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1.
Medicine (Baltimore) ; 99(4): e18648, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977854

RESUMO

RATIONALE: Micrognathia is a subtle facial malformation characterized by a small mandible and receding chin. Fetal micrognathia is often associated with chromosomal abnormalities, skeletal dysplasia, and various syndromes. Once it is dignosised, detailed fetal malformation screening and chromosome examination should be carried out. PATIENT CONCERN: One pregnant woman with suspicion of fetal micrognathia was referred from her local hospital to our hospital for detailed fetal malformation screening and fetal echocardiography. Examination of the fetus was performed using a two-dimensional and three-dimensional ultrasound probe in multiple planes. The fetus showed micrognathia without glossoptosis with features of the inferior facial angle (IFA) ≤50° and his tongue reached anterior mandibular border box during normal movement. DIAGNOSES: The fetus was diagnosed as isolated micrognathia prenatally without multisystem abnormalities. INTERVENTIONS: Amniocentesis was performed and the fetus was found to carry 46XN with 6q14.1 duplication, the significance of which was unclear. OUTCOMES: The fetus was labored through vagina at 38 weeks gestation. A small soft cleft palate was diagnosed after delivery. LESSONS: This case suggests that once prenatal diagnosis of the fetal micrognathia has been made, we should carefully examine the presence of fetus's multisystem developmental abnormalities and due consideration should be given for associated soft cleft palate.


Assuntos
Micrognatismo/diagnóstico , Ultrassonografia Pré-Natal/métodos , Amniocentese , Fissura Palatina/complicações , Fissura Palatina/diagnóstico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Micrognatismo/complicações , Micrognatismo/diagnóstico por imagem , Palato Mole/anormalidades , Gravidez
2.
J Craniofac Surg ; 31(1): 222-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31633663

RESUMO

INTRODUCTION: Mandibular distraction osteogenesis (MDO) is an effective treatment for severe micrognathia, as it helps to avoid tracheostomy but has some adverse effects on the temporomandibular joint (TMJ). TMJ ankylosis is a serious condition leading to feeding difficulties and growth impairment, and could result in worse consequences in cases with micrognathia who already have limited growth potential. Here, we aimed to report on cases with TMJ ankylosis-a rare but devastating complication of MDO. In total, we described 3 syndromic cases with TMJ ankylosis that developed after MDO and reviewed the associated literature. MATERIAL AND METHODS: We retrospectively enrolled 3 patients who presented with TMJ ankylosis following MDO at the Oral and Maxillofacial Surgery Department of the University Hospital of Lille, France. RESULTS: All 3 patients had craniofacial syndrome with micrognathia. MDO was performed at least twice in each case, and the 3 patients developed subsequent TMJ ankylosis. They all presented with TMJ ankylosis and micrognathia in our Department. DISCUSSION: MDO leads to a certain amount of stress on the TMJ, and in cases with congenital TMJ deformation, such stress could lead to TMJ ankylosis. To our knowledge, 12 cases of TMJ ankylosis after MDO have been described in studies involving 309 patients while it is not reported in other publications. They were all syndromic patients. Thus, TMJ health should be carefully monitored during and after MDO to avoid TMJ ankylosis, and alternative treatments such as costochondral grafts should be considered.


Assuntos
Anquilose/cirurgia , Mandíbula/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Anquilose/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Micrognatismo/diagnóstico por imagem , Micrognatismo/cirurgia , Osteogênese por Distração , Estudos Retrospectivos , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Resultado do Tratamento
3.
Int J Pediatr Otorhinolaryngol ; 128: 109735, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31675646

RESUMO

Coffin-Siris Syndrome (CSS) is a genetic syndrome associated with multiple congenital anomalies due to mutations in the BAF-complex or SOX gene. Although well characterized overall, the subunits of the BAF-complex or SOX gene affected demonstrate phenotypic differences which are continuing to be defined. Among the variants is the SMARCE1 mutation, the least common identified genotype. This case report presents a pediatric patient with SMARCE1-related CSS, the seventh case reported in the literature. The congenital anomalies are discussed and compared to the reported cases of SMARCE1-related CSS and CSS overall with an emphasis on otolaryngologic manifestations.


