RESUMO
BACKGROUND: Neurocysticercosis (NCC) is an unusual cause of seizures in high income settings. It typically presents as an afebrile seizure in a previously well child and can occur years after migration or travel. METHODS: Children diagnosed with neurocysticercosis from 01 July 2005 to 30 June 2020 were identified from the electronic medical records of a tertiary children's hospital in Australia. Additionally, a 10-year compilation of case reports of paediatric NCC in high income settings was performed by medline search (publication years 2011-2021). Diagnosis and treatment of neurocysticercosis were reviewed with reference to diagnostic criteria of Del Brutto et al., and the 2017 Infectious Diseases Society of America treatment guidelines. RESULTS: Over a fifteen-year period, eight children were diagnosed with NCC at our hospital in Sydney, Australia. Seizures and history of travel to or migration from South Asia were the two most frequently occurring findings. Children diagnosed after 2016 all received antiparasitic therapy. Outcomes were generally favorable, though long-term epilepsy resulted in some cases. Compiled case reports from high income settings revealed migration and travel exposures commensurate with local demographic patterns, and treatment approaches conforming with 2017 Infectious Diseases Society of America guidelines. CONCLUSIONS: Clinicians should be aware of NCC as a differential diagnosis in children from endemic areas presenting with unprovoked seizures as misdiagnosis can occur. Expert review of neuroimaging facilitates diagnosis and can avert unnecessary neurosurgery. In Australia, India was a key exposure country for NCC, reflecting its endemic burden of disease and local travel and migration patterns.
Assuntos
Epilepsia , Neurocisticercose , Criança , Países Desenvolvidos , Epilepsia/epidemiologia , Humanos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , Neuroimagem , Convulsões/complicaçõesRESUMO
Postnatal cytomegalovirus enterocolitis is uncommon in immunocompetent infants. We report a 10-week-old term boy with severe and prolonged secretory diarrhea, leading to dependence on total parenteral nutrition and a 10-week hospitalization. Cytomegalovirus enterocolitis was diagnosed based on duodenal biopsy in the context of marked viremia, and the child recovered promptly on initiation of ganciclovir. Collated case reports reveal delayed diagnoses as the norm but rapid improvement with antiviral treatment. Cytomegalovirus enterocolitis should be considered early as a differential diagnosis in infants with refractory diarrhea.
RESUMO
A precise genetic diagnosis is the single most important step for families with genetic disorders to enable personalized and preventative medicine. In addition to genetic variants in coding regions (exons) that can change a protein sequence, abnormal pre-mRNA splicing can be devastating for the encoded protein, inducing a frameshift or in-frame deletion/insertion of multiple residues. Non-coding variants that disrupt splicing are extremely challenging to identify. Stemming from an initial clinical discovery in two index Australian families, we define 25 families with genetic disorders caused by a class of pathogenic non-coding splice variant due to intronic deletions. These pathogenic intronic deletions spare all consensus splice motifs, though they critically shorten the minimal distance between the 5' splice-site (5'SS) and branchpoint. The mechanistic basis for abnormal splicing is due to biophysical constraint precluding U1/U2 spliceosome assembly, which stalls in A-complexes (that bridge the 5'SS and branchpoint). Substitution of deleted nucleotides with non-specific sequences restores spliceosome assembly and normal splicing, arguing against loss of an intronic element as the primary causal basis. Incremental lengthening of 5'SS-branchpoint length in our index EMD case subject defines 45-47 nt as the critical elongation enabling (inefficient) spliceosome assembly for EMD intron 5. The 5'SS-branchpoint space constraint mechanism, not currently factored by genomic informatics pipelines, is relevant to diagnosis and precision medicine across the breadth of Mendelian disorders and cancer genomics.
Assuntos
Íntrons , Splicing de RNA , Spliceossomos , Adolescente , Adulto , Fenômenos Biofísicos , Criança , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Hirschsprung's disease is characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. It is managed by excision of the aganglionic segment and anastomosis of the ganglionated bowel just above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies and/or full thickness biopsy on the antimesenteric border of the bowel to determine the level of pullthrough. The transition zone is described as being irregular, and hence a doughnut biopsy is recommended so that the complete circumference can be assessed. Herein, we described a child in whom there was a selective absence of ganglion cells in 30% of the circumference of the bowel along the mesenteric border for most of the transverse colon. This case defies the known concept of neural migration in an intramural and transmesenteric fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment.
