The Hybrid Norwood (HN) is a relatively new first stage procedure for neonates with Hypoplastic Left Heart Syndrome (HLHS), in which a sustainable univentricular circulation is established in a less invasive manner than with the standard procedure. A computational multiscale model of such HLHS circulation following the HN procedure was used to obtain detailed hemodynamics. Implementation of a reverse-BT shunt (RBTS), a synthetic bypass from the main pulmonary to the innominate artery placed to counteract aortic arch stenosis, and its effects on local and global hemodynamics were studied. A synthetic and a 3D reconstructed, patient derived anatomy after the HN procedure were utilized, with varying degrees of distal arch obstruction, or stenosis, (nominal and 90% reduction in lumen) and varying RBTS diameters (3.0, 3.5, 4.0 mm). A closed lumped parameter model (LPM) for the peripheral or distal circulation coupled to a 3D Computational Fluid Dynamics (CFD) model that allows detailed description of the local hemodynamics was created for each anatomy. The implementation of the RBTS in any of the chosen diameters under severe stenosis resulted in a restoration of arterial perfusion to near-nominal levels. Shunt flow velocity, vorticity, and overall wall shear stress levels are inverse functions of shunt diameter, while shunt perfusion and systemic oxygen delivery correlates positively with diameter. No correlation of shunt diameter with helicity was recorded. In the setting of the hybrid Norwood circulation, our results suggest: (1) the 4.0mm RBTS may be more thrombogenic when implemented in the absence of severe arch stenosis and (2) the 3.0mm and 3.5mm RBTS may be a more suitable alternative, with preference to the latter since it provides similar hemodynamics at lower levels of wall shear stress.

Denna uppsats behandlar interaktioner i ett diskussionsforum på Familjeliv.se, där deltagarna är föräldrar eller blivande föräldrar till barn eller foster med ett medfött hjärtfel. Syftet med studien är att undersöka hur detta forum kan fungera som en kunskapsresurs och en plats där deltagarna förhandlar sig fram till gemensamma förståelser om till exempel hjärtfelsdiagnosen och livet med ett medfött hjärtfel. Genom analyser av dels de inledande presentationerna från deltagare som positionerar sig som nya, dels av de diskussioner som följer på dessa presentationer fokuserar studien legitimitet i två bemärkelser: legitimiteten i medlemskapet och legitimeringar i interaktionerna som ingår i kunskapsförhandlingen och bygger upp gemensamma förståelser. Resultaten från studien visar inledningsvis att det finns tydligt återkommande drag i presentationerna, något som tyder på att det finns sociala normer och överenskommelser för vilka forumet är till för, hur deltagandet är uppbyggt och vad som utgör ett legitimt medlemskap. Därefter visar analyserna av de efterföljande diskussionerna bland annat hur deltagarna tydligt orienterar sig kring vad som är legitimt att säga och på vilka grunder, där exempelvis det egna barnets diagnos och erfarenheterna från denna verkar vara avgörande. Detta skisserar ut en bild av forumets funktion och visar på en medvetenhet hos deltagarna vad gäller vad de kan bidra med i förhållande till vården. Analyserna visar även hur interaktionerna är uppenbart flerröstade och rymmer såväl professionell expertis, i form av rekontextualiserade samtal med vårdpersonal, som rekontextualiseringar av deltagarnas egna erfarenheter av hjärtfelen. Genomgående innebär forumet också ett jämförelsematerial där deltagarnas rekontextualiseringar tillsammans bygger en bild av hur saker och ting förhåller sig, som sedan kan appliceras på enskilda deltagares situation. Studien indikerar därmed att forumet kan fungera som en intern kunskapsbank. / This thesis investigates the interaction on an online discussion forum, where the participants are parents or expectant parents of children with congenital heart defects. The aim of the study is to shed light on how this forum can function as a source of knowledge and a place where joint understandings about for example the diagnosis and the life with this medical condition are negotiated in interaction. Analyzing both the initial presentations written by newcomers in the forum, and the discussions following these presentations, the study draws on the concept of legitimacy in two ways: the legitimacy in relation to the forum membership and the legitimations that are used to construct a shared understanding between the participants. The results from the study indicate that there are recurring patterns in the presentations written by new members when introducing themselves in the forum threads. This in turn suggests that there are social norms regarding which participants the forum is directed towards, how the participation is organized and what constitutes a legitimate membership in the community. In addition, a key result from the analysis of the interactions following these presentations is the participants’ navigation of what information is legitimate in which situation, where the own child’s diagnosis and type of heart defect is of great importance. This shows awareness among the participants regarding the nature of the forum’s contribution in relation to healthcare professionals. Furthermore, the analysis also shows how the interactions are strikingly multi-voiced, in that the participants through the discursive process of recontextualization make use of both previous conversations with doctors and other medical professionals, as well as their own experience of the children’s heart defects. The forum then serves as a comparison where these recontextualizations are used to negotiate a joint understanding, which subsequently can be applied to the participants’ individual storylines. The study therefore indicates that the forum can function as a resource of knowledge.

