Suture Fusion Research Articles

S4A-17 SESSION 4A: GENERALITIES IN CRANIOSYNOSTOSIS – PART I LESSONS LEARNED FROM X-LINKED HYPOPHOSPHATEMIC RICKETS RELATED CRANIOSYNOSTOSIS:

Introduction: X-linked hypophosphatemic rickets (XLH) represents the most common form of hypophosphatemia and leads to vitamin D resistant rickets in children. Early closure of the cranial sutures leading to cranial vault and craniovertebral anomalies of potential craniofacial interest have been observed in XLH, the actual incidence of such anomalies is not yet established. Aim of this study is to describe and analyze the incidence of cranial and cervico-occipital junction (COJ) in children with XLH. Methods: Retrospective study of CT scans of the head and skull in 44 XLH children. The patency of the sutures was noted. The cranial index was calculated and the position of the cerebellar tonsils was analyzed Results: Forty-four XLH children, 15 boys and 29 girls, age 8.7 ± 3.9 years at time of CT scan. 25% of XLH children showed protrusion of the cerebellar tonsils (7 children > 5 mm and 3 children < 5 mm). 59% of XLH children had a complete or partial fusion of the sagittal suture and craniosynostosis was associated with abnormal descent of cerebellar tonsils. A history of dental abscesses was associated with craniosynostosis. Only 36% XLH children presented a cranial index <75%. Patients with craniosynostosis had a smaller cranial index compared to patients without craniosynostosis Conclusion: Sagittal suture fusion and Chiari malformation are two common complications of XLH. The association between the two entities underlines the potential consequences of a long lasting synostosis in this population. This study also highlights the particularities of metabolic synostosis that despite a mild deformation may have severe consequences. Because the diagnosis can be underestimated on a purely clinical basis, radiological studies should be considered in XLH children if a proper diagnosis is warranted.

S5A-05 SESSION 5A: GENERALITIES IN CRANIOSYNOSTOSIS – PART II LARGE SINGLE INSTITUTION SERIES OF ENDOSCOPICALLY TREATED INFANTS WITH CRANIOSYNOSTOSIS

Introduction: Endoscopic strip craniectomy (ESC) followed by helmeting for the treatment of craniosynostosis has gained increasing popularity since its introduction in the 1990s. Efficacy and safety remains to be determined. Methods: 500 consecutive infants who underwent ESC for craniosynostosis at a single institution from 2004 to 2018 by a single neurosurgeon were identified from a prospective database. Patient demographics, operative and postoperative variables were analyzed. Results: 500 infants (69% male) of median (IQR) age 3.0 (1.1–16.7) months and weight 5.9 (IQR 5.6–6.7) kg underwent ESC over the 15 year period. Median operative and anesthesia times were 47 and 140 minutes, respectively. Median length of hospital stay was 1 (IQR 1-1) day (3.2% admitted to ICU). The transfusion rate was 6.6% (95% CI: 5–9%) and postoperative complication rate was 1.4% (95% CI: 1–3%). Risk factors for blood transfusion were identified by multivariable logistic regression and included syndromic craniosynostosis (P=.01) and multiple fused sutures (P=.02). Complications included surgical site infections (n=4), skull defect (n=2), and CSF leak (n=1). 14 patients (2.8%; 95% CI: 2–5%) ultimately required an open procedure for correction of their craniosynostosis due to suture (re-)fusion (n=12) or inadequate cosmetic result (n=2). Infants with sagittal, coronal, and multi-suture craniosynostosis showed normalization of head circumference postoperatively at 12 months of age relative to World Health Organization normal head growth data (all P<.001, paired t-test). Head circumference remained within ±25 percentile points of baseline (WHO percentile) in 81% (95% CI: 77–84%) of infants by 12 months of age, decreasing by >25 in 7% (95%CI: 5–10%) and increasing by >25 in 12% (95% CI: 10–15%). Follow-up data demonstrated compliance with the recommended helmet therapy in 91.4% of patients (5.4% unknown); prior data from this cohort showed an average of 7 months of helmet therapy to achieve satisfactory correction. Conclusion: ESC is a safe, effective, and durable procedure for the correction of craniosynostosis in infants. ESC offers a short length of stay, low complication and transfusion rates, and excellent clinical outcomes including age-appropriate normalization of postoperative head growth in >90% of infants.

