Transcript A case of Prader Willi Syndrome

A CASE OF
PRADER WILLI
SYNDROME
IV TH MEDICINE UNIT
CHIEF
DR.G.BAGIALAKSHMI M.D
ASSISTANT PROFESSORS
DR.N.RAGAVAN M.D
DR.KRISHNASAMY PRASAD M.D
PRESENTOR:
DR.SREEKUMAR P.S (POST
GRADUATE)
• 16 yr male patient was brought to hospital with predominant
complaints of
INCREASED WEIGHT GAIN -10 years
EXCESSIVE FOOD INTAKE - 8 years
POOR SCHOLASTIC PERFORMANCE - 8 years
• INCREASED WEIGHT GAIN – since childhood,
associated with excess food intake
• EXCESSIVE FOOD INTAKE –insidious in onset
since 3 years of age
gradually increasing
attained the present weight
H/O Poor scholastic performance +
H/O day time sleepiness +
H/O decreased physical activity
H/O multiple meals (6-8) per day
H/O developmental delay +
Head Control 1 Year Of Age
Standing 2 Years
Walking 2 ½ Years
Speech Development Delayed
H/O dental caries+
• No h/o any chronic illness
• No h/o constipation
• No h/o head ache, visual disturbances
• No h/o joint pain/ back ache
• No h/o difficulty in breathing
• No h/o head injury
• No h/o meningitis/ encephalitis/seizures
Past history
• Patient had UNDESCENDED TESTIS both side for which he was
operated at age of 1 ½ years of age
• Evaluated for poor scholastic performance
– diagnosed to have hypothyroidism at age of 11 years
– started on treament T. Thyroxine 50 mic gm/day
-- discontinued treatment after 3 years
• Antenatal history: uneventful
• Natal history:H/O BIRTH ASPHYXIA+ -no records
• Post natal history:
 H/o feeding difficulties in infancy+
 H/o poor weight gain during early infancy+
 H/o floppiness during infancy+
 H/o high pitched cry +
 H/o excessive weight gain after infancy+
Personal
history
 Bladder bowel
habits – normal
• HYPERPHAGIA+
6-8 meals /day
• Excessive
sleeping+
Family history
Patient
General examination
• Conscious
• Oriented
• Afebrile
• No pallor/icterus/cyanosis/
• No clubbing/pedal
edema/lymphadenopathy.
• Oral cavity: DENTAL CARIES
• OBESITY: android type
• No markers of congenital heart disease
• No neuro cutaneous markers
• Axillary & pubic hair-absent
DENTAL CARIES
Anthropometry
Height – 150 cm
Weight -84 kg
BMI – 37.33 kg/m2 –OBESE
Head circumference 52 cm
ALMOND EYES
VITAL SIGNS
110/80mm
of Hg
88/min,
98%in
regular
Room air
SYSTEMIC EXAMINATION
Abdominal examination:
soft
no free fluid
no organomegaly
MICRO PENIS+
Testicular volume 2ml each
Pubic hair- absent
Other system examination - normal
MICRO PENIS
PROVISIONAL DIAGNOSIS
 CHILDHOOD OBESITY for evaluation
( ? Genetic /? Hormonal)
 Hypothyroidism
INVESTIGATIONS
Hb :11.1 gm%
Sr. urea: 24mg%
TC : 13200 cells/mm3
Sr. creatinine: 0.8mg%
DC : Neutrophils-77%
Urine routine
Lymphocytes-10 %
Albumin- Nil
Monocyte -7 %
Sugar- nil
Platelet count- 4.76lacs/mm3
Deposits- 0-3 pus cells
INVESTIGATIONS
Sr calcium- 9.6 mg/dl
T.CHOLESTEROL-115
RBS-118 mg/dl
TRIGLYCERIDES-76
FBS- 93 mg/dl
LDL-57
PPBS-129 mg/dl
HDL-42
PSYCHIATRIST OPINION
A c/o hypothyroidism/hypogonadotropic hypogonadism/? prader
willi syndrome
Advice:
IQ assesment
IQ TESTING done – MODERATE mental Retardation- IQ 52
OPHTHALMOLOGIST OPINION
• NO squint/nystagmus
• Fundus- normal
• EOM – full and free
OBESITY ASSOCIATED SYNDROMES
WITH DEVELOPMENTAL DELAY
WITHOUT DEVELOPMENTAL DELAY
