SF3B2 Haploinsufficiency Associated With Hirschprung Disease and Complex Cardiac Defect Without Craniofacial Microsomia.

Haploinsufficiency of SF3B2 is associated with craniofacial microsomia, characterized by mandibular hypoplasia and microtia, often with preauricular tags or pits, epibulbar dermoids, and cleft palate. In addition, extracraniofacial anomalies may be present, such as skeletal, cardiac renal, and abnormalities of the central nervous system. Variants have been either de novo or inherited, and both inter- and intrafamilial variability has been observed. Here we describe a patient referred for exome sequencing for a complex congenital heart defect and Hirschsprung disease found by exome sequencing to be heterozygous for a loss of function variant, c.945dup (p.Val316SerfsTer5), in SF3B2. This variant was inherited from a parent with an isolated cardiac defect. Interestingly, neither have the defining craniofacial features or other dysmorphisms. This report further illustrates the degree of phenotypic variability seen in SF3B2-related disease and expands the spectrum to include Hirschsprung disease.

Facial asymmetry outcome of orthognathic surgery in mild craniofacial microsomia compared to non-syndromic class II asymmetry.

OBJECTIVES: To compare the facial asymmetry after bimaxillary surgery between mild craniofacial microsomia (CFM) and non-syndromic class II asymmetry. MATERIALS AND METHODS: Cone-beam computed tomography scans of adults with Pruzansky-Kaban types I and IIA CFM (CFM groups, n = 20), non-syndromic skeletal class II asymmetry (Class II group, n = 20), and normal controls (control group, n = 20) were compared. The area asymmetry of lower face and jaw bones was quantified. Landmark-based method was used to evaluate the lower facial asymmetry regarding midline, cants, and contour. RESULTS: There were no significant postoperative differences in the hemi-facial and hemi-jaw area asymmetry between CFM and Class II groups, both of which were significantly larger than the control group. No significant difference was found in the midline deviation and lip and occlusal cants between CFM and Class II groups. The vertical contour asymmetry in CFM group became significantly larger than Class II group. Compared to the control group, the deviation of pronasale, subnasale, and soft-tissue menton, lip and occlusal cants, and sagittal and vertical contour asymmetry in CFM group were significantly larger, as were the deviation of subnasale and soft-tissue menton and vertical contour asymmetry in Class II group. CONCLUSIONS: The vertical contour asymmetry of mild CFM was significantly larger than non-CFM class II after surgery, while the area asymmetry, midline deviation, cants, and sagittal contour asymmetry of lower face showed no significant difference. CLINICAL RELEVANCE: Be aware that correcting vertical asymmetry of contour, lip, and dentition in CFM is still challenging.

Evaluation of post-activation mandibular remodelling in children with craniofacial microsomia treated with distraction osteogenesis.

OBJECTIVE: Patients with type IIA craniofacial microsomia (CFM) may benefit from mandibular distraction osteogenesis (MDO) treatment during childhood; however, remodelling of the mandible during the consolidation phase, which may affect the short-term outcomes of MDO, has not yet been quantitatively analysed using computed tomography. Therefore, we aimed to investigate bone remodelling of the mandible in children with type IIA CFM treated with MDO before distractor removal and the factors that influence ramus vertical elongation efficiency. MATERIALS AND METHODS: Twenty-three children with unilateral CFM were studied between 2020 and 2024. Longitudinal computed tomography data (preoperative, end of active phase and at pre-distractor removal) were analysed. Condyle positions and the mandibular cant were analysed using a paired-sample t test. The relapse rates of vertical lengthening and mandibular cant were calculated. The correlation between distraction efficiency and preoperative craniofacial morphology was analysed. RESULTS: The condyle on the affected side moved upwards and backwards by 28.84 ± 4.08 and 2.85 ± 4.33 mm, respectively during the active phase but lost 7.66 ± 2.64 mm of vertical extension during the consolidation phase. The relapse rates for vertical extension of the condyle and occlusal plane were 27% and 35%, respectively. The ratio of mandibular ramus height was positively related to EV. CONCLUSIONS: In children with CFM, attention should be paid to vertical elongation instability and relapse of mandibular inclination during consolidation. Severe mandibular ramus hypoplasia is a preoperative risk factor for vertical skeletal relapse during consolidation. Further efforts are required to reduce the stress that leads to relapse.

