Velopharyngeal insufficiency, speech, and language impairment in craniofacial microsomia: a scoping review.

This review provides a comprehensive overview of the literature on velopharyngeal insufficiency, associated anomalies, and speech/language impairment in patients with craniofacial microsomia (CFM). A systematic search of the literature was conducted to identify records on VPI and speech impairment in CFM from their inception until September 2022 within the databases Embase, PubMed, MEDLINE, Ovid, CINAHL EBSCO, Web of Science, Cochrane, and Google Scholar. Seventeen articles were included, analysing 1,253 patients. Velopharyngeal insufficiency results in hypernasality can lead to speech impairment. The reported prevalence of both velopharyngeal insufficiency and hypernasality ranged between 12.5% and 55%, while the reported prevalence of speech impairment in patients with CFM varied between 35.4% and 74%. Language problems were reported in 37% to 50% of patients. Speech therapy was documented in 45.5% to 59.6% of patients, while surgical treatment for velopharyngeal insufficiency consisted of pharyngeal flap surgery or pharyngoplasty and was reported in 31.6% to 100%. Cleft lip and/or palate was reported in 10% to 100% of patients with CFM; these patients were found to have worse speech results than those without cleft lip and/or palate. No consensus was found on patient characteristics associated with an increased risk of velopharyngeal insufficiency and speech/language impairment. Although velopharyngeal insufficiency is a less commonly reported characteristic of CFM than other malformations, it can cause speech impairment, which may contribute to delayed language development in patients with CFM. Therefore, timely recognition and treatment of speech impairment is essential.

Evaluation of Research Diagnostic Criteria in Craniofacial Microsomia.

Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on standardized clinical diagnostic criteria is available. The use of diagnostic criteria could improve research and communication among patients and healthcare professionals. Two sets of phenotypic criteria for research were independently developed and based on multidisciplinary consensus: the FACIAL and ICHOM criteria. This study aimed to assess the sensitivity of both criteria with an existing global multicenter database of patients with CFM and study the characteristics of patients that do not meet the criteria. A total of 730 patients with CFM from were included. Characteristics of the patients were extracted, and severity was graded using the O.M.E.N.S. and Pruzansky-Kaban classification. The sensitivity of the FACIAL and ICHOM was respectively 99.6% and 94.4%. The Cohen's kappa of 0.38 indicated a fair agreement between both criteria. Patients that did not fulfill the FACIAL criteria had facial asymmetry without additional features. It can be concluded that the FACIAL and ICHOM criteria are accurate criteria to describe patients with CFM. Both criteria could be useful for future studies on CFM to create comparable and reproducible outcomes.

Upper and Lower Limb Anomalies in Craniofacial Microsomia and Its Relation to the OMENS+ Classification: A Multicenter Study of 688 Patients.

BACKGROUND: Craniofacial microsomia (CFM) is characterized by several malformations related to the first and second pharyngeal arch. Patients typically present with facial asymmetry, but extracraniofacial organ systems might be involved, including limb anomalies. The purpose of this study was to analyze the occurrence of upper and lower limb anomalies in CFM patients. Furthermore, the relation between limb anomalies and the OMENS+ (orbital distortion; mandibular hypoplasia; ear anomaly; nerve involvement; soft-tissue deficiency; and associated extracraniofacial anomalies) classification was examined. METHODS: A retrospective study was conducted including patients with CFM from craniofacial units in three different countries. Patients were included when clinical and/or radiographic images were available. Demographic, radiographic, and clinical information was obtained. RESULTS: A cohort of 688 patients was available and selected for analysis. In total, 18.2% of the patients were diagnosed with at least one upper and/or lower limb anomaly. Upper and lower limb anomalies were seen in, respectively, 13.4% and 7.8% of patients. Patients with other extracraniofacial anomalies had a significantly higher risk for limb anomalies (OR, 27.98; P = 0.005). Laterality of CFM and a higher OMENS score were not associated with limb anomalies. CONCLUSIONS: More than one in six patients with craniofacial microsomia have limb anomalies. Therefore, clinical awareness for these anomalies is warranted. Examination and, if present, follow-up on limb abnormalities in patients with CFM should be implemented in the standard assessment of CFM patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

The Accuracy of Computer-Assisted Surgical Planning in Predicting Soft Tissue Responses After Le Fort I Osteotomy: Retrospective Analysis.

