RESUMEN
OBJECTIVES: Our objective was to reinforce clinical knowledge of hearing impairment in KBG syndrome. KBG syndrome is a rare genetic disorder due to monoallelic pathogenic variations of ANKRD11.The typical phenotype includes facial dysmorphism, costal and spinal malformation and developmental delay. Hearing loss in KBG patients has been reported for many years, but no study has evaluated audiological phenotyping from a clinical and an anatomical point of view. METHODS: This French multicenter study included 32 KBG patients with retrospective collection of data on audiological features, ear imaging and genetic investigations. RESULTS: We identified a typical audiological profil in KBG syndrome: conductive (71%), bilateral (81%), mild to moderate (84%) and stable (69%) hearing loss, with some audiological heterogeneity. Among patients with an abnormality on CT imaging (55%), ossicular chain impairment (67%), fixation of the stapes footplate (33%) and inner-ear malformations (33%) were the most common abnormalities. CONCLUSION: We recommend a complete audiological and radiological evaluation and an ENT-follow up in all patients presenting with KBG Syndrome. Imaging evaluation is necessary to determine the nature of lesions in the middle and inner ear.
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Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Sordera , Discapacidad Intelectual , Anomalías Dentarias , Humanos , Anomalías Múltiples/genética , Discapacidad Intelectual/genética , Enfermedades del Desarrollo Óseo/genética , Anomalías Dentarias/genética , Facies , Estudios Retrospectivos , Proteínas Represoras/genética , FenotipoRESUMEN
INTRODUCTION: Deletions or variants of the STRC gene coding for stereocilin cause congenital bilateral mild-to-moderate sensorineural hearing loss without vestibular disorder: DFNB16. Stereocilin is a protein present in vestibular kinocilia embedded in the otoconial membrane of the utricular macula. Benign paroxysmal positional vertigo (BPPV) is a rare form of vertigo in children. The present study reports recurrent positional vertigo in two DFNB16 siblings. OBSERVATION: Two patients, 10 and 15 years old, presented with recurrent disabling positional vertigo episodes, triggered by turning over in bed, with a falling sensation. The diagnosis of right posterior canal BPPV was confirmed on Dix-Hallpike maneuvers in one of the patients. Variations in the response of ocular vestibular-evoked myogenic potentials were observed. Probable BPPV was diagnosed in the second patient. Their other two siblings did not have hearing loss or vertigo. CONCLUSION: The absence of stereocilin due to homozygous deletions of the STRC gene in DFNB16 patients can cause vestibular dysfunction, including BPPV.
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Vértigo Posicional Paroxístico Benigno , Pérdida Auditiva Sensorineural , Niño , Humanos , Adolescente , Vértigo Posicional Paroxístico Benigno/diagnóstico , Vértigo Posicional Paroxístico Benigno/genética , Hermanos , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Mareo , Péptidos y Proteínas de Señalización IntercelularRESUMEN
The cause for the increased sensitivity of patients with fibromyalgia (FM) to painful stimuli is unclear but sensitization of dorsal horn spinal cord neurons has been suggested. There, critical changes of sensory information occur which depend on the plasticity of second-order neurons and descending pain modulation, including facilitation and inhibition. This study used repetitive stimuli that produce temporal-summation-of-second-pain (TSSP) and central sensitization, relevant mechanisms for patients with chronic pain. We examined spinal cord neural activation during TSSP in patients with FM and healthy controls (HC) and used its functional connectivity with several brainstem nuclei to model the observed blood-oxygen-level-dependent (BOLD) time-course with pain ratings. Sixteen HC and 14 FM participants received repetitive heat stimuli to the hand at 0.4 Hz to achieve TSSP during functional imaging with a 3 T-Philips Achieva MRI scanner. Stimuli were adjusted to each individual's pain sensitivity to achieve maximal pain ratings of 50 ± 10 on a numerical pain scale (0-100). Using a 16-channel neurovascular coil, multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. During repetitive, sensitivity-adjusted heat stimuli, pain ratings of all subjects increased as predicted, consistent with TSSP. HC and FM participants had similar temporal patterns of spinal activation: initial BOLD increase followed by deactivation. Structural equation modeling showed that the observed spinal activity during TSSP was associated with more BOLD activity across/within the brainstem in FM subjects than HC, suggesting differences in pain modulation.NEW & NOTEWORTHY "Windup" and its behavioral correlate "temporal-summation-of-second pain" (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.
