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Genes Dec 2023Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb... (Review)
Review
Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient's lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient's benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures.
Topics: Child; Humans; Young Adult; Adult; Mandibulofacial Dysostosis; Cleft Palate; Micrognathism; Syndrome; RNA Splicing Factors
PubMed: 38254920
DOI: 10.3390/genes15010029 -
Italian Journal of Pediatrics Feb 2012The Pierre Robin Sequence features were first described by Robin in 1923 and include micrognathia, glossoptosis and respiratory distress with an incidence estimated as... (Review)
Review
BACKGROUND
The Pierre Robin Sequence features were first described by Robin in 1923 and include micrognathia, glossoptosis and respiratory distress with an incidence estimated as 1:8,500 to 1:20,000 newborns. Upper airway obstruction and feeding difficulties are the main concerns related to the pathology. Mandibular distraction should be considered a treatment option (when other treatments result inadequate). PATIANTS AND METHODS: Ten patients between the ages of 1 month and 2 years with severe micrognathia and airway obstruction were treated with Mandibular Distraction Osteogenesis (MDO).All patients underwent fibroscopic examination of the upper airway and a radiographic imaging and/or computed tomography scans to detect malformations and to confirm that the obstruction was caused by posterior tongue displacement. All patients were evaluated by a multidisciplinary team. Indications for surgery included frequent apneic episodes with severe desaturation (70%). Gavage therapy was employed in all patients since oral feeding was not possible. The two tracheotomy patients were 5 months and 2 years old respectively, and the distraction procedure was performed to remove the tracheotomy tube. All patients were treated with bilateral mandibular distraction: two cases with an external multivector distraction device, six cases with an internal non-resorbable device and two cases with an internal resorbable device. In one case, the patient with Goldenhar's Syndrome, the procedure was repeated.
RESULTS
The resolution of symptoms was obtained in all patients, and, when present, tracheotomy was removed without complications. Of the two patients with pre-existing tracheotomies, in the younger patient (5 months old) the tracheotomy was removed 7 days postoperatively. In the Goldenhar's syndrome case (2 years old) a Montgomery device was necessary for 6 months due to the presence of tracheotomy-inducted tracheomalacia. Patients were discharged when the endpoint was obtained: symptoms and signs of airway obstruction were resolved, PAS and maxillomandibular relationship improved, and tracheotomy, when present, removed. During the follow-up, no injury to the inferior alveolar nerve was noted and scarring was significant in only the two cases treated with external devices.
CONCLUSION
Mandibular Distraction Osteogenesis is a good solution in solving respiratory distress when other procedures are failed in paediatric patients with severe micrognatia.
Topics: Airway Obstruction; Child, Preschool; Female; Goldenhar Syndrome; Humans; Infant; Infant, Newborn; Male; Mandible; Micrognathism; Osteogenesis, Distraction; Pierre Robin Syndrome; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 22300418
DOI: 10.1186/1824-7288-38-7 -
Journal of Advanced Pharmaceutical... Dec 2022The aim is to create awareness about Patterson syndrome among dental students. Patterson-Stevenson-Fontaine syndrome is a very rare condition marked by irregular facial...
The aim is to create awareness about Patterson syndrome among dental students. Patterson-Stevenson-Fontaine syndrome is a very rare condition marked by irregular facial bone and tissue growth (mandibulofacial dysostosis) as well as limb abnormalities. A recessed jaw (retrognathism), cleft palate, and external ear defects are all possible symptoms of this disorder. A total of 112 undergraduate dental students participated in a longitudinal cross-sectional sample. To assess college students' awareness about Patterson syndrome, a self-administered, closed-ended questionnaire was developed and distributed. The only language allowed was English. The results were analyzed in SPSS software version 23. 10.71% of females and 14.29% of males were aware about Patterson syndrome. 32.14% of females and 38.39% of males were aware that Patterson syndrome was a rare adrenal disorder. We can conclude that very few of the population which was only 25% of the dental students were aware about Patterson syndrome and this survey helped in creating awareness about this syndrome.
