Features Of Primary Ciliary Dyskinesia Research Articles

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by abnormal ciliary structure and function leading to impaired mucociliary clearance and chronic progressive sinopulmonary disease. Upper and lower respiratory tract manifestations are cardinal features of PCD. This review summarizes the current state of knowledge of respiratory tract disease in individuals with PCD and highlights the challenges in identifying and quantifying lung disease in very young children with PCD. No specific therapies are available to correct ciliary dysfunction in PCD. Treatment is not evidence based, and recommendations are largely extrapolated from cystic fibrosis and other conditions with impaired mucociliary clearance. There is a pressing need to develop and validate outcome measures, including patient-reported outcomes, that could be used to evaluate potential therapies in PCD. This review concludes with recommendations for clinical endpoints and outcome measures and a prioritized list of treatments to study in PCD clinical trials.

Discinesia ciliar primária revisitada: A propósito de três casos clínicos

Primary ciliary dyskinesia is a genetically and clinically heterogeneous disorder. Its pathogenesis reflects structural and functional compromise of the cilia.Common clinical manifestations include recurrent upper and lower respiratory tract infections and infertility, as well as situs inversus totalis in half of the affected patients.Besides its rarity and phenotypic heterogeneity its diagnosis usually requires a high suspicion index.The main purpose of this paper is to review the pathogenesis, clinical features, diagnostic and therapeutic approaches of primary ciliary dyskinesia beyond the discussion of three clinical reports.We report the cases of three patients all with a past history of neonatal respiratory distress and two with situs inversus totalis. The subsequent clinical manifestations included lower airway symptoms in two patients (chronic productive cough and recurrent pneumonia and wheezing) and upper respiratory tract disease in all patients. Age at primary ciliary dyskinesia diagnosis differed considerably among patients (8months, 5 and 12 years). The two patients with later diagnosis had already obstructive lung function compromise at the time of diagnosis.The authors discuss the different clinical patterns presented, therapeutic strategies and the clinical progression that ensued, factors possibly implicated in late diagnosis and its prognostic consequences.The main goal is to emphasize early and/or prevalent clinical features of primary ciliary dyskinesia in order to promote clinical awareness and early recognition of the disease.Rev Port Pneumol 2010; XVI (5): 837-847

Intérêt du prélèvement nasal pour le diagnostic des dyskinésies ciliaires primitives de l’enfant

Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder, characterized by chronic infections of the upper and lower airways, associated in 50% of cases with situs inversus, therefore, corresponding to Kartagener's syndrome. PCD is suspected on clinical features, including bronchitis, rhinosinusitis and chronic otitis media beginning in early childhood. The recurring infections eventually lead to bronchiectasis. The clinical features of PCD have been ascribed to primary defects in cilia, which lead to impairment of mucociliary clearance. Ciliary investigations looking for abnormalities in ciliary motion and ultrastructure can be easily performed at nasal level. Quantitative ultrastructural study of cilia is performed in cases of abnormal ciliary motion and/or clinical symptoms highly suggestive of PCD. In PCD, all or most of the cilia are abnormal, all bearing the same ultrastructural defects, mainly concerning dynein arms. In older children, the detection of a very low nasal NO output could also be useful for the diagnosis of PCD. As soon as the ciliary investigations are easy to perform at the nasal level, they could help for a better detection of PCD. This strategy could be especially useful in cases of atypical presentations, which are underestimated as a cause of recurrent airway infections. Diagnosis of PCD is important in order to prevent the development of bronchiectasis and to avoid any unnecessary procedure.

Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus.

Primary ciliary dyskinesia (PCD), also known as Kartagener's syndrome, is a human syndrome that results from ciliary dysfunction. This syndrome is characterized by recurrent respiratory infections, situs inversus and infertility. In some cases, hydrocephalus is also observed. We have characterized an insertional mutation in a mouse axonemal dynein heavy chain gene (Mdnah5) that reproduces most of the classical features of PCD, including recurrent respiratory infections, situs inversus and ciliary immotility. These mice also suffer from hydrocephalus and die perinatally. Electron microscopic studies demonstrate the loss of axonemal outer arms. These results show that mutations in Mdnah5 are a primary cause of PCD and provide direct evidence that mutations in an axonemal dynein can cause hydrocephalus. Mutations in the human DNAH5 have recently been identified in PCD patients. Comparison of the mouse model and the human data suggests that the degree of ciliary dysfunction is causally related to the severity of human PCD, particularly the presence of hydrocephalus.

Ciliary Dyskinesia Associated With Hydrocephalus and Mental Retardation in a Jordanian Family

To describe the presentation and genetic transmission of ciliary dyskinesia syndrome associated with hydrocephalus and mental retardation in 3 generations of a family. A large Jordanian family included 9 individuals in 3 generations with recurrent pulmonary infections; 4 male siblings have been diagnosed as having mental retardation, and a maternal uncle was believed to have been similarly affected. Chromosome analysis of the family showed a normal karyotype. Electron microscopy of the nasal cilia from 3 affected siblings showed features of primary ciliary dyskinesia. Computed tomographic scans of the brains of all 4 affected siblings showed hydrocephalus. The recurrent pulmonary infections and hydrocephalus in this large Jordanian family are likely related to ciliary dyskinesia, which appears to follow an autosomal recessive mode of inheritance. The unusual presentation of ciliary dyskinesia, hydrocephalus, and mental retardation may be due to a new genetic mutation.

Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome.

Ciliary disorientation has been proposed as a variant of primary ciliary dyskinesia (PCD); cilia have normal ultrastructure and normal or near normal ciliary beat frequency (CBF) but lack efficacy because their beat direction is disorientated. We have identified 11 patients, including two siblings, with the clinical features of PCD, who satisfy these criteria. A chest radiograph, pulmonary function tests, nasal mucociliary clearance (NMCC), CBF, ciliary ultrastructure, and orientation were assessed in each subject. One patient had biopsies taken from the nose and both main bronchi. Eight patients had a computed tomography scan (CT) of the thorax; the clinical features were compatible with PCD. Cilia ultrastructure was normal and NMCC was absent in all cases. Mean CBF was normal (11.6-14.9 Hz) in five cases and slow in six (range 8.4-9.7 Hz). Ciliary beat pattern was stiff in seven cases, six of which had slow CBF. The cilia were disorientated when measured by both the central pair (range, 21.8 degrees - 26.4 degrees) and basal feet (range, 20.6 degrees - 28.9 degrees) compared with 16 normal controls (range, 11.0 degrees - 15.5 degrees and 12.3 degrees - 17.6 degrees, respectively). Two siblings had the clinical features of PCD and ciliary disorientation alone on repeated biopsies taken 10 yr apart. Orientation of cilia from the nose and bronchus was similar. Two cases had unchanged ciliary disorientation after 3 mo of treatment with antibiotics and topical corticosteroids. We concluded that ciliary disorientation alone can lead to the clinical syndrome of PCD.