Craniosynostosis in Saudi Arabia: A Retrospective Analysis of Subtype Patterns, Syndromic Risk, and Postoperative Outcomes

Abstract

Background:

Craniosynostosis, the premature fusion of cranial sutures, results in skull deformities and potential complications such as increased intracranial pressure. Although well documented globally, local epidemiological studies and management strategies remain scarce. This study aimed to assess the prevalence, clinical characteristics, and surgical outcomes of craniosynostosis at King Abdullah Specialized Children’s Hospital in Riyadh, Saudi Arabia.

Methods:

A retrospective analysis was conducted, analyzing patients diagnosed with craniosynostosis from October 2019 to June 2023. Demographic, clinical, and surgical data were extracted from electronic medical records. Statistical comparisons between syndromic and nonsyndromic cases were performed using appropriate tests, with significance set at a P value less than 0.05.

Results:

A total of 77 patients were included, with a male predominance (70%) and a mean age at surgery of 26 months. Trigonocephaly (19%), anterior plagiocephaly (18%), and scaphocephaly (18%) were the most common subtypes. Syndromic cases (23%) were more likely to be complex (78% versus 32%, P < 0.001) and had higher rates of papilledema (33% versus 5.1%, P = 0.004) and increased intracranial pressure (33% versus 8.5%, P = 0.02). Surgical outcomes were favorable, with low complication rates and no postoperative mortality. Syndromic patients had longer hospital stays (median 8 versus 7 d, P = 0.002), but intraoperative blood loss was comparable between groups (P = 0.66).

Conclusions:

This study provides insights into craniosynostosis in Saudi Arabia, highlighting the need for earlier diagnosis and genetic studies due to high consanguinity rates. The findings contribute to the global understanding of craniosynostosis and may help improve clinical management strategies.

Takeaways

Question: What is the clinical profile of craniosynostosis in Saudi Arabia, and how do parental consanguinity and craniosynostosis type impact surgical outcomes?

Findings: This retrospective study highlighted key demographic and clinical features, revealing higher complexity and complication risks in syndromic cases. Surgical outcomes were generally favorable with low complication rates.

Meaning: Craniosynostosis in Saudi Arabia shares global trends but has unique clinical aspects. The male predominance, prevalence of trigonocephaly, and excellent surgical outcomes are notable, whereas delayed surgery emphasizes the need for improved early detection and referral pathways.

INTRODUCTION

The premature fusion of one or more cranial sutures is defined as craniosynostosis. Craniosynostosis leads to abnormal development of the skull.¹ Due to the significant functional and structural impacts, it is automatically classified as grade 5 under the Index of Orthognathic Functional Treatment Need system.² Growth arrest occurs perpendicular to the fused suture resulting in compensatory growth in a parallel direction.³ The resulting skull deformity depends on the affected sutures. Multiple pregnancies and uterine anomalies, such as a bicornuate uterus, are linked to a higher risk of craniosynostosis, possibly due to increased skull compression during pregnancy.³ Other theories about the mechanisms driving the early closure of cranial sutures in nonsyndromic craniosynostosis have been suggested. For example, in the 1850s, Virchow assumed that cretinism or meningeal inflammation was associated with craniosynostosis.⁴ Later in the 1920s, Park and Powers⁵ proposed that craniosynostosis was a product of congenital anomalies in the suture mesenchyme. The most recent theory attempting to explain the pathogenesis of craniosynostosis was that of Moss.⁶ According to the Moss’ theory, the major pathology in craniosynostosis is abnormal morphogenesis and development of the basicranium, which impairs the brain’s ability to grow. He proposed that these anomalies lead to different mechanical forces that are transferred to the cranial sutures through the dura mater, causing premature suture fusion.

Craniosynostosis is a common craniofacial anomaly in the United States, occurring in 1 out of every 2000 live births.⁷ A study at a tertiary hospital in Riyadh found craniosynostosis in 33% of craniofacial anomaly cases, making it the most common craniofacial condition reported locally.⁸ Based on the suture involved, craniosynostosis can be classified into 4 major types: sagittal, coronal, metopic, and lambdoid. Other less common types include squamosal and sphenofrontal craniosynostosis. With a male predominance, sagittal craniosynostosis is considered the most commonly reported subtype of craniosynostosis.⁹ Scaphocephaly is an increase in the anterior–posterior diameter of the skull caused by the fusion of the sagittal suture.^9,10 The second most common subtype of craniosynostosis is the fusion of the coronal suture that can be unilateral (anterior plagiocephaly) or bilateral (brachycephaly). Fusion of the metopic suture results in trigonocephaly, which is characterized by a triangular or wedge-shaped forehead.¹¹

