RESUMEN
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.
Asunto(s)
Anomalías Múltiples , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Factores de Transcripción SOXC , Humanos , Masculino , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Oído Externo/anomalías , Oído Externo/patología , Secuenciación del Exoma , Cara/anomalías , Cara/patología , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/patología , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Micrognatismo/genética , Micrognatismo/patología , Micrognatismo/diagnóstico , Mutación Missense/genética , Cuello/anomalías , Cuello/patología , Fenotipo , Factores de Transcripción SOXC/genéticaRESUMEN
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.
Asunto(s)
Micrognatismo , Embarazo , Femenino , Humanos , Micrognatismo/diagnóstico , Micrognatismo/genética , Estudios Prospectivos , Ultrasonografía Prenatal/métodos , Diagnóstico Prenatal/métodos , Feto , Factores de Elongación de Péptidos , Ribonucleoproteína Nuclear Pequeña U5RESUMEN
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.
Asunto(s)
Anomalías Múltiples , Cara/anomalías , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Cuello , Cuello/anomalías , Fenotipo , Factores de Transcripción , Humanos , Micrognatismo/genética , Micrognatismo/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Cuello/patología , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/diagnóstico , Masculino , Femenino , Factores de Transcripción/genética , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/patología , Niño , Preescolar , Lactante , Mutación/genética , Adolescente , Proteínas de Unión al ADN/genética , Predisposición Genética a la EnfermedadRESUMEN
Cerebro-costo-mandibular syndrome (CCMS) is a congenital condition with skeletal and orofacial abnormalities that often results in respiratory distress in neonates. The three main phenotypes in the thorax are posterior rib gaps, abnormal costovertebral articulation and absent ribs. Although the condition can be lethal, accurate diagnosis, and subsequent management help improve the survival rate. Mutations in the causative gene SNRPB have been identified, however, the mechanism whereby the skeletal phenotypes affect respiratory function is not well-studied due to the multiple skeletal phenotypes, lack of anatomy-based studies into the condition and rarity of CCMS cases. This review aims to clarify the extent to which the three main skeletal phenotypes in the thorax contribute to respiratory distress in neonates with CCMS. Despite the posterior rib gaps being unique to this condition and visually striking on radiographic images, anatomical consideration, and meta-analyses suggested that they might not be the significant factor in causing respiratory distress in neonates. Rather, the increase in chest wall compliance due to the rib gaps and the decrease in compliance at the costovertebral complex was considered to result in an equilibrium, minimizing the impact of these abnormalities. The absence of floating ribs is likely insignificant as seen in the general population; however, a further absence of ribs or vestigial rib formation is associated with respiratory distress and increased lethality. Based on these, we propose to evaluate the number of absent or vestigial ribs as a priority indicator to develop a personalized treatment plan based on the phenotypes exhibited.
Asunto(s)
Discapacidad Intelectual , Micrognatismo , Síndrome de Dificultad Respiratoria , Costillas/anomalías , Recién Nacido , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Micrognatismo/complicaciones , Micrognatismo/diagnóstico , Micrognatismo/genética , Síndrome de Dificultad Respiratoria/complicacionesRESUMEN
Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.
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Anomalías Múltiples , Cara/anomalías , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Adulto , Humanos , Niño , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Micrognatismo/genética , Micrognatismo/diagnóstico , Deformidades Congénitas de la Mano/genética , Cuello/anomalías , Fenotipo , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genéticaAsunto(s)
Anomalías Múltiples , Cara/anomalías , Deformidades Congénitas de la Mano , Hernias Diafragmáticas Congénitas , Discapacidad Intelectual , Micrognatismo , Cuello/anomalías , Embarazo , Femenino , Humanos , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/genética , Primer Trimestre del Embarazo , Secuenciación del Exoma , Discapacidad Intelectual/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Diagnóstico PrenatalAsunto(s)
Anomalías Múltiples , Discapacidad Intelectual , Micrognatismo , Humanos , Mosaicismo , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción/genéticaRESUMEN
INTRODUCTION: Although the whole-exome sequencing (WES) approach has been widely used in clinic, many rare diseases with syndromic and nonsyndromic neurological manifestations remain undiagnosed. Coffin-Siris syndrome (CSS) is a rare autosomal dominant genetic disease characterized by neurodevelopmental delay. A suspected diagnosis can be made based on the typical CSS clinical features; however, molecular genetic testing is necessary for a confirmed diagnosis. OBJECTIVES: Three CSS-like patients with negative results in the WES and chromosomal microarray analysis (CMA) were recruited in this study. METHODS: We used whole-genome sequencing (WGS) technology to sequence the peripheral blood of the three families. To further explore the possible pathogenesis of CSS, we performed RNA-sequencing (RNA-seq). RESULTS: WGS identified the three CSS patients were carrying de novo copy number variants of the ARID1B gene, which have not been reported before. RNA-seq identified 184 differentially expressed genes (DEGs), with 116 up-regulated and 68 down-regulated. Functional annotation of DEGs showed that two biological processes (immune response, chemokine activity) and two signaling pathways (cytokine-cytokine receptor interaction, chemokine activity) were highlighted. We speculated that ARID1B deficiency might trigger abnormal immune responses, which may be involved in the pathophysiologic mechanisms of CSS. CONCLUSION: Our research provided further support for WGS application in CSS diagnosis and made an investigational approach for the underlying mechanisms of CSS.