Transition of the cardiopulmonary circulation at birth requires functional closure of the ductus arteriosus (DA). The DA is an arterial shunt that is vital in the fetus for diverting the pulmonary circulation away from the uninflated lungs. Failure of the vessel to functionally close after birth is known as patent DA, which is the second most common congenital heart disease. Patent DA may seriously compromise neonatal health and current pharmacological treatments are often limited by serious complications or a significant failure rate, thereby increasing the necessity for surgical intervention. Recently, we were the first to show that genetic or pharmacological inactivation of cyclooxygenase (COX) -2 produces postnatal patent DA in mice. We also demonstrated that the DA expresses high levels of COX-2 during normal closure after birth, suggesting novel contractile actions of COX-2-dependent prostanoids in the DA. In humans, patent DA is more common in preterm infants than those born at full-term, however, mechanism(s) responsible for the reduced DA closure have not been identified. In the current studies, we examined COX-1 and COX-2 expression in the DA at multiple stages of gestation to determine whether alterations in the expression of these enzymes contribute to patent DA in preterm mice. Using real-time PCR, analysis of the time-course of COX-2 mRNA in the fetal mouse DA indicated that COX-2 expression significantly increased with advancing gestational age. The preterm (day 17.5) neonatal mouse DA showed attenuated COX-2 expression, as compared to the full-term (day 19.5) neonatal DA at 3 hours after birth. Furthermore, the DA of preterm neonatal mice showed incomplete closure after 3 hours of birth, a time-point when the DA of full-term neonates was completely remodeled. These data indicate a correlation between reduced DA closure and attenuated COX-2 expression. Additionally, COX-2 expression was significantly attenuated in the DA of mice deficient in the prostanoid receptor EP4, which also show a patent DA phenotype, suggesting the importance of this receptor for the induction of COX-2 required for DA closure. Overall, these studies suggest that attenuated expression of COX-2 may contribute to increased patent DA at preterm gestation.

A descriptive design was used in this study to describe the feeding behaviors (as defined by changes in body position) in infants with congestive heart failure secondary to congenital heart disease. In addition, short term physiologic changes associated with the behaviors were measured through the use of pulse oximetry and cardiorespiratory monitors. Nine infants were observed in this study as they were being fed by their nurses. The method chosen was naturalistic observation. Descriptive statistics were used to analyze the demographic data and the measured physiologic variables. A point by serial correlation was conducted to describe any relationships between the position changes and the measured physiologic variables. Statistically significant relationships were found between certain positions and oxygen saturation, heart rate and respiratory rate. The results indicate that infants do experience position changes that are accompanied by changes in physiologic variables during feeding. These position changes can be categorized as infant-mediated or nurse-mediated.

Background and aims: Many adults with congenitally malformed hearts are at risk for complications such as decreased function and capacity of the heart due to the heart defect and previously surgery. This advocates self-management behaviours related to medical treatments, physical activity, preventions of endocarditis, some restrictions regarding suitable employment and spare time activities, birth control and pregnancy, but also lifestyle concerns such as refraining from smoking and healthy eating. Sufficient knowledge and support are requirements for successful self-management. The overall aim of this thesis was to describe educational needs, develop a tool for assessing knowledge and to evaluate the effects of a follow-up model providing education and psychosocial support to adults with congenitally malformed hearts. Subjects and methods: Adults (≥18 years of age) with the ten most common heart defects namely ventricular septal defect, atrial septal defect, coarctation of the aortae, aortic valve stenosis (defined as uncomplicated heart defects) and tetralogy of Fallot, complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Ebstein anomaly and Eisenmenger syndrome (defined as complicated heart defects) were included in the studies. To apprehend the educational needs (I), sixteen adults with heart malformations, ranging from 19-55 years of age, were interviewed and data were analysed qualitatively using phenomenographic method. As a tool to evaluate knowledge, an instrument named Knowledge scale for adults with Congenital Malformed Hearts (KnoCoMH) was developed and psychometrically evaluated (II) in 19 + 114 adults with the ten most common heart defects average age 34 ± 13.5. A model for follow-up was described and initially evaluated (III) by 55 adults with the most common heart defects and finally tested in a randomised controlled trial (IV) with a total of 114 adults with congenitally malformed hearts (56 participants in intervention group and 58 in control group with average age 34 ± 13.5). The intervention group recived a model for follow-up with individualise and computer-based eduction and psychosocial support by a multidisciplinary team. Results: Two-way communication when given information was found to be crucial in order to enhance knowledge (I). Knowledge was seen as a tool for managing important areas in life. The KnoCoMH (II) was found to be a valid and reliable scale and can now be used to estimate knowledge in adults with congenitally malformed hearts. The model for follow-up (III) was effective in improving and maintaining knowledge (IV) about self-management in adults with heart malformation.

