Mathijssen, I.M.J.

Unilateral versus bilateral correction of unicoronal synostosis: An analysis of long-term results (Article)

2013-05-01T00:00:00Z

Introduction: Hollowing of the temporal region is a common problem after cranioplasty for unicoronal synostosis. In this study, first, the development of temporal hollowing pre- and postoperatively is evaluated. Second, the origin of temporal hollowing is investigated by comparing two operative techniques. Ultimately, the relation between timing of surgery and the development of hollowing is investigated. Methods: From 1979 to 2010, 194 patients with unicoronal synostosis were operated at our center. Patients were treated with a unilateral or bilateral correction of the supraorbital rim. A total of 48 patients qualified for the present study. Mean age at follow-up was 7.5 years. Cephalic landmarks were identified on radiographs prior to and after surgery to determine the growth of the forehead. For visual analysis, two independent observers evaluated normal photographs for the presence and severity of temporal hollowing. Results: Preoperative osseous asymmetry improved significantly after surgery. A total of 21 patients show an increase of temporal hollowing on photographs after surgery (46%). In 35 out of 48 patients, postoperative temporal hollowing was noted (73%). Bilaterally treated patients showed more severe temporal hollowing compared to unilaterally treated patients, though not significantly (23% vs. 6%, p = 0.229). Timing of surgery (before or after the age of 1 year) did not influence the occurrence of severe temporal hollowing. Conclusions: Fronto-supraorbital advancement was unable to achieve normal growth in the temporal region in a large proportion of patients, although more symmetry was achieved. The operative technique itself did not seem to influence the occurrence of temporal hollowing, nor did the timing of surgery.

Spring-assisted posterior vault expansion in multisuture craniosynostosis (Article)

2013-05-01T00:00:00Z

Purpose: Patients with Apert and Crouzon syndromes and craniofrontonasal dysplasia need a vault expansion within the first year of life to treat or prevent the development of raised intracranial pressure. Many craniofacial units perform a conventional posterior vault expansion as initial surgery; an alternative to this technique is the spring-assisted posterior vault expansion. The purpose of this study was to demonstrate the efficacy of spring-assisted posterior vault expansion and to compare this technique with the conventional method. Methods: A retrospective study was conducted among all consecutive patients who received a posterior vault expansion between 2006 and 2011. Patients treated with springs were compared with patients treated with the conventional technique for blood loss, duration of surgery, postoperative hospital admittance, increase in skull circumference and anterior-posterior length, and complications. Results: Of the 31 included patients, 15 were treated with springs, and 16, with the conventional technique. Patients treated with springs had a significantly larger increase in skull circumference and anterior-posterior length, and not significant changes in blood loss compared with the conventional group. Complications in the conventional group were the following: minor dural tear in three patients, problematic wound healing in one patient, and insufficient expansion in one patient. Spring-related complications included skin perforation in two patients, a minor dural tear in two patients, and leakage of cerebrospinal fluid after an unnoticed dural tear during spring placement in one patient. Conclusion: Spring-assisted posterior vault expansion has some advantages over the conventional technique and is, therefore, the preferred technique in our center.

Long-term assessment of facial features and functions needing more attention in treatment of Treacher Collins syndrome (Article)

2013-04-22T00:00:00Z

Aim: This study aimed to determine which facial features and functions need more attention during surgical treatment of Treacher Collins syndrome (TCS) in the long term. Method: A cross-sectional cohort study was conducted to compare 23 TCS patients with 206 controls (all ≥18 years) regarding satisfaction with their face. The adjusted Body Cathexis Scale was used to determine satisfaction with the appearance of the different facial features and functions. Desire for further treatment of these items was questioned. For each patient an overview was made of all facial operations performed, the affected facial features and the objective severity of the facial deformities. Results: Patients were least satisfied with the appearance of the ears, facial profile and eyelids and with the functions hearing and nasal patency (P < 0.001). Residual deformity of the reconstructed facial areas remained a problem in mainly the orbital area. The desire for further treatment and dissatisfaction was high in the operated patients, predominantly for eyelid reconstructions. Another significant wish was for improvement of hearing. Conclusion: In patients with TCS, functional deficits of the face are shown to be as important as the facial appearance. Particularly nasal patency and hearing are frequently impaired and require routine screening and treatment from intake onwards. Furthermore, correction of ear deformities and midface hypoplasia should be offered and performed more frequently. Residual deformity and dissatisfaction remains a problem, especially in reconstructed eyelids. Level of evidence: II.

Cellular interference in craniofrontonasal syndrome: Males mosaic for mutations in the x-linked EFNB1 gene are more severely affected than true hemizygotes (Article)

2013-04-01T00:00:00Z

Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundariesa process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5 untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69. The 5 UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females. © The Author 2013. Published by Oxford University Press. All rights reserved.

Orbital aspects following monobloc advancement in syndromic craniosynostosis (Article)

2013-01-25T00:00:00Z

The monobloc advancement with distraction is a treatment modality for syndromic craniosynostosis, to correct exorbitism, upper airway compromise and malocclusion. In this report orbital volume and movements of (peri-)orbital structures and globes of seven patients following monobloc distraction are evaluated. In preoperative and postoperative CT-scans orbital volume was assessed and a 3D coordinate system with eleven landmarks was used to measure the movements of orbital structures and globes and to measure the change of exorbitism. Correlation between orbital volume, movements of the orbital structures and change in exorbitism was studied. The orbital volume increased by 49.9% (left) and 50.4% (right). The average anterior movement of the bone was 13.6 mm (left) and 13.9 mm (right). The mean anterior movement of the left globe was 5.8 mm and of the right globe 5.3 mm. The ratio of globe/bone movement was 0.4. Exorbitism decreased with 7.8 mm (left) and 8.1 mm (right). Differences between left and right for orbital volume, for movements and for the decrease in exorbitism were not significant. Volume enlargement and decrease in exorbitism were correlated (p ≤ 0.05). Following monobloc advancement orbital volume increases, (peri-)orbital structures and the globe move forward and exorbitism diminishes.

