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International Journal of Oral and... Oct 2021The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial...
The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development.
Topics: Cohort Studies; Goldenhar Syndrome; Humans; Mandible; Prevalence; Retrospective Studies
PubMed: 33752938
DOI: 10.1016/j.ijom.2021.02.032 -
Journal of Plastic, Reconstructive &... Jun 2022This article provides a review of a decade of clinical research studies on clinical features, medical interventions, and surgical interventions for individuals with... (Review)
Review
AIM
This article provides a review of a decade of clinical research studies on clinical features, medical interventions, and surgical interventions for individuals with craniofacial microsomia (CFM). We also provide recommendations for future clinical research.
METHOD
A systematic search of literature was conducted in Embase and PubMed/MEDLINE Ovid. All publications from 2010 to 2020 that included at least 10 individuals with CFM were considered relevant for this study.
RESULTS
A total of 91 articles were included. In the past decade, many new studies on CFM have been published providing more insight on the diagnosis and management of patients with CFM. This review encompasses findings on the clinical difficulties patients with CFM encounter, including the craniofacial and extracraniofacial characteristics of patients with CFM and its related clinical consequences on breathing, feeding, speech, and hearing.
CONCLUSIONS
A considerable number of large multicenter studies have been published in recent years, providing new insights in the clinical consequences of CFM. The phenotypic variety between patients with CFM makes patient-specific treatment tailored to individual needs essential. The research and development of clinical care standards might be challenging because of the heterogeneity of CFM. Future research on clinical and patient-reported outcomes can help identify optimal treatment strategies. Cooperation between craniofacial centers, using uniform registration and outcome measurement tools, could enhance research and future care for these patients.
LEVEL OF EVIDENCE
Level IV.
Topics: Goldenhar Syndrome; Humans; PubMed
PubMed: 35365411
DOI: 10.1016/j.bjps.2022.02.058 -
Clinical Oral Investigations Dec 2020This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky-Kaban...
OBJECTIVES
This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky-Kaban classification system.
MATERIALS AND METHODS
Cone-beam computed tomography images of 48 adult CFM cases were collected. The asymmetry of the mandibular body and ramus was analyzed with 3D landmarks. The mirrored mandibular model was registered on the original model, yielding a color-coded distance map and an average distance (i.e., asymmetry score) to quantify the overall mandibular asymmetry.
RESULTS
The lengths of the mandibular body and ramus were significantly shorter on the affected than the contralateral side (p < 0.001). The ANB (p = 0.009), body and ramal lengths (both p < 0.001), and body and ramal length asymmetry (both p < 0.05) were significantly different between mild (types I/IIA) and severe (types IIB/III) cases. The mandibular asymmetry score correlated with mandibular body length asymmetry (r = 0.296, p = 0.046). CFM mandibles showed high variability in shape asymmetry.
CONCLUSIONS
CFM patients showed distinct body and ramal length asymmetries. In severe cases, mandibles were smaller, more retruded, and more asymmetric in length. The mandibular shape asymmetry was highly variable regardless of the Pruzansky-Kaban types, being a determinant in the extent of overall mandibular asymmetry.
CLINICAL RELEVANCE
The 3D morphologic analysis provides better insights into real mandibular asymmetry. Although the Pruzansky-Kaban classification was applied, high individual variability of the mandibular morphology still existed within the types. Therefore, individualized analyses and treatment plans for CFM patients are highly recommended.
Topics: Adult; Cone-Beam Computed Tomography; Facial Asymmetry; Goldenhar Syndrome; Humans; Imaging, Three-Dimensional; Mandible
PubMed: 32382927
DOI: 10.1007/s00784-020-03302-8 -
The Cleft Palate-craniofacial Journal :... Sep 2023To (1) appraise current international classification and clinical management strategies for craniofacial microsomia (CFM) and microtia, and (2) to assess agreement with...
