Pediatrics
May, 2001 (corrected February, 2002)
Health Care Supervision for Children With Williams
Syndrome.
ABBREVIATIONS. WS, Williams syndrome; FISH, fluorescence
in situ hybridization.
INTRODUCTION
Williams syndrome (WS, also Williams-Beuren syndrome),
now recognized to be caused by a microdeletion of
chromosome 7, is a multisystem disorder first identified as
a distinct clinical entity in 1961.[1] It is present at
birth and affects boys and girls equally. As routine
genetic amniocentesis does not typically detect chromosome
microdeletions, children with WS usually come to the
attention of pediatricians during infancy or childhood.
Initially thought to be a rare genetic disorder, increased
awareness of the clinical features and establishment of a
reliable diagnostic test have revealed WS to be one of the
more commonly recognized genetic disorders in childhood.
Williams syndrome is characterized by dysmorphic facies
(100%), cardiovascular disease (most commonly supravalvar
aortic stenosis [80%]), mental retardation (75%), a
characteristic cognitive profile (90%), and idiopathic
hypercalcemia (15%)[2-5] (Table 1).
TABLE 1. Medical Problems in Williams Syndrome(*)
by Organ System and Age
Organ System Age
Incidence (%) Infancy
Ocular and visual
Esotropia 50 x
Hyperopia 50
Auditory
Chronic otitis media 50 x
Hypersensitivity to sound 90 x
Dental
Malocclusion 85
Microdontia 95
Cardiovascular
Any abnormality (total) 80 x
SVAS 75 x
SVPS 25 x
PPS 50 x
Renal artery stenosis 45 x
Other arterial stenosis 20
VSD 10 x
Hypertension 50
Genitourinary
Structural anomaly 20 x
Enuresis 50
Nephrocalcinosis <5 x
Recurrent urinary tract infections 30
Gastrointestinal
Feeding difficulties 70 x
Constipation 40 x
Colon diverticula 30
Rectal prolapse 15 x
Integument
Soft lax skin 90 x
Inguinal hernia 40 x
Umbilical hernia 50 x
Prematurely gray hair 90
Musculoskeletal
Joint hypermobility 90 x
Joint contractures 50 x
Radioulnar synostosis 20 x
Kyphosis 20
Lordosis 40
Awkward gait 60
Calcium
Hypercalcemia 15 x
Hypercalciuria 30 x
Endocrine
Hypothyroidism 2 x
Early puberty (but rarely true
precocious puberty) 50
Diabetes mellitus 15
Obesity 30
Neurologic
Hyperactive deep tendon reflexes 75
Chiari I malformation 10 x
Hypotonia (central) 80 x
Hypertonia (peripheral) 50
Cognitive
Developmental delay 95 x
Mental retardation 75
Borderline intellectual functioning 20
Normal intelligence 5
Impaired visuospatial constructive 95
cognition
Behavioral
Attention-deficit hyperactivity disorder 70
Generalized anxiety disorder 80
Organ System Age
Childhood Adult
Ocular and visual
Esotropia
Hyperopia x x
Auditory
Chronic otitis media x
Hypersensitivity to sound x x
Dental
Malocclusion x x
Microdontia x x
Cardiovascular
Any abnormality (total) x x
SVAS x x
SVPS x x
PPS
Renal artery stenosis x x
Other arterial stenosis x x
VSD
Hypertension x x
Genitourinary
Structural anomaly x x
Enuresis x
Nephrocalcinosis x x
Recurrent urinary tract infections x
Gastrointestinal
Feeding difficulties x
Constipation x x
Colon diverticula x x
Rectal prolapse x
Integument
Soft lax skin x x
Inguinal hernia
Umbilical hernia
Prematurely gray hair x
Musculoskeletal
Joint hypermobility x
Joint contractures x x
Radioulnar synostosis x x
Kyphosis x
Lordosis x x
Awkward gait x x
Calcium
Hypercalcemia x
Hypercalciuria x x
Endocrine
Hypothyroidism x x
Early puberty (but rarely true
precocious puberty) x
Diabetes mellitus x
Obesity x
Neurologic
Hyperactive deep tendon reflexes x x
Chiari I malformation x x
Hypotonia (central) x
Hypertonia (peripheral) x x
Cognitive
Developmental delay x
Mental retardation x x
Borderline intellectual functioning x x
Normal intelligence x x
Impaired visuospatial constructive x x
cognition
Behavioral
Attention-deficit hyperactivity disorder x
Generalized anxiety disorder x x
(*) Percentages based on the following: 1) review of rates of
complications in several reports of series of patients with
Williams syndrome, and 2) database of 315 children and adults
with Williams syndrome evaluated by Colleen A. Morris, MD.
