Velopharyngeal dysfunction and speech-related characteristics in craniofacial microsomia: a retrospective analysis of 223 patients.

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P. VPD was significantly more prevalent in CFM with CL/P than in CFM without CL/P (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.9-8.7; P < 0.001). Multivariate logistic regression showed a significant association between CL/P and VPD in CFM patients (OR 7.4, 95% CI 2.1-26.3; P = 0.002). The presence of VPD was not associated with sex, the laterality or severity of CFM. Speech problems related to VPD appeared to be similar among the different groups (CFM without CL/P, CFM with CL/P, CL/P without CFM). As 15.2% of all CFM patients and 8.5% of CFM patients without CL/P had VPD, it is proposed that all patients with CFM, with or without CL/P, should be assessed by a speech and language therapist for the potential risk of VPD.

Hearing impairment and ear anomalies in craniofacial microsomia: a systematic review.

The aim of this systematic review was to review the literature on hearing impairment and ear anomalies in patients with craniofacial microsomia and to determine their prevalence. Sixty-two records including 5122 patients were included. Ear anomalies were present in 52-100% of patients. The most reported external ear malformations were microtia, pre-auricular tags, and atresia of the external auditory canal. Ossicular anomalies were the most reported middle ear malformations, whereas the most reported inner ear malformations included oval window anomalies, cochlear anomalies, and anomalies of the semicircular canals. Hearing loss in general was reported in 29-100% of patients, which comprised conductive hearing loss, mixed hearing loss, and sensorineural hearing loss. Between 21% and 51% of patients used hearing aids, and 58% underwent a surgical intervention to improve hearing. The relationship between different phenotypes of craniofacial microsomia and the type and severity of hearing loss is mostly unclear. In conclusion, the high prevalence of ear and hearing anomalies in patients with craniofacial microsomia underlines the importance of audiological screening in order to facilitate individual treatment.

Ocular and adnexal anomalies in craniofacial microsomia: Type and prevalence in a multicentre cohort study.

The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development.

Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients.

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n=32) and cardiac (n=13) anomalies were most frequently seen, followed by reproductive system (n=11), central nervous system (n=7), and limb (n=7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001-2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.

Ocular and adnexal anomalies in craniofacial microsomia: a systematic review.

Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7-100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis and strabismus were the most reported type III anomalies, and irregular astigmatism was the most reported type IV ocular anomaly. Visual impairment in general was reported in 8-71.4% of patients, with severe visual impairment in 11.1-71.4% and amblyopia in 16.3%. This study provides a detailed overview of ocular anomalies in CFM and their prevalence. Furthermore, we propose a new classification to organize ocular anomalies into four clinically relevant subtypes. Finally, the high prevalence of ocular anomalies and visual impairment in this study suggests that CFM patients should undergo ophthalmological screening at least once during the sensitive period.

Extracraniofacial anomalies in craniofacial microsomia: retrospective analysis of 991 patients.

Craniofacial microsomia (CFM) is characterized by unilateral or bilateral underdevelopment of the facial structures arising from the first and second pharyngeal arches, but extracraniofacial anomalies may also be present. This retrospective study provides an overview of the prevalence, types, and characteristics of extracraniofacial anomalies in patients with CFM. All patients diagnosed with CFM seen at four craniofacial centres were included. The patient charts were reviewed and data on patient characteristics and extracraniofacial anomalies were extracted. Of the 991 patients included, 462 (47%) had extracraniofacial anomalies. The prevalence of extracraniofacial anomalies in the various tracts was as follows: vertebral 28%, central nervous system 11%, circulatory system 21%, respiratory tract 3%, gastrointestinal tract 9%, and urogenital tract 11%. Compared to patients without extracraniofacial anomalies, those with an extracraniofacial anomaly were at higher risk of having additional extracraniofacial anomalies in other tracts. The prevalence of extracraniofacial anomalies was greater in patients with bilateral CFM, a more severe mandibular deformity, or facial nerve or soft tissue deformity. Patients with CFM should be screened for extracraniofacial anomalies by physical examination with specific attention to the circulatory, renal, and neurological tracts. Diagnostically, electrocardiography, echocardiography, spine radiography, and renal ultrasound should be performed for patients at risk of extracraniofacial anomalies.

