Congenital Heart Defects and Dysmorphic Facial Features in Patients Suspicious of 22q11.2 Deletion Syndrome in Southern Brazil.

22q11.2 deletion syndrome (22q11.2DS) is considered one of the most frequently observed chromosomal abnormalities in association with congenital heart disease (CHD), which can also include some combination of other features. Thus, the aim of this work was to verify the profile of dysmorphic features and heart defects found in patients referred to a reference center in Southern Brazil with clinical findings suggestive of 22q11.2DS. In the overall sample group, only patients with dysmorphic facial features (skull, eyes, ear, and nose) associated with CHD (obstructive pulmonary valve ring, truncus arteriosus, and bicuspid aortic valve associated with atrial septal defect and/or right aortic arch) had a 22q11.2 deletion. These findings proved to be reliable clinical criteria for referral to perform fluorescent in situ hybridization investigation for 22q11.2 deletion.

Cytogenomic Evaluation of Subjects with Syndromic and Nonsyndromic Conotruncal Heart Defects.

Despite considerable advances in the detection of genomic abnormalities in congenital heart disease (CHD), the etiology of CHD remains largely unknown. CHD is the most common birth defect and is a major cause of infant morbidity and mortality, and conotruncal defects constitute 20% of all CHD cases. We used array comparative genomic hybridization (array-CGH) to retrospectively study 60 subjects with conotruncal defects and identify genomic imbalances. The DNA copy number variations (CNVs) detected were matched with data from genomic databases, and their clinical significance was evaluated. We found that 38.3% (23/60) of CHD cases possessed genomic imbalances. In 8.3% (5/60) of these cases, the imbalances were causal or potentially causal CNVs; in 8.3% (5/60), unclassified CNVs were identified; and in 21.6% (13/60), common variants were detected. Although the interpretation of the results must be refined and there is not yet a consensus regarding the types of CHD cases in which array-CGH should be used as a first-line test, the identification of these CNVs can assist in the evaluation and management of CHD. The results of such studies emphasize the growing importance of the use of genome-wide assays in subjects with CHD to increase the number of genomic data sets associated with this condition.

Molecular screening for 22Q11.2 deletion syndrome in patients with congenital heart disease.

Few studies have investigated the prevalence of 22q11.2 deletion syndrome (22q11.2DS) among patients with isolated heart defects or nonconotruncal heart defects. Polymerase chain reaction (PCR) followed by length polymorphism restriction fragment analysis (RFLP) is useful for low-cost molecular diagnosis and screening. This cross-sectional study included 392 patients with congenital heart disease, described clinical features, and performed PCR-RFLP for analysis of polymorphism in three loci with a high heterozygosity rate located in the typically deleted region of 1.5 megabases. Heterozygosity excluded 22q11.2DS. Patients with homozygosity for the three markers underwent multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) for the final diagnosis, estimating the prevalence of 22q11.2DS. The use of PCR-RFLP excluded 22q11.2DS in 81.6 % (n = 320) of 392 patients. Of the remaining 72 patients, 65 underwent MLPA, showing 22q11.2DS in five cases (prevalence, 1.27 %). Four of these five patients underwent FISH, confirming the MLPA results. All five patients with the deletion had heart diseases commonly found with 22q11.2DS (interrupted aortic arch, persistent truncus arteriosus, tetralogy of Fallot, and ventricular septal defect plus atrial septal defect). Two patients had congenital extracardiac anomaly (one with arched palate and micrognathia and one with hypertelorism). Three patients reported recurrent respiratory infections, and one patient reported hypocalcemia. All were underweight or short in stature for their age. This study contributed to showing the prevalence of 22q11.2DS in patients with any congenital heart disease, with or without other features of the syndrome. Patients with 22q11.2DS may not have all the major features of the syndrome, and those that are found may be due to the heart defect.

Congenital heart diseases in a reference service: clinical evolution and associated illnesses.