I'm perfect (Inaugural Lecture)

2012-10-12T00:00:00Z

Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Plastische Chirurgie, in het bijzonder Craniofaciale Afwijkingen aan het Erasmus MC, Faculteit van de Erasmus Universiteit Rotterdam

Assessing nonacceptance of the facial appearance in adult patients after complete treatment of their rare facial cleft (Article)

2012-08-01T00:00:00Z

Background Treatment of patients with severe congenital facial disfigurements is aimed at restoring an aesthetic and functional balance. Besides an adequate level of satisfaction, an individual's acceptance of facial appearance is important to achieve because nonacceptance is thought to lead to daily psychological struggles. This study objectified the prevalence of nonacceptance among adult patients treated for their severe facial clefts, evaluated risk factors, and developed a screening tool. Methods The study included 59 adults with completed treatment for their severe facial cleft. All the patients underwent a semistructured in-depth interview and filled out the Body Cathexis Scale. Results Nonacceptance of facial appearance was experienced by 44 % of the patients. Of the nonaccepting patients, 72 % experienced difficulties in everyday activities related to their appearance versus 35 % of the accepting patients. Acceptance did not correlate with objective severity or bullying in the past. Risk factors for nonacceptance were high self-perceived visibility, a troublesome puberty period, and an emotion-focused coping strategy. Also, the presence of functional problems was shown to be highly associated. Conclusions The objective severity of the residual deformity did not correlate with the patients' acceptance of their facial appearance, but the self-perceived visibility did correlate. The process of nonacceptance resembles the process seen in patients with body dysmorphic disorders. Surgical treatment is no guarantee for an improvement in acceptance and is therefore discouraged for patients who match the risk factors for nonacceptance unless it solves a functional problem. The authors therefore recommend screening patients for nonacceptance and considering psychological treatment before surgery is performed. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Long-term psychological functioning of adults with severe congenital facial disfigurement (Article)

2012-01-01T00:00:00Z

BACKGROUND: In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a non-facially disfigured reference group. Also explored is the extent to which psychological functioning of the congenital group is related to satisfaction with facial appearance, fear of negative appearance evaluation by others, self-esteem, and severity of the facial deformity. METHODS: Fifty-nine adults with severe congenital facial disfigurement, 59 adults with a traumatically acquired facial deformity in adulthood, and 120 non-facially disfigured adults completed standardized psychological, physical, and demographic questionnaires, including the Fear of Negative Appearance Evaluation Scale, the Rosenberg Self-Esteem Scale, the Hospital Anxiety and Depression Scale, the Achenbach Adult Self-Report, the 36-Item Short-Form Health Survey, and a visual analogue scale. RESULTS: Adults with severe congenital facial disfigurement had relatively normal psychological functioning but appeared more prone to internalizing problems than the non-facially disfigured adults. Compared with patients with an acquired facial deformity, the congenital group displayed fewer problems on the physical component score of quality of life only. Satisfaction with facial appearance, fear of negative appearance evaluation, and self-esteem were good predictors of the different aspects of psychological functioning, with the exception of the physical component score of quality of life. CONCLUSIONS: Improving satisfaction with facial appearance (by surgery), enhancing self-esteem, or lowering fear of negative appearance evaluation (by psychological support) may enhance long-term psychological functioning. Future research should focus on the individual patient and risk factors for maladjustment. Copyright

Brain and ventricular volume in patients with syndromic and complex craniosynostosis (Article)

2012-01-01T00:00:00Z

Purpose: Brain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have normal brain volumes. The purpose of this study was to evaluate brain and ventricular volume measurements in patients with syndromic and complex craniosynostosis. This knowledge will improve our understanding of brain development and the origin of raised intracranial pressure in syndromic craniosynostosis. Methods: Brain and ventricular volumes were calculated from MRI scans of patients with craniosynostosis, 0.3 to 18.3 years of age. Brain volume was compared to age matched controls from the literature. All patient charts were reviewed to look for possible predictors of brain and ventricular volume. Results: Total brain volume in syndromic craniosynostosis equals that of normal controls, in the age range of 1 to 12 years. Brain growth occurred particularly in the first 5 years of age, after which it stabilized. Within the studied population, ventricular volume was significantly larger in Apert syndrome compared to all other syndromes and in patients with a Chiari I malformation. Conclusions: Patients with syndromic craniosynostosis have a normal total brain volume compared to normal controls. Increased ventricular volume is associated with Apert syndrome and Chiari I malformations, which is most commonly found in Crouzon syndrome. We advice screening of all patients with Apert and Crouzon syndrome for the development of enlarged ventricle volume and the presence of a Chiari I malformation.

Assessment of white matter microstructural integrity in children with syndromic craniosynostosis: A diffusion-tensor imaging study (Article)

2011-11-01T00:00:00Z

Purpose: To assess whether architectural alterations exist in the white matter of patients with syndromic and complex craniosynostosis. Materials and Methods: The medical ethics committee approved this study. Written informed consent was obtained from parents or guardians before imaging. A prospective study was performed in children with syndromic and complex craniosynostosis aged 6-14 years. Forty-five patients were included: four had Apert syndrome, 14 had Crouzon-Pfeiffer syndrome , eight had Muenke syndrome, 11 had Saethre-Chotzen syndrome, and eight had complex craniosynostosis. In addition, seven control subjects were evaluated. For diffusiontensor imaging, an echo-planar sequence was used with a diffusion gradient(b = 1000 sec/mm2) applied in 25 noncollinear directions. Regions of interest (ROIs) were placed in the following white matter structures: pontine crossing tract, corticospinal tracts, medial cerebral peduncles, uncinate fasciculus (measured bilaterally), anterior commissure, frontal and occipital white matter (measured bilaterally), fornix, corpus callosum (measured in the genu and splenium), and corpus cingulum (measured bilaterally). Eigenvalues were measured in all ROIs and fractional anisotropy (FA) was calculated. Results: Across all measured ROIs, FA values were generally lower in all patients combined than in the control subjects(P < .001). There were no significant differences among subgroups of patients. Conclusion: Diffusion-tensor imaging measurements of white matter tracts reveal significant white matter integrity differences between children with craniosynostosis and healthy control subjects. This could imply that the developmental delays seen in these patients could be caused by the presence of a primary disorder of the white matter microarchitecture.