Three-dimensional soft tissue prediction in orthognathic surgery: a clinical comparison of Dolphin, ProPlan CMF, and probabilistic finite element modelling.

Three-dimensional surgical planning is used widely in orthognathic surgery. Although numerous computer programs exist, the accuracy of soft tissue prediction remains uncertain. The purpose of this study was to compare the prediction accuracy of Dolphin, ProPlan CMF, and a probabilistic finite element method (PFEM). Seven patients (mean age 18years; five female) who had undergone Le Fort I osteotomy with preoperative and 1-year postoperative cone beam computed tomography (CBCT) were included. The three programs were used for soft tissue prediction using planned and postoperative maxillary position, and these were compared to postoperative CBCT. Accurate predictions were obtained with each program, indicated by root mean square distances: RMSDolphin=1.8±0.8mm, RMSProPlan=1.2±0.4mm, and RMSPFEM=1.3±0.4mm. Dolphin utilizes a landmark-based algorithm allowing for patient-specific bone-to-soft tissue ratios, which works well for cephalometric radiographs but has limited three-dimensional accuracy, whilst ProPlan and PFEM provide better three-dimensional predictions with continuous displacements. Patient or population-specific material properties can be defined in PFEM, while no soft tissue parameters are adjustable in ProPlan. Important clinical considerations are the topological differences between predictions due to the three algorithms, the non-negligible influence of the mismatch between planned and postoperative maxillary position, and the learning curve associated with sophisticated programs like PFEM.

Describing the mandible in patients with craniofacial microsomia based on principal component analysis and thin plate spline video analysis.

Craniofacial microsomia (CFM) is most often described as a unilateral malformation of derivatives of the first and second branchial arches. The mandible has been classified using several classification systems. However, all are based on two-dimensional imaging. The aim of this study was to mathematically describe the deformed mandible based on principal component analysis (PCA) in a three-dimensional way. This may aid in defining the flaws in existing surgical corrections of the mandible through the identification of the differences in shape compared with a normal mandible in a holistic view with the help of videos. Forty-three homologous landmarks were defined to describe a mandible with CFM. Computed tomography scans of 22 patients and 30 controls were marked manually. The changes in shape between the mandibles were visualized using videos. A lateral rotation with increase in posterior rotation of the condyle due to shortening of the condyle-gonial height and a longitudinal rotation with outward bending of the mandibular angle were noted on the affected side, as well as an inward bending of the angle on the unaffected side. Due to the compensatory remodelling of the mandible on the unaffected side, one could suggest that CFM is never truly unilateral.

Central nervous system anomalies in craniofacial microsomia: a systematic review.

Extracraniofacial anomalies, including central nervous system (CNS) anomalies, may occur in craniofacial microsomia (CFM). This systematic review was performed to provide an overview of the literature on the prevalence and types of CNS anomalies and developmental disorders in CFM, in order to improve the recognition and possible treatment of these anomalies. A systematic search was conducted and data on the number of patients, patient characteristics, type and prevalence of CNS anomalies or developmental delay, and correlations between CFM and CNS anomalies were extracted. Sixteen papers were included; 11 of these described developmental disorders. The most common reported anomalies were neural tube defects, corpus callosum agenesis or hypoplasia, intracranial lipoma, Arnold-Chiari malformations, hydrocephaly, ventriculomegaly, and cerebral hypoplasia. The prevalence of CNS anomalies in CFM varied from 2% to 69%. The prevalence of developmental disorders, such as intellectual disability, language or speech developmental delay, and neuropsychomotor delay, varied from 8% to 73%. This study suggests that CNS anomalies and developmental disorders are seen in a substantial proportion of patients with CFM. Further research should focus on determining which features of CFM are correlated with CNS anomalies to allow adequate screening and timely care.

Vertebral anomalies in craniofacial microsomia: a retrospective analysis of 991 patients.

