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European Journal of Paediatric Dentistry Dec 2023Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2...
Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2 gene. Mandibulofacial dysostoses are characterised by the core triad malar hypoplasia, maxillary hypoplasia and dysplastic ears, all derived by the impaired development of the first and second branchial arches. Differential diagnosis is often challenging. The early genetic diagnosis is extremely useful, not only for the correct management of cranial malformations, but also for the early diagnosis and treatment of the comorbidities associated to the disease, which greatly benefit from early treatment.
Topics: Humans; Branchial Region; Mandibulofacial Dysostosis; Diagnosis, Differential; Zygoma; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 38015115
DOI: 10.23804/ejpd.2023.24.04.03 -
Wiley Interdisciplinary Reviews.... May 2017Craniofacial anomalies account for approximately one-third of all congenital birth defects reflecting the complexity of head and facial development. Craniofacial... (Review)
Review
Craniofacial anomalies account for approximately one-third of all congenital birth defects reflecting the complexity of head and facial development. Craniofacial development is dependent upon a multipotent, migratory population of neural crest cells, which generate most of the bone and cartilage of the head and face. In this review, we discuss advances in our understanding of the pathogenesis of a specific array of craniofacial anomalies, termed facial dysostoses, which can be subdivided into mandibulofacial dysostosis, which present with craniofacial defects only, and acrofacial dysostosis, which encompasses both craniofacial and limb anomalies. In particular, we focus on Treacher Collins syndrome, Acrofacial Dysostosis-Cincinnati Type as well as Nager and Miller syndromes, and animal models that provide new insights into the molecular and cellular basis of these congenital syndromes. We emphasize the etiologic and pathogenetic similarities between these birth defects, specifically their unique deficiencies in global processes including ribosome biogenesis, DNA damage repair, and pre-mRNA splicing, all of which affect neural crest cell development and result in similar tissue-specific defects. WIREs Dev Biol 2017, 6:e263. doi: 10.1002/wdev.263 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Humans; Mandibulofacial Dysostosis; Neural Crest; Syndrome
PubMed: 28186364
DOI: 10.1002/wdev.263 -
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 -
Indian Journal of Dental Research :... 2013Goldenhar syndrome is a syndrome of complex structures developing from first and second branchial arches during blastogenesis. The etiology of this rare disease is not...
Goldenhar syndrome is a syndrome of complex structures developing from first and second branchial arches during blastogenesis. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. Here we present a unique case of Goldenhar syndrome with absence of left condyle, hypoplasia of the zygomatic bone, no pneumatization of the mastoid process, underdeveloped mandible, bifid tongue and the skin tags in the preauricular area.
Topics: Adolescent; Ear, External; Female; Goldenhar Syndrome; Humans; Mandible; Mandibular Condyle; Mastoid; Open Bite; Tongue; Zygoma
PubMed: 23852257
DOI: 10.4103/0970-9290.114952 -
American Journal of Medical Genetics.... Nov 2013Approximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one-third display craniofacial abnormalities which are a... (Review)
Review
Approximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one-third display craniofacial abnormalities which are a significant cause of infant mortality and dramatically affect national health care budgets. To date, more than 700 distinct craniofacial syndromes have been described and in this review, we discuss the etiology, pathogenesis and management of facial dysostoses with a particular emphasis on Treacher Collins, Nager and Miller syndromes. As we continue to develop and improve medical and surgical care for the management of individual conditions, it is essential at the same time to better characterize their etiology and pathogenesis. Here we describe recent advances in our understanding of the development of facial dysostosis with a view towards early in utero identification and intervention which could minimize the manifestation of anomalies prior to birth. The ultimate management for any craniofacial anomaly however, would be prevention and we discuss this possibility in relation to facial dysostosis.
Topics: Abnormalities, Multiple; Chromosome Deletion; Chromosomes, Human, Pair 11; Humans; Limb Deformities, Congenital; Mandibulofacial Dysostosis; Micrognathism; WAGR Syndrome
PubMed: 24123981
DOI: 10.1002/ajmg.c.31375 -
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 -
Journal of Pediatric Genetics Dec 2016Genetic etiologies for congenital anomalies of the facial skeleton, namely, the maxilla and mandible, are important to understand and recognize. Malocclusions occur when... (Review)
Review
Genetic etiologies for congenital anomalies of the facial skeleton, namely, the maxilla and mandible, are important to understand and recognize. Malocclusions occur when there exist any significant deviation from what is considered a normal relationship between the upper jaw (maxilla) and the lower jaw (mandible). They may be the result of anomalies of the teeth alone, the bones alone, or both. A number of genes play a role in the facial skeletal development and are regulated by a host of additional regulatory molecules. As such, numerous craniofacial syndromes specifically affect the development of the jaws. The following review discusses several genetic anomalies that specifically affect the bones of the craniofacial skeleton and lead to malocclusion.
PubMed: 27895973
DOI: 10.1055/s-0036-1593505 -
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 -
Frontiers in Bioscience (Landmark... Jan 2017Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A... (Review)
Review
Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A (TFAM), first cloned as an mtDNA transcription factor, is critical for packaging and maintaining mtDNA. To investigate functional aspects of TFAM, we identified many RNA-binding proteins as candidate TFAM interactors, including ERAL1 and p32. In this review, we first describe the functions of TFAM, replication proteins such as polymerase gamma and Twinkle, and mitochondrial RNA binding proteins. We describe the role of mitochondrial nucleic acid binding proteins within the mitochondrial matrix and two oxidative phosphorylation-related proteins within the mitochondrial intermembrane space. We then discuss how mitochondrial dysfunction is related to several diseases, including mitochondrial respiratory disease, Miller syndrome and cancer. We also describe p32 knockout mice, which are embryonic lethal and exhibit respiratory chain defects. Miller syndrome is a recessive disorder characterized by postaxial acrofacial dysostosis and caused by a mutation in . Finally, we explain that p32 and mitochondrial creatine kinase may be novel markers for the progression of prostate cancer.
Topics: Abnormalities, Multiple; Animals; Carrier Proteins; DNA Helicases; DNA Polymerase gamma; DNA, Mitochondrial; DNA-Binding Proteins; GTP-Binding Proteins; Humans; Limb Deformities, Congenital; Mandibulofacial Dysostosis; Mice; Micrognathism; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; Neoplasm Proteins; Neoplasms; RNA-Binding Proteins; Ribonuclease P; Transcription Factors
PubMed: 27814609
DOI: 10.2741/4479 -
Journal of Medical Genetics Oct 1977Four individuals in a single family affected with maxillofacial dysostosis are reported. Maxillary hypoplasia, delayed onset of speech, and poor development of language...
Four individuals in a single family affected with maxillofacial dysostosis are reported. Maxillary hypoplasia, delayed onset of speech, and poor development of language skills without associated hearing loss are the main characteristics of the syndrome which is transmitted as an autosomal dominant. Cephalometric analysis and speech and hearing evaluation of our patients confirmed the above findings.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Genes, Dominant; Genetic Variation; Humans; Male; Mandibulofacial Dysostosis; Maxilla; Pedigree; Phenotype
PubMed: 592352
DOI: 10.1136/jmg.14.5.355