RESUMO
The authors report the diagnosis and surgical treatment of 5 patients with dilated phase of hypertrophic cardiomyopathy (HCM). Features of these patients are progressive heart failure, double-level blood flow obstruction and the risk of apical aneurysms. Reconstructive remodeling surgery is a reasonable alternative to heart transplantation despite the existing risk.
Assuntos
Cardiomiopatia Hipertrófica , Transplante de Coração , Procedimentos de Cirurgia Plástica , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/cirurgia , Transplante de Coração/efeitos adversos , Hemodinâmica , HumanosRESUMO
Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and enables accurate recurrence risk counselling for the family. Here we used genomic sequencing to identify the causative genetic variant(s) in families with children affected by severe DCM. In an international collaborative effort facilitated by GeneMatcher, biallelic variants in PPP1R13L were identified in seven children with severe DCM from five unrelated families following exome or genome sequencing and inheritance-based variant filtering. PPP1R13L encodes inhibitor of apoptosis-stimulating protein of p53 protein (iASPP). In addition to roles in apoptosis, iASPP acts as a regulator of desmosomes and has been implicated in inflammatory pathways. DCM presented early (mean: 2 years 10 months; range: 3 months-9 years) and was progressive, resulting in death (n = 3) or transplant (n = 3), with one child currently awaiting transplant. Genomic sequencing technologies are valuable for the identification of novel and emerging candidate genes. Biallelic variants in PPP1R13L were previously reported in a single consanguineous family with paediatric DCM. The identification here of a further five families now provides sufficient evidence to support a robust gene-disease association between PPP1R13L and severe paediatric DCM. The PPP1R13L gene should be included in panel-based genetic testing for paediatric DCM.
Assuntos
Cardiomiopatia Dilatada/genética , Predisposição Genética para Doença , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pediatria , Proteínas Repressoras/genética , Alelos , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/terapia , Criança , Pré-Escolar , Exoma/genética , Feminino , Testes Genéticos , Humanos , Lactente , Masculino , LinhagemRESUMO
The paper describes 2 cases of immature ovarian teratoma with elements of nephroblastoma (ICD-0 code 9080/3) in patients aged 61 and 70 years. Microscopic examination revealed that both cases had blastemal cells with scant cytoplasm and basophil nuclei sticking together. Epidermal, glandular, rhabdomyoblastic, chondroid, bone, neuroectodermal, and histiocytic components were determined. Papillary and glomeruloid structures and primitive tubules were immured in the sarcomatous stroma. Immunohistochemical studies showed a strong reaction with Wilms tumor 1 (WT1), paired box gene (PAX-2), cytokeratin 7, desmin, smooth muscle actin, and α-1 antitrypsin. The recurrent tumors displayed a 1.8- to 6.1-fold increase in the level of p53. At the same time, the molecular genetic study revealed p53 gene mutation. In both cases, serous ovarian cystadenocarcinoma was misdiagnosed, ineffective chemotherapy was performed, and a recurrence occurred. The literature review revealed only 8 such cases.
Assuntos
Neoplasias Renais/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Tumor de Wilms/patologia , Idoso , Feminino , Humanos , Neoplasias Renais/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Teratoma/genética , Tumor de Wilms/genéticaRESUMO
The paper describes a case of chromophobe renal cell carcinoma growing into the muscular layer of the descending colon and with metastases in 4 lymph nodes of paranephral tissue in a 66-year-old woman. The tumor had a zonal structure with an alternation of epithelioid and sarcomatoid structural sites and with the signs of grades I, II and III according to the grading system by Paner and et al. (2010). The sarcomatoid renal component occupied about 70.0% of the tumor. There was a pronounced immunohistochemical reaction with VEGF-A (5 scores), a high Ki-67 proliferation index (70%), and a large number of tumor cells with nuclear p53 expression (85%) in the areas with minimal differentiation and sarcomatoid elements (Grade III). These signs can serve as criteria for the aggressive behavior of the tumor. A large volume of the sarcomatoid carcinoma component and a strong reaction with VEGF-A are indications for targeted therapy with anti-VEGF drugs.
