Rett Syndrome
Progressive Neurodevelopmental Regression
Key Features
Critical Must-Knows
- MECP2 Gene: X-linked. Males usually not viable.
- Regression: Normal development then regression at 6-18 months.
- Hand Stereotypies: Classic hand-wringing.
- Scoliosis: Nearly universal, often severe.
- Non-ambulatory: Most patients are wheelchair-bound.
Examiner's Pearls
- "MECP2 mutation
- "Hand-wringing stereotypies
- "Scoliosis is nearly universal
- "Females almost exclusively
Scoliosis Surgery Considerations
Scoliosis surgery in Rett Syndrome has unique considerations.
- Patients are non-communicative - pain assessment is difficult.
- High complication rate.
- Respiratory compromise common.
- Long fusions (often to pelvis) are needed.
- QOL benefits for sitting balance and caregiving.
Rett Syndrome Stages
| Stage | Age | Features |
|---|---|---|
| 6-18 months | Decelerated development, hypotonia | |
| 1-4 years | Loss of skills, hand stereotypies, seizures | |
| Preschool-adult | Stable, seizures, scoliosis develops | |
| Variable | Reduced mobility, severe scoliosis |
Rett Features
Memory Hook:RETT - Regression, MECP2, Stereotypies, Truncal (scoliosis).
Orthopaedic Issues
Memory Hook:SHF - Spine, Hips, Feet.
Surgery Challenges
Memory Hook:CRS - Communication, Respiratory, Seizures.
Overview/Epidemiology
Rett Syndrome is a neurodevelopmental disorder with regression.
- Genetics: X-linked dominant. Mutations in MECP2 gene (Xq28).
- Incidence: 1 in 10,000-15,000 females.
- Sex: Almost exclusively females. Males with MECP2 mutations usually die in utero.
- Natural History: Normal development followed by regression at 6-18 months.
Pathophysiology
Why Scoliosis Develops
- Central hypotonia and poor motor control.
- Asymmetric posture and muscle activity.
- Curves are typically long C-shaped thoracolumbar.
- Pelvic obliquity is common.
- Progression is relentless in most.
Hip Dysplasia
- Hypotonia + abnormal posture → subluxation.
- Often asymptomatic.
Classification Systems
Clinical Stages (Hagberg)
- Stage I (Early Onset Stagnation): 6-18 months. Developmental deceleration.
- Stage II (Rapid Developmental Regression): 1-4 years. Loss of hand skills, speech. Hand stereotypies begin.
- Stage III (Pseudostationary): Preschool-adult. Stable phase. Seizures, breathing irregularities. Scoliosis develops.
- Stage IV (Late Motor Deterioration): Reduced mobility, severe scoliosis, muscle wasting.
Clinical Assessment
History:
- Age of regression.
- Current mobility and communication status.
- Seizure history.
- Respiratory status.
- Feeding issues.
Physical Exam:
- General: Non-communicative. May be agitated.
- Hand Stereotypies: Hand-wringing, hand-mouthing.
- Spine: Scoliosis, often severe.
- Hips: Assess for subluxation.
- Feet: Equinovarus.
- Respiratory: Breathing irregularities (hyperventilation, breath-holding).
Investigations
Genetic Testing:
- MECP2 mutation: Confirmatory.
Imaging:
- Spine X-ray: Scoliosis assessment.
- Hip X-ray: Subluxation.
Cardiac:
- ECG: QT prolongation can occur.
Respiratory:
- Sleep study if needed.
Management Algorithm
Scoliosis Management
- Observation: Mild curves.
- Bracing (Seating Support): Does not prevent progression but aids sitting.
- Surgery: Posterior spinal fusion for curves greater than 40-50 degrees. Usually T2-pelvis.
Surgical Techniques
Posterior Spinal Fusion
Indications: Progressive scoliosis greater than 40-50 degrees.
Technique: Posterior approach. Long fusion (T2 to pelvis). Pelvic fixation with iliac screws or S2-alar-iliac screws. Pedicle screw constructs.
Considerations: High complication rate. Respiratory issues common. Non-communicative patients - pain assessment difficult. ICU post-op.
Complications
| Complication | Context | Management |
|---|---|---|
| Respiratory | Perioperative, disease-related | BiPAP, careful anesthesia |
| Infection | Wound, UTI | Prophylaxis, antibiotics |
| Pseudarthrosis | Long fusions | Revision if symptomatic |
| QT Prolongation | Anesthesia risk | ECG, avoid QT-prolonging drugs |
Postoperative Care
- ICU Monitoring: Respiratory.
- Pain Assessment: Difficult. Use behavioral scales.
- Mobilization: Sitting as tolerated.
- Long-Term: Orthotic support, ongoing medical care.
Outcomes/Prognosis
- Life Expectancy: Variable. Many survive to 40s-50s.
- Scoliosis Surgery: Improves sitting, caregiving ease. May not improve survival.
- QOL: Difficult to assess. Benefits often for caregivers.