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Prader-willi syndrome
Fragile x syndrome
Bardet biedel syndrome
Wilson turner syndrome
Cohen syndrome
Albrights hereditary
osteodystrophy
• Borjesson-Forssman-Lehmann
syndrome
Alstrom syndrome
Ulnar-mammary syndrome
Simpson-golabi-mehmel syndrome
Congenital leptin deficiency
Leptin receptor deficiency
POMC deficiency
Prohormone convertase deficiency
Melanocortin 4 receptor deficiency
ENDOCRINOLOGIST OPINION
• Obesity/hypogonadism/HYPERPHAGIA- PRESENT
• Testicular volume- 2cm each
• K/C/O Hypothroidism- not on regular treatment
IMPRESSION:
 HYPOTHYROIDISM
 HYPOGONADOTROPIC HYPOGONADISM
 ? PRADER WILLI SYNDROME
ADVICE:
 T4,TSH
 LH,FSH,PROLACTIN
 MS-PCR
 USG- ABDOMEN & PELVIS
 X RAY L HAND
HORMONAL ASSAY
HORMONE
PATIENT VALUE
REFERENCE VALUE
T4
98 ng/ml
70-124 ng/ml
TSH
6.2 mIU/ml
0.34-4.25 mIU/ml
LH
<0.07 mIU/ml
1.24-8.62 mIU/ml
FSH
<0.50 mIU/ml
1-12 mIU/ml
Testosterone
35.93 ng/dl
270-1070 ng/dl
GREEN- ELEVATED
RED-REDUCED
Usg abomen and scrotum:
Abdomen:
• no significant abnormality detected
Scrotum :
• Rt testis 4 ml
• Lt testis 7 ml
X ray L Wrist
•Joint space normal
•No lytic
Lesions/fractures
•Bone age <18 years
X Ray LS Spine
Indications for DNA testing in PWS
Age at assessment
Features sufficient to prompt DNA testing
Birth to 2 yr
Hypotonia with poor suck
2–6 yr
• Hypotonia with a history of poor suck
• Global developmental delay
• Short stature and/or growth failure associated with
accelerated weight gain
6–12 yr
• Hypotonia with a history of poor suck (hypotonia
often persists)
• Global developmental delay
• Excessive eating (hyperphagia,obsession with food)
with central obesity if uncontrolled
13 yr through adulthood
(OUR PATIENT)
 Cognitive impairment, usually mild mental retardation
 Excessive eating (hyperphagia,obsession with food)
with central obesity if uncontrolled
 Hypothalamic hypogonadism and/or typical behavior
problems(including temper tantrums and
obsessive-compulsive features)
Methylation specific polymerase chain reaction
(MS-PCR)
ENDOCRINOLOGIST REVIEW
DIAGNOSIS:
• Sub clinical hypothyroidism/ Prader Willi Syndrome
Advice:
Weight reduction
Diet modification
Inj Testosterone ½ c.c 15 days once
T.Thyroxine 100 micro gm 1/2-0-0
T.Metformin 500 mg 1-0-1
Periodic monitoring of thyroid and glycaemic status
FINAL DIAGNOSIS
 Genetic obesity
 PRADER
WILLI
SYNDROME
 Sub clinical
hypothyroidism
DISCUSSION
What is prader willi Syndrome?
• It was first described in 1956 by Andrea Prader, Heinrich Willi,
Alexis Labhart, Andrew Ziegler, and Guido Fanconi of
Switzerland
• Incidence (USA) 1 IN 15000-20000
• Incidence (INDIA) NOT AVILABLE
DEFINITION
• PWS arises from the lack of expression of genes on
the paternally derived chromosome 15q11-q13.
• Candidate genes for PWS in this region are
physiologically imprinted and silenced on the
maternally inherited chromosome .
• PWS develops if the paternal alleles are defective,
missing, or silenced.
Characteristics
• Symptoms are believed to be
caused by dysfunction of a
portion of the brain called the
hypothalamus.
• Although hypothalamic
dysfunction is believed to lead
to the symptoms of PWS, it is
unclear how the genetic
abnormality causes
hypothalamic dysfunction.
