Syndromic Congenital Heart Defects Research Articles

Familial recurrence of nonsyndromic congenital heart defects in first degree relatives of patients with deletion 22q11.2

The majority of nonsyndromic congenital heart defects (CHDs) are considered to follow a multifactorial model of inheritance. Multiple family members affected by CHD can occasionally be detected, and the involvement of several genetic loci interacting with environmental factors is suspected to be implicated. The DiGeorge/velo-cardio-facial syndrome related to microdeletion 22q11.2 (del22) is a genetic condition associated with CHD in most of the cases. We report here on five pedigrees of patients with del22, showing occurrence of nonsyndromic CHD in a first-degree relative of the proband case. Familial aggregation of syndromic and nonsyndromic CHD as observed in our series is to be considered as an unusual pattern of recurrence. The interaction between several different genes and environmental factors, a familial susceptibility predisposing to a specific cardiac malformation, or chance association can all be hypothesized searching an explanation for these particular observations.

Spectrum of middle and inner ear abnormalities in infants with congenital heart defect

Objectives: Congenital heart defects (CHD) occur in thousands of newborns and approximately 1,000,000 Americans with CHD are alive. A high incidence of hearing loss was documented in children with CHD; however, the histopathologic basis of hearing impairment in infants with CHD has not been systematically studied. The aim of this study was to evaluate temporal bone histopathology in infants with CHD. Methods: Forty temporal bones obtained from 20 infants with CHD were evaluated. Microdissection and serial sectioning methods were used to examine temporal bones. Subjects were divided into nonsyndromic CHD and syndromic CHD groups. The presence of temporal bone abnormalities and the incidence of abnormalities that may result in hearing impairment were determined. Results: Sixteen infants had nonsyndromic CHD and 4 had syndromic CHD. All nonsyndromic CHD cases had abnormalities such as mesenchymal remnant, malformed stapes, stapedial artery remnant, facial canal dehiscence, short cochlea, missing organ of Corti, strial basophilic deposits, widened and shortened spiral ligament, bulging Reissner’s membrane, and hypoplastic lateral semicircular canal. All syndromic CHD cases had abnormalities including large pinnae, external ear canal stenosis or atresia, narrow round window niche, facial canal dehiscence, strial deposits and cysts, and outer hair cell loss. Congenital middle and inner ear abnormalities that may impair hearing were observed in 4 subjects with nonsyndromic CHD and in 1 subject with syndromic CHD. Conclusions: A wide variety of temporal bone abnormalities were documented in infants with CHD. Congenital middle and inner ear abnormalities should be anticipated in the hearing assessment of infants with CHD.

Genetic basis of syndromes associated with congenital heart disease.

Numerous syndromes affecting patients have phenotypes that include congenital heart defects (CHDs). These disorders have fascinated physicians for many years, raising questions about how seemingly disparate aspects of human development can be perturbed together in striking, but consistent, ways. Paralleling the major advances in human genetics during recent decades, we have come to understand that some of these syndromes arise from gross defects in chromosomal number, some from subtler alterations in genomic regions, and still others from point mutations in specific genes. These disorders, largely mendelian in nature, have provided researchers with the wherewithal to discover disease genes underlying CHD. Although some of these medical conditions are relatively rare, their solution has often provided insights that could be applied toward understanding the basis of nonsyndromic CHD. In this review, recent progress toward uncovering the molecular basis of several forms of syndromic CHD is discussed.