Nonsyndromic Craniosynostosis Research Articles

Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?

Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC. Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age. Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041). ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.

Effect of Operative Timing and Bone Grafting on Postoperative Cephalometric Indices in Nonsyndromic Sagittal Synostosis.

Surgical repair of sagittal suture craniosynostosis is highly variable, and optimal timing/use of bone grafts remains a subset of parameters that continue to be studied. We sought to compare cephalometric outcomes of early surgical intervention without bone grafting compared to later intervention with bone grafting. Patients undergoing primary surgical repair of nonsyndromic sagittal suture craniosynostosis between 2015 and 2019 were followed with preoperative measurements of cephalic index along with postoperative measurements at 6 months to 1 year, respectively. Nineteen patients undergoing cranial vault reconstruction were studied in 2 groups, namely those younger than 6 months who did not have bone grafting performed during primary repair (31.6%) and patients 6 months and older who underwent cranial vault reconstruction with bone grafting during primary repair (68.4%). Mean 6-month to 1-year postoperative cranial index was significantly increased in both groups (P < 0.001). The average cephalic index change for both groups (younger than 6 months without bone grafting, CI value change 9; 6 months and older with bone grafting; CI value change 6) was not significantly different with regards to 95% confidence interval (P = 0.30). Patients older than 6 months of age undergoing cranial vault reconstruction with bone grafting have similar cephalometric outcomes as their younger counterparts undergoing cranial vault remodeling without bone grafting. Bone grafting in the appropriate cohort may improve functional and esthetic outcomes without compromising primary surgical goals of improving cranial vault cephalometric indices.

Comparison of Neurocognitive Outcomes in Postoperative Adolescents with Unilateral Coronal Synostosis

Unilateral coronal nonsyndromic craniosynostosis is associated with asymmetric skull growth, which may influence cerebral long-term function. Twenty affected adolescents who underwent cranial vault remodeling at a mean age of 8.2 months (12 from the Yale Craniofacial Clinic and eight from the Children's Hospital of Philadelphia) all completed a double-blinded neurodevelopmental assessment at an average age of 12.1 years. The study cohort included 55 percent female and 50 percent right-sided craniosynostosis. Mean verbal intelligence quotient was highest at 117.3, and mean performance intelligence quotient was 106.4, for a mean full-scale intelligence quotient of 112.5. Patients performed above the national average on all academic achievements except for numerical operations, which was significantly lower than word reading (p = 0.022). Patients performed below average on all Beery-Buktenica visual motor tests; motor-coordination was poorer than both visual motor integration and visual perception (p = 0.027 and p = 0.005). Significant positive correlations existed between paternal education/visual perception (r = 0.450; p = 0.046) and household income/verbal intelligence quotient (r = 0.628; p = 0.004). Patients with right unilateral coronal nonsyndromic craniosynostosis had improved spelling compared with left-sided patients on multivariate regression (p = 0.033). Female patients had higher motor coordination (p = 0.024). Breast-fed patients had better performance intelligence quotient (p = 0.024), visual motor integration (p = 0.014), and visual perception (p = 0.031). Adolescents who underwent cranial vault remodeling at two institutions had above average intelligence quotient scores, but worse mathematical and visual motor achievement compared with control subjects. Left-side craniosynostosis patients performed worse in spelling than right-side patients. Breast-feeding was an independent predictor for improved performance intelligence quotient, visual motor achievement, and visual perception performance. Study findings are limited by the cohort size. A larger population study is required, which could validate or modify the study conclusions.

Understanding families’ experiences following a diagnosis of non-syndromic craniosynostosis: a qualitative study

ObjectivesCraniosynostosis is typically diagnosed and surgically corrected within the first year of life. The diagnosis and surgical correction of the condition can be a very stressful experience for families. Despite...

A Technique for Minimizing the Need for Hemotransfusion in Non-Syndromic Craniosynostosis Surgery.

