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1.
Stomatologiia (Mosk) ; 103(3): 16-20, 2024.
Article in Russian | MEDLINE | ID: mdl-38904554

ABSTRACT

PURPOSE: To study the effect of magnetic therapy on the formation of distraction regenerate of the lower jaw in patients with lower micrognathia. MATERIALS AND METHODS: The study comprised 159 patients with inferior micrognathia of congenital and acquired etiology. The patients were divided into 2 groups. The main group consisted of 112 patients who received magnetic therapy: 55 patients with congenital micrognathia and 57 patients with acquired micrognathia. The control group included 47 patients who did not undergo magnetic therapy: 20 patients with congenital micrognathia and 27 patients with acquired micrognathia. Magnetic therapy was performed daily starting from day 1 or 2 after surgery. Ultrasound monitoring began on the 7th day of distraction and was carried out every 3-4 days, which made it possible to assess the dynamics of the formation of the distraction regenerate. RESULTS: Ultrasound examination on the 7th day of distraction revealed that in the main group the number of distraction regenerates of the normotrophic type was 36.5%, hypotrophic type 18%, hypertrophic type 54.5%. In the control group, the corresponding rates were 53%, 31% and 22%. CONCLUSION: Magnetic therapy induces osteogenesis and accelerates the maturation of the distraction regenerate. This makes it possible to accelerate the pace of distraction without reducing the quality of the regenerate.


Subject(s)
Magnetic Field Therapy , Micrognathism , Osteogenesis, Distraction , Humans , Osteogenesis, Distraction/methods , Male , Child , Female , Micrognathism/surgery , Magnetic Field Therapy/methods , Child, Preschool , Mandible/surgery , Treatment Outcome
2.
Res Dev Disabil ; 151: 104769, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38865789

ABSTRACT

ARID1B-related disorders constitute a clinical continuum, from classic Coffin-Siris syndrome to intellectual disability (ID) with or without nonspecific dysmorphic features. Here, we describe an 11-year-old boy with an ARID1B mutation whose phenotype changed from severe developmental delay and ID to a complex neurodevelopmental disorder with multidimensional impairments, including normal intelligence despite heterogeneous IQ scores, severe motor coordination disorder, oral language disorder and attention-deficit/hyperactivity disorder. Phenotypic changes occurred after early intensive remediation and paralleled the normalization of myelination impairments, as evidenced by early brain imaging. WHAT THIS PAPER ADDS?: This report describes a 10-year multidisciplinary follow-up of a child with an ARID1B mutation who received early intensive remediation and whose phenotype changed during development. Clinical improvement paralleled the normalization of myelination impairments. This case supports a dimensional approach for complex neurodevelopmental disorders.


Subject(s)
DNA-Binding Proteins , Intellectual Disability , Micrognathism , Phenotype , Transcription Factors , Humans , Male , Child , Intellectual Disability/genetics , Transcription Factors/genetics , DNA-Binding Proteins/genetics , Micrognathism/genetics , Micrognathism/diagnostic imaging , Follow-Up Studies , Face/abnormalities , Face/diagnostic imaging , Brain/diagnostic imaging , Brain/abnormalities , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnostic imaging , Neck/abnormalities , Neck/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/genetics , Magnetic Resonance Imaging , Neurodevelopmental Disorders/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnostic imaging , Developmental Disabilities/genetics , Motor Skills Disorders/genetics , Mutation , Foot Deformities, Congenital/genetics , Foot Deformities, Congenital/diagnostic imaging , Joint Instability/diagnostic imaging , Joint Instability/genetics
3.
Eur J Med Genet ; 69: 104945, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697389

ABSTRACT

To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2. Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented during the 1st year of life with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall mildly affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems. To our knowledge this is the first report of an inherited likely pathogenic variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.


Subject(s)
Abnormalities, Multiple , Face , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Neck , Pedigree , Transcription Factors , Adult , Female , Humans , Infant , Male , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , DNA-Binding Proteins/genetics , Face/abnormalities , Face/pathology , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/pathology , Intellectual Disability/genetics , Intellectual Disability/pathology , Micrognathism/genetics , Micrognathism/pathology , Mutation, Missense , Neck/abnormalities , Neck/pathology , Phenotype , Transcription Factors/genetics
5.
Eur J Med Genet ; 69: 104948, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735569

ABSTRACT

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.