Long-term results after 40 years experience with treatment of rare facial clefts: Part 2 - Symmetrical median clefts (Article)

2011-10-01T00:00:00Z

Background: Median facial clefts are reconstructive challenges, requiring multiple operations throughout life. Long-term results are often still far from ideal and could be improved. Due to surgical intervention and diminished intrinsic growth potential, surgical results may change from initially good into a progressively disappointing outcome. If, however, the ideal timing and type of surgery are known, in combination with the intrinsic growth potential, the results can be ameliorated. A guideline for surgical treatment is given. Methods: Twenty patients with a pure symmetrical median cleft were evaluated on intermediate and long-term surgical results. The final result was scored based on severity of the initial and the remaining facial deformities, and the need for revisional surgery. Results: The long-term surgical outcome was initially good for each of the affected facial parts and the face in general, but worsened over time, especially in the zone of the nose. An adequate and stable result of hypertelorism correction was observed for both the orbital box osteotomy and medial faciotomy, even when performed at a young age. Conclusions: The intrinsic growth restriction is mainly localised in the central midface. This leads to a complex and often unpredictable growth of the maturing face. It makes it difficult to achieve perfect reconstructions. Caution with surgical interventions of the nose at a young age is required. Once the face has matured, a midface advancement and secondary nose correction should be considered for satisfactory projection. Early referral to a specialised centre is essential.

Long-term results after 40 years experience with treatment of rare facial clefts: Part 1-oblique and paramedian clefts (Article)

2011-10-01T00:00:00Z

Background: Oblique and paramedian rare facial clefts impose a major reconstructive challenge and long-term assessments of the outcomes remain scarce. This study provides new details regarding surgical techniques and timing, influence of growth, and difficulties of this pathology on the long-term; a guideline for surgical treatment is given. Methods: Twenty-nine adults with an oblique or paramedian facial cleft and surgically treated in the authors' unit between 1969 and 2009, were included. The long-term evaluation was based on series of photographs, 3D-CT's, X-rays, operation data, and was specified per facial area. Results: The mean number of performed operations per patient was 10.6 (range: 1-26). Vertical dystopia is not caused by previous surgery, but by growth deficiencies of the maxilla. In all patients with vertical dystopia, its presence and severity were clear at the age of five, and it should ideally be treated shortly after that age. In mild cases grafting seems sufficient, but in more severe cases orbital translocation is necessary. Costochondral grafts showed the best long-term results in both orbital and nasal reconstructions. Major nose reconstruction is best delayed until adolescence. For an optimal final result in selected cases, correction of midface hypoplasia at adolescence is necessary. Conclusion: The three-dimensional underdevelopment of the midface region plays a central role in the deformities of most patients, but is complex and difficult to correct. The provided guideline should help to minimize the number of operations and ameliorate long-term results.

Are ultrasonography measurements of optic nerve sheath diameter an alternative to funduscopy in children with syndromic craniosynostosis? Clinical article (Article)

2011-09-01T00:00:00Z

Object. Children with syndromic or complex craniosynostosis are evaluated for increased intracranial pressure (ICP) using funduscopy to detect papilledema. However, papilledema is a late sign of increased ICP. Because papilledema might be preceded by an increase in optic nerve sheath (ONS) diameter, the authors conducted a prospective study to establish the validity and applicability of measuring the ONS using ultrasonography. Methods. From January 2007 to December 2009, 175 bilateral ultrasonography ONS measurements were performed in 128 patients with syndromic or complex craniosynostosis during the daytime. The measurements were correlated with ONS diameter assessed on CT and simultaneous funduscopy, when available. Furthermore, results were compared by using thresholds for ONS diameters on ultrasonography that are available in the literature. Results. The mean ONS diameter on ultrasonography was 3.1 &πλυσμν; 0.5 mm. The CT measurement was significantly correlated with the ultrasonography measurement (r = 0.41, p < 0.001). The mean ONS diameter in 38 eyes with papilledema was 3.3 &πλυσμν; 0.5 mm, compared with 3.1 &πλυσμν; 0.5 mm in the eyes of patients without papilledema (p = 0.039). Relative to the age-related thresholds, the ONS diameter was too large in 11 eyes (3%), particularly in patients with Crouzon syndrome. Compared with funduscopy, ultrasonography sensitivity was 11%, specificity was 97%, and positive and negative predictive values were 40% and 86%, respectively. Conclusions. Ultrasonography is a valid and easy way of quantifying the ONS. Although the ONS diameter is larger in children with papilledema, it cannot be used as a daytime screening tool instead of funduscopy. The ONS diameter is possibly a more real-time indicator of ICP.