S12-14 SESSION 12: FACIOCRANIOSYNOSTOSIS – PART II THE CLASSIFICATION OF APERT SYNDROME, BASED ON CRANIAL VAULT SUTURE SYNOSTOSIS ------DIFFERENT CRANIAL BASE ANGULATIONS AND AIRWAY COMPROMISE

Introduction: Apert syndrome patients are different in clinical pathology, including obstructive sleep apnea, cleft palate and mental deficiency. These functional deficiencies may be due to anatomic deformities, which may be caused by different forms of associated suture fusion. Therefore, a classification system of Apert syndrome based on the type of craniosynostosis pattern might be helpful in determining treatment choices. Methods: CT scans of 31 unoperated Apert syndrome and 51 controls were included and subgrouped as: class I. Bilateral coronal synostosis; class II. Pansynostosis; class III. Perpendicular combination synostosis: a. unilateral coronal and metopic synostosis; b. sagittal with bilateral/unilateral lambdoid synostosis; c. others. Results: Class I, bilateral coronal synostosis is the most common (55%) subtype. The cranial base angulation of class I was normal, however, the cranial base angulation on the cranium side of the skull in class II (N-S-BA) increased 12.16 degrees (p=0.006), while the facial side cranial base angle (N-SO-BA) of class III-a decreased 4.31 degrees (p=0.035) over time. The external cranial base linear measurements of class I showed more evident reduction in anterior craniofacial structures than posterior, while other subtypes developed more severe shortening in the posterior aspects. Conclusion: Bicoronal synostosis is the most common subtype of Apert syndrome with the normalized cranial base angulation. Combined pansynostosis patients have flatter cranial base, while the combined unilateral coronal synostosis have a kyphotic cranial base. Class I have more significant nasopharyngeal airway compromise in a vertical direction, while class II and class III have more limited oropharyngeal space.

S1-07 SESSION 1: NEUROSURGERY COHORT VALIDATION OF OPTICAL COHERENCE TOMOGRAPHY TO DETECT ELEVATED INTRACRANIAL PRESSURE IN CHILDREN WITH CRANIOSYNOSTOSIS

Introduction: Better diagnosis of elevated intracranial pressure (ICP) in patients with craniosynostosis may facilitate more timely intervention to improve neurocognitive outcomes. Spectral-domain optical coherence tomography (OCT) of the retinal laminae can non-invasively diagnose elevated ICP. We previously reported thresholds of maximal retinal nerve fiber layer (RNFL) thickness, retinal thickness, and anterior retinal projection measured with OCT that appeared to correlate with subacutely elevated ICP. This study sought to prospectively validate this OCT methodology in a cohort of patients with craniosynostosis. Methods: Infants and children with craniosynostosis were prospectively enrolled, and demographic, clinical, and radiographic characteristics collected. Retinal parameters were prospectively assessed in both eyes using spectral-domain OCT under general anesthesia. Subsequently, ICP was measured directly using a subdural catheter during cranial vault surgery. OCT retinal analysis was performed in a masked fashion, then compared to directly-measured ICP data. Results: Seventeen Nineteen subjects (aged 0.4-6.75.6 years) with craniosynostosis were enrolled; among these 3 (16%) were syndromic with bicoronal fusion, 8 (42%) had sagittal, 4 (21%) unicoronal, and 4 (21%) metopic suture fusion. The sample (mean age 1.9 years) included many patients with late diagnosis; 2 (67%) syndromic and 8 (50%) nonsyndromic patients had elevated ICP (>= 15mmHg.) OCT parameters (either maximal RNFL thickness or anterior retinal projection exceeding 2 standard deviations, in either eye) predicted elevated ICP in 10 patients, 7 of which were diagnosed with elevated ICP directly. This yielded OCT parameter sensitivity of 70%, and specificity of 80% when compared to the gold standard of direct ICP measurement. Sensitivity analysis of a modified protocol assessing bilateral anterior retinal projection was associated with increased specificity of 100%, but reduced sensitivity of 60%. Conclusions: Prospective assessment of a optical coherence tomography protocol to non-invasively detect elevated ICP suggests superior sensitivity and similar specificity to conventional methods in a small cohort of patients with craniosynostosis.