BACKGROUND: Several factors, which include prenatal diagnosis and availability of new therapeutic procedures, have contributed to change the profile of patients with congenital heart disease (CHD). Knowing these changes is important to a better health care. OBJECTIVES: Description of profile of patients with CHD in a reference service in the State of Rio Grande do Sul, Brazil. METHODS: It is a cross-sectional study including 684 patients with CHD in a service of pediatric cardiology from January 2007 to May 2008. We interviewed the patients (and/or their parents) and examined these patients (congenital malformations, anthropometric measures). Moreover, their charts were reviewed in order to detail heart diseases, procedures and echocardiography. RESULTS: Patients were from 16 days to 66 years old, 51.8% were female, and 93.7% were Caucasian. The mean age at diagnosis was 15.8 +/- 46.8 months. Ventricular septal defect, patent ductus arteriosus and Tetralogy of Fallot were the most prevalent CHD. 59.1% of examined patients, whose average age was 44.3 +/- 71.2 months, have been undergoing therapeutic procedures; 30.4% had congenital extracardiac malformations; and 12 patients had genetic syndrome. Regarding development, 46.6% had low weight and height gain, and 13.7% had neuropsychomotor delay. Furthermore, 18.4% had family history of congenital heart disease. CONCLUSIONS: Neuropsychomotor delay and low weight and height gain may be related to CHD. Establishing a profile of patients with CHD, who were treated at an institution of reference, may function as a basis in which health care of this population can be planed appropriately.

Cardiopatias congênitas em um serviço de referência: evolução clínica e doenças associadas / Congenital heart diseases in a reference service: clinical evolution and associated illnesses

FUNDAMENTO: Inúmeros fatores vêm contribuindo para a mudança do perfil do paciente com cardiopatia congênita (CC), incluindo o diagnóstico pré-natal e a disponibilidade de novos procedimentos terapêuticos. O conhecimento dessas mudanças é fundamental para um melhor atendimento. OBJETIVOS: Descrever o perfil dos pacientes com CC de um serviço de referência no Estado do Rio Grande do Sul, Brasil. MÉTODOS: Trata-se de um estudo transversal, com 684 pacientes portadores de CC, em um serviço de cardiologia pediátrica, de janeiro de 2007 a maio de 2008. Esses pacientes foram entrevistados (e/ou seus pais) e examinados (malformações congênitas, medidas antropométricas), além de terem seus prontuários revisados para mais detalhes sobre as cardiopatias, procedimentos e ecocardiografia. RESULTADOS: A idade dos pacientes variou de 16 dias a 66 anos, sendo 51,8 por cento do sexo feminino, com 93,7 por cento de brancos. A idade média determinada pelo diagnóstico foi de 15,8 ± 46,8 meses. As CC mais prevalentes foram a comunicação interventricular, a persistência do canal arterial e a Tetralogia de Fallot. Dos pacientes analisados, 59,1 por cento, com idade média de 44,3 ± 71,2 meses, realizaram algum procedimento terapêutico; 30,4 por cento tinham malformações congênitas extracardíacas; e 12 pacientes tinham síndrome genética comprovada. Quanto ao desenvolvimento, 46,6 por cento tiveram atraso ponderoestatural e 13,7 por cento atraso neuropsicomotor. Além disso, 18,4 por cento apresentaram história familiar de cardiopatia congênita. CONCLUSÕES: O atraso neuropsicomotor e o baixo ganho ponderoestatural podem estar associados às CC. Estabelecer um perfil dos pacientes com CC atendidos em uma instituição de referência pode servir como base para o planejamento adequado do atendimento desta população.

BACKGROUND: Several factors, which include prenatal diagnosis and availability of new therapeutic procedures, have contributed to change the profile of patients with congenital heart disease (CHD). Knowing these changes is important to a better health care. OBJECTIVES: Description of profile of patients with CHD in a reference service in the State of Rio Grande do Sul, Brazil. METHODS: It is a cross-sectional study including 684 patients with CHD in a service of pediatric cardiology from January 2007 to May 2008. We interviewed the patients (and/or their parents) and examined these patients (congenital malformations, anthropometric measures). Moreover, their charts were reviewed in order to detail heart diseases, procedures and echocardiography. RESULTS: Patients were from 16 days to 66 years old, 51.8 percent were female, and 93.7 percent were Caucasian. The mean age at diagnosis was 15.8 ± 46.8 months. Ventricular septal defect, patent ductus arteriosus and Tetralogy of Fallot were the most prevalent CHD. 59.1 percent of examined patients, whose average age was 44.3 ± 71.2 months, have been undergoing therapeutic procedures; 30.4 percent had congenital extracardiac malformations; and 12 patients had genetic syndrome. Regarding development, 46.6 percent had low weight and height gain, and 13.7 percent had neuropsychomotor delay. Furthermore, 18.4 percent had family history of congenital heart disease. CONCLUSIONS: Neuropsychomotor delay and low weight and height gain may be related to CHD. Establishing a profile of patients with CHD, who were treated at an institution of reference, may function as a basis in which health care of this population can be planed appropriately. (Arq Bras Cardiol 2010; 94(3):313-318)

