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1.
Am J Med Genet A ; 173(6): 1473-1488, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440899

RESUMO

Lissencephaly ("smooth brain," LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS-LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS. To address this challenge, we reviewed clinical, imaging and molecular data on 188 patients with LIS-SBH ascertained during the last 5 years, and reviewed selected archival data on another ∼1,400 patients. Using these data plus published reports, we constructed a new imaging based classification system with 21 recognizable patterns that reliably predict the most likely causative genes. These patterns do not correlate consistently with the clinical outcome, leading us to also develop a new scale useful for predicting clinical severity and outcome. Taken together, our work provides new tools that should prove useful for clinical management and genetic counselling of patients with LIS-SBH (imaging and severity based classifications), and guidance for prioritizing and interpreting genetic testing results (imaging based- classification).


Assuntos
Córtex Cerebral/fisiopatologia , Lisencefalia/fisiopatologia , Imageamento por Ressonância Magnética , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/classificação , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico por imagem , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Feminino , Humanos , Lactente , Recém-Nascido , Lisencefalia/classificação , Lisencefalia/diagnóstico por imagem , Lisencefalia/genética , Masculino , Proteínas Associadas aos Microtúbulos/genética , Mutação , Neuropeptídeos/genética , Fenótipo , Adulto Jovem
2.
Pract Neurol ; 15(2): 90-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25239628

RESUMO

Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS) have several subtypes, together forming a continuous spectrum of discrete and overlapping syndromes. Such is the heterogeneity within this spectrum that many physicians may be surprised to learn that these disorders are related pathophysiologically, and therefore share certain clinical features. These include history of antecedent infection, monophasic disease course and symmetrical cranial or limb weakness. The presence of cerebrospinal fluid albuminocytological dissociation (raised protein, normal cell count), antiganglioside antibodies and neurophysiological evidence of axonal or demyelinating neuropathy also support a diagnosis in many cases, but should not be relied upon. Mimics of GBS and MFS can broadly be divided into those presenting with symmetrical limb weakness and those presenting with brainstem signs. MFS and the pharyngeal-cervical-brachial variant of GBS are frequently mistaken for brainstem stroke, botulism or myasthenia gravis, whereas Bickerstaff's brainstem encephalitis is often diagnosed as Wernicke's encephalopathy. Chameleons or atypical presentations of GBS-related disorders include: paraparetic GBS, bifacial weakness with paraesthesias, acute ataxic neuropathy, acute ophthalmoparesis, acute ptosis and acute mydriasis. Many neurologists may also not be aware that deep tendon reflexes remain present or may even appear brisk in up to 10% of patients with GBS. Correct diagnosis of GBS-related disorders helps to avoid unnecessary investigations and allows early immunotherapy if appropriate.


Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/fisiopatologia , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/classificação , Síndrome de Guillain-Barré/classificação , Humanos
3.
Arch Neurol ; 66(8): 1007-15, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19667223

RESUMO

OBJECTIVE: With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype. DESIGN: Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly. INTERVENTIONS: Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined. RESULTS: Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly. CONCLUSION: Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Encéfalo/patologia , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Análise Mutacional de DNA , Genótipo , Imageamento por Ressonância Magnética , Proteínas Associadas aos Microtúbulos/genética , Exame Neurológico , Adolescente , Adulto , Criança , Pré-Escolar , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/classificação , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico , Feminino , Humanos , Lactente , Masculino , Fenótipo , Adulto Jovem
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