Hip displacement and scoliosis in Rett syndrome screening is required

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY ORIGINAL ARTICLE Hip displacement and scoliosis in Rett syndrome – screening is required | HEATHER GRAHAM M...
Author: Rafe Stanley
0 downloads 0 Views 439KB Size
DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY

ORIGINAL ARTICLE

Hip displacement and scoliosis in Rett syndrome – screening is required | HEATHER GRAHAM MBCHB 1 | H KERR GRAHAM MD FRCS (ED) FRACS 1 , 2 , 3 | HELEN LEONARD | DINAH REDDIHOUGH MD BSC FRACP FAFRM 1 , 2 , 3 | GORDON BAIKIE MD FRACP MRCP (UK) 1 , 3

GUAN TAY

MBBS

MBCHB MPH

4

1

1 Royal Children's Hospital, Melbourne, Australia. 2 University of Melbourne, Melbourne, Australia. 3 Murdoch Childrens Research Institute, Melbourne, Australia. 4 Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, West Perth, WA, Australia. Correspondence to Dr Gordon Baikie at Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia. E-mail: [email protected]

PUBLICATION DATA

AIM This study aimed to determine the prevalence of hip displacement and spinal deformity in a

Accepted for publication 24th March 2009. Published online 3rd July 2009.

clinic population of females with Rett syndrome to define implications for screening and management. METHOD Age, MECP2 gene status, gross motor function, prevalence of hip displacement, as measured by migration percentage, and spinal deformity, determined by measurement of Cobb angle, were recorded. RESULTS Thirty-one females with a mean age of 15 years 6 months (SD 5y 4mo) fulfilled a clinical diagnosis of Rett syndrome. Fifteen (48%, 95% confidence interval [CI] 30–67) of the cohort had a hip migration percentage of 30% of more. Eight of the 31 patients (95% CI 12–45) had undergone surgery for the prevention or treatment of hip displacement or dislocation. Twenty-seven of the 31 patients (95% CI 70–96) had a scoliosis, with a Cobb angle of less than 10; 20 patients (95% CI 45– 81) had a Cobb angle greater than 30. Eleven (95% CI 19–55) patients have required spinal fusion surgery. INTERPRETATION The prevalence of hip displacement and spinal deformity in a clinic cohort of females with Rett syndrome in Victoria, Australia, was very high. Early, repeated, and consistent clinical and radiological surveillance for hip displacement and spinal deformities is recommended in all young patients with Rett syndrome.

Rett syndrome is an X-linked, progressive, neurodevelopmental disorder with onset in early childhood. A recent epidemiological study has found that in Australia 1:8500 females will be diagnosed with this disorder by the age of 15 years.1 Another Australian epidemiological study has shown that 78% of women with Rett syndrome survive until the age of 25 years. Mutations of the X chromosome MECP2 gene account for about 80% of cases of Rett syndrome, and over 200 different mutations have been identified.2 The MECP2 gene codes for methyl-CPG-binding protein 2, which inhibits and activates gene transcription.3 There are emerging relationships between the type and position of the mutation and the phenotypic features of classic and variant Rett syndrome patients.3,4 Individuals with Rett syndrome and a mutation in the MECP2 gene cannot be differentiated from those without such a mutation, and thus, Rett syndrome remains a clinical diagnosis. This syndrome is characterized by the progressive loss of cognitive, communication, and motor skills, with deceleration of head growth and development of stereotypic hand movements, after a period of normal development.5 Neuromuscular deterioration may result in progressive loss of walking ability, ª The Authors. Journal compilation ª Mac Keith Press 2009

spasticity, and muscle imbalance,6 resulting in progressive deformities in many patients, including scoliosis, hip displacement, foot deformity, and joint contractures.7