Leri-Weill Dyschondrosteosis Syndrome: Analysis via 3DCT Scan

Background: Leri-Weill dyschondrosteosis (LWD) is a pseudoautosomal form of skeletal dysplasia, characterized by abnormal craniofacial phenotype, short stature, and mesomelia of the upper and lower limbs. Methods: We describe two female patients with LWD. Their prime clinical complaints were severe bouts of migraine and antalgic gait. Results: Interestingly, via a 3D reconstruction CT scan we encountered several major anomalies. Notable features of craniosynostosis through premature fusion of the squamosal sutures and partial closure of the coronal sutures were the reason behind the development of abnormal craniofacial contour. A 3D reconstruction CT scan showed apparent bulging of the clavarium through the partially synostosed coronal and totally synostosed squamosal sutures. Additional deformities include deficient number of ribs (10 ribs on both sides), defective ossification of the ischium and dysplasia of the iliac-ischial junction, and coxa valga have been noted. Conclusions: The constellation of observed deformities can be considered as a novel features associated with LWD.

Differential growth of seals and sea lions with paedomorphic and peramorphic adult skull morphologies

Links between behavior and skull morphology have been widely demonstrated in carnivorans. The skulls of more‐aggressive species tend to be more peramorphic, with greater crest development for the emplacement of muscles, compared to the more paedomorphic rounded skulls of less‐aggressive species. Are these two endpoints the result of differential growth patterns in dimorphic species?To answer this, we looked at skulls of seals and sea lions (n = 58, including 22 males, 14 females and 22 unknowns, usually juveniles) across 8 species. We categorized the individuals into ages from immature (teeth erupting, less fused sutures, smaller size), sub‐adult (teeth erupted but not worn, more sutural fusion), and adult (teeth with wear, fully‐fused sutures, and larger size). We compared these individuals by observing the placement of 26 bony landmarks using a geometric morphometric approach.We found that paedomorphic adults have juvenile‐looking skulls, e.g., a short or absent sagittal and nuchal crest, a narrow zygomatic width, and shorter skull length between the braincase and rostrum. Peramorphic adults had more growth resulting in traits including taller sagittal and nuchal crests, a wider zygomatic width, and a longer skull length. The brain case varied little between paedomorphic and peramorphic end points. The increase in skull length happens first through growth, and the width of the zygomatic arch and height of crests increases later, likely in response to the increase of size of the jaw‐closing muscles.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Emergent Properties of Facial Morphogenesis Regulated by Fgf Signaling

Craniosynostosis is a severe disorder that may be caused by activating mutations in Fibroblast growth factor receptors (FgfRs) that affects development of the skull and is characterized by premature fusion of the cranial sutures. In addition to dysmorphology of the skull, affected individuals also have facial dysmorphology. We have previously used an avian model to explore the role that a disease‐causing allele of FgfR2 (FgfR2C278F) plays in producing malformations of the middle and upper face at early stages of development. In that work we observed a wider midface, which resembles what is observed in human patients, and this was directly related to decreased cell proliferation and a disrupted net polarization of the mesenchymal cells in the growing facial primordia. We have extended this work by examining the role of the Map kinase, PLC‐gamma, and PI3K pathways downstream of Fgf signaling in producing facial dysmorphology, as well as directly blocking FgfR activation. We implanted beads soaked in small molecular inhibitors (MEK1/2: U0126, PLC‐gamma: U‐73122, PI3K: LY 294002, FgfR activation: SU5402) into the right side of the developing avian face at HH22 and examined morphological and cellular outcomes at various times of development. First, we determined that each inhibitor substantially and specifically down‐regulated its respective pathway using immunohistochemistry to assess expression of down‐stream targets of activation of each pathway. We then determined that each pathway significantly reduced cell proliferation and altered cell polarization in the mesenchyme. Blocking each pathway also created severe craniofacial malformations that were observed at early and late time points. There are many inputs to each of these pathways, and our data suggest that each participate in regulation of a similar set of cellular processes that contribute to the emergence of morphogenetic processes in facial development.Support or Funding InformationNIH: R01DE019638, R01DE018234, R21DE028198This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term impact of pediatric endoscopic endonasal skull base surgery on midface growth.