Audiological profile of children and young adults with syndromic and complex craniosynostosis (Article)

2011-08-01T00:00:00Z

Objectives: To determine syndrome-specific type, severity, and prevalence of hearing loss to facilitate follow-up and treatment. Design: Tertiary pediatric hospital craniofacial clinic survey study. If insufficient or no data were available for a child, he or she was referred to an audiologist for puretone audiometry. Setting: Academic research facility. Patients: Information was gathered regarding 132 children and young adults with craniosynostosis. Main Outcome Measures: The primary outcome was hearing assessment of children and young adults with various types of craniosynostosis. A secondary outcome was inference regarding the incidence of otitis media among children and young adults with craniosynostosis. Results: We found mild or moderate hearing loss in 44.0% of patients with Apert syndrome, in 28.5% with Crouzon syndrome, in 62.1% with Muenke syndrome, in 28.6% with Saethre-Chotzen syndrome, and in 6.7% with complex craniosynostosis. Hearing loss was conductive in most patients with Apert, Crouzon, and Saethre- Chotzen syndromes and it was predominantly sensorineural in patients with Muenke syndrome. Sensorineural hearing loss at lower frequencies was found only in patients with Muenke syndrome. Conclusions: Most patients with syndromic and complex craniosynostosis have recurrent otitis media with effusion, causing episodes of conductive hearing loss throughout their lives. Sensorineural hearing loss can occur in all 4 syndromes studied but is the primary cause of hearing loss in children and young adults with Muenke syndrome. For patients with these syndromes, we recommend routine visits to the general practitioner or otolaryngologist, depending on national standards of care, to screen for otitis media with effusion throughout life. We also advise early screening for sensorineural hearing loss among children and young adults with these syndromes.

Obstructive sleep apnea-specific quality of life and behavioral problems in children with syndromic craniosynostosis (Article)

2011-04-01T00:00:00Z

Objective: This study aimed at evaluating the impact of syndromic craniosynostosis on quality of life, assessing the association between the presence of craniosynostosis syndrome and prevalence of behavioral problems and assessing the impact of obstructive sleep apnea (OSA) in syndromic craniosynostosis compared with healthy controls. Method: A prospective study was carried out using the Obstructive Sleep Apnea-18 (OSA-18) survey and Child Behavior Checklist (CBCL) in 119 syndromic craniosynostosis patients and the OSA-18 survey in 459 controls. The craniosynostosis population underwent a polysomnography to diagnose OSA. Results: The total OSA-18 score and scores on the domains sleep disturbance, physical suffering, and caregiver concerns were significantly higher in the craniosynostosis group than in controls. Subgroup analysis revealed behavioral problems in 67% and 50% of boys with Apert and Muenke syndrome, respectively. Correlations between obstructive apnea-hypopnea index and total OSA-18 and CBCL scores were significant. Mean scores for the domains sleep disturbance and physical suffering were significantly higher in moderate OSA. Conclusions: OSA is related with a lower quality of life in children with syndromic craniosynostosis. Behavioral problems were more common in boys with Apert and Muenke syndrome. OSA-18 and CBCL scores were correlated with OSA severity. Copyright

Additional phenotypic features of Muenke syndrome in 2 Dutch families (Article)

2011-03-01T00:00:00Z

In about 30% of the patients with syndromal craniosynostosis, a genetic mutation can be traced. For the purpose of adequate genetic counseling and treatment of these patients, the full spectrum of clinical findings for each specific mutation needs to be appreciated. The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. A number of studies on the relationship between genotype and phenotype concerning this specific mutation have been published. Two Dutch families with Muenke syndrome were screened for the reported characteristics of this syndrome and for additional features. New phenotypical findings were hypoplasia of the frontal sinus, ptosis of the upper eyelids, dysplastic elbow joints with restricted elbow motion, and mild cutaneous syndactyly. Incidentally, polydactyly, severe ankylosis of the elbow, fusion of cervical vertebrae, and epilepsy were found. Upper eyelid ptosis is thought to be pathognomonic for Saethre-Chotzen syndrome but was also observed in our series of patients with Muenke syndrome. Because Muenke and Saethre-Chotzen syndrome can have similar phenotypes, DNA analysis is needed to distinguish between these syndromes, even when a syndrome diagnosis is already made in a family member. Copyright

Decision making in reconstruction of defects of the eyelid (Article)

2011-02-01T00:00:00Z

We present three patients with major defects of the eyelid who subsequently had them reconstructed. They included a defect of the lateral upper lid, a defect of the medial upper and lower lids, and a defect of the medial lower lid, cheek, and nose.

Vertical position of the orbits in nonsyndromic plagiocephaly in childhood and its relation to vertical strabismus (Article)

2011-01-01T00:00:00Z

Purpose: To determine the existence of a correlation between the vertical angle of strabismus and the vertical angle between the orbital axes in nonsyndromic plagiocephaly in childhood. Methods: Patients were included when diagnosed with plagiocephaly. Orthoptic measurements showed a vertical strabismus and three-dimensional computed tomographic (CT) imaging of the skull was available. Patients were excluded if plagiocephaly was part of a syndrome or if any surgical intervention had taken place before our measurements. Three-dimensional CT imaging was used to calculate the vertical angle between the orbital axes in 3 reference planes (VAO) perpendicular to a line of reference through the lower borders of the maxilla (VAOmax), both auditory canals (VAOaud), and the lower points of the external occipital protuberances (VAOocc). Results: Fourteen patients were included (mean age, 14 mo). Three-dimensional CT measurements showed a mean (SD) VAOmax of 1.70 (2.31) degrees, VAOaud of -1.54 (1.46) degrees, and VAOocc of -2.06 (4.29) degrees (a negative value indicates that the eye on the affected side was situated lower in the head). The mean vertical angle of strabismus was -2.39 (4.69) degrees in gaze toward the affected side, 3.66 (3.77) degrees in gaze ahead, and 8.14 (5.63) degrees in gaze toward the nonaffected side. The Pearson test showed no significant correlations. Conclusions: The clinical observation that vertical strabismus in adult plagiocephaly is correlated with the vertical angle of the orbital axes could not be confirmed in young children. Copyright

Health-related quality of life in children and adolescents with syndromic craniosynostosis (Article)