METHOD Participants Our cohort, ascertained retrospectively, comprised females who fulfilled the diagnostic criteria for Rett syndrome and had been assessed at the Rett Syndrome Clinic or the Orthopaedic Department at The Royal Children’s Hospital in Melbourne, Australia, between January 2000 and July 2005. Patients were ascertained during 2004 and 2005. Clinical observations We performed a clinical audit of case histories, to determine age, demographic data, results of genetic testing for MECP2 gene mutations, and the Functional Mobility Scale score at the last review.8 This scale is used to assess the gross motor ability of patients over three distinct distances – 5, 50, and 500 metres (Fig. 1) – each on a scale of 1 to 6. For example, a child who uses crutches to walk 5 metres but requires a wheelchair to travel 50 and 500 metres would score 3, 1, 1. DOI: 10.1111/j.1469-8749.2009.03359.x 93

Rating

Rating

4

1 Uses wheelchair

Rating

Uses sticks (one or two):

Rating 5

2 Uses Kaye walker or frame:

Independent on level surfaces:

Rating

Rating 3 Uses crutches:

6 Independent on all surfaces:

Figure 1: FunctionalMobility Scales scores.

Radiological observations All available radiographs of patients were reviewed. Anteroposterior radiographs of the pelvis were taken using a standardized protocol established for children with cerebral palsy (CP). These radiographs were taken with the patient supine, pelvis symmetrical, hips in neutral abduction ⁄ adduction, and lumbar spine flat.9 Standardized measurements of migration percentage10 and pelvic obliquity11 were made from these pelvic radiographs. A migration percentage greater than 30% was considered significant subluxation. Radiographs of the spine were taken with the patient standing, sitting, or supine, according to her developmental and functional status. Scoliosis was identified from the antero-posterior radiograph, the Cobb angle measured, and the location of the curve identified using previously described techniques.12,13 The first author (GT) performed all radiological measurements. Surgical outcomes When surgical procedures were required for the management of hip displacement, these were classified into the following three categories: preventative, reconstructive, or salvage procedures (as described for patients with CP).9 The prevalence of need for surgical intervention for scoliosis was recorded. 94 Developmental Medicine & Child Neurology 2010, 52: 93–98

The Royal Children’s Hospital ethics committee approved this audit.

Statistical analysis This was an observational study so raw numbers, proportions with binomial exact 95% CIs, or ranges are presented. RESULTS Participants By 31 July 2005, 31 females had been assessed at the Rett Clinic or the Orthopaedic Department. All patients with a clinical diagnosis of Rett syndrome or a variant were included in this study. Clinical observations The mean age at which the audit was undertaken was 15 years 6 months (SD 5y 4mo, range 7–29y). Genetic mutations were found at the MECP2 gene on the X chromosome in 27 patients (95% CI 70–96). One patient tested negative, and no genetic testing had been performed in the remaining three patients (95% CI 2–26; Table SI, supporting information published online). Twenty-four of the 31 patients (95% CI 59–90) had a Functional Mobility Scale score of 1, 1, 1, and were wheelchair

bound, requiring constant care. The remaining seven patients were able to ambulate short distances independently, with or without aids.

