Non-syndromic Trigonocephaly Research Articles

Intracranial Volume Not Correlated With Severity in Trigonocephaly.

Objectives:Severity of trigonocephaly varies and potentially affects intracranial volume (ICV) and intracranial pressure (ICP). The aim of this study is to measure ICV in trigonocephaly patients and compare it to normative data and correlate ICV with the severity of the skull deformity according to UCSQ (Utrecht Cranial Shape Quantifier).Design:Retrospective study.Setting:Primary craniofacial center.Patients, Participants:Nineteen preoperative patients with nonsyndromic trigonocephaly (age ≤12 months).Intervention:Intracranial volume was measured on preoperative computed tomography (CT) scans by manual segmentation (OsiriX Fondation). Utrecht Cranial Shape Quantifier was used to quantify the severity of the skull deformity. When present, papilledema as sign of elevated ICP was noted.Main Outcome Measures(s):Measured ICV was compared to Lichtenberg normative cranial volume growth curves, and Pearson correlation coefficient was used to correlate UCSQ with the ICV.Results:Mean age at CT scan was 6 months (2-11). Mean measured ICV was 842 mL (579-1124). Thirteen of h19 patients (11/15 boys and 2/4 girls) had an ICV between ±2 SD curves of Lichtenberg, 2 of 19 (1/15 boys and 1/4 girls) had an ICV less than −2 SD and 4 of 19 (3/15 boys and 1/4 girls) had an ICV greater than +2 SD. Mean UCSQ severity of trigonocephaly was 2.40 (−622.65 to 1279.75). Correlation between severity and ICV was negligible (r = −0.11). No papilledema was reported.Conclusions:Measured ICV was within normal ranges for trigonocephaly patients, in both mild and severe cases. No correlation was found between severity of trigonocephaly and ICV.

New method for quantification of the relative severity and (a)symmetry of isolated metopic synostosis

Trigonocephaly is the result of premature fusion of the metopic suture and its severity can vary widely. However, there is no gold standard for quantification of the severity. This study was performed to quantify severity using the Utrecht Cranial Shape Quantifier (UCSQ) and to assess forehead symmetry. Nineteen preoperative non-syndromic trigonocephaly patients (age ≤1 year) were included for the analysis of severity and symmetry. Severity according to the UCSQ was based on the following combined variables: forehead width and relative skull elongation. The UCSQ was compared to the most established quantification methods. A high correlation was found between the UCSQ and visual score (r=0.71). Moderate to negligible correlation was found between the UCSQ and frontal angle, binocular distance, inter-ocular distance, and frontal stenosis. Additionally, correlation between the visual score and these established quantification methods was negligible. Assessment of the frontal peak (a)symmetry (ratio of right to left triangle area in the curve) showed a mean right versus left triangle area ratio of 1.4 (range 0.9–2.4). The results suggest that the UCSQ is appropriate for the quantification of severity based on the high correlation with clinical judgement. Furthermore, a larger triangle area right than left was unexpectedly found, indicating forehead asymmetry.

\u201cBlack bone\u201d: the new backbone in CAD/CAM-assisted craniosynostosis surgery?

BackgroundComputer-assisted design and manufacturing (CAD/CAM) techniques have been implemented in craniosynostosis surgery to facilitate cranial remodeling. However, until now, computed tomography (CT) scans with ionizing radiation were necessary to plan the procedure and create guiding templates. The purpose of this study was to present our series using CAD/CAM techniques in planning and conducting fronto-orbital advancement surgery in patients with trigonocephaly with datasets acquired only by “black bone” magnetic resonance imaging (MRI).MethodsSix consecutively operated cases from 2019 were included in this study. All patients suffered from non-syndromic trigonocephaly with no primary surgeries. All patients underwent cranial MRI including black bone sequences. Preoperative planning and guides were created based on the DICOM datasets. We analyzed demographic data, clinical data, and outcome measured by Whitaker score.ResultsIn all cases, precise frontobasal advancement was possible with the CAD/CAM guides created by black bone MRI. The mean operation time and planning time were 222 and 32 min. The time on intensive and intermediate care unit (ICU/IMC) time was 4.5 days, respectively. All but one case were classified as Whitaker I.ConclusionIn trigonocephaly treatment by frontobasal advancement, black bone MRI-based CAD/CAM craniosynostosis surgery is safe and feasible. It offers the major advantage of completely avoiding CT scans and ionizing radiation with superior imaging quality of intracranial structures. Thus, it improves intraoperative safety and—at the same time—has the potential to reduce operating room (OR) time.

