RESUMO
Variable lung disease was documented in 2 infants with heterozygous TBX4 mutations; their clinical presentations, pathology, and outcomes were distinct. These findings demonstrate that TBX4 gene mutations are associated with neonatal respiratory failure and highlight the wide spectrum of clinicopathological outcomes that have implications for patient diagnosis and management.
Assuntos
Mutação/genética , Insuficiência Respiratória/genética , Insuficiência Respiratória/patologia , Proteínas com Domínio T/genética , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
El síndrome de Netherton (SN) es una enfermedad autosómica recesiva, muy poco frecuente, que se caracteriza por la presencia de eritrodermia ictiosiforme congènita, anomalías capilares y manifestaciones atópicas. Este síndrome es consecuencia de una mutación recesiva en el gen SPINK5. Las manifestaciones del síndrome de SN varían considerablemente entre las personas que lo padecen. Aquí informamos el caso de un recién nacido que presentaba insuficiencia respiratoria grave, hipotermia y eritrodermia, al que se le diagnosticó SN, confirmado mediante pruebas genéticas moleculares.
Netherton syndrome (NS) is a rare, autosomal recessive disease characterized with congenital ichthyosiform erythroderma, hair abnormality and atopic manifestations. This syndrome is caused by recessive mutation in the SPINK5 gene. Disease manifestations vary considerably among NS individuals. We report a newborn presented with severe respiratory insufficiency, hypothermia and erythroderma, was diagnosed as having NS and confirmed with molecular genetic testing.
Assuntos
Humanos , Masculino , Recém-Nascido , Insuficiência Respiratória/etiologia , Eritrodermia Ictiosiforme Congênita/etiologia , Síndrome de Netherton/diagnóstico , Insuficiência Respiratória/genética , Eritrodermia Ictiosiforme Congênita/genética , Síndrome de Netherton/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genética , Hipotermia/etiologia , Hipotermia/genética , MutaçãoRESUMO
Netherton syndrome (NS) is a rare, autosomal recessive disease characterized with congenital ichthyosiform erythroderma, hair abnormality and atopic manifestations. This syndrome is caused by recessive mutation in the SPINK5 gene. Disease manifestations vary considerably among NS individuals. We report a newborn presented with severe respiratory insufficiency, hypothermia and erythroderma, was diagnosed as having NS and confirmed with molecular genetic testing.
El síndrome de Netherton (SN) es una enfermedad autosómica recesiva, muy poco frecuente, que se caracteriza por la presencia de eritrodermia ictiosiforme congénita, anomalías capilares y manifestaciones atópicas. Este síndrome es consecuencia de una mutación recesiva en el gen SPINK5. Las manifestaciones del síndrome de SN varían considerablemente entre las personas que lo padecen. Aquí informamos el caso de un recién nacido que presentaba insuficiencia respiratoria grave, hipotermia y eritrodermia, al que se le diagnosticó SN, confirmado mediante pruebas genéticas moleculares.
Assuntos
Eritrodermia Ictiosiforme Congênita/etiologia , Síndrome de Netherton/diagnóstico , Insuficiência Respiratória/etiologia , Humanos , Hipotermia/etiologia , Hipotermia/genética , Eritrodermia Ictiosiforme Congênita/genética , Recém-Nascido , Masculino , Mutação , Síndrome de Netherton/genética , Insuficiência Respiratória/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genéticaRESUMO
As a ß2 integrin family member, Mac-1 plays an important role in the inflammatory response. Inflammation and lung injury are closely associated, but the involvement of Mac-1 in the occurrence and development of such pathologies remains poorly understood. We aimed to investigate the relationship between Mac-1 deficiency and respiratory failure in Mac-1 knockout {Mac-1-/-} mice, using C57BL/6J mice as a control. The newborn survival rate of Mac-1-/- mice was calculated, and mouse lung tissue was treated with hematoxylin and eosin and subjected to immunofluorescent staining. Moreover, western blotting and immunohistochemistry were used to detect the expression of molecules specific to type I and type II alveolar epithelial cells, as well as alveolar surfactant proteins secreted by the latter. Survival of Mac-1-/- pups was significantly lower than that of newborn C57BL/6J mice. In a float test, lung tissues from C57BL/6J mice were buoyant, whereas those of Mac-1-/- mice were not. Compared with C57BL/6J mice, expression of proSP-C {specific to type II alveolar epithelial cells} and alveolar surfactant proteins in Mac-1-/- mice was not significantly different, implying that type II cell function was unaltered. However, western blotting revealed expression of T1α, Aqp5, and Snx5 {type I alveolar epithelial cell markers} in Mac-1-/- mice to be significantly decreased {P < 0.05}. In conclusion, Mac-1 may play an important role in respiratory failure. Its absence leads to this condition not by influencing type II alveolar epithelial cells or their secreted surfactant proteins, but rather by reducing type I alveolar cell numbers.
