J Neurosurg Pediatrics 14:682–687, 2014 ©AANS, 2014
Does patient ethnicity affect site of craniosynostosis? Clinical article Ian A. Anderson, M.R.C.S.(Ed),1 Anand Goomany, M.B. Ch.B.,1 David T. Bonthron, Ph.D., 2 Maggie Bellew, Ph.D., 3 Mark I. Liddington, F.R.C.S.(Plast), 3 Ian M. Smith, F.R.C.S.(Plast), 3 John L. Russell, F.D.S., F.R.C.S.(Maxfac), 4 Lachlan M. Carter, F.R.C.S.(OMFS), 4 Velupandian Guruswamy, D.A., F.R.C.A., F.C.A.R.C.S.I., 5 John R. Goodden, F.R.C.S.(SN),1 and Paul D. Chumas, F.R.C.S.(SN)1 Department of Neurosurgery, Leeds General Infirmary; 2Leeds Institute of Biomedical and Clinical Sciences, University of Leeds; and Departments of 3Plastic, Reconstructive, and Hand Surgery, 4Oral and Maxillofacial Surgery, and 5Anaesthesia, Leeds General Infirmary, Leeds, United Kingdom
1
Object. There are no published papers examining the role of ethnicity on suture involvement in nonsyndromic craniosynostosis. The authors sought to examine whether there is a significant difference in the epidemiological pattern of suture(s) affected between different ethnic groups attending a regional craniofacial clinic with a diagnosis of nonsyndromic craniosynostosis. Methods. A 5-year retrospective case-notes analysis of all cases involving patients attending a regional craniofacial clinic was undertaken. Cases were coded for the patients’ declared ethnicity, suture(s) affected by synostosis, and the decision whether to have surgical correction of synostosis. The chi-square test was used to determine whether there were any differences in site of suture affected between ethnic groups. Results. A total of 312 cases were identified. Of these 312 cases, ethnicity data were available for 296 cases (95%). The patient population was dominated by 2 ethnic groups: white patients (222 cases) and Asian patients (56 cases). There were both more cases of complex synostosis and fewer cases of sagittal synostosis than expected in the Asian patient cohort (c2 = 9.217, p = 0.027). Conclusions. There is a statistically significant difference in the prevalence of the various sutures affected within the nonsyndromic craniosynostosis patient cohort when Asian patients are compared with white patients. The data from this study also suggest that nonsyndromic craniosynostosis is more prevalent in the Asian community than in the white community, although there may be inaccuracies in the estimates of the background population data. A larger-scale, multinational analysis is needed to further evaluate the relationship between ethnicity and nonsyndromic craniosynostosis. (http://thejns.org/doi/abs/10.3171/2014.9.PEDS14123)
Key Words • craniosynostosis • pediatric • ethnicity • nonsyndromic • epidemiology • genetic • craniofacial surgery
C
is defined as the premature fusion of one or more of the cranial sutures and is seen in approximately 1 in every 2000 live births.8 Anatomically, cases of craniosynostosis can be divided into simple (single suture involvement) or complex (multiple suture involvement) synostosis and then subdivided depending on the location of the suture(s) involved. While craniosynostosis may sometimes form part of a wider syndrome of abnormalities, such as Crouzon disease, Apert syndrome, or Pfeiffer syndrome, over 85% of cases of craniosynostosis are not associated with any othraniosynostosis
Abbreviation used in this paper: NHS = UK National Health Service.
682
er abnormality and are therefore termed “nonsyndromic craniosynostosis.”4 While cases of syndromic craniosynostosis will be associated with a known genetic abnormality, the etiology of nonsyndromic craniosynostosis is generally less well understood. Patient ethnicity is strongly linked with genetic lineage, and it follows, therefore, that any identifiable differences between patient cohorts of different ethnic groups may suggest underlying genetic (or indeed cultural) causes for craniosynostosis. This study was undertaken to investigate the role that ethnicity may play in the site of suture affected—specifically, whether there are any differences in the frequencies of the sutures affected in different ethnic groups. J Neurosurg: Pediatrics / Volume 14 / December 2014
Does patient ethnicity affect site of craniosynostosis? Methods
A retrospective case-notes study of all cases involving patients who attended a regional craniofacial clinic over a 5-year period was undertaken. All patients attending clinic are managed according to a standardized protocol. Children are evaluated at 6-month intervals until the age of 2 years; thereafter they are kept under annual review until the age of 7 years. We evaluate patients twice more, at the ages of 10 and 15, and after the latter evaluation they are discharged. All patients are seen by neurosurgeons, plastic surgeons, and maxillofacial surgeons at each clinic visit. The protocol also includes evaluation by consultants from ophthalmology, developmental neuropsychology, and clinical genetics. Patients with a diagnosis of nonsyndromic craniosynostosis were coded according to their “self-declared” ethnic groups (parents or those in loco parentis were asked to state their child’s ethnicity). The ethnic groups used were based upon categories that are employed by all NHS (UK National Health Service) Trusts, although the categories were simplified to form more basic groups in order to aid statistical analysis within the study (Table 1). Data regarding ethnicity are routinely collected for all patients attending outpatient clinics in the NHS. Where no data regarding patient ethnicity were available, patients were contacted directly to obtain this this information. The ethnic distribution of patients attending the craniofacial clinic was compared with population data for our regional catchment area as a whole (based on National Office for Statistics 2009 Population Statistics).9 TABLE 1: Original NHS ethnicity classifications and ethnicity classifications allocated for study (study ethnicity codes) Ethnicity Classification Allocated Arab Asian
black
Chinese mixed
white
other unknown
Original NHS Classification Arab Asian or Asian British—Indian Asian or Asian British—Pakistani Asian or Asian British—Bangladeshi Asian or Asian British—any other Asian background black or black British—Caribbean black or black British—African black or black British—any other black background Chinese mixed—white and black Caribbean mixed—white and black African mixed—white and Asian mixed—any other mixed background white—British white—Irish white—any other white background any other ethnic origin group not known prefer not to say
J Neurosurg: Pediatrics / Volume 14 / December 2014
In all cases, the diagnosis of craniosynostosis and classification of suture site affected was made by one of the two consultant neurosurgeons that run the craniofacial service. The diagnosis was based on preoperative radiographs (all cases) and was ratified at the time of surgery. CT scans were reviewed where available (in some cases these had already been obtained by the referring clinician and in other cases had been deemed to be clinically indicated by the craniofacial team, e.g., where concerns existed about intracranial pathology). The site of suture(s) affected was noted for each patient, and cases were coded as coronal (left, right or bicoronal), lambdoid (left or right or bilateral), metopic, sagittal, or complex synostosis (i.e., patients with ≥ 2 affected sutures, excluding cases of bicoronal synostosis). The frequencies were then compared using the chi-square test to determine whether there were any significant differences (p < 0.05) in site of suture affected in different ethnic groups. Finally, data were also collected regarding whether patients underwent surgery or not. The decision not to operate, reflecting either clinically “mild” cases or parental declination of surgery.
