Scoliosis, Hip Dysplasia & Perioperative Risk
- Prader-Willi syndrome is a genetic imprinting disorder caused by loss of the paternally expressed genes at 15q11-q13
- Scoliosis and developmental hip dysplasia are the two principal orthopaedic manifestations, both attributed largely to hypotonia
- Scoliosis starts early (median 4.5 years), so surveillance begins in the preschool years, not at adolescent screening age
- No subgroup can be screened less: sex, genotype, BMI and obesity predicted neither deformity
- Monitor the spine during growth-hormone therapy rather than reflexively withholding it
- Optimise weight and OSA and plan the anaesthetic in a multidisciplinary team before any operation
- “Prader-Willi = imprinting disorder (loss of paternal 15q11-q13); hypotonia evolving to hyperphagia/obesity, short stature, hypogonadism, developmental delay.
- “Miao n = 175: scoliosis 43.7% (78.8% mild) median onset 4.5 yrs; hip dysplasia 38.2% median onset 1.8 yrs. Sex, genotype, BMI and obesity predicted neither. Only ~1 in 8 affected children were treated.
- “Monitor the spine during rhGH rather than withholding it - but know that no trial shows rhGH accelerates curves; the caution is precautionary. Perioperative risk = obesity + OSA + hypotonia (anaesthetic/respiratory) - plan carefully, especially for spine surgery. PWS is not associated with malignant hyperthermia.
Overview
Prader-Willi syndrome (PWS) is a genetic imprinting disorder caused by loss of the paternally expressed genes at chromosome 15q11-q13. Neonatal hypotonia and feeding difficulty evolve into childhood hyperphagia and obesity, with short stature, hypogonadism, developmental delay and behavioural problems.
The orthopaedic footprint. The two principal manifestations are scoliosis and developmental dysplasia of the hip, both attributed largely to the underlying hypotonia. Both are common enough to be actively sought in every child with PWS, although most of the scoliosis found is mild.
The perioperative problem. For the orthopaedic surgeon the perioperative period is genuinely high-risk. Obesity, obstructive sleep apnoea (OSA), hypotonia with respiratory muscle weakness, altered temperature and pain responses and behavioural issues all raise anaesthetic and respiratory risk, which matters for any orthopaedic operation and especially for scoliosis correction.
The approach. Management is early diagnosis and surveillance within a multidisciplinary team. The spine and hips are monitored, each deformity is treated on its merits, and the systemic problems (weight, OSA) are optimised before any operation.
The Genetics: Imprinting, the Three Mechanisms, and Angelman
Genomic imprinting. Some genes are expressed from only one parental allele, because the other copy is epigenetically silenced (methylated) according to its parent of origin. At 15q11-q13 a cluster including SNRPN and the SNORD116 snoRNA cluster is normally expressed only from the paternal allele, and losing that paternal expression causes PWS.
Three mechanisms. Paternal expression is lost in one of three ways, and rarely through a paternal translocation:
- Paternal 15q11-q13 deletion - about 65-75%
- Maternal uniparental disomy, both chromosome 15s inherited from the mother - about 20-30%
- Imprinting-centre defect - about 1-3%
The Angelman contrast. Loss of the maternally expressed gene in the same region, UBE3A, causes Angelman syndrome, by maternal deletion, paternal uniparental disomy or UBE3A mutation. Its phenotype is entirely different (severe intellectual disability, ataxia, seizures, a happy demeanour), so parent of origin decides which syndrome results. The two syndromes share the common BP1–BP3 deletion interval.
Diagnosis. DNA methylation analysis of 15q11-q13 is the first-line test, because an abnormal methylation pattern detects all three mechanisms. FISH or microarray (for deletion) and microsatellite or uniparental-disomy studies then define the specific mechanism, which matters for recurrence-risk counselling.
Scoliosis
How common, how severe. In the largest paediatric series (Miao, n = 175) scoliosis was present in 43.7%. Most of it was mild: 78.8% mild, 15.2% moderate and only 6.1% severe.
When it appears. Scoliosis in PWS is variable and presents early. Median age at onset was 4.5 years, prevalence rose sharply at age 5 and again in adolescence, and the mean Cobb angle increased with age.
Treatment. Scoliosis is treated on its merits: observation, bracing, or surgery for progression, with the perioperative caveats set out below. The published cases run from casting and bracing to growth-preserving instrumentation and fusion.
Developmental Dysplasia of the Hip
Prevalence and timing. Hip dysplasia, related to hypotonia, was present in 38.2% of the Miao series and was detected at a median of 1.8 years. It is screened for and managed along standard DDH lines, with awareness of the syndrome.
Reading the natural history. Two findings temper how aggressively it is treated. Only 12.7% of affected children in that series received any orthopaedic treatment, and the mean acetabular index decreased (improved) with age across the cohort. That improvement is descriptive and cross-sectional, not a licence to observe, and it does not replace infant clinical and radiographic screening. What it does mean is that the published PWS hip data describe a largely untreated population.
Surveillance and Growth Hormone
No low-risk subgroup. In the Miao series sex, genotype (paternal deletion vs maternal uniparental disomy), BMI and obesity rate showed no significant association with scoliosis or hip dysplasia, or with their age of onset. A lean child with PWS is not protected, and a deletion genotype does not warrant different surveillance, so every child is screened on the same schedule.
When to look. Because onset is early, spinal surveillance starts in the preschool years, not at the usual adolescent screening age. The spine is monitored clinically and radiographically, particularly during growth spurts and growth-hormone therapy, and the hips are screened for DDH.
Growth hormone. Recombinant growth hormone (rhGH) is widely used in PWS for body composition and stature. Consensus is to monitor the spine during rhGH rather than reflexively withhold it. Be clear that no trial has shown rhGH causes or accelerates curve progression: the caution is precautionary, not evidence of harm.