Assuntos
Face/anormalidades , Deformidades Congênitas da Mão/complicações , Deficiência Intelectual/complicações , Micrognatismo/complicações , Pescoço/anormalidades , Anormalidades Múltiplas , Pré-Escolar , Proteínas Cromossômicas não Histona/genética , Fenda Labial/etiologia , Proteínas de Ligação a DNA/genética , Deficiências do Desenvolvimento/etiologia , Epiglote/anormalidades , Perda Auditiva Condutiva/etiologia , Humanos , Macroglossia/etiologia , Masculino , Micrognatismo/etiologia , Ventilação da Orelha Média , Mutação , Otite Média/etiologia , Otite Média/terapia , Palato/anormalidades , Traqueomalácia/congênito
4.
Int J Oral Maxillofac Surg ; 49(4): 421-431, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31526673

RESUMO

Maxillary hypoplasia in cleft lip and palate is a complex deformity. Despite surgical improvements, postoperative relapse persists. This systematic review was performed to determine the mean horizontal relapse rates for the surgical techniques used to treat maxillary hypoplasia: Le Fort I osteotomy with rigid fixation, Le Fort I distraction osteogenesis, and anterior maxillary distraction osteogenesis. This study followed the PRISMA statement. The PubMed, Embase, Science Direct, and Web of Science databases were searched through to June 2018. Studies on non-growing cleft lip and palate patients who had undergone one of the three surgical procedures and who had postoperative horizontal maxillary changes assessed at >6 months post-surgery were included. Stata SE was used to estimate pooled means, heterogeneity, and publication bias. The search strategy identified 326 citations, from which 24 studies were selected. Relapse rates following Le Fort I osteotomy with rigid fixation, Le Fort I distraction osteogenesis, and anterior maxillary distraction osteogenesis were 20%, 12%, and 12%, respectively. Relapse rates with and without bone grafting were 19% and 66%, respectively. The relapse rate following distraction osteogenesis with internal distraction was lower than that with external distraction. Study limitations were heterogeneity, which was above moderate, the low number of high-quality studies, and unidirectional assessment of postoperative maxillary movement.


Assuntos
Fenda Labial , Fissura Palatina , Micrognatismo , Osteogênese por Distração , Cefalometria , Humanos , Maxila , Osteotomia de Le Fort , Recidiva , Resultado do Tratamento
5.
J Craniofac Surg ; 31(1): 150-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31794444

RESUMO

BACKGROUND: Mandibular distraction with horizontal osteotomy of the ramus and vertical distraction vector has successfully treated airway obstruction in young Pierre Robin patients. Placing the osteotomy just above the dentoalveolar plane can minimize damage to the inferior alveolar nerve. This study maps the position of the mandibular foramen relative to the height of the dentoalveolar plane to demonstrate the safety of this technique in Pierre Robin neonates. METHODS: Retrospective review of 3D CT scans of Pierre Robin patients was performed with inclusion criteria: ≤1 year of age, bilateral micrognathia requiring surgical intervention for airway (ie, tracheostomy versus mandibular distraction), no prior mandible surgery, and pre-operative 3D CT study. Demographic information collected included: age at CT scan, age at surgery, and genetic diagnosis. Using the 3D study of each patient's right mandible, a line at the level of the mandibular dentoalveolar plane was drawn across the lingual surface of the ramus and the distance to the mandibular foramen at a length perpendicular to the dentoalveolar plane line was then measured. RESULTS: Fifteen patients were included in the study (at least 9 Pierre Robin). Average age at time of CT scan was 71.4 days old. The mandibular foramen was below the level of the dentoalveolar plane in all cases at an average distance of 4.7 mm. Average ramus height 46.2±13.4 CONCLUSIONS:: The dentoalveolar plane was consistently above the mandibular foramen in all patients. Thus, the horizontal corticotomy at a level just above the mandibular dentoalveolar plane spares the inferior alveolar nerve in neonatal Pierre Robin patients undergoing vertical vector mandibular distraction.


Assuntos
Mandíbula/cirurgia , Osteotomia/métodos , Síndrome de Pierre Robin/cirurgia , Obstrução das Vias Respiratórias , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Micrognatismo/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
J Clin Ultrasound ; 48(1): 48-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31638729

RESUMO

Cleft lip and cleft palate (CP) are the most common facial malformations. Two-dimensional (2D) ultrasound (US) is the first-line examination in the prenatal diagnosis of CP. Three-dimensional, four-dimensional US and MRI provide a better detection of facial clefts. We present two fetuses with micrognathia and suspected secondary CP on 2D US: fetal tongue appeared in an unusual position (low tip and high dorsum position) and showed uncoordinated movements. MRI did not confirm the US suspicion, but at birth the two fetuses were affected by Pierre Robin sequence.