Evidence Base
- Rett syndrome overview
- MECP2 mutation identified
- Clinical staging
- Scoliosis in Rett syndrome
- High progression rate
- Surgery beneficial
- Scoliosis natural history
- Nearly universal
- Progressive
- Review of scoliosis treatment
- Limited evidence
- Surgery improves sitting
- Rett syndrome diagnostic criteria
- Classic vs atypical forms
- MECP2 testing
Viva Scenarios
Practice these scenarios to excel in your viva examination
Scoliosis in Rett Syndrome
"10-year-old female with Rett Syndrome. Thoracolumbar scoliosis of 65 degrees with pelvic obliquity. Non-ambulatory, non-communicative. Seizures controlled on medication."
This patient needs **scoliosis surgery**. The 65-degree curve with pelvic obliquity is progressive and impacts sitting balance. I would perform **posterior spinal fusion from T2 to pelvis** with pelvic fixation (S2-alar-iliac or iliac screws). Pre-operatively, I would ensure **seizure control**, check **ECG** for QT prolongation (affects anesthetic drug choice), and brief the family on high complication rates. Postoperatively, **ICU monitoring** is needed. Pain assessment will be challenging - use behavioral pain scales.
Genetics of Rett
"What is the genetic cause of Rett Syndrome?"
Rett Syndrome is caused by mutations in the **MECP2 gene** located on the X chromosome (Xq28). It is **X-linked dominant**. Affected males usually do not survive (embryonic lethality), so the condition is seen almost exclusively in females. The MECP2 protein is involved in gene regulation and neuronal development.
Hip Management
"Same patient has bilateral hip subluxation (MP 40%). Should this be treated surgically?"
In Rett Syndrome, **hip surgery is rarely indicated**. The hips are often asymptomatic even when subluxated. Surgery has high failure rates in this population, and the functional benefit is minimal as the patient is non-ambulatory. I would observe and ensure proper seating. If the hip becomes **painful** (suspected based on behavior changes), salvage options (proximal femoral resection or valgus osteotomy) may be considered, but reconstruction is generally not recommended.
MCQ Practice Points
Genetics MCQ
Q: What gene is mutated in Rett Syndrome? A: MECP2 gene on Xq28.
Sex MCQ
Q: Why is Rett Syndrome almost exclusively seen in females? A: It is X-linked dominant. Males with MECP2 mutations usually have embryonic lethality.
Orthopaedic MCQ
Q: What is the incidence of scoliosis in Rett Syndrome? A: 80-90%.
Clinical MCQ
Q: What is the classic hand movement in Rett Syndrome? A: Hand-wringing stereotypies.
Surgery MCQ
Q: What is the extent of fusion for scoliosis in Rett Syndrome? A: T2 to pelvis with pelvic fixation (S2-alar-iliac or iliac screws).
Cardiac MCQ
Q: What cardiac issue should be checked before scoliosis surgery in Rett? A: QT prolongation on ECG - affects anesthetic drug choice.
Australian Context
- Genetic Testing: Available clinically.
- Multidisciplinary Care: Neurology, orthopaedics, respiratory.
- Scoliosis Surgery: High-risk, done at pediatric spine centers.
- Support: Rett Syndrome Association of Australia.
RETT SYNDROME
High-Yield Exam Summary
GENETICS
- •MECP2 Gene
- •Xq28
- •X-linked Dominant
- •Females almost exclusively
CLINICAL
- •Regression 6-18mo
- •Hand stereotypies
- •Seizures
- •Non-communicative
ORTHOPAEDIC
- •Scoliosis 80-90%
- •Hip subluxation
- •Equinovarus feet
- •Pelvic obliquity
SCOLIOSIS SURGERY
- •T2-pelvis fusion
- •Pelvic fixation essential
- •High complication rate
- •ICU post-op care
PRE-OP CHECKS
- •ECG for QT prolongation
- •Seizure control
- •Respiratory status
- •Nutrition assessment
PROGNOSIS
- •Survival to 40s-50s
- •Surgery improves sitting
- •Non-ambulatory most
- •QOL benefits caregivers
Self-Assessment Quiz
Differential Diagnosis
Other Neurodevelopmental Regression Disorders:
- Angelman Syndrome: Different gene (UBE3A), happy demeanor, seizures, no hand stereotypies.
- Autism Spectrum Disorder: Some features overlap but no regression pattern, no hand stereotypies.
- Cerebral Palsy: Non-progressive, different history.
- Infantile NCL (Neuronal Ceroid Lipofuscinosis): Progressive but different clinical features.
Key Differentiators for Rett Syndrome:
- MECP2 mutation is confirmatory.
- Classic hand-wringing stereotypies.
- Regression after period of normal development.
- Almost exclusively females.
Red Flags Suggesting Alternative Diagnosis:
- Male patient - very rare in Rett.
- No regression history - consider other causes.
- No hand stereotypies - less typical.
Additional Quiz Questions
Key Surgical Considerations
Pre-operative Assessment:
- ECG for QT prolongation - affects anesthetic drug choice.
- Seizure control on current medications.
- Nutritional status - many have gastrostomy.
- Respiratory function - breathing irregularities common.
Intra-operative Concerns:
- Avoid QT-prolonging anesthetic drugs.
- Careful monitoring for arrhythmias.
- High blood loss expected with long fusions.
Post-operative Challenges:
- Pain assessment in non-communicative patient.
- Respiratory monitoring in ICU.
- Early mobilization to seating.
- Careful wound care.