Results
Over a 5-year period, 312 cases of synostosis were identified. A breakdown by site of suture affected is provided in Table 2. Ethnicity data were obtained for 296 (95%) of the 312 patients; there were 16 patients whom we were unable to contact or who declined to disclose their ethnicity. A full breakdown of the frequency of suture affected for each ethnic group is given in Table 3. Within this study cohort, 2 ethnic groups predominated: white patients (222 cases) and Asian patients (56 cases). The chi-square test was used to determine whether there were any differences in site of suture affected in these 2 ethnic groups. This gave a chi-square value of 9.217 (p = 0.027), suggesting that there were significant differences between the expected distribution of suture sites if this were due to chance and the actual observed distribution of suture sites. The detail of the analysis revealed that this was due to more cases of complex craniosynostosis than would be expected in the Asian patients and fewer cases of sagittal synostosis than would be expected in the Asian patients. When our nonsyndromic craniosynostosis patient population data are compared with population data for our regional catchment area as a whole (based on NationTABLE 2: Relative frequencies of sutures affected Suture Site Affected
No. of Cases
% of Total No. of Cases
complex coronal lambdoid metopic sagittal total
22 62 1 89 138 312
7% 20% 0% 29% 44% 100%
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I. A. Anderson et al. TABLE 3: Relative frequencies of sutures affected for each ethnic group Ethnicity Classification Allocated
Complex
Coronal
Lambdoid
Metopic
Sagittal
Total
Arab Asian black Chinese mixed white other unknown total
0 8 1 0 0 13 0 0 22
0 16 0 0 2 42 1 1 62
0 0 0 0 0 1 0 0 1
0 16 0 0 5 61 2 5 89
0 16 2 0 2 105 3 10 138
0 56 3 0 9 222 6 16 312
al Office for Statistics 2009 Population Statistics) there is the suggestion that that Asian families are over-represented in the craniofacial clinic.9 Although only 7.1% of our catchment population is recorded as Asian in ethnicity, 17.9% of children seen in craniofacial clinic are Asian. Conversely, 88.8% of our patient population is thought to be of white ethnicity, although white ethnicity was reported for 71% of patients attending craniofacial clinic with nonsyndromic craniosynostosis. Table 4 shows data collected on whether patients underwent surgical correction of synostosis. There were 17 cases where it was not clear whether the patient had surgery or not from the databases used within this study. While it is highly likely that these patients did not undergo surgery (since admission and subsequent surgery would typically generate a large amount of documentation on multiple systems), they were excluded from this part of the analysis nonetheless. Table 5 shows the percentages of parents (for whom the outcome was known) that elected to have surgery. In the Asian cohort, 57% of patients underwent (or are on the waiting list to undergo) surgery, this compares with 68% in the white cohort. Table 6 shows these data broken down further, by suture site affected.
of the factors that predispose patients to nonsyndromic craniosynostosis. A wide spectrum of risk factors have been suggested for nonsyndromic craniosynostosis, and these include increasing maternal age, male sex, maternal smoking, and use of several medications, including maternal valproic acid use.14 The relationship between ethnicity and nonsyndromic craniosynostosis has been explored as a variable in previous publications. When ethnicity data for nonsyndromic craniosynostosis cases was compared with that for controls as part of the National Birth Defects Prevention Study in North America, there was a significantly increased number of white, non-Hispanic mothers in the nonsyndromic craniosynostosis group as compared with mothers in the control group (p < 0.001).14 One paper based on Australian patients concluded that ethnicity is not related to rates of nonsyndromic craniosynostosis.13 It has been previously observed that there seems to be a relatively high incidence of oxycephaly in patients who come from North Africa.11 It has also been shown in other articles that the incidence of nonsyndromic craniosynostosis in children born to black mothers is relatively reduced.1,3 There are no published papers examining the role that ethnicity has in which suture is affected in cases of nonsyndromic craniosynostosis. The definition of what constitutes ethnicity is itself a potentially contentious issue. According to one published glossary of terms relating to ethnicity, our “Asian” group most closely resembles the definition of people who are
Discussion
While there has been much work to investigate the genetic causes of many syndromes associated with craniosynostosis, we have a more limited understanding
TABLE 4: Decision to whether to undergo surgery stratified by ethnic group
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Ethnicity Classification Allocated
Surgery
No Surgery
Undecided
Unknown
Total
Arab Asian black Chinese mixed white other unknown total
0 31 0 0 5 142 2 7 187
0 22 3 0 4 64 4 7 104
0 1 0 0 0 3 0 0 4
0 2 0 0 0 13 0 2 17
0 56 3 0 9 222 6 16 312
J Neurosurg: Pediatrics / Volume 14 / December 2014
Does patient ethnicity affect site of craniosynostosis? TABLE 5: Percentage of parents electing to undergo surgical correction* Ethnicity Classification Allocated
Surgery
No Surgery
Undecided
Arab Asian black Chinese mixed white other unknown overall
— 57% 0% — 56% 68% 33% 50% 63%
— 41% 100% — 44% 31% 67% 50% 35%
— 2% 0% — 0% 1% 0% 0% 1%
* Data shown exclude patients for whom outcome was unknown.