PURPOSE: Mismatch between preoperative planning and surgical outcome in maxillofacial surgery relate to on-table replication of presurgical planning and predictive algorithm inaccuracy: software error was hereby decoupled from planning inaccuracy to assess a commercial software. The hypothesis was that soft tissue prediction error would be minimized if the surgical procedure was replicated precisely as planned and is independent of the extent of bone repositioning. MATERIALS AND METHODS: Cone-beam computed tomography scans of 16 Le Fort I osteotomy patients were collected at Boston Children's Hospital. Preoperative and postoperative models of bone and soft tissue were constructed and the maxilla repositioning was replicated. Each model was subdivided into 6 regions: mouth, nose, eyes, and cheeks. Soft tissue prediction (performed using Proplan CMF-Materialise) for each patient was compared with the relative postoperative reconstruction and error was determined. P <0.05 was considered significant. RESULTS: Le Fort I segment repositioning was replicated within 0.70±0.18 mm. The highest prediction error was found in the mouth (1.49±0.77 mm) followed by the cheeks (0.98±0.34 mm), nose (0.86±0.23 mm), and eyes (0.76±0.32). Prediction error on cheeks correlated significantly with mouth ( r =0.63, P < 0.01) and nose ( r =0.67, P < 0.01). Mouth prediction error correlated with total advancement ( r =0.52, P =0.04). CONCLUSIONS: ProPlan CMF is a useful outcome prediction tool; however, accuracy decreases with the extent of maxillary advancement even when errors in surgical replication are minimized.

The effect of natural growth on chin point deviation in patients with unilateral craniofacial microsomia: A retrospective study.

This study aimed to investigate the potential progressiveness of mandibular asymmetry and to study factors that influence chin point deviation in patients with unilateral craniofacial microsomia (CFM). Paediatric patients with unilateral CFM with available radiologic imaging and medical photographs were included. Chin point deviation was measured on clinical photographs. A Jonckheere-Terpstra test and linear mixed model for repeated measurements assessed the relation of chin point deviation on natural growth, Pruzansky-Kaban score, and soft tissue score. A total of 110 patients were included. The linear mixed model showed no statistically significant changes of chin point deviation during growth (effect estimate -0.006°, 95% CI -0.04° to -0.03°, p = 0.74). A statistical significant relation between both the Pruzansky-Kaban and soft tissue score on chin point deviation was found (effect estimate -5.10°, 95% CI -6.45° to -3.75°, p ≤ 0.001 and effect estimate -3.42°, CI -5.86° to -0.98°, p ≤ 0.001, respectively). Within the limitations of the study it seems that craniofacial microsomia may be a non-progressive disorder, because chin point deviation did not change over time.

A decade of clinical research on clinical characteristics, medical treatments, and surgical treatments for individuals with craniofacial microsomia: What have we learned?

AIM: This article provides a review of a decade of clinical research studies on clinical features, medical interventions, and surgical interventions for individuals with craniofacial microsomia (CFM). We also provide recommendations for future clinical research. METHOD: A systematic search of literature was conducted in Embase and PubMed/MEDLINE Ovid. All publications from 2010 to 2020 that included at least 10 individuals with CFM were considered relevant for this study. RESULTS: A total of 91 articles were included. In the past decade, many new studies on CFM have been published providing more insight on the diagnosis and management of patients with CFM. This review encompasses findings on the clinical difficulties patients with CFM encounter, including the craniofacial and extracraniofacial characteristics of patients with CFM and its related clinical consequences on breathing, feeding, speech, and hearing. CONCLUSIONS: A considerable number of large multicenter studies have been published in recent years, providing new insights in the clinical consequences of CFM. The phenotypic variety between patients with CFM makes patient-specific treatment tailored to individual needs essential. The research and development of clinical care standards might be challenging because of the heterogeneity of CFM. Future research on clinical and patient-reported outcomes can help identify optimal treatment strategies. Cooperation between craniofacial centers, using uniform registration and outcome measurement tools, could enhance research and future care for these patients. LEVEL OF EVIDENCE: Level IV.

Ocular and adnexal anomalies in Treacher Collins syndrome: a retrospective multicenter study.