Assuntos
Células Epiteliais Alveolares/metabolismo , Antígeno CD11b/genética , Insuficiência Respiratória/metabolismo , Animais , Antígeno CD11b/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Insuficiência Respiratória/genética , Insuficiência Respiratória/patologiaRESUMO
The aim of this study was to evaluate the pulmonary condition in a large family with Charcot-Marie-Tooth disease type 2 (CMT2). Eighteen participants diagnosed with CMT2 and 20 healthy individuals were evaluated by spirometry and maximal expiratory and maximal inspiratory pressures (MEP and MIP, respectively). Clinical disability was measured with CMT neuropathy score (CMTNS; range 0-36). One control group (CG) comprising 20 individuals, matched for age, sex and body mass index, were used for comparison. Eight patients were female (44.5%) and 10 patients were male (55.5%); mean age was 31.8 years (range 11-79) and CMTNS range was 6-26. Differences between CMT2 and CG in the spirometry and respiratory muscle strength were statistically significant for all dimensions. There were significant correlations between CMTNS and MIP (Pearson = -0.581) and MEP (Pearson = -0.5090). The results of this study show that patients with CMT, in spite of not showing clinical signs of advanced respiratory impairment, may present subclinical respiratory changes. The respiratory comprise in the CMT disease can be silent and insidious without presenting characteristic clinical signals.
Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Músculos Respiratórios/fisiopatologia , Paralisia Respiratória/fisiopatologia , Adulto , Brasil , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Aberrações Cromossômicas , Feminino , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Testes de Função Respiratória , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/genética , Paralisia Respiratória/diagnóstico , Paralisia Respiratória/genética , Adulto JovemRESUMO
Stüve-Wiedemann syndrome (SWS) is an autosomal recessive bone dysplasia (OMIM #601559) characterized by bowing of long bones, camptodactyly, respiratory insufficiency, hyperthermic episodes, and neonatal death from hyperthermia or apnea. We describe two female siblings with SWS born from consanguineous Gypsy parents. For a further delineation of SWS, we report hypothyroidism and ectopic thyroid as part of its phenotypic spectrum. Molecular study in the leukemia inhibitory factor receptor (LIFR) gene (OMIM *151 443) demonstrated the presence of a mutation. We observed that in one of our patients, oropharyngeal disruption in the swallowing process caused repetitive aspiration pneumonias, life-threatening events, and finally death. We emphasize that these features represent dysautonomic manifestations of SWS, and are probably related to pharyngoesophageal dyskinesia due to abnormal autonomic control of the anterior rami of cervical roots C1-C5.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Transtornos de Deglutição/mortalidade , Morbidade , Orofaringe/fisiopatologia , Osteocondrodisplasias/diagnóstico por imagem , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Pré-Escolar , Consanguinidade , Transtornos de Deglutição/congênito , Face/anormalidades , Evolução Fatal , Feminino , Genes Recessivos , Humanos , Hipotireoidismo/fisiopatologia , Lactente , Recém-Nascido , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Disautonomias Primárias/congênito , Radiografia , Insuficiência Respiratória/genética , Irmãos , Síndrome , Glândula Tireoide/anormalidadesRESUMO
Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate regulator of thyroid and lung morphogenesis and function in humans. We report 2 female siblings with congenital thyroid dysfunction and recurrent acute respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3, resulting in haploinsufficiency for the NKX2.1 gene. This observation further supports a physiologic role for thyroid transcription factor-1 in early human thyroid and pulmonary function.
Assuntos
Cromossomos Humanos Par 14 , Hipotireoidismo Congênito , Deleção de Genes , Hipotireoidismo/genética , Receptores dos Hormônios Tireóideos/genética , Insuficiência Respiratória/genética , Feminino , Heterozigoto , Humanos , Recém-Nascido , Núcleo Familiar , Tireotropina/sangueRESUMO
Prenatal diagnosis of Jarcho-Levin syndrome early in pregnancy has not been previously reported. We present a case in which ultrasound examination resulted in a tentative diagnosis at 22 weeks of pregnancy. The difficulties in arriving at a definite diagnosis are presented.