An updated protocol for mandibular reconstruction in nongrowing patients with craniofacial microsomia with temporomandibular joint total prosthesis.

The authors aim to present an updated protocol for mandibular reconstruction in nongrowing patients with Pruzansky/Kaban type IIb/III congenital craniofacial microsomia with customized temporomandibular joint (TMJ) prosthesis to reduce facial nerve (FN) damage and improve surgical accuracy. This is illustrated (using 3 cases) and is based on preoperative mapping of the FN using MRI for better virtual surgical planning of custom-made TMJ prosthesis. Intraoperative FN mapping and monitoring, as well as verification of the final result with intraoperative cone-beam computed tomography (CBCT) and 3D-reconstructed images is also achieved. All 3 patients presented mild transient postoperative facial palsy due to surgical soft tissue stretching which resolved within 2 months of surgery. All patients presented proper occlusion and mouth opening without pain, with an average incisal opening of 38.8 mm (range 35.5-42 mm) at two months of follow-up. Moreover, superposition of intraoperative and preoperative 3D reconstruction images ensured surgical accuracy and avoided the need for a potential reintervention. In conclusion, the proposed surgical protocol for mandibular reconstruction with customized alloplastic TMJ prosthesis in nongrowing patients with type IIb/III Pruzansky-Kaban congenital mandibular hypoplasia may reduce FN morbidity, improve surgical accuracy and final outcomes.

Dental anomalies in craniofacial microsomia and condylo-mandibular dysplasia: A retrospective study of 103 patients.

INTRODUCTION: Craniofacial microsomia (CFM) and camel-hump condylo-mandibular dysplasia (CMD) are developmental disorders affecting the mandible that share common clinical features. This study aimed to investigate and compare the dental anomalies (DA) between the two entities for differential diagnosis and to propose appropriate treatment. METHODS: This retrospective cross-sectional study was based on panoramic radiographs of patients diagnosed with CFM or CMD. DA were evaluated using the classification reported by Bilge. Delayed tooth eruption on the affected side was noted based on a comparison with the contralateral side. Nolla's stages of tooth calcification were used to assess dental development. RESULTS: A total of 103 patients were included, 80 subjects (77.7 %) in CFM group and 23 patients (22.3 %) in CMD group. The prevalence of DA among CFM and CMD-affected patients were 80.0 % and 95.7 %, respectively. Tooth ectopia, tooth impaction, dental development delay, and delayed tooth eruption on the affected side exhibited a significant association with the two craniofacial malformations. The overall affected teeth (molars, premolars, canines) differed between the two craniofacial malformations. Dental abnormalities such as oligodontia, hyperdontia, dentin dysplasia, and anomalies of shape were seen only in subjects affected by CFM. CONCLUSION: DA were widely observed in patients with CFM and CMD. The global distribution of affected teeth differed between the two conditions and some DA were detected only in CFM patients. When clinical diagnosis remains uncertain, some specific radiological characteristics of DA can be used to differentiate CFM from CMD.

"I can't provide what my child needs": Early feeding experiences of caregivers of children with craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) is a congenital condition that can be associated with feeding challenges in infants. As part of the larger 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program, this study described caregivers' early feeding experiences. DESIGN AND MATERIALS: US-based caregivers of 34 children with CFM participated in remote narrative interviews. Two authors completed inductive thematic analysis in an iterative process until consensus was reached. RESULTS: Caregivers' narratives outlined the inherent challenges of feeding an infant with special healthcare needs. The first theme 'Navigating Challenges and Managing Expectations' describes the distress participants experienced when they were unable to breastfeed and the negative emotional effect of switching to formula. The second theme 'Making Adaptations' outlines the methods participants tried, including breast pumps and feeding tubes. The third theme 'Accessing Support' describes participants' interactions with healthcare providers and challenges accessing feeding support. The final theme 'Growing from Adversity' recounts participants' relief once their child established a feeding pattern and the personal growth gained from their experiences. CONCLUSIONS: Caregivers reported several feeding related challenges associated with CFM, many of which negatively affected their wellbeing. Negative consequences were particularly pronounced in cases where caregivers' feeding experiences differed from their expectations. Participants identified challenges in accessing reliable feeding information and support. Despite difficult experiences, caregivers cited some positive outcomes, including increased confidence and resilience. PRACTICE IMPLICATIONS: Holistic feeding information and support for families affected by CFM should be inclusive of several feeding methods to improve care delivery, child health, and the caregiver experience.