Radiological observations At least one screening radiograph assessing hip subluxation had been taken in all patients. The number of surveillance radiographs taken varied widely, the mean being 4.4 (range 1–15). The proportion of patients with a hip migration percentage of 30% or more was 15 of 31 (95% CI 30–67). The proportion with hip dislocation was four out of 31 (95% CI 4–30). Eight patients had pelvic obliquity of 10 or more and, of these, three patients had pelvic obliquity of 20 or more with a dislocated hip on the high side. Spinal radiographs were taken in all patients in whom scoliosis was present clinically. Scoliosis was present (Cobb angle >10) in 27 of 31 patients, (95% CI 70–96), and a significant scoliosis (Cobb angle >30) was found in 20 of 31 patients (95% CI 45–81). The mean age of patients with any scoliosis was 16 years 5 months those without scoliosis had a mean age of 9 years 6 months. Of the 20 patients who had a clinically significant scoliosis, (Cobb angle of ‡30), 12 had typical long C-shaped thoracolumbar curves typical of neuromuscular disorders. Six children had a double major curve and two had thoracic curves. Surgical outcomes Overview Fifteen females had a hip migration greater than or equal to 30%. Of these, six patients (95% CI 7–37) had a migration percentage of 30% or more, had not required surgery but do require ongoing surveillance; five (95% CI 5–34) with a migration percentage of 30% or more, did not have hip dislocations, and were able to have preventative surgery. Four (95% CI 4–30) had hip dislocations, of whom three underwent surgery and one was unfit for surgery. All eight patients who underwent hip surgery had a Functional Mobility Scale score of 1, 1, 1. Subluxed hips not dislocated Five of the 31 patients (95% CI 5–34) underwent surgery for the prevention or treatment of hip displacement. At the most recent follow-up, four females with a mean age at the time of surgery of 14 years (range 11–18y) had mobile enlocated hips with a mean improvement in migration percentage from 46% (95% CI 39–50) to 26% (95% CI 18–38) at a mean of 31.5 months (range 15–41mo) after surgery. The remaining patient underwent preventative and reconstructive surgery. Complications resulted in salvage surgery 1 year after the original surgery and the patient subsequently died. Dislocated hips Four of the 31patients (95% CI 4–29) presented with a dislocated hip. Patient 1 (see Table SI) had spinal surgery at the age of 8 and re-presented at age 19 with a chronic irreducible dislocated left hip. Significant medical comorbidities prevented any surgery.

L R

Figure 2: Radiograph of patient 2 who presented with painful right hip dislocation.

Patient 2 presented with an acute painful right hip dislocation (see Fig. 2). Despite an initial successful closed reduction and soft tissue release, the hip again dislocated. Significant comorbidities prohibited reconstructive surgery. Salvage surgery may be necessary in future for pain relief. Patient 11 presented late with a painful dislocated right hip at the age of 12 years. She was not able to sit, toilet, or even tolerate perineal care. A medial open reduction and adductor and psoas release, together with an anterior obturator neurectomy were performed. Significant comorbidities prevented major reconstructive surgery. Sixteen months later, standing transfers were tolerated but she remained in a wheelchair. Repeat radiographs showed enlocated hips with early evidence of mild avascular necrosis of the right hip. At her latest review, she had bilateral mobile painless hips. Patient 28 presented with a painful dislocated left hip at the age of 9 years with no prior record of hip surveillance. An open reduction varus derotation osteotomy of the femur and adductor release was performed at 10 years with significant symptomatic and functional improvement. She was able to stand and ambulate short distances supported with a Kaye walker. She was then discharged but re-presented at 18 years with worsening pelvic asymmetry. No hip surveillance had been performed following surgery. She had a scoliosis, pelvic obliquity, and severe left hip subluxation with a migration percentage of 43%. A Dega pelvic osteotomy, varus derotation osteotomy of the femur, and percutaneous adductor releases were performed. Persistent adductor spasticity required an open adductor tenotomy and anterior branch obturator neurectomy a week later. At her last review, she had a painless, enlocated left hip with a good range of movement and an improvement in migration percentage from 43% to 8%. The courses of these four patients highlight the management limitations imposed by a late diagnosis and medical comorbidities.

Scoliosis Eleven of 20 patients with a Cobb angle of 30 or more had spinal fusions. Two families declined surgery for their daughHip Displacement and Scoliosis in Rett syndrome Guan Tay et al. 95

ters (patients 6 and 12). Two patients were deemed unsuitable for surgery secondary to significant medical comorbidities (patients 25 and 30). The remaining five had Cobb angles between 30 and 43 and, at the conclusion of the audit, had not had operations. A complete set of presurgery, post surgery, and current radiographs was available for nine of the 11 patients who underwent surgery. The mean presurgery Cobb angle was 85 (range 53–100). The mean correction was 63.5 (range 27– 102). The mean Cobb angle at the most recent follow-up was 29 (range 13–57). No mortality was associated with the surgical procedures undertaken for scoliosis in these 11 patients. Two patients had intensive care unit admissions post surgery for respiratory complications. All 11 patients who underwent spinal surgery had a Functional Mobility Scale score of 1, 1, 1.