BACKGROUND: Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by bilateral hypoplasia of facial structures and periorbital, ocular, and adnexal anomalies. The purpose of this multicenter study was to report the prevalence of ocular and adnexal anomalies in TCS and to identify patients at risk for visual impairment. METHODS: The medical records of patients seen at four craniofacial centers were reviewed retrospectively. The following data were reported: primary and secondary ocular and adnexal anomalies, orthoptic and ophthalmological findings, and severity of TCS based on the facial deformity. RESULTS: A total of 194 patients were included, of whom 49.5% were examined by an ophthalmologist or optometrist. The mean age at the first visual acuity measurement was 6.96 ± 6.83 years (range, 1.50-47.08); at final measurement, 11.55 ± 10.64 years (range, 1.75-62.58). Primary ocular anomalies were reported in 98.5% of cases, secondary anomalies in 34.5%, strabismus in 27.3%, refractive errors in 49.5%, and visual impairment in 4.6%. We found no association between ocular anomalies and visual impairment or between the severity of TCS and ocular anomalies or visual impairment, except for an increased prevalence of secondary ocular anomalies in patients with more severe manifestations of TCS. CONCLUSIONS: Ocular anomalies were present in nearly all patients with TCS, even in mild cases.

Correlation between head shape and volumetric changes following spring-assisted posterior vault expansion.

The aim of the study was to investigate whether different head shapes show different volumetric changes following spring-assisted posterior vault expansion (SA-PVE) and to investigate the influence of surgical and morphological parameters on SA-PVE. Preoperative three-dimensional skull models from patients who underwent SA-PVE were extracted from computed tomography scans. Patient head shape was described using statistical shape modelling (SSM) and principal component analysis (PCA). Preoperative and postoperative intracranial volume (ICV) and cranial index (CI) were calculated. Surgical and morphological parameters included skull bone thickness, number of springs, duration of spring insertion and type of osteotomy. In the analysis, 31 patients were included. SA-PVE resulted in a significant ICV increase (284.1 ± 171.6 cm3, p < 0.001) and a significant CI decrease (-2.9 ± 4.3%, p < 0.001). The first principal component was significantly correlated with change in ICV (Spearman ρ = 0.68, p < 0.001). Change in ICV was significantly correlated with skull bone thickness (ρ = -0.60, p < 0.001) and age at time of surgery (ρ = -0.60, p < 0.001). No correlations were found between the change in ICV and number of springs, duration of spring insertion and type of osteotomy. SA-PVE is effective for increasing the ICV and resolving raised intracranial pressure. Younger, brachycephalic patients benefit more from surgery in terms of ICV increase. Skull bone thickness seems to be a crucial factor and should be assessed to achieve optimal ICV increase. In contrast, insertion of more than two springs, duration of spring insertion or performing a fully cut through osteotomy do not seem to impact the ICV increase. When interpreting ICV increases, normal calvarial growth should be taken into account.

Correlation of Intracranial Volume With Head Surface Volume in Patients With Multisutural Craniosynostosis.

Intracranial volume (ICV) is an important parameter for monitoring patients with multisutural craniosynostosis. Intracranial volume measurements are routinely derived from computed tomography (CT) head scans, which involves ionizing radiation. Estimation of ICV from head surface volumes could prove useful as 3D surface scanners could be used to indirectly acquire ICV information, using a non-invasive, non-ionizing method.Pre- and postoperative 3D CT scans from spring-assisted posterior vault expansion (sPVE) patients operated between 2008 and 2018 in a single center were collected. Patients were treated for multisutural craniosynostosis, both syndromic and non-syndromic. For each patient, ICV was calculated from the CT scans as carried out in clinical practice. Additionally, the 3D soft tissue surface volume (STV) was extracted by 3D reconstruction of the CT image soft tissue of each case, further elaborated by computer-aided design (CAD) software. Correlations were analyzed before surgery, after surgery, combined for all patients and in syndrome subgroups.Soft tissue surface volume was highly correlated to ICV for all analyses: r = 0.946 preoperatively, r = 0.959 postoperatively, and r = 0.960 all cases combined. Subgroup analyses for Apert, Crouzon-Pfeiffer and complex craniosynostosis were highly significant as well (P < 0.001).In conclusion, 3D surface model volumes correlated strongly to ICV, measured from the same scan, and linear equations for this correlation are provided. Estimation of ICV with just a 3D surface model could thus be realized using a simple method, which does not require radiations and therefore would allow closer monitoring in patients through multiple acquisitions over time.

Dental anomalies in craniofacial microsomia: A systematic review.