Surgery for craniosynostosis is associated with excessive blood loss, as well as morbidity and mortality risks. This study investigated the effectiveness of a surgical technique for nonsyndromic craniosynostosis intervention in controlling bleeding, assessed based on the volume of blood transfused. The cohort included 73 children who underwent nonsyndromic craniosynostosis surgery during a 3-year period. Retrospective evaluation of patient parameters included sex, weight, and age at the time of surgery; type of craniosynostosis; duration of surgery; hemoglobin concentration before and after surgery; rate of transfusion; and volume of transfused blood (mL/kg). The surgical technique involved skin incision and subgaleal dissection using electrocautery with a Colorado needle tip. The pericranium was not removed but instead kept in situ, and orbiectomy was performed using piezosurgery. Of the 73 children in the cohort, 75.3% underwent fronto-orbital advancement and were included in the analysis. The average age was 10.9 months (range: 4-96 months), with 68.5% boys and 31.5% girls (P < 0.001). The most common type of craniosynostosis was trigonocephaly (57.5%), followed by scaphocephaly (19.2%). The mean duration of the surgery was 2 hours and 55 minutes. Blood transfusion was needed in 56.2% of patients, with a mean volume of 8.7 mL/kg body weight transfused intraoperatively. No complications or fatalities were observed. These results suggested that meticulous, continuous control of homeostasis is paramount in minimizing blood loss during surgical repair of nonsyndromic craniosynostosis.

A-068 Case Study: Neurodevelopment of Late Identification and Treatment of Nonsyndromic Multisutural Craniosynostosis

Abstract Objective Craniosynostosis, the premature closure of cranial sutures, is frequently associated with intracranial hypertension, neurocognitive deficits, and neuromotor deficits. Younger age at treatment is associated with improved outcomes. This case study will expand upon the existing literature by characterizing the neurodevelopment of an individual whose nonsyndromic multisutural craniosynostosis was identified and treated late, when the patient was nearly three years old. Method A 7-year, 1-month old male with a history of bicoronal and sagittal craniosynostosis was seen for neuropsychological assessment. Diagnosis and cranial vault reconstruction occurred just before his third birthday. Evidence of increased intracranial pressure was found on presurgical CT scan, and by the appearance of his dura at surgery. His development after reconstruction was notable for articulation disorder, expressive language disorder, executive dysfunction, and adaptive skills deficits. Results Assessment revealed average non-verbal cognitive skills and low average verbal cognitive skills. Receptive language was below average. Exceptionally low scores were found on tasks of oromotor sequencing, verbal list learning, and immediate visual memory. Teacher ratings of executive functioning suggest below average skills. Measures of attention and impulsivity suggest mild weaknesses. Academically, he earned below average and exceptionally low scores on measures of reading and writing, with low average to average mathematics scores. Conclusions The neurodevelopment of children with late diagnosis/treatment of craniosynostosis is not well characterized and may confer increased risks. Late diagnosis is presumed to lead to more significant neurocognitive impairments due to the impact of prolonged intracranial pressure. Neuropsychological assessment and follow-up is critical for monitoring and intervention planning.

Sphenoid Bone Structure and Its Influence on the Cranium in Syndromic Versus Nonsyndromic Craniosynostosis.

Little is known about the detailed growth of the sphenoidal and temporal bones, even though they contribute significantly to the cranial base and cranial fossa skeletons. They also serve to connect the cranial vault with facial structure. This study details their morphologic development in isolated bicoronal synostosis and associated syndromes. Eighty-one CT scans were included (nonsyndromic bicoronal synostosis, n = 28; Apert syndrome associated with bicoronal synostosis, n = 19; Crouzon syndrome associated with bicoronal synostosis, n = 8; and controls, n = 26), and measured using Materialize software. Sphenoidal and temporal bone volumes in nonsyndromic bicoronal synostosis are reduced 23% (P = 0.005) and 24%(P = 0.003) at 6 months of age, compared to controls. Apert and Crouzon syndrome patients developed similar reduced volumes. The greater wing of the sphenoid and pterygoid processes in nonsyndromic bicoronal synostosis are initially inferiorly rotated at 2 months of age, by 9.60° (P = 0.002) and 4.33° (P = 0.023), respectively. In Apert syndrome, these rotations were reduced by 4.82° (P = 0.003) and 12.60° (P < 0.001), (like Crouzon syndrome). However, in Apert syndrome, the length of pterygoid processes is shortened by 11% (P = 0.018) compared to nonsyndromic bicoronal synostosis. Crouzon syndrome skulls did not develop a statistically significant shortening relative to nonsyndromic bicoronal synostosis. Mediolateral expansion of the sphenoid in nonsyndromic bicoronal synostosis was less than normal (P = 0.023), and it was further reduced in syndromic skulls. Isolated bicoronal synostosis tends to reduce the volume of sphenoidal and temporal bones, and inferior and posterior rotation of the entire sphenoid. Syndromic conditions restrict sphenoidal rotation, and limit the expansion of sphenoidal greater wing and pterygoid plate.

