Complex Craniosynostosis Research Articles

Assessment of White Matter Microstructural Integrity in Children with Syndromic Craniosynostosis: A Diffusion-Tensor Imaging Study

To assess whether architectural alterations exist in the white matter of patients with syndromic and complex craniosynostosis. 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 diffusion-tensor imaging, an echo-planar sequence was used with a diffusion gradient (b = 1000 sec/mm(2)) 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. 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. 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.

Audiological Profile of Children and Young Adults With Syndromic and Complex Craniosynostosis

To determine syndrome-specific type, severity, and prevalence of hearing loss to facilitate follow-up and treatment. 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 pure-tone audiometry. Academic research facility. Information was gathered regarding 132 children and young adults with craniosynostosis. 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. 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. 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.

Achondroplasia with synostosis of multiple sutures

We report for the second time on a case of achondroplasia with synostosis of multiple sutures. The most common mutation for achondroplasia (FGFR3 Gly380Arg, resulting in 1138G>A) was identified. Imaging studies disclosed complex craniosynostosis and neurosurgical intervention was carried out, particularly for posterior plagiocephaly.

Reliability and Validity of the Obstructive Sleep Apnea-18 Survey in Healthy Children and Children With Syndromic Craniosynostosis

Obstructive sleep apnea (OSA) affects a person's quality of life. A questionnaire, the OSA-18, is available to measure quality of life in children with OSA not caused by specific craniofacial syndromes. We assessed the internal consistency, test-retest reliability, and discriminative validity of the OSA-18 in children with syndromic and complex craniosynostosis; we also applied the OSA-18 in healthy children to obtain reference values. The OSA-18 was translated in the Dutch language using the procedure of multiple forward and backward translations. Test-retest reliability and internal consistency were examined. In a prospective study, the craniosynostosis patients underwent an ambulatory polysomnography to diagnose OSA. The ability of the OSA-18 to discriminate between subgroups of patients with or without OSA was evaluated. We compared OSA-18 scores of children with syndromic or complex craniosynostosis with scores in healthy children. The Cronbach's alpha was ≥ 0.70 for the total OSA-18 score and for most of the domains in both the craniosynostosis and general population. In the craniosynostosis group, the test-retest intraclass correlation coefficients were ≥ 0.70, except for the domain physical suffering at 0.69. The discriminative validity of the domains sleep disturbance, physical suffering, caregiver concerns, and total OSA-18 score was significant between the general and craniosynostosis population. This study supports the reliability and validity of the OSA-18 in children with syndromic or complex craniosynostosis.

Antley–Bixler-Syndrome – Staged management of craniofacial malformations from birth to adolescence – A case report

In 1975 Antley and Bixler described an unusual syndromal disorder consisting of complex craniosynostosis with midfacial hypoplasia, dysplasia of ears and nose, radiohumeral synostosis, congenital fractures of the femur and upper airway impairment in a newborn. Additional urogenital and cardiac malformations can be associated however diagnosis is based on a characteristic craniofacial deformity in association with humeroradial synostosis. Complex disturbance of craniofacial growth due to premature synostoses of the cranial base and vault results in a characteristic phenotype. Steroidogenesis due to intrinsic or extrinsic disturbance by maternal fluconazole ingestion during early pregnancy may be impaired. The mode of inheritance is supposed to be autosomal recessive. Mutations in the fibroblast growth factor receptor 2 (FGFR2) as well as mutations in the cytochrome P450 oxidoreductase (OR) gene have been verified. Like in other craniofacial dysostosis syndromes malformation of neuro- and viscerocranium is complex and requires a staged age- and growth-related interdisciplinary management with respect to the individual situation. This case report of a female patient born in 1994 suffering from that rare syndrome describes the interdisciplinary long-term management in one craniofacial centre over 16 years from birth to adolescence.

Use of Ambulatory Polysomnography in Children With Syndromic Craniosynostosis

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.