To (1) appraise current international classification and clinical management strategies for craniofacial microsomia (CFM) and microtia, and (2) to assess agreement with the European Reference Network "European Guideline Craniofacial Microsomia" recommendations on screening and monitoring. This was a cross-sectional online survey study. The survey consisted of 44 questions on demographics, diagnostics and classification, obstructive sleep apnea, feeding difficulties, speech and language development, hearing, ocular abnormalities, visual development, orthodontic screening, genetic counselling, psychological wellbeing, and extracraniofacial anomalies. Respondents were participants of 3 international cleft and craniofacial conferences, members of the American Cleft Palate and Craniofacial Association and members of the International Society for Auricular Reconstruction. Respondents were requested to complete 1 questionnaire per multidisciplinary team. Fifty-seven responses were received from 30 countries (response rate ∼3%).The International Consortium for Health Outcomes Measurement diagnostic criteria were used by 86% of respondents, though 65% considered isolated microtia a mild form of CFM. The Orbit, Mandible, Ear, Facial Nerve and Soft Tissue classification system was used by 74% of respondents. Agreement with standardized screening and monitoring recommendations was between 61% and 97%. A majority of respondents agreed with screening for extracraniofacial anomalies (63%-68%) and with genetic counselling (81%). This survey did not reveal consistent agreement on the diagnostic criteria for CFM. Respondents mostly supported management recommendations, but frequently disagreed with the standardization of care. Future studies could focus on working towards international consensus on diagnostic criteria, and exploring internationally feasible management strategies.
Topics: Humans; Goldenhar Syndrome; Congenital Microtia; Cross-Sectional Studies; Mandible; Surveys and Questionnaires
PubMed: 35469463
DOI: 10.1177/10556656221093912 -
The Cleft Palate-craniofacial Journal :... Sep 2021To examine neurodevelopment in preschool-aged children with craniofacial microsomia (CFM) relative to unaffected peers.
OBJECTIVE
To examine neurodevelopment in preschool-aged children with craniofacial microsomia (CFM) relative to unaffected peers.
DESIGN
Multisite, longitudinal cohort study.
SETTING
Tertiary care centers in the United States.
PARTICIPANTS
We included 92 children with CFM ("cases") through craniofacial centers and clinics. Seventy-six children without CFM (controls) were included from pediatric practices and community advertisements. This study reports on outcomes assessed when participants were an average age of 38.4 months (SD = 1.9).
MAIN OUTCOME MEASURES
We assessed cognitive and motor skills using the (Bayley-III), and language function using subtests from the (CELF-P2).
RESULTS
Case-control differences were negligible for Bayley-III cognitive (effect sizes [ES] = -0.06, = .72) and motor outcomes (ES = -0.19, = .25). Cases scored lower than controls on most scales of the CELF-P2 (ES = -0.58 to -0.20, = .01 to .26). Frequency counts for "developmental delay" (ie, one or more scores > 1 SD below the normative mean) were higher for cases (39%) than controls (15%); however, the adjusted odds ratio = 1.73 ( = 0.21) was not significant. Case-control differences were most evident in children with microtia or other combinations of CFM-related facial features.
CONCLUSIONS
Cognitive and motor scores were similar for preschool-aged children with and without CFM. However, children with CFM scored lower than controls on language measures. We recommend early monitoring of language to identify preschoolers with CFM who could benefit from intervention.
Topics: Child; Child Development; Child, Preschool; Cognition; Developmental Disabilities; Goldenhar Syndrome; Humans; Infant; Language Development; Longitudinal Studies; United States
PubMed: 33322943
DOI: 10.1177/1055665620980223 -
Frontiers in Genetics 2020Defects in the development of the first and second pharyngeal arches and their derivatives result in abnormal formation of the craniofacial complex, consequently giving...
BACKGROUND
Defects in the development of the first and second pharyngeal arches and their derivatives result in abnormal formation of the craniofacial complex, consequently giving rise to facial dysostoses (FDs). FDs represent a group of rare and highly heterogeneous disease entities that encompass mandibulofacial dysostoses (MFDs) with normal extremities and acrofacial dysostoses (AFDs) with limb anomalies in addition to craniofacial defects.
