PI : The patient has presented with a clinical of congestive heart failure for 3 days, including limitation of normal activities, fatigability, edema, dyspea on exertion, and orthopnea. In addition, he has frequently taken a nap shortly with a loud snore even when he sits. Neither fever nor cough was noted.
PH: He was a full term newborn with a birth weight of 2400 gm. Since birh, he developed hypotonia and poor sucking, requiring gavage feeding. After initial investigations, he was referred to Chiang Mai University Hospital because he was suspected of having a severe neurological diseases.The complete neurological examination was normal, except hypotonia. The chromosome study was 46XY. On follow up, hypotonia and poor feeding improved. His body weight was within normal limit. Until during the past 3 years, he has become obese. He has had a loud snore when lying down and has slept while playing or studying in day time for 1 year.
Developmental assessment: The patient has mild global delayed development with articulation defects.

BW=31 kg, Ht=100 cm, BMI=31 kg/m2.
BP=100/70 mmHg, PR 140/min , RR=30/min , temp = 37 C
oxygen saturation 92%
GA : An obesity boy with irritible, having a nap while talking, slightly hypopigmentation, no acanthosis nigrican
HEENT: almond - shape eyes, grade-II tonsils
Heart: regular rhythm, no murmur, increased P2.
Lungs: no retraction, normal breath sound, fine crackle both lower lung fields.
Abdomen: no striae, no mass, no organmegaly.
Genitalia: normal.
Extremities: small hands and feet, no camptodactyly, mild edema at the dorsum of feet.

1. Congestive heart failure (cor pulmonale) and pulmonary edema.
2. Obstructive sleep apnea (snoring and day time sleep )
3. Morbid obesity with dysmorphic features (almond - shaped palpebral fissures, small hands and feet)
4. Mild global delay development with articulation defects
5. Hyperphagia started when he was 2 years old.
6. History of floppy infant and feeding difficulty

CBC: Hb 13.5 gm/dl, Hct 41%, WBC=22,100cell/cumm, Platelet 489,000/cumm
Fasting blood sugar : 73 mg/dl
Chest X-ray: cephalization and perihilar inflitration, no cardiomegaly
EKG: Right ventricular hypertrophy
Lipid profile and thyroid function test : are normal

Figure 2. Fluorescent in situ hybridization (FISH): A red signal demonstrates the common region of PWS (15q11-13) and a green signal is a control to demonstrate chromosome 15. The patient has has two chromosome15 but has only one normal region of 15q11-13(left). Another chromosome has no red signal, suggesting deletion on that chromosome(right).

Treatment:

Oxygen mask with bag
Lasix 1 MKD and oral fluid restriction less than 1,000 ml/day
Caloric restriction 450 cal/day
Exercise program for increasing heart rate up to 10% of the maximum rate
Genetic counseling

- Incidence: 1:10,000-1:20,000 (1)
- Etiology (1,2): 70-75% chromosomal deletion, 20-25% uniparental disomy (UPD): two copy of the maternal chromosome 15, no copy of the paternal chromosome, 2-4% imprinting defects, <1% balance translocation involve 15q11-13 (Figure 3)
- Natural History (3,4)
Newborn: low-normal birth weight, severe hypotonia, severe feeding difficulty and sometimes, require specific feeding tecniques, cryptochidism, hypogenitalia in male
Infant: during 6-12 months old; failure to thrive
Childhood: 18 months old: gradual improvement in muscle tone, 3 years old: significant weight gain, delayed milestones, unusal facial appearance, small hands and feet, 3-5 years old: behaviour problems
Teenage: Severe obesity, DM, behaviour problems such as stubbornnees and temper tantrum

CNS
Severe congenital hypotonia(central type) and improvement begins latter
EMG and NCV are normal
Severe feeding difficulty
Early delays in development milestones, mild mental retardation (63%)
Sleep disorders, cataplexy, OSAS
Albinidism
50% and all of them have microdeletion 15q11-13
Obesity
Low metabolic rate so they can not loose their weight even restrict caloric intake
Voracious appetite, food seeking behaviour
Sexual Development
Few or no sign of puberty
Craniofacial fetures
Narrow bifrontal diameter
Almond-shaped eyes, inverted V-shaped mouth
Limbs
Microsomic hands and feet

Diagnosis (5)

1. High-Resolution Chromosome analysis (550 bands) or at least a routine chromosome analysis before molecular diagnostic techniques.
2. Fluorescense In situ Hybridization (FISH) uses two probes: one at centromere of chromosome 15 to identify chromosome 15 and another probe within deletion region.
3. Methylation Analysis (Southern hybridization or PCR)
4. PCR to detect UPD to determine whether children have normal biparental chromosome or have only maternal inheritance

Table 1. Ability to diagnose Prader-Willi syndrome among various diagnostic tests (6)

Suggested reading:
1. Gelehrter TD,Collin FS,Ginsburg D.Principles of medical genetics, 2nd ed.USA:Williams-Wilkins;1998.p.174-7.
2.Spinner NB,Emanuel BS.Deletion and other structural abnormalities of the autosome.in.Rimoin DL,Connor JM,Pyeritz RE,Korf BR,editors.Emery and Rimoin's Principles and practice of medical genetics.4th ed.USA: Churchill Livingstone;2002.p.1213-4.
3.Gorlin RJ,Cohen MM,Hennekam RCM.Clinical syndrome of the head and neck,4thed.USA:Oxford university press;2001.p.419-24.
4.Holm VA,Cassidy SB,Butler MG,Hanchett JM,Greenswang LR,Whitman BY,Greenberg F.Prader-Willi syndrome:consensus diagnositic Criteria.Pediatrics1993;91:398-402.
5.American society of human genetics/American college of medical genetics test and technology transfer committee.ASHG/ACMG report Diagnostic testing for Prader-Willi and Angleman syndrome:Report of the ASHG/ACMG test and technology transfer committee.Am J Hum Genet1996;58:1085-8.
6.Schwatz S,Cassidy SB.Prader-Willi syndrome2000 June [cited 2002 Jun 5].Available from URL http://www.genesclinic.com.
7.Carrel AL,Myers ES,Whitman BY,Allen DB.Benefits of long term GH therapy in Prader-Willi syndrome: a 4 year study.J Clin Endocrinol Metab 2002;87:1581-5.