Assuntos
Colestase/etiologia , Testes Genéticos/métodos , Icterícia Idiopática Crônica/diagnóstico , Icterícia Idiopática Crônica/genética , Porfirinas/urina , Biópsia por Agulha , Colestase/diagnóstico , Colestase/genética , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Recém-Nascido , Hepatopatias , Testes de Função Hepática , Doenças Raras , Fatores de Tempo , UrináliseRESUMO
AIM: To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. METHODS: In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. RESULTS: The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. CONCLUSION: The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining.
Assuntos
Retardo do Crescimento Fetal/metabolismo , Fator de Crescimento Placentário/metabolismo , Placenta/diagnóstico por imagem , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Retardo do Crescimento Fetal/epidemiologia , Humanos , Imuno-Histoquímica , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
Pathogenic variants in mitochondrial aminoacyl-tRNA synthetases result in a broad range of mitochondrial respiratory chain disorders despite their shared role in mitochondrial protein synthesis. LARS2 encodes the mitochondrial leucyl-tRNA synthetase, which attaches leucine to its cognate tRNA. Sequence variants in LARS2 have previously been associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss (OMIM #615300). In this study, we report variants in LARS2 that are associated with a severe multisystem metabolic disorder. The proband was born prematurely with severe lactic acidosis, hydrops, and sideroblastic anemia. She had multisystem complications with hyaline membrane disease, impaired cardiac function, a coagulopathy, pulmonary hypertension, and progressive renal disease and succumbed at 5 days of age. Whole exome sequencing of patient DNA revealed compound heterozygous variants in LARS2 (c.1289C>T; p.Ala430Val and c.1565C>A; p.Thr522Asn). The c.1565C>A (p.Thr522Asn) LARS2 variant has previously been associated with Perrault syndrome and both identified variants are predicted to be damaging (SIFT, PolyPhen). Muscle and liver samples from the proband did not display marked mitochondrial respiratory chain enzyme deficiency. Immunoblotting of patient muscle and liver showed LARS2 levels were reduced in liver and complex I protein levels were reduced in patient muscle and liver. Aminoacylation assays revealed p.Ala430Val LARS2 had an 18-fold loss of catalytic efficiency and p.Thr522Asn a 9-fold loss compared to wild-type LARS2. We suggest that the identified LARS2 variants are responsible for the severe multisystem clinical phenotype seen in this baby and that mutations in LARS2 can result in variable phenotypes.
RESUMO
Congenital mesoblastic nephroma (CMN) is the most frequent renal neoplasm of newborns and young infants. Four cases presenting with hemorrhagic manifestations have been reported in the English literature (Hu et al, 2006; Bolande et al, 1967). We report the unusual clinical and radiographic findings of a 2-day-old neonate with hematuria secondary to a CMN. The first ultrasound was equivocal. Repeat ultrasound followed by magnetic resonance imaging confirmed the diagnosis. He underwent a right nephroureterectomy with histopathology revealing a cellular variant of CMN without classical translocation (t12:15). Neonates presenting with hematuria require close follow-up and serial imaging to rule out occult renal tumors. Classical translocation may not be demonstrable in all the cases.
Assuntos
Neoplasias Renais/congênito , Neoplasias Renais/diagnóstico , Nefroma Mesoblástico/congênito , Nefroma Mesoblástico/diagnóstico , Hematúria/etiologia , Humanos , Recém-Nascido , Neoplasias Renais/complicações , Masculino , Nefroma Mesoblástico/complicaçõesRESUMO
BACKGROUND: The Northern Territory has the highest rates of perinatal morbidity and mortality in Australia. Placental histopathology has not been studied in this high-risk group of women. METHODS: This is the first study to detail the placental pathology in Indigenous women and to compare the findings with non-Indigenous women in the Northern Territory. There were a total of 269 deliveries during a three-month period from the 27(th) of June to the 27(th) of August 2009. Seventy-one (71%) percent of all placentas were examined macroscopically, sectioned then reviewed by a Perinatal Pathologist, blinded to the maternal history and outcomes. RESULTS: Indigenous women were found to have higher rates of histologically confirmed chorioamnionitis and or a fetal inflammatory response compared with non-Indigenous women (46% versus 26%; OR 2.4, 95% CI 1.3-4.5). In contrast, non-Indigenous women were twice as likely to show vascular related pathology (31% versus 14%; OR 2.77, 95% CI 1.3-5.9). Indigenous women had significantly higher rates of potentially modifiable risk factors for placental inflammation including genitourinary infections, anaemia and smoking. After adjusting for confounders, histological chorioamnionitis and fetal inflammatory response was significantly associated with rural or remote residence (Adjusted OR 2.5, 95% CI 1.08 - 5.8). CONCLUSION: This study has revealed a complex aetiology underlying a high prevalence of placental inflammation in the Northern Territory. Placental inflammation is associated with rural and remote residence, which may represent greater impact of systemic disadvantage, particularly affecting Indigenous women in the Northern Territory.