SVAS indicates supravalvar aortic stenosis; SVPS, supravalvular
pulmonic stenosis, PPS, peripheral pulmonary artery stenosis;
and VSD, ventricular septal defect.
|
| The diagnosis
historically has been made on the basis of clinical
criteria (Fig 1), but recently it has been shown that 99%
of patients with WS have a hemizygous submicroscopic
deletion of 7q11.23 detectable by fluorescence in situ
hybridization (FISH).[6-8] Chromosome analysis and the
Williams Syndrome Chromosomal Region FISH test are
recommended for confirmation of the diagnosis. (A child
with the clinical features of WS and a negative FISH
result should be referred to a clinical geneticist for
further evaluation.) The deleted portion of the chromosome
includes the ELN gene that codes for the structural
protein elastin, an important component of the elastic
fibers found in the connective tissue of many organs. The
elastin deletion explains some of the characteristics of
WS, such as some of the facial features, hoarse voice,
bladder and bowel diverticula, cardiovascular disease, and
orthopedic problems. The pathogenesis of other
characteristics, such as hypercalcemia, mental
retardation, and unique personality traits, remains
unexplained. One possibility is that the loss of 1 or more
genes contiguous to the ELN gene contributes to the
phenotype. Figure 1. Williams syndrome diagnostic
scoring table: clinical diagnosis.
Growth (Past or Present Evidence of)
If 3 of 5 items are checked, score 1 point
[] Post-term birth [is greater than] 41 wk gestation []
Failure to thrive/height and weight [is less than] 5th
percentile [] Vomiting or gastroesophageal reflux []
Prolonged colic [is greater than] 4 m irritability []
Chronic constipation
Behavior and Development
If 3 of 6 items are checked, score 1 point
[] _Overly friendly personality [] Hypersensitivity to
sound [] Anxiety [] Developmental delay or mental
retardation [] Visuospatial problems [] Delayed speech
acquisition, followed by excessive talking
Facial Features
If 8 of 17 items are checked, score 3 points
[] Bitemporal narrowing [] Epicanthal folds or flat
nasal bridge [] Strabismus (present or past) [] Short nose
or anteversion of nares [] Full cheeks [] Long philtrum []
Small, widely spaced teeth [] Wide mouth [] Prominent ear
lobes [] Broad brow [] Periorbital fullness [] Stellate
lacy iris pattern [] Bulbous or full nasal tip [] Malar
hypoplasia (flat cheek bones) [] Full prominent lips []
Malocclusion [] Small jaw
Cardiovascular Problems (by Echocardiography) (a)
If 1 of 2 items are checked, score 5 points
[] SVAS([dagger]) [] Peripheral pulmonary artery
stenosis
Cardiovascular Problems (b)
If 1 of 3 items are checked, score 1 point
[] Other congenital heart disease [] Cardiac murmur []
Hypertension
Connective Tissue Abnormality
If 2 of 6 items are checked, score 2 points
[] Hoarse voice [] Inguinal hernia [] Bowel or bladder
diverticula [] Long neck or sloped shoulders [] Joint
limitation or laxity [] Rectal prolapse |
| Calcium Studies
If 1 of 2 items are checked, score 2 points
[] Hypercalcemia [] Hypercalciuria
Total Points:
(*) If the score is [is less than] 3, a diagnosis of
Williams syndrome is unlikely. If the score is [is greater
than or equal to] 3, FISH studies should be considered.
(Mean score for Williams syndrome was 9 [standard
deviation = 2.86]. The scoring system is based on a study
of 107 persons with Williams syndrome [confirmed by FISH]
evaluated by Colleen A. Morris, MD; Frank Greenberg, MD;
Paige Kaplan, MD; Martin Levinson, MD; and Barbara Pober,
MD; with data analysis by Carolyn B. Mervis, PhD and Byron
F. Robinson, MA; presented at the 1994 Williams Syndrome
Association Convention; July 31, 1994; San Diego, CA.)
([dagger]) If supravalvar aortic stenosis (SVAS) is
present, referral to a geneticist and FISH studies are
recommended.