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Fibromialgia/fisiopatología , Umbral del Dolor , Médula Espinal/fisiopatología , Adulto , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/fisiopatología , Sensibilización del Sistema Nervioso Central , Conectoma , Femenino , Fibromialgia/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Percepción del Dolor , Médula Espinal/diagnóstico por imagenRESUMEN
Heimler syndrome is a rare syndrome associating sensorineural hearing loss with retinal dystrophy and amelogenesis imperfecta due to PEX1 or PEX6 biallelic pathogenic variations. This syndrome is one of the less severe forms of peroxisome biogenesis disorders. In this chapter, we will review clinical, biological, and genetic knowledges about the Heimler syndrome.
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Amelogénesis Imperfecta , Pérdida Auditiva Sensorineural , Uñas Malformadas , Trastorno Peroxisomal , ATPasas Asociadas con Actividades Celulares Diversas/genética , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/metabolismo , Amelogénesis Imperfecta/patología , Amelogénesis Imperfecta/fisiopatología , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/metabolismo , Pérdida Auditiva Sensorineural/patología , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Proteínas de la Membrana/genética , Uñas Malformadas/genética , Uñas Malformadas/metabolismo , Uñas Malformadas/patología , Uñas Malformadas/fisiopatología , Trastorno Peroxisomal/genética , Trastorno Peroxisomal/metabolismo , Trastorno Peroxisomal/patología , Trastorno Peroxisomal/fisiopatologíaRESUMEN
The immune state is an essential component of survival as it directly influences physiological performance and health status. Variation in the leukocyte profile, a significantly increase in body temperature, and a detriment of the eco-physiological performance are among the possible consequences of an unhealthy state. In this study we analyse and discuss how field body temperature, preferred body temperature, the speed for sprint and long runs, locomotor stamina, and body condition can be affected by the immunological state (i.e. leukocyte profile) in a wild population of Liolaemus sarmentoi. Juveniles and adult males with a high percentage of eosinophils, basophils, and a low percentage of monocytes preferred higher body temperatures in a thermal gradient, while pregnant females maintained thermal preferences independently of leukocyte profile. Although juveniles with a high percentage of heterophils showed less locomotor stamina, adult males and pregnant females showed no differences in locomotor performance in relation to leukocyte profile. This study represents a starting point in eco-immunology of a wild lizard population of Liolaemus in cold and temperate environments of Patagonia where the southward shift in the geographic ranges of pathogen populations due to global warming represents a threat to resident host populations.
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Conducta Animal/fisiología , Temperatura Corporal/inmunología , Lagartos/sangre , Lagartos/inmunología , Actividad Motora/inmunología , Aclimatación , Animales , Temperatura Corporal/fisiología , Femenino , Lagartos/fisiología , Masculino , Actividad Motora/fisiología , EmbarazoRESUMEN
OBJECTIVES: Pycnodysostosis is a rare genetic disorder caused by a mutation of the cathepsin K gene involved in bone turnover. It is responsible, in particular, for a combination of dwarfism and bone fragility. Upper airway obstruction may be observed, but associated stridor has never been previously described. MATERIALS AND METHODS: Single-centre retrospective study over a period of 15 years with review of the literature. RESULTS: Three children (aged 2-18 months) were managed for stridor and obstructive sleep apnoea syndrome confirmed by polysomnography. Physical examination of these children revealed stridor with laryngomalacia, characteristic dysmorphic features and failure to thrive. Patient 1 presented typical laryngomalacia treated by surgical section of the aryepiglottic folds. Patient 2 presented upper airway obstruction with a narrow nasopharynx and long soft palate, treated by surgery and noninvasive ventilation. Patient 3 presented moderate laryngomalacia and nasal obstruction, treated by surgery and noninvasive ventilation. CONCLUSION: The diagnosis of pycnodysostosis must be considered in the presence of atypical laryngomalacia associated with multifactorial upper airway obstruction, failure to thrive and dysmorphic syndrome. A genetics consultation is essential in these patients.