OBJECTIVE:  To provide an overview on the prevalence and types of dental anomalies in patients with craniofacial microsomia (CFM). Eligibility criteria: Inclusion criteria were CFM and dental anomalies. The following data were extracted: number of patients, methodology, mean age, sex, affected side, severity of mandibular hypoplasia, dentition stage and dental anomalies. INFORMATION SOURCES: Cochrane, EMBASE, PubMed, MEDLINE Ovid, Web of Science, CINAHL EBSCOhost and Google Scholar, searched until the 30 August 2019. Risk of bias: The quality was examined with the OCEBM Levels of Evidence. INCLUDED STUDIES: In total, 13 papers were included: four retrospective cohort studies, four prospective cohort studies, four case-control studies and one case series. Synthesis of results: The studies reported information on dental agenesis, delayed dental development, tooth size anomalies, tooth morphology and other dental anomalies. Description of the effect: Dental anomalies are more often diagnosed in patients with CFM than in healthy controls and occur more often on the affected than on the non-affected side. Strengths and limitations of evidence: This is the first systematic review study on dental anomalies in CFM. However, most articles were of low quality. INTERPRETATION: Dental anomalies are common in CFM, which might be linked to the development of CFM. The pathophysiology of CFM is not entirely clear, and further research is needed.

What Are the Characteristics of the Upper Airway in Patients With Craniofacial Microsomia?

PURPOSE: Obstructive sleep apnea (OSA) is a common problem in patients with craniofacial microsomia (CFM); however, the exact pathophysiology in patients with CFM remains unclear. The first aim of this study was to evaluate upper airway volume and morphology in patients with CFM. The second aim was to identify risk factors for the presence of OSA. MATERIALS AND METHODS: A cross-sectional study was set up and 3 study groups were identified: 1) CFM with OSA, 2) CFM without OSA, and 3) control. Computed tomographic (CT) scans of the head and neck were included and used to create 3-dimensional models. The age-matched control group consisted of patients evaluated for traumatic head injury or epilepsy. Volumetric and morphologic parameters were measured. The results of patients with CFM were compared among the 3 study groups. Descriptive statistics were computed using the Pearson χ2 test for categorical variables and nonparametric tests for continuous variables. A multiple variable regression model was used to identify risk factors for OSA. RESULTS: In total, 79 patients with CFM were included, of which 25 patients were diagnosed with OSA. A total of 145 CT scans could be analyzed. In addition, a control population of 88 patients was identified. Oropharynx volume, mean cross-sectional area (CSA), minimal CSA, and minimal retropalatal area were found to be markedly smaller in patients with CFM compared with the control population. In contrast, in patients with CFM and OSA, minimal retroglossal area, sphericity, and uniformity markedly differed from those in patients without OSA. Sphericity was identified as the main predicting variable of OSA in patients with CFM. CONCLUSIONS: The upper airway of patients with CFM is markedly smaller and puts them at risk for developing OSA. Patients with CFM diagnosed with OSA have a markedly smaller CSA behind the base of the tongue and a difference in sphericity.

Surgical Correction of Craniofacial Microsomia: Evaluation of Interventions in 565 Patients at Three Major Craniofacial Units.

BACKGROUND: Craniofacial microsomia is characterized by an asymmetric hypoplasia of derivatives of the first and second pharyngeal arch, leading to a variety of phenotypic presentations. Studies on surgical correction of patients with craniofacial microsomia have small cohorts, leaving controversial opinions on the optimal treatment modality, the indication for surgery, and the optimal timing of surgery. The purpose of this study was to evaluate the types of, timing of, and total number of surgical corrections performed and the number of surgical procedures in correlation to the severity of the phenotype. METHODS: A retrospective chart study was conducted including patients diagnosed with craniofacial microsomia from three large craniofacial units. Demographic, radiographic, and clinical information was obtained, including type and number of surgical procedures and age at the time of surgery. RESULTS: A total of 565 patients were included. In total, 443 (78.4 percent) of all patients underwent some form of surgery during their life, varying from skin tag removal to major craniofacial operations. The number of surgical interventions was higher with increasing severity of phenotype, bilateral presentation, and a younger age at the first intervention. CONCLUSIONS: Multiple surgical corrections are frequently seen in patients with a more severe or bilateral presentation. Furthermore, those who are treated earlier in life for correction of asymmetry of the mandible will undergo significantly more surgical procedures to correct the asymmetry later on, independent of the Pruzansky-Kaban type mandible. A prospective international multicenter study is designed with a uniform registration and outcome measurement tool to identify the optimal treatment strategy.

