Epidemiologic Assessment of Craniosynostosis in Mississippi's Pediatric Population from 2015 to 2020.

OBJECTIVES: This study aimed to report geographic and demographic patterns of patients with craniosynostosis (CS) treated at Children's of Mississippi, the state's only American Cleft Palate-Craniofacial Association-approved craniofacial team. METHODS: Patients with CS were treated at a tertiary pediatric hospital cared for by craniofacial surgeons and neurosurgeons from 2015 to 2020. Demographic, geographic, and CS diagnosis details, including sex, gestational age, race, ethnicity, insurance status, and affected cranial suture type(s), number, and associated syndromic diagnosis were collected, including birth county and total live births from state data. Significant differences between prevalence of CS in four regions of Mississippi were examined using two-tailed t tests (P < 0.05). RESULTS: Among 222,819 live births in Mississippi between 2015 and 2020, 79 pediatric patients presented to Children's of Mississippi with CS, with an overall incidence of 0.355/1000 live births. Most cases were nonsyndromic CS (82%, n = 65) affecting a single major cranial suture (81%, n = 64). The overall incidence of CS was higher in the coastal and central regions compared with northeast Mississippi, at 0.333 and 0.527 vs 0.132/1000 live births (P = 0.012 and P = 0.004), respectively. CONCLUSIONS: Results from this study suggest regional patterns of CS in Mississippi, which may reflect actual incidence patterns or proximity to Children's of Mississippi. Further study could reveal regional differences in risk factors underlying CS incidence or access to specialized CS care for different regions in the state. This will lead to opportunities for institutional outreach to decrease the burden of CS care in Mississippi.

Use of piezoelectric instrumentation in craniofacial surgery.

PURPOSE OF REVIEW: The use of piezoelectric instrumentation is increasingly recognized as an alternative to traditional bone-cutting techniques across a wide array of surgeries. Here, we provide an overview of the technique, including device principles, benefits, and drawbacks. We also review its use in craniofacial surgery. RECENT FINDINGS: Piezoelectric surgery is a minimally invasive bone-cutting system with lower risk of damage to surrounding soft tissue structures. Indications for its use are rapidly expanding across multiple fields, including craniofacial surgery. To date, piezosurgical techniques have been most widely adopted and studied in the contexts of rhinoplasty, orthognathic surgery, and cranioplasty in craniosynostosis. Piezosurgery can facilitate more precise and consistent osteotomies while decreasing morbidities associated with traditional osteotomy techniques. Primary limitations include cost and concerns regarding increased operative times secondary to operator learning curves and decreased cutting efficiency. SUMMARY: Piezoelectric surgery represents an alternative to traditional bone-cutting modalities to improve precision, consistency, and safety of osteotomies. Further research is needed to better understand the efficacy of the technique as well as potential for additional applications.

Plastic Surgery Outreach Clinics Expand Access to Cleft and Craniofacial Care in Mississippi.

ABSTRACT: Accessing treatment at ACPA (American Cleft Palate-Craniofacial Association)-approved centers is challenging for individuals in rural communities. This study aims to assess how pediatric plastic surgery outreach clinics impact access for patients with orofacial cleft and craniosynostosis in Mississippi. An isochrone map was used to determine mean travel times from Mississippi counties to the sole pediatric hospital and the only ACPA-approved team in the state. This analysis was done before and after the establishment of two outreach clinics to assess differences in travel times and cost of travel to specialized plastic surgery care. Two sample t-tests were used for analysis.The addition of outreach clinics in North and South Mississippi led to a significant reduction in mean travel times for patients with cleft and craniofacial diagnoses across the state's counties (1.81 hours vs 1.46 hours, P < 0.001). Noteworthy travel cost savings were observed after the introduction of outreach clinics when considering both the pandemic gas prices ($15.27 vs $9.80, P < 0.001) and post-pandemic prices ($36.52 vs $23.43, P < 0.001).The addition of outreach clinics in Mississippi has expanded access to specialized healthcare for patients with cleft and craniofacial differences resulting in reduced travel time and cost savings for these patients. Establishing specialty outreach clinics in other rural states across the United States may contribute significantly to reducing burden of care for patients with clefts and craniofacial differences. Future studies can further investigate whether the inclusion of outreach clinics improves follow-up rates and surgical outcomes for these patients.