Identification of a de novo PUF60 variant associated with craniofacial microsomia.

Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.

A Conceptual Thematic Framework of Psychological Adjustment in Caregivers of Children with Craniofacial Microsomia.

OBJECTIVE: Children with craniofacial microsomia (CFM) have complex healthcare needs, resulting in evaluations and interventions from infancy onward. Yet, little is understood about families' treatment experiences or the impact of CFM on caregivers' well-being. To address this gap, the NIH-funded 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program sought to develop a conceptual thematic framework of caregiver adjustment to CFM. DESIGN: Caregivers reported on their child's medical and surgical history. Narrative interviews were conducted with US caregivers (n = 62) of children aged 3-17 years with CFM. Transcripts were inductively coded and final themes and subthemes were identified. RESULTS: Components of the framework included: 1) Diagnostic Experiences, including pregnancy and birth, initial emotional responses, communication about the diagnosis by healthcare providers, and information-seeking behaviors; 2) Child Health and Healthcare Experiences, including feeding, the child's physical health, burden of care, medical decision-making, surgical experiences, and the perceived quality of care; 3) Child Development, including cognition and behavior, educational provision, social experiences, and emotional well-being; and 4) Family Functioning, including parental well-being, relationships, coping strategies, and personal growth. Participants also identified a series of "high" and "low" points throughout their journey and shared their priorities for future research. CONCLUSIONS: Narrative interviews provided rich insight into caregivers' experiences of having a child with CFM and enabled the development of a conceptual thematic framework to guide clinical care and future research. Information gathered from this study demonstrates the need to incorporate evidence-based psychological support for families into the CFM pathway from birth onward.

Prenatal findings in 11 cases with craniofacial microsomia using the Alberta Congenital Anomalies Surveillance System, 1997-2019.

Craniofacial microsomia (CFM) primarily includes specific head and neck anomalies that co-occur more frequently than expected. The anomalies are usually asymmetric and affect craniofacial features; however, there are frequently additional anomalies of variable severity. Published prenatal findings for CFM are limited. This study contributes 11 cases with CFM and their anomalies identified prenatally. Cases born between January 1, 1997 and December 31, 2019 with CFM were abstracted from the Alberta Congenital Anomalies Surveillance System, which is a population-based program ascertaining congenital anomalies for livebirths, stillbirths, and termination of pregnancies for fetal anomalies. There were 11 cases ascertained with prenatal findings including facial anomalies: one each with left cleft lip, right microtia, and bilateral microphthalmia. Two cases had vertebral anomalies. In addition, anomalies of the kidneys, brain, heart, and radial ray were identified. Six (55%) had a single umbilical artery, five (45%) were small for gestational age, and three (27%) were from a twin pregnancy that were discordant for anomalies. Four (36%) overlapped another proposed recurrent constellations of embryonic malformation condition. This study describes prenatal findings for 11 cases with CFM. Comparable to prior published cases, there were recurring anomalies on prenatal imaging, including anomalies of the brain, eye, heart, kidneys, and radial ray, which may aid in the prenatal diagnosis of CFM.

Caregiver strategies supporting community participation among children and youth with or at risk for disabilities: a mixed-methods study.

Introduction: The purpose of this mixed-methods study is to examine the role of caregiver strategies to support community participation among children and youth with disabilities and those at risk, from the caregiver perspective. For the quantitative phase, we tested the hypothesized positive effect of participation-focused caregiver strategies on the relationship(s) between participation-related constructs and community participation attendance and involvement. For the qualitative phase, we solicited caregiver perspectives to explain the quantitative findings. Methods: An explanatory sequential mixed-methods design (QUAN > qual) was used. For the quantitative phase, we conducted secondary analyses of data collected during a second follow-up phase of a longitudinal cohort study, including 260 families of children and youth (mean age: 13.5 years) with disabilities and those at risk [i.e., 120 families of children and youth with craniofacial microsomia (CFM); 140 families of children and youth with other types of childhood-onset disabilities]. Data were collected through the Participation and Environment Measure-Children and Youth, the Pediatric Quality of Life Inventory, and the Child Behavior Checklist and analyzed using structural equation modeling. For the qualitative phase, we conducted semi-structured interviews with eight caregivers of children and youth with disabilities and those at risk (i.e., three caregivers of children and youth with CFM; five caregivers of children and youth with other childhood-onset disabilities). Interviews were transcribed verbatim and inductively content-analyzed. Results: Our model reached acceptable to close model fit [CFI = 0.952; RMSEA = 0.068 (90% CI = 0.054-0.082); SRMR = 0.055; TLI = 0.936], revealing no significant effect of the number of participation-focused caregiver strategies on the relationships between participation-related constructs (e.g., activity competence, environment/context) and community participation in terms of attendance and involvement. The qualitative findings revealed three main categories for how caregivers explained these quantitative results: (1) caregiver workload and supports needed for implementing strategies; (2) caregivers careful strategy quality appraisal; and (3) community setting characteristics hindering successful strategy implementation. Discussion: The findings suggest that the insignificant effect of the number of caregiver strategies may be explained by the intensified need for caregiver effort and support to develop and implement quality strategies that are responsive to community setting characteristics.

