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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 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Apr 2021Children with microtia are often associated with maxillofacial dysostosis, such as Treacher Collins syndrome, Goldenhar syndrome, and Nager syndrome, and they are prone... (Review)
Review
Children with microtia are often associated with maxillofacial dysostosis, such as Treacher Collins syndrome, Goldenhar syndrome, and Nager syndrome, and they are prone to suffer from obstructive sleep apnea(OSA). Obstruction widely occurred in the upper airway is the main mechanism of OSA in these children, and dysplasia of the pharynx and neurodevelopmental abnormalities may also participate. Early diagnosis requires symptom screening and polysomnography. Imaging techniques and endoscopy can be adopted to fully assess the upper airway status to guide further treatment. According to the child's condition and the main obstruction site, treatment methods include maxillofacial deformity correction, continuous positive pressure ventilation and tracheotomy. OSA in microtia children with maxillofacial dysostosis needs to be identified and treated in time to reduce the adverse effects on the growth and development of children.
Topics: Child; Congenital Microtia; Craniofacial Dysostosis; Eye Abnormalities; Humans; Maxillofacial Abnormalities; Sleep Apnea, Obstructive; Speech Disorders
PubMed: 33794641
DOI: 10.13201/j.issn.2096-7993.2021.04.020 -
The Journal of Craniofacial SurgeryFacial advancement represents the essence of the surgical treatment of syndromic craniosynostosis. Frontofacial monobloc distraction is an effective surgical approach to...
BACKGROUND
Facial advancement represents the essence of the surgical treatment of syndromic craniosynostosis. Frontofacial monobloc distraction is an effective surgical approach to correct midface retrusion although someone consider it very hazardous procedure. The authors evaluated a group of patients who underwent frontofacial monobloc distraction with the aim to identify the advancement results performed in immature skeletal regarding the midface morphologic characteristics and its effects on growth.
METHODS
Sixteen patients who underwent frontofacial monobloc distraction with pre- and postsurgical computed tomography (CT) scans were evaluated and compared to a control group of 9 nonsyndromic children with CT scans at 1-year intervals during craniofacial growth. Three-dimensional measurements and superimposition of the CT scans were used to evaluate midface morphologic features and longitudinal changes during the craniofacial growth and following the advancement. Presurgical growth was evaluated in 4 patients and postsurgical growth was evaluated in 9 patients.
RESULTS
Syndromic maxillary width and length were reduced and the most obtuse facial angles showed a lack in forward projection of the central portion in these patients. Three-dimensional distances and images superimposition demonstrated the age did not influence the course of abnormal midface growth.
CONCLUSION
The syndromic midface is hypoplastic and the sagittal deficiency is associated to axial facial concavity. The advancement performed in mixed dentition stages allowed the normalization of facial position comparable to nonsyndromic group. However, the procedure was not able to change the abnormal midface architecture and craniofacial growth.
Topics: Child; Craniofacial Dysostosis; Craniosynostoses; Face; Facial Bones; Female; Humans; Male; Maxilla; Osteogenesis, Distraction; Treatment Outcome
PubMed: 33136785
DOI: 10.1097/SCS.0000000000006997 -
Indian Pediatrics Feb 2005
Topics: Female; Hallermann's Syndrome; Humans; Infant
PubMed: 15767716
DOI: No ID Found -
Indian Journal of Ophthalmology Jul 1993
Topics: Aphakia; Female; Hallermann's Syndrome; Humans; Microphthalmos; Middle Aged; Nystagmus, Pathologic; Radiography; Skull; Vision Disorders
PubMed: 8262609
DOI: No ID Found -
Indian Journal of Ophthalmology Jun 1973
Topics: Abnormalities, Multiple; Adolescent; Child, Preschool; Dermoid Cyst; Ear, External; Eye Neoplasms; Female; Humans; Lipoma; Mandibulofacial Dysostosis; Syndrome
PubMed: 4789118
DOI: No ID Found -
American Journal of Medical Genetics.... May 2020Craniofacial morphogenesis is regulated in part by signaling from the Endothelin receptor type A (EDNRA). Pathogenic variants in EDNRA signaling pathway components...