Attention Deficit/Hyperactivity Disorder in Individuals with Non-Syndromic Craniosynostosis: A Systematic Review and Meta-Analysis.

It is not yet understood whether, and to what extent, craniosynostosis impacts the development of Attention Deficit/Hyperactivity Disorder (ADHD). This PRISMA compliant and PROSPERO pre-registered (ID: CRD42023458640) systematic review and meta-analysis examines the association of single-suture, non-syndromic craniosynostosis with ADHD and inattention/hyperactivity symptoms. Data from 17 independent studies (Nparticipants = 2,389; Mage = 7.3 years) were analyzed, taking into consideration suture location, surgical status, age, and measures administered, where feasible. Few differences were found between cases and controls, but some studies reported high symptom levels. Additional research is required utilizing larger sample sizes and more comprehensive assessment of ADHD.

Perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II.

OBJECTIVE: We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2). CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene. CONCLUSION: Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.

Endoscopic surgery for craniosynostosis: A systematic review and single-arm meta analysis.

BACKGROUND: Craniosynostosis, a developmental craniofacial anomaly, can impair brain development and cause abnormal skull shape due to premature closure of one or more cranial sutures. Traditional surgical treatments have evolved from open operations to minimally invasive endoscopic techniques. This systematic review and meta-analysis aim to evaluate the effectiveness and safety of the endoscopic approach in craniosynostosis correction. METHODS: Adhering to Cochrane Group standards and the PRISMA framework, this review utilized databases like PubMed, Embase, and Web of Science, focusing on clinical and surgical outcomes of endoscopic craniosynostosis operations up to December 2023. Inclusion criteria emphasized studies with at least five patients undergoing endoscopic procedures, while exclusion criteria involved non-English papers, incomplete texts, and overlapping data. Statistical analysis used R software with various packages, and methodological bias was assessed using the ROBINS-I framework. RESULTS: The review included 30 studies (4 prospective, 26 retrospective) with 2561 patients. The median age at operation was 3.20 months. Findings showed a mean operative time of 68.06 min, median hospital stay of 1.28 days, and mean blood loss of 29.89 ml. Blood transfusion was required in 9.97% of cases. Helmet therapy post-operation was common, with a median duration of 9 months. The rate of postoperative complications was 1.86%, and the reoperation rate was 3.07%. No procedure-related mortality was observed. The study noted substantial variations in the handling of craniosynostosis and a lack of consensus on the optimal timing and surgical approach. CONCLUSION: Endoscopic techniques for craniosynostosis repair demonstrate safety and effectiveness, characterized by low complication risks and favorable surgical outcomes. However, due to the limitations of observational studies and inherent heterogeneity, further comprehensive and controlled trials are needed to validate these findings and understand the long-term outcomes of the endoscopic approach.

A computational modelling tool for prediction of head reshaping following endoscopic strip craniectomy and helmet therapy for the treatment of scaphocephaly.

