RESUMEN
Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.
Asunto(s)
Ano Imperforado , Displasia Ectodérmica , Trastornos del Crecimiento , Pérdida Auditiva Sensorineural , Células Madre Pluripotentes Inducidas , Mutación , Ubiquitina-Proteína Ligasas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Ubiquitina-Proteína Ligasas/genética , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Preescolar , Displasia Ectodérmica/genética , Displasia Ectodérmica/patología , Ano Imperforado/genética , Ano Imperforado/patología , Heterocigoto , Nariz/patología , Nariz/anomalías , Línea Celular , Insuficiencia Pancreática Exocrina/genética , Insuficiencia Pancreática Exocrina/patología , Sordera/genética , Sordera/patología , Diferenciación Celular , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Hipotiroidismo , Enfermedades PancreáticasRESUMEN
Trichorhinophalangeal syndrome (TRPS) is a genetic disorder caused by point mutations or deletions in the gene-encoding transcription factor TRPS1. TRPS patients display a range of skeletal dysplasias, including reduced jaw size, short stature, and a cone-shaped digit epiphysis. Certain TRPS patients experience early onset coxarthrosis that leads to a devastating drop in their daily activities. The etiologies of congenital skeletal abnormalities of TRPS were revealed through the analysis of Trps1 mutant mouse strains. However, early postnatal lethality in Trps1 knockout mice has hampered the study of postnatal TRPS pathology. Here, through epigenomic analysis we identified two previously uncharacterized candidate gene regulatory regions in the first intron of Trps1. We deleted these regions, either individually or simultaneously, and examined their effects on skeletal morphogenesis. Animals that were deleted individually for either region displayed only modest phenotypes. In contrast, the Trps1Δint/Δint mouse strain with simultaneous deletion of both genomic regions exhibit postnatal growth retardation. This strain displayed delayed secondary ossification center formation in the long bones and misshaped hip joint development that resulted in acetabular dysplasia. Reducing one allele of the Trps1 gene in Trps1Δint mice resulted in medial patellar dislocation that has been observed in some patients with TRPS. Our novel Trps1 hypomorphic strain recapitulates many postnatal pathologies observed in human TRPS patients, thus positioning this strain as a useful animal model to study postnatal TRPS pathogenesis. Our observations also suggest that Trps1 gene expression is regulated through several regulatory elements, thus guaranteeing robust expression maintenance in skeletal cells.
Asunto(s)
Proteínas de Unión al ADN , Enfermedades del Cabello , Síndrome de Langer-Giedion , Ratones Noqueados , Nariz , Proteínas Represoras , Animales , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patología , Ratones , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Nariz/anomalías , Nariz/patología , Enfermedades del Cabello/genética , Enfermedades del Cabello/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Modelos Animales de Enfermedad , Humanos , Dedos/anomalías , Secuencias Reguladoras de Ácidos Nucleicos/genética , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , FenotipoRESUMEN
OBJECTIVE: To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the corresponding changes. METHODS: One hundred and fifty-two patients who underwent orthodontic treatment with premolar extraction were enrolled. Lateral cephalograms were obtained before and after the treatment. For each record, the outlines of the nose-lip-chin profile and corresponding 21 cephalometric variables were extracted. The AI method classified pretreatment records into three subject groups based on the feature variables extracted from the outline. Dentoskeletal and soft tissue facial form changes observed after treatment were compared statistically (P < 0.05) between the groups using ANOVA. Multivariate regression models were used for each group. RESULTS: Group 1 (n = 59) was characterized by Class II high-angle retrognathic mandible with an incompetent lip, group 2 (n = 55) by Class I malocclusion with retruded and thin lips, and group 3 (n = 38) by Class I malocclusion with an everted superior lip before treatment. The ratios of anteroposterior soft tissue to hard tissue movements in Group 1 were 56% (r = 0.64) and 83% (r = 0.75) for the superior and inferior lips, respectively, whereas those in Group 2 were 49% (r = 0.78) and 91% (r = 0.80), and 40% (r = 0.54) and 79% (r = 0.70), respectively, in Group 3. CONCLUSIONS: The modes of facial form changes differed depending on the pre-treatment profile patterns classified by the AI. This indicates that the determination of the pre-treatment profile pattern can help in the selection of soft tissue to hard tissue movement ratios, which helps estimate the post-treatment facial profile with a moderate to high correlation.