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Picnodisostosis/diagnóstico , Humanos , Lactante , Masculino , Picnodisostosis/complicaciones , Ruidos Respiratorios/etiología , Estudios RetrospectivosRESUMEN
Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.
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Hibridación Genómica Comparativa/métodos , Asesoramiento Genético/ética , Asesoramiento Genético/métodos , Hallazgos Incidentales , Revelación/ética , Femenino , Francia , Genes Dominantes/genética , Genes Recesivos/genética , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Masculino , Análisis por Micromatrices/métodos , Relaciones Médico-Paciente/ética , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to a heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: (i) intrauterine growth retardation and postnatal short stature, (ii) feeding difficulties and/or gastro-oesophageal reflux, (iii) microcephaly, (iv) intellectual disability, and (v) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and 3 in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for 20 cases which do not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counselling.
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Síndrome de Cornelia de Lange/genética , Cara/anomalías , Asimetría Facial/genética , Mutación de Línea Germinal , Mutación , Proteínas/genética , Proteínas de Ciclo Celular , Síndrome de Cornelia de Lange/diagnóstico , Asimetría Facial/diagnóstico , Facies , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Mucosa Bucal/metabolismo , Fenotipo , Análisis de Secuencia de ADN/métodosRESUMEN
Ninety genes have been identified to date that are involved in non-syndromic hearing loss, and more than 300 different forms of syndromic hearing impairment have been described. Mutations in SOX10, one of the genes contributing to syndromic hearing loss, induce a large range of phenotypes, including several subtypes of Waardenburg syndrome and Kallmann syndrome with deafness. In addition, rare mutations have been identified in patients with isolated signs of these diseases. We used the recent characterization of temporal bone imaging aspects in patients with SOX10 mutations to identify possible patients with isolated hearing loss due to SOX10 mutation. We selected 21 patients with isolated deafness and temporal bone morphological defects for mutational screening. We identified two SOX10 mutations and found that both resulted in a non-functional protein in vitro. Re-evaluation of the two affected patients showed that both had previously undiagnosed olfactory defects. Diagnosis of anosmia or hyposmia in young children is challenging, and particularly in the absence of magnetic resonance imaging (MRI), SOX10 mutations can mimic non-syndromic hearing impairment. MRI should complete temporal bones computed tomographic scan in the management of congenital deafness as it can detect brain anomalies, cochlear nerve defects, and olfactory bulb malformation in addition to inner ear malformations.
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Pérdida Auditiva/genética , Mutación , Factores de Transcripción SOXE/genética , Hueso Temporal/patología , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Diagnóstico Diferencial , Oído Interno/anomalías , Femenino , Estudios de Asociación Genética , Pérdida Auditiva Sensorineural/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Datos de Secuencia Molecular , Fenotipo , Factores de Transcripción SOXE/química , Síndrome de Waardenburg/genéticaRESUMEN
Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss-of-function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype-phenotype correlations. Most mutation-negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity.
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Predisposición Genética a la Enfermedad/genética , Haploinsuficiencia/genética , Disostosis Mandibulofacial/genética , Fenotipo , Proteínas de Unión al ARN/genética , Secuencia de Bases , Femenino , Genes Dominantes/genética , Humanos , Masculino , Disostosis Mandibulofacial/patología , Datos de Secuencia Molecular , Mutación/genética , Factores de Empalme de ARN , Análisis de Secuencia de ADNRESUMEN
Hearing impairment is characterized by great genetic heterogeneity. We report the identification, by whole exome sequencing, of two different nonsense mutations (c.1558C>T; p.Gln520 and c.2773C>T; p.Arg925) in the otogelin-like gene (OTOGL), in a child affected by mild to moderate isolated deafness. Parental genotypes allowed us to conclude that these mutations are present in the compound heterozygous state in the patient. In addition, our clinical data establish that the tectorial membrane and/or the outer hair cells are defective in this form of deafness.