Anaesthetic Considerations (Including the Malignant-Hyperthermia Myth)
Airway and breathing. Obesity, OSA and hypotonia with weak respiratory muscles combine with a blunted ventilatory response to hypoxia and hypercapnia, and with thick secretions. The result is a difficult airway and a high risk of postoperative hypoventilation and respiratory failure, so a preoperative sleep study is valuable and extended postoperative respiratory monitoring is required.
Temperature. Hypothalamic dysfunction causes altered thermoregulation and intraoperative temperature instability, either hyper- or hypothermia, so temperature must be monitored.
Despite the hypotonia, PWS is not associated with malignant hyperthermia, and volatile agents and succinylcholine are not contraindicated on MH grounds. The misconception is a common exam trap.
Growth hormone and the airway. A sleep study or ENT assessment is recommended before rhGH is started. rhGH can worsen OSA early in treatment (adenotonsillar and lymphoid tissue) and has been linked with sudden death in children with severe respiratory compromise, so respiratory status is optimised first and the airway is monitored alongside the spine.
Other hazards. Beyond the airway and temperature:
- Delayed gastric emptying and hyperphagia raise aspiration risk
- Pain may be under-reported because perception is altered
- Sensitivity to sedatives is heightened
- Obesity makes intravenous access and positioning difficult
- Behavioural issues can complicate care
Planning. Weight and OSA are optimised before surgery, and any operation, above all scoliosis correction, is planned with endocrinology, respiratory medicine and anaesthesia in a multidisciplinary team. Plan the anaesthetic as carefully as the operation.
Mnemonics & Memory Aids
PWS
Hook:PWS: Paternal 15q loss/hyPotonia, Weight+OSA (anaesthetic risk), Scoliosis + hip dysplasia (Surveil, monitor spine on rhGH).
Clinical Decision Scenarios
Practise clinical reasoning and management decisions out loud
“What are the orthopaedic issues in a child with Prader-Willi syndrome, and what would you be cautious about before operating?”
What it is
- Imprinting disorder: loss of paternal genes at 15q11-q13
- Neonatal hypotonia evolving to hyperphagia/obesity, short stature, hypogonadism, developmental delay
- Hypotonia drives the orthopaedic deformities
Orthopaedic manifestations
- Scoliosis 43.7% - 78.8% mild, 15.2% moderate, 6.1% severe; median onset 4.5 yrs, rising at 5 and in adolescence
- Developmental hip dysplasia 38.2%; median onset 1.8 yrs; acetabular index improved with age
- Sex, genotype, BMI, obesity: NO association with either deformity or its onset
- Only 10.6% / 12.7% received treatment - the published data are largely untreated natural history
- Monitor the spine during rhGH; no trial shows rhGH accelerates curves
Perioperative risk
- Obesity + obstructive sleep apnoea + hypotonia/respiratory weakness
- Altered temperature regulation and pain perception; behavioural issues
- Optimise weight/OSA; multidisciplinary planning; close postoperative respiratory monitoring
Evidence & Key Studies
Orthopedic manifestations in children with Prader-Willi syndrome
- Retrospective single-centre review of 175 children with PWS at a Chinese tertiary children's hospital (Zhejiang), to March 2023. Scoliosis in 66 (43.7%) and hip dysplasia in 47 (38.2%) - note the percentages are calculated on the subsets who had the relevant imaging (roughly 151 and 123 respectively), not on all 175, so they are prevalence among those investigated.
- Scoliosis severity: 52 mild (78.8%), 10 moderate (15.2%), 4 severe (6.1%). Median age at scoliosis 4.5 years, prevalence rising sharply at age 5 and again in adolescence, mean Cobb angle increasing with age. Median age at hip dysplasia 1.8 years, and mean acetabular index DECREASED with age.
- Treatment uptake was strikingly low: only 7 of 66 scoliosis patients (10.6%) and 6 of 47 with hip dysplasia (12.7%) received any orthopaedic treatment - so this cohort describes the largely UNTREATED natural history, not the results of management.
- NEGATIVE findings that matter: no significant difference in sex, genotype (deletion vs uniparental disomy), BMI, or obesity rate in relation to scoliosis or hip dysplasia, or to their age of onset. Obesity and genotype did not predict who developed a deformity.
- Limitations: single centre, retrospective, cross-sectional; no follow-up duration and NO outcome data, so the authors' closing statement that early diagnosis and treatment matter for prognosis is a recommendation, not a result of this study.
The prevalences (scoliosis 43.7%, 78.8% of it mild; hip dysplasia 38.2%), the median onset ages (4.5 and 1.8 years), the Cobb-angle and acetabular-index trends with age, the low treatment uptake (10.6% and 12.7%) and the negative associations with sex, genotype, BMI and obesity all come from the Miao series (DOI) - a single-centre Chinese retrospective study with no follow-up or outcome data. The imprinting genetics (loss of paternal 15q11-q13), the role of hypotonia, and the perioperative risks (obesity, OSA, hypotonia, and the absence of a malignant-hyperthermia association) are standard, well-established teaching.
Be precise about growth hormone. Miao reported only that the prevalence of hip dysplasia among children treated with rhGH was low; that study did not test whether rhGH causes, accelerates or protects against scoliosis. The recommendation to monitor the spine during rhGH rather than withhold it is consensus practice, not a finding of this cohort, and no randomised trial has established a causal effect of rhGH on curve progression in PWS. No validated PWS-specific curve-progression risk score, bracing threshold or surveillance interval has been published; the age-targeted screening described here is extrapolated from the onset ages above.