Craniofacial morphogenesis is regulated in part by signaling from the Endothelin receptor type A (EDNRA). Pathogenic variants in EDNRA signaling pathway components EDNRA, GNAI3, PCLB4, and EDN1 cause Mandibulofacial Dysostosis with Alopecia (MFDA), Auriculocondylar syndrome (ARCND) 1, 2, and 3, respectively. However, cardiovascular development is normal in MFDA and ARCND individuals, unlike Ednra knockout mice. One explanation may be that partial EDNRA signaling remains in MFDA and ARCND, as mice with reduced, but not absent, EDNRA signaling also lack a cardiovascular phenotype. Here we report an individual with craniofacial and cardiovascular malformations mimicking the Ednra mouse phenotype, including a distinctive micrognathia with microstomia and a hypoplastic aortic arch. Exome sequencing found a novel homozygous missense variant in EDNRA (c.1142A>C; p.Q381P). Bioluminescence resonance energy transfer assays revealed that this amino acid substitution in helix 8 of EDNRA prevents recruitment of G proteins to the receptor, abrogating subsequent receptor activation by its ligand, Endothelin-1. This homozygous variant is thus the first reported loss-of-function EDNRA allele, resulting in a syndrome we have named Oro-Oto-Cardiac Syndrome. Further, our results illustrate that EDNRA signaling is required for both normal human craniofacial and cardiovascular development, and that limited EDNRA signaling is likely retained in ARCND and MFDA individuals. This work illustrates a straightforward approach to identifying the functional consequence of novel genetic variants in signaling molecules associated with malformation syndromes.
Topics: Animals; Craniofacial Abnormalities; Ear; Ear Diseases; GTP-Binding Protein alpha Subunits, Gi-Go; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Humans; Loss of Function Mutation; Mandibulofacial Dysostosis; Mice; Mice, Knockout; Morphogenesis; Neural Crest; Phenotype; Receptor, Endothelin A; Signal Transduction
PubMed: 32133772
DOI: 10.1002/ajmg.a.61531 -
The Cleft Palate-craniofacial Journal :... Jan 2021The study aim was to assess behavioral adjustment in preschool children with and without craniofacial microsomia (CFM).
OBJECTIVE
The study aim was to assess behavioral adjustment in preschool children with and without craniofacial microsomia (CFM).
DESIGN
Multisite cohort study of preschoolers with CFM ("cases") or without CFM ("controls").
PARTICIPANTS
Mothers (89%), fathers (9%), and other caregivers (2%) of 161 preschoolers.
OUTCOME MEASURE
Child Behavior Check List (CBCL 1.5-5); linear regressions with standardized effect sizes (ES) adjusted for sociodemographic confounds.
RESULTS
Child Behavior Check Lists for 89 cases and 72 controls (average age 38.3 ± 1.9 months). Children were male (54%), white (69%), and of Latino ethnicity (47%). Cases had microtia with mandibular hypoplasia (52%), microtia only (30%), or other CFM-associated features (18%). Nearly 20% of cases had extracranial anomalies. Composite CBCL scores were in the average range compared to test norms and similar for cases and controls. On the subscales, cases' parents reported higher Anxious/Depressed scores (ES = 0.35, = .04), Stress Problems (ES = 0.40, = .04), Anxiety Problems (ES = 0.34, = .04), and Autism Spectrum Problems (ES = 0.41, = .02); however, the autism subscale primarily reflected speech concerns. Among cases, more problems were reported for children with extracranial anomalies and certain phenotypic categories with small ES.
CONCLUSIONS
Behavioral adjustment of preschoolers with CFM was comparable to peers. However, parental reports reflected greater concern for internalizing behaviors; thus, anxiety screening and interventions may benefit children with CFM. Among cases, more problems were reported for those with more complex presentations of CFM. Craniofacial microsomia-related speech problems should be distinguished from associated psychosocial symptoms during developmental evaluations.
Topics: Adult; Caregivers; Child, Preschool; Cohort Studies; Congenital Microtia; Female; Goldenhar Syndrome; Humans; Male; Mothers
PubMed: 32783465
DOI: 10.1177/1055665620947987 -
The International Journal of... Jun 2009Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1... (Review)
Review
Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. An animal model of the severe form of TCS, generated through mutation of the mouse homologue Tcof1 has recently revealed significant insights into the etiology and pathogenesis of TCS (Dixon and Dixon, 2004; Dixon et al., 2006; Jones et al 2008). During early embryogenesis in a TCS individual, an excessive degree of neuroepithelial apoptosis diminishes the generation of neural crest cells. Neural crest cells are a migratory stem and progenitor cell population that generates most of the tissues of the head including much of the bone, cartilage and connective tissue. It has been hypothesized that mutations in Tcof1 disrupt ribosome biogenesis to a degree that is insufficient to meet the proliferative needs of the neuroepithelium and neural crest cells. This causes nucleolar stress activation of the p53-dependent apoptotic pathway which induces neuroepithelial cell death. Interestingly however, chemical and genetic inhibition of p53 activity can block the wave of apoptosis and prevent craniofacial anomalies in Tcof1 mutant mice [Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33]. These findings shed new light on potential therapeutic avenues for the prevention of not only TCS but also other congenital craniofacial disorders which share a similar etiology and pathogenesis.
Topics: Animals; Humans; Intracellular Signaling Peptides and Proteins; Mandibulofacial Dysostosis; Mice; Nuclear Proteins; Phosphoproteins
PubMed: 19027870
DOI: 10.1016/j.biocel.2008.10.026 -
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