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Alelos , Codón sin Sentido , Trastornos de la Audición/genética , Glicoproteínas de Membrana/genética , Preescolar , Conexina 26 , Conexinas , Humanos , MasculinoRESUMEN
OBJECTIVES: To evaluate the management of prenatally diagnosed cleft lip with or without cleft palate and the immediate postnatal outcome. MATERIAL AND METHODS: Retrospective study of all cases of cleft lip with or without cleft palate referred to our fetal medicine unit, between January 2005 and January 2011. The anatomical type of cleft, associated malformations, and the postnatal outcome were reviewed. RESULTS: Forty-three cases of fetal cleft lip with or without cleft palate were reviewed. The mean gestational age at diagnosis was 24 weeks ± 4. The postnatal distribution of clefts was: 30 cleft lip and palate (70%) and 13 cleft lip (30%). The prenatal diagnosis of the cleft type was exact in 27 cases (62.8%). Nine cases had associated anomalies (21%), detected prenatally in three cases (37.5%). There was no karyotypical abnormality. Six pregnancies were terminated (14%). The immediate postnatal outcome was comparable with unselected newborns. CONCLUSION: The prenatal diagnosis of cleft lip with or without cleft palate is correct, with two thirds of exact diagnoses. Large clefts palate are the best detected. Associated malformations cannot always be diagnosed by prenatal ultrasound, but have to be searched for because they modify the fetal outcome.
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Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Diagnóstico Prenatal , Labio Leporino/complicaciones , Labio Leporino/embriología , Fisura del Paladar/complicaciones , Fisura del Paladar/embriología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Cariotipificación , Embarazo , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
BACKGROUND AND PURPOSE: Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. MATERIALS AND METHODS: Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. RESULTS: Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). CONCLUSIONS: In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.
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Oído Interno/anomalías , Factores de Transcripción SOXE/genética , Hueso Temporal/anomalías , Síndrome de Waardenburg/genética , Síndrome de Waardenburg/patología , Adolescente , Adulto , Niño , Preescolar , Cóclea/anomalías , Cóclea/diagnóstico por imagen , Cóclea/patología , Nervio Coclear/anomalías , Nervio Coclear/diagnóstico por imagen , Nervio Coclear/patología , Diagnóstico Diferencial , Oído Interno/diagnóstico por imagen , Oído Interno/patología , Femenino , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Bulbo Olfatorio/anomalías , Bulbo Olfatorio/diagnóstico por imagen , Bulbo Olfatorio/patología , Glándula Parótida/anomalías , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/patología , Radiografía , Estudios Retrospectivos , Canales Semicirculares/anomalías , Canales Semicirculares/diagnóstico por imagen , Canales Semicirculares/patología , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/patología , Síndrome de Waardenburg/diagnóstico por imagen , Adulto JovenRESUMEN
Hearing loss is the most common sensory disability with an incidence of one over 1000 newborns. Hearing loss may be caused by environmental and genetic factors; inherited causes are assumed in two thirds of cases. There is a great clinical and genetic heterogenicity. All inheritance modes have been described. Mutations in the GJB2 gene, which encodes connexin 26, are mainly responsible for sensorineural deafness resulting in prelingual non syndromic autosomal recessive phenotypes DFNB1. The 35 delG mutation of this gene is very frequent (70% of the cases). Thus, 35 delG is, with the delta F508 mutation of the CFTR gene, the most frequent human pathogenic mutation known. Hearing loss might also be associated with other clinical features. Some of these syndromes, including hearing loss, have to be looked for systematically because of their frequency, of their possible clinical presentation as an isolated hearing loss and of the possibility of a medical treatment.