The pediatrician can use knowledge of the clinical
manifestations (Table 1) and natural history of WS to
anticipate medical problems and to educate the family.
Most children with WS are described as having similar
facial features.[4,9] Although these features are often
subtle, they tend to become more distinctive with
advancing age. Facial features often include periorbital
fullness, short nose with bulbous nasal tip, long
philtrum, wide mouth, full lips, and mild micrognathia.
Infants have full cheeks and a flat facial profile,
whereas older children and adults often have a long narrow
face and a long neck.[10,11] Blue- and green-eyed children
with WS have a prominent "starburst" pattern to their
irides (stellate iris).[12] Mild prenatal growth
deficiency and a postnatal growth rate about 75% of normal
are consistently observed features of the condition,[8,13]
The majority of children with WS have cardiovascular
anomalies.[1,2,4] The most common cardiovascular defect is
supravalvar aortic stenosis, an often progressive
condition that may require surgical repair.[10,11]
Peripheral pulmonary artery stenosis is often present in
infancy and usually improves over time. Coarctation of the
aorta, renal artery stenosis, and systemic hypertension
are complications that when present may worsen over
time.[4,11,14,15] Because the elastin protein is an
important component of elastic fibers in the arterial
wall, any artery may become narrowed.
Idiopathic infantile hypercalcemia is an intriguing
feature of WS that can contribute to the presence of
extreme irritability, vomiting, constipation, and muscle
cramps associated with this condition.[4,9] Symptomatic
hypercalcemia usually resolves during childhood, but
lifelong abnormalities of calcium and vitamin D metabolism
may persist. Hypercalciuria is common and predisposes to
nephrocalcinosis. The cause of the abnormality in calcium
metabolism is unknown.
An infant with WS often has difficulty feeding and may
be brought for medical care because of gastroesophageal
reflux, colic, or failure to thrive.[4,9,16] Other medical
problems include Chiari I malformation, strabismus,[12]
hyperopia,[12] chronic otitis media, hypodontia,
malocclusion, bowel or bladder diverticula, hernias, joint
laxity, joint contractures,[17] kyphosis, lordosis, renal
or urinary tract malformations,[14,15] hypothyroidism, and
rectal prolapse. |
| Children with WS
have a unique cognitive and behavioral profile.[3,5,18]
Cognitive, motor, and language delay are universal, and in
75% of the children, mental retardation is ultimately
diagnosed.[19,20] Older children demonstrate a relative
strength in language and auditory memory, with a
significant weakness in visuospatial cognition.[5,18]
Behavioral problems may include hypersensitivity to sound,
sleep problems, attention-deficit/hyperactivity
disorder,[20] and anxiety. Overfriendliness and an
empathetic nature are commonly observed.[17] The medical
care of children with WS requires an understanding of the
natural history of the disorder, awareness of potential
clinical complications, and ongoing assessment and
periodic review at appropriate ages (Fig 2). Because the
clinical manifestations during the neonatal period are
variable, the diagnosis may not be suspected during early
infancy. Accordingly, this statement includes a series of
evaluations that should be considered at the time the
diagnosis is suspected clinically; the diagnosis should be
confirmed by FISH analysis. The evaluations include the
following:
* Complete physical and neurologic examination
* Growth parameters plotted on WS growth charts (Fig
3A-F)
* Cardiology evaluation
--Full clinical evaluation by a cardiologist with
expertise and experience in pediatric patients that