BACKGROUND: Endoscopic strip craniectomy followed by helmet therapy (ESCH) is a minimally invasive approach for correcting sagittal craniosynostosis. The treatment involves a patient-specific helmet designed to facilitate lateral growth while constraining sagittal expansion. In this study, finite element modelling was used to predict post-treatment head reshaping, improving our comprehension of the necessary helmet therapy duration. METHOD: Six patients (aged 11 weeks to 9 months) who underwent ESCH at Connecticut Children's Hospital were enrolled in this study. Day-1 post-operative 3D scans were used to create skin, skull, and intracranial volume models. Patient-specific helmet models, incorporating areas for growth, were designed based on post-operative imaging. Brain growth was simulated through thermal expansion, and treatments were modelled according to post-operative Imaging available. Mechanical testing and finite element modelling were combined to determine patient-specific mechanical properties from bone samples collected from surgery. Validation compared simulated end-of-treatment skin surfaces with optical scans in terms of shape matching and cranial index estimation. RESULTS: Comparison between the simulated post-treatment head shape and optical scans showed that on average 97.3 ± 2.1 % of surface data points were within a distance range of -3 to 3 mm. The cranial index was also accurately predicted (r = 0.91). CONCLUSIONS: In conclusion, finite element models effectively predicted the ESCH cranial remodeling outcomes up to 8 months postoperatively. This computational tool offers valuable insights to guide and refine helmet treatment duration. This study also incorporated patient-specific material properties, enhancing the accuracy of the modeling approach.

Posterior Vault Distraction in the Acute Setting.

ABSTRACT: Posterior vault distraction osteogenesis (PVDO) has been shown to resolve acute intracranial hypertension (AIH) while carrying an acceptable perioperative morbidity profile. PVDO has been associated with symptomatic improvement and fewer surgeries in those requiring ventriculoperitoneal shunts. The authors' experience using PVDO as an acute intervention is presented, demonstrating its safety and efficacy for management of AIH. Four cases of children with craniosynostosis that underwent PVDO in the acute setting are outlined. All patients presented with papilledema and symptoms of AIH. One patient with slit ventricle syndrome (SVS) presented with a nonfunctioning shunt following multiple shunt revisions. No intraoperative complications during distractor placement or removal were reported. Distraction protocol for all patients began on postoperative day 1 at 1-2 mm per day, resulting in an average total distraction of 30.25 mm. For the 3 cases with no shunt, the average length of stay was 7 days. As part of the planned treatment course, the patient with SVS required externalization of the shunt during distraction followed by early distractor removal and planned shunt replacement. One case of surgical site infection (in an immunocompromised patient) required premature distractor removal during the consolidation period. Computed tomography (CT) in all patients indicated increased intracranial volume following distraction, and symptomatic improvement was reported. Six-month follow-up showed resolution of papilledema in all patients. The authors' experience using PVDO in the acute setting is reported, alongside a review of current literature, in order to provide supporting evidence for the efficacy of PVDO as a tool for resolving AIH.

Validating the Supraorbital Notch-Nasion-Supraorbital Notch Angle as a Marker for Metopic Craniosynostosis Severity.

OBJECTIVE: Metopic craniosynostosis (MCS) can be difficult to differentiate from metopic ridge (MR) or normal frontal morphology. This study assess whether the supraorbital notch-nasion-supraorbital notch (SNS) angle can help identify MCS. METHODS: Records of 212 patients with preoperative three-dimensional computed tomography scans were examined. The SNS angles, surgeon craniofacial dysmorphology rankings, and CranioRate metopic severity scores (MSSs) were compared with the Spearman rank correlation coefficient. Receiver operating characteristic (ROC) curves with Youden J-statistic and cross-validation of regression models assessed the ability of these measures to predict surgery. RESULTS: A total of 212 patients were included, consisting of 78 MCS, 37 MR, and 97 controls. Both the mean SNS angle (MCS: 111.7 ± 10.7 degrees, MR: 126.0 ± 8.2 degrees, controls: 130.7 ± 8.8 degrees P < 0.001) and MSS (MCS: 5.9 ± 2.0, MR: 1.4 ± 1.9, controls: 0.2 ± 1.9, P < 0.001) were different among the cohorts. The mean SNS angle (111.5 ± 10.7 versus 129.1 ± 8.8, P < 0.001) was lower in those who had surgery and CranioRate score (5.9 ± 2.1 versus 0.8 ± 2.2, P < 0.001) was higher in those who underwent surgery. SNS angles were positively correlated with surgeon craniofacial dysmorphology rankings ( r = 0.41, P < 0.05) and CranioRate MSS ( r = 0.54, P < 0.05). The ROC curve requiring high sensitivity revealed an SNS angle of 124.8 degrees predicted surgery with a sensitivity of 88.7% and a specificity of 71.3%. A ROC curve using the CranioRate MCC values ≥3.19 predicted surgery with 88.7% sensitivity and 94.7% specificity. CONCLUSION: Orbital dysmorphology in patients with MCS is well captured by the supraorbital-nasion angle. Both the SNS angle and CranioRate MSS scores accurately predict surgical intervention.

