An eye on the future for defeating hydrocephalus, ciliary dyskinesia-related hydrocephalus: review article.

Congenital hydrocephalus affects approximately one in 1000 newborn children and is fatal in approximately 50% of untreated cases. The currently known management protocols usually necessitate multiple interventions and long-term use of healthcare resources due to a relatively high incidence of complications, and many of them mostly provide a treatment of the effect rather than the cause of cerebrospinal fluid flow reduction or outflow obstruction. Future studies discussing etiology specific hydrocephalus alternative treatments are needed. We systematically reviewed the available literature on the effect of ciliary abnormality on congenital hydrocephalus pathogenesis, to open a discussion on the feasibility of factoring ciliary abnormality in future research on hydrocephalus treatment modalities. Although there are different forms of ciliopathies, we focused in this review on primary ciliary dyskinesia. There is growing evidence of association of other ciliary syndromes and hydrocephalus, such as the reduced generation of multiple motile cilia, which is distinct from primary ciliary dyskinesia. Data for this review were identified by searching PubMed using the search terms 'hydrocephalus,' 'Kartagener syndrome,' 'primary ciliary dyskinesia,' and 'immotile cilia syndrome.' Only articles published in English and reporting human patients were included. Seven studies met our inclusion criteria, reporting 12 cases of hydrocephalus associated with primary ciliary dyskinesia. The patients had variable clinical presentations, genetic backgrounds, and ciliary defects. The ependymal water propelling cilia differ in structure and function from the mucus propelling cilia, and there is a possibility of isolated non-syndromic ependymal ciliopathy causing only hydrocephalus with growing evidence in the literature for the association ependymal ciliary abnormality and hydrocephalus. Abdominal and thoracic situs in children with hydrocephalus can be evaluated, and secondary damage of ependymal cilia causing hydrocephalus in cases with generalized ciliary abnormality can be considered.

Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report.

BACKGROUND: Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing. CASE PRESENTATION: Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells. CONCLUSIONS: NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.

Primary ciliary dyskinesia in Japan: systematic review and meta-analysis.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder. Although the genetic tests and new diagnostic algorithms have recently been recommended, clinical signs and electron microscope (EM) findings have historically been the mainstays of diagnosis in Asia. To characterize PCD previously reported in Japan, we conducted a systematic review and meta-analysis. METHODS: A search using MEDLINE, EMBASE, and Japana Centra Revuo Medicina (in Japanese) databases was carried out to identify articles reporting PCD, Kartagener syndrome, or immotile cilia syndrome in Japanese patients and published between 1985 and 2015. RESULTS: After excluding duplication from 334 reports, we extracted 316 patients according to the criteria. Diagnosis was most frequently made in adulthood (148 patients [46.8%] ≥ 18 years old, 24 patients [7.6%] < 1 year old, 68 patients [21.5%] 1-17 years old and 76 patients [24.1%] lacking information). Of the 230 patients (72.8%) who received EM examination, there were patients with inner dynein arm (IDA) defects (n = 55; 23.9%), outer dynein arm (ODA) defects (14; 6.1%), both ODA and IDA defects (57; 24.8%), other structural abnormalities (25; 10.9%), no abnormalities (4; 1.7%), and no detailed conclusion or description (75; 32.6%). CONCLUSION: Delayed diagnosis of this congenital disease with high frequency of IDA defects and low frequency of ODA defects appear to be historical features of PCD reported in Japan, when EM was a main diagnostic tool. This review highlights problems experienced in this field, and provides basic information to establish a modernized PCD diagnosis and management system in the future.

Primary ciliary dyskinesia among Arabs: Where do we go from here?

Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is a rare genetic disease that is inherited in an autosomal recessive manner. Several studies have explored certain aspects of PCD in the Arab world, yet much is still lacking in terms of identifying the different characteristics of this disease. In this paper, we aim to briefly cover those studies published about PCD in Arab countries, as well as to provide recommendations and guidelines for future studies.

Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia.