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Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/genética , Conexina 26 , Conexinas/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Humanos , Recién Nacido , Proteínas de Transporte de Membrana/genética , Mutación , Factores del Dominio POU/genética , Transportadores de SulfatoRESUMEN
Mutations of the COCH gene inherited in an autosomal dominant mode are responsible for late-onset cochleovestibular impairment on both sides. Our objective is to report the youngest patient (3 years) associating a molecular variant of the COCH gene and a cochleovestibular impairment on both sides. The clinical sequence has started with a vestibular dysfunction in a two-year-old child: recurrent rotatory dizziness during 12 months. At the age of 3, a sensorineural hearing loss on both sides has occured associated with spontaneous variation during 6 months. The lack of mutation of the connexin 26, connexin 30 and pendrin genes has reorientated the genetic investigation. A molecular variant of the COCH gene was found in the vWFA2 domain. It was an in-frame deletion predicting the synthesis of an abnormal protein in which 21 aminoacid were missing. Others family members with mutation were asymptomatics. In this isolated case report, the study was in favor of a non pathogenic molecular variant of the COCH gene. For all that, mutations of the COCH gene could be searched in progressive cochleovestibular dysfunctions on both sides in children, even without family affect.
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Secuencia de Aminoácidos , Proteínas de la Matriz Extracelular/genética , Pérdida Auditiva Sensorineural/genética , Eliminación de Secuencia/genética , Enfermedades Vestibulares/genética , Preescolar , Humanos , MasculinoAsunto(s)
Conexinas/genética , Sordera , Proteínas de Transporte de Membrana/genética , Edad de Inicio , Audiometría , Análisis Químico de la Sangre , Niño , Preescolar , Conexina 26 , Sordera/diagnóstico , Sordera/genética , Genes Recesivos , Pruebas Genéticas , Genotipo , Humanos , Lactante , Recién Nacido , Fenotipo , Índice de Severidad de la Enfermedad , Transportadores de SulfatoRESUMEN
Cerebral, ocular, dental, auricular, skeletal syndrome (CODAS, OMIM 600373) is a very rare congenital malformation syndrome. This clinical entity is highly distinctive and associates mental retardation, cataract, enamel abnormalities, malformations of the helix, epiphyseal and vertebral malformations, and characteristic dysmorphic features. Since 1991, only three affected children have been reported. The etiology and pattern of inheritance of CODAS syndrome still remain unknown. We describe a new sporadic case presenting with all the characteristic features of CODAS syndrome associated with previously unreported malformations of the heart, larynx, and liver. All investigations such as karyotype, metabolic screening and array CGH were normal.
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Anomalías Múltiples/diagnóstico , Huesos/anomalías , Catarata/diagnóstico , Corteza Cerebral/anomalías , Atrios Cardíacos/anomalías , Discapacidad Intelectual/diagnóstico , Músculo Esquelético/anomalías , Anomalías Dentarias/diagnóstico , Anomalías Múltiples/genética , Catarata/congénito , Catarata/genética , Preescolar , Humanos , Discapacidad Intelectual/genética , Masculino , Síndrome , Anomalías Dentarias/genéticaRESUMEN
This article focuses on six questions raised by genetic testing in human: (1) the use of genetic tests, (2) information given to relatives of patients affected with genetic disorders, (3) prenatal and preimplantatory diagnosis for late onset genetic diseases and the use of pangenomic tests in prenatal diagnosis, (4) direct-to-consumer genetic testing, (5) population screening in the age of genomic medicine and (6) incidental findings when genetic testing are used.
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Pruebas Genéticas/legislación & jurisprudencia , Confidencialidad/ética , Confidencialidad/legislación & jurisprudencia , Salud de la Familia , Femenino , Francia , Pruebas Genéticas/ética , Humanos , Masculino , Embarazo , Diagnóstico Preimplantación/ética , Diagnóstico Prenatal/ética , AutocuidadoRESUMEN
X-linked deafness is a rare cause of hereditary isolated hearing impairment estimated as at least 1% or 2% of the non-syndromic hearing loss. To date, four loci for DFN have been identified and only one gene, POU3F4 responsible for DFN3, has been cloned. In males, DFN3 is characterized by a progressive deafness associated with perilymphatic gusher at stapes surgery and with a characteristic inner ear malformation. The phenotype of eight independent females carrying POU3F4 anomalies is defined, and a late-onset hearing loss is found in three patients. Only one has an inner ear malformation. No genotype/phenotype correlation is identified.