DISCUSSION Our study has highlighted the frequency of hip disease and scoliosis and the importance of recognizing these conditions. The youngest female to have a hip migration percentage of more than 30% was 11 years, and the youngest to have a dislocated hip diagnosed was 14 years. Scoliosis was detected clinically or on radiographs at a mean age of 9 years and 8 months (range 2y 8mo–25y 1mo). All but one female older than 13 years had a scoliosis with a Cobb angle greater than 30. Although our data set is far from complete, there is a strong implication that clinically significant hip displacement and clinically significant scoliosis are related to both age and loss of walking ability. Previous reports have provided limited information. Guidera et al.6 reported one case of hip subluxation in nine patients with a mean age of 9 years. Loder et al.7 reported that five of 36 patients with a mean age of 8 years 7 months had hip contractures and only seven patients had had hip radiographs. Hennessy and Hass5 reported no case of hip dislocation in 16 patients with a mean age of 11 years 2 months. However, they did note an increase in mean centre–edge angles compared with a comparison group, suggestive of hip instability. In a series of 22 patients with a mean age of 12 years, two cases of hip dislocation and four other patients with reduced hip movement were reported.14 The younger ages or lack of radiological investigations may account for the differences from our results. In a study of 70 patients with Rett syndrome, a significant increase in hip contractures and scoliosis was noted following a deterioration in mobility.15 It has been reported that about a quarter of affected children will have scoliosis by the age of 6 years and about three-quarters by the age of 13 years.16 In contrast, our study demonstrated a higher frequency of significant pathology; this difference may be accounted for by the more frequent use of radiographs, longer follow-up, or by selection bias (see below). When hip subluxation is diagnosed early, simple preventative surgery may be performed and often has good results. In contrast, a delayed diagnosis of hip displacement will often 96 Developmental Medicine & Child Neurology 2010, 52: 93–98

limit the surgical options available, resulting in the need for complex reconstructive or salvage surgery that has a high rate of associated complications, morbidity, and mortality.9,13 An inoperable dislocated hip may result in chronic pain that is often refractory to treatment. Following guidelines established from the CP literature, it is our practice to recommend surgery when the hip migration percentage exceeds 30%.9,10,14 Each patient is assessed individually, and surgery may be postponed if the rate of subluxation is slow, the tone is low, the range of movement of the hips is adequate, or respiratory comorbidities preclude operative intervention. The aim of operating at this migration percentage, even in asymptomatic patients, is to prevent hip dislocation. Even preventative hip surgery may cause a significant care burden to families, particularly if associated with prolonged abduction splinting. We recommend increased surveillance of scoliosis when the Cobb angle reaches 30 and consideration of surgical correction when the Cobb angle exceeds 40 and has been shown to be progressive on serial radiographs. This general rule is modulated by a number of factors, including the parents’ wish to proceed and the child’s fitness for operation. The urgency is determined by the rate of curve progression. Major spinal surgery is associated with significant intraoperative and postoperative risks. However, the consequence of no intervention is progressive postural deformity and progressive restrictive lung disease. Our study has a number of limitations. The population was ascertained cross-sectionally, though we did have access to prior clinic notes and radiographs. However, the age at presentation of individuals varied, making it difficult to provide data that were comparable between patients. The number of patients was small, and we studied a clinic population, which may have resulted in bias towards a more severe patient group. We have described only 31 patients but there are 54 living females under 18 years and resident in Victoria on the Australian Rett Syndrome Register (Helen Leonard, personal communication 2006). Even if none of the remaining patients had significant scoliosis or hip subluxation, the corresponding frequencies would still be 27% (95% CI 16–42) and 37% (95% CI 24–51). After making an approximate allowance for patients not seen at our centre, the high rates of hip subluxation and of scoliosis are very substantial. We would hypothesize that the primary determinant of both hip subluxation and scoliosis in Rett syndrome is ambulatory ability, as it is in CP. In children with CP, the prime determinant of hip subluxation is Gross Motor Function Classification System level.17 This measure is specific to CP and cannot be directly applied to individuals with Rett syndrome, in whom progressive motor deterioration makes them quite distinct from individuals with CP. All females who underwent either hip or spinal surgery had a Functional Mobility Scale score of 1, 1, 1. The Functional Mobility Scale score8 is a quick, accurate and sensitive tool for monitoring motor function. This scale has been shown to be a valid and reliable measure of mobility in children with CP and