defined as “South Asian”: “A person whose ancestry is in the countries of the Indian subcontinent, including India, Pakistan, Bangladesh, and Sri Lanka.”2 Even this carefully constructed glossary does not provide a robust and comprehensive structure for issues such as how a family’s defined ethnicity may vary from one generation to the next and as potentially different ethnicities intermix. It is important to remember that any system of labeling used to define ethnicity exists solely to facilitate comparison; such systems do not guarantee common genetic or indeed social traits within the groups. The results of this study rely on ethnicity data that was precoded at our institution. There is evidence to suggest that while the accuracy of the ethnic group information that is routinely recorded in NHS hospital records is reliable for those of a white British background (only 2.2% of these entries are incorrect), for other ethnic groups it can be far less accurate; between 39.7 and 42.7% of entries are incorrect in these groups.12 It was concluded that the current levels of accuracy of ethnicity information collected by the NHS are sufficient to support valid profiling of white/non-white ethnic differences in epidemiological studies, but that profiling of ethnic differences
in process or outcome measures for specific minority groups may contain a substantial and variable degree of misclassification error. This would lend support to our decision to amalgamate some of the ethnic subgroups, such as the Southern Asian nations to make more general, less specific cohorts to compare (Table 1). Our paper shows a statistically different distribution of sutures affected in the Asian cohort, as compared with the white cohort. The reasons for this are unclear. It is possible that the differences observed are due to social or cultural reasons, although we would hypothesize that it signifies an underlying genetic difference between the groups in question. Rates of consanguinity are higher in Asian communities than in the United Kingdom as a whole, and there has been suggestion that within the UK population, consanguinity rates are higher among Asian communities (http://consang.net).10 More specifically, rates of consanguinity have been noted to be especially elevated in Pakistani communities. One study, undertaken in 1988, suggested that the rates of consanguinity seen within this particular ethnic group in the West Yorkshire region were rising and that as many as 55% of British Pakistani new mothers were in consanguineous relationships. 5 While consanguinity has been noted in the records of some of our patients, this has not been coded reliably enough for further analysis in this retrospective analysis. It is noted that, within the Asian patient cohort analyzed in our study, 46 (82%) of the 56 patients described their ethnicity as “Asian—Pakistani.” We plan to examine this factor prospectively in a future study. The specialist nature of craniofacial neurosurgical clinics in the UK is such that a single unit can have a relatively large catchment area. Unfortunately, the referrals process for these patients is not sufficiently well defined that we can be truly sure what exactly constitutes our catchment area. It follows that it is difficult to accurately approximate the ethnic mix within our background population and hence to define incidences of nonsyndromic craniosynostosis in our region with statistical reliability. Despite this, we feel our data do suggest that relatively high numbers of Asian children with nonsyndromic cra-
TABLE 6: Differences in attitudes towards surgery in white and Asian groups, stratified by site of synostosis* Ethnicity/Tx Choice
Complex
Coronal
Lambdoid
Metopic
Sagittal
Total
Asian surgery no surgery undecided unknown white surgery no surgery undecided unknown overall
8 7 (100%) 0 0 1 13 9 (90%) 0 1 (10%) 3 21
16 12 (80%) 3 (20%) 0 1 42 29 (74%) 10 (26%) 0 3 58
0 0 0 0 0 1 0 1 (100%) 0 0 1
16 12 (80%) 3 (20%) 0 1 61 33 (56%) 26 (44%) 0 2 77
16 6 (38%) 10 (63%) 0 0 105 71 (71%) 27 (27%) 2 (2%) 5 121
56 37 16 0 3 222 142 64 3 13 278
* Percentages expressed as proportion of patients for whom outcome is known. Tx = treatment.