Orientador: José Paes de Oliveira Filho / Resumo: A doença de acúmulo de glicogênio tipo II (GSD-II) e a síndrome miastênica congênita (CMS) são enfermidades autossômicas recessivas importantes no gado Brahman. Nenhum estudo avaliou previamente a prevalência de mutações responsáveis pelo GSD II (E7, c.1057_1058delTA e E13, c.1783C> T) ou CMS (CHRNE, c.470del20) nos bovinos Brahman brasileiro. O objetivo deste estudo foi investigar a presença dessas mutações em 276 amostras de bulbos pilosos de bovinos PO brasileiros e em 35 amostras de sêmen de touros da raça Brahman, rotineiramente utilizadas em programas de melhoramento genético no Brasil. Dos 276 bovinos Brahman testados, 7,3% foram identificados como heterozigotos para E7. Enquanto, todos os bovinos Brahman estudados eram wild-type para E13. Para as amostras de sêmen foi identificado 8,6% (3/35) heterozigotos para a E7 e para a E13 nenhum animal foi identificado. A mutação CHRNE, 0,73% das amostras de bulbo piloso são heterozigotos, enquanto para as amostras de sêmen, nenhum animal foi considerado heterozigoto. Este resultado indica que as mutações E7 e CHRNE estão presentes no rebanho Brahman brasileiro, e medidas de controle devem ser adotadas para evitar um aumento na incidência de GSD-II e CMS no gado Brahman no Brasil. / Abstract: Glycogen storage disease type II (GSD-II) and congenital myasthenic syndrome (CMS) are important autosomal recessive disorders in Brahman cattle. No study has previously evaluated the prevalence of mutations responsible for GSD II (E7, c.1057_1058delTA; and E13, c.1783C>T) or CMS (CHRNE, c.470del20) in Brazilian Brahman cattle. The objective of this study was to investigate the presence of these mutations in 276 hair roots from purebred Brazilian Brahman cattle and in 35 semen samples from purebred Brahman bulls that were routinely used in breeding programmes in Brazil. Of the 276 Brahman cattle tested, 7.3% were identified as heterozygous for E7. All Brahman cattle studied were homozygous for the wild-type E13 allele. The E7 mutations was identified as heterozygous in 8.6% (3/35) of the commercial semen samples, whereas the E13 mutations was not identified. The CHRNE mutation was identified as heterozygous in 0.73% of the hair root samples, but this mutation was not present in any semen sample assessed. In summary, the E7 and CHRNE mutations are present in the Brazilian Brahman herd, and control measures should be adopted to prevent an increase in the incidence of GSD-II and CMS in Brahman cattle in Brazil. / Mestre

A hérnia diafragmática congênita (CDH) tem incidência de aproximadamente 1:2500 nascidos vivos e mortalidade de aproximadamente 70%. A hipertensão arteiral pulmonar é umas das principais complicações neonatais e pode levar à sobrecarga cardíaca. A principal estratégia de tratamento para os casos de grave hipoplasia pulmonar no período pré-natal é a traqueo-oclusão fetal (TO), no entanto, as consequências geradas ao tecido cardíaco são incertas, tanto na CDH quanto no tratamento com TO. Troponininas (cTnI e cTnT) são proteínas intracelulares miocárdicas utilizadas como indicativo de lesão cardiomiocítica. Portanto, nosso objetivo foi avaliar as alterações anatômicas, funcionais e bioquímicas dos ventrículos esquerdo (VE) e direito (VD) na CDH e CDHTO por meio das análises de ecocardiografia (ECO), histologia e bioquímica no modelo experimental de CDH. Para isso, foram utilizados neonatos de coelhos (n=10) divididos em três grupos: controle (C), hérnia diafragmática congênita (CDH), e hérnia