Early Experiences of Parents of Children With Craniofacial Microsomia.

OBJECTIVE: To describe the early health care experiences of parents of children with craniofacial microsomia (CFM), a congenital diagnosis often identified at birth. DESIGN: Qualitative descriptive. SETTING: Homes of participants. PARTICIPANTS: Parents of 28 children with CFM from across the United States. METHODS: We interviewed participants (27 mothers individually and one mother and father together) via telephone or teleconference and used reflexive thematic analysis to derive themes that represented early health care experiences of parents of children with CFM. RESULTS: Participants' narratives included detailed recounting of their birth and early care experiences. We identified two overarching themes. The first overarching theme, Stressors, included four subthemes that represented difficulties related to emotional reactions and negative experiences with health care providers. The second overarching theme, Finding Strength, included four subthemes that represented participants' positive adjustment to stressors through independent information seeking about CFM, adaptive coping, positive experiences with health care providers, and drawing on external supports. CONCLUSION: Participants often described early experiences as challenging. Findings have implications for improving early care, including increasing open and supportive communication by health care professionals, expanding access to CFM information, screening for mental health concerns among parents, strengthening coping among parents, and linking families to resources such as reliable online CFM information and early intervention programs.

3D-CT measurements of facial symmetry in severe CFM patients: A comparative study between mandibular ascending ramus distraction osteogenesis and bone grafting.

This study aims to compare the effects of mandibular distraction osteogenesis (MDO) and bone grafting on the facial symmetry of children with Pruzansky-Kaban type IIB and III craniofacial microsomia (CFM). Medical records and three-dimensional computed tomography (3D-CT) data of CFM patients who had primarily undergone MDO and bone grafting were collected. A retrospective analysis of pre-and post-operative 3D imaging data was conducted to compare the improvement rate in facial symmetry between the two groups based on occlusal cant, affected/unaffected ramus height ratio and chin point deviation. The data were tested for normality using the Shapiro-Wilk test. When the data followed a normal distribution, a paired sample t-test was employed for the comparison between preoperative and postoperative data. When the data did not follow a normal distribution, the Wilcoxon signed-rank test for paired samples was used for preoperative and postoperative comparison. The study included 18 children with type IIB and III CFM, 11 in the MDO group and 7 in the bone grafting group. In the MDO group, postoperative Gn-FH and Gn-Cor distances increased significantly, whereas the postoperative Gn-Mid distance decreased significantly. Occlusal cant decreased significantly and ramus height affected/unaffected ratio increased significantly after MDO. In the bone graft group, there was no statistically significant difference in the postoperative ratios of chin deviation, occlusal cant, and ramus height affected/unaffected compared to the preoperative values. Compared to bone grafting, MDO can significantly enhance ramus height ratio, level occlusal plane, and centralize the chin point among patients with CFM. Furthermore, MDO achieves superior enhancements in facial symmetry.

Velopharyngeal insufficiency, speech, and language impairment in craniofacial microsomia: a scoping review.

