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The Cleft Palate-craniofacial Journal :... Apr 2024Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial...
OBJECTIVE
Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype-phenotype correlation in MFDM.
METHODS
Forty articles comprising 156 patients were evaluated. The genotype-phenotype correlation was analyzed using a chi-square or Fisher's exact test.
RESULTS
The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype-phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity.
CONCLUSION
Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype-phenotype relationships in this disease.
Topics: Humans; Mandibulofacial Dysostosis; Ribonucleoprotein, U5 Small Nuclear; Peptide Elongation Factors; Mutation; Microcephaly
PubMed: 36317361
DOI: 10.1177/10556656221136177 -
Plastic and Reconstructive Surgery Jun 2024Children born with hemifacial microsomia (HFM) can experience airway compromise. There is a paucity of data correlating degree of HFM severity with airway difficulty....
BACKGROUND
Children born with hemifacial microsomia (HFM) can experience airway compromise. There is a paucity of data correlating degree of HFM severity with airway difficulty. This study aims to determine the relationship between the degree of micrognathia and airway insufficiency in the HFM population.
METHODS
Patient demographics, airway function, Kaban-Pruzansky (KP) grade, and Cormack-Lehane (CL) grade were collected and compared with appropriate statistics for HFM patients treated between 2000 and 2022.
RESULTS
Seventy patients underwent 365 operations with KP grading as follows: 34% KP grade I, 23% KP grade IIA, 11% KP grade IIB, and 33% KP grade III. Goldenhar syndrome was present in 40% of patients and 16% had bilateral disease. KP grade ( P < 0.001) predicted mean number of airway-affecting procedures undergone and difficult airway status ( P < 0.001), with 75% of difficult airways in KP grade III patients. There was no association of airway compromise with Goldenhar syndrome, laterality, or age ( P > 0.05). Most CL grades were I (61%) or IIA (13%), with fewer grade IIB, grade III, and grade IV (4% to 7%). KP grade predicted CL grade ( P < 0.001), with 71% of grade IV views and 64% of grade III views seen in KP grade III patients.
CONCLUSIONS
KP grade correlated with airway severity in HFM. Patients do not appear to outgrow their CL grade, as previously hypothesized, suggesting that KP grade III patients remain at increased risk for airway insufficiency into the teen years. Given the potential significant morbidity associated with airway compromise, proper identification and preparation for a challenging airway is a critical part of caring for patients with HFM.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, III.
Topics: Humans; Female; Male; Infant; Goldenhar Syndrome; Severity of Illness Index; Child, Preschool; Child; Retrospective Studies; Airway Obstruction; Infant, Newborn; Adolescent; Facial Asymmetry
PubMed: 37257130
DOI: 10.1097/PRS.0000000000010785 -
Journal of Obstetric, Gynecologic, and... May 2024To describe the early health care experiences of parents of children with craniofacial microsomia (CFM), a congenital diagnosis often identified at birth.
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.
Topics: Humans; Female; Male; Parents; Adult; Qualitative Research; Adaptation, Psychological; United States; Goldenhar Syndrome; Stress, Psychological; Child; Infant, Newborn; Child, Preschool; Infant
PubMed: 38320743
DOI: 10.1016/j.jogn.2024.01.001 -
Practical Neurology Oct 2023
Topics: Humans; Goldenhar Syndrome; White Matter
PubMed: 37193601
DOI: 10.1136/pn-2023-003741 -
International Journal of Molecular... Apr 2024Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible,...
Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of . knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in mutants. mRNA injections and or knockout significantly rescued pharyngeal arch cartilage dysplasia, while mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between and HFM, primarily through the inhibition of proliferation and disruption of pharyngeal chondrocyte differentiation.
Topics: Animals; Zebrafish; Humans; Male; Female; Goldenhar Syndrome; Apoptosis; Neural Crest; Exome Sequencing; Cell Proliferation; Phenotype; Mutation; Gene Knockout Techniques
PubMed: 38731925
DOI: 10.3390/ijms25094707 -
The Cleft Palate-craniofacial Journal :... Aug 2023To fix a gray zone left in Tessier's classification of rare clefts with cleft 6 and to give a more comprehensive description of cleft 6 anatomy. (Review)
Review
OBJECTIVE
To fix a gray zone left in Tessier's classification of rare clefts with cleft 6 and to give a more comprehensive description of cleft 6 anatomy.