Low Prevalence of Clinically Significant Hyponatremia following Cranial Vault Reconstruction for Single-Suture Craniosynostosis.

BACKGROUND: Patients are commonly monitored for hyponatremia after intracranial procedures, yet the prevalence of hyponatremia after cranial vault reconstruction (CVR) remains unclear. The purpose of this study is to define the prevalence, risk factors, and complications of hyponatremia after CVR to optimize postoperative sodium surveillance protocols. METHODS: Patients with nonsyndromic, single-suture craniosynostosis who underwent primary CVR between 2009 and 2020 at Michigan Medicine were included (n = 231). Demographic, intraoperative, and postoperative characteristics were compared by postoperative hyponatremia status at P < 0.05 significance. Hyponatremia was defined as mild (<135 mEq/L), moderate (<130 mEq/L), or severe (<125 mEq/L) based on the lowest postoperative laboratory draw. RESULTS: Twenty-three patients (10.0%) developed mild postoperative hyponatremia. No patient developed moderate or severe postoperative hyponatremia. On multivariable regression, decreased preoperative sodium level (P = 0.03) and decreased preoperative weight (P = 0.02) were significantly associated with mild postoperative hyponatremia. No patient developed complications or required hospital readmission because of hyponatremia. CONCLUSIONS: This large retrospective cohort study of patients with nonsyndromic single-suture craniosynostosis demonstrated a 10% prevalence of mild, clinically inconsequential hyponatremia and 0% prevalence of moderate or severe, clinically significant hyponatremia after primary CVR. Patients with low preoperative sodium level or weight were at increased risk for developing mild postoperative hyponatremia. The results suggest that patients with preoperative sodium greater than 140 mEq/L or preoperative weight greater than 10 kg may be candidates for limited postoperative sodium surveillance; however, future prospective studies are warranted before implementation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Heart rate variability and vasovagal tone index in brachycephalic dogs.

Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher values of heart rate variability and vagal tone index. The aim of this study was to establish a computerized electrocardiographic study and an assessment of the vagus sympathetic balance through heart rate variability and vagal tone index of five brachycephalic breeds compared to mesocephalic dogs. Sixty dogs were used, divided into groups made up of Boxers, English Bulldogs, French Bulldogs, Pugs, Shih-Tzu and no defined breed mesocephalic dogs. Statistical analysis was carried out using the Shapiro-Wilk test, Kruskal-Wallis and Dunn's test or ANOVA and Bonferroni (p<0.05). In the evaluation of vagal sympathetic balance among all the dogs, there was a negative correlation between heart rate and HRV 10RR (r = - 0.7678; p < 0.0001), HRV 20RR (r = - 0.8548, p < 0.0001) and VVTI (r = - 0.2770; p = 0.0321). It can therefore be concluded that the dog's breed and morphology did not alter its electrocardiographic parameters or heart rate variability. The vagal tone index, which in other studies differed in brachycephalic dogs, showed no difference when compared separately in brachycephalic breeds.

Geospatial and Socioeconomic Disparities Influencing the Management of Craniosynostosis.