Subject(s)
Abnormalities, Multiple , Anorectal Malformations , DNA-Binding Proteins , Face , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Neck , Transcription Factors , Humans , Female , Micrognathism/genetics , Micrognathism/pathology , Child, Preschool , Intellectual Disability/genetics , Intellectual Disability/pathology , Transcription Factors/genetics , Neck/abnormalities , Neck/pathology , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/pathology , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , DNA-Binding Proteins/genetics , Anorectal Malformations/genetics , Face/abnormalities , Face/pathology , DNA Helicases/genetics , Nuclear Proteins/genetics , Anal Canal/abnormalities , Anal Canal/pathology , Phenotype
6.
BMC Med Genomics ; 17(1): 142, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790056

ABSTRACT

Coffin-Siris syndrome (CSS) is a rare autosomal dominant inheritance disorder characterized by distinctive facial features, hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, hypotonia, hirsutism/hypertrichosis, sparse scalp hair and varying kind of congenital anomalies. CSS can easily be misdiagnosed as other syndromes or disorders with a similar clinical picture because of their genetic and phenotypic heterogeneity. We describde the genotype-phenotype correlation of one patient from a healthy Chinese family with a novel genotype underlying CSS, who was first diagnosed in the ophthalmology department as early-onset high myopia (eoHM). Comprehensive ophthalmic tests as well as other systemic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. Real-time quantitative PCR (RT-qPCR) technology was used to detect the relative mRNA expression levels of candidate genes between proband and normal family members. The pathogenicity of the identified variant was determined by The American College of Medical Genetics and Genomics (ACMG) guidelines. STRING protein-protein interactions (PPIs) network analysis was used to detect the interaction of candidate gene-related proteins with high myopia gene-related proteins. The patient had excessive eoHM, cone-rod dystrophy, coarse face, excessive hair growth on the face, sparse scalp hair, developmental delay, intellectual disability, moderate hearing loss, dental hypoplasia, patent foramen ovale, chronic non-atrophic gastritis, bilateral renal cysts, cisterna magna, and emotional outbursts with aggression. The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5), which are strongly associated with the typical clinical features of CSS patients. The test results of RT-qPCR showed that mRNA expression of the ARID1B gene in the proband was approximately 30% lower than that of the normal control in the family, suggesting that the variant had an impact on the gene function at the level of mRNA expression. The variant was pathogenic as assessed by ACMG guidelines. Analysis of protein interactions in the STRING online database revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4, whereas the ARID1A protein antagonizes the ARID1B protein. Therefore, in this paper, we are the first to report a de novo heterozygous frameshift insertion variant in the ARID1B gene causing CSS with excessive eoHM. Our study extends the genotypic and phenotypic spectrums for ARID1B-CSS and supplies evidence of significant association of eoHM with variant in ARID1B gene. As CSS has high genetic and phenotypic heterogeneity, our findings highlight the importance of molecular genetic testing and an interdisciplinary clinical diagnostic workup to avoid misdiagnosis as some disorders with similar manifestations of CSS.


Subject(s)
DNA-Binding Proteins , Face , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Myopia , Neck , Pedigree , Transcription Factors , Humans , Intellectual Disability/genetics , Transcription Factors/genetics , Face/abnormalities , Male , Micrognathism/genetics , Female , Hand Deformities, Congenital/genetics , Myopia/genetics , DNA-Binding Proteins/genetics , Neck/abnormalities , Neck/pathology , Abnormalities, Multiple/genetics , Adult , Asian People/genetics , Genetic Association Studies , China , Phenotype , Exome Sequencing , Mutation , East Asian People
7.
Am J Med Genet A ; 194(8): e63626, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38591849