J Neurosurg: Pediatrics / Volume 14 / December 2014
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I. A. Anderson et al. niosynostosis are being seen in clinic. The reasons for this apparent phenomenon are unclear; it may either represent a primary increase in incidence or be sociocultural (i.e., patients from an Asian background may be more likely to present with relatively minor phenotypes than are white patients). Should Asian cases of craniosynostosis be found to present with relatively more minor phenotypes, then this may be a contributory factor in explaining why Asian families seem less likely to elect for surgical correction than are white families (57% of patients in the Asian cohort eventually underwent surgery compared with 68% of the white cohort). This is not a factor that has previously been explored in the published literature. The overall proportion of patients with synostosis who had surgery in our study was 63%. There are limited previously published data available with which to compare this figure, since the majority of papers on craniosynostosis have focused only on groups of patients who have undergone surgical correction or in whom surgical correction is planned. In one previously described group of patients with sagittal synostosis, surgery was performed in 8 (44%) of 18 cases.6 Another study that followed 84 consecutive patients that were reviewed in a craniofacial unit in Illinois with a diagnosis of “single-suture synostosis” (excludes lambdoid synostosis) reported that 63 (75%) of the patients underwent surgery.7 It is possible that the seemingly low numbers of patients for whom surgery was elected simply represent the current parental attitude toward what could be regarded as cosmetic surgery (for children with asymptomatic craniosynostosis). That said, there will almost certainly be multiple factors involved in the decision-making process for these patients, and there is clearly scope for further exploration of these. Parents will base their decisions, at least in part, on the information presented to them by the medical team. Examining attitudes toward surgery both before and after clinic visits may shed further light on this variable. Conversely, changes in parental attitudes may mean that children who would previously not have been either brought to their general practitioner or subsequently referred on to a craniofacial clinic are now being referred. This would mean a relative increase in the numbers of patients with phenotypically mild craniosynostosis, the assumption being that the “milder” cases are less likely to be treated surgically. As was mentioned previously, our data suggest that white families are more likely to opt for surgical correction than are Asian families (57% in the Asian cohort and 68% in the white). It may be that the differences in attitude between these two groups are due to the differences in suture affected, but it may also suggest that there are cultural differences between the communities and that Asian families are more accepting of cosmetic differences than are white groups. We undertook further analysis of attitudes within the Asian and white cohorts to further investigate this (Table 6). While the numbers are small, they suggest that Asian patients with sagittal synostosis are much less likely to undergo surgery than are white patients; however, the reverse is true where cases of metopic synostosis are concerned. The majority of patients with coronal or complex synostosis are treated surgically, irre686
spective of ethnicity. Clearly, larger data sets are required before attitudes toward surgery can be further explored, and this was not the primary objective of this study.
Conclusions
There is a statistically significant difference in the prevalence of the various sutures affected within the nonsyndromic craniosynostosis patient cohort when Asian patients are compared with white patients. Our data indicate that multiple sutures are significantly more frequently affected in Asian patients with nonsyndromic craniosynostosis than in white patients. Conversely, the incidence of sagittal suture nonsyndromic craniosynostosis is significantly less common in the Asian cohort. Our data would also suggest that nonsyndromic craniosynostosis is more prevalent in the Asian community than in the white community, although without accurate background population data it is not possible to attribute statistical scrutiny to this suggestion. A larger-scale, multicenter analysis needs to be performed to further evaluate the relationship between ethnicity and nonsyndromic craniosynostosis. It is hoped that if the proposed differences can be confirmed in larger studies, further work can be performed to examine the underlying etiology of any differences. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Anderson, Chumas, Bonthron. Acquisition of data: Anderson, Goomany. Analysis and interpretation of data: Anderson, Goomany, Bellew. Drafting the article: Anderson. Critically revising the article: Anderson, Bellew, Chumas. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Anderson. Statistical analysis: Anderson, Bellew. Administrative/ technical/material support: Anderson. Study supervision: Chumas. References 1. Alderman BW, Lammer EJ, Joshua SC, Cordero JF, Ouimette DR, Wilson MJ, et al: An epidemiologic study of craniosynostosis: risk indicators for the occurrence of craniosynostosis in Colorado. Am J Epidemiol 128:431–438, 1988 2. Bhopal R: Glossary of terms relating to ethnicity and race: for reflection and debate. J Epidemiol Community Health 58: 441–445, 2004 3. Boulet SL, Rasmussen SA, Honein MA: A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003. Am J Med Genet A 146A:984–991, 2008 4. Cohen MJ, MacLean RE: Craniosynostosis: Diagnosis, Evaluation and Management, ed 2. New York: Oxford University Press, 2000 5. Darr A, Modell B: The frequency of consanguineous marriage among British Pakistanis. J Med Genet 25:186–190, 1988 6. Hemple DJ, Harris LE, Svien HJ, Holman CB: Craniosynostosis involving the sagittal suture only: guilt by association? J Pediatr 58:342–355, 1961 7. Kapp-Simon KA: Mental development and learning disorders in children with single suture craniosynostosis. Cleft Palate Craniofac J 35:197–203, 1998
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Does patient ethnicity affect site of craniosynostosis? 8. Kimonis V, Gold JA, Hoffman TL, Panchal J, Boyadjiev SA: Genetics of craniosynostosis. Semin Pediatr Neurol 14:150– 161, 2007 9. Office for National Statistics: Population Estimates by Ethnic Group: Methodology Paper. Newport, UK: Office for National Statistics, 2011 10. Overall AD, Ahmad M, Thomas MG, Nichols RA: An analysis of consanguinity and social structure within the UK Asian population using microsatellite data. Ann Hum Genet 67:525– 537, 2003 11. Renier D, Cinalli G, Lajeunie E, Arnaud E, Marchac D: [Oxycephaly, a severe craniosynostosis. Apropos of a series of 129 cases.] Arch Pediatr 4:722–729, 1997 (Fr) 12. Saunders CL, Abel GA, El Turabi A, Ahmed F, Lyratzopoulos G: Accuracy of routinely recorded ethnic group information compared with self-reported ethnicity: evidence from the English Cancer Patient Experience survey. BMJ Open 3: e002882, 2013
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13. Singer S, Bower C, Southall P, Goldblatt J: Craniosynostosis in Western Australia, 1980-1994: a population-based study. Am J Med Genet 83:382–387, 1999 14. Texas Department of State Health Services: Birth Defect Risk Factor Series: Craniosynostosis. Austin, TX: Department of State Health Services, 2011
Manuscript submitted March 9, 2014. Accepted September 3, 2014. Please include this information when citing this paper: published online October 17, 2014; DOI: 10.3171/2014.9.PEDS14123. Address correspondence to: Ian A. Anderson, M.R.C.S.(Ed), Department of Neurosurgery, Leeds General Infirmary, Great George St., Leeds LS1 3EX, United Kingdom. email: ian.anderson @leedsth.nhs.uk.