BACKGROUND: Various social determinants of health have been described as predictors of clinical outcomes for the craniosynostosis population. However, literature lacks a granular depiction of socioeconomic factors that impact these outcomes, and little is known about the relationship between patients' proximity to the care center and management of the condition. METHODS/DESIGN: This study retrospectively evaluated patients with craniosynostosis who presented to a tertiary children's hospital between 2000 and 2019. Outcomes of interest included age at presentation for surgery, incidence of reoperation, and length of follow-up. Patient addresses were geocoded and plotted on two separate shapefiles containing block group information within San Diego County. The shapefiles included percent parental educational attainment (bachelor's degree or higher) and median household income from 2010. The year 2010 was chosen for the shapefiles because it is the median year of data collection for this study. Multivariate linear, logistic, and polynomial regression models were used to analyze the relationship between geospatial and socioeconomic predictors and clinical outcomes. RESULTS: There were 574 patients with craniosynostosis included in this study. The mean ± SD Haversine distance from the patient's home coordinates to the hospital coordinates was 107.2 ± 321.2 miles. After adjusting for the suture fused and insurance coverage, there was a significant positive correlation between distance to the hospital and age at index surgery (P = 0.018). There was no correlation between distance and incidence of reoperation (P = 0.266) or distance and duration of follow-up (P = 0.369). Using the same statistical adjustments, lower parental percent educational attainment and lower median household income correlated with older age at index surgery (P = 0.008 and P = 0.0066, respectively) but were not correlated with reoperation (P = 0.986 and P = 0.813, respectively) or duration of follow-up (P = 0.107 and P = 0.984, respectively). CONCLUSIONS: The results offer evidence that living a greater distance from the hospital and socioeconomic disparities including parental education and median household income may serve as barriers to prompt recognition of diagnosis and timely care in this population. However, the geospatial and socioeconomic factors studied do not seem to hinder incidence of reoperation or length of follow-up, suggesting that, once care has been initiated, longitudinal outcomes may be less impacted.

New diagnostic criteria for metopic ridges and trigonocephaly: a 3D geometric approach.

BACKGROUND: Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly. METHODS: Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification. RESULTS: We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures. CONCLUSION: Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.

Child-Patient Perspective on Results After Correction of Sagittal Synostosis and the Difference Between Child-Patient and Parent's Perspectives.

OBJECTIVE: This study assesses the level of child-patient satisfaction with the surgical result after scaphocephaly correction and the difference between child-patient and parents' perspectives. METHODS: A questionnaire was sent out to children between 6 and 18 years old with isolated sagittal synostosis, who had undergone either a frontobiparietal remodeling or extended strip craniotomy, and separately to their parents. RESULTS: The questionnaire was completed by 96 patients, 81.2% of the patients considered their head to be similar or slightly different from others. Despite the majority being satisfied with the outcome, 33% would change the shape of their head if they could. Patients who underwent extended strip craniotomy wanted to change the back of their head more often ( P = 0.002), whereas patients who underwent frontobiparietal remodeling wanted to change their forehead ( P = 0.005). The patients' own perspective on head shape was independent of the cephalic index (CI). However, patients with a relatively narrow CI received more remarks from others about their heads ( P = 0.038). Parent and child agreement was 49.7% on average. Differences between child-patients and parents were found in reporting adaptive behavior. CONCLUSION: The majority of patients were satisfied with the outcome of their intervention. The child's perspective seems to be a valuable addition to evaluate sagittal synostosis surgery as it is independent of the CI and differentiates between different surgical techniques. In addition, the patient's perspective is comparable to the parent's perspective, but gives more details on adaptive behavior.

VACTERL Association in Patients With Metopic Synostosis: Is There a Link?

VACTERL association is diagnosed based on the non-random co-occurrence of at least 3 out of 6 congenital malformations. The prevalence is thought to be less than 1 in 10,000 to 1 in 40,000. There is no known link between VACTERL association and metopic synostosis in the literature. There were 122 operated cases of metopic synostosis at our institution from 1999 to 2023, with a 2.3:1 male-to-female ratio. The authors describe the co-occurrence of VACTERL association and metopic synostosis in 3 female patients with no identifiable genetic variants. Given that VACTERL association is a diagnosis of exclusion, other rare syndromes were considered but ultimately excluded. This suggests that the co-occurrence of VACTERL association and metopic synostosis is a potentially rare finding, and underlying pathogenic variants are yet to be identified.