CONCLUSION: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD). The observed decrease in serum precipitating antibodies (precipitins) against Pseudomonas aeruginosa may indicate a beneficial effect of combined endoscopic sinus surgery (ESS) and concomitant medical treatment. OBJECTIVES: The purpose of this research, which is the first study addressing bacteriology in the sinuses of patients with PCD, was to examine the association between sinus and lung infections. METHODS: We reviewed findings of bacterial pathogens from the sinuses obtained during ESS and the lung infection status in eight PCD patients over a 6 year period. Precipitins against P. aeruginosa were used as a marker of severity of chronic infection and effect of treatment. RESULTS: Preoperatively, seven of the eight patients (88%) exhibited intermittent or chronic pulmonary infection with P. aeruginosa. Sinus cultures were obtained during ESS in seven patients. The sinuses were colonized with P. aeruginosa in four of seven patients (57%). Bacterial sinusitis was found in five of seven patients (71%) and the same bacterium was found in the sinuses and lungs in all cases. Decreasing precipitins against P. aeruginosa were observed postoperatively in three of four evaluable patients.

Primary ciliary dyskinesia: overlooked and undertreated in children.

Primary ciliary dyskinesia (PCD) is a multi-organ disorder associated with chronic oto-sino-pulmonary disease, neonatal respiratory distress, situs abnormalities and reduced fertility. Repeated respiratory tract infections leads to the almost universal development of bronchiectasis. These clinical manifestations are a consequence of poorly functioning motile cilia. However, confirming the diagnosis is quite difficult and is often delayed, so the true incidence of PCD may be significantly higher than current estimates. Nasal nitric oxide has been earmarked as a useful screening tool for identifying patients, but its use is limited in pre-school-aged children. Due to the rarity of PCD, the evidence base for management is somewhat limited, and treatment regimens are extrapolated from other suppurative lung disorders, like cystic fibrosis.

Primary ciliary dyskinesia diagnosed on nasal mucosal biopsy in two newborns.

Primary ciliary dyskinesia (PCD) is a genetic disease that causes abnormalities in ciliary structure and/or function. Ciliated cells line the upper and lower respiratory tracts and the Eustachian tube. Impairment of mucus clearance at these sites leads to sinusitis, repeated pulmonary infections, bronchiectasis, and chronic otitis media. Situs inversus occurs randomly in approximately 50% of subjects with PCD. The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. PCD is usually an autosomal recessive disease, but occasional instances of X-linked transmission have been reported. Specific diagnosis requires examination of ciliary function or structure on light and electron microscopy. Early diagnosis and respiratory management are important in order to prevent the development of bronchiectasis and deterioration in lung function. We report early diagnosis of PCD on nasal mucosal biopsy in two newborns who presented with prolonged respiratory distress and rhinorrhea.

Kartagener syndrome.

Kartagener syndrome is a rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract and fallopian tube. Patients usually present with chronic recurrent rhinosinusitis, otitis media, pneumonia, and bronchiectasis caused by pseudomonal infection. Situs inversus can be seen in about 50% of cases. Diagnosis can be made by tests to prove impaired cilia function, biopsy, and genetic studies. Treatment is supportive. In severe cases, the prognosis can be fatal if bilateral lung transplantation is delayed. We present a case of a 66-year-old woman with chronic recurrent upper respiratory infections, pseudomonal pneumonia, and chronic bronchiectasis who presented with acute respiratory failure. She was diagnosed with Kartagener syndrome based on her clinical presentation and genetic studies. She expired on ventilator with refractory respiratory and multiorgan failure.

An unusual presentation of immotile-cilia syndrome with azoospermia: Case report and literature review.

Immotile-cilia syndrome is a rare disorder characterized by chronic recurrent sino-pulmonary infection, impaired tracheobronchial clearance, situs inversus in about 50% of cases, and living but immotile spermatozoa of normal morphology in semen analysis. In this report, we describe an unusual presentation of immotile-cilia syndrome with azoospermia in a 32-year-old male patient. The diagnosis was based on history of recurrent respiratory tract infection, bronchiectasis, maxillary sinusitis, hypoplasia of frontal sinuses, dextrocardia with situs inversus, impaired nasal mucociliary clearance, etc. Semen analysis revealed azoospermia without any evidence of obstruction in epididymides or vas deference. Normal spermatogenesis was seen on testicular biopsy.