METHODS
We examined 11 families with variable clinical symptoms of FDs, in most of which only one member was affected. We applied two custom gene panels-first comprising 37 genes related to the genetic disorders of craniofacial development such as FDs (On-Demand AmpliSeq Thermo Fisher Scientific gene panel with two primer pools) and second composed of 61 genes and 11 single nucleotide variants (SNVs) known to be involved in the development of skull malformations, mainly in the form of craniosynostoses (SureSelect Agilent Technologies). Targeted next-generation sequencing (NGS) was performed using the Ion Torrent S5 platform. To confirm the presence of each detected variant, we have analyzed a genomic region of interest using Sanger sequencing.
RESULTS
In this paper, we summarized the results of custom targeted gene panel sequencing in the cohort of sixteen patients from 11 consecutive families affected by distinct forms of FDs. We have found three novel pathogenic variants in the gene-c.2145_2148dupAAAG p.(Ser717Lys 42), c.4370delA p.(Lys1457Arg 118), c.83G>C p.(Arg28Pro) causing Treacher Collins syndrome type 1, two novel missense variants in the gene-c.491A>G p.(Asp164Gly) and c.779T>A p.(Ile260Asn) in two female patients affected by acrofacial dysostosis Guion-Almeida type, one previously reported-c.403C>T (p.Arg135Cys), as well as one novel missense variant-c.128C>T p.(Pro43Leu) in the gene in the male patient with Miller syndrome and finally one known pathogenic variant c.574G>T p.(Glu192) in the gene in the patient with Nager syndrome.
CONCLUSION
Our study confirms the efficiency and clinical utility of the targeted gene panel sequencing and shows that this strategy is suitable and efficient in the molecular screening of variable forms of FDs.
PubMed: 33262786
DOI: 10.3389/fgene.2020.580477 -
PLoS Genetics Jul 2016Ribosome biogenesis is a global process required for growth and proliferation of all cells, yet perturbation of ribosome biogenesis during human development often leads...
Ribosome biogenesis is a global process required for growth and proliferation of all cells, yet perturbation of ribosome biogenesis during human development often leads to tissue-specific defects termed ribosomopathies. Transcription of the ribosomal RNAs (rRNAs) by RNA polymerases (Pol) I and III, is considered a rate limiting step of ribosome biogenesis and mutations in the genes coding for RNA Pol I and III subunits, POLR1C and POLR1D cause Treacher Collins syndrome, a rare congenital craniofacial disorder. Our understanding of the functions of individual RNA polymerase subunits, however, remains poor. We discovered that polr1c and polr1d are dynamically expressed during zebrafish embryonic development, particularly in craniofacial tissues. Consistent with this pattern of activity, polr1c and polr1d homozygous mutant zebrafish exhibit cartilage hypoplasia and cranioskeletal anomalies characteristic of humans with Treacher Collins syndrome. Mechanistically, we discovered that polr1c and polr1d loss-of-function results in deficient ribosome biogenesis, Tp53-dependent neuroepithelial cell death and a deficiency of migrating neural crest cells, which are the primary progenitors of the craniofacial skeleton. More importantly, we show that genetic inhibition of tp53 can suppress neuroepithelial cell death and ameliorate the skeletal anomalies in polr1c and polr1d mutants, providing a potential avenue to prevent the pathogenesis of Treacher Collins syndrome. Our work therefore has uncovered tissue-specific roles for polr1c and polr1d in rRNA transcription, ribosome biogenesis, and neural crest and craniofacial development during embryogenesis. Furthermore, we have established polr1c and polr1d mutant zebrafish as models of Treacher Collins syndrome together with a unifying mechanism underlying its pathogenesis and possible prevention.
Topics: Animals; Cell Differentiation; Craniofacial Abnormalities; DNA-Directed RNA Polymerases; Developmental Disabilities; Disease Models, Animal; Embryonic Development; Humans; Mandibulofacial Dysostosis; Mutation; Neural Crest; Tumor Suppressor Protein p53; Zebrafish
PubMed: 27448281
DOI: 10.1371/journal.pgen.1006187 -
BMC Ophthalmology Aug 2018Goldenhar syndrome has variable presentations and can affect multiple regions of the body. Diagnoses are based on clinical manifestations. The association of Goldenhar...