diafragmática congênita + traqueo-oclusão (CDHTO). A cirurgia de CDH foi realizada no dia 25 da gestação (DG) da coelha (termo = 31 dias), e a TO no 27DG. A coleta foi realizada em 30DG, a ECO neonatal foi realizada imediatamente após retirada do útero e após o sacrifício os pulmões e coração foram coletados. A mortalidade da CDH fi de 20% e de CDHTO de 30%. Os resultados da ECO e da histologia mostraram hipoplasia de VE nos grupos CDH e CDHTO (*p<0,05), sendo que no VD, o grupo CDH apresentou dilatação e o grupo CDHTO apresentou hipoplasia. Na imunofluorescência (IF), western blotting (WB) e RT-qPCR houve aumento de cTnI no VD dos grupos CDH e CDHTO em relação à C (*p<0,05), sem alteração de expressão de cTnI no VE (NS); cTnT não apresentou alteração em ambos ventrículos (NS). Concluímos que as alterações cardíacas em CDH e CDHTO podem ser verificadas logo após o nascimento e há associação das alterações ecocardiográficas, histométricas e bioquímicas, como a hipoplasia de VE e dilatação de VD associada ao aumento tecidual de cTnI no VD no grupo CDH, indicando sofrimento cardíaco ainda no período fetal. Além disso, a realização do tratamento fetal pela TO no grupo CDH (CDHTO) não apresentou melhora das alterações do comprometimento do miocárdio. / Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1: 2500 live births and a mortality rate of approximately 70%. Pulmonary hypertension is one of the major neonatal complications and can lead to cardiac overload. The main treatment strategy for cases of severe prenatal pulmonary hypoplasia is fetal tracheal occlusion (TO), however, the consequences in the cardiac tissue are uncertain, in both the CDH and the TO treatment. cTnI and cTnT are myocardial intracellular proteins used as an indicative of cardiomyocyte injury that could be measured in neonates with CDH. Therefore, our aim was to evaluate the anatomical, functional and biochemical alterations in the left ventricle (LV) and in the right ventricle (RV) of neonates with CDH and CDHTO through echocardiography (ECO), histology and biochemistry analysis in the experimental rabbit CDH model. Neonates of rabbits (n = 10) were divided into three groups: C (control), CDH (congenital diaphragmatic hernia) and CDHTO (congenital diaphragmatic hernia + tracheal occlusion). CDH surgery was performed on day 25 of gestation (GD) of the rabbit (term = 31 days), and TO treatment on 27GD. The harvest was performed in 30GD, followed by neonatal ECO immediately after birth, then after sacrifice the lungs and heart were harvested. The mortality in the surgical groups was 20% CDH and 30% CDHTO. The ECO and histology results showed LV hypoplasia in the CDH and CDHTO (* p <0.05) groups. In the RV, the CDH group presented dilation and the CDHTO group presented hypoplasia. In the immunofluorescence (IF), western blotting (WB) and RTqPCR analysis there was an increase of cTnI in the RV of CDH and CDHTO groups in comparison with C group (* p<0.05), with no alteration of cTnI expression in the LV (NS). There was no difference of cTnT expression in both ventricles (NS). We conclude that cardiac alterations in CDH and CDHTO can be verified soon after birth, also there is an association of echocardiographic, histometric and biochemical alterations, such as LV hypoplasia and RV dilation with increased cTnI tissue expression in the RV of CDH group, indicating cardiac distress still in the fetal period. In addition, the performance of CDH fetal treatment by TO, (CDHTO) group, did not improve the myocardial detriment.

