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The Journal of Hand Surgery Apr 2015
Review
Topics: Abnormalities, Multiple; Humans; Mandibulofacial Dysostosis; Musculoskeletal Abnormalities; Phenotype; Upper Extremity Deformities, Congenital
PubMed: 25543163
DOI: 10.1016/j.jhsa.2014.10.064 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jan 2022To explore the clinical diagnosis, otological treatment and molecular etiology in a rare syndromic hearing loss case characterized by mandibulofacial dysostosis with... (Review)
Review
To explore the clinical diagnosis, otological treatment and molecular etiology in a rare syndromic hearing loss case characterized by mandibulofacial dysostosis with microcephaly(MFDM). The proband underwent detailed history collection, systematic physical examination and phenotypic analysis, as well as audiological examination, chest X-ray, temporal bone CT and brain MRI and other imaging examinations. The blood DNA of the proband and his parents was extracted and tested by the whole exom sequencing. The EFTUD2-related-MFDM literatures published by the end of 2020 were searched and sifted in PubMed and CNKI databases,the clinical characteristics of MFDM were summarized. In this study, the patient presented with hypoplasia of auricle, micrognathia, microcephaly, developmental retardation, severe sensorineural hearing loss in both ears, and developmental malformation of middle and inner ear. Genetic analysis revealed a de novo deletion c.623_624delAT in EFTUD2 gene. According to the clinical features and genetic test results, the patient was diagnosed as MFDM. In order to solve the problem of hearing loss, the patient was further performed bilateral cochlear implantation, and part of the electrodes responded well during and after operation. This is the first domestic reported case of MFDM caused by EFTUD2 gene mutation. The key problem of cochlear implantation for this kind of patient is to avoid damaging the malformed facial nerve during the operation.The effect of speech rehabilitation after cochlear implant operation is related to many factors such as intelligence development of the patients.
Topics: Cochlear Implantation; Humans; Mandibulofacial Dysostosis; Microcephaly; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear; Syndrome
PubMed: 34979617
DOI: 10.13201/j.issn.2096-7993.2022.01.008 -
Annals of Cardiac Anaesthesia Jan 2017Goldenhar syndrome or oculo-auriculo-vertebral dysplasia was defined by Goldenhar in 1952 and redefined by Grolin et al. later. As the name denotes, children with this... (Review)
Review
Goldenhar syndrome or oculo-auriculo-vertebral dysplasia was defined by Goldenhar in 1952 and redefined by Grolin et al. later. As the name denotes, children with this syndrome present with craniofacial and vertebral anomalies which increase the risk of airway compromise. Neonates and infants with this syndrome often have premature internal organs, low birth weight, and airway disorders. For this reason, safe anesthesia in such infants requires a complete knowledge regarding metabolism and side effects of the drugs. The association of cardiovascular abnormalities is not uncommon and possesses additional challenge for anesthetic management. The aim of this review is to draw attention to the various perioperative problems that can be faced in these infants when they undergo surgery or the correction of the underlying cardiac problem.
Topics: Adult; Anesthesia; Anesthesiologists; Cardiac Surgical Procedures; Child; Goldenhar Syndrome; Humans; Infant; Infant, Newborn
PubMed: 28074825
DOI: 10.4103/0971-9784.197802 -
Clinical Genetics Nov 2015The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome,... (Review)
Review
The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.
Topics: Choanal Atresia; Clubfoot; DEAD-box RNA Helicases; Deafness; Eukaryotic Initiation Factor-4A; Facies; Female; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Intellectual Disability; Male; Mandibulofacial Dysostosis; Micrognathism; Mutation; Peptide Elongation Factors; Pierre Robin Syndrome; RNA Splicing Factors; RNA-Binding Proteins; Ribonucleoprotein, U5 Small Nuclear; Ribs; Spliceosomes
PubMed: 25865758
DOI: 10.1111/cge.12596 -
European Journal of Medical Genetics May 2022Mandibulofacial dysostosis with microcephaly (MFDM, OMIM#610536) is an extremely rare genetic syndrome characterised by microcephaly, external ear deformity, hearing...