Craniofacial microsomia (CFM) is characterized by an underdevelopment of the facial structures arising from the first and second branchial arches, but extracraniofacial anomalies such as vertebral anomalies may be present. This retrospective study was performed to determine the prevalence and types of vertebral anomalies and the association with other extracraniofacial anomalies in patients with CFM. The charts of all patients diagnosed with CFM seen in four craniofacial centres were reviewed for the presence of vertebral anomalies, symptoms, extracraniofacial anomalies, and the OMENS classification including the Pruzansky-Kaban type of mandibular deformity. A total of 991 patients were included and 28% of the patients had vertebral anomalies. The most common vertebral anomalies included scoliosis, block vertebrae, and hemivertebrae. Only 44% of the patients with vertebral anomalies had clinical symptoms; torticollis, back or neck pain, and limited neck movement were the most frequently seen. The prevalence of vertebral anomalies was greater in patients with bilateral CFM and in patients with a more severe mandibular deformity, and/or orbit, facial nerve, and/or soft tissue involvement. Patients with vertebral anomalies had significantly more extracraniofacial anomalies than patients without vertebral anomalies. Therefore, patients with vertebral anomalies should undergo cardiac, renal, and neurological evaluation.

Vertebral anomalies in craniofacial microsomia: a systematic review.

Craniofacial microsomia (CFM) is characterized by a heterogeneous underdevelopment of the facial structures arising from the first and second branchial arches, but extracraniofacial malformations such as vertebral anomalies also occur. This systematic review provides an overview of the literature on the types and prevalence of vertebral anomalies found in patients with CFM. A systematic search was conducted. Data on the number of patients, patient characteristics, types and prevalence of vertebral anomalies, and other associations between CFM and vertebral anomalies were extracted from the articles identified. Thirty-one articles were included. Seventeen articles described both the prevalence and types of vertebral anomalies in CFM, five articles described solely the types of vertebral anomalies in CFM, and nine articles reported solely the prevalence of vertebral anomalies in CFM. The vertebral anomalies most often reported in CFM are hemivertebrae, block vertebrae, scoliosis/kyphoscoliosis, and spina bifida. These anomalies are mostly present in the cervical and thoracic spine and ribs. The reported prevalence of vertebral anomalies in CFM varies from 8% to 79%. To diagnose vertebral anomalies early in patients with CFM, further research should focus on determining which patients with CFM are at risk of vertebral anomalies.

Obstructive sleep apnoea in craniofacial microsomia: analysis of 755 patients.

A retrospective cohort study was set up to analyse the prevalence and treatment of obstructive sleep apnoea (OSA) in relation to the severity of the deformity in patients with craniofacial microsomia (CFM). This study included a population of 755 patients with CFM from three craniofacial centres. Medical charts were reviewed for severity of the deformity, types of breathing difficulty, age at which breathing difficulty first presented, treatment for OSA, and treatment outcome. In total, 133 patients (17.6%) were diagnosed with OSA. Patients with Pruzansky IIB/III classification or bilateral craniofacial microsomia were significantly more often diagnosed with OSA than unilaterally affected patients of Pruzansky I/IIA classification. The initial treatment of OSA consisted of adenotonsillectomy, tracheotomy, or non-invasive positive pressure ventilation. Thirty-seven patients received more than one treatment (range 1-3). In this study, the prevalence of OSA in patients with CFM was higher than the prevalence in the healthy population described in the literature. Although several treatment modalities are available for the treatment of OSA in patients with CFM, treatment should be individualized and based on clinical symptoms, the severity of the deformity, and comorbidities.

Accuracy of three-dimensional soft tissue prediction for Le Fort I osteotomy using Dolphin 3D software: a pilot study.

Three-dimensional (3D) soft tissue prediction is replacing two-dimensional analysis in planning for orthognathic surgery. The accuracy of different computational models to predict soft tissue changes in 3D, however, is unclear. A retrospective pilot study was implemented to assess the accuracy of Dolphin 3D software in making these predictions. Seven patients who had a single-segment Le Fort I osteotomy and had preoperative (T0) and >6-month postoperative (T1) cone beam computed tomography (CBCT) scans and 3D photographs were included. The actual skeletal change was determined by subtracting the T0 from the T1 CBCT. 3D photographs were overlaid onto the T0 CBCT and virtual skeletal movements equivalent to the achieved repositioning were applied using Dolphin 3D planner. A 3D soft tissue prediction (TP) was generated and differences between the TP and T1 images (error) were measured at 14 points and at the nasolabial angle. A mean linear prediction error of 2.91±2.16mm was found. The mean error at the nasolabial angle was 8.1±5.6°. In conclusion, the ability to accurately predict 3D soft tissue changes after Le Fort I osteotomy using Dolphin 3D software is limited.