ABSTRACT

De novo germline variants of the SRY-related HMG-box 11 gene (SOX11) have been reported to cause Coffin-Siris syndrome-9 (CSS-9), a rare congenital disorder associated with multiple organ malformations, including ear anomalies. Previous clinical and animal studies have found that intragenic pathogenic variant or haploinsufficiency in the SOX11 gene could cause inner ear malformation, but no studies to date have documented the external ear malformation caused by SOX11 deficiency. Here, we reported a Chinese male with unilateral microtia and bilateral sensorineural deafness who showed CSS-like manifestations, including dysmorphic facial features, impaired neurodevelopment, and fingers/toes malformations. Using trio-based whole-exome sequencing, a de novo missense variant in SOX11 (NM_003108.4: c.347A>G, p.Y116C) was identified and classified as pathogenic variant as per American College of Medical Genetics guidelines. Moreover, a systematic search of the literature yielded 12 publications that provided data of 55 SOX11 intragenic variants affecting various protein-coding regions of SOX11 protein. By quantitatively analyzing phenotypic spectrum information related to these 56 SOX11 variants (including our case), we found variants affecting different regions of SOX11 protein (high-mobility group [HMG] domain and non-HMG regions) appear to influence the phenotypic spectrum of organ malformations in CSS-9; variants altering the HMG domain were more likely to cause the widest range of organ anomalies. In summary, this is the first report of CSS with external ear malformation caused by pathogenic variant in SOX11, indicating that the SOX11 gene may be not only essential for the development of the inner ear but also critical for the morphogenesis of the external ear. In addition, thorough clinical examination is recommended for patients who carry pathogenic SOX11 variants that affect the HMG domain, as these variants may cause the widest range of organ anomalies underlying this condition.


Subject(s)
Abnormalities, Multiple , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , SOXC Transcription Factors , Humans , Male , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Ear, External/abnormalities , Ear, External/pathology , Exome Sequencing , Face/abnormalities , Face/pathology , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/pathology , Intellectual Disability/genetics , Intellectual Disability/pathology , Micrognathism/genetics , Micrognathism/pathology , Micrognathism/diagnosis , Mutation, Missense/genetics , Neck/abnormalities , Neck/pathology , Phenotype , SOXC Transcription Factors/genetics
9.
Clin Oral Investig ; 28(5): 252, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627272

ABSTRACT

OBJECTIVE: Craniofacial anomalies are widely discussed as predisposing factors of breathing disorders. Since many more cofactors exist, this study investigated the association between maxillary micrognathia and morphological changes of posterior airway space and adenoids in these patients. MATERIAL AND METHODS: Cephalometric radiographs of n = 73 patients were used for data acquisition. The patients were divided into two groups according to certain skeletal characteristics: maxillary micrognathia (n = 34, 16 female, 18 male; mean age 10.55 ± 3.03 years; defined by a SNA angle < 79°) and maxillary eugnathia (n = 39, 19 female, 20 male; mean age 10.93 ± 3.26 years; defined by a SNA angle > 79°). The evaluation included established procedures for measurements of the maxilla, posterior airway space and adenoids. Statistics included Kolmogorov-Smirnov-, T- and Mann-Whitney-U-Tests for the radiographs. The level of significance was set at p < 0.05. RESULTS: The cephalometric analysis showed differences in the superior posterior face height and the depth of the posterior airway space at palatal level among the two groups. The depth of the posterior airway space at mandibular level was the same for both groups, just as the size of the area taken by adenoids in the nasopharynx. CONCLUSIONS: Skeletal anomalies affect the dimension of the posterior airway space. There were differences among the subjects with maxillary micrognathia and these with a normal maxilla. However, the maxilla was only assessed in the sagittal direction, not in the transverse. This study showed that the morphology of the maxilla relates to the posterior airway space whereas the adenoids seem not to be affected. CLINICAL RELEVANCE: Maxillary micrognathia is significantly associated with a smaller depth of the posterior airway space at the palatal level compared to patients with maxillary eugnathia.


Subject(s)
Adenoids , Micrognathism , Humans , Male , Female , Child , Adolescent , Micrognathism/diagnostic imaging , Nasopharynx , Maxilla/diagnostic imaging , Respiratory System , Cephalometry/methods
10.
Clin Oral Investig ; 28(5): 287, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38684576

ABSTRACT

OBJECTIVES: Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms. MATERIALS AND METHODS: We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4. RESULTS: A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing. CONCLUSIONS: Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis. CLINICAL RELEVANCE: This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis.


Subject(s)
Anodontia , Exome Sequencing , Face , Intellectual Disability , Micrognathism , Mutation, Missense , Neck , SOXC Transcription Factors , Animals , Female , Humans , Male , Mice , Abnormalities, Multiple/genetics , Anodontia/genetics , Face/abnormalities , Hand Deformities, Congenital/genetics , In Situ Hybridization, Fluorescence , Micrognathism/genetics , Neck/abnormalities , SOXC Transcription Factors/genetics
11.
Mol Genet Genomic Med ; 12(4): e2441, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38618928

ABSTRACT

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.