The literature is lacking on local epidemiological studies of patients with craniosynostosis as well as management strategies. Herein, we aimed to study the prevalence of craniosynostosis at King Abdullah Specialized Children’s Hospital (KASCH) in Riyadh. This study aimed to provide a detailed overview of craniosynostosis by describing key demographic and clinical features, including age, sex, family history, parental consanguinity, intracranial pressure, papilledema, and type of craniosynostosis (syndromic versus nonsyndromic). Additionally, it evaluated surgical outcomes, such as blood loss and intra- and postoperative complications.

The study also analyzed associations between parental consanguinity, craniosynostosis type, and key clinical and surgical outcomes, including intracranial pressure, papilledema, blood loss, and complications. Findings of the present study will add great value to both national and international literature to elevate the care of patients diagnosed with craniosynostosis.

MATERIALS AND METHODS

Study Sitting and Sample

This was a single-center retrospective cohort study conducted at KASCH, Riyadh, Saudi Arabia. KASCH is a government-funded academic tertiary hospital offering clinical care, training, research, and cutting-edge medical technology. It serves as the principal referral center for pediatric patients nationwide. The study included all patients diagnosed with craniosynostosis at KASCH from October 2019 to June 2023. The diagnosis of syndromic craniosynostosis was based on comprehensive clinical evaluation, including characteristic craniofacial features (eg, midface hypoplasia and orbital anomalies), involvement of multiple cranial sutures on 3-dimensional computed tomography imaging, and associated extracranial anomalies (eg, limb or cardiac abnormalities). The BESTCare electronic system (ezCareTech, South Korea) was used to access patients’ medical records and extract demographic and clinical data.

Recorded Variables

The extracted information included sex, age at surgery, family history, and the presence of parental consanguinity. Clinical features, such as increased intracranial pressure, papilledema, and the type of craniosynostosis (scaphocephaly, trigonocephaly, plagiocephaly, brachycephaly, or pansynostosis), were documented. Craniosynostosis was further classified as syndromic or nonsyndromic and simple or complex, with associated syndromes noted when present. Operative details, including intraoperative and postoperative complications, operation duration, blood loss, and the length of hospitalization, were also recorded.

Statistical Analysis

All statistical analyses were performed using R statistical programming version 4.4.0. Descriptive statistics were presented as frequencies and percentages for categorical variables, whereas continuous variables were expressed as mean ± SD and median with interquartile range (Q1–Q3). The normality of continuous variables was assessed using the Shapiro–Wilk test. Categorical variables were compared between groups (complex versus simple, syndromic versus nonsyndromic) using the chi-square test for independence. When the expected cell frequencies were less than 5, the Fisher exact test was applied instead. For continuous variables (duration of hospitalization and blood loss), the Wilcoxon rank sum test was used, as the data did not follow a normal distribution. Statistical significance was set at a P value less than 0.05, and all tests were 2-tailed. Missing data were reported transparently and not imputed. The results were presented in tables with exact P values to 3 decimal places, except when a P value was less than 0.001. Data visualization was done where appropriate.

Ethical Approval

The study received approval from the institutional review board of the King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (NRC23R/478/07). Due to its retrospective design, the requirement for informed consent was waived. Data access was limited to the research team, ensuring strict confidentiality, with no use of patient names or medical record numbers. Privacy was protected, and all data, both physical and digital, were securely stored within the premises of the Ministry of National Guard Health Affairs. The study adhered to the principles outlined in the Declaration of Helsinki.

RESULTS

Baseline Characteristics

Our study analyzed 77 patients diagnosed with craniosynostosis, revealing a predominantly male cohort with 70% male representation. The patients’ ages at surgery ranged from 8 to 132 months, with a mean age of 26 months (±24 mo) and a median of 16 months. Only 5 patients (6.5%) had a first-degree relative with the condition. Parental consanguinity was present in 36% of cases. Detailed demographic characteristics are presented in Table 1.

Table 1.