2010-12-01T00:00:00Z

Syndromic craniosynostosis is a congenital disorder characterised by premature fusion of calvarial sutures combined with other anomalies. The facial appearance is different and patients may show physical impairment, mental or developmental disabilities, elevated intracranial pressure and obstructive sleep apnoea. The impact of this condition on daily functioning has not been studied before. The aim of this study is to assess the health-related quality of life in children and adolescents with syndromic or complex craniosynostosis and to determine the impact of these syndromes on parents. A prospective study was performed in 111 children. Health-related quality of life was measured by international standardised quality-of-life questionnaires, the Infant Toddler Quality of Life Questionnaire (ITQoL), Child Health Questionnaire Parental Form 50 (CHQ-PF50), Child Health Questionnaire Child Form 87 (CHQ-CF87) and Short-Form Health Survey (SF-36). For comparison, we used Dutch population norms of health-related quality-of-life-scores. Parents' scores for patients with syndromic or complex craniosynostosis were significantly lower than those for the norm population. Apert syndrome had the largest impact on the different domains. Scores on the CHQ-PF50 scales for 'physical functioning', 'parental impact emotional' and 'family activities' for these patients were significantly lower than scores for patients with other syndromes, possibly due to the complexity of the syndrome, which includes complex syndactyly, cognitive impairment and behaviour problems. Parents reported a reduced health-related quality of life for themselves, mostly psychosocial with clearly significantly lower general health perceptions. In conclusion, syndromic craniosynostosis has a large impact on the health-related quality of life of these children and their parents, both physical and psychosocial.

Satisfaction with facial appearance and its determinants in adults with severe congenital facial disfigurement: A case-referent study (Article)

2010-10-01T00:00:00Z

Background: Patients with severe congenital facial disfigurement have a long track record of operations and hospital visits by the time they are 18 years old. The fact that their facial deformity is congenital may have an impact on how satisfied these patients are with their appearance. This study evaluated the level of satisfaction with facial appearance of congenital and of acquired facially disfigured adults, and explored demographic, physical and psychological determinants of this satisfaction. Differences compared with non-disfigured adults were examined. Methods: Fifty-nine adults with a rare facial cleft, 59 adults with a facial deformity traumatically acquired in adulthood, and a reference group of 201 non-disfigured adults completed standardised demographic, physical and psychological questionnaires. Results: The congenital and acquired groups did not differ significantly in the level of satisfaction with facial appearance, but both were significantly less satisfied than the reference group. In facially disfigured adults, level of education, number of affected facial parts and facial function were determinants of the level of satisfaction. High fear of negative appearance evaluation by others (FNAE) and low self-esteem (SE) were strong psychological determinants. Although FNAE was higher in both patient groups, SE was similar in all three groups. Conclusion: Satisfaction with facial appearance of individuals with a congenital or acquired facial deformity is similar and will seldom reach the level of satisfaction of non-disfigured persons. A combination of surgical correction (with attention for facial profile and restoring facial functions) and psychological help (to increase SE and lower FNAE) may improve patient satisfaction.

Long-term functional outcome in 167 patients with syndromic craniosynostosis; Defining a syndrome-specific risk profile (Article)

2010-10-01T00:00:00Z

Objective: Little is known about the long-term prevalence of elevated intracranial pressure (ICP), obstructive sleep apnoea (OSA), level of education, language and motor skills, impaired sight and hearing in craniosynostosis syndromes. The objective of this study was to define the prevalence per syndrome of elevated ICP, OSA, impaired sight and impaired hearing. Methods: A retrospective study was undertaken on 167 consecutive patients diagnosed with Apert, Crouzon, Pfeiffer, Muenke or Saethre-Chotzen syndrome, aged 1-25 years and treated between 1983 and 2008. The mean age at time of referral and review was 1 years and 2 months and 10 years and 3 months, respectively. Results: Patients with Apert and Crouzon/Pfeiffer syndromes had the highest prevalence of elevated ICP (33% and 53%, respectively) and OSA (31% and 27%, respectively), while Saethre-Chotzen syndrome was also associated with a fair risk for elevated ICP (21%). The prevalence of impaired sight (61%) and hearing (56%) was high in all syndromes. Conclusion: Based on these data, a syndrome-specific risk profile with suggestions for screening and treatment is presented.

Use of ambulatory polysomnography in children with syndromic craniosynostosis (Article)

2010-09-01T00:00:00Z

Children with syndromic or complex craniosynostosis are at risk of developing obstructive sleep apnea (OSA) because of midface hypoplasia and collapse of the pharynx. The criterion standard in diagnosing OSA is polysomnography. The aims of this study were to analyze the feasibility of a home cardiorespiratory monitor in children with syndromic or complex craniosynostosis and to analyze whether oximetry alone or the sum of the amplitudes of the thoracic and abdominal movements (X flow) are valuable alternative assessments to diagnose OSA at home, when complete recording was not achieved.We performed a prospective study of 129 children and analyzed 200 different ambulatory polysomnographies.In 41% of the measurements, a complete analysis of the obstructive apnea-hypopnea index was possible based on the adequate recording of all sensors. Oximetry in comparison with polysomnography had a positive predictive value of 82% and a negative predictive value of 79% for diagnosing OSA. Moderate OSA could be excluded with a negative oximetry. Comparing the X flow and the nasal flow signals that the hypopneas were adequately recorded in 86% and the obstructive apneas in 55%, resulting in an underestimation of the severity of OSA in 10%.In conclusion, in children with syndromic or complex craniosynostosis, diagnosing OSA using home cardiorespiratory monitoring is feasible. Oximetry alone can be used as a rough estimate screening, and with a negative test result, moderate OSA can be excluded. X flow can be helpful in diagnosing OSA in the absence of nasal flow. Copyright

Guidelines for reconstruction of the eyelids and canthal regions (Article)

2010-09-01T00:00:00Z

A large number of reports are available on the options for reconstructing specific defects of the eyelids or (peri) orbital area, which may complicate decision making in choosing the most optimal technique for a particular defect. Based on more than 40 years' experience in reconstruction of eyelids and periorbital defects, combined with an extensive literature review, general principles on reconstruction are presented and illustrated. Surgical techniques are outlined with respect to anatomical layer, depth, size and location of the defect. Adherence to specific principles for eyelid and canthal reconstruction will lead to predictable, stable and functionally good results.