Introdução: As infecções virais respiratórias agudas são as doenças mais comuns em humanos e estão associadas a grande morbidade e mortalidade em crianças, principalmente menores de 2 anos de idade, sobretudo nos países em desenvolvimento e em idosos nos países desenvolvidos. As crianças que apresentam cardiopatias congênitas estão mais susceptíveis a adquirir infecção viral devido à sua mecânica pulmonar alterada, o que pode gerar diversas complicações tanto no período pré-operatório quanto no período pós-operatório, tais como aumento no tempo de internação hospitalar, maior tempo de ventilação mecânica e maiores taxas de mortalidade. Este estudo teve como objetivo identificar a epidemiologia das infecções virais respiratória em crianças com cardiopatia congênita e comparar os desfechos: tempo de internação, tempo de ventilação mecânica e mortalidade, na presença ou não de infecção viral respiratório e determinar qual o momento que essas crianças adquirem a infecção viral. Trata-se de estudo longitudinal, observacional, do tipo coorte. Foram coletadas amostras de secreção nasofaringe no período pré e pós operatório de todos os pacientes submetidos à cirurgia cardíaca e analisados os dados gerais dos pacientes durante o tempo de internação no centro de terapia intensiva pediátrica, por meio de prontuário médico, entre maio de 2013 a maio de 2014. Resultados: Foram analisados 43 pacientes. Foi encontrada elevada prevalência de vírus respiratórios (39%) em crianças com cardiopatia congênita. No presente estudo não houve diferença estatisticamente dos desfechos em relação a infecção viral respiratória no modelo estatístico bivariável, por motivo de interferência de variáveis confundidoras, idade e RACHS-1. A seguir, foram ajustados modelos de regressão multivariável, para analisar os desfechos com a variáveis idade, RACHS-1 e infecção viral. A variável infecção viral respiratória apresentou efeito estatisticamente significativo no desfecho diferença arteriovenosa de oxigênio, enquanto as covariáveis idade e RACHS-1 tiveram efeito significativamente em todos os desfechos pesquisados no estudo. Conclusão: A prevalência de infecção viral respiratória em crianças submetidas a cirurgia cardíaca é alta. A infecção viral respiratória não apresentou efeito sobre os principais desfechos, apenas na diferença arteriovenosa de oxigênio / Introduction: Acute respiratory viral infections are the most common diseases in humans and are associated with high morbidity and mortality in children, especially those under two years of age, particularly in developing countries, and in the elderly from developed countries. Children with congenital heart disease are more likely to get viral infections due to their altered lung mechanics, which can lead to several complications in both the preoperative and postoperative period, such as increased hospital stay, longer mechanical ventilation and higher mortality rates. This study aimed to identify the epidemiology of respiratory viral infections in children with congenital heart disease, to compare the outcomes: hospital stay, duration of mechanical ventilation and mortality, in the presence or absence of respiratory viral infection, and determine the time when these children acquire viral infection. This is a longitudinal, observational cohort study. Nasopharyngeal secretion samples were collected pre- and postoperatively for all patients undergoing cardiac surgery. General data of patients were obtained during hospital stay from medical records, from May 2013 to May 2014. Results: We enrolled 43 patients. We found a high prevalence of respiratory viruses (39%) in children with congenital heart disease. In this study there was no statistically significant difference in outcomes in relation to respiratory viral infection in bivariate statistical model, because of interference from confounding variables, age and RACHS-1. We then used multivariate regression models to analyze outcomes with respect to independent variables age, RACHS-1 and viral infection. Respiratory viral infection showed a statistically significant effect on the outcome arteriovenous oxygen difference, while the covariables age and RACHS-1 showed significant effects on all outcomes investigated in the study. Conclusion: The prevalence of respiratory viral infection in children undergoing cardiac surgery is high. Respiratory viral infection did not affect the outcome, just in arteriovenous oxygen difference

Este trabalho teve como objetivo compreender os efeitos psicológicos da cardiopatia congênita do irmão em crianças saudáveis. A análise da literatura revelou que pouca atenção tem sido dada a esse tema, ainda que se saiba que os irmãos sadios sofrem sentindo-se excluídos e isolados das relações familiares, bem como do tratamento de crianças com doenças crônicas. Foram avaliadas cinco crianças, com idades entre três e onze anos, cujos irmãos, no momento da coleta de dados, estavam internados para tratamento da cardiopatia congênita. A pesquisa foi realizada através de análise qualitativa com referencial psicanalítico de dados colhidos durante entrevista semidirigida com os pais e observação de hora lúdica com as crianças. Foram encontrados temas comuns na vivência desses irmãos saudáveis como alteração na rotina familiar, com acréscimo de responsabilidades e conhecimento e interesse a respeito da doença e tratamento do irmão. Os irmãos saudáveis manifestaram sentimentos preponderantemente de empatia e solidariedade para com a dor e desconforto da criança