Assuntos
Corioamnionite/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Placenta/patologia , População Branca/estatística & dados numéricos , Adulto , Anemia/epidemiologia , Anemia/etnologia , Corioamnionite/epidemiologia , Corioamnionite/patologia , Estudos de Coortes , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Northern Territory/epidemiologia , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/etnologia , Prevalência , Infecções do Sistema Genital/epidemiologia , Infecções do Sistema Genital/etnologia , Fatores de Risco , População Rural/estatística & dados numéricos , Fumar/epidemiologia , Fumar/etnologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etnologia , Adulto JovemRESUMO
We report the case of an 8-year-old boy with pyridoxamine 5'-phosphate oxidase (PNPO) deficiency. He developed seizures at 24 h of age that were refractory to standard anticonvulsant therapy and a trial of pyridoxine but responded to pyridoxal phosphate (PLP) at 28 days of life. Genetic testing identified compound heterozygous mutations in the PNPO gene. Management of encephalopathic episodes required escalation of PLP dose to 100 mg/kg/day by 2 years of age. Routine blood tests at this time showed significantly deranged liver function tests (LFTs). A wedge liver biopsy showed early cirrhosis with marked elevation of pyridoxal and pyridoxic acid levels in the liver sample. Despite extensive investigation, no cause other than PLP therapy could be identified for the cirrhosis. The PLP dose was weaned to 50 mg/kg/day before episodes of encephalopathy recurred. Concurrent with the reduction of his PLP dose, LFTs showed improvement. However, at 8 years of age, there is persistent evidence of hepatic fibrosis and early portal hypertension. We hypothesise that hepatic toxicity due to PLP or its degradation products is the cause of cirrhosis in this boy. Until further evidence becomes available, we would suggest that people with PNPO deficiency are treated with the minimum dose of PLP required to prevent episodes of encephalopathy.
RESUMO
An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development.
Assuntos
Variações do Número de Cópias de DNA , Metilação de DNA , Síndrome da Persistência do Padrão de Circulação Fetal/genética , RNA Longo não Codificante/genética , Cromatina/metabolismo , Cromossomos Humanos Par 16/genética , Ilhas de CpG , Elementos Facilitadores Genéticos , Evolução Fatal , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Impressão Genômica , Células HEK293 , Humanos , Recém-Nascido , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas Nucleares/metabolismo , Síndrome da Persistência do Padrão de Circulação Fetal/diagnóstico , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , Deleção de Sequência , Transcrição Gênica , Proteína Gli2 com Dedos de ZincoRESUMO
Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (pâ=â0.001 and pâ=â0.007), which was not observed in placentae infected with other microorganisms (pâ=â0.62 and pâ=â0.71) (nâ=â7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (pâ=â0.0003 and p<0.0001) (nâ=â25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (pâ=â0.0001 and pâ=â0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury.
Assuntos
Quimiocina CCL2/metabolismo , Infecções por Citomegalovirus/metabolismo , Citomegalovirus/imunologia , Placenta/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Natimorto , Fator de Necrose Tumoral alfa/metabolismo , Células Cultivadas , Quimiocina CCL2/genética , Citocinas/metabolismo , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/virologia , Feminino , Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Técnicas de Cultura de Tecidos , Trofoblastos/virologia , Fator de Necrose Tumoral alfa/genética , Regulação para Cima , Replicação ViralRESUMO
BACKGROUND: Types II and III pleuropulmonary blastoma (PPB) are aggressive sarcomas of lung and pleura in young children. Similar to cavoatrial extension of Wilms tumor, PPB may extend into thoracic great vessels and the heart and may involve both venous and arterial circulations and right and left cardiac chambers. Serious embolic complications occur. PROCEDURE: Review International PPB Registry databases and literature (1) for PPB cases with vascular/cardiac extension and (2) for neoadjuvant chemotherapy results in vascular extension cases. RESULTS: Among 179 Registry-confirmed and approximately 200 literature Type II and III PPB cases, 11 examples (approximately 3%) of great vessel/cardiac extension were identified; 1 case is presented in detail. Nine cases involved the left circulation, one the right and one both. Various radiographic techniques including echography, computed tomography and gated magnetic resonance imaging identified vascular tumor. Seven children had arterial embolic events: cerebrovascular accidents (six, including one femoral artery occlusion) and acute aortic occlusion (1). Six of these seven died from complications that may be attributed to vascular involvement. In three of four children with vascular involvement, neoadjuvant chemotherapy lessened the involvement; in one the effect could not be assessed. None of these four had embolic events. Effect on survival could not be assessed due to small numbers. CONCLUSIONS: Involvement of thoracic great vessels and the heart is a serious complication of PPB, with fatal embolic complications possible. Radiographic evaluation of the central circulation should be performed in children with suspected or diagnosed PPB to identify this complication.
