Genetically transmitted polymalformative syndrome
characterized by bronchiectasis, situs inversus, and chronic sinusitis.
Afzelius Syndrome; Dextrocardia-Bronchiectasis-Sinusitis;
Immotile Cilia Syndrome, Kartagener type; Primary Ciliary Dyskinesia (PCD),
Kartagener Type; Siewert Syndrome.
Genetic disorder first described by Siewert in 1904, but
identified as a syndrome by the Swiss internist Manes Kartagener (1897-1975) in 1933.
1:32 000 live births. Primary ciliary dyskinesia (PCD), of
which Kartagener's is a subtype, has an incidence of 1:16,000 live births.
Only 20 to 25% of patients with situs inversus also have bronchiectasis
Autosomal recessive trait. The axoneme of
cilia contains 200 different proteins, and defects in genes coding for any
one of these products could conceivably be responsible for PCD and thus
Kartagener syndrome. Classically, Kartagener syndrome is caused by mutations
in the gene encoding axonemal dynein intermediate chain (DNAI1), which maps
to 9p21-p13. Other linkage studies have mapped the phenotype to 19q and 5p
in Arabic families. Another mutation causing Kartagener syndrome has been
mapped to the DNAH5 gene (5p15-p14).
Kartagener syndrome is essentially a subtype of an
inherited disorder called primary ciliary dyskinesia (PCD), a heterogeneous disease characterized by
functionally abnormal cilia that are “dysmotile” or, rarely, absent.
Defects of all of the axonemal structures, alone or in combination, have
been identified in association with PCD. Overly long, overly short, and
normally appearing but randomly oriented cilia have been associated with PCD
and Kartagener syndrome. Finally, normal ciliary ultrastructure has been
described in patients with the clinical picture of Kartagener syndrome.
Lack of dynein arms, which are structures that form temporary cross-bridges
between adjacent ciliary filaments and are believed to be responsible for
generating movement in cilia and sperm tails, remains the most common defect
identified (type 1) and the one classically associated with Kartagener
syndrome. Cilia of the respiratory tract and sperms are dysmotile or
nonfunctional. It has also been postulated that normal visceral asymmetry is
determined by movement of cilia in certain embryonic epithelial tissues;
failure of embryonic cilia to function normally results in situs inversus.
The most important historical fact is the onset of upper
and lower respiratory tract symptoms shortly after birth in the presence of
situs inversus. Family history of PCD or Kartagener syndrome is very
helpful, but the diagnosis may require examination of ciliary
ultrastructure. To confirm the diagnosis, biopsy of respiratory mucosa or
microscopic examination of sperms is required. Measurements of airway
mucociliary clearance may be a valuable screening tool for excluding PCD
because absent mucociliary clearance is a hallmark of the syndrome.
Kartagener syndrome is a clinical triad of
chronic bronchorrhea with bronchiectasis, chronic sinusitis, and situs
inversus. It can be regarded as a subgroup of primary ciliary dyskinesia
(male sterility, bronchiectasis, sinusitis) because the clinical
consequences are the same. Clinical signs appear soon after birth or early
in childhood. Chronic rhinitis with nasal polyposis (approximately 30% of
patients), agenesis of the ...