There are two generally recognized
stages of the symptoms associated
with PWS
• Stage 1
In the first stage, infants with
PWS are hypotonic or "floppy",
with very low muscle tone.
Weak cry and a poor suck reflex
are typical. Babies with PWS
usually are unable to breastfeed
and frequently require tube
feeding.
These infants may suffer from
"failure to thrive" if feeding
difficulties are not carefully
monitored and treated.
As these children grow older,
strength and muscle tone
generally improve.
Motor milestones are achieved,
but are usually delayed.
Stage 2
An unregulated appetite
characterizes the second stage of
PWS.
This stage most commonly begins
between ages 2 and 6 years old.
Individuals with PWS lack normal
hunger and satiety cues.
They usually are not able to
control their food intake and will
overeat if not closely monitored.
Food seeking behaviors are very
common.
In addition, the metabolic rate of
persons with PWS is lower than
normal.
Left untreated, the combination
of these problems will lead to
morbid obesity and its many
complications.
Other characteristics
oPrader-Willi syndrome is
considered a spectrum disorder,
meaning not all symptoms will
occur in everyone affected and
the symptoms may range from
mild to severe.
oPeople with Prader-Willi often
have some mental strengths as
well, such as skills in jigsaw
puzzles.
oIf obesity is prevented, people
with the syndrome can live a
normal lifespan.
oBehavioral problems, usually during
transitions and unanticipated
changes, such as stubbornness or
temper tantrums
oDelayed motor skills and speech due
to low muscle tone
oCognitive problems, ranging from
near normal intelligence to mild
mental retardation; learning
disabilities are common
oRepetitive thoughts and
verbalizations
oCollecting and hoarding of
possessions
oPicking at skin
oLow sex hormone levels
Indications for DNA testing
Age at assessment
Features sufficient to prompt DNA testing
Birth to 2 yr
Hypotonia with poor suck
2–6 yr
• Hypotonia with a history of poor suck
• Global developmental delay
• Short stature and/or growth failure associated with
accelerated weight gain
6–12 yr
• Hypotonia with a history of poor suck (hypotonia
often persists)
• Global developmental delay
• Excessive eating (hyperphagia,obsession with food)
with central obesity if uncontrolled
13 yr through adulthood
(OUR PATIENT)
 Cognitive impairment, usually mild mental retardation
 Excessive eating (hyperphagia,obsession with food)
with central obesity if uncontrolled
 Hypothalamic hypogonadism and/or typical behavior
problems(including temper tantrums and
obsessive-compulsive features)
• Because imprinted genes demonstrate differential DNA
methylation dependent on parental origin , patients with
PWS have a maternal-only imprint because they are lacking
a paternal contribution.
• DNA methylation analysis is the only technique, which can
both confirm and reject the diagnosis of PWS, and
therefore should typically be the initial investigation of
Choice.
• Fluorescence in situ hybridization (FISH) analysis will detect
only 60% of interstitial chromosome Deletions
• Negative FISH or karyotype analysis does not exclude the
diagnosis and so if done first should be followed by DNA
methylation analysis.
Treatment
In multiple studies, HUMAN GROWTH HORMONE (HGH) has been found to be beneficial
in treating Prader-Willi syndrome.
In June of 2000, HGH was officially recognized by the Federal Drug Administration (FDA)
in the United States and other countries for use in patients with Prader-Willi syndrome.
HGH is effective not only in increasing height, but also
Decreasing body fat, increasing muscle mass
 Improving weight distribution
 Increasing stamina,
 Increasing bone mineral density
Despite this, many difficult symptoms associated with PWS remain untreated.
To date, no effective medications have been found to regulate appetite.
Inability to control food intake is often the biggest obstacle keeping those with PWS
from living independently.
In addition, medical treatment of the psychiatric and behavioral issues associated with
PWS has produced inconsistent results.
Other Treatments
Exercise and physical activity can help control weight and help with
motor skills.
Speech therapy may be needed to help with oral skills.
REFERENCES:
 JOURNAL . Clin. Endocrinol. Metab. 2008 93:4183-4197
(originally published on Aug 12, 2008)
 Willliams text book of endocrinology
 Endocrinology adult and pediatric 6th edition
STILL HUNGRY FOR A CURE??