Assuntos
Fissura Palatina/diagnóstico por imagem , Micrognatismo/diagnóstico por imagem , Síndrome de Pierre Robin/diagnóstico por imagem , Língua/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Gravidez , Língua/embriologia
9.
Indian J Dent Res ; 30(4): 625-629, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31745063

RESUMO

Severe restriction of airway volume in the orofacial region, caused by temporomandibular joint (TMJ) ankylosis, may lead to obstructive sleep apnea (OSA). If the TMJ ankylosis is progressive, rarely, the caregivers may fail to notice the problem. Such patients may have only symptoms of snoring, daytime sleepiness, fatigue, inability to concentrate, and irritability. At times, emergency tracheostomy may be needed to increase the oxygen supply. Distraction osteogenesis (DO) is a less invasive surgical technique in the management of such OSA by correcting the reduced airway space. In DO, the angulation of the distractors and the pace of activation determine the success of the neo-generation of segments of bone. The formation of a well-corticated mandibular canal (MC) in the newly generated bone is an evidence of the success of the procedure. Such bilateral formation of the MC is not reported from this part of the world. We report a case of a 4-year-old boy who was struggling with OSA due to TMJ ankylosis. He was successfully treated by bilateral mandibular DO. The formation and cortication of the MC is discussed with emphasis on the neural regeneration.


Assuntos
Anquilose , Micrognatismo , Osteogênese por Distração , Síndromes da Apneia do Sono , Pré-Escolar , Humanos , Masculino , Mandíbula , Traqueostomia
10.
J Hum Genet ; 64(12): 1237-1242, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31591492

RESUMO

VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis-Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis-Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis-Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis-Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Mutação de Sentido Incorreto/genética , Degeneração Estriatonigral/genética , Displasia Cleidocraniana/genética , Displasia Ectodérmica/genética , Feminino , Genótipo , Homozigoto , Humanos , Lactente , Deformidades Congênitas dos Membros/genética , Micrognatismo/genética , Fenótipo
11.
Cytogenet Genome Res ; 159(1): 1-11, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31658463

RESUMO

The switch/sucrose non-fermenting (SWI/SNF) complex is an ATP-dependent chromatin remodeller that regulates the spacing of nucleosomes and thereby controls gene expression. Heterozygous mutations in genes encoding subunits of the SWI/SNF complex have been reported in individuals with Coffin-Siris syndrome (CSS), with the majority of the mutations in ARID1B. CSS is a rare congenital disorder characterized by facial dysmorphisms, digital anomalies, and variable intellectual disability. We hypothesized that mutations in genes encoding subunits of the ubiquitously expressed SWI/SNF complex may lead to alterations of the nucleosome profiles in different cell types. We performed the first study on CSS-patient samples and investigated the nucleosome landscapes of cell-free DNA (cfDNA) isolated from blood plasma by whole-genome sequencing. In addition, we studied the nucleosome landscapes of CD14+ monocytes from CSS-affected individuals by nucleosome occupancy and methylome-sequencing (NOMe-seq) as well as their expression profiles. In cfDNA of CSS-affected individuals with heterozygous ARID1B mutations, we did not observe major changes in the nucleosome profile around transcription start sites. In CD14+ monocytes, we found few genomic regions with different nucleosome occupancy when compared to controls. RNA-seq analysis of CD14+ monocytes of these individuals detected only few differentially expressed genes, which were not in proximity to any of the identified differential nucleosome-depleted regions. In conclusion, we show that heterozygous mutations in the human SWI/SNF subunit ARID1B do not have a major impact on the nucleosome landscape or gene expression in blood cells. This might be due to functional redundancy, cell-type specificity, or alternative functions of ARID1B.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Face/anormalidades , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Micrognatismo/genética , Pescoço/anormalidades , Proteínas Nucleares/genética , Nucleossomos/genética , Fatores de Transcrição/genética , Adolescente , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Criança , Pré-Escolar , Feminino , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Monócitos/citologia , Adulto Jovem
12.
J Hum Genet ; 64(12): 1173-1186, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31530938

RESUMO

Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.