Assuntos
Neoplasias Cardíacas/patologia , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias Vasculares/patologia , Pré-Escolar , Feminino , Humanos , Miocárdio/patologia , Invasividade Neoplásica , Artéria Pulmonar/patologia , Blastoma Pulmonar/patologia , Veias Pulmonares/patologia , Veias Cavas/patologiaAssuntos
Sequestro Broncopulmonar/diagnóstico por imagem , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico por imagem , Radiografia Abdominal , Sequestro Broncopulmonar/complicações , Sequestro Broncopulmonar/cirurgia , Malformação Adenomatoide Cística Congênita do Pulmão/complicações , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Humanos , Recém-Nascido , Masculino , Ultrassonografia Pré-NatalRESUMO
Desmoid-type fibromatosis, aggressive fibromatosis, or desmoid tumor is an uncommon benign but locally aggressive fibroblastic lesion. Although intraabdominal desmoid-type fibromatoses are well described in association with adenomatous polyposis syndrome, their occurrence along the neuraxis is extremely rare. The authors report the case of a 14-year-old boy with metachronous intracranial and spinal desmoid-type fibromatoses with preceding medulloblastoma. He was ultimately diagnosed with adenomatous polyposis syndrome. This is the first reported case of spinal desmoid-type fibromatosis in association with adenomatous polyposis syndrome. The identification of an underlying genetic instability allows for screening to detect lesions and institute measures to avoid preventable mortality from nonneurological tumors.
Assuntos
Polipose Adenomatosa do Colo/patologia , Neoplasias do Ventrículo Cerebral/patologia , Fibromatose Agressiva/patologia , Genes APC , Neoplasias Primárias Múltiplas/patologia , Polipose Adenomatosa do Colo/genética , Adolescente , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Neoplasias do Ventrículo Cerebral/genética , Saúde da Família , Fibromatose Agressiva/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/genética , Meduloblastoma/patologia , Neoplasias Primárias Múltiplas/genética , LinhagemRESUMO
We present three cases of pleuropulmonary blastoma (PPB) in Australian children. Each had a family history of childhood tumors which collectively included PPB, infant lung cyst, cystic nephroma, medullo-epithelioma and a Sertoli-Leydig ovarian tumor. Two of the patients also had additional malignancies: a concurrent bladder rhabdomyosarcoma and a post therapy non-PPB malignant lung tumor. In two cases, the family histories were elicited years after the PPB diagnosis. Archived pathology material allowed revision of pathologic diagnoses from decades earlier. These cases illustrate the importance of detailed inquiry into family medical history and the pleiotropy of the PPB-related familial cancer predisposition syndrome, which appears to result from heterozygous DICER1 mutations.