Cleft characteristics and treatment outcomes in hemifacial microsomia compared to non-syndromic cleft lip/palate.

The goal of this study was to describe the clinical characteristics and treatment outcomes of patients with hemifacial microsomia (HFM) and cleft lip/palate (CL/P), and to compare them to a historic cohort of patients with non-syndromic CL/P treated at the same centre. A retrospective review of patients with HFM and CL/P was performed; the main outcome measures assessed were cleft type/side, surgical outcome, midfacial retrusion, and speech. Twenty-six patients (13 male, 13 female; mean age 22.7±14.9, range 1-52 years) with cleft lip with/without cleft palate (CL±P) were identified: three with cleft lip (12%), two with cleft lip and alveolus and an intact secondary palate (8%), and 21 with cleft lip and palate (CLP) (81%; 15 unilateral and six bilateral). Four patients (19%) had a palatal fistula after palatoplasty. Twelve of 22 patients aged >5 years (55%) had midfacial retrusion and two (9%) required a pharyngeal flap for velopharyngeal insufficiency (VPI). Fisher's exact test demonstrated a higher frequency of complete labial clefting (P=0.004), CLP (P=0.009), midfacial retrusion (P=0.0009), and postoperative palatal fistula (P=0.03) in HFM compared to non-syndromic CL±P. There was no difference in VPI prevalence. This study revealed that patients with HFM and CL±P have more severe forms of orofacial clefting than patients with non-syndromic CL±P. Patients with HFM and CL±P have more severe midfacial retrusion and a higher palatal fistula rate compared to patients with non-syndromic CL±P.

The prevalence of obstructive sleep apnea in symptomatic patients with syndromic craniosynostosis.

The reported prevalence of obstructive sleep apnea (OSA) in patients with syndromic craniosynostosis (SCS) varies due to inconsistent definitions of OSA, lack of uniform diagnostic testing, and different mixes of syndromic diagnoses. The purpose of this study was to determine the prevalence of OSA in symptomatic patients with SCS, and to determine whether this differs by phenotypic diagnosis. A retrospective cohort study of children with SCS was conducted. The primary outcome was presence of OSA diagnosed by polysomnography. The prevalence of OSA was calculated and stratified by diagnosis to compare differences in prevalence and severity (mild, moderate, or severe). The prevalence of OSA in symptomatic patients was 74.2%. Patients with Apert syndrome had the highest prevalence (80.6%), followed by Pfeiffer, Crouzon with acanthosis nigricans, and Crouzon syndromes (72.7%, 66.7%, and 64.7%, respectively). Severe OSA was most common in patients with Pfeiffer syndrome (45.5%), while patients with Apert and Crouzon syndromes were more likely to have moderate OSA (29.0% and 23.5%, respectively). Given that 56.4% of patients with SCS are symptomatic and that 74.2% of these symptomatic patients have OSA, it is recommended that a screening level I polysomnography be part of the clinical care for all patients with SCS.

Vitamin D metabolism and regulation in pediatric MSCs.