Cranial base development plays a large role in anterior and vertical maxillary growth through 7 years of age, and the effect of early endonasal cranial base surgery on midface growth is unknown. The authors present their experience with pediatric endoscopic endonasal surgery (EES) and long-term midface growth. This is a retrospective review of cases where EES was performed from 2000 to 2016. Patients who underwent their first EES of the skull base before age 7 (prior to cranial suture fusion) and had a complete set of pre- and postoperative imaging studies (CT or MRI) with at least 1 year of follow-up were included. A radiologist performed measurements (sella-nasion [S-N] distance and angles between the sella, nasion, and the most concave points of the anterior maxilla [A point] or anterior mandibular synthesis [B point], the SNA, SNB, and ANB angles), which were compared to age- and sex-matched Bolton standards. A Z-score test was used; significance was set at p < 0.05. The early surgery group had 11 patients, with an average follow-up of 5 years; the late surgery group had 33 patients. Most tumors were benign; 1 patient with a panclival arteriovenous malformation was a significant outlier for all measurements. Comparing the measurements obtained in the early surgery group to Bolton standard norms, the authors found no significant difference in postoperative SNA (p = 0.10), SNB (p = 0.14), or ANB (0.67) angles. The S-N distance was reduced both pre- and postoperatively (SD 1.5, p = 0.01 and p = 0.009). Sex had no significant effect. Compared to patients who had surgery after the age of 7 years, the early surgery group demonstrated no significant difference in pre- to postoperative changes with regard to S-N distance (p = 0.87), SNA angle (p = 0.89), or ANB angle (p = 0.14). Lesion type (craniopharyngioma, angiofibroma, and other types) had no significant effect in either age group. Though our cohort of patients with skull base lesions demonstrated some abnormal measurements in the maxillary-mandibular relationship before their operation, their postoperative cephalometrics fell within the normal range and showed no significant difference from those of patients who underwent operations at an older age. Therefore, there appears to be no evidence of impact of endoscopic endonasal skull base surgery on craniofacial development within the growth period studied.

Quantitative evaluation of local head malformations from three-dimensional photography: application to craniosynostosis.

The evaluation of head malformations plays an essential role in the early diagnosis, the decision to perform surgery and the assessment of the surgical outcome of patients with craniosynostosis. Clinicians rely on two metrics to evaluate the head shape: head circumference (HC) and cephalic index (CI). However, they present a high inter-observer variability and they do not take into account the location of the head abnormalities. In this study, we present an automated framework to objectively quantify the head malformations, HC, and CI from three-dimensional (3D) photography, a radiation-free, fast and non-invasive imaging modality. Our method automatically extracts the head shape using a set of landmarks identified by registering the head surface of a patient to a reference template in which the position of the landmarks is known. Then, we quantify head malformations as the local distances between the patient's head and its closest normal from a normative statistical head shape multi-atlas. We calculated cranial malformations, HC, and CI for 28 patients with craniosynostosis, and we compared them with those computed from the normative population. Malformation differences between the two populations were statistically significant (p<0.05) at the head regions with abnormal development due to suture fusion. We also trained a support vector machine classifier using the malformations calculated and we obtained an improved accuracy of 91.03% in the detection of craniosynostosis, compared to 78.21% obtained with HC or CI. This method has the potential to assist in the longitudinal evaluation of cranial malformations after surgical treatment of craniosynostosis.