Nonsyndromic Craniosynostosis Is Associated with Increased Risk for Psychiatric Disorders.

Craniosynostosis is one of the most common craniofacial malformations demanding surgical treatment in infancy. Data on overall psychiatric morbidity among children with nonsyndromic craniosynostosis remain limited. This study investigated the risk of psychiatric disorders in nonsyndromic craniosynostosis. The authors reviewed a register-based cohort of all individuals born with nonsyndromic craniosynostosis in Sweden between 1973 to 1986 and 1997 to 2012 (n = 1238). The nonsyndromic craniosynostosis cohort was compared with a matched community cohort (n = 12,380) and with unaffected full siblings (n = 1485). The authors investigated the risk of psychiatric disorders, suicide attempts, and suicides by using Cox regression adjusted for perinatal and somatic factors, season and birth year, sex, parental socioeconomic factors, and parental psychiatric disorders. Children with nonsyndromic craniosynostosis had a higher risk of any psychiatric disorder (adjusted Cox-derived hazard ratio, 1.70; 95 percent CI, 1.43 to 2.02), including intellectual disability (adjusted Cox-derived hazard ratio, 4.96; 95 percent CI, 3.20 to 7.70), language disorders (adjusted Cox-derived hazard ratio, 2.36; 95 percent CI, 1.57 to 3.54), neurodevelopmental disorders (adjusted Cox-derived hazard ratio, 1.30; 95 percent CI, 1.01 to 1.69), and other psychiatric disorders (adjusted Cox-derived hazard ratio, 1.43; 95 percent CI, 1.11 to 1.85). Full siblings with nonsyndromic craniosynostosis were more likely, in the crude analyses, to be diagnosed with any psychiatric disorder, including intellectual disability, language disorders, and neurodevelopmental disorders compared with nonaffected siblings. The higher risk for any psychiatric disorder and intellectual disability remained after adjusting for confounders. Children with nonsyndromic craniosynostosis demonstrated higher risks of any psychiatric disorder compared with children without nonsyndromic craniosynostosis. This risk cannot fully be explained by familial influences (i.e., genetic or environmental factors). Risk, III.

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Dysfunction of the gonadotropin-releasing hormone (GnRH) axis causes a range of reproductive phenotypes resulting from defects in the specification, migration and/or function of GnRH neurons. To identify additional molecular components of this system, we initiated a systematic genetic interrogation of families with isolated GnRH deficiency (IGD). Here, we report 13 families (12 autosomal dominant and one autosomal recessive) with an anosmic form of IGD (Kallmann syndrome) with loss-of-function mutations in TCF12, a locus also known to cause syndromic and non-syndromic craniosynostosis. We show that loss of tcf12 in zebrafish larvae perturbs GnRH neuronal patterning with concomitant attenuation of the orthologous expression of tcf3a/b, encoding a binding partner of TCF12, and stub1, a gene that is both mutated in other syndromic forms of IGD and maps to a TCF12 affinity network. Finally, we report that restored STUB1 mRNA rescues loss of tcf12 in vivo. Our data extend the mutational landscape of IGD, highlight the genetic links between craniofacial patterning and GnRH dysfunction and begin to assemble the functional network that regulates the development of the GnRH axis.

