RESUMO
The Harlequin syndrome is a rare autonomic disorder, characterized by unilateral diminished sweating and flushing of the face in response to heat or exercise. We present two new cases and evaluate the data of 83 patients described in the literature. We provide diagnostic and therapeutic guidelines.
Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/terapia , Ictiose Lamelar/complicações , Ictiose Lamelar/terapia , Adulto , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Afogueamento , Feminino , Humanos , Ictiose Lamelar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Esforço Físico , Guias de Prática Clínica como Assunto , SudoreseRESUMO
OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity. RESULTS: Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations. CONCLUSIONS: Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.
Assuntos
Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Adulto , Fatores Etários , Feminino , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estudos Retrospectivos , Adulto JovemRESUMO
Thirteen classical ataxia telangiectasia (A-T) patients, varying in age from 1 to 25 years, were studied clinically, electrophysiologically as well as by muscle ultrasound to chart the development and spectrum of neuromuscular abnormalities in A-T. The most prominent finding was a progressive axonal sensorimotor polyneuropathy, apparent by electromyography and muscle ultrasound from the age of 8 years and becoming clinically discernible around 12 years of age. Before the age of 8 years decreased tendon reflexes and slightly slowed sensory nerve conduction velocities could already be observed. With routine electrophysiological techniques the severe polyneuropathy precludes conclusions about the presence of anterior horn cell loss in older patients.
Assuntos
Ataxia Telangiectasia/complicações , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Condução Nervosa/fisiologia , Doenças Neuromusculares , Adolescente , Adulto , Criança , Pré-Escolar , Estimulação Elétrica/métodos , Eletromiografia , Feminino , Humanos , Lactente , Masculino , Condução Nervosa/efeitos da radiação , Doenças Neuromusculares/diagnóstico por imagem , Doenças Neuromusculares/etiologia , Doenças Neuromusculares/patologia , Ultrassonografia Doppler/métodosAssuntos
Síndrome de Guillain-Barré/tratamento farmacológico , Imunossupressores/administração & dosagem , Ácido Micofenólico/análogos & derivados , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Projetos PilotoRESUMO
The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy. AT was proven by genetic studies showing ATM mutations and a reduced level of ATM. ATM activity, as measured by phosphorylation of p53, was close to normal, indicating that the p53 response is not the only factor in preventing neural damage in anterior horn cells in AT.
Assuntos
Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Ataxia Telangiectasia/complicações , Proteínas Mutadas de Ataxia Telangiectasia , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Atrofia Muscular Espinal/complicaçõesRESUMO
Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, due to defects in the NBS1 gene and belongs to the DNA repair disorders. We report neuropathological findings of the first ever recognised case of the about 60 described cases of NBS. This patient showed severe microcephaly with a simplified gyral pattern especially in the frontal lobes. There were no signs of a degenerative disease, or of a primary migration disorder. A bulge on top of the corpus callosum, most probably a very large remnant of the involuting striae longitudinales mediales et laterales, was found. This can be considered as an incomplete development of limbic structures. The severe diminishment of neocortical neurones suggests an important role for the NBS1 gene in corticogenesis in man, as suggested earlier in animal studies of other DNA-repair genes.
Assuntos
Encéfalo/patologia , Proteínas de Ciclo Celular/genética , Quebra Cromossômica/genética , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Reparo do DNA/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Criança , Pré-Escolar , Evolução Fatal , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterised by cerebellar ataxia, telangiectasia, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to cell kill by ionising radiation and abnormally resistant to inhibition of DNA synthesis by ionising radiation. The responsible gene, 'ataxia telangiectasia mutated' (ATM) plays a crucial role in a signal transduction pathway, regulating the cell cycle, and in preventing damaged DNA from being reproduced. This rare genetic disorder manifests itself during childhood. The illness is progressive and most individuals die in their second or third decade of life due to infections or cancer. AT is difficult to diagnose due to its rarity and clinical heterogeneity. Both a physical examination and several laboratory tests are necessary for establishing its proper diagnosis.