Asunto(s)
Inteligencia Artificial , Diente Premolar , Cefalometría , Cara , Labio , Maloclusión Clase I de Angle , Nariz , Extracción Dental , Humanos , Cefalometría/métodos , Cara/anatomía & histología , Femenino , Masculino , Labio/anatomía & histología , Adolescente , Nariz/anatomía & histología , Nariz/patología , Maloclusión Clase I de Angle/terapia , Mentón/anatomía & histología , Mentón/patología , Maloclusión Clase II de Angle/terapia , Maloclusión Clase II de Angle/diagnóstico por imagen , Mandíbula , Técnicas de Movimiento Dental/métodos , Niño , Adulto Joven , Maloclusión/terapia , Maloclusión/clasificaciónRESUMEN
Despite the widespread adoption of nasal endoscopy (NE) in the evaluation of sinonasal disease, its diagnostic potential may still be underutilized. Developments in endoscopic technology have led to significant improvements in video quality and maneuverability. However, there is concern that NE continues to be used primarily for the identification of gross pathology, with relative neglect of more subtle findings such as surface features of inflammation and mucus. With fewer technical limitations to perceive these abnormalities, there is potential to greatly improve the diagnostic value of NE. The reader is herein asked to consider several important visual nuances encountered during NE, with the hope that this engenders an appreciation of the versatility of NE as a diagnostic tool.
Asunto(s)
Endoscopía , Humanos , Endoscopía/métodos , Senos Paranasales/diagnóstico por imagen , Enfermedades de los Senos Paranasales/diagnóstico , Nariz/patología , Enfermedades Nasales/diagnósticoRESUMEN
Meier-Gorlin syndrome (MGORS) is an autosomal recessive disorder characterized by short stature, microtia, and patellar hypoplasia, and is caused by pathogenic variants of cellular factors involved in the initiation of DNA replication. We previously reported that biallelic variants in GINS3 leading to amino acid changes at position 24 (p.Asp24) cause MGORS. Here, we describe the phenotype of a new individual homozygous for the Asp24Asn variant. We also report the clinical characteristics of an individual harboring a novel homozygous GINS3 variant (Ile25Phe) and features suggestive of MGORS. Modification of the corresponding residue in yeast Psf3 (Val9Phe) compromised S phase progression compared to a humanized Psf3 Val9Ile variant. Expression of Psf3 Val9Phe in yeast also caused sensitivity to elevated temperature and the replicative stress-inducing drug hydroxyurea, confirming partial loss of function of this variant in vivo and allowing us to upgrade the classification of this variant. Taken together, these data validate the critical importance of the GINS DNA replication complex in the molecular etiology of MGORS.
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Microtia Congénita , Trastornos del Crecimiento , Rótula , Niño , Femenino , Humanos , Masculino , Proteínas Cromosómicas no Histona/genética , Microtia Congénita/genética , Replicación del ADN/genética , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , Homocigoto , Inestabilidad de la Articulación/genética , Inestabilidad de la Articulación/patología , Micrognatismo/genética , Mutación , Nariz/anomalías , Nariz/patología , Rótula/anomalías , Rótula/patología , Fenotipo , Saccharomyces cerevisiae/genéticaRESUMEN
AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case.This report examines the case of a 70-year-old woman who sought evaluation for a sensation of something moving in her nose. The sensation began during a trip to South America and persisted after she returned home to Switzerland. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.