Three-dimensional airway changes after le fort III advancement in syndromic craniosynostosis patients (Article)

2010-08-01T00:00:00Z

Background: To investigate the changes of upper airway volume in syndromic craniosynostosis patients following Le Fort III advancement, computed tomographic scans were analyzed and related to the amount of advancement. Methods: In this retrospective study, the preoperative and postoperative computed tomographic scans of 19 patients with syndromic craniosynostosis who underwent Le Fort III advancement were analyzed. In four cases, preoperative polysomnography demonstrated obstructive sleep apnea. The airway was segmented using a semiautomatic region growing method with a fixed Hounsfield threshold value. Airway volumes of hypopharynx and oropharynx (compartment A) and nasopharynx and nasal cavity (compartment B) were analyzed separately, as was the total airway volume. Advancement of the midface was recorded using lateral skull radiographs. Data were analyzed for all patients together and for patients with Crouzon/Pfeiffer and Apert syndromes separately. Results: Airway volume increased significantly in compartment A (20 percent; p = 0.044) and compartment B (48 percent; p < 0.001), as did total airway volume in (37 percent; p < 0.001) in the total study group. No significant differences in volume changes were found comparing Apert with Crouzon/Pfeiffer patients. No distinct relation could be found between advancement of the midface and volume gain either in the total study group or in Apert and Crouzon/Pfeiffer patient groups separately. Postoperative polysomnography showed significant improvement of obstructive sleep apnea in all four patients. Conclusions: A significant improvement of the upper airway after Le Fort III advancement in syndromic craniosynostosis patients is demonstrated. No distinct relation could be observed between advancement and airway volume changes. Copyright

Letters to the editor (Letter To Editor)

2010-07-01T00:00:00Z

Can parents predict obstructive sleep apnea in children with syndromic or complex craniosynostosis? (Article)

2010-05-01T00:00:00Z

Obstructive sleep apnea (OSA) is a clinical syndrome characterized by snoring, apneas and difficulty in breathing. These symptoms can be rated and a risk score (Brouillette score) can be calculated to estimate the likelihood of OSA. This study aimed at establishing the predictive value of the Brouillette score and observation by parents at home in children with syndromic or complex craniosynostosis, compared with ambulatory polysomnography. This prospective study included 78 patients (37 boys, mean age 7.3 years). Sensitivity and negative predictive values were calculated. Polysomnography showed clinically significant OSA in 11 children. The Brouillette score had a negative predictive value of 90% and a sensitivity of 55% in comparison with polysomnography. More than three-quarters of all patients snored. The single question 'Is there difficulty with breathing during sleep?' showed a sensitivity of 64% and a high negative predictive value of 91%. Thus, asking parents whether the child has difficulty in breathing during sleep can exclude the presence of clinical significant OSA and avoid polysomnography in children with syndromic and complex craniosynostosis.

Internal carotid dissection after Le Fort III distraction in Apert syndrome: A case report (Article)

2010-03-18T00:00:00Z

A 10-year-old girl with Apert syndrome underwent a Le Fort III osteotomy with the positioning of internal and external distraction devices. The operation was straightforward with no intraoperative complications. Very soon after completion of surgery an anisocoria (unilateral dilation of a pupil) was noticed. This was followed by intracranial oedema which was fatal. The aetiology was dissection of the right internal carotid artery is reported. The complications of Le Fort osteotomies are discussed regarding patients with complex syndromal craniosynostosis and midface hypoplasia, such as Apert syndrome.

Obstructive sleep apnea in children with syndromic craniosynostosis: long-term respiratory outcome of midface advancement (Article)

2010-02-01T00:00:00Z

Almost 50% of patients with Apert, Crouzon or Pfeiffer syndrome develop obstructive sleep apnea (OSA), mainly due to midface hypoplasia. Midface advancement is often the treatment of choice, but the few papers on long-term outcome report mixed results. This paper aimed to assess the long-term respiratory outcome of midface advancement in syndromic craniosynostosis with OSA and to determine factors contributing to its efficacy. A retrospective study was performed on 11 patients with moderate or severe OSA, requiring oxygen, continuous positive airway pressure (CPAP), or tracheostomy. Clinical symptoms, results of polysomnography, endoscopy and digital volume measurement of the upper airways on CT scan before and after midface advancement were reviewed. Midface advancement had a good respiratory outcome in the short term in 6 patients and was ineffective in 5. In all patients without respiratory effect or with relapse, endoscopy showed obstruction of the rhino- or hypopharynx. The volume measurements supported the clinical and endoscopic outcome. Despite midface advancement, long-term dependence on, or indication for, CPAP or tracheostomy was maintained in 5 of 11 patients. Pharyngeal collapse appeared to play a role in OSA. Endoscopy before midface advancement is recommended to identify airway obstruction that may interfere with respiratory improvement after midface advancement.

Papilledema in isolated single-suture craniosynostosis: Prevalence and predictive factors (Article)

2010-01-01T00:00:00Z

The purpose of this retrospective study was to assess the prevalence of papilledema in patients with isolated craniosynostosis. Second, we wanted to assess if the presence of ventricular dilatation on computed tomography (CT) scan is a predictive factor for the occurrence of papilledema.We included 205 consecutive children with an isolated single-suture craniosynostosis, who had at least 1 fundus examination. Preoperative CT scans of the brain were examined for the presence of ventricular dilatation.Papilledema developed in 14 of 205 patients: 10 developed papilledema before surgery and 4 during the follow-up period. Ten of the patients with papilledema had a synostosis of the sagittal suture, and 4 of the metopic suture. Prevalence of papilledema in scaphocephaly was 9.7%, and in trigonocephaly, 5.6%. Based on evaluation of all CT scans, ventricular dilatation seemed not to be a predictive factor for papilledema in children with isolated craniosynostosis.The incidence of papilledema in almost 10% of scaphocephaly patients is remarkably higher than expected. Therefore, we recommend routine preoperative screening, especially for patients with scaphocephaly, but also for patients with trigonocephaly. Postoperative screening is recommended in all patients when there is any uncertainty.