The role of endoscopic third ventriculostomy in the treatment of hydrocephalus associated with faciocraniosynostosis

The aim of this study was to assess the efficacy of endoscopic third ventriculostomy (ETV) in the treatment of hydrocephalus in children with complex craniosynostosis. Medical charts from 2194 children treated at the Craniofacial Unit of Necker Enfants Malades between 1995 and 2008 were reviewed. Among them, 293 were affected by a syndromic faciocraniosynostosis. The management of cases with hydrocephalus treated using ETV was examined and analyzed with regard to successes and failures. Forty-six children with associated progressive hydrocephalus were identified, and 11 (8 boys, 3 girls) had undergone an ETV. All were affected by a faciocraniosynostosis (Crouzon syndrome in 5, Pfeiffer syndrome in 3, and unclassifiable in 3). A descent of the cerebellar tonsils was found in 5 children. In 7 children the hydrocephalus was controlled by an ETV. In the remaining 4 cases a ventriculoperitoneal shunt was also needed. The delay between the 2 surgeries ranged from 1 week to 6 months in these 4 patients. The follow-up period ranged from 11 months to 13 years. Performing an ETV may facilitate control of hydrocephalus associated with faciocraniosynostosis in select cases. However, because of the relatively high failure rate of this procedure, a close clinical and radiological monitoring of these children is mandatory.

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

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.

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

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.

Effectiveness of skull models and surgical simulation: comparison of outcome between different surgical techniques in patients with isolated brachycephaly

The aim of this study was to emphasize the importance of preoperative surgical planning using 3D skull models in craniosynostosis surgery. By using 3D polymethyl methacrylate skull models manufactured using 3D tomography images, the authors previously showed that after fronto-parietal osteotomy, instead of fixing the fronto-parietal bone flap without rotation, angled advancement with horizontal osteotomy provides maximum increase in intracranial volume, in a bilateral coronal craniosynostosis model. After changing the operation technique using data gathered from previous studies, we reviewed two bilateral craniosynostosis patients operated with the new technique and compared it with two patients that were operated with the old technique. Comparing cranial indexes (CI), significant improvement was detected in both groups. The decrease in CI in the second group was slightly better than the first group. In the comparison of intracranial volume (ICV), there was an increase in ICV values in both groups. The percentage of increase between two groups was similar. The morphological outcome was satisfactory in all patients. There were no major or minor complications and morbidity. Current multislice tomography technology and stereolithographic procedures provide an excellent surgical simulation model to find new techniques and predict the outcome. These models should be used in all complex and syndromic craniosynostosis for both better results and reducing the operative time and associated blood loss.

Midface advancement in craniofacial anomalies

Midface hypoplasia is a common finding in patients with complex craniosynostosis, like Apert, Crouzon and Pfeiffer syndrome. Midface hypoplasia presents with several clinical findings, most notably at the level of the airway, orbits, occlusion with reduced facial aesthetics and related psychosocial problems. These patients are at high risk for upper airway obstruction and undetected obstructive sleep apnoea syndrome (OSAS), but other factors such as adenotonsillar hypertrophy may be involved as well.

Lessons from a case of osteopetrosis oxycephaly and Chiari type I malformation: a case report

We report a child with osteopetrosis, oxycephaly and Chiari type I malformation who presented with raised intracranial pressure. During cranial expansion surgery the patient developed sudden cardiac arrest which we believe was probably related to the Chiari malformation. The case highlights a previously unrecognized association between osteopetrosis, craniosynostosis and a persistently open fontanelle at age 4 years. In addition it supports the existing literature in emphasizing the need for careful preoperative work up, choice of approach and operative technique in children with complex craniosynostosis and Chiari malformation.