Why do metopic sutural synostoses angulate? The concept of nasion sutural complex and its implication on the management of hypotelorism-early results and proof of concept.

Angulation at the suture is a hallmark of metopic synostoses amongst all craniosynostoses. No other sutural synostoses demonstrate angulation at synostoses consistently. We look into the possible aetiology and the implication of the understanding in the treatment goals of trigonocephaly. We hypothesise that the nasal bone and nasofrontal suture viz. "nasion sutural complex" are involved in trigonocephaly along with the well-accepted role of metopic suture. We propose that it is the angulation at this junction which leads to trigonocephaly and its secondary features. The study included seven infants, who underwent correction for trigonocephaly at our paediatric craniofacial division at Amrita Institute of Medical Sciences and Research Centre, Kochi, India, between the period July 2015 to March 2018. The cohort included were infants with trigonocephaly who had CT head for diagnosis. We analysed the multidimensional CT (MDCT) of these infants and compared to an equal number of age-matched controls. The controls were infants with other forms of sutural synostosis with metopic uninvolved and normal infants where MDCT was done for other reasons. Sutural characteristic at the nasion and metopic suture recorded in comparison with an equal number of age-matched controls. We performed spring cranioplasty for three infants after metopic suturectomy, extending the release beyond the nasion sutural complex, placing springs to distract the suture. The infants who underwent spring cranioplasty were followed up for the aesthetic outcome. Remaining infants of the study underwent standard frontorbital correction for metopic craniosynostoses. We could demonstrate a fusion of nasofrontal and nasal suture in all cases (n = 7) of trigonocephaly included in the study on MDCT and intraoperatively. We performed spring cranioplasty for three infants (n = 3/7), where we released the internasal suture. At 3months follow-up, along with correction of the angulation, the hypotelorism improved significantly. Other infants in the study (4/7) underwent classical frontorbital advancement. Fusion of nasion sutural complex along with metopic sutures may explain the angulation in trigonocephaly. We propose that all minimally invasive techniques for correction of trigonocephaly and associated hypotelorism should consider this fact for an improved outcome.

Characterization of Perinatal Risk Factors and Complications Associated With Nonsyndromic Craniosynostosis.

Certain intrauterine risk factors are known to increase the risk of premature cranial suture fusion and may cause complications during birth. Some of these risk factors may be modifiable. Therefore, the authors sought to characterize the institutional patterns of prenatal risk factors and perinatal complications in nonsyndromic craniosynostosis patients compared to normal births from the surrounding area to identify areas for possible intervention or prevention. The medical records of all infants with nonsyndromic craniosynostosis and full birth records born at Duke University Health System from 2006 to 2017 were retrospectively reviewed. Maternal comorbidities, prenatal risk factors, and perinatal complications were collected. The North Carolina State Center for Health Statistics was queried for perinatal statistics from Durham county and the Northeastern Perinatal Care Region to represent a control cohort of normal births from the same time period and region. The primary outcome investigated was the incidence of prenatal risk factors and complications at birth associated with premature fusion of cranial sutures. Eighty births with nonsyndromic craniosynostosis were included in this study. The majority of these patients were males (61.7%) and born via cesarean section (55.0%). Intrauterine growth restriction occurred in 10.0% and head trauma during delivery occurred in 2.5%. Twinning (14.8% vs 3.6%, P < 0.0001), cesarean births (55.5% vs 30.0%, P < 0.0001), and breech presentation (17.3% vs 3.2%, P < 0.0001) were significantly more common in craniosynostosis patients. Prenatally, mothers of craniosynostosis infants had higher incidence of gestational diabetes (13.5% vs 5.0%, P < 0.0001) and oligohydramnios (6.1% vs 1.3%, P < 0.0001) compared to regional controls. This study demonstrates that premature suture fusion is associated with prenatal risk factors such as gestational diabetes and oligohydramnios. Continued research into potentially modifiable prenatal risk factors and more refined prenatal diagnostic tools has the potential to reduce both the incidence of premature suture fusion and the sequelae of birth complications in this population.