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Does patient ethnicity affect site of craniosynostosis? Clinical article Ian A. Anderson, M.R.C.S.(Ed),1 Anand Goomany, M.B. Ch.B.,1 David T. Bonthron, Ph.D., 2 Maggie Bellew, Ph.D., 3 Mark I. Liddington, F.R.C.S.(Plast), 3 Ian M. Smith, F.R.C.S.(Plast), 3 John L. Russell, F.D.S., F.R.C.S.(Maxfac), 4 Lachlan M. Carter, F.R.C.S.(OMFS), 4 Velupandian Guruswamy, D.A., F.R.C.A., F.C.A.R.C.S.I., 5 John R. Goodden, F.R.C.S.(SN),1 and Paul D. Chumas, F.R.C.S.(SN)1 Department of Neurosurgery, Leeds General Infirmary; 2Leeds Institute of Biomedical and Clinical Sciences, University of Leeds; and Departments of 3Plastic, Reconstructive, and Hand Surgery, 4Oral and Maxillofacial Surgery, and 5Anaesthesia, Leeds General Infirmary, Leeds, United Kingdom
1
Object. There are no published papers examining the role of ethnicity on suture involvement in nonsyndromic craniosynostosis. The authors sought to examine whether there is a significant difference in the epidemiological pattern of suture(s) affected between different ethnic groups attending a regional craniofacial clinic with a diagnosis of nonsyndromic craniosynostosis. Methods. A 5-year retrospective case-notes analysis of all cases involving patients attending a regional craniofacial clinic was undertaken. Cases were coded for the patients’ declared ethnicity, suture(s) affected by synostosis, and the decision whether to have surgical correction of synostosis. The chi-square test was used to determine whether there were any differences in site of suture affected between ethnic groups. Results. A total of 312 cases were identified. Of these 312 cases, ethnicity data were available for 296 cases (95%). The patient population was dominated by 2 ethnic groups: white patients (222 cases) and Asian patients (56 cases). There were both more cases of complex synostosis and fewer cases of sagittal synostosis than expected in the Asian patient cohort (c2 = 9.217, p = 0.027). Conclusions. There is a statistically significant difference in the prevalence of the various sutures affected within the nonsyndromic craniosynostosis patient cohort when Asian patients are compared with white patients. The data from this study also suggest that nonsyndromic craniosynostosis is more prevalent in the Asian community than in the white community, although there may be inaccuracies in the estimates of the background population data. A larger-scale, multinational analysis is needed to further evaluate the relationship between ethnicity and nonsyndromic craniosynostosis. (http://thejns.org/doi/abs/10.3171/2014.9.PEDS14123)
Key Words • craniosynostosis • pediatric • ethnicity • nonsyndromic • epidemiology • genetic • craniofacial surgery
C
is defined as the premature fusion of one or more of the cranial sutures and is seen in approximately 1 in every 2000 live births.8 Anatomically, cases of craniosynostosis can be divided into simple (single suture involvement) or complex (multiple suture involvement) synostosis and then subdivided depending on the location of the suture(s) involved. While craniosynostosis may sometimes form part of a wider syndrome of abnormalities, such as Crouzon disease, Apert syndrome, or Pfeiffer syndrome, over 85% of cases of craniosynostosis are not associated with any othraniosynostosis
Abbreviation used in this paper: NHS = UK National Health Service.
682
er abnormality and are therefore termed “nonsyndromic craniosynostosis.”4 While cases of syndromic craniosynostosis will be associated with a known genetic abnormality, the etiology of nonsyndromic craniosynostosis is generally less well understood. Patient ethnicity is strongly linked with genetic lineage, and it follows, therefore, that any identifiable differences between patient cohorts of different ethnic groups may suggest underlying genetic (or indeed cultural) causes for craniosynostosis. This study was undertaken to investigate the role that ethnicity may play in the site of suture affected—specifically, whether there are any differences in the frequencies of the sutures affected in different ethnic groups. J Neurosurg: Pediatrics / Volume 14 / December 2014
Does patient ethnicity affect site of craniosynostosis? Methods
A retrospective case-notes study of all cases involving patients who attended a regional craniofacial clinic over a 5-year period was undertaken. All patients attending clinic are managed according to a standardized protocol. Children are evaluated at 6-month intervals until the age of 2 years; thereafter they are kept under annual review until the age of 7 years. We evaluate patients twice more, at the ages of 10 and 15, and after the latter evaluation they are discharged. All patients are seen by neurosurgeons, plastic surgeons, and maxillofacial surgeons at each clinic visit. The protocol also includes evaluation by consultants from ophthalmology, developmental neuropsychology, and clinical genetics. Patients with a diagnosis of nonsyndromic craniosynostosis were coded according to their “self-declared” ethnic groups (parents or those in loco parentis were asked to state their child’s ethnicity). The ethnic groups used were based upon categories that are employed by all NHS (UK National Health Service) Trusts, although the categories were simplified to form more basic groups in order to aid statistical analysis within the study (Table 1). Data regarding ethnicity are routinely collected for all patients attending outpatient clinics in the NHS. Where no data regarding patient ethnicity were available, patients were contacted directly to obtain this this information. The ethnic distribution of patients attending the craniofacial clinic was compared with population data for our regional catchment area as a whole (based on National Office for Statistics 2009 Population Statistics).9 TABLE 1: Original NHS ethnicity classifications and ethnicity classifications allocated for study (study ethnicity codes) Ethnicity Classification Allocated Arab Asian
black
Chinese mixed
white
other unknown
Original NHS Classification Arab Asian or Asian British—Indian Asian or Asian British—Pakistani Asian or Asian British—Bangladeshi Asian or Asian British—any other Asian background black or black British—Caribbean black or black British—African black or black British—any other black background Chinese mixed—white and black Caribbean mixed—white and black African mixed—white and Asian mixed—any other mixed background white—British white—Irish white—any other white background any other ethnic origin group not known prefer not to say
J Neurosurg: Pediatrics / Volume 14 / December 2014
In all cases, the diagnosis of craniosynostosis and classification of suture site affected was made by one of the two consultant neurosurgeons that run the craniofacial service. The diagnosis was based on preoperative radiographs (all cases) and was ratified at the time of surgery. CT scans were reviewed where available (in some cases these had already been obtained by the referring clinician and in other cases had been deemed to be clinically indicated by the craniofacial team, e.g., where concerns existed about intracranial pathology). The site of suture(s) affected was noted for each patient, and cases were coded as coronal (left, right or bicoronal), lambdoid (left or right or bilateral), metopic, sagittal, or complex synostosis (i.e., patients with ≥ 2 affected sutures, excluding cases of bicoronal synostosis). The frequencies were then compared using the chi-square test to determine whether there were any significant differences (p < 0.05) in site of suture affected in different ethnic groups. Finally, data were also collected regarding whether patients underwent surgery or not. The decision not to operate, reflecting either clinically “mild” cases or parental declination of surgery.
