RESUMO
BACKGROUND: Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young adults. METHODS: We prospectively collected clinical, demographic, and autopsy information on all cases of sudden cardiac death among children and young adults 1 to 35 years of age in Australia and New Zealand from 2010 through 2012. In cases that had no cause identified after a comprehensive autopsy that included toxicologic and histologic studies (unexplained sudden cardiac death), at least 59 cardiac genes were analyzed for a clinically relevant cardiac gene mutation. RESULTS: A total of 490 cases of sudden cardiac death were identified. The annual incidence was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved boys or young men. Persons 31 to 35 years of age had the highest incidence of sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to 20 years of age had the highest incidence of unexplained sudden cardiac death (0.8 cases per 100,000 persons per year). The most common explained causes of sudden cardiac death were coronary artery disease (24% of cases) and inherited cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases) was the predominant finding among persons in all age groups, except for those 31 to 35 years of age, for whom coronary artery disease was the most common finding. Younger age and death at night were independently associated with unexplained sudden cardiac death as compared with explained sudden cardiac death. A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%) of unexplained sudden cardiac death in which genetic testing was performed. During follow-up, a clinical diagnosis of an inherited cardiovascular disease was identified in 13% of the families in which an unexplained sudden cardiac death occurred. CONCLUSIONS: The addition of genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death among children and young adults. (Funded by the National Health and Medical Research Council of Australia and others.).
Assuntos
Doenças Cardiovasculares/genética , Causas de Morte , Morte Súbita Cardíaca/epidemiologia , Testes Genéticos , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Austrália/epidemiologia , Autopsia , Doenças Cardiovasculares/mortalidade , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Nova Zelândia/epidemiologia , Estudos Prospectivos , Adulto JovemRESUMO
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, neonatally lethal developmental disorder of the lung with defining histologic abnormalities typically associated with multiple congenital anomalies (MCA). Using array CGH analysis, we have identified six overlapping microdeletions encompassing the FOX transcription factor gene cluster in chromosome 16q24.1q24.2 in patients with ACD/MPV and MCA. Subsequently, we have identified four different heterozygous mutations (frameshift, nonsense, and no-stop) in the candidate FOXF1 gene in unrelated patients with sporadic ACD/MPV and MCA. Custom-designed, high-resolution microarray analysis of additional ACD/MPV samples revealed one microdeletion harboring FOXF1 and two distinct microdeletions upstream of FOXF1, implicating a position effect. DNA sequence analysis revealed that in six of nine deletions, both breakpoints occurred in the portions of Alu elements showing eight to 43 base pairs of perfect microhomology, suggesting replication error Microhomology-Mediated Break-Induced Replication (MMBIR)/Fork Stalling and Template Switching (FoSTeS) as a mechanism of their formation. In contrast to the association of point mutations in FOXF1 with bowel malrotation, microdeletions of FOXF1 were associated with hypoplastic left heart syndrome and gastrointestinal atresias, probably due to haploinsufficiency for the neighboring FOXC2 and FOXL1 genes. These differences reveal the phenotypic consequences of gene alterations in cis.
Assuntos
Displasia Broncopulmonar/genética , Cromossomos Humanos Par 16/genética , Fatores de Transcrição Forkhead/genética , Deleção de Genes , Inativação Gênica , Mutação/genética , Alvéolos Pulmonares/patologia , Anormalidades Múltiplas/genética , Capilares/anormalidades , Pré-Escolar , Mapeamento Cromossômico , Doxorrubicina/análogos & derivados , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Alvéolos Pulmonares/irrigação sanguínea , Veias Pulmonares/anormalidadesRESUMO
Congenital midline cervical cleft (CMCC) is an uncommon malformation. We report a case of a baby girl aged 3 days with a CMCC associated with a cyst reported as a bronchogenic cyst (BC). The pathology is not specific. The association of BC and CMCC is extremely rare and only five cases have been found in the literature. We report our case and review the relevant literature.