This review provides a comprehensive overview of the literature on velopharyngeal insufficiency, associated anomalies, and speech/language impairment in patients with craniofacial microsomia (CFM). A systematic search of the literature was conducted to identify records on VPI and speech impairment in CFM from their inception until September 2022 within the databases Embase, PubMed, MEDLINE, Ovid, CINAHL EBSCO, Web of Science, Cochrane, and Google Scholar. Seventeen articles were included, analysing 1,253 patients. Velopharyngeal insufficiency results in hypernasality can lead to speech impairment. The reported prevalence of both velopharyngeal insufficiency and hypernasality ranged between 12.5% and 55%, while the reported prevalence of speech impairment in patients with CFM varied between 35.4% and 74%. Language problems were reported in 37% to 50% of patients. Speech therapy was documented in 45.5% to 59.6% of patients, while surgical treatment for velopharyngeal insufficiency consisted of pharyngeal flap surgery or pharyngoplasty and was reported in 31.6% to 100%. Cleft lip and/or palate was reported in 10% to 100% of patients with CFM; these patients were found to have worse speech results than those without cleft lip and/or palate. No consensus was found on patient characteristics associated with an increased risk of velopharyngeal insufficiency and speech/language impairment. Although velopharyngeal insufficiency is a less commonly reported characteristic of CFM than other malformations, it can cause speech impairment, which may contribute to delayed language development in patients with CFM. Therefore, timely recognition and treatment of speech impairment is essential.

Risk factors and characteristics of the birth of patients with craniofacial microsomia, a case-control study.

BACKGROUND: Craniofacial microsomia (CM) is characterized by changes in the first and second branchial arches. It is a clinical condition whose etiology is still uncertain, but studies have shown that genetic, nutritional, and environmental factors can result in disorders of blastogenesis of the branchial arches. This study evaluates gestational aspects, focusing on possible risk factors associated with CM. METHODS: This is a case-control study conducted with patients monitored at a medical genetics service and compared to a control group of patients without evidence of malformations, born in a mother and child hospital, both located in Porto Alegre, Southern Brazil. Mothers' data were obtained using questionnaires and by reviewing medical records. The sample consisted of 43 patients with CM (cases) and 129 patients without evidence of malformations (controls), paired by sex, totaling three controls for each case. Data analysis was performed using the two-tailed Fisher's exact test, Pearson's chi-square test, and the t-test. RESULTS: We identified several factors associated with the development of CM, including the use of abortion methods by the mothers of these babies (p = .001), maternal diabetes (p = .009), advanced maternal age (p = .035), and a history of vaginal bleeding (p < .001). Furthermore, these patients exhibited a tendency to be born prematurely (p = .027), with low birth weight (p = .007), and lower Apgar scores (p = .003) when compared to healthy infants. Using a multivariate model, the use of abortion methods (p = .003) and vaginal bleeding (p = .032) remained independently associated with craniofacial microsomia. CONCLUSIONS: We have identified several risk factors for the development of CM, including a propensity for premature birth, low birth weight, and respiratory difficulties. Additionally, women of advanced maternal age and/or those who used abortion methods and/or have diabetes have a higher risk of giving birth to a baby with CM. This information can be valuable in clinical practice, especially for the prevention of future cases.

Condylar resorption post mandibular distraction osteogenesis in craniofacial microsomia: A retrospective study.

The aim of this study was to investigate the characteristics of condylar resorption in craniofacial microsomia (CFM) patients following mandibular distraction osteogenesis (MDO). Patients with unilateral type-IIa and type-IIb CFM, who had completed MDO and mandibular distractor extraction (MDE), were recruited. The height and volume of the condyle were measured on three-dimension models created by the analysis of computed tomography (CT) data. Normality analysis was performed using the Shapiro-Wilk test. Data for the affected and unaffected sides were compared using the paired t-test or Wilcoxon signed-rank test. Data for both type-IIa and type-IIb CFM were compared using the independent-samples t-test or Mann-Whitney U test. The Pearson or Spearman correlation was used to determine the correlations of condylar resorption rate with related measurements. In total, 48 type-IIa and 48 type-IIb CFM patients were included. The condylar resorption rate in type-IIa CFM (0.35 ± 0.32) was significantly associated with the height of the condyle (r = 0.776, p < 0.001) and distraction distance (r = 0.447, p = 0.001), while the condylar resorption rate in type-IIb CFM (0.49 ± 0.46) was significantly associated with the height of the condyle (r = 0.924, p < 0.001). However, there was no significant difference in condylar resorption rate between type-IIa and type-IIb CFM (p = 0.075). In addition to occlusal changes, no other negative symptoms of the TMJ were observed with condylar resorption. Condylar resorption was evident in CFM patients following mandibular distraction osteogenesis, and the condylar resorption rate showed a relationship with distraction distance and condylar height.

Non-progressive mandibular changes in children with Type I and II craniofacial microsomia.