Asunto(s)
Nariz , Humanos , Femenino , Anciano , Diagnóstico Diferencial , Nariz/patologíaRESUMEN
This retrospective cross-sectional study reviewed adult patients with operated cleft lip and/or palate (CL/P) and normal control, and performed comprehensive craniofacial and nasal morphological analyses based on lateral cephalometric radiographs. Pearson or Spearman correlation coefficient assessed intraclass correlation. Seven hundred fifty-seven operated patients with CL/P, and 165 noncleft normal controls were enrolled. Among the normal and CL/P groups, S-N-A angle registered positive correlations with nasal base prominence (S-N'-Sn, degrees). Upper facial height (N-ANS, mm) had positive correlations with nasal dorsum length (N'-Prn, mm) and nasal bone length (N-Na, mm). Although in patients with bilateral cleft lip and palate, there were moderate negative correlations ( r =-0.541, P <0.05) with soft tissue facial profile angle (FH-N'Pog', degree) and nasolabial angle (Cm-Sn-ULA, degree). Correlation exists between the morphology of jaw bones and external nose among patients with CL/P. Maxillary sagittal insufficiency is associated with concave nasal profile, and maxilla height is associated with nasal length.
Asunto(s)
Cefalometría , Labio Leporino , Fisura del Paladar , Nariz , Humanos , Labio Leporino/patología , Labio Leporino/diagnóstico por imagen , Labio Leporino/cirugía , Fisura del Paladar/patología , Fisura del Paladar/diagnóstico por imagen , Fisura del Paladar/cirugía , Estudios Retrospectivos , Femenino , Masculino , Estudios Transversales , Adulto , Nariz/diagnóstico por imagen , Nariz/anatomía & histología , Nariz/patología , Estudios de Casos y Controles , Adolescente , Maxilar/diagnóstico por imagen , Maxilar/patologíaRESUMEN
Here we report the case of a young boy with developmental delay, thin sparse hair, early closure of the anterior fontanel, bilateral choanal atresia, brachyturicephaly; and dysmorphic features closely resembling those seen in trichorhinophalangeal syndrome (TRPS). These features include sparse hair, sparse lateral eyebrows, a bulbous pear shaped nose, a long philtrum, thin lips, small/hypoplastic nails, pes planovalgus; bilateral cone-shaped epiphyses at the proximal 5th phalanx, slender long bones, coxa valga, mild scoliosis, and delayed bone age. Given that TRPS had been excluded by a thorough genetic analysis, whole exome sequencing was performed and a heterozygous likely pathogenic variant was identified in the FBXO11 gene (NM_001190274.2: c.1781A > G; p. His594Arg), confirming the diagnosis of the newly individualized IDDFBA syndrome: Intellectual Developmental Disorder, dysmorphic Facies, and Behavioral Abnormalities (OMIM# 618,089). Our findings further delineate the clinical spectrum linked to FBXO11 and highlight the importance of investigating further cases with mutations in this gene to establish a potential genotype-phenotype correlation.
Asunto(s)
Proteínas F-Box , Fenotipo , Humanos , Masculino , Proteínas F-Box/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patología , Nariz/anomalías , Nariz/patología , Dedos/anomalías , Dedos/patología , Niño , Atresia de las Coanas/genética , Atresia de las Coanas/patología , Mutación , Enfermedades del Cabello , Proteína-Arginina N-MetiltransferasasAsunto(s)
Máscaras , Pénfigo , Humanos , Pénfigo/patología , Pénfigo/etiología , Máscaras/efectos adversos , Masculino , Femenino , Nariz/patología , Persona de Mediana EdadRESUMEN
OBJECTIVE: Though the endoscopic endonasal approach (EEA) is a widely accepted treatment for skull base tumors, the specific use of EEA for olfactory groove meningiomas (OGMs) is debated, with variable outcomes reported in the literature. We review the surgical results of OGM resections for one surgeon including the operative approach, surgical nuances, and outcomes, with a focus on factors relating to patient selection which favor EEA over transcranial approaches. METHODS: We retrospectively reviewed thirteen cases of endoscopic endonasal resection of olfactory groove meningiomas. Patient characteristics, clinical characteristics, surgical outcomes, and complications were analyzed. Extent of resection was determined based on volumetric analysis of pre- and postoperative MRI. RESULTS: Anatomic characteristics that render a tumor difficult to access fully are lateral extension beyond the mid-orbit and anterior extension to the falx. Simpson Grade I resection was achieved in 11/13 (84.6 %) cases. Mean pre-operative tumor volume was 8.99 cm3 (range 2.19-16.79 cm3), and 92 % of tumors were WHO grade I. We demonstrate 2 cases of smell preservation, possible with small unilateral tumors and tumors that are confined to either the anterior or posterior portion of the cribriform plate. The post-operative CSF leak rate was 7.7 %, without prophylactic lumbar CSF drainage. The mortality rate was 7.7 % (n = 1) after infectious complications following CSF leak. CONCLUSIONS: Endoscopic endonasal resection of olfactory groove meningiomas is an effective and safe operative method with outcomes and complication rates comparable to transcranial approaches. Key considerations include careful patient selection and familiarity with technical nuances of endoscopic endonasal approach for this specific tumor type.