Asunto(s)
Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Humanos , Proteínas de Unión al ADN/genética , Transcriptoma/genética , Factores de Transcripción/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Micrognatismo/diagnóstico , Micrognatismo/genética , Micrognatismo/patología , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/terapia , Cuello/patología , QuimiocinasRESUMEN
Coffin-Siris syndrome (CSS) is a rare congenital genetic syndrome, a multisystem disease related to congenital abnormalities, that manifests with abnormal features, causes repeated infections and is associated with developmental delays. Here, we report a newborn male with CSS from Baoding in the Hebei Province of China.
Asunto(s)
Anomalías Múltiples , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Recién Nacido , Humanos , Masculino , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , CuelloRESUMEN
Coffin-Siris syndrome (CSS) 6 is caused by heterozygous pathogenic variants in the AT-rich interaction domain 2 (ARID2) gene on 12q12. Currently, only 26 cases with both detailed clinical and genetic information have been documented in the literature. Microdeletions of the entire ARID2 gene are rare. In this study, we report a 5-year-7-month-old Chinese female who underwent whole-exome sequencing to discover that she had a de novo 1.563 Mb heterozygous copy number loss at 12q12q13.11, involving an entire deletion of ARID2. The female had severe short stature with obvious dysmorphic facial features, global developmental delay and hypoplastic fingers and toes. Her growth hormone level was normal, with reduced IGF-1 and increased CA19-9 levels. After a review of the 27 patients with ARID2 deficiency, a significant positive correlation was observed between age and height standard deviation score (SDS) (r = 0.71, p = 0.0002), suggesting a possibility of growth catch-up. This study expands the genetic and phenotypic spectrum of CCS6 and provides a decision-making reference for growth hormone therapy.
Asunto(s)
Anomalías Múltiples , Enanismo , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Femenino , Humanos , Lactante , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Enanismo/genética , Cara/patología , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/patología , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Micrognatismo/diagnóstico , Micrognatismo/genética , Micrognatismo/patología , Cuello/patología , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Pathogenic heterozygous variants in BICRA have recently been identified in patients with SWI/SNF-related intellectual disability (SSRIDD) - Coffin-Siris syndrome 12. So far, only one article reported SSRIDD associated with pathogenic variants in BICRA. CASE PRESENTATION: The patient's phenotype include low birth weight, microcephaly, neurodevelopment delay, visual, gastrointestinal, urinary tract impairment, and craniofacial dysmorphism. Whole exome sequencing revealed a novel pathogenic heterozygous variant in exon 6 of BICRA gene c.535C > T (p.(Gln179*)). Sanger sequencing confirmed de novo origin. CONCLUSION: The clinical findings confirm and supplement the previous study which showed that pathogenic variant in BICRA is commonly characterized by neurodevelopmental, gastrointestinal, and ophthalmologic symptoms, growth retardation, as well as craniofacial dysmorphism.
Asunto(s)
Anomalías Múltiples , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Humanos , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Micrognatismo/genética , Micrognatismo/diagnóstico , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/diagnóstico , Cuello , FenotipoAsunto(s)
Anomalías Múltiples , Discapacidad Intelectual , Micrognatismo , Síndrome de Sotos , Humanos , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Cara , Micrognatismo/diagnóstico , Micrognatismo/genética , CuelloRESUMEN
Coffin-Siris Syndrome (CSS) is a rare multi-system dominant condition with a variable clinical presentation mainly characterized by hypoplasia/aplasia of the nail and/or distal phalanx of the fifth digit, coarse facies, hirsutism/hypertrichosis, developmental delay and intellectual disability of variable degree and growth impairment. Congenital anomalies may include cardiac, genitourinary and central nervous system malformations whereas congenital diaphragmatic hernia (CDH) is rarely reported. The genes usually involved in CSS pathogenesis are ARID1B (most frequently), SMARCA4, SMARCB1, ARID1A, SMARCE1, DPF2, and PHF6. Here, we present two cases of CSS presenting with CDH, for whom Whole Exome Sequencing (WES) identified two distinct de novo heterozygous causative variants, one in ARID1B (case 1) and one in SMARCA4 (case 2). Due to the rarity of CDH in CSS, in both cases the occurrence of CDH did not represent a predictive sign of CSS but, on the other hand, prompted genetic testing before (case 1) or independently (case 2) from the clinical hypothesis of CSS. We provide further evidence of the association between CSS and CDH, reviewed previous cases from literature and discuss possible functional links to related conditions.