cardiopata, apresentando comportamentos de cuidado para com o irmão e a família e, de forma encoberta, ciúme e rivalidade. A hora lúdica teve um caráter, além de diagnóstico, interventivo para essas crianças. Atualmente a literatura aponta para a necessidade de intervenções com essa população. A partir dos resultados desta pesquisa, espera-se ter contribuído na produção de conhecimento sobre esses irmãos saudáveis e na criação de propostas para intervenções com o intuito de prevenir ou minimizar possíveis efeitos adversos do convívio com um irmão cardiopata / This study aimed to understand the psychological effects of congenital heart of siblings in healthy children. The literature review revealed that little attention has been paid to this issue, although it is known that the healthy siblings suffer from feeling excluded and isolated from family relationships and the treatment of children with chronic diseases. We evaluated five children, aged between three and eleven, whose siblings, at the time of data collection, were hospitalized for treatment of congenital heart disease. The research was conducted through qualitative analysis with psychoanalysis reference of semistructured interview with parents and observation play therapy hour with children. We found common themes in the experience of healthy siblings as change in family routine, with increased responsibilities and interest in and knowledge about the disease and treatment of their siblings. The healthy siblings predominantly expressed feelings of empathy and solidarity with the pain and discomfort of the child with heart disease, presenting behaviors of care for their siblings and family and, covertly, jealousy and rivalry. The play therapy hour had a interventional character for these children. Currently, the literature points to the need for interventions with this population. From the results of this research is expected to have contributed in knowledge about this healthy siblings and to create proposals for interventions in order to prevent or minimize possible adverse effects of living with a sibling with heart disease

Introdução: O hipotireoidismo congênito é a causa mais comum de retardo mental evitável em crianças, sua incidência varia de 1:2000 a 1:3000 nascidos vivos. É estimado que 15-20% dos casos de HC são conseqüentes de falhas na síntese dos hormônios tireoidianos. Entre as alterações genéticas mais freqüentes destaca-se o defeito na atividade da tireoperoxidase. Objetivos: rastrear mutações em duas pacientes com HC, com defeito parcial de incorporação de iodeto e verificar o efeito funcional de alterações do gene da tireperoxidase. Casuística e métodos: duas pacientes com HC, bócio e diagnóstico molecular não conhecido. Amostras de sangue periférico e de tecido tireoidiano das pacientes e amostras de DNA de indivíduos controles. Sequenciamento dos genes TPO, DUOX2 e DUOXA2. Análise da expressão gênica de TPO, TG, NKX2.1, PDS, PAX8, NIS e rTSH por PCR bem tempo real. Avaliação da expressão de luciferase sob controle do promotor da TPO e avaliação da atividaede da TPO do tecido as pacientes. Resultados: Nas pacientes foi identificada a alteração -95G>T, em homozigose, na região promotora da TPO. Verificamos diminuição da atividade enzimática da TPO no tecido tireoideano das pacientes e diminuição da expressão do RNAm desse gene. Também se encontrou diminuída a expressão dos genes NKX2.1 e PAX8. Já os genes TG, rTSH, PDS, NIS, a expressão do RNAm apresentou-se aumentada. A análise funcional da alteração -95G>C não mostrou diminuição da expressão do gene repórter. Conclusão: O HC das pacientes deve-se a diminuição da atividade enzimática da TPO, contudo alterações de sequência não foram encontradas no gene da TPO que expliquem a diminuição da atividade. Alterações epigenéticas ou nos introns no gene da TPO poderiam explicar o HC das pacientes. / Introduction: Congenital hypothyroidism is the most common cause of preventable mental retardation in children, its incidence varies from 1:2000 to 1:3000 live births. It is estimated that 15-20% of cases of CH are consistent failures in the synthesis of thyroid hormones. Among the most frequent genetic changes highlight the defect in the activity of thyroid peroxidase. Objectives: Identify mutations in two patients with CH and partial defect in iodide incorporation and verify the functional effect of changes in gene tireperoxidase. Methods: Two patients with CH, goiter and molecular diagnosis unknown. Samples of peripheral blood and thyroid tissue of patients and DNA samples from control subjects. Sequencing of the TPO gene, DUOX2 and DUOXA2. Analysis of gene expression of TPO, TG, NKX2.1, PDS, PAX8, NIS and TSHr by real time. Evaluation of the expression of luciferase under control of the promoter of TPO and TPO activity evaluation of the patients tissue. Results: The patients were identified change-95G> T homozygous, in the promoter region of TPO. We observed decrease in enzymatic activity of TPO in thyroid tissues of patients and decreased RNAm expression of this gene. Also found decreased expression of genes NKX2.1 and PAX8. Since the genes TG, TSHr, PDS, NIS mRNA expression presented increased. Functional analysis of the change -95G>T showed no descrease in reporter gene expression. Conclusion: The CH of patients due to decreased enzymatic activity of TPO, but changes were not found in the sequence of TPO gene to explain the decrease in activity. Epigenetic alterations in introns or in the TPO gene could explain the HC patients