RESUMEN
We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/patología , Enfermedades Gastrointestinales/patología , Encefalomiopatías Mitocondriales/patología , Adulto , Biopsia/métodos , Cerebelo/patología , Enfermedad de Charcot-Marie-Tooth/complicaciones , Enfermedad de Charcot-Marie-Tooth/genética , Análisis Mutacional de ADN/métodos , Femenino , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/genética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Microscopía Electrónica de Transmisión/métodos , Encefalomiopatías Mitocondriales/complicaciones , Encefalomiopatías Mitocondriales/genética , Músculos/patología , Mutación , Fibras Nerviosas Mielínicas/patología , Fibras Nerviosas Mielínicas/ultraestructura , Conducción Nerviosa/fisiología , Estudios Retrospectivos , Timidina Fosforilasa/genética , Timidina Fosforilasa/metabolismoAsunto(s)
Trastornos del Desarrollo Sexual/patología , Osteocondrodisplasias/patología , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Adolescente , Trastornos del Desarrollo Sexual/complicaciones , Cara/anomalías , Femenino , Humanos , Discapacidad Intelectual/complicaciones , Cariotipificación , Osteocondrodisplasias/complicaciones , SíndromeRESUMEN
Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, two of which were associated with TAA and one with AD. Segregation analysis showed that the distribution of these vascular abnormalities was more likely compatible with a single genetic defect with an autosomal dominant pattern of inheritance. There were no clinical signs of Marfan, Elhers-Danlos vascular type or Char syndromes. Genetic linkage analysis was performed for seven genes or loci implicated in familial TAA/AD disease (COL3A1, FBN1, 3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-q24), Char syndrome (TFAP2B) or autosomal recessive PDA (12q24). Using different genetic models, linkage with these seven loci was excluded. Familial TAA/AD with PDA is likely to be a particular heritable vascular disorder, with an as yet undiscovered Mendelian genetic basis.
Asunto(s)
Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/genética , Disección Aórtica/complicaciones , Disección Aórtica/genética , Conducto Arterioso Permeable/genética , Conducto Arterioso Permeable/fisiopatología , Disección Aórtica/fisiopatología , Aneurisma de la Aorta Torácica/fisiopatología , Muerte Súbita/etiología , Conducto Arterioso Permeable/complicaciones , Femenino , Francia , Ligamiento Genético/genética , Humanos , Masculino , Repeticiones de Microsatélite/genética , Linaje , Accidente Cerebrovascular/complicacionesRESUMEN
We report here the fourth case of hypomandibular faciocranial dysostosis (HFD). The diagnosis was made at birth on the association of severe retrognathia, microstomia, severe hypoglossia with glossoptosis, persistent buccopharyngeal membrane, median cleft palate, bifid uvula, down-slanting palpebral fissures, short nose with anteverted nares, laryngeal hypoplasia, and low-set ears. A severe microstomia and micrognathia were detected by ultrasound at 31 weeks of gestation. Interestingly, even though the present case exhibits many facial dysmorphic features characteristic of HFD, craniosynostosis was absent. This report suggests that craniosynostosis is not mandatory for the diagnosis of this condition. Furthermore, we present a new argument for an autosomal recessive mode of inheritance for HFD.