includes 4-limb blood pressure measurements and
echocardiography
* Genitourinary system evaluation
--Ultrasonography of bladder and kidneys
--Renal function studies (serum urea nitrogen and
creatinine levels)
--Urinalysis
* Calcium determinations (serum calcium, spot urine
calcium, and creatinine levels) (Table 2)
* Thyroid function tests
* Ophthalmologic evaluation
* Multidisciplinary developmental evaluation (older
than 2 years)
* FISH to determine ELN deletion
Fig 2. Health supervision for children with Williams Syndrome(*)
Infancy (NB - 1 Year)
Diagnosis Neonatal 2 mos
Karyotype/FISH Review([dagger]) (a)
Phenotype Review([dagger]) (a)
Recurrence Risks([dagger]) (a)
Anticipatory Guidance
Early Intervention (a) (a)
Family Support (a) (a)
Support Groups([dagger]) (a) (a)
Long-term Planning
Sexuality
Therapy (pt, ot, speech)
Medical evaluation o o
Growth feeding o ([parallel])
Thyroid Screening
Hearing Screening
Vision Screening s/o s/o
2-Arm Blood Pressure o
Cardiology Evaluation([dagger]) (**)
UA/BUN/Cr([dagger]) o
Urine Ca/Cr([dagger]) o ([dagger][dagger])
Serum Calcium([dagger]) o
Renal Ultrasonography([dagger]) o
Musculoskeletal Eval o
Pneumovax
Psychosocial
Development s/o s/o
School Performance
Socialization
Infancy
(NB - 1 year)
Diagnosis 4 mos 6 mos
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention (a) (a)
Family Support (a) (a)
Support Groups([dagger])
Long-term Planning
Sexuality
Therapy (pt, ot, speech)
Medical evaluation o o
Growth feeding
Thyroid Screening
Hearing Screening s/o
Vision Screening s/o s/o
2-Arm Blood Pressure o
Cardiology Evaluation([dagger])
UA/BUN/Cr([dagger])
Urine Ca/Cr([dagger])
Serum Calcium([dagger])
Renal Ultrasonography([dagger])
Musculaskeletal Eval
Pneumorax
Psychosocial
Development s/o s/o
School Performance
Socialization
Early
Infancy Childhood
(NB - 1 (1-5
Year) Years)
Diagnosis 9 mos 12 mos
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention (a) (a)
Family Support (a) (a)
Support Groups([dagger]) (a)
Long-term Planning (a)
Sexuality
Therapy (pt, ot, speech)
Medical evaluation o o
Growth feeding
Thyroid Screening
Hearing Screening s/o ([double
dagger])
Vision Screening s/o ([double s/o
dagger])
2-Arm Blood Pressure o
Cardiology Evaluation([dagger]) (**)
UA/BUN/Cr([dagger]) o
Urine Ca/Cr([dagger]) o
Serum Calcium([dagger])
Renal Ultrasonography([dagger])
Musculaskeletal Eval o
Pneumorax
Psychosocial
Development s/o s/o
School Performance
Socialization s
Early Childhood
(1-5 Years)
Diagnosis 15 mos 18 mos
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention (a) (a)
Family Support (a) (a)
Support Groups([dagger])
Long-term Planning
Sexuality
Therapy (pt, ot, speech)
Medical Evaluation
Growth feeding o o
Thyroid Screening
Hearing Screening
Vision Screening
2-Arm Blood Pressure
Cardiology Evaluation([dagger])
UA/BUN/Cr([dagger])
Urine Ca/Cr([dagger])
Serum Calcium([dagger])
Renal Ultrasonography([dagger])
Musculaskeletal Eval
Pneumorax
Psychosocial
Development s/o s/o
School Performance
Socialization
Early Childhood (1-5 Years)
Diagnosis 24 mos 3 yr
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention (a)
Family Support (a) (a)
Support Groups([dagger])
Long-term Planning
Sexuality
Therapy (pt, ot, speech) (**) ([sections])
Medical Evaluation
Growth feeding o o
Thyroid Screening
Hearing Screening s/o ([double
dagger])
Vision Screening s/o s/o
2-Arm Blood Pressure o o
Cardiology Evaluation([dagger]) (**) (**)
UA/BUN/Cr([dagger]) o o
Urine Ca/Cr([dagger]) o
Serum Calcium([dagger]) o
Renal Ultrasonography([dagger])
Musculaskeletal Eval o o
Pneumorax (a)
Psychosocial
Development s/o s/o
School Performance o
Socialization s
Early
Childhood
(1-5 Years)
Late Childhood
Diagnosis 4 yr 5-13 yrs Annual
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention
Family Support (a) (a)
Support Groups([dagger]) (a) ([paragraph])
Long-term Planning (a) ([paragraph])
Sexuality (a)
Therapy (pt, ot, speech) (**) ([sections])
Medical Evaluation
Growth feeding o o
Thyroid Screening o (#)
Hearing Screening s/o ([double s/o ([paragraph])
dagger])
Vision Screening s/o ([double s/o ([sections])
dagger])
2-Arm Blood Pressure o o
Cardiology Evaluation([dagger]) ([dagger]) (**) ([paragraph])
([sections])
UA/BUN/Cr([dagger]) o o (#)
Urine Ca/Cr([dagger]) o ([paragraph])
Serum Calcium([dagger]) o
Renal Ultrasonography([dagger])
Musculaskeletal Eval o o
Pneumorax
Psychosocial
Development s/o s/o
School Performance o o
Socialization s
Adolescence
Diagnosis 13-21 yrs Annual
Karyotype/FISH Review([dagger])
Phenotype Review([dagger])
Recurrence Risks([dagger])
Anticipatory Guidance
Early Intervention
Family Support (a)
Support Groups([dagger])
Long-term Planning (a) ([paragraph])
Sexuality (a)
Therapy (pt, ot, speech) (**) ([sections])
Medical Evaluation
Growth feeding o
Thyroid Screening o (#)
Hearing Screening s/o ([paragraph])
Vision Screening s/o ([sections])
2-Arm Blood Pressure o
Cardiology Evaluation([dagger]) (**) ([paragraph]) ([sections])
UA/BUN/Cr([dagger]) o (#)
Urine Ca/Cr([dagger]) o ([paragraph])
Serum Calcium([dagger]) o
Renal Ultrasonography([dagger])
Musculaskeletal Eval o
Pneumorax
Psychosocial
Development s/o
School Performance o
Socialization s
(*) Assure compliance with the AAP "Recommendations for
Preventive Pediatric Health Care
([dagger]) Or at time of diagnosis
([double dagger]) Discuss referral to specialist
([sections]) As needed
(**) Referral
([parallel]) Per state law
([paragraph]) Once in this age group
(#) Every 2 years
([dagger][dagger]) If hypercalciuria found, 2 repeat carine
calcium (am and pm) should be sent. If still positive, repeat
serum calcium, renal ultrasound for nephrocalcinosis and
initiate dietary counseling
(a) = To be performed
s = subjective (by history)
o = Objective (by a standard testing method)
|
[ILLUSTRATION
OMITTED]TABLE 2. Normal Values for Random Urinary Calcium-Creatinine
Ratios[21]
Age Calcium-Creatinine Ratio (mg/mg ratio)
(95th Percentile for Age)
<7 mo 0.86
7-18 mo 0.6
19 mo-6 y 0.42
Adults 0.22
Referral to a clinical geneticist should be considered
for individualized assessment and recommendations; a more
extensive discussion of the clinical manifestations,
natural history, recurrence risks, and future reproductive
options; and evaluation of genetic risks for other family
members.
SPECIAL CONSIDERATIONS FOR THE CHILD DIAGNOSED WITH WS
1. Do not give multivitamin preparations to children
with WS because of the potential deleterious effects of
vitamin D. Recommend diligent use of sunscreen to minimize
autologous production of vitamin D.
2. Perform periodic cardiovascular evaluations, even
after a baseline examination with normal findings.
3. Baseline cardiology evaluation should be performed
by a cardiologist with pediatric expertise and experience.
4. Screen for the development of hypertension
periodically according to guidelines of the American
Academy of Pediatrics.
5. Establish a medical home with clear emphasis on
continuity of care and the role of the family members as
partners in the ongoing management and care of the child.
HEALTH SUPERVISION FROM BIRTH TO 1 YEAR (INFANCY)
Examination
1. Review and note clinical features and confirm
diagnosis with FISH analysis
2. Routine health maintenance examinations and baseline
evaluation
3. Growth and developmental evaluations using WS growth
charts (Fig 3A-F)
4. Baseline cardiology evaluation by a cardiologist
with pediatric expertise and experience
5. Review feeding issues (reflux, refusal, disordered
suck or swallow, vomiting or symptoms of colic).