Feeding difficulties in craniofacial microsomia: A multicenter retrospective analysis of 755 patients.

A retrospective cohort study was initiated to analyse the prevalence, risk factors and treatment modalities of feeding difficulties in patients with craniofacial microsomia. This study included 755 subjects with craniofacial microsomia from three craniofacial centres. Medical charts were reviewed for severity of the deformity, documented feeding difficulties, age at which feeding difficulties first presented and treatment, presence of cleft lip/palate, extracraniofacial anomalies, and obstructive sleep apnoea. In total, 199 patients (26.4%) had documented feeding difficulties. Patients with bilateral involvement, Pruzansky-Kaban III classification, cleft lip/palate, or obstructive sleep apnoea were significantly more at risk for developing feeding difficulties and significantly more often needed additional feeding via a nasogastric tube than patients without these risk factors.

Part 2: Is the maxillary canting and its surgical correction in patients with CFM correlated to the mandibular deformity?

INTRODUCTION: Patients with Craniofacial Microsomia (CFM) mandibles Types I/IIa benefit from combined LeFort 1 osteotomy and Mandibular Distraction Osteogenesis (LeFort + MDO); Type IIb from LeFort + MDO or Bimaxillary osteotomy (BiMax); and Type III from BiMax (with 50% of cases having preceding mandibular procedures, including patient-fitted prosthesis); as seen in Part 1. This leads to the question how maxillary and mandibular hypoplasia are correlated and influence the types of maxillary correction. MATERIAL AND METHODS: A retrospective chart study was conducted including patients diagnosed with CFM from 2 large craniofacial units. Radiographic and clinical information were obtained. Unilateral affected patients with available (ConeBeam) CT-scan of the maxillary-mandibular complex, without treatment of the upper jaw prior to the CT-scan were included. A maxillary cant grading system was set up and evaluated. Pearson correlation coefficients were used to correlate the maxillary cant and the severity of the mandibular hypoplasia. RESULTS: Eighty-one patients were included, of whom 39.5% had a Pruzansky-Kaban type III mandible and 42% a mild maxillary cant. There was a significant positive correlation between severity of the mandibular hypoplasia and the categorized canting (r = 0.370; p < 0.001; n = 81). Twenty-four patients had maxillary surgery, mainly a BiMax. CONCLUSION: There is a positive correlation between the severity of mandibular hypoplasia and maxillary cant. The severity of mandibular hypoplasia seems to dictate an intervention for both maxillary and mandibular surgery.

Surgical correction of the midface in craniofacial microsomia. Part 1: A systematic review.

INTRODUCTION: Mandibular reconstruction in craniofacial microsomia (CFM) has been described and reviewed at length although final results are not always (aesthetically) satisfactory due to maxillo-mandibular asymmetry, for which optimal correction techniques remain unclear. The aim of this systematic review is to provide an overview of the surgical options for maxillary correction in patients with unilateral CFM. MATERIAL AND METHODS: MEDLINE/Pubmed, Embase, Cochrane and Web of Science databases were searched up to April 15, 2017. Inclusion criteria were: studies reporting patients with unilateral CFM (n > 4) who had maxillary correction (with/without simultaneous mandibular correction) with a minimal follow-up of 6 months. The outcome measures included type of treatment (including preceding facial procedures), type and severity of mandibular deformity (by Pruzansky-Kaban system: Types I/IIa/IIb/III), asymmetry analysis method, outcome (i.e. occlusion, canting, stability, esthetic result, facial symmetry), complications and additional treatment needed. RESULTS: Nine studies met the inclusion criteria. Analysis showed that Le Fort I + mandibular distraction osteogenesis (LeFort + MDO) and BiMaxillary osteotomy (BiMax) were used for treatment, as single or multiple-stage procedures. All studies reported aesthetic and functional improvement. CONCLUSION: Types I/IIa benefited from LeFort + MDO; Type IIb from LeFort + MDO or BiMax; and Type III from BiMax (with 50% of cases having preceding mandibular procedures, including patient-fitted prosthesis) at a mean age of 20.2 years. Four studies recommended additional (esthetic) procedures.

Is There a Difference in Orbital Volume Between Affected and Unaffected Sides in Patients With Unilateral Craniofacial Microsomia?

