Improved prognosis for congenital nephrotic syndrome of the Finnish type in Irish families

Congenital nephrotic syndrome of the Finnish type is a rare autosomal recessive disease with a high infant mortality without aggressive treatment. The biochemical basis of the disease is not understood fully but the disease locus has been mapped recently to chromosome 19q12-q13.1 in Finnish families. This paper describes the clinical features and outcome of 20 patients in Ireland with congenital nephrotic syndrome of the Finnish type who have presented since 1980. Before 1987, all infants died by the age of 3 years. After the introduction of daily intravenous albumin infusion, nutritional support, elective bilateral nephrectomy, and renal transplantation, mortality in the past decade has fallen to 30%, with no deaths in the past five years. Genetic linkage analysis was performed in six families in whom DNA was available and the locus responsible was mapped to the same region on chromosome 19 as in Finnish families, suggesting that Irish families share the same disease locus.

Structure-Phenotype Correlations of Human CYP21A2 Mutations in Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH) is a family of autosomal recessive disorders involving impaired synthesis of cortisol from cholesterol by adrenal cortex. The predominant causes of the disorder are mutations in the CYP21A2 gene that encodes a Cytochrome P450 21-hydroxylase enzyme, which is central to steroidogenesis. The severity of the disease depends upon the extent of impaired enzymatic activity and can be classified under severe Classical form or the mild Non-Classical form, Molecular characterisation of CYP21A2 mutations can be used to predict clinical phenotype and disease severity based upon changes it brings in 21-hydroxylase enzyme structure. A humanized model of CYP21A2 has been used to map and investigate the structural role of all known disease-causing mutations. A structural explanation of clinical manifestation allows us to put forward criteria that might allow the prediction of clinical severity of the disease.

A sibling-controlled, prospective study of outcomes at home and school in children with severe congenital heart disease

Objectives: The objectives of this study were to compare behaviour problems and competencies, at home and school, in 7-year-old children with congenital heart disease with a sibling control group, to examine the prospective determinants of outcome from infancy, and to explore whether any gains were maintained in our sub-group of children who had participated in a previous trial of psychological interventions in infancy.
Methods: A total of 40 children who had undergone surgery to correct or palliate a significant congenital heart defect in infancy were compared (Child Behavior Checklist) with a nearest-age sibling control group (18 participants). Comparisons were made between sub-groups of children and families who had and had not participated in an early intervention trial.
Results: Problems with attention, thought and social problems, and limitations in activity and school competencies, were found in comparison with siblings. Teacher reports were consistent with parents, although problems were of a lower magnitude. Disease, surgical, and neurodevelopmental functioning in infancy were related to competence outcomes but not behaviour problems. The latter were mediated by family and maternal mental health profiles from infancy. Limited, but encouraging, gains were maintained in the sub-group that had participated in the early intervention programme.
Conclusions: The present study is strengthened by its longitudinal design, use of teacher informants, and sibling control group. The patterns of problems and limitations discerned, and differential determinants thereof, have clear implications for interventions. We consider these in the light of our previously reported intervention trial with this sample and current outcomes at the 7-year follow-up.

A Randomized Controlled Trial of Interventions to Promote Adjustment in Children With Congenital Heart Disease Entering School and Their Families

Objective: To report on a randomized controlled trial of psychological interventions to promote adjustment in children with congenital heart disease and their families.
Method: Following baseline assessment, 90 children (aged 4–5 years) and their families were randomly assigned to an Intervention or Control group before entering school. 68 (76%) were retained at 10-month follow-up.
Results: Gains were observed on measures of maternal mental health and family functioning. Although no differences were found on measures of child behavior at home or school, children in the intervention group were perceived as “sick” less often by their mother and missed fewer days from school. A regression model, using baseline measures as predictors, highlighted the importance of maternal mental health, worry and child neurodevelopmental functioning for child behavioral outcomes almost a year later.
Conclusions: The intervention promoted clinically significant gains for the child and family. The program is of generalizable significance.

Examination of the physical and psychosocial determinants of health behaviour in 4-5-year-old children with congenital cardiac disease

To assess the general health and activity levels of 4- and 5-year-old children after intervention for congenital cardiac disease.

A controlled trial of early interventions to promote maternal adjustment and development in infants born with severe congenital heart disease

Background: Congenital heart disease can have a negative impact on both infant development and maternal adjustment. This study considered the impact of a new programme of early psychosocial interventions on such outcomes, following the birth of a child with severe congenital heart disease.
Methods: Seventy infants and their mothers were assigned to an intervention or control group based on order of presentation to the unit. Interventions aimed at bolstering mother–infant transactions, through psychoeducation, parent skills training and narrative therapy techniques were implemented.
Results: Clinically and statistically signi?cant gains were observed at 6-month follow-up on the mental (but not the psychomotor) scale of the Bayleys-II. Positive gains were also manifested on feeding practices, maternal anxiety, worry and appraisal of their situation.
Conclusions: A programme of generalizable psychosocial interventions is shown to have a positive impact on the infant with severe congenital heart disease and the mother.

Determinants of neuropsychological and behavioural outcomes in early childhood survivors of congenital heart disease

To evaluate the relative effect of cyanosis, surgical interventions and family processes on neuropsychological and behavioural outcomes in 4-year-old survivors of serious congenital heart disease (CHD).

Predictors of psychological functioning in mothers and fathers of infants born with severe congenital heart disease

This study examined mental health and coping styles in both mothers and fathers of infants born with a severe congenital heart defect. Factors associated with mental health outcomes were elucidated. Parents of 70 infants, recently born with a severe congenital heart defect, completed questionnaires which examined psychological functioning and coping strategies. Disease, surgical and psychosocial factors were examined for their significance in predicting psychological functioning. Findings indicated elevated levels of clinically significant psychological distress in mothers, compared to fathers, and differences between parents in coping styles. Regression analyses suggested that the extent of distress in both parents was not primarily predicted by illness or demographic factors. Rather, certain coping styles, knowledge, subjective worry and family functioning emerged as significant predictive variables. Implications for early intervention are discussed.

Diagnosis and management of congenital and idiopathic erythrocytosis

An erythrocytosis occurs when there is an increased red-cell mass. The causes of erythrocytosis are divided into primary, when there is an intrinsic defect in the erythroid cell, and secondary, when the cause is extrinsic to the erythroid cell. An idiopathic erythrocytosis occurs when the increased red-cell mass has no identifiable cause. Primary and secondary defects can be further classified as either congenital or acquired causes. The diagnostic pathway starts with a careful history and examination followed by measurement of the erythropoietin (EPO) levels. This allows a division of those patients with a low EPO level, who can then be investigated for primary causes of erythrocytosis, and those with a normal or high EPO level, where the oxygen-sensing pathway needs to be explored further. Physiological studies in those with congenital defects in the oxygen-sensing pathway show many changes in the downstream metabolism adapting to the defect, which has a bearing on the management of the disorders. Low-dose aspirin and venesection to an achievable target are the main therapeutic options that can be considered in the management of erythrocytosis. Specific guidance on venesection options should be considered with certain causes such as high oxygen-affinity hemoglobins.

Exercise training improves activity in adolescents with congenital heart disease

To ascertain if motivational techniques and a structured exercise programme can increase activity in adolescents afflicted with congenital heart disease (CHD).