S8A-12 SESSION 8A: METOPIC SYNOSTOSIS OPHTHALMOLOGIC ABNORMALITIES IN CHILDREN WITH TRIGONOCEPHALY

Introduction: Little has been described in the literature regarding ophthalmic abnormalities in non-syndromic midline craniosynostosis. The few studies on non-syndromic trigonocephaly and ocular abnormalities have shown that non-syndromic trigonocephaly is associated with a greater risk of abnormal visual functioning in young children, up to the age of 8 years. However, visual functioning in children after that age, when optic development is complete, hasn’t been studied yet. The purpose of this study is therefore to assess the prevalence of visual abnormalities in children with non-syndromic trigonocephaly between the age of 8 to 18 years. Methods: A retrospective, cross-sectional study of patients between the age of 8 and 18 years, with non-syndromic trigonocephaly was conducted. Ophthalmologic records were assessed for the following parameters: refractive errors, astigmatism, strabismus, and a history of amblyopia. Refractive error was determined using autorefraction or skiascopy after use of cycloplegia. Myopia was classified as spherical equivalent (SE) < -0.50 dioptre (D), emmetropia as SE between -0.50 D and +0.50 D, mild hyperopia as SE between +0.50 D and +2.00 D, moderate hyperopia as SE between +2.00 D and +6.00 D, and high hyperopia as SE > +6.00 D. Astigmatism was defined as > 1.00 D. Strabismus was subdivided in manifest and latent strabismus. Presence of strabismus and amblyopia was determined using the cover test, binocular sensory testing, and visual acuity. Results: We included 83 patients with non-syndromic trigonocephaly, with a mean age of 10.5 years (SD 2.0). Thirty-three of these 83 patients had abnormal visual functioning (39.7%). Of all 83 patients, 23 had hyperopia (27.7%), 7 had myopia (8.4%), 19 had astigmatism (22.9%), 7 had amblyopia (8.3%), and 12 had strabismus (14.3%). Manifest strabismus was present in 7 patients (8.3%), while latent strabismus was present in 5 patients (6.0%). Conclusion: Prevalence of hyperopia, astigmatism, amblyopia, and strabismus was higher in patients with non-syndromic trigonocephaly, compared to the prevalence found in the healthy paediatric population. Therefore, long-term surveillance of visual functioning of paediatric patients with non-syndromic trigonocephaly by an ophthalmologist is recommended.

Clinical Evaluation of Standardized Fronto-Orbital Advancement for Correction of Isolated Trigonocephaly.

Corrective surgery of trigonocephaly is a major challenge, owing to the complex development of the craniofacial skull. Although reports on the clinical success of standardized fronto-orbital advancement have been promising, there is a lack of studies, assessing this method. Hence, the aim of our study was to evaluate the clinical outcome of a standardized fronto-orbital advancement procedure for correction of isolated nonsyndromic trigonocephaly, in our patient cohort. The retrospective study included 30 patients from 2008 to 2015. Inclusion criteria were treatment-naive children with isolated nonsyndromic trigonocephaly, being treated with standardized frontoorbital advancement in our department. We considered postoperative complications and the Whitaker Score to evaluate the success of the clinical outcome. Surgery was performed at a mean age of 9.3 months. The mean operation time was 153 minutes. All patients were assigned I according to the Whitaker score. One patient suffered from a small inconsequential subdural hematoma. Another patient suffered from dural tears, which were identified and treated intraoperatively. No major complications occurred within our patient cohort. The standardized fronto-orbital advancement is a safe and successful method, as it is associated with a high morphological outcome and low complication rate.

Clinical and neuroradiological features of the 9p deletion syndrome.

The 9p deletion syndrome is a rare condition, which associates trigonocephaly, facial dysmorphism and developmental delay. The neuroradiological aspects of this syndrome have not yet been described. The purpose of this article is to identify the clinical and neuroradiological features, that should be recognized by all specialists treating these children, for a proper and early diagnosis. Among patients with trigonocephaly treated at our institution, we retrospectively analyzed the clinical and neuroradiological aspects of children with genetically confirmed 9p deletion syndrome. 6 patients were identified. Beside trigonocephaly, the most frequent clinical findings were small ears, long philtrum, upslanting palpebral fissures, flat nasal bridge and variable psycho-motor delay. Hypertelorism was present in 4 of 6 patient, which is opposite to the hypotelorism typical of non-syndromic trigonocephaly. Among neuroradiological findings, large, anteriorly rotated sylvian cisterns and altered shape of the septum pellucidum were found in all patients, as well as the compression of the frontal cortex due to the metopic synostosis (MS). A thin or dysmorphic corpus callosum and a diffuse white matter hypoplasia were present in more than half of the cases. Futhermore we compared these MRI findings with those of a control group of 30 non-syndromic trigonocephalies. Some recurrent neuroradiological alterations can be found in 9p deletion syndrome. The presence of these signs on MRI of a trigonocephalic patient should raise the suspicion of an underlying chromosomal alteration, such as the 9p deletion syndrome and prompt genetic investigations.