Demographic Characteristics of Patients

Characteristic	N = 77
Age at surgery, mo
Minimum–maximum	8–132
Mean (±SD)	26 (±24)
Median (Q1–Q3)	16 (12–36)
Sex, n (%)
Female	23 (30)
Male	54 (70)
Family history (first-degree relative), n (%)
Yes	5 (6.5)
No	65 (84)
Unknown	7 (9.1)
Parental consanguinity, n (%)
Yes	28 (36)
No	40 (52)
Unknown	9 (12)

Disease Characteristics

Increased intracranial pressure was observed in 14% of patients with papilledema present in 12%. The most common types of craniosynostosis were trigonocephaly (19%), anterior plagiocephaly, multisuture craniosynostosis, and scaphocephaly (each at 18%). The majority of cases (57%) were classified as simple craniosynostosis, and 77% were nonsyndromic. Among the 18 syndromic cases, Apert syndrome was most prevalent (50%), followed by Muenke syndrome (17%), and Crouzon and Pfeiffer syndromes (11% each). Detailed disease characteristics are presented in Table 2.

Table 2.

Disease Characteristics

Characteristic	N = 77
Presence of increased intracranial pressure, n (%)	11 (14)
Presence of papilledema, n (%)	9 (12)
Type of craniosynostosis, n (%)
Trigonocephaly	15 (19)
Anterior plagiocephaly	14 (18)
Multisuture craniosynostosis	14 (18)
Scaphocephaly	14 (18)
Brachycephaly	9 (12)
Pansynostosis	6 (7.8)
Frontal plagiocephaly	2 (2.6)
Turricephaly	2 (2.6)
Posterior plagiocephaly	1 (1.3)
Complexity of synostosis, n (%)
Simple	44 (57)
Complex	33 (43)
Syndromic status, n (%)
Nonsyndromic	59 (77)
Syndromic	18 (23)
Distribution of syndromic craniosynostosis, n (%)	N = 18
Apert syndrome	9 (50)
Muenke syndrome	3 (17)
Crouzon syndrome	2 (11)
Pfeiffer syndrome	2 (11)
Bainbridge–Ropers syndrome	1 (5.6)
Saethre–Chotzen syndrome	1 (5.6)

Perioperative Characteristics

Regarding operation type, frontoorbital advancement with total cranial vault reconstruction was the predominant surgical procedure (58%), followed by total cranial vault reconstruction (18%). Only 2.6% of patients required reoperation, though 22% needed second-stage reconstruction. Surgical outcomes were generally favorable, with no postoperative mortality or morbidity. Complications were minimal, with only 1 case (1.3%) of postoperative surgical site infection and 4 cases (5.2%) of intraoperative dural tears. The mean duration of hospitalization was 8.7 days (±9.8 d), with a median of 7 days. Intraoperative blood loss ranged from 50 to 1000 mL, with a mean of 321 mL (±185 mL). Detailed operative characteristics and outcomes are presented in Table 3.

Table 3.

Perioperative Characteristics

Characteristic	N = 77
Underwent reoperation, n (%)	2 (2.6)
Need for second-stage reconstruction, n (%)	17 (22)
Postoperative complications, n (%)	1 (1.3)
Surgical site infection	1 (100)
Duration of hospitalization, d
Minimum–maximum	4.0–88.0
Mean (±SD)	8.7 (±9.8)
Median (Q1–Q3)	7.0 (6.0–8.0)
Intraoperative complications, n (%)	4 (5.2)
Dural tear	4 (100)
Postoperative mortality, n (%)
No	77 (100)
Postoperative morbidity (eg, neurological deficit, blindness, etc.), n (%)
No	77 (100)
Blood loss, mL
Minimum–maximum	50–1000
Mean (±SD)	321 (±185)
Median (Q1–Q3)	300 (200–400)

Comparison of Clinical Characteristics and Surgical Outcomes Between Syndromic and Nonsyndromic Craniosynostosis

The analysis revealed significant differences between syndromic craniosynostosis and nonsyndromic cases across several parameters. Syndromic cases were more likely to be classified as complex (78% versus 32%, P < 0.001), whereas nonsyndromic cases were predominantly simple (68% versus 22%). There was no significant association between family history or parental consanguinity and syndromic versus nonsyndromic craniosynostosis (P = 0.28 and P = 0.16, respectively). Syndromic patients showed significantly higher rates of papilledema (33% versus 5.1%, P = 0.004) and increased intracranial pressure (33% versus 8.5%, P = 0.02). Intraoperative complications were also more frequent in syndromic cases (17% versus 1.7%, P = 0.04). Hospital stays were longer for syndromic patients (median 8.0 versus 7.0 d, P = 0.002), though blood loss was comparable between groups (P = 0.66). Detailed clinical features, surgical parameters, and outcomes are presented in Table 4.