6. Consider pediatric ophthalmologic evaluation for
strabismus, amblyopia, and refractive errors
7. Check for inguinal hernia
8. Objective hearing assessment at 6 to 12 months
(recurrent otitis media is common)
9. Blood pressure measurement (both arms) annually and
careful evaluation of femoral pulses
10. Early recognition and management of constipation
11. Pediatric anesthesia consultation for any child
requiring surgery (several reports of unexpected deaths
have been associated with the administration of
anesthesia)[22]
Laboratory
1. Williams Syndrome Chromosomal Region FISH to confirm
clinical diagnosis
2. Serum creatinine level
3. Urinalysis
4. Calcium levels
a. Serum(*)
b. Spot urine test to determine calcium-creatinine
ratio([dagger])
5. Thyroid screen for newborns (according to state
mandate)
6. Baseline ultrasonographic examination of the bladder
and kidneys |
| Anticipatory
Guidance 1. Individual support for the family (by
family, friends, clergy), support groups, or both (see
list)
2. Review increased risk for otitis media
3. Feeding (difficulty in transition to textured foods)
4. Do not prescribe multivitamin preparations
containing vitamin D
5. Refer to early childhood intervention program
HEALTH SUPERVISION FROM 1 TO 5 YEARS (EARLY CHILDHOOD)
Examination
1. Annual health maintenance examinations and baseline
evaluation (including careful auscultation of chest and
abdomen for murmurs or bruits)
2. Developmental evaluation and growth evaluation using
WS growth charts (Fig 3A-F)
3. Annual cardiology evaluation from 1 to 5 years
4. Feeding issues: watch for rectal prolapse and avoid
constipation with stool softeners if necessary
5. Annual hearing and vision screening; objective
audiologic evaluation and an ophthalmologic evaluation
before age 3 years
6. Orthopedic issues: musculoskeletal and neurologic
assessments to evaluate joints, muscle tone, spasticity,
and hyperactive reflexes[17]
7. Pediatric anesthesia consultation for any child
requiring surgery (several reports of unexpected deaths
have been associated with the administration of
anesthesia)[22]
8. Annual blood pressure measurement (both arms) and
careful examination of femoral pulses
9. Multidisciplinary developmental assessment and
treatment in early intervention programs (0-3 years) or
school based programs (3 years and older)[1,15,19]
10. Dental referral
Laboratory
1. Yearly urinalysis
2. Annual total calcium measurement if the level was
elevated at baseline or as needed if the child becomes
symptomatic; if level was normal, measure every 2 to 3
years
3. Urinary calcium-creatinine ratio every 2 years
4. Thyroid function test every 4 years
5. Serum creatinine level every 4 years
Anticipatory Guidance
1. Individual support for the family (by family,
friends, clergy), support groups, or both
2. Review increased risk for otitis media
3. Ongoing feeding and dietary assessments
4. Therapy as needed (physical, speech and language,
and occupational, including sensory integration)
5. Review constipation as a possible problem
6. Children with unexplained fever should be evaluated
for urinary tract infection
7. Discuss developmental status, early intervention
programs, and preschool programs
HEALTH SUPERVISION FROM 5 YEARS TO 12 YEARS (LATE
CHILDHOOD)
Examination
1. Annual health maintenance examinations and baseline
evaluation
2. Developmental evaluation and growth evaluation using
WS growth charts (Fig 3A-F)
[ILLUSTRATION OMITTED]
3. Annual blood pressure measurements (both arms) and
careful evaluation of femoral pulses |
| 4. Cardiology
evaluation as indicated by previous clinical findings. If
results of previous evaluations are negative, repeated
cardiology evaluation (for arterial stenoses,
hypertension) should be performed at puberty 5.
Ophthalmologic evaluation for strabismus and hyperopia
6. Orthopedic problems (eg, joint limitation, kyphosis,
lordosis, scoliosis, and spasticity)
7. Hearing and vision screening annually
8. Pediatric anesthesia consultation for any child
requiring surgery (several reports of unexpected deaths
have been associated with the administration of
anesthesia[22])
9. School readiness and placement and Individual
Educational Plan at 5 years
10. Developmental and psychoeducational assessment;
formal evaluation for attention-deficit hyperactivity
disorder, anxiety, or both and discussion of treatment
options[23]
Laboratory
1. Yearly urinalysis
2. Thyroid function tests every 4 years
3. Annual total calcium level if baseline result was
elevated or child becomes symptomatic; otherwise measure
level every 4 years
4. Urinary calcium-creatinine ratio every 2 years
5. Serum creatinine level every 2 to 4 years
Anticipatory Guidance
1. School readiness and placement
2. Therapy as needed (physical, speech and language,
and occupational, including sensory integration)
3. Long-term vocational planning
4. Discuss sexuality and adolescence; puberty is often
early in WS, but true precocious puberty is rare
5. Discuss diet and exercise as obesity may become
apparent in late childhood
6. Discuss treatment options for anxiety (counseling,
relaxation techniques, and medications)
7. Estate planning for parents of a child with special
needs
HEALTH SUPERVISION FROM 13 YEARS TO 18 YEARS
(ADOLESCENCE)
Progressive medical problems including hypertension,
progressive joint limitations, recurrent urinary tract
infections, and gastrointestinal problems are common
beginning in this age group and continuing throughout
adult life.