Assuntos
Carcinoma de Células Renais/genética , Antígeno Ki-67/genética , Proteína Supressora de Tumor p53/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Diferenciação Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Terapia de Alvo MolecularRESUMO
The paper describes a case of eosinophilic granuloma of the parietal bone in a 32-year-old man. Histological examination revealed a large number of bean-shaped Langerhans cell histiocytes with lobed nuclei and nuclear grooves. The histiocytes alternated with the foci of obvious eosinophilic infiltration and with eosinophilic microabscesses. There were osteoclast-like multinucleated giant cells, bone resorption, and numerous bone rods covered with osteoblast chains. The histiocytes expressed CD1α, langerin, CD68, S100, and p53 (in 90.0% of the tumor cells). The Ki-67 proliferation index was 18.0%. A molecular genetic study identified BRAFV600E mutation (nucleotide substitution s.1799 T>A (p.V600E) in the heterozygous state). Clinical and morphological data and the results of molecular genetic studies led to the conclusion that there was eosinophilic granuloma of the right parietal bone (the unifocal form of Langerhans cell histiocytosis (LCH), type I, group A1, with the monoossal nature of lesion and with BRAFV600E mutation). In adults, this disease is extremely rare (2-5 cases of LCH per million people, bone loss in the fourth decade of life in 2.5% of the patients).
Assuntos
Granuloma Eosinófilo/patologia , Histiocitose de Células de Langerhans/patologia , Osso Parietal/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Granuloma Eosinófilo/diagnóstico , Granuloma Eosinófilo/diagnóstico por imagem , Granuloma Eosinófilo/genética , Histiócitos , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/genética , Humanos , Imuno-Histoquímica , Masculino , Mutação , Osso Parietal/diagnóstico por imagemRESUMO
BACKGROUND: The nosological nature of "idiopathic" arrhythmias and the effect of etiotropic and pathogenetic treatment are often unknown. METHODS AND RESULTS: 19 patients (42.6±11.3 years, 9 women) with atrial fibrillation (n = 16), supraventricular (n = 10) and ventricular (n = 4) premature beats, supraventricular (n = 2) and ventricular tachycardia (n = 1), left bundle branch block (n= 2), AV block (n = 2) without structural heart changes. Viruses were identified (polymerase chain reaction, PCR) along with measurement of anti-heart antibodies (AHA) and endomyocardial biopsy (EMB). EMB allowed to establish diagnosis in all patients: infectious-immune myocarditis (n = 11, parvovirus-positive in 1),parvovirus-positive endomyocarditis (n = 1),systemic (n = 2) and myocardial (n = 1) vasculitis,Fabry's disease (n = 1), arrhythmogenic right ventricular dysplasia (n = 1),unspecified genetic cardiomyopathy (n = 2, herpes virus 6 one positive). Level of AHA had the greatest significance for myocarditis diagnostics. All patients with myocarditis/vasculitis had background therapy: acyclovir (n = 10), IV immunoglobulin (n = 2), meloxicam (n = 12), hydroxychloroquine (n = 15), steroids (n = 14, 31.1±12.5 mg/day), azathioprine 150 mg/day (n = 2). Median follow-up was 4 years. Treatment significantly reduced the rate of arrhythmias (8 [5;8] to 3 [1.25;7.75] points); disappearance of bundle branch block was noted. CONCLUSION: EMB allowed to diagnose immune-mediated inflammatory diseases in 78.9% patients with 'idiopathic' arrhythmias and genetic diseases in 21.1%. Background therapy of myocarditis improved the antiarrhythmic efficiency, and allowed the best premed for interventional treatment.
RESUMO
BACKGROUND: Most of mutations in the LMNA gene are unique and have been found in only a few unrelated families. The clinical interpretation of new genetic variants, especially beyond the coding area and canonical splice sites, is proving to be difficult and requires advanced investigation. METHODS: This study included patients with progressive cardiac conduction defects with neuromuscular involvement. The clinical evaluation included medical history and 24-h Holter monitoring. The genetic evaluation included mutation screening in the LMNA gene by the Sanger sequence. Sanger sequencing was followed by RT-PCR of the target fragment of cDNA. In silico modeling was performed with CCBulder and Modeller software. RESULTS: The diagnosis of limb-girdle muscular dystrophy type 1B (LGMD1B) was established. The new intronic variant c.513+45T>G was found in the LMNA gene in the proband and affected daughter. The insertion of 45bp was confirmed in the proband's cDNA. The structural and possible functional effects of the aberrant protein were predicted. CONCLUSIONS: Variant c.513+45T>G in the LMNA gene likely translates into the longer lamin A/C proteins with additional 15 amino acids. This variant is thought to be pathogenic. Intronic variants in the LMNA gene located beside canonic splice sites may be responsible for some genotype-negative cases with clinical phenotype of laminopathies.