Cognitive performance of preschool children with different types of non-syndromic craniosynostosis

AbstractBackground:Craniosynostosis is defined as a premature fusion of one or more cranial sutures. Several studies have revealed cognitive deficits in some children who had undergone surgery to treat craniosynostosis. However, no general distinction has been drawn in the cognitive abilities between the various types of craniosynostosis. The purpose of the present study was to analyze if there is a difference in cognitive and motor function among the different types of non-syndromic craniosynostosis in preschool children.Methods:Twenty-seven children with different types of non-syndromic craniosynostosis were assessed using the Wechsler Preschool and Primary Scale of Intelligence – Third Edition, as well as the Quantitative, Memory and Motor scales of McCarthy Scales of Children’s Abilities (MSCA). The children were aged between 3 and 5 years and 11 months. The various types of craniosynostosis were compared.Results:The unicoronal synostosis group performed significantly worse than the multisuture synostosis group on the MSCA Motor scale. No differences in cognitive functions were found between the various types of craniosynostosis.Conclusions:Children with unicoronal synostosis may experience impaired motor skills and screening of their motor ability is recommended.

Craniometric and Volumetric Analyses of Cranial Base and Cranial Vault Differences in Patients With Nonsyndromic Single-Suture Sagittal Craniosynostosis.

How different from "normal" are the cranial base and vault of infants with nonsyndromic, single-suture sagittal synostosis (NSSS)? This study quantitatively addresses this question utilizing computed tomography (CT) analytic technology. Head CT scans of infants with NSSS and normocephalic controls were analyzed using Mimics to calculate craniometric angles, distances, and segmented volumes. Craniometric measurements and asymmetry indices were compared between NSSS and control groups using linear regressions controlling for age. Ratios of anterior-, middle-, and posterior-to-total cranial vault volume were compared between groups using beta regressions controlling for age. Seventeen patients with NSSS and 19 controls were identified. Cranial index and interoccipital angle were significantly smaller in NSSS compared with controls (P = 0.003 and <0.001, respectively). Right-but not left-external acoustic meatus angle and internal acoustic meatus-to-midline distance were significantly greater in NSSS than in controls (P = 0.021 and 0.016, respectively). NSSS patients and controls did not significantly differ in any asymmetry indices, except for the articular fossa angle asymmetry index (P = 0.016). Anterior vault volume proportion was greater in NSSS relative to controls (proportion ratio = 1.63, P < 0.001). NSSS trended toward a smaller posterior vault volume proportion (P = 0.068) yet did not differ in middle vault volume proportion compared with controls. In this small study, patients with nonsyndromic, single-suture sagittal craniosynostosis had relatively similar cranial base measurements, and larger anterior vault volumes, when compared with controls. Further work is needed to confirm the possibility of rightward asymmetry of the anterior cranial base.

Public Perception of a Normal Head Shape in Children With Sagittal Craniosynostosis

Twenty-two unique images were presented via an online crowdsourcing survey of a severe case of non-syndromic sagittal craniosynosis gradually corrected to an age and gender matched normalized head shape. Participants were recruited via the Sick Kids Twitter account. Participants were invited to rate the head shapes as "normal" or "abnormal." The 538 participants completed the online survey. Participants were able to reliably and consistently identify normal and abnormal head shapes with a Kappa Score >0.775. Furthermore, participants indicated that a correction of 70% is required in order for the cranial deformity to be regarded as "normal." This threshold closely reflects a normal Cranial Index, which is a widely used morphometric outcome in craniosynostosis. Crowdsourcing provides an ideal method for capturing the general population's perspective on what constitutes a normal and acceptable head shape in children with sagittal craniosynostosis. Laypersons are able to reliably and consistently distinguish cranial deformities from a "normal" head shape. The public indicates a threshold correction of 70% in sagittal craniosynosis to regard it as a "normal" head shape.

What Is the Skull Structure Influence of Squamosal Suture Synostosis in Nonsyndromic and Syndromic Crouzon Craniosynostosis?: Erratum.

What Is the Skull Structure Influence of Squamosal Suture Synostosis in Nonsyndromic and Syndromic Crouzon Craniosynostosis?: Erratum.

The Effect of Fronto-Orbital Advancement on Frontal Sinus Development and Function in Non-Syndromic and Syndromic Craniosynostosis.