Examination
1. Annual health maintenance examinations and baseline
evaluation; blood pressure measurement (both arms)
2. Developmental evaluation and growth evaluation using
WS growth charts (Fig 3A-F)
3. Cardiology evaluation if indicated by previous
clinical findings
4. Pediatric anesthesia consultation for any child
requiring surgery (several reports of unexpected deaths
have been associated with the administration of
anesthesia[22])
5. Consider ophthalmologic evaluation for hyperopia
6. Orthopedic problems (eg, joint limitation, kyphosis,
lordosis, scoliosis, and spasticity)
7. Hearing and vision screening annually
8. Developmental and psychoeducational assessment;
school placement and resource enhancement; vocational
training; social skills training for peer
interaction[10,11] |
| 9.
Gastrointestinal issues: consider diverticulitis and
diverticulosis, cholelithiasis, and chronic constipation
in adolescents with abdominal pain 10. Screen for
generalized anxiety disorder[19]
Laboratory
1. Yearly urinalysis
2. Thyroid function test every 4 years
3. Total calcium level only if adolescent becomes
symptomatic, otherwise, every 4 years
4. Urinary calcium-creatinine ratio every 2 years
5. Bladder and renal ultrasonography at puberty and
every 5 years thereafter
6. Serum creatinine level every 2 to 4 years
Anticipatory Guidance
1. School placement
2. Therapy as needed (physical, occupational, speech,
and language)
3. Discuss diagnosis with the adolescent; support
groups for the adolescent (see American Academy of
Pediatrics statement on "Transition of Care Provided for
Adolescents With Special Needs")[24]
4. Discuss sexuality and reproductive issues
5. Encourage career counseling
6. Foster independence
7. Assist in transition to adult care (especially for
cardiology care). Many pediatricians feel comfortable
continuing to provide primary care well into young
adulthood
8. Encourage daily exercise to include range of motion
9. Encourage prompt medical attention for urinary tract
or gastrointestinal symptoms
10. Mental health issues
COMMITTEE ON GENETICS, 2000-2001
Christopher Cunniff, MD, Chairperson
Jaime L. Frias, MD
Celia I. Kaye, MD, PhD
John Moeschler, MD
Susan R. Panny, MD
Tracy L. Trotter, MD
LIAISONS
Felix de la Cruz, MD, MPH
National Institute of Child Health and Human
Development
John Williams III, MD
American College of Obstetricians and
Gynecologists
James W. Hanson, MD
American College of Medical Genetics
Cynthia A. Moore, MD, PhD
Centers for Disease Control and Prevention
Michele Lloyd-Puryear, MD, PhD
Health Resources and Services Administration
SECTION LIAISON
H. Eugene Hoyme, MD
Section on Genetics
CONSULTANTS
Paige Kaplan, MD
Ron Lacro, MD
Karen Levine, PhD
Martin Levinson, MD
Carolyn Mervis, PhD
Colleen A. Morris, MD
Beth A. Pletcher, MD
Barbara Pober, MD
Laurie Sadler, MD
Paul Wang, MD
STAFF
Lauri A. Hall
(*) If hypercalcemia is found, dietary calcium
restriction should be implemented and diet should be
monitored in conjunction with a pediatric
dietician/nutritionist. Referral to a pediatric renal
specialist should be considered.
([dagger]) If hypercalciuria is found, 2 repeated urine
studies of the calcium-creatinine ratio (morning and
afternoon) should be performed. If the level is still
elevated, repeat measurement of the serum calcium level
and perform renal ultrasonography for nephrocalcinosis.
Assess dietary calcium intake. (21)
REFERENCES
[1.] Williams JC, Barratt-Boyes BG, Lowe JB.
Supravalvular aortic stenosis. Circulation.
1961;24:1311-1318
[2.] Beuren AJ. Supravalvular aortic stenosis: a
complex syndrome with and without mental retardation. Natl
Found March Dimes Birth Defects Orig Art Ser. 1972;8:45-56 |
| [3.] Burn J.
Williams syndrome. J Med Genet. 1986;23:389-395 [4.]
Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL.
Natural history of Williams syndrome: physical
characteristics. J Pediatr. 1988; 113:318-326
[5.] Udwin O, Yule W. A cognitive and behavioural
phenotype in Williams syndrome. J Clin Exp Neuropsychol.