Three dimensional methylacrylate and wax skull modeling preparing cranioplasty in the treatment of complex craniosynostosis and skull malformation

Three dimensional methylacrylate and wax skull modeling preparing cranioplasty in the treatment of complex craniosynostosis and skull malformation

Papilledema in Patients With Apert, Crouzon, and Pfeiffer Syndrome

Patients with syndromic craniosynostosis are at risk for elevated intracranial pressure because of various physiologic and anatomic abnormalities. The aims of this study were to determine the prevalence of papilledema in syndromic craniosynostosis, to evaluate the results of the treatment, and to examine the risk factors. This is a retrospective study on 84 patients with Apert, Crouzon, or Pfeiffer syndrome. Papilledema was defined as blurring of the margins of the optic disk. The association between clinical symptoms, beaten-copper pattern on skull radiograph, ventricular dilatation on computed tomography scan, and papilledema was assessed. Papilledema was present in 51% of the patients. No relation between specific clinical symptoms and papilledema was found. The significant associations were complex craniosynostosis, exorbitism, and ventricular dilatation. The prevalence of papilledema in patients with Apert, Crouzon, or Pfeiffer syndrome is high, not only before cranial decompression but also after vault expansion. Annual fundoscopy is recommended to screen for papilledema. We consider that early decompressive surgery (within the first year of age) prevents the development of papilledema and, most likely, elevated intracranial pressure.

Cytogenetic and molecular characterization of a de-novo cryptic deletion of 7p21 associated with an apparently balanced translocation and complex craniosynostosis

We describe a female infant with complex craniosynostosis, significant craniofacial dysmorphism and developmental delay in which a de-novo apparently balanced translocation between chromosomes 7 and 18 [46,XX,t(7;18)(p15.3;q11.2)] was identified. Additional cytogenetic and molecular investigations identified a cryptic interstitial 7.6-10.6-Mb deletion of the region between bands 7p21.2 and 7p21.3 on the derivative chromosome 18. The deletion was of paternal origin and contained the TWIST1 gene, although her features were not completely characteristic of Saethre-Chotzen syndrome. The phenotype of this patient is likely further complicated by loss of other genes within the deleted region and/or disruption of a critical gene(s) at the sites of the breakpoints on chromosomes 7 and 18. This case illustrates the need for a systematic molecular study of breakpoints and the surrounding chromosomal regions in patients with apparently balanced rearrangements and phenotypic abnormalities.

Evaluation of bioresorbable vis-à-vis titanium plates and screws for craniofacial fractures and osteotomies

Background: Rigid internal fixation with metals is a reliable method of achieving osteosynthesis while allowing the patient passive or even functional loading of the fracture or osteotomised bone segments. The disadvantages with metals have led to the introduction of resorbable polymers in rigid internal fixation. Methods: This study was conducted to evaluate the efficacy of these polymers as compared to titanium in fixation of bone segments fixation in 40 patients of zygomatic complex fractures and craniosynostosis management. The cases were followed up for one year. Result: The stability of the fixation was found to be comparable to metallic fixation though the armamentarium and procedure of fixation of resorbable system was more demanding and the technique sensitive. Conclusion: The resorbable system is a good system for rigid internal fixation in specific conditions where muscular and stress forces are not a determining factor in fragment displacement.

S434: Diagnosis and Management of Craniosynostoses

Craniosynostosis consists of the premature fusion of one or more cranial sutures, which result in an abnormal head shape. It may result from a primary defect of ossification (primary craniosynostosis) or, more commonly, from a failure of brain growth (secondary craniosynostosis). Simple craniosynostosis is a term used when only one suture fuses prematurely. Complex or compound craniosynostosis is used to describe premature fusion of multiple sutures. When children with craniosynostosis, usually complex, also display other body deformities, this is termed syndromic craniosynostosis.