DESIGN
The material used for the research was a series of 26 clinical cases of patients with assessed cleft 6 and 44 cases found out of a literature review with enough data to be useful. The 70 cases were cross-examined by the authors.
STUDY SETTING
The authors are senior craniofacial surgeons working in high-case load department from university centers where the patients are documented and receive primary as well as secondary treatment and follow-up.
PATIENTS
The patients were selected out of the series of craniofacial deformities taken care of by the authors' department as rare clefts.
MAIN OUTCOME
We describe the full spectrum of cleft 6 as an autonomous entity that could present itself in three subtypes: 6a is the most proximal and could be associated with cleft 8. The subtype 6b is medial toward the zygomatic arch and frequently associated with a bone and teeth appendage (frequently described as a "maxillary duplication"). The subtype 6C goes toward the external ear between the helix crus and the auditory meatus.
CONCLUSIONS
The Tessier's opinion is that Treacher Collins syndrome was the association of clefts 6, 7, and 8 and is no longer sustainable in the light of modern genetics. Most of the cleft 6 are misdiagnosed in the literature.
Topics: Humans; Cleft Palate; Maxilla; Zygoma; Craniofacial Abnormalities; Mandibulofacial Dysostosis
PubMed: 35285292
DOI: 10.1177/10556656221086459 -
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Feb 2024To study the clinical and CT features of the abnormal whole-course wide of eustachian tube (AWWET) with microtia and atresia(MA). The clinical and CT data of 19...
To study the clinical and CT features of the abnormal whole-course wide of eustachian tube (AWWET) with microtia and atresia(MA). The clinical and CT data of 19 patients (20 ears) from January 2017 to December 2021 with AWWET with MA were retrospectively analyzed, including 15 males and 4 females. The age ranged from 5 to 16 years, with an average of 9.5 years. 50 patients with common MA without wide eustachian tube(ET) as a case control group, including 32 males and 18 females.The age ranged from 5 to 16 years, with an average of 9.2 years. 20 patients (40 ears) who had normal ear CT for tinnitus, otalgia as a normal control group, including 12 males and 8 females. The age ranged from 5 to 16 years, with an average of 12.5 years. We measured the dimension and length of the bony portion of the ET, the total length, the angle between the bony portion and the cartilage portion, and the horizontal angle of ET on CT imagings, and compared with 40 normal ears by SPSS 27.0 software. According to the relationship between AWWET and tympanum, patients were divided into the communicated group and the blocked group. A male predominance, left ear predominance, with high incidence of hemifacial microsomia exhibited in both groups. AWWET was presented as a widened lumen on CT. In 11 ears (4 ears in the communicated group, 7 ears in the blocked group), ETs bifurcated, the upper bony tube extended to the sphenoid body, the lower part continued down to cartilaginous ET and opened onto the nasopharynx, with"mastoid-like"pneumatization of the sphenoid body in 6 ears. The middle ear deformity in case group was more serious than MA control group, especially the blocked group. The incidence of otitis media in the communicated group was lower than that in the MA control group, and 4 cases in the blocked group had effusion in the ET. Compaired with normal ear, the bony ET elongated significantly in the AWWET groups, and the whole course of ET was significantly shortened, specially in the blocked group. The angle between the bony ET and the cartilaginous ET was decreased and the horizontal angle of the ET increased in the AWWET groups, the difference was considered to indicate statistical significance(<0.05). AWWET with MA is rare, a male predominance, left ear predominance, and with high incidence of hemifacial microsomia. The middle ear deformity is more serious than common MA, especially in the blocked group. The incidence of otitis media in the communicated group is significantly lower than that in the common MA, and the blocked group may be accompanied by ET inflammation.
Topics: Female; Humans; Male; Child, Preschool; Child; Adolescent; Eustachian Tube; Congenital Microtia; Retrospective Studies; Goldenhar Syndrome; Otitis Media; Tomography, X-Ray Computed; Otitis Media with Effusion
PubMed: 38369794
DOI: 10.3760/cma.j.cn115330-20230913-00090 -
Clinical Dysmorphology Oct 2023Treacher Collins syndrome (TCS) is a rare disorder of craniofacial development following different patterns of inheritance. To date, mutations in four genes ( TCOF1,...