Stereolithographic skull models in the surgical planning of fronto-supraorbital bar advancement for non-syndromic trigonocephaly

BackgroundFronto-supraorbital bar advancement in the treatment for trigonocephaly is associated with extensive intraoperative blood loss and compensatory erythrocyte transfusions. Since both are related to the length of surgery, efforts have been focused on optimizing preoperative preparations. The utilization of three-dimensional skull models in surgical planning allows for familiarization with the patient's anatomy, the optimization of osteotomies, the preparation of bone grafts and the selection of fixation plates. MethodsStereolithographic skull models were used in the surgical planning for five patients with non-syndromic trigonocephaly treated in Wilhelmina Children's Hospital in 2012. A comparison group was composed of six patients with non-syndromic trigonocephaly treated by the same surgical team. Once all patients had received surgery, a retrospective chart review was performed to identify the volumes of perioperative blood loss and erythrocyte transfusions and the length of the procedure. Furthermore, the educational value of the models was assessed in a round table discussion with the surgical team and residents. ResultsIn the model group patients were transfused a mean 24 ml/kg (27% of Estimated Blood Volume [EBV]) compared to 16 ml/kg (18% of EBV) in the comparison group (P = 0.359) for a mean perioperative blood loss of 53 ml/kg (60% of EBV) in the model group against 40 ml/kg (41% of EBV) in the comparison group (P = 0.792). The mean length of surgery in the model groups was 256 min versus 252 min in the comparison group (P = 0.995). Evaluation of educational purposes demonstrated that the models had a role in the instruction of residents and communication to parents, but did not improve the insight of experienced surgeons. ConclusionThe usage of stereolithographic skull models in the treatment of non-syndromic trigonocephaly does not reduce the mean volume of perioperative erythrocyte transfusions, the mean volume of perioperative blood loss nor the mean length of the surgical procedure. Nonetheless, the models do facilitate the education of the patient's parents as well as support the training of residents.

Non-syndromic trigonocephaly: surgical decision making and long-term cosmetic results

Surgical correction is often required for cosmetic correction of trigonocephaly. The purpose of this paper was to report the long-term aesthetic outcome as appreciated by the parents/patients themselves. The self-evaluation of cosmetic outcome after trigonocephaly correction has not previously been reported. The management and different surgical techniques utilized over a 16-year period are discussed. An observational study was undertaken of the clinical outcome, operative data, complications and cosmetic satisfaction of these trigonocephaly patients. The parents/child were asked to rate their satisfaction with the cosmetic outcome both in terms of head shape and scar appearance, on a five-point scale (excellent-5, very good-4, good-3, fair-2 and poor-1). Sixty-three patients presented with non-syndromic trigonocephaly over the 16 years. Nineteen of 63 had a mild form of trigonocephaly and were managed conservatively. The remainder underwent surgical correction. Forty-two of 44 (95%) underwent fronto-orbital advancement with either barrel staving (26/44) or frontal bone rotation/re-modelling (16/44), with 2 of 44 having burring of the metopic ridge. Head shape rating was regarded as excellent in 25 of 63 (40%), very good in 18 of 63 (28%), good in 18 of 63 (28%) and fair in 2 of 63 (4%). Of those that underwent surgery, the scar was zigzag in 32 of 44 and straight in 12 of 44. Scar was rated as being excellent in 21 of 44 (48%), very good in 12 of 44 (28%) good in 11 of 44 (24%). Metopic synostosis can result in varying degrees of severity. Milder forms can be treated conservatively, with more severe forms requiring both frontal bone re-modelling and fronto-orbital advancement. Surgical correction results in a high level of patient/parent satisfaction.

Behavioral, developmental, and educational problems in children with nonsyndromic trigonocephaly

The neurobehavioral morbidity of nonsyndromic trigonocephaly is incompletely understood. The purpose of this study was twofold: first, to assess the degree of developmental, educational, and behavioral problems in patients with nonsyndromic trigonocephaly and second, to establish whether patients with mild degrees of trigonocephaly had a lower frequency of such problems. The authors performed an observational study of the frequency of developmental, educational, and behavioral problems in 63 children with trigonocephaly at the National Craniofacial Centre in the Republic of Ireland between 1989 and 2004. The parents of the children completed a follow-up questionnaire. Thirty percent of patients had a mild form of trigonocephaly and were treated conservatively. The remainder underwent surgical correction. Speech and/or language delay was reported in 34% of the children. Thirty-three percent of the children needed to be assessed by a school psychologist, and 47% were receiving remedial or resource hours within the school system. Twenty percent of children required a special needs classroom assistant because of behavioral issues, and 37% of parents expressed concerns about their child's behavior. There were no statistically significant differences between children treated with surgery and those who had a mild deformity and were treated conservatively. Nonsyndromic trigonocephaly is associated with a high frequency of developmental, educational, and behavioral problems. The frequency of these problems is not related to the severity of the trigonocephaly.