Assuntos
Anormalidades Múltiplas/genética , Face/anormalidades , Predisposição Genética para Doença/genética , Variação Genética/genética , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Micrognatismo/genética , Pescoço/anormalidades , Estudos de Coortes , Estudos de Associação Genética/métodos , Humanos
13.
J Craniofac Surg ; 30(6): 1745-1749, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449217

RESUMO

Maxillary hypoplasia is a common developmental deformity affecting patients with cleft lip and palate. Various surgical techniques including conventional orthognathic surgery, total maxillary distraction osteogenesis, and anterior maxillary segmental distraction have been applied to address the deformity. With the evolution of 3D computed tomography imaging, the visualization of skeletal complexities in different perspectives is greatly enhanced and comprehensive surgical planning is achieved. Intraoperative efficiency is also improved with the fabrication of 3D-printed templates. The study aims to present different surgical techniques with virtual surgical planning (VSP) and 3D-printed surgical templates and the solution of representative cases. From January 2014 to January 2019, VSP was transferred to actual surgery or distraction precisely in 80 adult patients with cleft-related maxillary hypoplasia. The accuracy was analyzed and the relapse was also estimated and observed in 18 patients after 1-year follow-up. Based on our experience, VSP provides a more reliable and effective option to conventional model surgery. It facilitates the preoperative planning and accurately transfers the virtual plan to correct the cleft-related maxillary hypoplasia.


Assuntos
Maxila/cirurgia , Micrognatismo/cirurgia , Adulto , Fenda Labial/complicações , Fenda Labial/cirurgia , Coleta de Dados , Feminino , Humanos , Masculino , Micrognatismo/etiologia , Procedimentos Cirúrgicos Ortognáticos/métodos , Procedimentos Ortopédicos , Impressão Tridimensional , Recidiva , Adulto Jovem
14.
J Craniofac Surg ; 30(8): 2486-2489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469743

RESUMO

We reported a 16-year-old patient with chin defect accompanying micrognathia and airway stenosis owing to a traffic accident. The treatment of this patient involved a modified genioplasty associated with orthognathic surgeries. Through data analysis, we found that the patient's facial morphology and airway space are greatly improved compared with preoperation: y-axis(T4-T1) = -4.5 degree; FCA (T4-T1) = -18 degree; CSAmin(T4-T1) = 227 mm. In conclusion, the modified genioplasty associated with orthognathic surgeries is an effective way to reshape the defected chin and treat micrognathia and airway stenosis in this case.


Assuntos
Obstrução das Vias Respiratórias/cirurgia , Queixo/cirurgia , Mentoplastia , Micrognatismo/cirurgia , Adolescente , Humanos , Masculino , Procedimentos Cirúrgicos Ortognáticos
15.
Nat Commun ; 10(1): 2966, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273213

RESUMO

Mutations in genes encoding components of BAF (BRG1/BRM-associated factor) chromatin remodeling complexes cause neurodevelopmental disorders and tumors. The mechanisms leading to the development of these two disease entities alone or in combination remain unclear. We generated mice with a heterozygous nervous system-specific partial loss-of-function mutation in a BAF core component gene, Smarcb1. These Smarcb1 mutant mice show various brain midline abnormalities that are also found in individuals with Coffin-Siris syndrome (CSS) caused by SMARCB1, SMARCE1, and ARID1B mutations and in SMARCB1-related intellectual disability (ID) with choroid plexus hyperplasia (CPH). Analyses of the Smarcb1 mutant animals indicate that one prominent midline abnormality, corpus callosum agenesis, is due to midline glia aberrations. Our results establish a novel role of Smarcb1 in the development of the brain midline and have important clinical implications for BAF complex-related ID/neurodevelopmental disorders.


Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Corpo Caloso/crescimento & desenvolvimento , Face/anormalidades , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Micrognatismo/genética , Pescoço/anormalidades , Proteína SMARCB1/genética , Anormalidades Múltiplas/diagnóstico por imagem , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/patologia , Alelos , Animais , Criança , Pré-Escolar , Corpo Caloso/citologia , Corpo Caloso/diagnóstico por imagem , Modelos Animais de Doenças , Embrião de Mamíferos , Face/diagnóstico por imagem , Feminino , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Mutação com Perda de Função , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Transgênicos , Micrognatismo/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Neuroglia/patologia , Cultura Primária de Células
16.
J Hum Genet ; 64(9): 875-883, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273320

