heart chambers. In AVSD, all four chambers are connected, but the exact characteristics of holes and malformations may vary between patients. Even within the categories of "complete" and "partial" AVSD, multiple morphologies exist, with varying clinical consequences. Clinical and physiological manifestations of disease may also change over time, in response to continued stress. Genetic Relationship Like other congenital heart defects, major associations have been found between AVCD and genes regulating embryonic cell cilia. These human cell cilia normally contain receptors for signal molecules that regulate the healthy and organized tissue. Dysfunctional cilia can create multiple disease manifestations, leading to broad syndromes. Chromosome 21 harbors important regulators for cilia, and trisomy 21 (Down syndrome) can de-regulate them. Diagnosis AVSDs can be detected by cardiac auscultation; they cause atypical murmurs and loud heart tones. Confirmation of findings from cardiac auscultation can be obtained with a cardiac ultrasound (echocardiography - less invasive) and cardiac catheterization (more invasive). It is also possible to diagnose AVSD in-utero via routine fetal ultrasounds or, more conclusively, fetal echocardiograms. Classification A variety of different classifications have been used, but the defects are usefully divided into "partial" and "complete" forms. In the partial AVSD, there is a small or partial defect in the interventricular septum, and a primum atrial septal defect, which is a moderate or large connection between the atria, often featuring mitral valve regurgitation. Partial AVSD may be asymptomatic in early childhood, but typically progresses by late childhood or adulthood into symptoms of heart failure. The onset of symptoms may be earlier in children with more significant mitral regurgitation. In the complete AVSD (CAVSD), there is a large ventricular component beneath either or both the superior or inferior bridging leaflets of the AV valve. The defect involves the whole area of the junction of the upper and lower chambers of the heart, i.e. where the atria join the ventricles. There is a large hole between the lower portion of the atria and the upper or 'inlet' portion of the ventricles and this is associated with a significant abnormality of the valves separating the atria from the ventricles. The valves in effect become a common atrio-ventricular valve, and the severity of the defect depends largely on the supporting attachments of the valve to the ventricles and whether the valve allows dominant flow from the right atrium to right ventricle and from left atrium to left ventricle ("unbalanced" flow).