Comparison between SSD and VR 3D-CT Reconstructions in the Evaluation of Complex Craniosynostoses

The craniosynostoses are serious abnormalities of infancy and childhood. The term craniosynostosis indicates a cranial or craniofacial dysmorphism characterized by skull growth disorder due to premature fusion of one or more sutures. It is a common clinical problem requiring the attention of many specialists. The suspicion is usually clinical, based on a cranial deformity. The diagnosis has always been almost exclusively radiological, due to the introduction of three-dimensional reconstruction techniques with Computed Tomography (3D-CT), including especially the Shaded Surface Display (SSD) and Volume Rendering (VR) algorithms. We examined 26 patients in our department with complex craniosynostosis of different types over a period of four years. Considering the data in the literature we analyze the role of 3D-CT and the results of our comparison between the two reconstruction methods in the diagnosis and management of craniosynostoses.

Intracranial pressure monitoring in children with single suture and complex craniosynostosis: a review

One third of patients with craniofacial dysostosis syndromes and about 15-20% of children with single suture craniostenosis have a documented increase in intracranial pressure (ICP). The early detection of intracranial hypertension is important in order to reduce the risks for brain development and visual function. However, in children with craniosynostosis, the clinical manifestations of abnormally increased ICP are difficult to detect, as the majority of patients may have neither warning signs nor symptoms for a long period of time. Moreover, data from the literature suggest that neither fundoscopic nor radiological findings are necessarily related to intracranial pressure recordings in this type of pathology. In this context prolonged ICP monitoring seems actually to be the most valuable diagnostic tool. Extradural, subdural, and intraparenchymal devices have been used, and different softwares have been employed for PC storage and analysis of the data obtained. Most recent series consider mean ICP combined with plateaux waves as the most sensitive indicators in the final evaluation of the results. The analysis of the literature demonstrates a significant difference in the prevalence of raised ICP preoperatively between non-syndromic and syndromic patients. Among the non-syndromic children, a direct relation between the number of sutures involved and raised ICP is documented. The analysis of plateaux waves seems to be particularly important in children with borderline mean ICP values. Persistent postoperative raised ICP has been described in 6-15% of patients with craniofacial dysostosis. It must be related to the multifactorial etiology of increased ICP in these patients, which includes cerebral venous congestion, upper airway obstruction, and hydrocephalus.

How low can you go? Intracranial pressure, cerebral perfusion pressure, and respiratory obstruction in children with complex craniosynostosis

Elevated intracranial pressure (ICP) is a well-recognized complication affecting children suffering from complex forms of craniosynostosis. The effects of ICP, including those on vision, and the underlying mechanisms involved remain uncertain. The aim of this study was to examine the relationships among ICP, cerebral perfusion pressure (CPP), and the episodic alterations in respiratory obstruction that are common in children with craniosynostosis. Eleven children with complex craniosynostosis underwent monitoring overnight, including simultaneous recording of subdural ICP, arterial blood pressure (ABP), and a variety of respiratory parameters. Sleep status was also analyzed. Mean values were calculated for all variables, including ICP, CPP, and ABP, during both quiet and active sleep. Mean ICP during quiet sleep was elevated in five patients, borderline in three, and normal in three children. During active sleep, plateaus of high mean ICP were observed in all patients. Marked decreases in CPP were demonstrated during active sleep with absolute values as low as 14 mm Hg. During quiet sleep, the mean baseline CPP was 53.3 mm Hg (range 34-70 mm Hg). During active sleep, CPP fell to a mean of 32.6 mm Hg (range 23-52 mm Hg). All patients experienced obstructive breathing problems, including 10 with obstructive sleep apnea, the effects of which demonstrated a temporal relationship to the alterations in sleep status, ICP, and CPP. Elevations of ABP appeared modest and remained within the normal limits for age. The findings of this study indicate that ICP, CPP, and respiratory obstruction interact in a vicious cycle, an observation that helps explain the pattern of plateau waves of elevated ICP characteristic among children with complex forms of craniosynostosis. The data gathered in this series revealed levels of CPP considerably lower than those described previously in clinical reports. Such reductions in CPP most likely contribute to the neurological, cognitive, and ophthalmological morbidity from which these children suffer frequently; therefore, the results of this study have important implications for the management of children with complex forms of craniosynostosis as well as for our understanding of the control of cerebral blood flow in general.