Asunto(s)
Anomalías Múltiples , Deformidades Congénitas de la Mano , Hernias Diafragmáticas Congénitas , Discapacidad Intelectual , Micrognatismo , Humanos , Cara/anomalías , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Micrognatismo/diagnóstico , Micrognatismo/genética , Micrognatismo/patología , Hernias Diafragmáticas Congénitas/diagnóstico , Hernias Diafragmáticas Congénitas/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/patología , Cuello/anomalías , ADN Helicasas/genética , Proteínas Nucleares , Factores de Transcripción/genética , Proteínas Cromosómicas no Histona , Proteínas de Unión al ADN/genéticaRESUMEN
Coffin-Siris syndrome (CSS, MIM135900) is a rare multiple congenital anomaly syndrome caused by pathogenic variants in the BAF complex; up to 28% of patients have previously been reported to have seizures, however, a comprehensive review of epilepsy has not been undertaken in this population. The International CSS Patient Report Database was queried for patients with self-reported seizures, epilepsy, and EEG results. Data gathered included demographic data, pathogenic gene variants, seizure characteristics and treatments, and EEG findings. In addition, a PubMed search was performed using keywords "Coffin-Siris syndrome" and "epilepsy," "seizures," or "EEG." Results from relevant papers are reported. Twenty-four (7.2%) of 334 patients in the database reported having seizures, EEG abnormalities, and/or epilepsy. Median age of seizure onset was 2. 7 years. Fifteen of the 23 patients with seizures or epilepsy had an ARID1B causative variant. Seventeen patients (5.1%) reported EEG abnormalities, the majority of which were described as focal or multifocal (87.5%). In all but one patient, seizures were controlled on antiseizure medications (ASMs). The literature review yielded 311 unique CSS patients, 82 of which (26.4%) carried diagnoses of seizures or epilepsy. Details on seizure type(s), EEG findings, and response to treatment were limited.
Asunto(s)
Anomalías Múltiples , Epilepsia , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Humanos , Micrognatismo/diagnóstico , Micrognatismo/genética , Micrognatismo/patología , Deformidades Congénitas de la Mano/complicaciones , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Proteínas de Unión al ADN/genética , Discapacidad Intelectual/diagnóstico , Cara/anomalías , Cuello/anomalías , Estudios de Asociación Genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/epidemiología , Anomalías Múltiples/genética , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/epidemiología , Convulsiones/epidemiología , Convulsiones/genética , Convulsiones/patologíaRESUMEN
Coffin-Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic variants in any of 9 BAF chromatin-remodeling complex encoding genes or the genes SOX11 and PHF6. Herein, we performed whole-exome sequencing (WES) and a series of analyses of growth-related, auditory, and radiological findings in two probands with syndromic sensorineural hearing loss and inner ear malformations who exhibited distinctive facial features, intellectual disability, growth retardation, and fifth finger malformation. Two de novo variants in the SOX11 gene (c.148A>C:p.Lys50Asn; c.811_814del:p.Asn271Serfs*10) were detected in these probands and were identified as pathogenic variants as per ACMG guidelines. These probands were diagnosed as having CSS based upon clinical and genetic findings. This is the first report of CSS caused by variants in SOX11 gene in Chinese individuals. Deleterious SOX11 variants can result in sensorineural hearing loss with inner ear malformation, potentially extending the array of phenotypes associated with these pathogenic variants. We suggest that both genetic and clinical findings be considered when diagnosing syndromic hearing loss.