1991;13:232-244
[6.] Ewart AK, Morris CA, Atkinson D, et al.
Hemizygosity at the elastin locus in a developmental
disorder, Williams syndrome. Nat Genet. 1993;5:11-16
[7.] Lowery MC, Morris CA, Ewart A, et al. Strong
correlation of elastin deletions, detected by FISH, with
Williams syndrome: evaluation of 235 patients. Am J Hum
Genet. 1995;57:49-53
[8.] Wu Y-Q, Sutton VR, Nickerson E, et al. Delineation
of the common critical region in Williams syndrome and
clinical correlation of growth, heart defects, ethnicity,
and parental origin. Am J Med Genet. 1998;78: 82-89
[9.] Martin ND, Snodgrass GJ, Cohen RD. Idiopathic
infantile hypercalcemia: a continuing enigma. Arch Dis
Child. 1984;59:605-613
[10.] Lopez-Rangel E, Maurice M, McGillivray B,
Friedman JM. Williams syndrome in adults. Am J Med Genet.
1992;44:720-729
[11.] Morris CA, Leonard CO, Dilts C, Demsey SA. Adults
with Williams syndrome. Am J Med Gen Suppl. 1990;6:102-107
[12.] Greenberg F, Lewis RA. The Williams syndrome:
spectrum and significance of ocular features.
Ophthalmology. 1988;95:1608-1612
[13.] Saul RA, Stevenson RE, Rogers RC, Skinner SA,
Prouty LA, Flannery DB. Williams syndrome. In: Proceedings
of the Greenwood Genetic Center. Greenwood, SC: Greenwood
Genetic Center; 1988:204-209
[14.] Pankau R, Partsch C-J, Winter M, Gosch A, Wessel
A. Incidence and spectrum of renal abnormalities m
Williams-Beuren syndrome. Am J Med Genet. 1996;63:301-304
[15.] Pober BR, Lacro RV, Rice C, Mandell V, Teele RL.
Renal findings in 40 individuals with Williams syndrome.
Am J Med Genet. 1993;46:271-274
[16.] Morris CA, Mervis CB. Williams syndrome. In:
Goldstein S, Reynolds CR, eds. Handbook of
Neurodevelopmental and Genetic Disorders in Children. New
York, NY: The Guilford Press; 1999;555-590)
[17.] Kaplan P, Kirschner M, Watters G, Costa MT.
Contractures in patients with Williams syndrome.
Pediatrics. 1989;84:895-899)
[18.] Wang PP, Hesselink JR, Jernigan TL, Doherty S,
Bellugi U. Specific neurobehavioral profile of Williams'
syndrome is associated with neocerebellar hemispheric
preservation. Neurology. 1992;42:1999-2002
[19.] Chapman CA, du Plessis A, Pober BR. Neurologic
findings in children and adults with Williams syndrome. J
Child Neurol. 1996;11:63-65
[20.] Pober BR, Filiano JJ. Association of Chiari I
malformations and Williams syndrome. Pediatr Neurol.
1995;12:84-88
[21.] Sargent JD, Stukel TA, Kresel J, Klein RZ. Normal
values for random urinary calcium to creatinine ratios in
infancy. J Pediatr. 1993;123: 393-397 |
| [22.] Bird LM,
Billman GF, Lacro RV, et al. Sudden death in Williams
syndrome: report of ten cases. J Pediatr. 1996;129:926-931
[23.] Power TJ, Blum NJ, Jones SM, Kaplan PE. Brief
report: response to methylphenidate in two children with
Williams syndrome. J Autism Dev Dis. 1997;27:79-87
[24.] American Academy of Pediatrics, Committee on
Children With Disabilities. Transition of care provided
for adolescents with special health care needs.
Pediatrics. 1996;98:1203-1206
RESOURCES FOR PARENTS
March of Dimes, 1275 Mamaroneck Ave, White Plains, NY
10605; Telephone: 914/428-7100; http.//www.modimes.org
The Williams Syndrome Association, PO Box 297, Clawson,
MI 48017; Telephone: 248/541-3630;
http://www.williams-syndrome.org
Williams Syndrome Foundation, University of California,
Irvine, CA 92697; Telephone: 949/824-7259;
http://www.wsf.org
The recommendations in this statement do not indicate
an exclusive course of treatment or serve as a standard of
medical care. Variations, taking into account individual
circumstances, may be appropriate. |
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