Practical Computed Tomography Scan Findings for Distinguishing Metopic Craniosynostosis from Metopic Ridging.

Background:Premature fusion of the metopic suture (ie, metopic craniosynostosis) can be difficult to discriminate from physiological closure of the metopic suture with ridging (MR). Yet, MCS is treated surgically, whereas MR is treated nonsurgically. Often, the diagnosis can be made by physical examination alone, but in difficult cases, a computed tomography (CT) scan can add additional diagnostic information.Methods:We de-identified, randomized, and analyzed the CT scans of patients with MCS (n = 52), MR (n = 20) and age-matched normative controls (n = 52) to identify specific findings helpful in distinguishing between MCS and MR. Four expert clinicians were blinded to the clinical diagnosis and assessed each CT for features of the orbits, frontal bones, and inner table of calvaria.Results:Although no single feature was diagnostic of MCS, we identified several signs that were correlated with MCS, MR, or controls. Features such as “posteriorly displaced frontal bone” and “frontal bone tangent to mid-orbit or medial” demonstrated higher correlation with MCS than MR and the addition of other features improves the accuracy of diagnosis as did inclusion of the interfrontal divergence angle.Conclusion:The presence of a closed metopic suture in addition to other CT scan findings may improve the accuracy of diagnosing MCS, MR, and normocephaly.

Classification of Subtypes of Apert Syndrome, Based on the Type of Vault Suture Synostosis.

Apert syndrome patients are different in clinical pathology, including obstructive sleep apnea, cleft palate, and mental deficiency. These functional deficiencies may be due to anatomic deformities, which may be caused by different forms of associated suture fusion. Therefore, a classification system of Apert syndrome based on the type of craniosynostosis pattern might be helpful in determining treatment choices. CT scans of 31 unoperated Apert syndrome and 51 controls were included and subgrouped as: class I. Bilateral coronal synostosis; class II. Pansynostosis; and class III. Perpendicular combination synostosis: a. unilateral coronal and metopic synostosis; b. sagittal with bilateral/unilateral lambdoid synostosis; and c. others. Class I is the most common (55%) subtype. The cranial base angulation of class I was normal; however, the cranial base angulation on the cranium side of the skull in class II increased 12.16 degrees (P = 0.006), whereas the facial side cranial base angle of class IIIa decreased 4.31 degrees (P = 0.035) over time. The external cranial base linear measurements of class I showed more evident reduction in anterior craniofacial structures than posterior, whereas other subtypes developed more severe shortening in the posterior aspects. Bicoronal synostosis is the most common subtype of Apert syndrome with the normalized cranial base angulation. Combined pansynostosis patients have flatter cranial base, whereas the combined unilateral coronal synostosis have a kyphotic cranial base. Class I has more significant nasopharyngeal airway compromise in a vertical direction, whereas classes II and III have more limited oropharyngeal space.

Ultrasonography as first line imaging for the diagnosis of positional plagiocephaly: our experience and literature review.

In the last years, numerous studies evaluated different tools for the diagnosis of positional plagiocephaly (PP). The purpose of this study was to evaluate ultrasonography (US) as a first line screening test of lambdoid sutural patency in child with PP and to compare our results with the literature. All consecutive patients who referred to our Institute from January 2016 to October 2017 with the suspicion of PP, were included in the study and performed US examination of the lambdoid sutures. A 3-6 month clinical follow up was performed by a paediatric neurosurgeon or a paediatrician to confirm the diagnosis of PP. Thirty-five children performed US examination and in all cases the diagnosis of PP was confirmed. No cases of anticipated suture fusion were examined during this period. The concordance between US findings and clinical exam follow-up was 100%. Ultrasonography of the lambdoid sutures represents an ideal first-line screening test and reliable alternative to other diagnostic techniques for lambdoid sutural patency in child with PP, being radiation free, fast and cheap.

