This study sought to define the incidence of cardiac anomalies in first-degree relatives of Keywords: congenital heart disease, genetics, recurrence risk, aortic valve, coarctation, These values were compared with normal values, using a database .. Pomerance A. Pathogenesis of aortic stenosis and its relation to age. Define congenial. congenial synonyms, congenial pronunciation, congenial translation, English dictionary definition of congenial. adj. 1. Having the same tastes. Congenital hypothyroidism is inadequate thyroid hormone production of infants with goiter and hypothyroidism in a defined geographic area.
Twelve women who were followed in their 3rd pregnancies had all normal infants: One woman, followed up in 4 pregnancies, after the first child with TGA and who had another distant relative affected with an undefined CHD, delivered normal offspring in the subsequent pregnancies.
Table 2 shows in detail the total recurrence rates in the various subgroups of CHD present in the index cases, distinguishing the total rates, and those in siblings, offspring, and distant relatives.
Journal of Pregnancy
It is evident that the recurrence rates of different types of CHD varied between the categories of index cases i. A high recurrence rate of 8. Surprisingly, severe anomalies such as HLV and univentricular heart had in our series a low recurrence rate of 1. Concordance between index cases and affected fetuses is summarized in Table S1 available as a supplementary file. In 34 cases The type of recurrence could not be defined in 4 cases because of a nonspecific diagnosis of the cardiac anomaly in the index case.
Table 3 shows the relative risk ratios for specific cardiac defects as compared to the data of Moons et al. Relative risks ratios—comparison between our series and normal population Moons et al. Discussion Epidemiology and genetics of cardiac malformations have been an object of several studies over several last decades. In the population of nonsyndromic children, there was a recurrence of 4. Nora [ 1 ] introduced in the hypothesis of a multifactorial mode of inheritance of CHD in the majority of cases, suggesting that several loci could interact in association with environmental factors.
Subsequent studies of Burn et al. Higher recurrence rates in the offspring of mothers with CHD with and without surgical treatment of A positive family history of CHD is a frequent cause for the referral for prenatal cardiac investigation which led to the first study of the recurrence of CHD in the population of mothers referred for fetal echocardiography for a family history [ 13 ].
In a more recent large study in a similar population, Tynan et al. The present study included also the cases studied by fetal echocardiography because of a family history of CHD in either first degree or more distant relatives. We insisted on a final cardiologic examination of the child at least at 6 months of age or later, in order to detect even those smaller anomalies, that are difficult to visualize in the fetus [ 20 ].
Our results demonstrate a higher recurrence rate for CHD than do the above two fetal studies, with a total recurrence rate of 3. The recurrence rate would have been lower if we have had considered only cases diagnosed during fetal life 3. We felt it essential that we should consider as recurrent even the milder congenital heart lesions, such as small VSDs, discovered after birth that are often not detectable by fetal echocardiography as well as ASD that cannot usually be seen in the fetus, unless they are truly large.
Familial aggregation of congenital hydrocephalus in a nationwide cohort | Brain | Oxford Academic
The occurrence of these defects are important for the family that is usually very anxious after a previous experience with a cardiac problem and also for our own knowledge of the recurrence. As for the single categories of familial risk, the recurrence rate in our study was 3. Our recurrence rates for siblings and offspring correspond to those reported by Nora and Nora [ 3 ] and Rose et al. We found a difference between the recurrences in offspring of affected mothers and fathers.
On the whole, mothers with CHD are very likely to be more vulnerable to teratogens than fathers [ 8 ]. Frequency of CHD found among our affected fetuses corresponds to the figures reported in a large epidemiological study of Moons et al. Another recent study in Sweden, in contrast, reported a much lower prevalence of 2. These differences show how difficult it is to determine the correct prevalence and relative risk for CHD, very likely due to different assessment policies. Recurrence risk ratios of our series with familial history of CHD show high figures in comparison to the data of the study of Moons et al.