RESUMO

Micrognathia is a common craniofacial deformity which represents hypoplastic development of the mandible, accompanied by retrognathia and consequent airway problems. Usually, micrognathia is accompanied by multiple systematic defects, known as syndromic micrognathia, and is in close association with genetic factors. Now, large quantities of pathogenic genes of syndromic micrognathia have been revealed. However, how these different pathogenic genes could lead to similar phenotypes, and whether there are some common characteristics among these pathogenic genes are still unknown. In this study, we proposed a genetic-phenotypic classification of syndromic micrognathia based on pathogenic genes information obtained from Phenolyzer, DAVID, OMIM, and PubMed database. Pathogenic genes of syndromic micrognathia could be divided into four groups based on gene function, including cellular processes and structures, cell metabolism, cartilage and bone development, and neuromuscular function. In addition, these four groups exhibited various clinical characteristics, and the affected systems, such as central nervous system, skeletal system, cardiovascular system, oral and dental system, respiratory system and muscle, were different in these four groups. This classification could provide meaningful insights into the pathogenesis of syndromic micrognathia, and offer some clues for understanding the molecular mechanism, as well as guiding precise clinical diagnosis and treatment for syndromic micrognathia.


Assuntos
Mandíbula/patologia , Micrognatismo/classificação , Micrognatismo/genética , Micrognatismo/patologia , Fenótipo , Humanos , Síndrome
18.
Taiwan J Obstet Gynecol ; 58(4): 566-569, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307753

RESUMO

OBJECTIVE: We present a case with prenatal diagnosis of Treacher-Collins syndrome in which micrognathia and other facial and ear abnormalities were described using a three- and four-dimensional (3D/4D) ultrasonography in utero. CASE REPORT: A 39-year-old Japanese pregnant woman was referred because of polyhydramnios at 29 weeks' gestation. Conventional ultrasonography showed a hypoplastic mandible on the sagittal section of fetal head. Continuous observation using a 3D ultrasonography additionally demonstrated bilateral downslanting palpebral fissures with symmetry and macrostomia as well as micrognathia. Both ears were microtia and no polydactyly or missing fingers were found. CONCLUSION: The advantage of the rendering mode of 3D images covering entire face including ears and limbs was enhanced by a continuous observation, so called 4D ultrasonography, under a condition of polyhydramnios, providing visual diagnosis in utero.


Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Imageamento Tridimensional , Disostose Mandibulofacial/diagnóstico por imagem , Poli-Hidrâmnios/diagnóstico por imagem , Resultado da Gravidez , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal , Adulto , Feminino , Idade Gestacional , Humanos , Imagem por Ressonância Magnética/métodos , Micrognatismo/diagnóstico por imagem , Gravidez , Diagnóstico Pré-Natal/métodos , Doenças Raras , Síndrome
19.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243159

RESUMO

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NBS) are 2 overlapping syndromes caused by mutations in genes of the barrier-to-autointegration factor chromatin-remodeling complex, presenting with multiple malformations and intellectual disability. Musculoskeletal changes such as noninflammatory prominence of interphalangeal joints in hands, feet, and, to a lesser extent, knee joints are common in NBS (up to 85%) and also reported in CSS. We present the case of a 7-year-old boy with polyarthritis of several years' duration (without uveitis), developmental delay, microcephaly, and dysmorphic features reminiscent of NBS. Sanger sequencing of the SMARCA2 gene revealed no mutations. Laboratory test results were normal. With synovial biopsy, we confirmed a chronic inflammatory synovitis. Brain MRI revealed dysgenesis of the corpus callosum. Treatment with methotrexate and, subsequently, etanercept led to significant clinical improvement. Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the ARID1B gene, resulting in a premature stop codon (c.C5404T; p.R1802×), a genotype consistent with CSS. The absence of significantly raised inflammatory markers and a clinical diagnosis of a genetic syndrome associated with noninflammatory joint changes may have contributed to this patient's polyarthritis being missed for several years. We propose that some patients with CSS may have inflammatory arthritis (with or without coexisting skeletal dysplasia), which may be helped by treatment as described herein. Early recognition and treatment of inflammatory arthritis in CSS would have a significant impact on reducing disease burden and improving quality of life for patients with this rare genetic syndrome.


Assuntos
Anormalidades Múltiplas/diagnóstico , Artrite/diagnóstico , Face/anormalidades , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Micrognatismo/diagnóstico , Pescoço/anormalidades , Anormalidades Múltiplas/genética , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/tratamento farmacológico , Criança , Códon sem Sentido , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Etanercepte/uso terapêutico , Facies , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas da Mão/genética , Humanos , Hipotricose/diagnóstico , Deficiência Intelectual/genética , Masculino , Metotrexato/uso terapêutico , Micrognatismo/genética , Fatores de Transcrição/genética
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