Table I: World Health Organization criteria for screening.1 1. The condition sought should be an important health problem for the individual and community. 2. There should be an accepted treatment or useful intervention for patients with the disease. 3. The natural history of the disease should be adequately understood. 4. There should be a latent or early symptomatic stage. 5. There should be a suitable and acceptable screening test or examination. 6. Facilities for diagnosis and treatment should be available. 7. There should be an agreed policy on whom to treat as patients. 8. Treatment started at an early stage should be of more benefit than treatment started later. 9. The cost should be economically balanced in relation to possible expenditure on medical care as a whole. 10. Case finding should be a continuing process and not a once and for all project.

other disabilities, including children with myelomeningocele.8 We propose that the Functional Mobility Scale score may be of benefit to evaluate motor function in Rett syndrome. The particular difficulty that individuals with Rett syndrome have with using hand-held mobility aids would make it unusual for them to receive a rating 3 or 4 (see Fig. 1). Further specific evaluative studies are required. Screening for hip pathology should involve regular examinations of hip movements and hip radiographs.9 Examination alone is insufficient, as it is dependent on patient compliance and examiner technique and experience. In analysing radiographs, the migration percentage,10 centre–edge angle,18,19 and acetabular index20 are used to measure hip displacement and acetabular dysplasia in individuals with CP. In our study, only migration percentage was recorded. The migration percentage provides a good quantitative estimate of the degree of femoral head subluxation, which cannot be inferred from a decrease in the centre–edge angle of Wiberg.19 Preoperative migration percentage has been shown to be a significant predictor of outcome following soft tissue surgery in patients with CP.20 The prevalence of hip subluxation and dislocation demonstrated in this study shows that an average of 4.4 hip radiographs per patient is inadequate. Just as in CP, children with Rett syndrome are in the ‘at-risk’ population for hip displacement and fulfil all but two of the criteria for implementation of a screening programme as determined by the World Health Organization (Table I).21 The unfulfilled criteria are the inadequate knowledge about the natural history of hip displacement and the detailed economic analysis, both of which require further longitudinal study. We would propose that scoliosis and hip screening should follow the principles established in CP, with regular examina-

tions and 12-monthly radiographs from the age of 18 months until skeletal maturity is achieved. The efficacy of a hip surveillance clinic for children with CP has been demonstrated.9 More frequent radiographs may be required if there is rapid progression of hip displacement. Marked deterioration may occur in association with loss of ambulatory ability, and renewed vigilance for rapid deterioration in hip subluxation and scoliosis at this time is recommended. Any patient with either a rapidly increasing migration percentage or a migration percentage greater than 30% should be referred to an orthopaedic surgeon. The radiation dose resulting from having hip radiographs taken yearly from the age of two until 18 is equivalent to 5 years’ background radiation.22 Minimizing the dose by using appropriate techniques and shielding, counselling parents of the potential risks, and defining the age at onset and optimum frequency of imaging with further longitudinal study are of critical importance. We strongly believe that screening should be conducted for every child with Rett syndrome with early referral to an orthopaedic unit when significant musculoskeletal pathology is diagnosed. A central register is recommended to remind families of the need for repeat assessments. Digital X-ray imaging allows easy and reliable transfer of films for review by practitioners experienced in this field. Patients should be screened clinically for spinal deformity and pelvic obliquity every 12 months. When scoliosis is noted, radiographs should be taken yearly or more frequently where progression is rapid, for example during times of accelerated growth. Any patient with Rett syndrome and a Cobb angle greater than 10 should be referred to an orthopaedic surgeon.

CONCLUSION Hip displacement and scoliosis are extremely common in patients with Rett syndrome. Early diagnosis of these problems allows timely and effective intervention. In contrast, delayed diagnosis limits potential interventions, which may result in substantial pain and adverse impact on quality of life. Radiological and clinical screening for hip displacement and scoliosis is recommended. SUPPORTING INFORMATION Additional Supporting Information may be found in the online version of this article: Table SI: Summary of results. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.

