Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry1. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.

OBJECTIVE

To evaluate otologic features in children with primary ciliary dyskinesia (PCD).

DESIGN

retrospective study

SETTING

pediatric referral center

PATIENTS

58 PCD patients, distributed in four age-groups (I: 0–5 years; II: 6–11 years; III: 12–17 years and IV: above 18 years with 47, 50, 34 and 10 cases, respectively). Follow-up: 2 to 6 years in each age-group. Ultrastructural defects of outer or inner dynein arms, and central complex (CC): 33, 13 and 11 cases, respectively.

MAIN OUTCOME MEASURES

Frequency of: acute otitis media (AOM), otitis media with effusion (OME), otorrhea, chronic otitis media, hearing loss, middle ear surgery and type of antibiotic regimen according to age and type of defect.

RESULTS

Recurrent AOM decreased from group I (68%) to group IV (0%), p<0.00001. OME was more severe in groups I to III than in group IV, p=0.02. Otorrhea decreased in group IV: 30% versus 80% in other groups, p<0.001. One half of patients with tubes eventually had tympanic perforation. Hearing loss was moderate in groups I to III and mild in group IV. Continuous antibiotics could be slightly reduced only in group IV. CC defect was a significant marker of severity for all of these criteria.

CONCLUSIONS

Despite continuous antibiotics, the middle ear condition in PCD remained severe throughout childhood with improvement only after the age of 18 years. Grommet placement failed to improve the middle ear condition. CC defect is a marker of severity.