Results
Over a 5-year period, 312 cases of synostosis were identified. A breakdown by site of suture affected is provided in Table 2. Ethnicity data were obtained for 296 (95%) of the 312 patients; there were 16 patients whom we were unable to contact or who declined to disclose their ethnicity. A full breakdown of the frequency of suture affected for each ethnic group is given in Table 3. Within this study cohort, 2 ethnic groups predominated: white patients (222 cases) and Asian patients (56 cases). The chi-square test was used to determine whether there were any differences in site of suture affected in these 2 ethnic groups. This gave a chi-square value of 9.217 (p = 0.027), suggesting that there were significant differences between the expected distribution of suture sites if this were due to chance and the actual observed distribution of suture sites. The detail of the analysis revealed that this was due to more cases of complex craniosynostosis than would be expected in the Asian patients and fewer cases of sagittal synostosis than would be expected in the Asian patients. When our nonsyndromic craniosynostosis patient population data are compared with population data for our regional catchment area as a whole (based on NationTABLE 2: Relative frequencies of sutures affected Suture Site Affected
No. of Cases
% of Total No. of Cases
complex coronal lambdoid metopic sagittal total
22 62 1 89 138 312
7% 20% 0% 29% 44% 100%
683
I. A. Anderson et al. TABLE 3: Relative frequencies of sutures affected for each ethnic group Ethnicity Classification Allocated
Complex
Coronal
Lambdoid
Metopic
Sagittal
Total
Arab Asian black Chinese mixed white other unknown total
0 8 1 0 0 13 0 0 22
0 16 0 0 2 42 1 1 62
0 0 0 0 0 1 0 0 1
0 16 0 0 5 61 2 5 89
0 16 2 0 2 105 3 10 138
0 56 3 0 9 222 6 16 312
al Office for Statistics 2009 Population Statistics) there is the suggestion that that Asian families are over-represented in the craniofacial clinic.9 Although only 7.1% of our catchment population is recorded as Asian in ethnicity, 17.9% of children seen in craniofacial clinic are Asian. Conversely, 88.8% of our patient population is thought to be of white ethnicity, although white ethnicity was reported for 71% of patients attending craniofacial clinic with nonsyndromic craniosynostosis. Table 4 shows data collected on whether patients underwent surgical correction of synostosis. There were 17 cases where it was not clear whether the patient had surgery or not from the databases used within this study. While it is highly likely that these patients did not undergo surgery (since admission and subsequent surgery would typically generate a large amount of documentation on multiple systems), they were excluded from this part of the analysis nonetheless. Table 5 shows the percentages of parents (for whom the outcome was known) that elected to have surgery. In the Asian cohort, 57% of patients underwent (or are on the waiting list to undergo) surgery, this compares with 68% in the white cohort. Table 6 shows these data broken down further, by suture site affected.
of the factors that predispose patients to nonsyndromic craniosynostosis. A wide spectrum of risk factors have been suggested for nonsyndromic craniosynostosis, and these include increasing maternal age, male sex, maternal smoking, and use of several medications, including maternal valproic acid use.14 The relationship between ethnicity and nonsyndromic craniosynostosis has been explored as a variable in previous publications. When ethnicity data for nonsyndromic craniosynostosis cases was compared with that for controls as part of the National Birth Defects Prevention Study in North America, there was a significantly increased number of white, non-Hispanic mothers in the nonsyndromic craniosynostosis group as compared with mothers in the control group (p < 0.001).14 One paper based on Australian patients concluded that ethnicity is not related to rates of nonsyndromic craniosynostosis.13 It has been previously observed that there seems to be a relatively high incidence of oxycephaly in patients who come from North Africa.11 It has also been shown in other articles that the incidence of nonsyndromic craniosynostosis in children born to black mothers is relatively reduced.1,3 There are no published papers examining the role that ethnicity has in which suture is affected in cases of nonsyndromic craniosynostosis. The definition of what constitutes ethnicity is itself a potentially contentious issue. According to one published glossary of terms relating to ethnicity, our “Asian” group most closely resembles the definition of people who are
Discussion
While there has been much work to investigate the genetic causes of many syndromes associated with craniosynostosis, we have a more limited understanding
TABLE 4: Decision to whether to undergo surgery stratified by ethnic group
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Ethnicity Classification Allocated
Surgery
No Surgery
Undecided
Unknown
Total
Arab Asian black Chinese mixed white other unknown total
0 31 0 0 5 142 2 7 187
0 22 3 0 4 64 4 7 104
0 1 0 0 0 3 0 0 4
0 2 0 0 0 13 0 2 17
0 56 3 0 9 222 6 16 312
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Does patient ethnicity affect site of craniosynostosis? TABLE 5: Percentage of parents electing to undergo surgical correction* Ethnicity Classification Allocated
Surgery
No Surgery
Undecided
Arab Asian black Chinese mixed white other unknown overall
— 57% 0% — 56% 68% 33% 50% 63%
— 41% 100% — 44% 31% 67% 50% 35%
— 2% 0% — 0% 1% 0% 0% 1%
* Data shown exclude patients for whom outcome was unknown.