Asunto(s)
Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Meningioma/patología , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/cirugía , Nariz/cirugía , Nariz/patología , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study is to measure the morphological changes of the nose and lip in patients with unilateral cleft lip and palate before and after cheiloplasty with primary rhinoplasty (primary correction) in conjunction with Korat-NAM usage. DESIGN: Longitudinal cohort study. SETTING: Cleft Center Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand. SUBJECTS: Twenty-six patients with unilateral cleft lip and palate. INTERVENTIONS: Control group: only active obturator before primary correction. Experimental group: an active obturator and Korat-NAM I before primary correction. A customized endotracheal tube was retained in the nostril for 3 weeks before switching to Korat-NAM II for 1 year. MAIN OUTCOME MEASURES: Six measurements comprising nostril rim length, nostril height, nostril sill width, columella angle, vertical lip height, and horizontal lip length were measured from the patients' photographs. All measurements, except the columella angle, were reported as the cleft side/non-cleft side value ratio. Measurements were taken at the initial appointment, immediately before, 3 weeks after, and 1 year after primary correction. RESULTS: Nostril rim length ratio, nostril height ratio, nostril sill width ratio, columella angle on the cleft side, and vertical lip height ratio were improved using Korat-NAM before and 3 weeks after primary correction. Nostril rim length and height ratios were significantly better than the control group. CONCLUSIONS: Korat-NAM improved nose and lip morphology before primary correction. An overcorrection improved the nose and lip morphology on the cleft side. The nostril rim length and vertical lip height on the cleft side also improved with Korat-NAM II 1 year after primary correction.
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Labio Leporino , Fisura del Paladar , Labio , Nariz , Rinoplastia , Humanos , Labio Leporino/cirugía , Labio Leporino/patología , Fisura del Paladar/cirugía , Fisura del Paladar/patología , Nariz/patología , Rinoplastia/métodos , Masculino , Femenino , Labio/patología , Estudios Longitudinales , Modelado Nasoalveolar , Obturadores Palatinos , Niño , LactanteRESUMEN
Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.
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Neoplasias Nasales , Papiloma Invertido , Neoplasias de los Senos Paranasales , Senos Paranasales , Humanos , Papiloma Invertido/diagnóstico , Papiloma Invertido/cirugía , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/cirugía , Senos Paranasales/patología , Nariz/patología , Tomografía Computarizada por Rayos X , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/cirugía , Neoplasias Nasales/patología , Estudios RetrospectivosRESUMEN
ABSTRACT: In case of excision of nasal basal cell carcinoma (BCC), bilobed flaps are considered the criterion standard of reconstruction for defect less than 15 mm in size. However, there is still a risk of trapdoor deformity formation, of which its treatment is less discussed. A 44-year-old woman who was diagnosed with nasal BCC and underwent tumor excision with bilobed flap reconstruction presented with trapdoor deformity postoperatively. The computed Vancouver Scar Scale was 7. After early intervention of multiple laser modalities, including 2 sessions of 585-nm pulsed dye laser with a fluence of 9 J/cm2, pulse duration of 6 milliseconds, and spot size of 6 mm, 2940-nm Er-yttrium aluminum garnet (YAG) laser with a pulse energy of 800-900 mJ, repetition rate of 8-9 Hz, and laser spot size of 3-7 mm, and 5 sessions of 1064-nm Nd:YAG fractional picosecond laser with a pulse energy of 2.30-2.70 mJ, repetition rate of 8 Hz, and laser spot size of 6 mm from 5 to 23 weeks postoperatively, the Vancouver Scar Scale score improved to 1, with significant reduction of trapdoor scar erythema and puffiness. Although BCC is often curable, tumor excision causes unsatisfactory appearance satisfaction problem, owing to the apparent location of the lesion. Factors, such as sebaceous tissue thickness, reconstruction over multiple aesthetic subunits of nose, and damage to nasal cartilage framework structure during tumor removal, may increase the risk of trapdoor formation. Early intervention with multiple laser treatment can significantly revise the deformity.