Table 4.

Clinical Features, Surgical Parameters, and Outcomes in Syndromic Versus Nonsyndromic Craniosynostosis Patients

Characteristic	Nonsyndromic, N = 59	Syndromic, N = 18	P
Classification 2*, n (%)			<0.001
Complex	19 (32)	14 (78)
Simple	40 (68)	4 (22)
Family history (first-degree relative), n (%)			0.28
Not available	4 (6.8)	3 (17)
No	50 (85)	15 (83)
Yes	5 (8.5)	0 (0)
Parental consanguinity, n (%)			0.16
Yes	24 (41)	4 (22)
No	30 (51)	10 (56)
Not available	5 (8.5)	4 (22)
Presence of papilledema, n (%)	3 (5.1)	6 (33)	0.004
Presence of increased intracranial pressure, n (%)	5 (8.5)	6 (33)	0.02
Intraoperative complications, n (%)	1 (1.7)	3 (17)	0.04
Duration of hospitalization, d			0.002
Minimum–maximum	4.0–10.0	6.0–88.0
Mean (±SD)	6.7 (±1.3)	15.0 (±19.3)
Median (Q1–Q3)	7.0 (6.0–8.0)	8.0 (7.0–15.0)
Blood loss, mL			0.66
Minimum–maximum	50–750	100–1000
Mean (±SD)	314 (±156)	342 (±262)
Median (Q1–Q3)	300 (200–400)	300 (200–400)

Statistical comparisons were made using the Fisher exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables.

^*The Pearson chi-square test.

DISCUSSION

This study aimed to evaluate the clinical features and surgical outcomes of craniosynostosis at a tertiary care center in Saudi Arabia. Our results highlighted important areas for comparison with worldwide data and offered insightful information about the local patterns of craniosynostosis. This study highlighted both distinctive regional features and widely accepted trends in the treatment of craniosynostosis by identifying important demographic, clinical, and surgical outcome variables. Our findings provided insights into the local patterns of craniosynostosis and highlighted critical areas for comparison with global data. By identifying key demographic, clinical, and surgical outcome variables, this study underscored both unique regional characteristics and universally recognized trends in craniosynostosis management.

Demographic Findings

A marked male predominance of 70% in our sample is consistent with other research showing a higher frequency of craniosynostosis in men.¹² This gender gap is especially noticeable in some subtypes, such as metopic craniosynostosis, where a 3.3 to 1 male-to-female ratio has been noted.¹³ The fundamental causes of this gender disparity remain unknown and deserve more exploration, possibly focusing on genetic and hormonal variables. The median age at surgery in our cohort was 16 months, which is considered relatively late compared with international standards. Surgery at an earlier age, ideally before 12 months, is generally recommended to optimize neurological outcomes and minimize complications related to increased intracranial pressure.^14,15 Bellew et al¹⁵ concluded that surgery performed at younger ages was associated with better neurocognitive outcomes when assessed at 10 and 15 years of age. Additionally, they showed that patients who underwent surgery before 6 months of age had a higher full-scale IQ, higher verbal IQ, and superior abilities in various cognitive domains compared with those treated later.¹⁵ Delayed presentation and surgical intervention can be attributed to a multitude of factors, including delayed diagnosis, caregiver unawareness, and limited access to expert therapy. Late intervention may increase the risk of complications, such as excessive intracranial pressure, emphasizing the significance of timely diagnosis and treatment.¹⁶

Patterns of Craniosynostosis: Regional Versus Global Trends

In the present study, trigonocephaly was found to be the most common type of craniosynostosis, in contrast to some global trends where sagittal synostosis (scaphocephaly) is often reported as the most common type.¹⁷ Our finding, however, is in agreement with a recent study from Saudi Arabia that similarly recognized trigonocephaly as the most common type of craniosynostosis.¹⁸ This regional variation may be due to genetic or environmental factors specific to the Saudi population and warrants further investigation. Among syndromic cases, Apert syndrome was the most common, followed by Muenke syndrome. This distribution differs slightly from some reports where Crouzon syndrome is often cited as the most frequent syndromic form.¹² The prevalence of specific syndromes can vary across populations, and our findings contribute to the understanding of syndromic craniosynostosis patterns in Saudi Arabia.