Mandibulofacial dysostosis with microcephaly (MFDM, OMIM#610536) is an extremely rare genetic syndrome characterised by microcephaly, external ear deformity, hearing loss, and distinct facial appearance, including zygomatic hypoplasia and micrognathia. Occasionally, various malformations in other internal organs, including oesophageal atresia or tracheoesophageal fistula, may lead to life-threatening situations. Haploinsufficiency of EFTUD2 is responsible for MFDM. Here, we present the phenotypic and genetic characteristics of six Korean children who were diagnosed with MFDM by molecular genetic testing. All but one patient had occipitofrontal circumferences below the -2.0 standard deviation score. Micrognathia was identified in all patients. A cleft palate (66.7%) and other facial dysmorphisms, including facial asymmetry (50%) and malar hypoplasia (50%), were also frequently observed. Hearing loss was observed in all patients along with one or more internal and external ear deformities, including ossicular anomalies, auditory canal stenosis, and microtia. Two patients (33.3%) had undergone surgery for tracheoesophageal fistula type C. Most patients were initially misdiagnosed as other better-known syndromes with overlapping characteristics, such as Treacher Collins or CHARGE syndrome. The first three patients were diagnosed using exome sequencing. However, after increased awareness of MFDM in the first three patients, MFDM was considered one of the initial differential diagnoses and could be diagnosed by target gene analysis in the remaining three cases. Thus, we recommend targeted EFTUD2 analysis as the initial workup for the rapid diagnosis of MFDM in patients with facial dysostosis, microcephaly, and otologic problems.
Topics: Abnormalities, Multiple; Child; Hearing Loss; Humans; Mandibulofacial Dysostosis; Microcephaly; Micrognathism; Peptide Elongation Factors; Republic of Korea; Ribonucleoprotein, U5 Small Nuclear; Tracheoesophageal Fistula
PubMed: 35395430
DOI: 10.1016/j.ejmg.2022.104478 -
The British Journal of Oral &... Sep 2014Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti-Zwahlen-Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard... (Review)
Review
Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti-Zwahlen-Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard and soft tissues of the first and second branchial arches. Early operations focus on maintaining the airway, protecting the eyes, and supporting auditory neurological development. Later operations include staged reconstruction of the mouth, face, and external ear. Bimaxillary surgery can improve the maxillomandibular facial projection, but correction of malar, orbital rim, and temporal defects may be more difficult. We present a clinical review of the syndrome with a chronological approach to the operations.
Topics: Age Factors; Face; Facial Bones; Humans; Mandibulofacial Dysostosis; Plastic Surgery Procedures
PubMed: 24776174
DOI: 10.1016/j.bjoms.2014.02.007 -
Proceedings of the National Academy of... Aug 2022Ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a critical rate-limiting step in ribosome biogenesis, which is essential for cell survival. Despite its...
Ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a critical rate-limiting step in ribosome biogenesis, which is essential for cell survival. Despite its global function, disruptions in ribosome biogenesis cause tissue-specific birth defects called ribosomopathies, which frequently affect craniofacial development. Here, we describe a cellular and molecular mechanism underlying the susceptibility of craniofacial development to disruptions in Pol I transcription. We show that Pol I subunits are highly expressed in the neuroepithelium and neural crest cells (NCCs), which generate most of the craniofacial skeleton. High expression of Pol I subunits sustains elevated rRNA transcription in NCC progenitors, which supports their high tissue-specific levels of protein translation, but also makes NCCs particularly sensitive to rRNA synthesis defects. Consistent with this model, NCC-specific deletion of Pol I subunits , , and associated factor in mice cell-autonomously diminishes rRNA synthesis, which leads to p53 protein accumulation, resulting in NCC apoptosis and craniofacial anomalies. Furthermore, compound mutations in Pol I subunits and associated factors specifically exacerbate the craniofacial anomalies characteristic of the ribosomopathies Treacher Collins syndrome and Acrofacial Dysostosis-Cincinnati type. Mechanistically, we demonstrate that diminished rRNA synthesis causes an imbalance between rRNA and ribosomal proteins. This leads to increased binding of ribosomal proteins Rpl5 and Rpl11 to Mdm2 and concomitantly diminished binding between Mdm2 and p53. Altogether, our results demonstrate a dynamic spatiotemporal requirement for rRNA transcription during mammalian cranial NCC development and corresponding tissue-specific threshold sensitivities to disruptions in rRNA transcription in the pathogenesis of congenital craniofacial disorders.