Seis minutos de caminhada em hipertensão pulmonar associada a cardiopatias congênitas / Six minutes walking test in pulmonary hypertension related to congenital heart disease

Objetivo: Avaliar a utilidade do teste de seis minutos de caminhada em pacientes com hipertensão pulmonar associada a cardiopatias congênitas e validar um protocolo simples de capacidade física em pacientes em acompanhamento ambulatorial, para futuros estudos. Métodos: Dezesseis pacientes com hipertensão arterial pulmonar associada a cardiopatias congênitas e 18 indivíduos normais foram submetidos ao teste de seis minutos de caminhada, conforme padronização internacional, com monitorização da saturação periférica de oxigênio. Resultados: Todos os pacientes caminharam durante seis minutos. A média ± desvio-padrão da saturação de oxigênio (SaO2) no repouso foi de 94±5% no grupo dos pacientes e 99±1% nos controles. A queda média da SaO2 após o exercício foi de 6±8% nos pacientes e não apresentou variação nos controles (p<0,05). A distância percorrida pelos pacientes foi 386±85 metros e pelos controles, 602±50m (p<0,001). Os pacientes com insuficiência cardíaca classe III percorreram distância menor que os pacientes em classe funcional I e II, porém sem diferença estatística. A queda da saturação média de oxigênio foi maior quanto pior a classe funcional, também sem diferença estatística. A dispnéia referida pela escala de Borg (0-10) antes e após o teste esteve de acordo com a classificação funcional da NYHA estabelecida a partir da anamnese ambulatorial. Conclusões: O protocolo estudado foi adequado para mostrar diferenças na tolerância ao exercício entre os grupos. O teste de seis minutos de caminhada pode ser útil para o estudo de novas estratégias de tratamento e, eventualmente, poderia predizer morbidade e mortalidade

Objectives: To examine the utility of the six-minute walk test in patients with pulmonary hypertension related to congenital heart disease and to validate a simplified exercise protocol. Methods: Sixteen patients with pulmonary arterial hypertension associated to congenital heart disease and 18 normal subjects underwent a standardized six-minute walk test with monitoring of arterial oxygen saturation (SaO2). Results: All patients walked 6 minutes. The mean ± SD SaO2-rest was 94 ± 5% in patients and 99 ± 1% in controls. The mean SaO2-exercise decrease 6 ± 8% in patients and didn’t vary in controls (p <0.05). The mean ± distance walked was 386 ± 85 m in patients and 602 ± 50 m in normal subjects (p < 0.001). The patients classified in the NYHA III reach smaller distance than the patients in NYHA I and II, not statistic significant. The decrease of SaO2 was higher in the NYHA II and III, not significant too. The dispnea reported by the Borg scale before and after the test was in accordance with the clinical NYHA classification. Conclusions: The studied protocol was able to show differences in exercise capacity between both groups. The six-minute walk test might be useful for studying new treatment strategies

Cardiac surgery unmasks latent hypoparathyroidism in a child with the 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome is a developmental field defect of the third and fourth pharyngeal pouches characterized by a spectrum of thymic and parathyroid gland abnormalities and conotruncal cardiac defects. Latent hypoparathyroidism, defined as normocalcaemia at rest but reduced ability to secrete parathyroid hormone (PTH) in response to pharmacologically evoked hypocalcaemia, is found in 30-50% of people with this syndrome. Its natural history is unknown. We describe a 1.5 year-old girl with tetralogy of Fallot, normal calcium metabolism and few facial dysmorphic features who developed transient hypoparathyroidism in the postoperative period, which lasted months and waxed and waned during this observation period. The clinical picture led us to the diagnosis of 22q11.2 deletion syndrome.