Asunto(s)
Deformidades Congénitas de la Mano , Pérdida Auditiva Sensorineural , Discapacidad Intelectual , Micrognatismo , Humanos , Micrognatismo/diagnóstico , Micrognatismo/genética , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Cuello/anomalías , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Factores de Transcripción SOXC/genéticaRESUMEN
PURPOSE: Coffin-Siris syndrome (CSS) is a rare genetic disorder characterized by the presence of particular facies, congenital malformations, intellectual developmental disorder, behavioral issues, and speech and language impairment. Thorough neuropsychological assessments in the case of CSS have been reported infrequently, and its subdomains are poorly defined. A detailed description of the clinical, neurocognitive, behavioral, socio-adaptive sequelae of the patient with CSS is provided. RESULTS: The clinical diagnosis in the patient was confirmed by genetic analysis, which identified the presence of mutation of ARID1B gene; the parents' Sanger sequencing reported normal. The neuropsychological assessments revealed borderline intellectual functioning (IQ-75, verbalâ>âperformance) with a mild socio-adaptive deficit score of 64 as suggested by the adaptive scale. The behavioral profile reported that the child had significant difficulties in the attention subdomain with concern in social and thought subdomains. The child met the profile for mild severity of Autism Spectrum Disorder and did not meet the criteria for Attention Deficit Hyperactivity Disorder. In addition, the child had scholastic difficulties in reading and mathematical skills. CONCLUSION: Neurocognitive, behavioral, socio-adaptive functioning and comorbidity assessment in order to provide holistic management of such children after thorough evaluation is essential for their overall functioning.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Micrognatismo , Anomalías Múltiples , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Niño , Proteínas de Unión al ADN/genética , Cara/anomalías , Deformidades Congénitas de la Mano , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Cuello/anomalías , Factores de Transcripción/genéticaAsunto(s)
Anomalías Múltiples , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Adulto , Proteínas de Unión al ADN/genética , Cara/anomalías , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Cuello/anomalías , Factores de Transcripción/genéticaRESUMEN
The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby's microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11(26,797,508_27,052,080)×1â¼2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.
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Anomalías Múltiples/diagnóstico , Feto Abortado/patología , Proteínas de Unión al ADN/genética , Cara/anomalías , Deformidades Congénitas de la Mano/diagnóstico , Discapacidad Intelectual/diagnóstico , Micrognatismo/diagnóstico , Cuello/anomalías , Fenotipo , Factores de Transcripción/genética , Anomalías Múltiples/genética , Adulto , Femenino , Deformidades Congénitas de la Mano/genética , Humanos , Discapacidad Intelectual/genética , Micrognatismo/genética , Mutación , Embarazo , Diagnóstico PrenatalRESUMEN
BACKGROUND: The literature shows no consensus on whether two- or three-segment surgically assisted rapid maxillary expansion is the best operative technique. METHODS: The present clinical trial was designed to compare the outcome of two- and three-segment osteotomy surgically assisted rapid maxillary expansion. Thirty-two adult patients with transverse maxillary deficiency greater than or equal to 5 mm were randomly assigned to two- and three-segment groups (n = 16). Dimensional and psychological assessments (Oral Health Impact Profile and Brazilian Orthognathic Quality of Life Questionnaire) were carried out before surgical intervention and at one of the following time points: completion of expansion, removal of expanding device, 6 months after completion of expansion, or 10 months after completion of expansion. Dimensional assessments for asymmetric expansion of the maxilla and for changes in the area and volume of the palatine vault were performed on digital data from tomographic and laser scanning with the aid of an engineering inspection software. RESULTS: No statistically significant differences were found in asymmetry or stability outcomes between groups. The psychological benefit provided by the three-segment technique did not spread through the domains of the quality-of-life questionnaires. CONCLUSIONS: The current findings suggest that three-segment surgically assisted rapid maxillary expansion outcomes do not exceed those obtained with its two-segment counterpart regarding symmetry of maxillary expansion and stability of area and volume of the palatine vault. Furthermore, psychological nuances evidenced in two- and three-segment groups with the tools used play a limited, short-lasting role, or a specific, more sensitive assessment tool needs to be developed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
Asunto(s)
Maxilar/cirugía , Micrognatismo/cirugía , Osteotomía Le Fort/métodos , Técnica de Expansión Palatina , Adolescente , Adulto , Cefalometría , Femenino , Humanos , Masculino , Maxilar/anomalías , Micrognatismo/diagnóstico , Micrognatismo/psicología , Persona de Mediana Edad , Calidad de Vida , Factores de Tiempo , Adulto JovenRESUMEN
In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this study was to find risk factors for predicting difficult airways in children with mandibular hypoplasia, and compare upper airway anatomical differences using three-dimensional computed tomography (3D CT) between children with mandibular hypoplasia and demographically matched healthy controls. There were significant discrepancies in relative tongue position (P < 0.01) and anterior distance of the hyoid bone (P < 0.01) between patients with mandibular hypoplasia and healthy controls. All mandibular measures were significantly different between the two groups, except for the height of the ramus of the mandible. After adjusting for age and sex, the anterior distance of hyoid bone and inferior pogonial angle were significantly associated with a difficult airway (P = 0.01 and P = 0.02). Quantitative analysis of upper airway structures revealed significant discrepancies, including relative tongue position, hyoid distance, and mandible measures between patients with mandibular hypoplasia and healthy controls. The anterior distance of the hyoid bone and inferior pogonial angle may be risk factors for a difficult airway in patients with mandibular hypoplasia.