Trigonocephaly in Muenke syndrome

Saethre-Chotzen syndrome is caused by mutations in the TWIST gene on chromosome 7p21.2. However, Muenke et al. [(1997); Am J Hum Genet 91: 555-564] described a new subgroup carrying the Pro250Arg mutation in the fibroblast growth factor receptor (FGFR) 3 gene on chromosome 4p16. Uni or bicoronal synostosis appears to be the main clinical finding in both syndromes. We observed trigonocephaly as a new manifestation in Muenke syndrome. As a consequence we advise to routinely perform mutation analysis of the FGFR1, 2, and 3 genes in children with non-syndromic trigonocephaly.

Trigonocephaly

Trigonocephaly accounts for approximately 10% of all craniosynostosis. Severe trigonocephaly results in a triangular-shaped forehead, superior-lateral orbital depression, hypotelorism, and compensatory occipital-parietal calvarial changes. Radiographic findings include ovoid orbits with parallel medial borders, thickened keel-shaped frontal bone, small ethmoid sinuses, and a short anterior cranial fossa with pitched sphenoid wings. Our experience with 50 infantile cases of severe nonsyndromic trigonocephaly patients treated from 1987 to 2005 is clinically reviewed to assess long-term growth based on a standardized operative technique. The average age of the patients at surgery was 6 months and the mean follow-up was 12 years. Our complication rate was 2%; the reoperative rate was 12%. The use of resorbable rigid plate fixation combined with alloplastic augmentation has improved the cosmetic outcome in patients treated since 1996 and reduced the reoperative rate.

Molecular screening for microdeletions at 9p22‐p24 and 11q23‐q24 in a large cohort of patients with trigonocephaly

Trigonocephaly is a rare form of craniosynostosis characterized by the premature closure of the metopic suture. To contribute to a better understanding of the genetic basis of metopic synostosis and in an attempt to restrict the candidate regions related to metopic suture fusion, we studied 76 unrelated patients with syndromic and non-syndromic trigonocephaly. We found a larger proportion of syndromic cases in our population and the ratio of affected male to female was 1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all patients and deletions in seven of them were detected, corresponding to 19.4% of all syndromic cases. Deletions were not found in non-syndromic patients. We suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24 should be offered to all syndromic cases with an apparently normal karyotype because it can potentially elucidate the cause of trigonocephaly in this subset of patients. We also suggest that genes on the X-chromosome play a major role in syndromic trigonocephaly.

Clinical and genetic aspects of trigonocephaly: A study of 25 cases

We reviewed 25 patients ascertained through the finding of trigonocephaly/metopic synostosis as a prominent manifestation. In 16 patients, trigonocephaly/metopic synostosis was the only significant finding (64%); 2 patients had metopic/sagittal synostosis (8%) and in 7 patients the trigonocephaly was part of a syndrome (28%). Among the nonsyndromic cases, 12 were males and 6 were females and the sex ratio was 2 M:1 F. Only one patient with isolated trigonocephaly had an affected parent (5.6%). All nonsyndromic patients had normal psychomotor development. In 2 patients with isolated metopic/sagittal synostosis, FGFR2 and FGFR3 mutations were studied and none were detected. Among the syndromic cases, two had Jacobsen syndrome associated with deletion of chromosome 11q 23 (28.5%). Of the remaining five syndromic cases, different conditions were found including Say-Meyer syndrome, multiple congenital anomalies and bilateral retinoblastoma with no detectable deletion in chromosome 13q14.2 by G-banding chromosomal analysis and FISH, I-cell disease, a new acrocraniofacial dysostosis syndrome, and Opitz C trigonocephaly syndrome. The last two patients were studied for cryptic chromosomal rearrangements, with SKY and subtelomeric FISH probes. Also FGFR2 and FGFR3 mutations were studied in two syndromic cases, but none were found. This study demonstrates that the majority of cases with nonsyndromic trigonocephaly are sporadic and benign, apart from the associated cosmetic implications. Syndromic trigonocephaly cases are causally heterogeneous and associated with chromosomal as well as single gene disorders. An investigation to delineate the underlying cause of trigonocephaly is indicated because of its important implications on medical management for the patient and the reproductive plans for the family.