Assuntos
Neoplasias Pulmonares/genética , Neoplasias Primárias Múltiplas/genética , Neoplasias Pleurais/genética , Blastoma Pulmonar/genética , Austrália , Pré-Escolar , Feminino , Humanos , Lactente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/patologiaRESUMO
BACKGROUND: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare, locally aggressive vascular tumors. Although currently classified as separate entities, they are becoming increasingly recognized as a spectrum of the same pathology. There is a well-recognized association with Kasabach-Merritt phenomenon KHE and TA are considered neoplasms of intermediate malignancy because of infiltrative growth, local aggressiveness, and variable prognosis. To date, definitive treatment for these vascular tumors has had limited success. AIM: To evaluate the safety, efficacy, and role of vincristine in the treatment of KHE and TA. METHODS: Case review of patient files and pathology reports at The Children's Hospital at Westmead from 1995 to 2009. RESULTS: Twelve cases with KHE or TA were identified. Seven cases were treated with vincristine. The survival rate in the vincristine group was 100%. Mean age of diagnosis was 30 months (range birth to 9 y). 6 patients were female (85.7%). Mean time of the follow-up was 4 years (range 4 mo to 8 y). Out of the 7 cases treated with vincristine, 3 patients had associated Kasabach-Merritt phenomenon (43%). Complete resolution, regression in size, and improvement in analgesia were found in 1 case (14%), 3 cases (43%) and 2 cases (29%), respectively. Vincristine related side effects occurred in 2 cases (29%). CONCLUSIONS: Vincristine is an effective treatment option for KHE/TA. It is associated with a low side effect profile and should be considered as the first-line agent.
Assuntos
Antineoplásicos/uso terapêutico , Hemangioendotelioma/tratamento farmacológico , Hemangioma/tratamento farmacológico , Vincristina/uso terapêutico , Criança , Pré-Escolar , Feminino , Hemangioendotelioma/mortalidade , Hemangioendotelioma/patologia , Hemangioma/mortalidade , Hemangioma/patologia , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Mutations in dynamin-2 (DNM2) cause autosomal dominant centronuclear myopathy (CNM). We report a series of 12 patients from eight families with CNM in whom we have identified a number of novel features that expand the reported clinicopathological phenotype. We identified two novel and five recurrent missense mutations in DNM2. Early clues to the diagnosis include relative weakness of neck flexors, external ophthalmoplegia and ptosis, although these are not present in all patients. Pes cavus was present in two patients, and in another two members of one family there was mild slowing of nerve conduction velocities. Whole-body MRI examination in two children and one adult revealed a similar pattern of involvement of selective muscles in head (lateral pterygoids), neck (extensors), trunk (paraspinal) and upper limbs (deep muscles of forearm). Findings in lower limbs and pelvic region were similar to that previously reported in adults with DNM2 mutations. Two patients presented with dystrophic changes as the predominant pathological feature on muscle biopsies; one of whom had a moderately raised creatine kinase, and both patients were initially diagnosed as congenital muscular dystrophy. DNM2 mutation analysis should be considered in patients with a suggestive clinical phenotype despite atypical histopathology, and MRI findings can be used to guide genetic testing. Subtle neuropathic features in some patients suggest an overlap with the DNM2 neuropathy phenotype. Missense mutations in the C-terminal region of the PH domain appear to be associated with a more severe clinical phenotype evident from infancy.
Assuntos
Dinamina II/genética , Predisposição Genética para Doença/genética , Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Deformidades do Pé/genética , Deformidades do Pé/patologia , Marcadores Genéticos/genética , Testes Genéticos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Mutação de Sentido Incorreto/genética , Miopatias Congênitas Estruturais/fisiopatologia , Condução Nervosa/genética , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fenótipo , Estrutura Terciária de Proteína/genéticaRESUMO
INTRODUCTION/BACKGROUND: Ectopic nephrogenic rests (ENR) are rare. The incidental discovery of these lesions in children has particular clinicosurgical implications, especially given the association between ENR and the development of extrarenal Wilms' tumors (ERWT). METHODOLOGY: We reviewed the hospital records of patients with ERWT and ENR treated at our hospital over a 10-year period to identify those patients with histopathologically confirmed ENR and/or ERWT. RESULTS: Ninety-five children with Wilms' tumor (WT) were identified, but only 1 case of ENR and ERWT. This patient was a 14-month-old boy who was incidentally found to have a mass in the left inguinal canal during orchiopexy. After histology, a provisional diagnosis of ENR was made. Six months later, the child went on to develop an ERWT at the same site. Periodic postsurgical follow-up has been uneventful. DISCUSSION AND CONCLUSIONS: This was the only case of ENR and ERWT in child in a 10-year review of patients with WT at our hospital. Our experience stresses the importance of including ENR in any working differential diagnosis of unexpected masses in the inguinal canal in children and underscores why careful long-term follow-up is mandatory. The reasons for the malignant transformation of ENR into primary ERWT are unknown, but our experience lends support for the theory that ENR are precursor lesions to the development of WT even in ectopic sites. The case also provides an example of the kind of technical difficulties presented by paratesticular masses during laparoscopy.