Adult Medical Issues

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As individuals with Williams syndrome age, they will often have new medical issues.  Anxiety, depression, diabetes and gastro-intestinal disorders are not uncommon.  The following is a compilation of unique issues concerning adults with Williams syndrome.

 

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

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

Clinical Implications

    • 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
    • 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
    • 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

Recommendations re: Thyroid Screening

Diabetes & Abnormal Glucose Tolerance

Oral glucose tolerance test (OGTT)

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

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

Conclusions

Recommendations

NOTE: * = (>30 years of age)

    • 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
    • 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
    • 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
    • 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
    1. Insulin deficiency
      vs
    2. Insulin resistance
    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
      - being overweight is additional risk
    4. Speculate absence of a gene in WS , possibly STX1A gene, contributes to abnormal glucose tolerance.
    • 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.

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

Causes of Abdominal pain

Prevention /Management of GI problems

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

Diagnoses by direct interview by Yale psychiatrist - 20 Adult subjects

Treatment for Psychiatric Dx

    • 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
    • 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)
    • 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