RESUMO
Thanatophoric dysplasia (TD) is a lethal form of short-limb skeletal dysplasia that is associated with macrocephaly, and variably cloverleaf skull. Two types of TD are clinically recognized, TD1 and TD2, mainly distinguished by their radiographic characteristics. The differences between the two are principally observed in the femur, which appears curved in TD1, while it remains straight but with a proximal medial spike in TD2, and are a less severe overall affectation in TD2. Both types of TD are caused by mutations in different functional domains of the FGFR3 gene. However, whereas several mutations in the different domains of FGFR3 cause TD1, the K650E mutation involving the change of a lysine to glutamic acid ("Lys650Glu") has been found in all TD2 cases to date. Here we describe a newborn infant with TD2 associated with brain defects that have either been infrequently observed (encephalocele) or not hitherto described (holoprosencephaly). Based on recent studies, we consider encephaloceles described in TD to be pseudoencephaloceles, since they are secondary to the intracranial pressure generated by severe hydrocephaly and to severe cranial structural anomalies. Finally, to analyze the mechanisms of holoprosencephaly observed in the case described here, we include a concise review on the current understanding of how FGFs and their receptors are expressed in the rostral signaling center (particularly Fgf8). In addition, we evaluated recent observations that FGF ligands and receptors (including FGFR3) act in concert to organize the whole telencephalon activity, rather than independently patterning different areas.
Assuntos
Encefalocele/genética , Holoprosencefalia/genética , Holoprosencefalia/fisiopatologia , Fenótipo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Encefalocele/patologia , Evolução Fatal , Feminino , Holoprosencefalia/patologia , Humanos , Recém-Nascido , Mutação de Sentido Incorreto/genética , Crânio/anormalidades , Crânio/patologia , Displasia Tanatofórica/genética , Displasia Tanatofórica/patologiaAssuntos
Complexo III da Cadeia de Transporte de Elétrons/deficiência , Mutação , ATPases Associadas a Diversas Atividades Celulares , Acidose Láctica/complicações , Acidose Láctica/genética , Criança , Pré-Escolar , Complexo III da Cadeia de Transporte de Elétrons/genética , Feminino , Humanos , Lactente , Recém-Nascido , Nefropatias/complicações , Nefropatias/genética , Falência Hepática/complicações , Falência Hepática/genética , Masculino , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/genéticaRESUMO
OBJECTIVE: Anti-HLA antibodies posttransplantation are associated with the appearance of acute and chronic rejection. The goal of this study was to determine the association between the presence of anti-HLA antibodies posttransplantation in children and the clinical outcome. PATIENTS AND METHODS: We studied the presence and the level of class I and II anti-HLA antibodies by microbead technology (Luminex) in 32 children after kidney transplantation; 87% underwent a first transplantation. Their mean age was 13.9 +/- 2.52 years. When anti-HLA was positive, 60% of children showed an increase in creatinine within the previous 3 months. The statistical analysis was performed with the SPSS 9.0 program. RESULTS: Only 4/32 children displayed class I anti-HLA antibodies at low levels (5-7.2) and 43% class II anti-HLA antibodies (level: 5-308). We did not observe an association between the presence of antibodies and age, sex, type of donor, immunosuppression, hypertension, proteinuria, time from transplantation, or reason to evaluate antibodies; 37.5% showed good graft function. The presence of anti-HLA antibodies posttransplantation was associated with retransplantations and with the percentage of antibodies by panel-reactive antibodies. There was trend towards an association with a previous acute rejection episode (P = .072); 62.5% of children with C4d-positive biopsies displayed anti-HLA antibodies vs 20% of those who were C4d-negative (P = .088). Graft survival was 100%. CONCLUSIONS: The presence of anti-HLA antibodies posttransplantation was influenced by pretransplantation factors-previous level of anti-HLA antibodies, retransplantation, DR matching- and also by posttransplantation factors, such as the occurrence of an acute rejection episode.