Lower ratios were found for the 2nd- and 3rd-degree relatives. Their study includes, however, also cases with associated chromosomal or extracardiac anomalies. Concordance of Congenital Heart Lesions Our results confirm a large variability in the recurrence of cardiac lesions, both in cases with multiple familial risk factors and in consecutive pregnancies, in agreement with other reports [ 813 ]. In our series we found a complete concordance of recurrent CHD in A higher concordance was reported by Corone et al.
We found also a case of recurrence of PS after the previous pulmonary atresia. Information on primary congenital hydrocephalus was obtained from the National Patient Discharge Register. Using binomial log-linear regression, we estimated recurrence risk ratios of congenital hydrocephalus.
The importance of adult sibling relationships
An alternative log-linear regression model was applied to quantify the genetic effect and the maternal effect. Of 1 live-born children, had a diagnosis of idiopathic congenital hydrocephalus 1. Of those, 75 3. Significantly increased recurrence risk ratios of primary congenital hydrocephalus were observed for same-sex twins, first- and second-degree relatives as follows: Recurrence risk ratio for third-degree relatives was 1.
A maternal component was supported by the facts that recurrence risk ratios for opposite-sex twins This population-based study found strong evidence of familial aggregation of primary congenital hydrocephalus, which supports the existence of a genetic component to the aetiology. In addition, the pattern of association suggests that a strong maternal component contributes to the familial aggregation. If left untreated, the condition leads to various degrees of cognitive impairment, cerebral palsy and visual deficits.Relational Database Concepts
In severe cases the condition is fatal. In developed countries, most patients undergo surgical treatment, but the long-term prognosis is highly variable Christensen et al. Very few environmental factors have consistently been associated with congenital hydrocephalus. Genetic factors may be involved in congenital hydrocephalus, although studies on this topic are also limited as reviewed elsewhere Zhang et al.
One human hydrocephalus gene has been identified so far and is located on the X-chromosome Kanemura et al. The affected gene L1CAM encodes L1 protein, which is a neuronal cell adhesion molecule essential for nervous system development and function.
The phenotype characteristics include congenital hydrocephalus due to aqueductal stenosis, adducted thumbs, agenesis or hypoplasia of corpus callosum and corticospinal tracts, mental retardation and spastic paraplegia. According to Zhang et al. This estimate is based on case reports and few observational studies among small populations comprising only congenital hydrocephalus cases with aqueductal stenosis and case reports Jansen, ; Halliday et al.
Hence, the proportion of X-linked hydrocephalus among all types of primary congenital hydrocephalus cases is rather uncertain. This estimate is based on three publications from Bay et al. Based on information obtained by interview, The fact that the diagnoses of affected family members rely on proxy interviews challenges the reliability of the diagnoses and more importantly may be influenced by differential misclassification e.
The study does not report the specific underlying aetiologies of hydrocephalus among the affected family members. Since acquired hydrocephalus generally is far more common than idiopathic congenital hydrocephalus, the diagnoses of most of the relatives may in fact be incomparable to the diagnoses of the index patients.
Based on the existing literature, a genetic component to the aetiology is assumed in addition to the known gene defect causing X-linked congenital hydrocephalus. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve.
Conclusions The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk. Observations of family clustering of LVOTO malformations support the hypothesis that LVOTO lesions share a common cause 8 — 11 that may involve abnormal intracardiac flow-induced morphogenetic alterations as a convergent mechanism.
BAV is a risk factor for aortic valve disease in adults.
It may be the most common CCVM, with an estimated incidence of 0. In 2 large, published autopsy series, the incidence of BAV was 0. Brenner et al 7 performed echocardiograms on relatives of 11 infants with HLHS, where they observed 5 of 41 first-degree relatives with unrecognized BAV. Huntington et al 5 performed echocardiography on first-degree relatives of 30 adults with BAV.
The importance of adult sibling relationships - MSU Extension
They found 17 subjects 9. Progress in echocardiographic methods over the last decade has made it possible to reevaluate the incidence of anatomic anomalies in families of LVOTO probands with greater confidence and precision. Seeking to investigate further the genetic components of LVOTO malformations, we conducted a prospective echocardiographic study of the cardiac morphology in relatives of infants and children ascertained with LVOTO malformations.
Once these affected children also called the proband were identified, we contacted the families and enrolled them after obtaining informed consent.