Assuntos
Cisto Broncogênico/patologia , Pescoço/anormalidades , Pescoço/cirurgia , Anormalidades da Pele/cirurgia , Cisto Broncogênico/cirurgia , Feminino , Humanos , Recém-Nascido , Procedimentos de Cirurgia Plástica/métodosAssuntos
Vírus BK/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/virologia , Infecções por Polyomavirus/diagnóstico , Idoso , Fosfatase Alcalina/análise , Apraxias/etiologia , Ataxia/etiologia , Encéfalo/patologia , Encéfalo/virologia , DNA Viral/análise , Evolução Fatal , Feminino , Humanos , Linfoma de Células B/complicações , Imageamento por Ressonância Magnética , Microscopia Eletrônica de Transmissão , Infecções Oportunistas/virologia , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , gama-Glutamiltransferase/análiseAssuntos
Mutação da Fase de Leitura , Deleção de Genes , Miopatias Congênitas Estruturais/genética , Proteínas Tirosina Fosfatases não Receptoras/genética , Derrame Subdural/genética , Hemorragia Cerebral/congênito , Hematoma/congênito , Humanos , Recém-Nascido , Masculino , Miopatias Congênitas Estruturais/diagnóstico , GêmeosRESUMO
Background: This case involved a 35-year-old G6P0 with multiple uterine fibroids detected at 12 weeks gestation. Fibroid growth was monitored throughout pregnancy, and intrauterine growth restriction (< 5th centile) was detected at 20 weeks. Fetal demise occurred at 22+ weeks gestation at which time the largest of fibroids measured 150 × 100 × 118 mm and labour was induced. Materials and methods: Serial ultrasounds following delivery showed features of reduced vascularity and separation of the fibroid from the myometrium, consistent with spontaneous degeneration. Our patient re-presented with severe pain and went on to expel the fibroid spontaneously 41 days post induction of labour. Histopathology confirmed fibroid degeneration. Conclusion: This case demonstrates spontaneous fibroid degeneration and expulsion without embolisation. This may have resulted from the hormonal and mechanical effects of induction of labour. This case also demonstrated the effects of large intrauterine fibroids on fetal growth and increased risk of fetal demise, highlighting the importance of closer monitoring of fetal growth in such pregnancies.
RESUMO
This case demonstrates the ability to diagnose a significant duodenal atresia coexisting with an oesophageal atresia with associated tracheo-oesophageal fistula within the first trimester, however the mechanisms underlying the sonographic features remain uncertain.
RESUMO
A woman presenting with recurrent purpura fulminans was eventually found to have inflammatory bowel disease. We suggest the inflammatory state resulted in a deficiency of functional protein C.
Assuntos
Vasculite por IgA/etiologia , Doenças Inflamatórias Intestinais/complicações , Adulto , Colite/complicações , Colite/diagnóstico , Colonoscopia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Vasculite por IgA/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Úlceras Orais/etiologia , Recidiva , Úlcera Cutânea/etiologiaRESUMO
Placental mesenchymal dysplasia is an uncommon disorder in which the placenta is enlarged with abnormal, large, and often cystic villi with dilated and/or thick-walled vessels. These placental changes can mimic a partial hydatidiform mole but in contrast to a partial mole can coexist with a fully viable fetus. Fetal anatomical and vascular anomalies frequently coexist with placental mesenchymal dysplasia. In this case, placental mesenchymal dysplasia was associated with preterm labor at 33 weeks' gestation, fetal compromise, and a large abdominal mass with a large hepatic cyst that was de-roofed at exploratory laparotomy. The neonate remained critically ill with hypoxic ischaemic encephalopathy and coagulopathy and died despite intensive care. Biopsy and autopsy findings showed a large cystic mesenchymal hamartoma affecting the left lobe of the liver. This appears to be the 3rd histologically confirmed association of placental mesenchymal dysplasia with mesenchymal hamartoma of the liver in the English language literature.
Assuntos
Doenças Fetais/patologia , Hamartoma/complicações , Hepatopatias/complicações , Doenças Placentárias/patologia , Feminino , Hamartoma/patologia , Humanos , Recém-Nascido , Hepatopatias/patologia , Mesoderma/patologia , Trabalho de Parto Prematuro , Placenta/patologia , Gravidez , Nascimento Prematuro , Ultrassonografia Pré-NatalRESUMO
Prenatal specimens were received from a fetus with abnormalities noted on ultrasound. A supernumerary marker chromosome (SMC) was detected: 47,XY,+mar. Fluorescence in situ hybridisation (FISH) further classified this to be partial tetrasomy for chromosome 14. We compare this finding with other cases of SMC (14) and further classify phenotype with karyotype.
Assuntos
Aneuploidia , Cromossomos Humanos Par 14 , Diagnóstico Pré-Natal , Adulto , Amniocentese , Encéfalo/anormalidades , Anormalidades Craniofaciais/genética , Feminino , Idade Gestacional , Humanos , Hibridização in Situ Fluorescente , Deformidades Congênitas dos Membros/genética , Masculino , Reação em Cadeia da Polimerase , Gravidez , Ultrassonografia Pré-NatalRESUMO
The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.