Topics: Animals; Craniofacial Abnormalities; Mandibulofacial Dysostosis; Mice; Neural Crest; Proto-Oncogene Proteins c-mdm2; RNA Polymerase I; RNA, Ribosomal; Ribosomal Proteins; Skull; Transcription, Genetic; Tumor Suppressor Protein p53
PubMed: 35881792
DOI: 10.1073/pnas.2116974119 -
Oral Diseases Sep 2023The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve,... (Review)
Review
The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis.
Topics: Humans; Goldenhar Syndrome; Facial Asymmetry; Mandible
PubMed: 36648381
DOI: 10.1111/odi.14508 -
American Journal of Medical Genetics.... Feb 2021Mandibulofacial dysostosis with microcephaly (MFDM) is due to haploinsufficiency of spliceosomal GTPase EFTUD2. Features include microcephaly, craniofacial...
Mandibulofacial dysostosis with microcephaly (MFDM) is due to haploinsufficiency of spliceosomal GTPase EFTUD2. Features include microcephaly, craniofacial dysmorphology, developmental disability, and other anomalies. We surveyed parents of individuals with MFDM to expand knowledge about health, development, and parental concerns. Participants included attendees of the inaugural MFDM family conference in June 2019 and members of the MFDM online group. To explore MFDM variable expressivity, we offered targeted Sanger sequencing for untested parents. Forty-seven parents participated in the survey. 59% of individuals with MFDM were male, with mean age 6.4 years (range 8 months to 49 years). Similar to the literature (n = 123), common features include microcephaly, cleft palate, choanal stenosis, tracheoesophageal fistula, heart problems, and seizures. New information includes airway intervention details, age-based developmental outcomes, rate of vision refractive errors, and lower incidences of prematurity and IUGR. Family concerns focused on development, communication, and increased support. Targeted Sanger sequencing for families of seven individuals demonstrated de novo variants, for a total of 91.9% de novo EFTUD2 variants (n = 34/37). This study reports the largest single cohort of individuals with MFDM, expands phenotypic spectrum and inheritance patterns, improves understanding of developmental outcomes and care needs, and identifies development as the biggest concern for parents.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Female; GTP Phosphohydrolases; Genetic Predisposition to Disease; Haploinsufficiency; Humans; Infant; Male; Mandibulofacial Dysostosis; Microcephaly; Middle Aged; Mutation; Peptide Elongation Factors; Phenotype; Ribonucleoprotein, U5 Small Nuclear; Spliceosomes; Young Adult
PubMed: 33247512
DOI: 10.1002/ajmg.a.61977 -
Clinics in Plastic Surgery Jul 2021Phenotypic severity dictates the timing and type of surgical intervention required. Mandibular distraction in children without respiratory and feeding difficulties... (Review)
Review
Phenotypic severity dictates the timing and type of surgical intervention required. Mandibular distraction in children without respiratory and feeding difficulties remains controversial with regard to long-term mandibular growth outcomes and reducing surgical burden. Early mandibular distraction does not obviate secondary orthognathic surgery at skeletal maturity; it provides improved functional, aesthetic, and psychosocial outcomes, at least in the short term. Costochondral rib grafting for Pruzansky type IIB and III mandibles can produce reliable results, especially when combined with subsequent mandibular distraction. Secondary 2-jaw orthognathic surgery plus genioplasty at skeletal maturity benefits from improved bone volume from prior mandibular distraction.
Topics: Algorithms; Bone Transplantation; Child; Child, Preschool; Genioplasty; Goldenhar Syndrome; Humans; Infant, Newborn; Mandible; Mandibular Advancement; Orthognathic Surgical Procedures; Osteogenesis, Distraction; Phenotype; Tomography, X-Ray Computed
PubMed: 34051892
DOI: 10.1016/j.cps.2021.02.001