Make a confusing case based on the prader willi rsyndrome without any direct symptoms,give secondary symptoms Make it as difficult as possible
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Searching PubMed
"Prader-Willi syndrome" AND diagnosis
The Case File: "The Patient Who Never Complained"
Setting: Emergency Department, then multi-specialty consult chain over one admission.
Presentation
A 19-year-old man is brought in by his group-home caregiver for progressive leg swelling and breathlessness over three weeks. He denies chest pain. Vitals: SpO2 88% on room air, RR 24, HR 102. Height 165 cm, weight 128 kg. He is noted to be unusually placid and answers questions slowly but appropriately.
History, pieced together from old records (each clue dropped in a different specialty's note, never labeled as "Prader-Willi")
Neonatal note (pediatrics, retrospective): "Described by mother as an exceptionally quiet, still baby. Poor suck reflex, required nasogastric feeding for the first 10 weeks of life. Cried rarely."
Ophthalmology, age 4: "Patched right eye for six months for amblyopia secondary to esotropia."
Orthopedics, age 8: "Underwent bilateral hip pinning for developmental dysplasia." Age 13: "Posterior spinal fusion T4-L2 for progressive juvenile-onset scoliosis, curve painless despite 55-degree magnitude at presentation."
Dental, age 11: "Twelve carious teeth extracted. Saliva noted to be unusually thick and scant, poor natural clearance of food debris."
Surgery, age 14: "Presented 4 days after onset of vague abdominal fullness, minimal reported pain. Intraoperatively found to have a perforated, gangrenous appendix with generalized peritonitis. Patient had continued eating throughout the illness and never vomited."
Endocrinology, age 16: "Referred for absent spontaneous pubertal development. Testes 1-2 mL bilaterally, cryptorchid history. Started on testosterone injections. LH/FSH low-normal for age."
Psychiatry, age 12-18: "Longstanding rigidity around routines, skin-picking excoriations on forearms and legs (diagnosed as excoriation disorder), and explosive temper outbursts when routines were disrupted. New this year: two-week episode of paranoid ideation and disorganized speech, resolved with low-dose risperidone."
Dermatology, incidental: "Notably fairer skin and lighter hair than both parents and siblings, all of whom are olive-skinned."
Current admission workup:
- ABG: pH 7.34, pCO2 58, HCO3 30, PaO2 52
- Hemoglobin 18.9 g/dL (secondary polycythemia)
- Echo: severely dilated right ventricle, estimated PASP 65 mmHg, findings consistent with cor pulmonale
- Sleep study (done years ago, never followed up): AHI 42, mixed obstructive and central events
- HbA1c 8.1%, new diagnosis of diabetes
- DEXA (ordered for the fracture below): Z-score -2.6, osteoporotic range
- Incidental old healed midshaft tibial fracture on chest/abdomen CT scout film - "no history of a fall or injury reported by the patient or caregiver"
The question
No note anywhere says "hypotonic infant," "hyperphagia," "obesity," "dysmorphic facies," or "intellectual disability." Every specialist closed their own loop: amblyopia treated, hips fixed, scoliosis fused, teeth pulled, appendix out, testosterone started, skin-picking managed, psychosis resolved, OSA old news, now it's just a cor pulmonale/heart failure admission. What ties all of it together?
The Reveal: Prader-Willi Syndrome (15q11-q13 paternal deletion / maternal UPD / imprinting defect)
Every clue above is a well-documented secondary or associated feature rather than a core diagnostic criterion, which is exactly what makes this pattern easy to miss when each specialist only sees their own organ system.
| Clue in the case | Underlying PWS mechanism |
|---|---|
| Quiet, poorly-feeding neonate needing NG feeds | Neonatal hypotonia presenting as a feeding/behavioral issue rather than being labeled "hypotonia" |
| Esotropia/amblyopia | Strabismus is a recognized associated finding - Tintinalli's Emergency Medicine, p. 2704 |
| Hip dysplasia, painless severe scoliosis | Skeletal features (hip dysplasia, juvenile scoliosis) - Miller's Review of Orthopaedics, p. 7503 |
| Thick, scant saliva and dental disease | Reduced salivary flow/viscous saliva is a described feature contributing to caries |
| Painless perforated appendicitis, no vomiting despite peritonitis | Decreased pain sensitivity and inability to vomit are specifically listed PWS features - Tintinalli's Emergency Medicine, p. 2704 |
| Absent puberty, cryptorchidism, low gonadotropins | Hypothalamic hypogonadism - K.J. Lee's Essential Otolaryngology, p. 1135; Emery's Elements of Medical Genetics, p. 89 |
| Skin-picking, rigidity, temper outbursts, transient psychosis | Behavioral phenotype and psychiatric vulnerability (psychosis risk is notably higher in the maternal UPD subtype) |
| Fair skin/light hair vs. family | OCA2 gene loss within the deleted 15q region causing relative hypopigmentation |
| Height 165 cm / weight 128 kg (never named "obese") | Short stature plus weight gain driven by chronic hyperphagia and elevated ghrelin, which does not suppress postprandially as it does in typical obesity (Sleisenger and Fordtran's GI and Liver Disease) |
| Chronic hypoventilation, polycythemia, cor pulmonale, OSA with central events | Combined obstructive and central sleep apnea from hypotonia plus hypothalamic respiratory drive abnormalities, leading to pulmonary hypertension and right heart failure - Tintinalli's, p. 2704 |
| New-onset diabetes | NIDDM associated with PWS-related weight pattern - K.J. Lee's Essential Otolaryngology, p. 1135 |
| Osteoporosis, painless old fracture | Low bone density plus decreased pain sensitivity masking the original fracture |
Confirmatory test: DNA methylation analysis of the SNRPN/SNURF locus (15q11-q13), which detects essentially all cases regardless of mechanism (paternal deletion ~70%, maternal uniparental disomy ~25%, imprinting center defect ~2-5%). Follow-up FISH or microsatellite/UPD studies determine the specific mechanism, which matters for recurrence risk counseling (Emery's Elements of Medical Genetics and Genomics, p. 89; Thompson & Thompson Genetics and Genomics in Medicine, 9e).
Why this case is deliberately hard
The diagnosis is almost never made from a single "textbook" sign in adulthood. It is made by refusing to let five or six specialists each close their own chart without asking whether a single upstream cause explains a hypotonic infancy, painless surgical emergencies, absent puberty, skeletal disease, skin-picking, transient psychosis, and adult-onset cor pulmonale in one person.
Recent evidence note: A 2024 systematic review confirms clinically significant psychotic illness occurs in a meaningful subset of PWS patients, especially with maternal uniparental disomy (Aman et al., Orphanet J Rare Dis 2024, PMID 38360662), and a 2024 meta-analysis quantifies elevated epilepsy prevalence in PWS (Pascual-Morena et al., PMID 38663143) - both reinforce that the psychiatric and neurologic "side plots" in this case are genuine, described associations rather than embellishment.
If you want, I can turn this into a formatted exam-style vignette with multiple-choice distractors (e.g., Bardet-Biedl syndrome, Angelman syndrome, MEHMO syndrome) to make it usable for teaching.
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