OBJECTIVE: To describe the mandibular growth of craniofacial microsomia (CFM) patients during early childhood to adolescence with attention to symmetry. MATERIALS AND METHODS: Altogether 61 CFM patients were studied at the Cleft Palate and Craniofacial Center, Helsinki University Hospital between 1986 and 2006. In this cohort study, we measured and analysed 293 radiographs (posteroanterior, panoramic and lateral); 165 radiographs of 40 patients met the final inclusion criteria. The vertical height of the ramus in anteroposterior and panoramic radiographs, the length of the mandible in anteroposterior radiographs and the maxillary protrusion and mandibular retrognathia in lateral cephalograms were measured in four different age groups. RESULTS: A statistical difference existed between the groups in the vertical height of the ramus and in the mandibular length. The vertical height of the ramus measured from the panoramic radiograph grew on both sides, and the ratios remained unchanged. In the sagittal dimension, the maxilla and mandible grew forward, but no significant differences emerged between the groups. CONCLUSIONS: Results suggest that mild-type CFM is not progressive in nature. During growth, mandibular asymmetry measured in the horizontal, vertical and sagittal planes did not increase.

Conductive Hearing Loss in Children.

A variety of congenital and acquired disorders result in pediatric conductive hearing loss. Malformations of the external auditory canal are invariably associated with malformations of the middle ear space and ossicles. Isolated ossicular malformations are uncommon. Syndromes associated with external and middle ear malformations are frequently associated with abnormal development of first and second pharyngeal arch derivatives. Chronic inflammatory disorders include cholesteatoma, cholesterol granuloma, and tympanosclerosis.

Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene.

BACKGROUND: Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. METHODS: Trio whole-exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. RESULTS: The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. CONCLUSION: For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.

Respiratory outcome of mandibular distraction osteogenesis on obstructive sleep apnea in craniofacial microsomia: A retrospective study.

This study aimed to evaluate the effect of mandibular distraction osteogenesis (MDO) on respiratory function in CFM patients with obstructive sleep apnea (OSA) according to polysomnography (PSG). This study retrospectively analyzed patients with CFM who underwent PSG before surgery and after completion of mandible distraction. Patients who met the inclusion criteria were selected. The Pediatric Sleep Questionnaire (PSQ) was used to assess patients' signs and symptoms related to OSA. The obstructive apnea-hypopnea index (OAHI) and lowest oxygen saturation (LSaO2) were imported into SPSS version 26.0. The Wilcoxon signed-rank test was used to assess the differences in PSG before and after MDO. Other data were described using descriptive statistics. A P-value less than 0.05 was considered statistically significant. A total of 25 unilateral CFM patients were included in this study. Most patients (72%) had mild OSA; moderate and severe OSA were 12% and 16%, respectively. Snoring (52%) was the most common symptom among these patients. After completion of mandibular distraction, snoring and other OSA-related symptoms were significantly improved. Twelve patients had normalized PSG and the severity of OSA improved significantly in 3 patients. The total effective rate of MDO for OSA was 60%. The statistical results showed that OAHI (P = 0.045) decreased and LSaO2 (P = 0.009) increased significantly compared to preoperative values. MDO can improve OSA-related symptoms in CFM patients. In addition, respiratory function was improved in most patients after MDO, based on PSG. CFM patients, especially those with OSA, can benefit from MDO.

Oculoauriculofrontonasal syndrome: Refining the phenotype through a new case series and literature review.

The oculoauriculofrontonasal syndrome (OAFNS) is a rare condition, with unknown etiology, characterized by the association of frontonasal dysplasia (FND) and oculoauriculovertebral spectrum (OAVS). Main clinical findings include widely spaced eyes, epibulbar dermoid, broad nose, mandibular hypoplasia, and preauricular tags. Here, we describe a case series of 32 Brazilian individuals with OAFNS and review the literature ascertaining individuals presenting phenotypes compatible with the diagnosis of OAFNS, aiming to refine the phenotype. This series emphasizes the phenotypic variability of the OAFNS and highlights the occurrence of rare craniofacial clefts as a part of the phenotype. The ectopic nasal bone, a hallmark of OAFNS, was frequent in our series, reinforcing the clinical diagnosis. The absence of recurrence, consanguinity, chromosomal, and genetic abnormalities reinforces the hypothesis of a nontraditional inheritance model. The phenotypic refinement provided by this series contributes to an investigation regarding the etiology of OAFNS.