The impact of fronto-orbital advancement (FOA) on frontal sinus development and function is anecdotally variable. The aim of this study was to assess the impact of FOA on development of frontal sinuses, and additionally to identify the complications that might arise out of such procedures. This was a retrospective case-control study. Non-syndromic and syndromic craniosynostosis patients (n = 58) who underwent FOA at an early age and also had a skull radiograph or CT scan after the age of 12 were selected. Age matched trauma patients with CT scans done beyond 12 years of age were used as controls. Age at first FOA surgery, total number of procedures and age at imaging was noted. Presence or absence of frontal sinuses was assessed using imaging studies initially. Patients with a formed frontal sinus and a CT scan were further chosen for volumetric studies. Complications related to frontal sinus and secondary surgeries were recorded. One of 27 non-syndromic patients had absent frontal sinuses. Seven of 31 syndromic patients had absent sinuses. Among 20 controls, only 1 patient did not develop frontal sinuses. The mean age at first FOA was 11.81 months and 18.25 months for non-syndromic and syndromic groups, respectively. The average number of procedures before 12 years of age was 1.25 and 1.51 for non-syndromic and syndromic patients, respectively. The mean age at imaging was 17.74, 20.96, and 20.25 years for non-syndromic, syndromic and control groups, respectively. The mean frontal sinus volumes were 13050.36, 15039.02, and 8459.48 mm for non-syndromic, syndromic and control groups, respectively. In conclusion, FOA does not seem to have an impact on rate of pneumatization in the background of similar rates in the non-syndromic and control groups. The low pneumatization rate in syndromic group might be a virtue of the disease itself. There were significant frontal sinus complications that occurred after fronto orbital advancement and this should be borne in mind during the surgical consenting process.

Gain-of-function variants and overexpression of RUNX2 in patients with nonsyndromic midline craniosynostosis.

Craniosynostosis (CS), the premature fusion of one or more cranial sutures, is a relatively common congenital anomaly, occurring in 3-5 per 10,000 live births. Nonsyndromic CS (NCS) accounts for up to 80% of all CS cases, yet the genetic factors contributing to the disorder remain largely unknown. The RUNX2 gene, encoding a transcription factor critical for bone and skull development, is a well known CS candidate gene, as copy number variations of this gene locus have been found in patients with syndromic craniosynostosis. In the present study, we aimed to characterize RUNX2 to better understand its role in the genetic etiology and in the molecular mechanisms underlying midline suture ossification in NCS. We report four nonsynonymous variants, one intronic variant and one 18bp in-frame deletion in RUNX2 not found in our study control population. Significant difference in allele frequency (AF) for the deletion variant RUNX2 p.Ala84-Ala89del (ClinVar 257,095; dbSNP rs11498192) was observed in our sagittal NCS cohort when compared to the general population (P=1.28×10-6), suggesting a possible role in the etiology of NCS. Dual-luciferase assays showed that three of four tested RUNX2 variants conferred a gain-of-function effect on RUNX2, further suggesting their putative pathogenicity in the tested NCS cases. Downregulation of RUNX2 expression was observed in prematurely ossified midline sutures. Metopic sites showed significant downregulation of promoter 1-specific isoforms compared to sagittal sites. Suture-derived mesenchymal stromal cells showed an increased expression of RUNX2 over matched unfused suture derived cells. This demonstrates that RUNX2, and particularly the distal promoter 1-isoform group, are overexpressed in the osteogenic precursors within the pathological suture sites.

Early Extended Midline Strip Craniectomy for Sagittal Synostosis.

Isolated sagittal synostosis is the most common form of nonsyndromic craniosynostosis. The surgical management of this condition ranges from strip craniectomy to total cranial vault remodeling. In our unit, passive correction of sagittal synostosis utilizing open extended midline strip craniectomy with bilateral micro-barrel staving is performed before 22 weeks corrected age. The aim of this prospective study is to identify the effectiveness and morbidity associated with this technique. Nonsyndromic patients who underwent OMEC at a tertiaryreferral-center (Alder Hey Children's Hospital, Liverpool, UK) over a 3-year period (2014-2016) were included. In particular, we looked at pre- and postoperative cranial index (CI), as well as other secondary outcomes such as rates of transfusion and reoperation. A total of 44 patients (12 female, 32 male) met the inclusion criteria. Median age at operation was 132 (range 99-171) days. Median operative time was 117 (range 89-171) minutes. Twenty-four patients underwent a blood transfusion. Median pre-op CI was 66 (range 61-74.7)%. The first post-op CI, taken a median of 56 (range 12-107) days postoperatively, was 78 (range 73-87)%. No patients required reoperation. There were no perioperative deaths. Early open extended midline strip craniectomy with bilateral micro-barrel staving for correction of isolated nonsyndromic sagittal synostosis is a safe and effective technique, associated with minimal morbidity, producing sustained satisfactory head shape morphology on short to medium-term follow-up.