PubMed: 36798544
DOI: 10.4103/japtr.japtr_382_22 -
AJNR. American Journal of Neuroradiology Feb 2011A variety of congenital syndromes affecting the face occur due to defects involving the first and second BAs. Radiographic evaluation of craniofacial deformities is... (Review)
Review
A variety of congenital syndromes affecting the face occur due to defects involving the first and second BAs. Radiographic evaluation of craniofacial deformities is necessary to define aberrant anatomy, plan surgical procedures, and evaluate the effects of craniofacial growth and surgical reconstructions. High-resolution CT has proved vital in determining the nature and extent of these syndromes. The radiologic evaluation of syndromes of the first and second BA should begin first by studying a series of isolated defects (cleft lip with or without CP, micrognathia, and EAC atresia) that compose the major features of these syndromes and allow a more specific diagnosis. After discussion of these defects and the associated embryology, we discuss PRS, HFM, ACS, TCS, Stickler syndrome, and VCFS.
Topics: Branchial Region; DiGeorge Syndrome; Ear; Ear Diseases; Facial Asymmetry; Humans; Mandibulofacial Dysostosis; Pierre Robin Syndrome; Radiography
PubMed: 20360348
DOI: 10.3174/ajnr.A2073 -
Pediatric Research Dec 2022Accurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve...
BACKGROUND
Accurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve services and outcomes. The aim is to describe the association between CFA, ID and ASD using linked population data.
METHODS
All births (1983-2005; n = 566,225) including CFA births (comprising orofacial clefts, craniosynostosis, craniofacial microsomia and mandibulofacial dysostosis) surviving to 5 years were identified from the birth, death, birth defects and midwives population data sets. Linked data from these data sets were followed for a minimum of 5 years from birth until 2010 in the intellectual disability database to identify ID and ASD. These associations were examined using a modified Poisson regression.
RESULTS
Prevalence of ID and ASD was higher among CFA (especially with additional anomalies) than those without [prevalence ratio 5.27, 95% CI 4.44, 6.25]. It was higher among CFA than those with other gastrointestinal and urogenital anomalies but lower than nervous system and chromosomal anomalies. Children with CFA and severe ID had a higher proportion of nervous system anomalies.
CONCLUSIONS
Findings indicate increased ID and ASD among CFA but lower than nervous system and chromosomal anomalies. This population evidence can improve early identification of ID/ASD among CFA and support service planning.
IMPACT
Our study found about one in ten children born with craniofacial anomalies (CFA) are later identified with intellectual disability (ID). Prevalence of ID among CFA was higher than those with other gastrointestinal, urogenital, and musculoskeletal birth defects but lower than those with the nervous system and chromosomal abnormalities. Most children with craniofacial anomalies have a mild-to-moderate intellectual disability with an unknown aetiology. On average, intellectual disability is identified 2 years later for children born with non-syndromic craniofacial anomalies than those with syndromic conditions. Our findings can improve the early identification of ID/ASD among CFA and support service planning.
Topics: Child; Pregnancy; Female; Humans; Autism Spectrum Disorder; Intellectual Disability; Cleft Lip; Australia; Cleft Palate
PubMed: 35352007
DOI: 10.1038/s41390-022-02024-9 -
The Journal of Pediatrics Jul 2018To determine whether infant cases with craniofacial microsomia (CFM) evidence poorer neurodevelopmental status than demographically similar infants without craniofacial... (Observational Study)
Observational Study
OBJECTIVES
To determine whether infant cases with craniofacial microsomia (CFM) evidence poorer neurodevelopmental status than demographically similar infants without craniofacial diagnoses ("controls"), and to examine cases' neurodevelopmental outcomes by facial phenotype and hearing status.
STUDY DESIGN
Multicenter, observational study of 108 cases and 84 controls aged 12-24 months. Participants were assessed by the Bayley Scales of Infant and Toddler Development-Third Edition and the Preschool Language Scales-Fifth Edition (PLS-5). Facial features were classified with the Phenotypic Assessment Tool for Craniofacial Microsomia.
RESULTS
After adjustment for demographic variables, there was little difference in Bayley Scales of Infant and Toddler Development-Third Edition or Preschool Language Scales-Fifth Edition outcomes between cases and controls. Estimates of mean differences ranged from -0.23 to 1.79 corresponding to standardized effect sizes of -.02 to 0.12 (P values from .30 to .88). Outcomes were better among females and those with higher socioeconomic status. Among cases, facial phenotype and hearing status showed little to no association with outcomes. Analysis of individual test scores indicated that 21% of cases and 16% of controls were developmentally delayed (OR 0.68, 95% CI 0.29-1.61).
CONCLUSIONS
Although learning problems have been observed in older children with CFM, we found no evidence of developmental or language delay among infants. Variation in outcomes across prior studies may reflect differences in ascertainment methods and CFM diagnostic criteria.