defined as “South Asian”: “A person whose ancestry is in the countries of the Indian subcontinent, including India, Pakistan, Bangladesh, and Sri Lanka.”2 Even this carefully constructed glossary does not provide a robust and comprehensive structure for issues such as how a family’s defined ethnicity may vary from one generation to the next and as potentially different ethnicities intermix. It is important to remember that any system of labeling used to define ethnicity exists solely to facilitate comparison; such systems do not guarantee common genetic or indeed social traits within the groups. The results of this study rely on ethnicity data that was precoded at our institution. There is evidence to suggest that while the accuracy of the ethnic group information that is routinely recorded in NHS hospital records is reliable for those of a white British background (only 2.2% of these entries are incorrect), for other ethnic groups it can be far less accurate; between 39.7 and 42.7% of entries are incorrect in these groups.12 It was concluded that the current levels of accuracy of ethnicity information collected by the NHS are sufficient to support valid profiling of white/non-white ethnic differences in epidemiological studies, but that profiling of ethnic differences
in process or outcome measures for specific minority groups may contain a substantial and variable degree of misclassification error. This would lend support to our decision to amalgamate some of the ethnic subgroups, such as the Southern Asian nations to make more general, less specific cohorts to compare (Table 1). Our paper shows a statistically different distribution of sutures affected in the Asian cohort, as compared with the white cohort. The reasons for this are unclear. It is possible that the differences observed are due to social or cultural reasons, although we would hypothesize that it signifies an underlying genetic difference between the groups in question. Rates of consanguinity are higher in Asian communities than in the United Kingdom as a whole, and there has been suggestion that within the UK population, consanguinity rates are higher among Asian communities (http://consang.net).10 More specifically, rates of consanguinity have been noted to be especially elevated in Pakistani communities. One study, undertaken in 1988, suggested that the rates of consanguinity seen within this particular ethnic group in the West Yorkshire region were rising and that as many as 55% of British Pakistani new mothers were in consanguineous relationships. 5 While consanguinity has been noted in the records of some of our patients, this has not been coded reliably enough for further analysis in this retrospective analysis. It is noted that, within the Asian patient cohort analyzed in our study, 46 (82%) of the 56 patients described their ethnicity as “Asian—Pakistani.” We plan to examine this factor prospectively in a future study. The specialist nature of craniofacial neurosurgical clinics in the UK is such that a single unit can have a relatively large catchment area. Unfortunately, the referrals process for these patients is not sufficiently well defined that we can be truly sure what exactly constitutes our catchment area. It follows that it is difficult to accurately approximate the ethnic mix within our background population and hence to define incidences of nonsyndromic craniosynostosis in our region with statistical reliability. Despite this, we feel our data do suggest that relatively high numbers of Asian children with nonsyndromic cra-
TABLE 6: Differences in attitudes towards surgery in white and Asian groups, stratified by site of synostosis* Ethnicity/Tx Choice
Complex
Coronal
Lambdoid
Metopic
Sagittal
Total
Asian surgery no surgery undecided unknown white surgery no surgery undecided unknown overall
8 7 (100%) 0 0 1 13 9 (90%) 0 1 (10%) 3 21
16 12 (80%) 3 (20%) 0 1 42 29 (74%) 10 (26%) 0 3 58
0 0 0 0 0 1 0 1 (100%) 0 0 1
16 12 (80%) 3 (20%) 0 1 61 33 (56%) 26 (44%) 0 2 77
16 6 (38%) 10 (63%) 0 0 105 71 (71%) 27 (27%) 2 (2%) 5 121
56 37 16 0 3 222 142 64 3 13 278
* Percentages expressed as proportion of patients for whom outcome is known. Tx = treatment.