PURPOSE: Craniofacial microsomia (CFM) is characterized by malformations of structures derived from the first and second pharyngeal arches. The orbit is variably affected. The purpose of this study was to determine whether there is a difference in orbital volume between affected and unaffected sides in patients with unilateral CFM. The specific aims were to 1) measure orbital volume, 2) compare affected and unaffected sides, 3) evaluate the correlation between clinical evaluation of orbital size and volumetric measurement, and 4) determine whether there is a correlation between orbital volume and severity of mandibular deformity. MATERIALS AND METHODS: This study is a retrospective case series of patients with unilateral CFM from Boston Children's Hospital (Boston, MA) who had a computed tomographic (CT) scan. Manual segmentation of the orbit using Mimics software (Materialise, Leuven, Belgium) was performed on CT images of the 2 orbits. The predictor variable was laterality (affected vs unaffected side) and the primary outcome variable was orbital volume. Wilcoxon signed rank test was used to compare these measurements and determine whether the affected side differed from the unaffected side. The correlation between orbital volume and Pruzansky-Kaban type of mandibular deformity, as documented in the medical record, was determined using the Spearman rank correlation coefficient. RESULTS: Thirty-nine patients were included. Orbital volume was 10% smaller on the affected side (P = .001) in 80% of patients. There was no correlation between orbital size and severity of mandibular involvement. CONCLUSION: The results of this study showed a marked difference in orbital volume between affected and unaffected sides in patients with unilateral CFM. These differences were small and might not be clinically relevant. Orbital volume did not correlate with severity of mandibular deformity.

Evaluation of Swallow Function in Patients with Craniofacial Microsomia: A Retrospective Study.

Craniofacial microsomia (CFM) is characterized by underdevelopment of the structures derived from the first and second pharyngeal arches resulting in aesthetic, psychological, and functional problems including feeding and swallowing difficulties. The aim of this study is to gain more insight into swallowing difficulties in patients with CFM. A retrospective study was conducted in the population of patients diagnosed with CFM at three major craniofacial units. Patients with feeding difficulties and those who underwent video fluoroscopic swallow (VFS) studies were included for further analyses. The outcome of the VFS-studies was reviewed with regard to the four phases of swallowing. In our cohort, 13.5% of the 755 patients were diagnosed with swallowing difficulties. The outcome of the VFS-studies of 42 patients showed difficulties in the oral and pharyngeal phases with both thin and thick liquids. Patients with more severe mandibular hypoplasia showed more difficulties to form an appropriate bolus compared to patients who were less severely affected. This is the first study to document swallowing problems in patients with CFM. Difficulties were seen in both the oral and pharyngeal phases. We recommend routine screening for swallowing issues by a speech and language therapist in all patients with CFM and to obtain a VFS-study in patients with a type III mandible.

Craniofacial and extracraniofacial anomalies in craniofacial microsomia: a multicenter study of 755 patients'

PURPOSE: Craniofacial microsomia (CFM) is a congenital malformation of structures derived from the first and second pharyngeal arches leading to underdevelopment of the face. However, besides the craniofacial underdevelopment, extracraniofacial anomalies including cardiac, renal and skeletal malformation have been described. The aim of this study is to analyse a large population of patients with regard to demographics, typical phenotypes including craniofacial and extracraniofacial anomalies, and the correlations between the different variables of this condition. MATERIAL AND METHODS: A retrospective study was conducted in patients diagnosed with CFM with available clinical and/or radiographic images. All charts were reviewed for information on demographic, radiographic and diagnostic criteria. The presence of cleft lip/palate and extracraniofacial anomalies were noted. Pearson correlation tests and principal component analysis was performed on the phenotypic variables. RESULTS: A total of 755 patients were included. The male-to-female ratio and right-to-left ratio were both 1.2:1. A correlation was found among Pruzansky-Kaban, orbit and soft tissue. Similar correlations were found between ear and nerve. There was no strong correlation between phenotype and extracraniofacial anomalies. Nevertheless, extracraniofacial anomalies were more frequently seen than in the 'normal' population. Patients with bilateral involvement had a more severe phenotype and a higher incidence of extracraniofacial and cleft lip/palate. CONCLUSION: Outcomes were similar to those of other smaller cohorts. Structures derived from the first pharyngeal arch and the second pharyngeal arch were correlated with degree of severity. Extracraniofacial anomalies were positively correlated with CFM. The findings show that bilaterally affected patients are more severely affected and should be approached more comprehensively.