Perioperative management of patients undergoing craniosynostosis repair

Craniosynostosis is a type of craniofacial malformation because of premature fusion of cranial suture. The primary treatment is surgical correction which is usually done in stages over years to get best possible outcome. We did a retrospective analysis of five years from 1st August 2011 to 30th July 2016 in which we included twelve patients of craniosynostosis requiring corrective surgeries under general anaesthesia in our institution.

Detection of G338R FGFR2 mutation in a Vietnamese patient with Crouzon syndrome.

Crouzon syndrome is a rare autosomal dominant genetic disorder, which causes the premature fusion of the cranial suture. Fibroblast growth factor receptor 2 (FGFR2) mutations are well-known causatives of Crouzon syndrome. The current study aimed to assess the FGFR2 gene associated with Crouzon syndrome in a Vietnamese family of three generations and to characterize their associated clinical features. The family included in the present study underwent complete clinical examination. A patient was clinically examined and presented with typical features of Crouzon syndrome including craniosynostosis, shallow orbits, ocular proptosis and midface hypoplasia. However the patient had normal hands and feet, a normal hearing ability and normal intelligence. Genomic DNA collected from all family members (except from a 16 week-old-foetus) and 200 unrelated control subjects from the same population was extracted from leukocytes obtained from peripheral blood samples. Genomic DNA was extracted from the 16-week-old foetus via the amniotic fluid of the mother. All coding sequences of FGFR2 were amplified via polymerase chain reaction and directly sequenced. A heterozygous FGFR2 missense mutation (c.1012G>C, p.G338R) in exon 10 was identified in the patient with Crouzon but not in other family members, the 16 week-old-foetus or the controls. This mutation was therefore determined to be the causative agent of Crouzon syndrome. In addition, a novel heterozygous silent mutation (c.1164C>T, p.I388I) in exon 11 of the FGFR2 gene was identified in the patient with Crouzon, his mother and the 16-week-old fetus, but not in other family members. The mutation in exon 10 of FGRF2 was confirmed via restriction-enzyme digestion. The gain of the BsoBI site confirmed the FGFR2 mutation in exon 10 of the patient with Crouzon. This molecular finding may provide useful information to aid clinicians in the diagnosis of Crouzon syndrome and may also aid early prenatal diagnoses.

Premaxillary-maxillary suture development in the first trimester : An ultrasound study.

Our study was designed to investigate premaxillary-maxillary suture growth in fetuses from the first trimester of pregnancy using the B‑ultrasound technique in order to determine the suture fusion time. We selected 169 healthy Han singleton pregnancies as subjects. All subjects received routine pregnancy tests and were divided into three groups based on the gestational age of the fetus: group1, the 11th gestational week; group2, the 12th gestational week; and group3, the 13th gestational week. Fetal biometric measurements were recorded during consecutive prenatal ultrasonographic examinations. These measurements included nuchal translucency thickness, crown-rump length, and premaxillary-maxillary length. Intergroup comparisons were performed using analysis of variance (ANOVA). The premaxillary-maxillary suture grows gradually and its measured length at the 11th, 12th and 13th week was 0.54 cm, 0.65 cm, and 0.74 cm, respectively. We observed asignificant linear correlation between the premaxillary-maxillary length and the week of gestation in the first trimester. The growth rate of the maxilla at the 11th, the 12th and the 13th week are significantly different with adescending order of growth rates being week12, week11 and week13, with the 12th week rate being the most rapid. The premaxillary and maxillary growth at 11 and 12 gestational weeks in the first trimester steadily accelerated, peaking at the 12th week. The rate of growth slows down after week 12 which may be associated with the fusion of the premaxillary-maxillary suture.