Subject(s)
Ear Diseases , Ear , Micrognathism , Humans , Infant, Newborn , Male , China , Ear/abnormalities , Phospholipase C beta , East Asian People
12.
Otolaryngol Clin North Am ; 57(4): 551-557, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38503668

ABSTRACT

Oral causes of dysphagia in infancy may involve the lips, the tongue, or the palate. Whereas ankyloglossia is commonly diagnosed in infants with dysphagia, assessment of the need for surgical intervention may be less straightforward. Tongue size (macroglossia) may be associated with dysphagia as it may cause limitation of movement of the food or milk bolus by the lips or cheeks. Congenital conditions such as cleft lip and palate, micrognathia, or craniofacial microsomia may also be associated with dysphagia. Diagnosis and treatment of these conditions can be improved with the engagement of lactation and feeding experts as well as multidisciplinary craniofacial teams.


Subject(s)
Deglutition Disorders , Tongue , Humans , Deglutition Disorders/etiology , Deglutition Disorders/diagnosis , Deglutition Disorders/therapy , Infant , Tongue/physiopathology , Child , Ankyloglossia , Cleft Palate/complications , Cleft Palate/surgery , Cleft Lip/complications , Cleft Lip/surgery , Lip/physiopathology , Mouth Abnormalities/surgery , Mouth Abnormalities/complications , Micrognathism/complications
13.
Eur J Hum Genet ; 32(7): 786-794, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38467731

ABSTRACT

Biallelic pathogenic variants in CDC45 are associated with Meier-Gorlin syndrome with craniosynostosis (MGORS type 7), which also includes short stature and absent/hypoplastic patellae. Identified variants act through a hypomorphic loss of function mechanism, to reduce CDC45 activity and impact DNA replication initiation. In addition to missense and premature termination variants, several pathogenic synonymous variants have been identified, most of which cause increased exon skipping of exon 4, which encodes an essential part of the RecJ-orthologue's DHH domain. Here we have identified a second cohort of families segregating CDC45 variants, where patients have craniosynostosis and a reduction in height, alongside common facial dysmorphisms, including thin eyebrows, consistent with MGORS7. Skipping of exon 15 is a consequence of two different variants, including a shared synonymous variant that is enriched in individuals of East Asian ancestry, while other variants in trans are predicted to alter key intramolecular interactions in α/ß domain II, or cause retention of an intron within the 3'UTR. Our cohort and functional data confirm exon skipping is a relatively common pathogenic mechanism in CDC45, and highlights the need for alternative splicing events, such as exon skipping, to be especially considered for variants initially predicted to be less likely to cause the phenotype, particularly synonymous variants.


Subject(s)
Cell Cycle Proteins , Exons , Humans , Cell Cycle Proteins/genetics , Craniosynostoses/genetics , Craniosynostoses/pathology , Female , Male , Alternative Splicing , Pedigree , Growth Disorders , Micrognathism , Patella/abnormalities , Congenital Microtia
14.
Nat Struct Mol Biol ; 31(7): 1018-1022, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38347147

ABSTRACT

ARID1B is a SWI/SNF subunit frequently mutated in human Coffin-Siris syndrome (CSS) and it is necessary for proliferation of ARID1A mutant cancers. While most CSS ARID1B aberrations introduce frameshifts or stop codons, the functional consequence of missense mutations found in ARID1B is unclear. We here perform saturated mutagenesis screens on ARID1B and demonstrate that protein destabilization is the main mechanism associated with pathogenic missense mutations in patients with Coffin-Siris Syndrome.