Familial History and Consanguinity

Family history was found in only 5% of patients, with no significant association with syndromic craniosynostosis. This low rate of family occurrence is in line with the body of research indicating that most cases of craniosynostosis are sporadic.^19,20 However, the high proportion of paternal consanguinity (36%) in our sample is noteworthy, even though it did not reveal a significant relationship with syndromic cases. These findings imply that although consanguinity is prevalent in our population, it may not play a major role in the development of syndromic craniosynostosis, which is most likely caused by specific genetic mutations.

Surgical Outcomes and Complications

Our study also demonstrated favorable surgical outcomes, with a zero mortality rate and low intra- and postoperative complication rates. Recent literature supports these findings. Morrison et al²¹ presented a 20-year experience at a large academic medical facility and found a 0% death rate, 1.2% complication rate, and 2.5% reoperation rate for open craniosynostosis procedures. Similarly, a national study on craniosynostosis patients who underwent surgical intervention found a mortality rate of less than 1% and a complication rate of approximately 10%.²² The relatively low complication rates reflect the surgical expertise of the managing team and the implementation of meticulous perioperative protocols.

Hospital Stay Duration: Syndromic Versus Nonsyndromic Cases

The median hospital stay of 7 days, with significantly longer stays for syndromic cases, is consistent with the complex nature of syndromic craniosynostosis and the often more extensive surgical procedures required for these patients. For nonsyndromic craniosynostosis, hospital stays are typically shorter. According to Texas Children’s Hospital,²³ the total time in hospital for most cases ranges from 3 to 5 days. Similarly, Johns Hopkins All Children’s Hospital²⁴ reports that patients treated with open cranial vault reconstruction usually remain in the hospital for 3–4 nights on average. However, patients with syndromic craniosynostosis often require more complex surgical interventions and longer hospitalization periods. The management of syndromic craniosynostosis is very selective and personalized due to the unique nature of each case.²⁵ The extended hospital stay for syndromic cases can be attributed to several factors, including the need for intensive care unit monitoring, management of potential complications, and the time required for swelling to subside postsurgery.

Intracranial Pressure and Syndromic Cases

In the present study, we found that patients with syndromic craniosynostosis had significantly higher rates of increased intracranial pressure and papilledema. These observations are consistent with past research, which has highlighted the greater risk of intracranial hypertension in syndromic craniosynostosis due to factors such as multiple suture involvement and related craniofacial deformities.²⁶ In the literature, the prevalence of elevated intracranial pressure varied from 15% to 20% in nonsyndromic craniosynostosis to 30% to 40% in syndromic cases, with patients having multiple sutures involved at higher risk of increased intracranial pressure and papilledema.²⁷ Several pathophysiological factors contribute to this elevated risk, including multiple suture involvement, which limits skull growth, craniocephalic disproportion, venous hypertension, and associated craniofacial anomalies that interfere with normal intracranial dynamics.²⁸ The higher frequency of elevated intracranial pressure and papilledema in syndromic craniosynostosis may be explained by a combination of these factors, emphasizing the crucial significance of comprehensive monitoring and early management to prevent potential neurocognitive and visual complications.

Limitations

This study has several important limitations that warrant consideration. The retrospective design inherently carries risks of selection bias and potential gaps in clinical data availability. Notably, the lack of genetic testing, particularly in light of the observed high consanguinity rate, represents a significant constraint, as molecular characterization could have provided valuable insights into genetic etiologies. Furthermore, as a single-center investigation, the generalizability of our findings to diverse populations or healthcare systems may be limited. Although these constraints reflect common challenges in retrospective surgical studies, they nevertheless underscore the need for cautious interpretation of our results and highlight important directions for future multicenter prospective studies incorporating genetic analyses.

CONCLUSIONS

Our study provides foundational data on craniosynostosis from a tertiary center in Saudi Arabia, highlighting both similarities and differences with global trends. The male predominance, prevalence of trigonocephaly, and excellent surgical outcomes are particularly noteworthy. However, the relatively late age at surgery suggests a need for improved early detection and referral pathways. The high consanguinity rate and unique syndromic distribution warrant further genetic studies in this population. These findings contribute meaningfully to understanding craniosynostosis in the region and lay the groundwork for future multicenter studies with extended follow-up to further validate these trends.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.