RESUMO
Complex cortical malformations associated with mutations in tubulin genes: TUBA1A, TUBA8, TUBB2B, TUBB3, TUBB5 and TUBG1 commonly referred to as tubulinopathies, are a heterogeneous group of conditions with a wide spectrum of clinical severity. Among the 106 patients selected as having complex cortical malformations, 45 were found to carry mutations in TUBA1A (42.5%), 18 in TUBB2B (16.9%), 11 in TUBB3 (10.4%), three in TUBB5 (2.8%), and three in TUBG1 (2.8%). No mutations were identified in TUBA8. Systematic review of patients' neuroimaging and neuropathological data allowed us to distinguish at least five cortical malformation syndromes: (i) microlissencephaly (n = 12); (ii) lissencephaly (n = 19); (iii) central pachygyria and polymicrogyria-like cortical dysplasia (n = 24); (iv) generalized polymicrogyria-like cortical dysplasia (n = 6); and (v) a 'simplified' gyral pattern with area of focal polymicrogyria (n = 19). Dysmorphic basal ganglia are the hallmark of tubulinopathies (found in 75% of cases) and are present in 100% of central pachygyria and polymicrogyria-like cortical dysplasia and simplified gyral malformation syndromes. Tubulinopathies are also characterized by a high prevalence of corpus callosum agenesis (32/80; 40%), and mild to severe cerebellar hypoplasia and dysplasia (63/80; 78.7%). Foetal cases (n = 25) represent the severe end of the spectrum and show specific abnormalities that provide insights into the underlying pathophysiology. The overall complexity of tubulinopathies reflects the pleiotropic effects of tubulins and their specific spatio-temporal profiles of expression. In line with previous reports, this large cohort further clarifies overlapping phenotypes between tubulinopathies and although current structural data do not allow prediction of mutation-related phenotypes, within each mutated gene there is an associated predominant pattern of cortical dysgenesis allowing some phenotype-genotype correlation. The core phenotype of TUBA1A and TUBG1 tubulinopathies are lissencephalies and microlissencephalies, whereas TUBB2B tubulinopathies show in the majority, centrally predominant polymicrogyria-like cortical dysplasia. By contrast, TUBB3 and TUBB5 mutations cause milder malformations with focal or multifocal polymicrogyria-like cortical dysplasia with abnormal and simplified gyral pattern.
Assuntos
Agenesia do Corpo Caloso/diagnóstico , Lisencefalia/diagnóstico , Malformações do Desenvolvimento Cortical/diagnóstico , Microcefalia/diagnóstico , Mutação/genética , Tubulina (Proteína)/genética , Adolescente , Adulto , Agenesia do Corpo Caloso/epidemiologia , Agenesia do Corpo Caloso/genética , Cerebelo/anormalidades , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Lisencefalia/epidemiologia , Masculino , Malformações do Desenvolvimento Cortical/epidemiologia , Microcefalia/epidemiologia , Microcefalia/genética , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/genética , Fenótipo , Adulto JovemRESUMO
Holoprosencephaly is frequently accompanied by midline facial abnormalities such as hypotelorism, cyclopia, etmocephaly and cebocephaly. Cebocephaly is a very rare congenital anomaly combining with semilobar holoprosencephaly. Chromosomal analysis shows normal karyotyping. Lissencephaly and holoprosencephaly are rare associations, that have not been reported yet with cebocephaly. Herein we present the first case of cebocephaly with severe semilobar holoprosencephaly and lissencephaly.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Holoprosencefalia/diagnóstico , Lisencefalia/diagnóstico , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Comorbidade , Anormalidades Craniofaciais/epidemiologia , Anormalidades Craniofaciais/genética , Feminino , Holoprosencefalia/epidemiologia , Holoprosencefalia/genética , Humanos , Recém-Nascido , Lisencefalia/epidemiologia , Lisencefalia/genética , Índice de Gravidade de DoençaAssuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Lisencefalia/genética , Lisencefalia/fisiopatologia , Agenesia do Corpo Caloso , Cerebelo/anormalidades , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/epidemiologia , Corpo Caloso/fisiopatologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Expressão Gênica , Humanos , Lisencefalia/epidemiologia , Masculino , Mutação Puntual/genéticaRESUMO
OBJECTIVE: Our objective in this retrospective study was to assess the hippocampal abnormalities, associate them with various congenital brain malformations, and define the frequency of the association in specific anomaly subgroups. METHODS: A total of 62 patients with congenital malformations of the brain who had thin-slice coronal T2-weighted, fluid attenuated inversion recovery, IR, or T1-weighted 3D gradient echo images were retrospectively evaluated for the type of congenital brain malformation and morphological or rotational hippocampal abnormalities. Medical records were reviewed for age, sex, and symptoms. CONCLUSION: Hippocampal abnormalities are found in 55.8% of all patients with different kinds of congenital brain malformations that are mostly associated with cortical dysplasia, lissencephaly, and total agenesis of the corpus callosum. The severity of the injury may have an effect on the extent of the involvement of the brain.