Subject(s)
DNA-Binding Proteins , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Mutation, Missense , Protein Stability , Transcription Factors , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Micrognathism/genetics , Hand Deformities, Congenital/genetics , Intellectual Disability/genetics , Abnormalities, Multiple/genetics , Face/abnormalities , Neck/abnormalities
15.
J Craniofac Surg ; 35(4): 1163-1169, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38376164

ABSTRACT

AIM: The aim of this cross-sectional study was to evaluate, via cone-beam computed tomography, the long-term postoperative outcome in children treated with mandibular distraction osteogenesis. MATERIALS AND METHODS: All young patients treated with mandibular distraction osteogenesis (MDO), during a 16-year period, at the University Department of Oral and Maxillofacial Surgery of a Pediatric Hospital, were recalled, and various clinical and radiographic parameters were recorded. RESULTS: Eleven patients were included: 5 with hemifacial microsomia (HFM) and 6 with mandibular micrognathia. In all cases, MDO had been successful in regular follow-up and decannulation, soon after MDO, was achieved in all tracheostomy cases. The long-term result in cases of HFM was found stable, functionally and esthetically accepted, although less satisfactory than in regular follow-up; in micrognathia patients, relapse of different degrees was registered in 4 of 6 cases, without any need for tracheostomy though. Detailed and accurate information was obtained by cone-beam computed tomography (CBCT). The shape of the regenerated bone was irregular in HFM cases and relatively normal in the micrognathia cases. Quality of the regenerated bone was normal in all patients. The irregular shape registered in HFM cases did not compromise a safe orthognathic operation. CONCLUSIONS: Distraction osteogenesis remains an early treatment choice in cases of mandibular deformities. Long-term findings showed that there is a degree of relapse with growth, which was more obvious in mandibular micrognathia cases. Computed tomography contributes to detailed evaluation of changes at the distraction site.


Subject(s)
Cone-Beam Computed Tomography , Mandible , Micrognathism , Osteogenesis, Distraction , Humans , Osteogenesis, Distraction/methods , Female , Child , Male , Adolescent , Cross-Sectional Studies , Mandible/surgery , Mandible/diagnostic imaging , Treatment Outcome , Micrognathism/surgery , Micrognathism/diagnostic imaging , Facial Asymmetry/surgery , Facial Asymmetry/diagnostic imaging , Child, Preschool
16.
J Coll Physicians Surg Pak ; 34(2): 187-192, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38342870

ABSTRACT

OBJECTIVE: To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023. METHODOLOGY: Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission. RESULTS: Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins. CONCLUSION: Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome. KEY WORDS: Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.


Subject(s)
Abnormalities, Multiple , Chromosome Deletion , Guillain-Barre Syndrome , Limb Deformities, Congenital , Mandibulofacial Dysostosis , Micrognathism , Respiratory Insufficiency , WAGR Syndrome , Humans , Guillain-Barre Syndrome/diagnosis , Neutrophils , Cross-Sectional Studies , Biomarkers , Lymphocytes , Chromosomes, Human, Pair 11
17.
J Craniomaxillofac Surg ; 52(4): 469-471, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38369394

ABSTRACT

The aim of this study is to present a sequential strategy of soft-tissue, non-osteogenic distraction with a novel device, followed by microvascular bony reconstruction for severe cases of mandibular hypoplasia. The case of a 21-year-old woman with Goldenhar syndrome is presented, whose mandible remained severely hypoplastic despite previous attempts at distraction and was not suitable for further osteogenic distraction. Soft tissue deficiency and pin track scarring prevented free fibular transfers. A personalized distractor, anchored to the cranium and the mandibular symphysis, was designed to expand the soft tissues while allowing for physiological temporomandibular joint (TMJ) movement without compression forces. Internal distractors were placed along the osteotomies to prevent condylar luxation. After completion of the soft tissue distraction, the native mandible was resected except for the condyles and reconstructed with two free fibula flaps. This report represents the proof of concept of a sequential approach to severe lower face soft-tissue and bone deficiency, which preserves TMJ function and avoids the transfer of poorly matched skin to the face.


Subject(s)
Goldenhar Syndrome , Micrognathism , Osteogenesis, Distraction , Plastic Surgery Procedures , Female , Humans , Young Adult , Adult , Goldenhar Syndrome/diagnostic imaging , Goldenhar Syndrome/surgery , Mandible/diagnostic imaging , Mandible/surgery , Mandible/abnormalities , Micrognathism/surgery , Skull/surgery
18.
J Ultrasound Med ; 43(3): 491-499, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38164991

ABSTRACT

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.