A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10-8): rs781716 (P = 4.71 × 10-9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10-8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10-9; OR = 0.34), located ~ 155kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10-8, OR = 0.45; P = 3.31 × 10-8, OR = 0.45; P = 1.09 × 10-8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10-8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10-6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Epidemiology of craniosynostosis in Norway.

The authors present population-based epidemiological data for craniosynostosis regarding incidence, age at diagnosis, sex differences, and frequency of syndromic and familial cases. The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve data on all individuals with craniosynostosis treated between 2003 and 2017. The cohort was divided into three 5-year groups based on year of birth: 2003-2007, 2008-2012, and 2013-2017. The authors identified 386 individuals with craniosynostosis. Of these, 328 (85%) consented to be registered with further information. The incidence increased significantly during the study period and was 5.5 per 10,000 live births (1/1800) in the last 5-year period. The increase was seen almost exclusively in the nonsyndromic group. Syndromic craniosynostosis accounted for 27% of the cases, and the incidence remained stable throughout the three 5-year periods. Both syndromic and nonsyndromic craniosynostosis were highly suture specific. There was a male preponderance (male/female ratio 2:1), and males accounted for 75% of the individuals with midline synostosis. Overall, 9.5% were index individuals in families with more than one affected member; of these, 73% were nonsyndromic cases. The incidence of craniosynostosis increased during the study period, and the observed incidence is among the highest reported. The authors attribute this to increasing awareness among healthcare professionals. The number of syndromic cases was high, likely due to a broader definition compared to the majority of earlier reports. The study revealed a high number of familial cases in both syndromic and nonsyndromic craniosynostosis, thus highlighting the importance of genetics as an underlying cause of craniosynostosis.

Single-suture craniosynostosis: is there a correlation between preoperative ophthalmological, neuroradiological, and neurocognitive findings?

In spite of literature data stating that children with single-suture craniosynostosis have an increased risk for neuropsychological deficits, no data are present clarifying the potential risk factors. All children with non-syndromic single-suture craniosynostosis operated on from January 2014 to January 2017 were enrolled. A comprehensive neurocognitive and neuro-ophthalmological evaluation was performed before surgery and 6months after surgery. A further neurocognitive evaluation was performed 12months after surgery. All children had a preoperative CT/MR study. One hundred forty-two patients were enrolled; 87 are affected by sagittal craniosynostosis, 38 by trigonocephaly, and 17 by plagiocephaly. A global neurocognitive impairment was documented in 22/87 children with scaphocephaly, 5/38 children with trigonocephaly, and 6/17 children with anterior plagiocephaly. There was a significant relationship between results of the ophthalmological evaluation, global IQ, and CT findings at diagnosis (r= 0.296, p< 0.001; r=0.187, p 0.05). Though a significant recovery was documented after surgery, a persistence of eye coordination deficits was present at 6months in 1 out of 3 children with abnormal preoperative exams. A significant correlation was found between pathological CT findings and persistence of below average neuro-ophthalmological and neurocognitive findings 6months after surgery, as well as between CT findings and neurocognitive scores at the 1year follow-up (r= 0.411; p< 0.01). The presence of neuroradiological abnormalities appears to be related to both ophthalmological and neurocognitive deficits at diagnosis. This relationship is maintained in spite of the surgical treatment in children who show the persistence of ophthalmological and neurocognitive deficits during the follow-up.

Discussion: Secondary Suture Fusion after Primary Correction of Nonsyndromic Craniosynostosis: Recognition of the Problem and Identification of Risk Factors.

Dallas, Texas From The Craniofacial Center. Received for publication July 30, 2019; accepted August 8, 2019. Disclosure:The author has no financial interest to declare in relation to the content of this Discussion or of the associated article. No funding was received for this work. Jeffrey A. Fearon, M.D., The Craniofacial Center, 7777 Forest Lane, Suite C-700, Dallas, Texas 75230, [email protected], Twitter: @Jeffrey_Fearon