RESUMO
Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare soft tissue sarcoma in childhood. We present the case of a newborn male who experienced a severe hemorrhage in utero from the tumor on the scalp. He died at the age of 24 hours owing to hemorrhagic shock. The tumor was posthumously diagnosed as PMMTI. A literature search indicated that cases of severe hemorrhage from soft tissue sarcomas in utero or at birth are limited to infantile fibrosarcoma. This is the first case of PMMTI with massive hemorrhage. Clinicians must be aware of hemorrhagic complications of PMMTI.
Assuntos
Fibrossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Recém-Nascido , Humanos , Lactente , Masculino , Fibrossarcoma/complicações , Fibrossarcoma/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/patologia , Hemorragia/etiologiaRESUMO
Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal/citologia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Biomarcadores , Gasometria , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Eletroencefalografia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/metabolismo , Recém-Nascido , Masculino , Projetos PilotoRESUMO
Congenital microcephaly with intracranial calcification is a rare condition presented in heterogeneous diseases. Here, we report the case of a 1-year-old boy with severe congenital microcephaly and diffuse calcification. Neuroimaging studies showed a diffuse simplified gyral pattern; a very thin cortex; ventricular dilatation; very small basal ganglia, thalamus, and brainstem; and cerebellar hypoplasia with diffuse calcification. Clinical features of intrauterine infections, such as neonatal jaundice, hepatomegaly, and thrombocytopenia, were not found. Serological tests, cultures, and polymerase chain reaction analysis were negative for viral infections. The etiology of pseudo-toxoplasmosis, rubella, cytomegalovirus, and herpes simplex syndrome is still unknown. This study describes the most severe form of pseudo-toxoplasmosis, rubella, cytomegalovirus, and herpes simplex syndrome reported to date, with the patient showing microcephaly and calcification or band-like intracranial calcification with simplified gyration and polymirogyria.
Assuntos
Encefalopatias/congênito , Tronco Encefálico/anormalidades , Calcinose/congênito , Cerebelo/anormalidades , Encefalopatias/patologia , Tronco Encefálico/patologia , Calcinose/patologia , Cerebelo/patologia , Humanos , Lactente , Masculino , Microcefalia/patologiaRESUMO
Shwachman-Diamond syndrome (SDS) is a rare hereditary disorder characterized by pancreatic exocrine insufficiency, bone marrow dysfunction and skeletal changes. Recently, the cause of SDS was identified as mutations of Shwachman-Bodian-Diamond syndrome gene (SBDS) and most mutations are caused by gene conversion between SBDS and its highly homologous pseudogene. Clinical variations especially in skeletal and bone marrow abnormalities are well known in this syndrome. To study the relationship between SBDS mutation and its clinical features, we analyzed 9 Japanese patients including one sibling and detected the three different SBDS mutations in 7 patients: a mutation that disrupts the donor splice site of intron 2, deletes 8 bp of the exon 2 and produces premature termination (258+2 T > C), a dinucleotide change that replaces a lysine at 62 nd amino acid to a termination codon (183-184 TA > CT), and a 4-bp deletion that causes premature termination by frameshift (292-295 delAAAG). The 5 patients represent compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. One patient is a compound heterozygote of the 258+2 T > C and 292-295 delAAAG mutations, and in the remaining one case only a 258+2 T > C mutation could be detected. Thus, the 258+2 T > C and 183-184 TA > CT mutations are prevalent among Japanese patients. No mutations were found in two cases, despite the clinical features. Of the 7 patients with SBDS mutations, persistent hematologic abnormalities and skeletal changes were not observed in 3 and 2 patients, respectively. Notably, clinical variations are present even among the patients with the identical genotype: compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. Further study will be required to explain the clinical heterogeneity.
