol.
    • Normal glucose tol.
    		 = 2/20 (10%)
    = 7/20 (35%)
    = 9/20 (45%)
    = 2/20 (10%)

    Mechanism of Abnormal Glucose Tolerance

    1. Insulin deficiency

      2. vs
    2. Insulin resistance

    Study of WS vs Age-Gender-BMI Matched Controls*

    Conclusions

    1. An increased frequency of Impaired Glucose Tolerance and Silent Diabetes in WS vs matched controls.
    2. Abnormality occurs in WS adults & adolescents.
    3. Major risk factor appears to be WS

      4.   - being overweight is additional risk
    4. Speculate absence of a gene in WS , possibly STX1A gene, contributes to abnormal glucose tolerance.

    Recommendations

    • Perform OGTT on adults with WS.
    • Avoid large glucose loads over short time period.
    • Avoid diabetogenic drugs.
    • Prevent excess weight gain.
    • Continue "active" lifestyle.
    • Treatment guidelines under discussion.

    NOTE: * = (>30 years of age)

Weight gain

  • Most youngsters with WS are "thin"
  • In adults we observe:
    • ~1/2 remain thin
    • ~1/2 gain weight in central (pear-shaped) distribution
    • small proportion have "myxedema" of legs
  • Do not know cause of weight gain
    • genetic predisposition
    • lifestyle

Dental Problems in Adults

  • Increased frequency of malocclusion, missing teeth, malformed teeth & malaligned teeth
  • Almost universal problem is poor dental hygiene -> to cavities, gum disease & extractions

    •   (2° poor visual spatial motor skills)
  • Among 20 Yale research study adults (>30 yrs):
    • Good hygiene - 2/20
    • Fair hygiene - 8/20
    • Poor hygiene - 9/20
    • Not assessed - 1/20

    Recommendations for Dental Care

    • Weekly parent/caregiver supervision of brushing
    • Parent/caregiver assistance with flossing
    • Electronic toothbrush
    • Dental cleanings every 3-4 months, rather than 6 month intervals

Gastrointestinal problems

  • GI problems very common (based on medical literature & own observations)
  • Most common problems reported
    • Abdominal pain
    • Constipation
    • Diverticulitis

    GI problems among 20 Yale research study adults

    • Any GI problems
    • Abdominal pain
    • Constipation
    • Diarrhea
    • Diverticulitis
    • Bowel surgery
    		 = 15/20
    = 8/20
    = 9/20
    = 8/20
    = 5/20
    = 6/20

    Bowel surgery

    • Partial colon resection
        for diverticular disease
    		 4
    • Hemorrhoidectomy
    • Gallbladder removal
    • Appendectomy
    		 1
    1
    1

    Causes of Abdominal pain

    • Diverticular disease
    • Reflux (heartburn)
    • Constipation
    • Diarrhea
    • Possible Celiac disease ("sprue or glutein sensitivity")
    • Possible Irritable Bowel syndrome
    • Anxiety (diagnosis of exclusion)

    Prevention /Management of GI problems

    • Prevent chronic constipation!!
      • Use dietary supplements
      • Use medication, under the supervision of MD
    • Prompt medical evaluation of "heartburn", weight loss, abdominal pain (especially with fever), change in bowel habits
    • Cause of chronic abdominal pain not always found; consider "biofeedback techniques" once medical disease is excluded

Published Adult Behavioral Profiles

  • Udwin
 N=119 Hi freq of behavior & emotional difficulties
  • Borghgraef
 N=8 No excess problems vs. comparable controls
  • Gosch & Pankau
 N=57 More anxious & depressed vs youngsters; less lively
  • Davies
 N=71 Hi freq social, emotional & behavioral difficulties

    Data from Udwin (N=119)

    • Solitary
    • Restless
    • Cannot settle
    • Worried
    • Fearful
    • Aches & pains
    • Preoccupations/obsessions
    		 71%
    71%
    77%
    87%
    73%
    67%
    82%

    Diagnoses by direct psychiatric interview - 20 Adult subjects

    • Most adults have anxiety disorder
      • waxes & wanes over time; truly incapacitating in minority
    • Most have phobias (thunderstorms, escalators)
    • ~20% experience depressive episode(s)
    • <10% obsessive compulsive or sexual impulse control disorder
    • ~5% experience serious psychiatric problems � psychiatric hospitalization
    • Problems ameliorate with multi-faceted Rx

    Diagnoses by direct interview by Yale psychiatrist - 20 Adult subjects

    • Anxiety disorder
      • Mild anxiety (= 2/20)
      • Moderate anxiety (= 9/20)
      • Severe anxiety (= 2/20)
    • Specific phobia (= 6/20)
    • Depression (= 2/20)
    • Obsessive compulsive disorder (= 1/20)
    • Sexual impulse control problem (= 1/20)
    • Panic attacks (= 1/20)

    Treatment for Psychiatric Dx

    • Anxiety
      • Counseling / Therapy
      • Biofeedback / Relaxation techniques
      • Anti-anxiety medication
    • Use very low doses of medication! People with WS seem sensitive to many of these medications
    • All other disorders
      • Psychiatric evaluation, therapy, behavior modification, medication

Possible Accelerated Aging in WS

  • Parental concerns about accelerated physical & cognitive aging
  • Medical evidence for premature aging
    • Premature greying of hair
  • 19/20 Yale adult research study subjects
  • Average age of greying= 29 yrs (16-41)
    • Presbycusis
    • Diabetes?
    • Wrinkling of skin?

Possible Accelerated cognitive aging

  • Possible evidence of accelerated cognitive aging
    • � Evidence of decline in IQ over time
    • No evidence of memory loss
    • MRI changes suggestive of aging
  • Clinically, older persons don't seem as "sharp" as when younger
  • Need more studies...

Living Arrangements & Employment Among 20 Yale Research Study Adults

  • Current living arrangements
    • Parents
    • Group home
    • Supervised apartment
    • Retirement community
    		 8/20
    5/20
    5/20
    2/20
  • Current employment (average hrs/wk=23)
    • Paid, unsupervised
    • Paid, supervised
    • Sheltered workshop
    • Not employed
    		 1/20
    6/20
    7/20
    6/20

 
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