This has been shown to generate a net leftward flow in mouse and chick embryos, and sweeps the protein to the left, triggering normal asymmetrical development.However, in some individuals with PCD, mutations thought to be in the gene coding for the key structural protein left-right dynein (lrd) result in monocilia which do not rotate. There is therefore no flow generated in the node, Shh moves at random within it, and 50% of those affected develop situs inversus, which can occur with or without dextrocardia, where the laterality of the internal organs is the mirror-image of normal. Affected individuals therefore have Kartagener syndrome. This is not the case with some PCD-related genetic mutations: at least 6% of the PCD population have a condition called situs ambiguus or heterotaxy, where organ placement or development is neither typical (situs solitus) nor totally reversed (situs inversus totalis) but is a hybrid of the two. Splenic abnormalities such as polysplenia, asplenia and complex congenital heart defects are more common in individuals with situs ambiguus and PCD, as they are in all individuals with situs ambiguus.The genetic forces linking failure of nodal cilia and situs issues and the relationship of those forces to PCD are the subject of intense research interest. However, knowledge in this area is constantly advancing.
Goals of therapy are to control urinary protein loss and swelling, provide good nutrition to allow the child to grow, and prevent complications. Early and aggressive treatment is required to control the disorder. Patients with severe urine protein loss require albumin infusions help replace protein loss and diuretic medications help rid the body of excess fluid. For patients with mild to moderate urine protein losses, ACE inhibitor medications (like Captopril and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein (albumin) in the urine. Removal of the kidneys (one at the time or both) can decrease protein loss and limit the number of albumin infusions needed. Infants with WT1 mutations will undergo bilateral kidney removal to prevent development of Wilms tumor.Antibiotics may be needed to control infections. Immunizations are recommended after kidney removal but prior to transplantation. Patients may also take iron supplements, potassium chloride, thyroxine and other vitamins to replenish what minerals the kidneys have leaked out. Anticoagulants (such as aspirin, dipyridamole, and warfarin) are used to prevent clot formation.Dietary modifications may include the restriction of sodium and use of dietary supplements as appropriate for the nature and extent of malnutrition. Fluids may be restricted to help control swelling. Children with this disease require diets high in calories and protein, and many patients require a feeding tube (nasogastric tube or gastrostomy tube (g-tube)) for medication and/or feeds. Some patients develop oral aversions and will use the tube for all feeds.