Assuntos
Síndrome de Brugada/genética , Lamina Tipo A/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação , Adulto , Síndrome de Brugada/etiologia , Doença do Sistema de Condução Cardíaco , Simulação por Computador , Creatina Quinase/sangue , Feminino , Humanos , Íntrons , Lamina Tipo A/metabolismo , Masculino , Distrofia Muscular do Cíngulo dos Membros/etiologia , Linhagem , Sítios de Splice de RNA , Splicing de RNARESUMO
The data of clinical, macro- and micrometric, histological, and immunohistochemical studies of the heart were analyzed in patients with left ventricular noncompaction (LVNC). Materials from 7 patients: 5 hearts of recipients after heart transplantation, one heart of a dead patient, and one endomyocardial biopsy specimen were investigated. The investigations showed that this disease was accompanied by a preponderance of a noncompact layer with its ratio to a compact layer (2.4:6.6) in the left ventricle and by myocardial hypertrophy and fibrosis in all cases, by endocardial fibroelastosis and discomplexation of muscle fibers by more than 15% of the specimen area in 6 of the 7 cases, by right ventricular hypertrabeculation and myocarditis in 5 cases, and by lipomatosis and impaired connexin 43 expression in 4 cases. Only one of the four patients was found to have MYH 7 gene mutation. The results of MRI of the extracted heart coincided with morphological findings in 100% of cases. The comparative study demonstrated that this disease had simultaneously morphological features of both LVNC and restrictive, hypertrophic, dilated cardiomyopathy. The findings may suggest that the LVNC phenotype may be formed under the influence of various modifying factors (hemodynamic and inflammatory ones).
Assuntos
Cardiomegalia/patologia , Ventrículos do Coração/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Adulto , Criança , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Myocardial crypts were initially described in patients with hypertrophic cardiomyopathy. Modern diagnostic data show that this structural abnormality can be found in patients with other diseases, or might represent the variant of normal heart development in healthy individuals. The prognostic significance of this finding is uncertain. In this publication we present a clinical case of the combination of myocardial crypt and Barlows syndrome.
Assuntos
Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/patologia , Ventrículos do Coração/patologia , Prolapso da Valva Mitral/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Patient P., 50 years old, male, with type I Brugada syndrome was examined. The patient had aborted sudden death event (2006) in his clinical history, ICD Gem III VR was implanted in 2006, ICDLumax DR was reimplanted in 2012. The patient had coved type pattern in right precordial ECG-leads. The p.E553X mutation in SCN5A gene, whish encodes the sodium channel α-subunit, was found. Noninvasive electrocardiographic mapping was performed. Significant changes of local unipolar electrograms including QRS fragmentation, ST segment elevation and late ventricular potentials were identified in the epicardium of the right ventricle outflow tract. Thus, the presented case demonstrates that noninvasive electrocardiographic mapping methodology allows to determine and visualize arrhythmogenic substrate in patients with inherited channelopathies.
Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Síndrome de Brugada/diagnóstico , Frequência Cardíaca/fisiologia , Síndrome de Brugada/fisiopatologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Patient P., 50 years old, male, with type I Brugada syndrome was examined. The patient had aborted sudden death event (2006) in his clinical history, ICD Gem III VR was implanted in 2006, ICDLumax DR was reimplanted in 2012. The patient had coved type pattern in right precordial ECG-leads. The p.E553X mutation in SCN5A gene, whish encodes the sodium channel -subunit, was found. Noninvasive electrocardiographic mapping was performed. Significant changes of local unipolar electrograms including QRS fragmentation, ST segment elevation and late ventricular potentials were identified in the epicardium of the right ventricle outflow tract. Thus, the presented case demonstrates that noninvasive electrocardiographic mapping methodology allows to determine and visualize arrhythmogenic substrate.
RESUMO
Mutations in LMNA gene produce a wide spectrum of disorders called laminopathies. In this article, the first cases of laminopathies from Russia are reported. In 10 unrelated families, 9 different mutations were identified: Asp47His, Gly232Arg, c.[781_783delAAG, 781insGTGGAGCAGTATAAGAAA], Arg249Gln (in two families), Arg377His, Arg541His, Ala350Pro, Leu52Pro, and Gly635Asp. Mutations Arg249Gln, Arg377His, and Arg541His were reported previously, others are novel. Four cases present de novo mutations, among them two cases with Arg249Gln are found. Because this mutation occurred de novo also in other reported cases, a mutational 'hot spot' was supposed. Three phenotypes were observed: autosomal dominant (AD) Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle MD type 1B, and AD dilated cardiomyopathy with conduction defect type 1A (DCM1A). Atypical clinical presentations were a very severe EDMD and an infantile DCM1A.