Assuntos
Doenças da Medula Óssea/genética , Osso e Ossos/anormalidades , Insuficiência Pancreática Exócrina/genética , Mutação , Osteocondrodisplasias/genética , Proteínas/genética , Sequência de Bases , Criança , Pré-Escolar , Cromossomos/ultraestrutura , DNA/química , Análise Mutacional de DNA , Primers do DNA/química , Éxons , Feminino , Mutação da Fase de Leitura , Deleção de Genes , Variação Genética , Heterozigoto , Humanos , Lactente , Recém-Nascido , Íntrons , Japão , Cariotipagem , Lisina/química , Masculino , Dados de Sequência Molecular , Oligonucleotídeos , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , SíndromeRESUMO
Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a disorder characterized by an idiopathic failure of the automatic control of breathing. CCHS is frequently complicated with neurocristopathies such as Hirschsprung's disease (HSCR). The genes involved in the RET-GDNF signaling and/or EDN3-EDNRB signaling pathways have been analyzed as candidates for CCHS; however, only a few patients have mutations of the RET, EDN3, and GDNF genes. Recently, mutations of the PHOX2B gene, especially polyalanine expansions, have been detected in two thirds of patients. We studied the RET, GDNF, GFRA1, PHOX2A, PHOX2B, HASH-1, EDN1, EDN3, EDNRB, and BDNF genes in seven patients with isolated CCHS and three patients with HSCR. We detected polyalanine expansions and a novel frameshift mutation of the PHOX2B gene in four patients and one patient, respectively. We also found several mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes in patients with or without mutations of the PHOX2B gene. Our study confirmed the prominent role of mutations in the PHOX2B gene in the pathogenesis of CCHS. Mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes may also be involved in the pathogenesis of CCHS. To make clear the pathogenesis of CCHS, the analysis of more cases and further candidates concerned with the development of the autonomic nervous system is required.
Assuntos
Apneia do Sono Tipo Central/genética , Idade de Início , Substituição de Aminoácidos , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Lactente , Masculino , Fatores de Crescimento Neural/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genética , Respiração Artificial , SíndromeRESUMO
Charcot-Marie-Tooth disease type 1 (CMT1) is a heterogeneous disorder. Most CMT1 patients are associated with a duplication of 17p11.2-p12 (CMT1A duplication), but a small number of patients have mutations of peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), connexin 32 (Cx32) and early growth response 2 (EGR2) genes. In our previous study, we identified the responsible mutations in 72 of 128 Japanese CMT1 patients as CMT1A duplication in 40, PMP22 mutation in 6, MPZ mutation in 12 and Cx32 mutation in 14 patients. A total of 56 Japanese CMT1 patients with no identified mutations were screened for EGR2 mutation by denaturing gradient gel electrophoresis (DGGE). We detected a heterozygous Asp383Tyr mutation of EGR2 in one patient with severe CMT1, Dejerine-Sottas syndrome. EGR2 mutation is rare cause of CMT1 in Japan as in other nations. We were unable to identify the responsible mutation in 55 of 128 CMT1 patients and need further analysis to identify their candidate genes.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas de Ligação a DNA/genética , Transativadores/genética , Adulto , Ácido Aspártico/genética , Conexinas/genética , Análise Mutacional de DNA , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Japão/epidemiologia , Masculino , Dados de Sequência Molecular , Mutação , Proteína P0 da Mielina/genética , Proteínas da Mielina/genética , Regulador Transcricional ERG , Tirosina/genética , Proteína beta-1 de Junções ComunicantesRESUMO
Recently, a few genetic abnormalities were identified in congenital central hypoventilation syndrome (CCHS or Ondine's curse). CCHS is often associated with other neurocristopathies, especially with Hirschsprung's disease (HSCR). Mutations of the genes involved in the receptor tyrosine kinase RET (REarranged during Transfection) (RET)-glial cell line-derived neurotrophic factor (GDNF) and/or endothelin 3 (EDN3)-endothelin receptor-B (EDNRB) signaling pathway have been found in some of HSCR patients. In this study, we analyzed candidates for HSCR, namely the RET, GDNF, EDN3 and EDNRB genes in three isolated CCHS patients to confirm the hypothesis that some CCHS patients have a common genetic abnormality with patients having HSCR or other neurocristopathies. We found a novel R114H mutation of the RET gene in one patient. The R114H mutation is unlikely to be a polymorphism and appears to be associated with CCHS. In addition, we also examined the HOX11L2 (RNX) gene, for which knock-out mice showed CCHS-like syndrome in these isolated CCHS patients and did not detected any mutation. Further cases should be analyzed for more candidates to clarify the pathophysiology of CCHS.