REFERENCES 1. Laurvick CL, de Klerk N, Bower C, et al. Rett syndrome in Australia: a review of the epidemiology. J Pediatr 2006; 148: 347–52.

2. Christodoulou J, Grimm A. RettBASE: IRSA MECP2 Variation database. Hun Mutat 21: 466–72.

3. Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008; 320: 1224–9.

Hip Displacement and Scoliosis in Rett syndrome Guan Tay et al. 97

4. Bebbington A, Anderson A, Ravine D, et al. Investigating

10. Reimers J. The stability of the hip in children: a radiological

genotype–phenotype relationships in Rett syndrome using an

study of the results of muscle surgery in cerebral palsy. Acta

international data set. Neurology 2008; 70: 868–75.

Orthop Scand 1980; 184: 11–100.

5. Hennessy MJ, Haas RH. The orthopaedic management of Rett syndrome. J Child Neurol 1988; 3:(Suppl.) S43–7. 6. Guidera K, Borelli J, Raney E, Thompson-Rangel T, Ogden JA. Orthopaedic manifestations of Rett Syndrome. J Pediatr Orthop 1991; 11: 204–8.

11. Obrien MF, Kukho TR, Blanke KM, et al. Radiographic Measurement Manual. Memphis: Medtronic Sofamor Danek USA, Inc., 2005: 69. 12. Cobb JR. Outline for the study of scoliosis. Am Acad Orthop Surg Instr Course Lect 1948; 5: 261.

17. Soo B, Howard JJ, Boyd RN, et al. Hip displacement in cerebral palsy. J Bone Joint Surg Am 2006; 88: 121–9. 18. To¨nnis D. Congenital Dysplasia and Dislocation of the Hip. Berlin: Springer-Verlag, 1987: 100–42. 19. Wiberg G. Studies on dysplastic acetabulum and congenital subluxation of the hip with special reference to the complication of osteoarthritis. Acta Chir Scand Suppl 1939; 58: 7– 38.

7. Loder RT, Lee CL, Richards BS. Orthopaedic aspects of

13. Lowe T, Berven SH, Schwab FJ. The SRS classification for

20. Cornell MS, Hatrick CN, Boyd R, Baird G, Spencer JD.

Rett syndrome: a multicenter review. J Pediatr Orthop 1989;

adult spinal deformity. Building on the King ⁄ Moe and

The hip in children with cerebral palsy: Predicting the out-

9: 557–62.

Lenke classification systems. Spine 2006; 31: S119–25.

come of soft tissue surgery. Clin Orthop Relat Res 1997;

8. Graham HK, Harvey A, Rodda J, Nattrass GR, Pirpiris M. The Functional Mobility Scale. J Pediatr Orthop 2004; 24: 514–20. 9. Dobson F, Boyd RN, Parrott J, Nattrass GR, Graham HK. Hip surveillance in children with cerebral palsy. J Bone Joint Surg 2002; 84B: 720–6.

14. Roberts AP, Conner AN. Orthopaedic aspects of Rett’s Syndrome: brief report. J Bone Joint Surg 1988; 70B: 674. 15. Naidu S, Murphy M, Moser HW, Rett A. Rett syndrome – natural history in 70 cases. Am J Med Genet 1986; 24: 61– 72. 16. Ager S, Fyfe S, Christodoulou J, Jacoby P, Schmitt L, Leonard H. Predictors of scoliosis in Rett syndrome. J Child Neurol 2006; 21: 809–13.

98 Developmental Medicine & Child Neurology 2010, 52: 93–98

340: 165–71. 21. Wilson JMG, Jungner G. Principles and practice of screening for disease. : Publ Hlth Pap World Health Organization, 1968: 34. 22. Mazrani W, McHugh K, Marsden PJ. The radiation burden of radiological investigations. Arch Dis Child 2007; 92: 1127–31.

Suggest Documents