Reconstruction of an extensive traumatic hemipelvectomy defect using a free lower leg fillet flap (Article)

2010-01-01T00:00:00Z

Distraction assisted treatment of a unilateral complex facial cleft (Article)

2009-07-01T00:00:00Z

Unilateral maxillary hypoplasia is a characteristic feature of an oblique facial cleft. This three-dimensional shortage of osseous structures and soft tissue becomes more prominent over the years and is difficult to correct. The authors describe a 17-year-old boy born with a unilateral nasomaxillary dysplasia and nasal dysplasia (Tessier type 1, 2, 3) who underwent a hemi-Le Fort III distraction with a rigid external distraction (RED) system. This distraction, in combination with initial peroperative advancement and retained with elastic traction with a facial mask, achieved a substantial horizontal improvement of the hemi-midface; this resulted in a better projection of the left cheek, infra-orbital rim, nasal ala, and improved occlusion. Owing to the underdevelopment of the maxilla and zygoma in all three dimensions, contour deformities remain. Creating several bone segments for multidirectional distraction would jeopardize vascularization of the bone. Good long-term planning is essential in these complicated cases, and more long-term results need to be assessed. The major reconstructive challenge for this complex pathology continues.

Frontorhiny, a Distinctive Presentation of Frontonasal Dysplasia Caused by Recessive Mutations in the ALX3 Homeobox Gene (Article)

2009-05-15T00:00:00Z

We describe a recessively inherited frontonasal malformation characterized by a distinctive facial appearance, with hypertelorism, wide nasal bridge, short nasal ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. Additional recurrent features present in a minority of individuals have been upper eyelid ptosis and midline dermoid cysts of craniofacial structures. Assuming recessive inheritance, we mapped the locus in three families to chromosome 1 and identified mutations in ALX3, which is located at band 1p13.3 and encodes the aristaless-related ALX homeobox 3 transcription factor. In total, we identified seven different homozygous pathogenic mutations in seven families. These mutations comprise missense substitutions at critical positions within the conserved homeodomain as well as nonsense, frameshift, and splice-site mutations, all predicting severe or complete loss of function. Our findings contrast with previous studies of the orthologous murine gene, which showed no phenotype in Alx3-/-homozygotes, apparently as a result of functional redundancy with the paralogous Alx4 gene. We conclude that ALX3 is essential for normal facial development in humans and that deficiency causes a clinically recognizable phenotype, which we term frontorhiny.

On the origin of bitemporal hollowing (Article)

2009-05-01T00:00:00Z

INTRODUCTION: Long-term results after cranioplasty for trigonocephaly often show bitemporal hollowing and a residual hypotelorism. Both findings fuel the perception that the growth of the periorbital region and the forehead as a whole continues to be restricted, even after correction. The aim of this study was to evaluate the growth process of the periorbital region after correction for trigonocephaly in the long term. MATERIALS AND METHODS: From 1972 to 2004, 184 patients underwent a cranioplasty for the correction of nonsyndromatic trigonocephaly. Cephalometric analysis was performed in 33 of these patients who had their radiographs taken on the same day as the photograph, at least 1 year postoperative and before the age of 6 years. Cephalic landmarks were used to analyze the growth of the forehead. Because of the lack of standardized cephalograms, growth ratios were used instead of absolute measurements. For visual analysis, normal anteroposterior photographs were used, which were taken on the same day as the radiograph. Two observers evaluated the anteroposterior photographs for the presence and level of temporal hollowing. A score of 0 (normal), 1 (moderate deformity), or 2 (severe deformity) was assigned to each of the photographs. RESULTS: A significant relation was found between a severe deformation seen at postoperative photographic evaluation and a lower growth ratio. The preoperative photo score was not of predicting value for the postoperative growth ratio and therefore, indirectly, for the postoperative photo score. The mean preoperative photo score dropped 5% after surgery. The age at operation had no influence on this postoperative photo score. The experience of the surgeon, however, was a significant contributing factor. CONCLUSIONS: Temporal hollowing seems to be of bony origin and can be explained by skeletal growth inhibition in the affected area. When present immediately after operation, they seem to persist through the years, which makes surgical skill another factor of importance.

The increase of metopic synostosis: A pan-European observation (Article)

2009-03-01T00:00:00Z

Metopic synostosis is thought to have an incidence of about 1 in 15,000 births. Traditionally, this makes it the third most frequent single-suture craniosynostosis, after scaphocephaly (1 in 4200-8500) and plagiocephaly (1 in 11,000). Our units have, independently from each other, noted a marked increase in the number of metopic synostosis over the recent years. This is a pan-European, retrospective epidemiological study on the number of cases with metopic synostosis born between January 1, 1997, and January 1, 2006. This number was compared to the prevalence of scaphocephaly, the most frequently seen craniosynostosis. In the 7 units, a total of 3240 craniosynostosis were seen from 1997 until 2006. Forty-one percent (n = 1344) of those were sagittal synostosis, and 23% (n = 756) were metopic synostosis. There was a significant increase of the absolute number as well as of the percentage of metopic synostosis over these years (regression analysis, P = 0.017, R = 0.578) as opposed to a nonsignificant increase in the percentage of sagittal synostosis (P > 0.05, R = 0.368). The most remarkable increase occurred around 2000-2001, with the average of metopics being 20.1% from 1997 to 2000 and 25.5% from 2001 to 2005 (independent t-test, P = 0.002). The sagittal synostosis showed a smaller and nonsignificant increase in the same years: from 39.9% in 1997-2000 leading up to 42.5% in 2001-2005 (independent t-test, P > 0.05). The number of metopic synostosis has significantly increased over the reviewed period in all of our units, both in absolute numbers as in comparison to the total number of craniosynostosis.

