Первичная дискинезия ресничек: симптомы, диагностика и лечение.

Around 80% of people with primary ciliary dyskinesia experience respiratory problems beginning within a day of birth. Many have a collapsed lobe of the lung and blood oxygen low enough to require treatment with supplemental oxygen. The main consequence of impaired ciliary function is reduced or absent mucus clearance from the lungs, and susceptibility to chronic recurrent respiratory infections, including sinusitis, bronchitis, pneumonia, and otitis media. Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults). However, diagnosis is often missed early in life despite the characteristic signs and symptoms. In males, immotility of sperm can lead to infertility, although conception remains possible through the use of in vitro fertilization, there also are reported cases where sperm were able to move. Trials have also shown that there is a marked reduction in fertility in females with Kartagener's syndrome due to dysfunction of the oviductal cilia. Many affected individuals experience hearing loss and show symptoms of otitis media which demonstrates variable responsiveness to the insertion of myringotomy tubes or grommets. Some patients have a poor sense of smell, which is believed to accompany high mucus production in the sinuses (although others report normal – or even acute – sensitivity to smell and taste). Clinical progression of the disease is variable, with lung transplantation required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung disease progression. The predicted incidence is 1 in approximately 7500. which are made up of approximately 250 proteins. of individuals with PCD have ultrastructural defects affecting protein(s) in the outer and/or inner dynein arms, which give cilia their motility, with roughly 38%

There is an international effort to identify genes that code for inner dynein arm proteins or proteins from other ciliary structures (radial spokes, central apparatus, etc.) associated with PCD. Type OMIM Gene Locus CILD1 DNAI1 9p21 p13 CILD2 ? 19q13.3 qter CILD3 DNAH5 5p CILD4 ? 15q13 CILD5 ? 16p12 CILD6 TXNDC3 7p14 p13 CILD7 DNAH11 7p21 CILD8 ? 15q24 q25 CILD9 DNAI2 17q25 CILD10 KTU 14q21.3 CILD11 RSPH4A 6q22 CILD12 RSPH9 6p21 CILD13 LRRC50 16q24.1

Another gene associated with this condition is GAS2L2.

This condition is genetically inherited. Structures that make up the cilia, including inner and/or outer dynein arms, central apparatus, radial spokes, etc. are missing or dysfunctional and thus the axoneme structure lacks the ability to move. Axonemes are the elongated structures that make up cilia and flagella. Additionally, there may be chemical defects that interfere with ciliary function in the presence of adequate structure. Whatever the underlying cause, dysfunction of the cilia begins during and impacts the embryologic phase of development. such that they describe a D shape rather than a circle. However, in some individuals with PCD, mutations thought to be in the gene coding for the key structural protein left right dynein (lrd) 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.

Several diagnostic tests for this condition have been proposed. These include nasal nitric oxide levels as a screening test, light microscopy of biopsies for ciliary beat pattern and frequency and electron microscopic examination of dynein arms, as the definite diagnosis method. Genetic testing has also been proposed but this is difficult given that there are multiple genes involved. (only 50% of primary ciliary dyskinesia cases include situs inversus).

There are no standardized effective treatment strategies for the condition. Current therapies for PCD are extrapolated from Cystic Fibrosis and patients with non CF bronchiectasis and lack validation for PCD specific use. Severe fatal respiratory failure can develop; long term treatment with macrolides such as clarithromycin, erythromycin and azithromycin has been empirically applied for the treatment of primary ciliary dyskinesia in Japan, though controversial due to the effects of the medications.

There is no reliable estimate of life expectancy for people with PCD. However, there is evidence that PCD, is a life altering life shortening multi system condition, with some people progressing to lung transplant. Decline in lung function in people with PCD has been observed in most studies, with FEV1 decline causing deterioration in health, impacting on, and reducing quality of life. With such a genetically and phenotypically heterogenous group, observation of median/mean decline in lung function risks regression to the mean, missing those groups with significantly worse lung function, masked by those with milder phenotypes. While prospective outcome data is limited due to the early stage patient registries, there is a growing body of evidence that dispels any "myth that PCD is a mild disease. The studies presented here demonstrate that children with PCD typically have worse lung function than those with cystic fibrosis. it is key to note that poor lung function is repeatedly observed in children with PCD

The classic symptom combination associated with PCD was first described in 1904 by A. K. Siewert, while Manes Kartagener published his first report on the subject in 1933. The disorder is rarely referred to as Siewert's syndrome or Siewert Kartagener syndrome.