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I. A. Anderson et al. niosynostosis are being seen in clinic. The reasons for this apparent phenomenon are unclear; it may either represent a primary increase in incidence or be sociocultural (i.e., patients from an Asian background may be more likely to present with relatively minor phenotypes than are white patients). Should Asian cases of craniosynostosis be found to present with relatively more minor phenotypes, then this may be a contributory factor in explaining why Asian families seem less likely to elect for surgical correction than are white families (57% of patients in the Asian cohort eventually underwent surgery compared with 68% of the white cohort). This is not a factor that has previously been explored in the published literature. The overall proportion of patients with synostosis who had surgery in our study was 63%. There are limited previously published data available with which to compare this figure, since the majority of papers on craniosynostosis have focused only on groups of patients who have undergone surgical correction or in whom surgical correction is planned. In one previously described group of patients with sagittal synostosis, surgery was performed in 8 (44%) of 18 cases.6 Another study that followed 84 consecutive patients that were reviewed in a craniofacial unit in Illinois with a diagnosis of “single-suture synostosis” (excludes lambdoid synostosis) reported that 63 (75%) of the patients underwent surgery.7 It is possible that the seemingly low numbers of patients for whom surgery was elected simply represent the current parental attitude toward what could be regarded as cosmetic surgery (for children with asymptomatic craniosynostosis). That said, there will almost certainly be multiple factors involved in the decision-making process for these patients, and there is clearly scope for further exploration of these. Parents will base their decisions, at least in part, on the information presented to them by the medical team. Examining attitudes toward surgery both before and after clinic visits may shed further light on this variable. Conversely, changes in parental attitudes may mean that children who would previously not have been either brought to their general practitioner or subsequently referred on to a craniofacial clinic are now being referred. This would mean a relative increase in the numbers of patients with phenotypically mild craniosynostosis, the assumption being that the “milder” cases are less likely to be treated surgically. As was mentioned previously, our data suggest that white families are more likely to opt for surgical correction than are Asian families (57% in the Asian cohort and 68% in the white). It may be that the differences in attitude between these two groups are due to the differences in suture affected, but it may also suggest that there are cultural differences between the communities and that Asian families are more accepting of cosmetic differences than are white groups. We undertook further analysis of attitudes within the Asian and white cohorts to further investigate this (Table 6). While the numbers are small, they suggest that Asian patients with sagittal synostosis are much less likely to undergo surgery than are white patients; however, the reverse is true where cases of metopic synostosis are concerned. The majority of patients with coronal or complex synostosis are treated surgically, irre686
spective of ethnicity. Clearly, larger data sets are required before attitudes toward surgery can be further explored, and this was not the primary objective of this study.
Conclusions
There is a statistically significant difference in the prevalence of the various sutures affected within the nonsyndromic craniosynostosis patient cohort when Asian patients are compared with white patients. Our data indicate that multiple sutures are significantly more frequently affected in Asian patients with nonsyndromic craniosynostosis than in white patients. Conversely, the incidence of sagittal suture nonsyndromic craniosynostosis is significantly less common in the Asian cohort. Our data would also suggest that nonsyndromic craniosynostosis is more prevalent in the Asian community than in the white community, although without accurate background population data it is not possible to attribute statistical scrutiny to this suggestion. A larger-scale, multicenter analysis needs to be performed to further evaluate the relationship between ethnicity and nonsyndromic craniosynostosis. It is hoped that if the proposed differences can be confirmed in larger studies, further work can be performed to examine the underlying etiology of any differences. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Anderson, Chumas, Bonthron. Acquisition of data: Anderson, Goomany. Analysis and interpretation of data: Anderson, Goomany, Bellew. Drafting the article: Anderson. Critically revising the article: Anderson, Bellew, Chumas. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Anderson. Statistical analysis: Anderson, Bellew. Administrative/ technical/material support: Anderson. Study supervision: Chumas. References 1. Alderman BW, Lammer EJ, Joshua SC, Cordero JF, Ouimette DR, Wilson MJ, et al: An epidemiologic study of craniosynostosis: risk indicators for the occurrence of craniosynostosis in Colorado. Am J Epidemiol 128:431–438, 1988 2. Bhopal R: Glossary of terms relating to ethnicity and race: for reflection and debate. J Epidemiol Community Health 58: 441–445, 2004 3. Boulet SL, Rasmussen SA, Honein MA: A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003. Am J Med Genet A 146A:984–991, 2008 4. Cohen MJ, MacLean RE: Craniosynostosis: Diagnosis, Evaluation and Management, ed 2. New York: Oxford University Press, 2000 5. Darr A, Modell B: The frequency of consanguineous marriage among British Pakistanis. J Med Genet 25:186–190, 1988 6. Hemple DJ, Harris LE, Svien HJ, Holman CB: Craniosynostosis involving the sagittal suture only: guilt by association? J Pediatr 58:342–355, 1961 7. Kapp-Simon KA: Mental development and learning disorders in children with single suture craniosynostosis. Cleft Palate Craniofac J 35:197–203, 1998
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Does patient ethnicity affect site of craniosynostosis? 8. Kimonis V, Gold JA, Hoffman TL, Panchal J, Boyadjiev SA: Genetics of craniosynostosis. Semin Pediatr Neurol 14:150– 161, 2007 9. Office for National Statistics: Population Estimates by Ethnic Group: Methodology Paper. Newport, UK: Office for National Statistics, 2011 10. Overall AD, Ahmad M, Thomas MG, Nichols RA: An analysis of consanguinity and social structure within the UK Asian population using microsatellite data. Ann Hum Genet 67:525– 537, 2003 11. Renier D, Cinalli G, Lajeunie E, Arnaud E, Marchac D: [Oxycephaly, a severe craniosynostosis. Apropos of a series of 129 cases.] Arch Pediatr 4:722–729, 1997 (Fr) 12. Saunders CL, Abel GA, El Turabi A, Ahmed F, Lyratzopoulos G: Accuracy of routinely recorded ethnic group information compared with self-reported ethnicity: evidence from the English Cancer Patient Experience survey. BMJ Open 3: e002882, 2013
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13. Singer S, Bower C, Southall P, Goldblatt J: Craniosynostosis in Western Australia, 1980-1994: a population-based study. Am J Med Genet 83:382–387, 1999 14. Texas Department of State Health Services: Birth Defect Risk Factor Series: Craniosynostosis. Austin, TX: Department of State Health Services, 2011
Manuscript submitted March 9, 2014. Accepted September 3, 2014. Please include this information when citing this paper: published online October 17, 2014; DOI: 10.3171/2014.9.PEDS14123. Address correspondence to: Ian A. Anderson, M.R.C.S.(Ed), Department of Neurosurgery, Leeds General Infirmary, Great George St., Leeds LS1 3EX, United Kingdom. email: ian.anderson @leedsth.nhs.uk.
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