Parental satisfaction with hospital care for children with non-syndromic craniosynostosis: A mixed-method study.

PURPOSE: The study aims to investigate factors influencing parents' satisfaction with hospital care for children with craniosynostosis during hospitalization for surgery. DESIGN AND METHODS: A mixed-methods study with a convergent, parallel design was used. Ninety-five parents responded to the Swedish Pyramid Questionnaire for Treatment, a 25-item questionnaire with six quality domains. In addition, 20 parents were interviewed about their experiences. Frequencies were calculated, and content analysis was used to analyze free-text comments and transcribed interviews. RESULTS: Parents' assessment of the overall quality of care was high (mean 87%, range 10-100%). They were most satisfied in the domain staff attitudes and less satisfied with information routines and participation. Content analysis of the interviews gave two overarching themes: Factors that parents experienced as facilitating good quality of care and Factors that parents experienced as impeding good quality of care. CONCLUSIONS: Parents were generally satisfied with the care provided, and interviews captured parents´ views on important factors. Staff attitudes affected parents' perception of quality of care. PRACTICAL IMPLICATIONS: Clear information and dialogue as well as making parents feel they are part of their child's team can result in higher satisfaction, and allowing families to stay together in the hospital can ease the hospitalization experience. Using a theoretical model can help in suggesting relevant caring actions based on parents' reported care experiences.

Syndromic craniosynostosis caused by a novel missense variant in MAP4K4: Expanding the genotype-phenotype relationship in RASopathies.

RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras/MAPK pathways. Recently, a novel disease-gene association was implicated in MAPK kinase kinase kinase 4 (MAP4K4), which regulates the upstream signals of the MAPK pathways. However, to our knowledge, only two studies have reported the genotype-phenotype relationships in the MAP4K4-related disorder. This study reports on a Korean boy harboring a novel de novo missense variant in MAP4K4 (NM_001242559:c.569G>T, p.Gly190Val), revealed by trio exome sequencing, and located in the hotspot of the protein kinase domain. The patient exhibited various clinical features, including craniofacial dysmorphism, language delay, congenital heart defects, genitourinary anomalies, and sagittal craniosynostosis. Our study expands the phenotypic association of the MAP4K4-related disorder to include syndromic craniosynostosis, thereby providing further insights into the role of the RAS/MAPK pathways in the development of premature fusion of calvarial sutures.

An Ultra-Rare Mixed Phenotype with Combined AP-4 and ERF Mutations: The First Report in a Pediatric Patient and a Literature Review.

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management.

Visuospatial abilities and 3D-printed based learning.

PURPOSE: The use of 3D-printing in every field of medicine is expanding, notably as an educational tool. The aim of this study was to assess how visuospatial abilities (VSA) of students may impact learning helped with 3D-printed models. METHODS: Participants were undergraduate medical school students during their clinical rotation in oral and maxillofacial surgery in two French Universities. Students were included prospectively and consecutively from September 2021 to June 2023. First, a lecture about craniosynostosis was performed with the help of 3D-printed models of craniosynostotic skulls. Then, a mental rotation test (MRT) followed by a multiple-choice questions (MCQs) form about craniosynostosis presentations were submitted to the students. RESULTS: Forty undergraduate students were finally included. Median MRT score was 15 (10.75;21) and median score to the MCQs was 13 (11.75;14). There was a significantly weak correlation between the MRT-A score and the score to the MCQs (rs = 0.364; p = 0.022). A simple linear regression was calculated to predict the result to the MCQs on MRT-A score [ (F(1,39) = 281.248; p < 0.0001), with a R2 of 0.878 ]. CONCLUSION: This study showed that VSA has an impact on the recognition of complex clinical presentations, i.e. skulls with craniosynostosis. The correlation found between VSA and complex 3D shape recognition after learning aided with 3D-printed model is emphasizing the importance of VSA when using innovative technologies. Thus, VSA training should be envisioned during the curriculum.