A triage system for referrals of pediatric skull deformities (Article)

2008-11-01T00:00:00Z

The clinical pathways for craniosynostosis and nonsynostotic skull deformity are entirely different. At the Dutch Craniofacial Center (DCFC), all patients were assessed in the same multidisciplinary craniofacial clinic, a common practice in countries with developed health care. However, the high volume of referrals of nonsynostotic cases frequently resulted in the capacity of these clinics being exceeded, with some patients being assessed in the general pediatric plastic surgery clinic instead. In these general clinics, not all the multidisciplinary team members are routinely present, so patients with craniosynostosis had to make a second journey for further assessment, causing inconvenience, expense, and potential delay in treatment. With triage at the community level unreliable and triage at clinic level inefficient, we decided to trial a triage system to increase efficiency and to ensure patients enter the correct clinical pathway earlier.The 2 craniofacial secretaries were issued with a flowchart to be completed for each new referral. The flowcharts were designed to triage the patients into true craniosynostosis with an appointment for the multidisciplinary clinic or nonsynostotic deformity with an appointment with the craniofacial nurse practitioner (CNP). During a 3-month period, 107 referrals were made. The triage category listed on the initial flowchart for each patient was compared, with the final diagnosis made in the multidisciplinary and CNP clinics.None of the patients triaged as nonsynostotic deformity on the flowcharts were found to be true craniosynostosis after clinical assessment by the CNP. Radiographic assessment or assessment by the craniofacial surgeons in the DCFC confirmed this.The flowchart questionnaire used at the DCFC is a highly sensitive and therefore safe method for detecting craniosynostosis. It has helped to improve efficiency by ensuring patients are seen in an appropriate setting.

Advancement of the midface, from conventional Le Fort III osteotomy to Le Fort III distraction: review of the literature (Article)

2008-09-01T00:00:00Z

Since its introduction in about 1950, the Le Fort III (LF III) procedure has become a widely accepted treatment for correction of midface hypoplasia and related functional and esthetic problems. As long-term surgical experience grows and improvements are made in technique, equipment and peri-operative care, the number of LF III procedures performed worldwide is increasing. A number of fundamental questions concerning the technique remain unclear, and large, conclusive studies are lacking owing to the relative rarity of severe midface hypoplasia. This literature review aims to address problems, such as the indication field, timing of surgery, rate of relapse and the use of distraction osteogenesis. An overview of the history and technique of LF III osteotomy and distraction is provided, together with a comprehensive review of the available clinical data.

The frontosphenoidal suture: Fetal development and phenotype of its synostosis (Article)

2008-04-01T00:00:00Z

Background: Isolated synostosis of the frontosphenoidal suture is very rare and difficult to diagnose. Little has been reported on the clinical presentation and fetal development of this suture. Objective: To understand the development of the frontosphenoidal suture and the outcome of its synostosis. Materials and methods: We studied the normal fetal development of the frontosphenoidal suture in dry human skulls and the clinical features of four patients with isolated synostosis of the frontosphenoidal suture. Results: The frontosphenoidal suture develops relatively late during the second trimester of pregnancy, which explains the mild phenotype when there is synostosis. This rare craniosynostosis results in a deformity that causes recession of the lateral part of the frontal bone and supraorbital rim, with minimal facial asymmetry. Three-dimensional CT is the best examination to confirm the diagnosis. Conclusion: Isolated frontosphenoidal synostosis should be considered in patients with unilateral flattening of the forehead at birth that does not improve within the first few months of life.

RAB23 mutations in carpenter syndrome imply an unexpected role for Hedgehog signaling in cranial-suture development and obesity (Article)

2007-10-22T00:00:00Z

Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranialsuture biogenesis - an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components - and provides a new molecular target for studies of obesity.

Benchmarking for craniosynostosis (Article)

2007-03-01T00:00:00Z

The quality of care for craniofacial malformations is thought to be improved through benchmarking. The benchmarking process identifies the best practice within the participating centers and leads to new protocols and guidelines, which are implemented by the participants. It also allows for comparison of outcome between the various centers. Among the International Society for Craniofacial Surgery (ISCFS) a first international pilot study was undertaken on benchmarking for craniosynostosis, and a preliminary set of recommendations is made. A controlled number of centers including multidisciplinary teams was a prerequisite. A minimum number of patients operated per year seemed to be a valid parameter for decreasing morbidity.

Measuring surgical outcomes in congenital craniofacial surgery: An objective approach (Article)

2007-01-01T00:00:00Z

Assessment of surgical outcome in congenital craniofacial malformations is necessary to evaluate treatment efficiency since the results of early surgery are influenced by surgical technique and timing. Available outcome measurements all have their limitations, especially for application in congenital craniofacial malformations. Therefore a new outcome measurement was developed, in which each facial unit is scored in a standardized way. For each facial unit, deformities of shape or contour, malposition and soft tissue involvement were evaluated, besides scoring for specific congenital malformations of that area. The final result was tested on pre- and postoperative photographs of patients with rare facial clefts and reliability and validity were demonstrated. The new developed instrument showed the ability to provide quantification of outcome. Because of its properties it can serve as an instrument to compare outcome between techniques, surgeons and centers in a more objective and standardized way. Copyright

Craniosynostosis: clinical and fundamental aspects (Doctoral Thesis)

2000-10-25T00:00:00Z

Prior to the discovery of the genetic background of craniosynostosis, its classification was purely based on clinical features. This classification system did however have its pitfalls which became more obvious after comparing it with the detected genetic mutations. Because this classification has been the basis for clinical practice for years and still is applied world wide, this chapter will begin by giving a historical and clinical view on craniosynostosis before discussing the genetic aspects.