Vitamin D is crucial for mineral homeostasis and contributes to bone metabolism by inducing osteoblast differentiation of marrow stromal cells (MSCs). We recently reported that MSCs from adults demonstrate 1α-hydroxylase activity in vitro and express vitamin D-related genes; this raises a possible autocrine/paracrine role for D activation in pre-osteoblasts. In this studies, we tested the hypotheses that pediatric MSCs have 1α-hydroxylase activity and express vitamin D-related genes. With IRB approval, we isolated MSCs from discarded excess iliac marrow graft from 6 male and 6 female subjects (age 8-12 years) undergoing alveolar cleft repair. 1α-hydroxylation of substrate 25(OH)D3 was measured by ELISA for 1α,25(OH)2D. RT-PCR was used for gene expression. Pediatric MSCs showed a range of 1α-hydroxylase activity in vitro. There was constitutive expression of vitamin D receptor (VDR), megalin, d-hydroxylases (CYP27B1, CYP27A1, CYP2R1, and CYP24A1), and estrogen receptor (ER). There was 2.6-fold greater expression of CYP27B1 and 3.5-fold greater expression of CYP24A1 in MSCs from boys compared with girls. There was 2.4-fold greater expression of ERα and 3.2-fold greater expression of megalin in MSCs from boys. In preliminary studies, treatment of female pediatric MSCs with 10nM 17ß-estradiol resulted in upregulation of CYP27B1 and CYP24A1, as well as VDR, megalin, ERα, and ERß. Treatment with 25(OH)D3 upregulated CYP27B1, VDR, and ERα. Expression and regulation of vitamin D related genes in pediatric hMSCs reinforces an autocrine/paracrine role for vitamin D in hMSCs. Finding striking gender differences in MSCs from children was not seen with MSCs from adults and adds insight to the metabolic environment of bone and presents a research approach for investigating and optimizing pediatric bone health.

Malocclusion in children caused by temporomandibular joint effusion.

Two unusual cases of temporomandibular joint effusion in children are presented. The differential diagnosis, radiographic imaging, treatment, and possible etiologies are described.

Anatomical differences in lower third molars visualized by 2D and 3D X-ray imaging: clinical outcomes after extraction.

The purpose of this study was to evaluate the relationship between third molars and the inferior alveolar canal using panoramic radiographs and cone beam computed tomography (CBCT) scans and to assess clinical outcomes after third molar removal retrospectively. The degree of superimposition, buccolingual position (buccal, central, and lingual) and physical relationship (separation, contact, and involved) were measured using CBCT scanning. Post-extraction complications were recorded. Based on radiographic evaluation, 45.9% of third molar roots were inside the inferior alveolar canal, 21.3% were in contact with the inferior alveolar canal, and 32.8% were separated from the canal. The frequency at which the mandibular canal was separated from the root apex was significantly higher when the canal was in the buccal position (80.0%) than in the central (20.0%) and lingual positions (0.0%). Although on panoramic radiographs all third molars were directly superimposed on the inferior alveolar canal, CBCT showed direct contact or canal involvement in 67.2% and separation of the canal from the root apex in 32.8%. Complications occurred in nine patients: eight had third molar root apices inside or in contact with the inferior alveolar canal. The prevalence of post-extraction complications correlated with the absence of cortication around the inferior alveolar canal.

Facial infiltrating lipomatosis.

Facial infiltrating lipomatosis is a rare congenital disorder in which mature lipocytes invade adjacent tissue. The phenotypic features include soft-tissue and skeletal hypertrophy, premature dental eruption, and regional macrodontia. There is a high risk for regrowth after resection that is, perforce, subtotal. The etiology, natural history, optimal management, and relationship to other disorders of fatty overgrowth are unclear. In this study, the clinical features, radiographic findings, histopathology, and postoperative results were analyzed in 13 patients with facial infiltrating lipomatosis. The condition was diagnosed in infancy (eight male subjects, five female subjects) and characterized by enlargement of the cheek (n = 12) or chin (n = 1). Other findings included cutaneous capillary blush (n = 9), ipsilateral macroglossia (n = 8), and mucosal neuromas (n = 6). Most patients had early eruption of ipsilateral deciduous and permanent teeth (n = 12). Computed tomography and magnetic resonance imaging showed an infiltrated soft-tissue mass of fatty density (n = 13) and skeletal overgrowth (n = 9). Multiple resection was performed on six patients (mean number of operations per patient, 2.5; range, one to six operations); regrowth and/or worsening of the capillary stain occurred in all six patients. Because surgical removal of the mass is usually unsuccessful, specific management of this condition will require insight into its etiopathogenesis. Given the presence of mucosal neuromas and lipomatosis, this study included testing for the known mutations in three entities that are associated with these soft-tissue findings (Cowden syndrome, Bannayan-Riley-Ruvalcava syndrome, and multiple endocrine neoplasia type 2B). Results of DNA analyses for these germline mutations were negative. It is more likely that this disorder is caused by a somatic mutation involving a local increase in growth factor(s).