Topics: Case-Control Studies; Child Development; Female; Goldenhar Syndrome; Hearing Loss; Humans; Infant; Male; Neurodevelopmental Disorders; Socioeconomic Factors
PubMed: 29685618
DOI: 10.1016/j.jpeds.2018.02.076 -
Clinical Genetics Sep 2016Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single...
Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.
Topics: Abnormalities, Multiple; DNA-Binding Proteins; Female; Humans; Limb Deformities, Congenital; Male; Mandibulofacial Dysostosis; Mosaicism; Mutation, Missense; Pedigree; Phenotype; Pregnancy
PubMed: 26706854
DOI: 10.1111/cge.12721 -
The Journal of Craniofacial Surgery Sep 2023Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on...
Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on standardized clinical diagnostic criteria is available. The use of diagnostic criteria could improve research and communication among patients and healthcare professionals. Two sets of phenotypic criteria for research were independently developed and based on multidisciplinary consensus: the FACIAL and ICHOM criteria. This study aimed to assess the sensitivity of both criteria with an existing global multicenter database of patients with CFM and study the characteristics of patients that do not meet the criteria. A total of 730 patients with CFM from were included. Characteristics of the patients were extracted, and severity was graded using the O.M.E.N.S. and Pruzansky-Kaban classification. The sensitivity of the FACIAL and ICHOM was respectively 99.6% and 94.4%. The Cohen's kappa of 0.38 indicated a fair agreement between both criteria. Patients that did not fulfill the FACIAL criteria had facial asymmetry without additional features. It can be concluded that the FACIAL and ICHOM criteria are accurate criteria to describe patients with CFM. Both criteria could be useful for future studies on CFM to create comparable and reproducible outcomes.
Topics: Humans; Goldenhar Syndrome; Facial Asymmetry; Face; Health Personnel; Patients
PubMed: 37264504
DOI: 10.1097/SCS.0000000000009446 -
International Journal of Molecular... Mar 2021The nucleoli are membrane-less nuclear substructures that govern ribosome biogenesis and participate in multiple other cellular processes such as cell cycle progression,... (Review)
Review
The nucleoli are membrane-less nuclear substructures that govern ribosome biogenesis and participate in multiple other cellular processes such as cell cycle progression, stress sensing, and DNA damage response. The proper functioning of these organelles is ensured by specific proteins that maintain nucleolar structure and mediate key nucleolar activities. Among all nucleolar proteins, treacle encoded by gene emerges as one of the most crucial regulators of cellular processes. was initially discovered as a gene involved in the Treacher Collins syndrome, a rare genetic disorder characterized by severe craniofacial deformations. Later studies revealed that treacle regulates ribosome biogenesis, mitosis, proliferation, DNA damage response, and apoptosis. Importantly, several reports indicate that treacle is also involved in cancer development, progression, and response to therapies, and may contribute to other pathologies such as Hirschsprung disease. In this manuscript, we comprehensively review the structure, function, and the regulation of /treacle in physiological and pathological processes.
Topics: Cell Nucleolus; Homeostasis; Humans; Mandibulofacial Dysostosis; Nuclear Proteins; Phosphoproteins
PubMed: 33804586
DOI: 10.3390/ijms22052482 -
Journal of Developmental Biology Jul 2022Mandibulofacial dysostosis (MFD) is a human congenital disorder characterized by hypoplastic neural-crest-derived craniofacial bones often associated with outer and...
Mandibulofacial dysostosis (MFD) is a human congenital disorder characterized by hypoplastic neural-crest-derived craniofacial bones often associated with outer and middle ear defects. There is growing evidence that mutations in components of the spliceosome are a major cause for MFD. Genetic variants affecting the function of several core splicing factors, namely , , , and , are responsible for MFD in five related but distinct syndromes known as Nager and Rodriguez syndromes (NRS), craniofacial microsomia (CFM), mandibulofacial dysostosis with microcephaly (MFDM), cerebro-costo-mandibular syndrome (CCMS) and Burn-McKeown syndrome (BMKS), respectively. Animal models of NRS and MFDM indicate that MFD results from an early depletion of neural crest progenitors through a mechanism that involves apoptosis. Here we characterize the knockdown phenotype of Eftud2, Snrpb and Txnl4a in embryos at different stages of neural crest and craniofacial development. Our results point to defects in cranial neural crest cell formation as the likely culprit for MFD associated with , and haploinsufficiency, and suggest a commonality in the etiology of these craniofacial spliceosomopathies.
PubMed: 35893124
DOI: 10.3390/jdb10030029