Treacher Collins syndrome (TCS) is a rare disorder of craniofacial development following different patterns of inheritance. To date, mutations in four genes ( TCOF1, POLR1D, POLR1C , and POLR1B ) have been found to cause the condition. The molecular defect remains unidentified in a significant proportion of patients. In the current study, whole exome sequencing including analysis of copy number variants was applied for genetic testing of eight Egyptian patients with typical TCS phenotype, representing the first molecular analysis of TCS patients in Egypt as well as in Arab countries. Five heterozygous frameshift mutations were reported, including four variants in the TCOF1 gene (c.3676_3694delinsCTCTGG, c.3984_3985delGA, c.4366_4369delGAAA, and c.3388delC) and one variant in the POLR1D gene (c.60dupA). Four variants were novel extending the disease mutation spectrum. In three affected individuals, no variants of interest were identified in genes associated with TCS or clinically overlapping conditions. Additionally, no relevant variant was detected in genes encoding other subunits of RNA polymerase (pol) I. Molecular analysis is important to provide accurate genetic counseling. It would also contribute to reduced disease incidence. Further studies should be designed to investigate other possible etiologies when no pathogenic variants were revealed in either of the known genes.
Topics: Humans; Egypt; Mandibulofacial Dysostosis; Frameshift Mutation; Genetic Counseling; Genetic Testing; DNA-Directed RNA Polymerases
PubMed: 37646764
DOI: 10.1097/MCD.0000000000000470 -
Journal of Ultrasound in Medicine :... Mar 2024To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening.
OBJECTIVE
To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening.
METHODS
Between January 2019 and December 2022, a normal range of IFA to evaluate the facial profile in fetuses with micrognathia in a Chinese population between 11 and 20 gestational weeks was established, and the pregnancy outcomes of fetal micrognathia were described. The medical records of these pregnancies were collected, including family history, maternal demographics, sonographic findings, genetic testing results, and pregnancy outcomes.
RESULTS
Ultrasound identified 25 patients with fetal micrognathia, with a mean IFA value of 43.6°. All cases of isolated fetal micrognathia in the initial scans were non-isolated in the following scans. A total of 78.9% (15/19) cases had a genetic cause confirmed, including 12 with chromosomal abnormalities and 3 with monogenic disorders. Monogenic disorders were all known causes of micrognathia, including two cases of campomelic dysplasia affected by SOX9 mutations and one case of mandibulofacial dysostosis with an EFTUD2 mutation. In the end, 19 cases were terminated, 1 live birth was diagnosed as Pierre Robin syndrome, and 5 cases were lost to follow-up.
CONCLUSION
IFA is a useful indicator and three-dimensional ultrasound is a significant support technique for fetal micrognathia prenatal diagnosis. Repeat ultrasound monitoring and genetic testing are crucial, with CMA recommended and Whole exome sequencing performed when normal arrays are reported. Isolated fetal micrognathia may be an early manifestation of monogenic disorders.
Topics: Pregnancy; Female; Humans; Micrognathism; Prospective Studies; Ultrasonography, Prenatal; Prenatal Diagnosis; Fetus; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 38164991
DOI: 10.1002/jum.16379 -
Annals of Plastic Surgery Sep 2023Deep learning algorithms based on automatic 3D cephalometric marking points about people without craniomaxillofacial deformities have achieved good results. However,...
Deep learning algorithms based on automatic 3D cephalometric marking points about people without craniomaxillofacial deformities have achieved good results. However, there has been no previous report about hemifacial microsomia (HFM). The purpose of this study is to apply a new deep learning method based on a 3D point cloud graph convolutional neural network to predict and locate landmarks in patients with HFM based on the relationships between points. The authors used a PointNet++ model to investigate the automatic 3D cephalometry. And the mean distance error (MDE) of the center coordinate position and the success detection rate (SDR) were used to evaluate the accuracy of systematic labeling. A total of 135 patients were enrolled. The MDE for all 32 landmarks was 1.46 ± 1.308 mm, and 10 landmarks showed SDRs at 2 mm over 90%, and only 4 landmarks showed SDRs at 2 mm under 60%. Compared with the manual reproducibility, the standard distance deviation and coefficient of variation values for the MDE of the artificial intelligence system was 0.67 and 0.43, respectively. In summary, our training sets were derived from HFM computed tomography to achieve accurate results. The 3D cephalometry system based on the graph convolutional network algorithm may be suitable for the 3D cephalometry system in HFM cases. More accurate results may be obtained if the HFM training set is expanded in the future.
Topics: Humans; Cephalometry; Goldenhar Syndrome; Deep Learning; Artificial Intelligence; Reproducibility of Results; Anatomic Landmarks; Algorithms; Imaging, Three-Dimensional
PubMed: 37566820
DOI: 10.1097/SAP.0000000000003647