Immotile Cilia Syndrome (Primary Ciliary Dyskinesia), Including Kartagener Syndrome

ABSTRACT

• The immotile cilia syndrome is a genetically determined disorder characterized by dysmotility or even complete immotility of the cilia in the airways and elsewhere. Usually spermatozoa are also either immotile or poorly motile.

• Kartagener syndrome is a subgroup of the immotile cilia syndrome and is further characterized by situs inversus viscerum. Situs inversus, bronchiectasis, and chronic sinusitis form the classic Kartagener triad.

• The reason for the ciliary immotility or dysmotility usually can be seen with an electron-microscopic investigation of a ciliated mucosal biopsy or of the spermatozoa of an ejaculate. Certain specific defects in the ciliary axoneme are regarded to be pathognomonic of the syndrome, principally a lack of dynein arms. Cilia and sperm tails normally exhibit the same defects in the same patient. Motility can be evaluated by light-microscopic examination of living cilia or spermatozoa and the functional capacity of cilia by measurement of mucociliary transport.

• The clinical consequences of the immotile cilia syndrome include chronic cough and expectoration, bronchiectasis, chronic rhinitis and nasal polyposis, chronic or recurrent sinusitis, and often an agenesis of the frontal sinuses. Otosalpingitis and otitis are common. Obstructive lung disease may develop and is expressed as chronic airflow limitation. Most clinical manifestations date from early childhood. Neonatal asphyxia occurs often.

• Males are usually sterile. Females may be fertile or infertile.

• Treatment is symptomatic and directed against complications in the upper and lower respiratory tract. Physiotherapy often should be started early in life. With modern care and abstinence from smoking, the prognosis in the immotile cilia syndrome is good.

• The immotile cilia syndrome clearly is a genetically heterogeneous disease, although its clinical profile is fairly uniform. Many genes participate in the construction of a cilium, and an error in any one of them will prevent the cilia from working properly. The inheritance in most cases is autosomal recessive. In families in which the immotile cilia syndrome occurs, on average, half the affected siblings have situs inversus. Presumably, chance alone decides between situs inversus and situs solitus in homozygotes of the syndrome.

INTRODUCTION

In a paper in 1933, Manes Kartagener published the case histories of four persons who all had situs inversus totalis, bronchiectasis, and chronic sinusitis.¹ Siewert previously had described one such patient.² This combination of symptoms later came to be known as Kartagener syndrome or Kartagener triad. It is caused by a structural and generalized abnormality of cilia, making the cilia immotile, feebly motile, or dysmotile^3,4 and, hence, nonfunctional. Ciliary dysmotility is associated with situs inversus in only about half the patients. Because situs inversus per se usually has no serious implications, this chapter will address the immotile cilia syndrome in its entirety and will include Kartagener syndrome as a subgroup of the immotile cilia syndrome.

PREVALENCE

Most authors estimate the prevalence of Kartagener syndrome at 1 in 30,000 to 1 in 60,000 persons.^5,6...