RESUMO
Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Assuntos
Arteriosclerose/complicações , Síndromes de Imunodeficiência/complicações , Síndrome Nefrótica/complicações , Osteocondrodisplasias/complicações , Embolia Pulmonar/complicações , Anormalidades Dentárias/etiologia , Alelos , Anodontia/etiologia , Arteriosclerose/genética , Dente Pré-Molar/anormalidades , Proteína Morfogenética Óssea 4/análise , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , DNA Helicases/análise , DNA Helicases/genética , Fibroblastos/patologia , Humanos , Síndromes de Imunodeficiência/genética , Dente Molar/anormalidades , Mutação/genética , Síndrome Nefrótica/genética , Odontogênese/genética , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária , Embolia Pulmonar/genética , Pele/citologia , Germe de Dente/patologia , Raiz Dentária/anormalidades , Dente Decíduo/anormalidades , Transcrição Gênica/genética , Fator de Crescimento Transformador beta1/análise , Proteína Wnt3A/análiseRESUMO
We report the unique CNS findings in a patient with a proximal chromosome 14q interstitial deletion. Conventional MR imaging allowed the clear delineation of agenesis of the corpus callosum, SOD, and diffuse lissencephaly. DTI tractography played a significant role in the evaluation of the proximal 14q deletion-associated abnormalities, delineating the extent of the dysmorphic connections of the Probst bundles and clarifying that apparent areas of heterotopias were the corticospinal tracts.
Assuntos
Anormalidades Múltiplas/diagnóstico , Agenesia do Corpo Caloso/diagnóstico , Imagem de Tensor de Difusão , Lisencefalia/diagnóstico , Displasia Septo-Óptica/diagnóstico , Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Humanos , Lactente , Lisencefalia/genética , Masculino , Displasia Septo-Óptica/genéticaRESUMO
Attention to a careful diagnostic work-up should be given to patients with postaxial polydactyly or apparently isolated hypothalamic hamartomas. Early recognition of the condition is critical for management, particularly for anticipating and preventing endocrine emergencies. Conservative management of the hypothalamic hamartoma should be stressed. Finally, detailed genetic counseling should be provided to the family regarding autosomal-dominant inheritance as well as the wide range of interfamilial and intrafamilial variability.
Assuntos
Encefalopatias/complicações , Encefalopatias/diagnóstico , Hamartoma/complicações , Hamartoma/diagnóstico , Hipotálamo/fisiopatologia , Unhas Malformadas , Polidactilia/complicações , Pré-Escolar , Feminino , Humanos , Hipotálamo/patologia , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Polidactilia/diagnósticoAssuntos
Orelha/anormalidades , Dedos/anormalidades , Palato/anormalidades , Feminino , Humanos , Masculino , SíndromeAssuntos
Anormalidades Múltiplas , Anormalidades Craniofaciais , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/cirurgia , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/cirurgia , Craniossinostoses/cirurgia , Estética , Fácies , Feminino , Humanos , Masculino , Cirurgia PlásticaRESUMO
Pallister-Hall syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations. This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene. Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct. The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of GCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 7 , Proteínas de Ligação a DNA/genética , Mutação da Fase de Leitura , Hamartoma/genética , Proteínas do Tecido Nervoso , Polidactilia/genética , Proteínas Repressoras , Proteínas de Xenopus , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Feminino , Humanos , Doenças Hipotalâmicas/genética , Recém-Nascido , Fatores de Transcrição Kruppel-Like , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Síndrome , Fatores de Transcrição/genética , Proteína Gli3 com Dedos de Zinco , Dedos de ZincoRESUMO
Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%) associated with mental retardation. In those cases, the mental deficiency is presumed to be a consequence of intracranial hemorrhage due to the thrombocytopenia. We report on 2 infants with TAR syndrome. One had developmental delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI). Such findings have not been noted in the literature, but may not have been investigated in most cases. The other infant with TAR syndrome, who has had normal psychomotor development, has a normal brain on MRI scan. Detailed neuroimaging studies, preferably MRI, should be considered in the evaluation of patients with TAR syndrome, especially when there are documented signs of developmental delay, with or without a history of intracranial hemorrhage.