Subject(s)
Micrognathism , Pregnancy , Female , Humans , Micrognathism/diagnosis , Micrognathism/genetics , Prospective Studies , Ultrasonography, Prenatal/methods , Prenatal Diagnosis/methods , Fetus , Peptide Elongation Factors , Ribonucleoprotein, U5 Small Nuclear
19.
Am J Med Genet A ; 194(6): e63540, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38243407

ABSTRACT

Coffin-Siris Syndrome (CSS, MIM 135900) is now a well-described genetic condition caused by pathogenic variants in the Bromocriptine activating factor (BAF) complex, including ARID1B, ARID1A, ARID2, SMARCA4, SMARCE1, SMARCB1, SOX11, SMARCC2, DPF2, and more recently, BICRA. Individuals with CSS have a spectrum of various medical challenges, most often evident at birth, including feeding difficulties, hypotonia, organ-system anomalies, and learning and developmental differences. The classic finding of fifth digit hypo- or aplasia is seen variably. ARID2, previously described, is one of the less frequently observed gene changes in CSS. Although individuals with ARID2 have been reported to have classic features of CSS including hypertrichosis, coarse facial features, short stature, and fifth digit anomalies, as with many of the other CSS genes, there appears to be a spectrum of phenotypes. We report here a cohort of 17 individuals with ARID2 variants from the Coffin-Siris/BAF clinical registry and detail their medical challenges as well as developmental progress. Feeding difficulties, hypotonia, and short stature occur often, and hip dysplasia appears to occur more often than with other genes, however more severe medical challenges such as significant brain and cardiac malformations are rarer. Individuals appear to have mild to moderate intellectual impairment and may carry additional diagnoses such as ADHD. Further phenotypic description of this gene will aid clinicians caring for individuals with this rarer form of CSS.


Subject(s)
Abnormalities, Multiple , Face/abnormalities , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Neck , Neck/abnormalities , Phenotype , Transcription Factors , Humans , Micrognathism/genetics , Micrognathism/diagnosis , Intellectual Disability/genetics , Intellectual Disability/pathology , Neck/pathology , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnosis , Male , Female , Transcription Factors/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Child , Child, Preschool , Infant , Mutation/genetics , Adolescent , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease
20.
Acta Anaesthesiol Scand ; 68(4): 466-475, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38164092

ABSTRACT

BACKGROUND: We investigated how syndromic versus nonsyndromic forms of micrognathia impacted difficult intubation outcomes in children. Primary outcome was the first-attempt success rate of tracheal intubation, secondary outcomes were number of intubation attempts and complications. We hypothesized that syndromic micrognathia would be associated with lower first-attempt success rate. METHODS: In micrognathic patients enrolled in the Pediatric Difficult Intubation Registry (08/2012-03/2019) we retrospectively compared demographic and clinical characteristics between children with nonsyndromic and syndromic micrognathia using standardized mean differences (SMD) and assessed the association of the presence of syndrome with the primary and secondary outcomes using propensity score matching analysis with and without matching for airway assessment findings. RESULTS: Nonsyndromic patients (628) were less likely to have additional airway abnormalities. Syndromic patients (216) were less likely to have unanticipated difficult intubation (2% vs. 20%, SMD 0.59). First-attempt success rates of intubation were: 38% in the syndromic versus 34% in the nonsyndromic group (odds ratio [OR] 1.18; 95% confidence intervals [95% CI] 0.74, 1.89; p = .478), and 37% versus 37% (OR 0.99; 95% CI 0.66, 1.48; p = .959). Median number of intubation attempts were 2 (interquartile range [IQR]: 1, 3; range: 1, 8) versus 2 (IQR: 1, 3; range 1, 12) (median regression coefficient = 0; 95% CI: -0.7, 0.7; p = .999) and 2 (IQR: 1, 3; range: 1, 12) versus 2 (IQR: 1, 3; range 1, 8) (median regression coefficient = 0; 95% CI: -0.5, 0.5; p = .999). Complication rates were 14% versus 22% (OR 0.6; 95% CI 0.34, 1.04; p = .07) and 16% versus 21% (OR 0.71; 95% CI 0.43, 1.17; p = .185). CONCLUSIONS: Presence of syndrome was not associated with lower first-attempt success rate on intubation, number of intubation attempts, or complication rate among micrognathic patients difficult to intubate, despite more associated craniofacial abnormalities. Nonsyndromic patients were more likely to have unanticipated difficult intubations, first attempt with direct laryngoscopy.


Subject(s)
Micrognathism , Child , Humans , Retrospective Studies , Intubation, Intratracheal , Laryngoscopy , Registries
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