Determination of age from fusion of skull vault sutures

Background: Cranial suture closure has long been recognized as a character of human development related to aging. For this reason, it has been utilized for various forensic and archaeological studies to determine the age of an unidentified/or skeletonized individuals. Various cadaveric studies have established the role of lambdoid suture in age estimation, but not routinely practiced. Age estimation is an integral part of the biological profile employed by forensic anthropologists in order to assist in achieving an identification of an unknown deceased individual. The main objective of this article is to determine the pattern of cranial vault suture closure in relation to age. Material and methods: Total number of 90 subjects, 25 years and beyond were included in the study, and divided into four groups with an age interval of 10 years. Each individual was subjected to radiological examination of the skull with a view to• study the Sagittal, Coronal and Lambdoid sutures, a special view was evolved by trial in order to get all the basic three sutures in one film. Ectocranial and endocranial closure pattern were studied. Result: A significant difference was observed between the age group and suture closure. Coronal suture was the first to fuse followed by sagittal suture. Lambdoid suture. Endocranially, starts fusing at the age of 25‐30 yrs. Closure was found earlier in females compared to males. Conclusion: Suture obliteration occurs earlier on endocranial surface. Based on endocranial suture fusion, Coronal suture was first to close followed by sagittal suture, lambdoid suture sequentially.

Endoscopic-assisted craniosynostosis surgery: First case series in India

<br><b>Introduction:</b> Craniosynostosis is a congenital pathological condition resulting from premature fusion of sutures of the cranial vault and leads to an abnormal head shape with a significant risk of raised intracranial pressure. Surgical correction techniques have seen a constant evolution from an extensive open procedure to the relatively new minimally invasive craniosynostosis technique. The current center introduced this new procedure in India since 2015. <b>Aims and Objectives:</b> This article documents our experience as the first team in the country to correct craniosynostosis endoscopically with emphasis on planning, surgical techniques, and helmet therapy to achieve the optimum result. <b>Materials and Methods:</b> This is a prospective case series of six patients with anterior craniosynostosis corrected endoscopically and followed up with postoperative custom-made cranial helmet. All patients were nonsyndromic with no associated anomalies. The mean age of surgical intervention was 92.6 days (84–100 days), mean duration of surgery was 61.7 min (54–74 min), mean blood loss was 55 ml (50 ml–60 ml), and mean duration of hospital stay was 2 days (2–3 days). No complications and mortality were reported. <b>Conclusion:</b> This case series has demonstrated that endoscopically assisted craniosynostosis correction is a safe, effective, and reliable technique in the armamentarium of a craniofacial surgeon. The minimally invasive nature allows early intervention in children. Parental compliance is important in helmet therapy which forms an integral part of this surgery for correction of the abnormal head shape. We believe that every patient with nonsyndromic single-suture craniosynostosis should be offered endoscopic correction before the age of 6 months.<br>

The antenatal diagnosis of isolated sagittal craniosynostosis

Introduction Isolated sagittal craniosynostosis is the most common premature sutural fusion, but is rarely diagnosed antenatally. There are now a number of reports in the literature describing delivery issues in infants later diagnosed with sagittal synostosis(1-6). The aim of this study was to investigate whether delivery issues are more common in children diagnosed with sagittal synostosis, and identify markers at antenatal ultrasound that could help diagnose the condition before birth. Methods The antenatal ultrasound images of children born in South Australia and the Northern Territory after 1/1/2000 who have diagnosed with isolated sagittal synostosis were compared with antenatal imaging from normal infants without any craniofacial defects. The delivery details from the affected children were also compared to the population delivery data over an extended time period. Results There was a statistically significantly higher rate of malpresentation and surgical delivery in the sagittal synostosis population. There no significant difference in the cephalic index between the 2 groups at mid trimester morphology scanning. The ultrasound scans showed progressive scaphocephaly during the second half of pregnancy in the affected children while the control population showed minimal change in head shape with a slight tendency towards brachycephaly. Conclusions 1. Isolated sagittal synostosis typically begins in the second half of pregnancy, and is not detectable antenatally at the mid trimester morphology scan. 2. It is possible to diagnose sagittal synostosis in the third trimester by noting a progressive decrease in the fetal cephalic index, which should provoke 3D ultrasound scanning of the fetal skull to examine the sagittal suture. 3. There is a clear relationship between the presence of sagittal craniosynostosis and breech presentation at delivery in affected fetuses, with a marked increase in the rate surgical deliveries in this group of infants.