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Primary ciliary dyskinesia, an orphan disease

European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease, caused by specific primary structural and/or functional abnormalities of the motile cilia, in contrast with the transitory abnormalities seen in secondary ciliary dyskinesia. Disease-causing mutations in at least 16 genes have already been identified. The true incidence of PCD may be higher than currently reported, because the diagnosis is challenging and often missed. For the confirmation of PCD, both ciliary motility as well as ciliary ultrastructure must be evaluated. An early and adequate diagnosis and therapy can theoretically prevent bronchiectasis. Measurement of nasal nitric oxide has some value as a screening test but cannot be performed in young children. In the respiratory tract epithelium, impaired mucociliary clearance leads to chronic and/or recurrent upper and lower respiratory tract infections. In up to 75 % of the patients, respiratory manifestations start in the newborn period, although the diagnosis is often missed at that time. During embryogenesis, nodal cilia, which are motile cilia, determine the correct lateralization of the organs. Dysfunction of these cilia leads to random lateralization and thus situs inversus in approximately 50 % of the patients with PCD. The tail of a spermatozoon has a structure similar to that of a motile cilium. Consequently, male infertility due to immotile spermatozoa is often part of the characteristics of PCD. Given the heterogeneity and the rarity of the disorder, therapy is not evidence-based. Many treatment schedules are proposed in analogy with the treatment for cystic fibrosis.

Conclusion

Respiratory infections, situs inversus and male infertility are typical manifestations of PCD, a rare autosomal recessive disorder.

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Abbreviations

CBF:

Ciliary beat frequency

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator

DNAH:

Dynein axonemal heavy chain

DNAI:

Dynein axonemal intermediate chain

DNAL:

Dynein axonemal light chain

ENT:

Ear nose and throat

HRCT:

High-resolution computed tomography

IDA:

Inner dynein arm

IVF:

In vitro fertilization

nNO:

Nasal nitric oxide

NO:

Nitric oxide

ODA:

Outer dynein arm

OME:

Otitis media with effusion

PCD:

Primary ciliary dyskinesia

SCD:

Secondary ciliary dyskinesia

SI:

Situs inversus

TEM:

Transmission electron microscopy

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Correspondence to Mieke Boon.

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This overview is dedicated to the late professor L. Corbeel, former editor of this journal.

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Boon, M., Jorissen, M., Proesmans, M. et al. Primary ciliary dyskinesia, an orphan disease. Eur J Pediatr 172, 151–162 (2013). https://doi.org/10.1007/s00431-012-1785-6

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