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Carcinoma Basocelular , Láseres de Estado Sólido , Neoplasias Cutáneas , Femenino , Humanos , Adulto , Cicatriz/patología , Nariz/cirugía , Nariz/patología , Carcinoma Basocelular/cirugía , Carcinoma Basocelular/patología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To describe the clinical presentation, novel surgical approach, and outcome of a dog diagnosed with chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH). ANIMAL: 5-year-old castrated male Yorkshire Terrier. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: The dog was presented with chronic upper respiratory noise, congestion, facial swelling, ocular discharge, and an abscess on the nasal bridge. Two CT scans were performed 4 months apart. The CT scans yielded similar results: cyst-like nasal masses with severely destructive bilateral rhinitis with extensive polyostotic bony lysis. A dorsal rhinotomy with a turbinectomy and debridement of the nasal cavity were performed. A poorly defined but extensive lesion was found occupying the entirety of the left frontal sinus as well as the nasal cavity. TREATMENT AND OUTCOME: Histopathology revealed a mass consistent with COREAH. The dog recovered well from surgery, except for self-limiting subcutaneous emphysema, and 3 weeks postoperatively was reportedly doing well, with mild nasal discharge. Stridor, nasal discharge, and sneezing episodes were reported postoperatively; however, these were improved. At 18 months postoperatively, the dog died from uncontrolled seizures while hospitalized for suspected acute hemorrhagic diarrhea syndrome at a different hospital. CLINICAL RELEVANCE: COREAH should be considered a potential cause of destructive bilateral rhinitis and bony lysis in dogs. Dorsal rhinotomy can be a surgical treatment for dogs with possible COREAH with acceptable outcome, though complete remission of clinical signs may not be achieved. This is the first clinical description of COREAH in a dog.
Asunto(s)
Adenoma , Enfermedades de los Perros , Hamartoma , Neoplasias Nasales , Rinitis , Perros , Masculino , Animales , Nariz/patología , Cavidad Nasal/patología , Rinitis/veterinaria , Neoplasias Nasales/veterinaria , Adenoma/veterinaria , Hamartoma/diagnóstico , Hamartoma/cirugía , Hamartoma/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/cirugía , Enfermedades de los Perros/patologíaRESUMEN
Medial petrous apex cholesterol granuloma is a benign lesion which treatment is generally based on a trans-nasal marsupialization. When the artificial ostium is created, it is usually kept open with local flaps, like the septal nasopharyngeal "kite flap", a reliable local vascularized flap. Laryngoscope, 134:2111-2114, 2024.
Asunto(s)
Neoplasias del Oído , Granuloma de Cuerpo Extraño , Humanos , Hueso Petroso/cirugía , Colesterol , Granuloma/cirugía , Colgajos Quirúrgicos/patología , Nariz/patología , Granuloma de Cuerpo Extraño/cirugíaRESUMEN
KEY POINTS: Resumption of continuous positive airway pressure (CPAP) in the immediate postoperative period after endoscopic endonasal approaches (EEA) for pituitary adenomas can be safe.