BACKGROUND
Goldenhar syndrome has variable presentations and can affect multiple regions of the body. Diagnoses are based on clinical manifestations. The association of Goldenhar syndrome with blepharophimosis and limb deformities has not previously been reported. Here, we describe a patient who was diagnosed with Goldenhar syndrome in association with blepharophimosis, ocular hypertelorism, hearing loss and limb deformities.
CASE PRESENTATION
A 10-year-old male was first referred to our ophthalmology clinic on 2009-2-11 for ocular hypertelorism and microphthalmia when he had chin-up position. In the first ophthalmic examination, his palpebral fissure length was 19 mm on the right and 20 mm on the left, both palpebral fissure height was 4 mm, the inner intercanthal distance was 63 mm, both upper margin reflex distances were - 1 mm, the myodynamia of the levator palpebrae muscle was 2 mm on the right and 3 mm on the left, and his visual acuity was 20/40 on the right and 20/32 on the left. A physical examination revealed the patient had developed limb deformities in his hands, wrists, elbows and shoulders along with hearing loss. The patient was diagnosed with Goldenhar syndrome because his clinical presentations included ocular hypertelorism, hearing loss, and multiple acral joint deformities. He underwent a first operation in 2009 and a second in 2015. The second operation achieved a satisfactory result in which the horizontal fissure length was 28 mm on both sides, both palpebral fissure height was 10 mm, the inner intercanthal distance was 30 mm, and both of the upper margin reflex distances were 4 mm. He continued to wear hearing aids as usual. His hearing loss and joint deformities were slated for long-term follow-up at his parents' request.
CONCLUSION
The patient, diagnosed with Goldenhar syndrome in association with blepharophimosis, ocular hypertelorism, hearing loss and limb deformities, underwent two operations and achieved a satisfactory result. The patient was submitted to long-term follow-up observations and symptomatic treatments that vary with age and systemic associations, as needed. When treating patients with Goldenhar syndrome, ophthalmology specialists should cooperate with a multi-disciplinary team of clinicians and reach agreement regarding the appropriate systemic and comprehensive treatments.
Topics: Abnormalities, Multiple; Blepharophimosis; Child; Eyelids; Goldenhar Syndrome; Humans; Limb Deformities, Congenital; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Tomography, X-Ray Computed; Visual Acuity
PubMed: 30134872
DOI: 10.1186/s12886-018-0872-5 -
Molecular Genetics & Genomic Medicine Oct 2020Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, comprises a variable phenotype with the most common features including microtia and...
BACKGROUND
Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, comprises a variable phenotype with the most common features including microtia and mandibular hypoplasia on one or both sides, in addition to lateral oral clefts, epibulbar dermoids, cardiac, vertebral, and renal abnormalities. The etiology of CFM is largely unknown. The MYT1 gene has been reported as a candidate based in mutations found in three unrelated individuals. Additional patients with mutations in this gene are required to establish its causality. We present two individuals with CFM that have rare variants in MYT1 contributing to better understand the genotype and phenotype associated with mutations in this gene.
METHODS/RESULTS
We conducted genetic analysis using whole-exome and -genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants. Sanger sequencing was used to confirm these mutations.
CONCLUSION
We identified two additional individuals with CFM who carry rare variants in MYT1, further supporting the presumptive role of this gene in the CFM spectrum.
Topics: Child; Congenital Microtia; DNA-Binding Proteins; Female; Goldenhar Syndrome; Humans; Male; Mutation; Syndrome; Transcription Factors
PubMed: 32871052
DOI: 10.1002/mgg3.1401 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2023By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome(TCS), the biological causes of the disease...
By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome(TCS), the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the gene: c. 1350_1351dupGG(p. A451Gfs*43) and c. 4362_4366del(p. K1457Efs*12), resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance(CAP) score was 6, and the Speech Intelligibility Rating(SIR) score was 4. Assessment using the Meaningful Auditory Integration Scale(MAIS) showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Topics: Child; Humans; Mandibulofacial Dysostosis; Quality of Life; Speech; Parents; Mutation; Nuclear Proteins; Phosphoproteins
PubMed: 37640998
DOI: 10.13201/j.issn.2096-7993.2023.09.011