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APLASIA OF RESPIRATORY TRACT CILIA
1283
APLASIA OF RESPIRATORY TRACT CILIA
SIR,-Ultrastructurall
and
functional2
disturbances of cilia
or
combinations of both have been found to cause syndromes, characterised by chronic airway obstruction3and expressing themselves in a variety of clinical manifestations.We describe here the first cases of total aplasia of secondary cilia in the upper and lower airways in four children, all girls, aged between 3 months and 9 years. The four girls represent two sibships, the two mothers being sisters. The fathers are also consanguineous. All patients had been seen many times for chronic obstructive lung disease leading to cough in all and to irreversible atelectasis in one. All of them had diffuse peribronchial thickening on radiography: some segmental lung changes suggested bronchiectasis.
After exclusion of cystic fibrosis and immunodeficiency posterior nasal and bronchial mucosal specimens were obtained by brushing or by biopsy. Electron microscopy revealed, in all patients, epithelia, both of the nasal cavity and of the tracheobronchial tree, with columnar or pseudostratified pattern. Mostly in the apical region of the epithelial cells some secretory granules were seen. Normal goblet cells were rare. From the free cell surface only numerous cytofila (elongated branched microvilli with central filaments5 projected into the superficial mucous layer (fig 1). The
2-In apical part of cytofila-bearing cells numerous mitochondria and irregularly orientated rootlet material are seen.
Fig
Broken lines enclose
complexes
of striated filaments. Bar= = 11"
m.
filaments, similar to rootlets, also occurred (fig 2). Normal primary were detected in only one epithelial and in one
centrioles
mesenchymal
cell.
Thus, besides the "immotile cilia syndrome" with ciliary abnormalities due to infection and injury or as an inborn disorder,6 we now have a hereditary form of "aplasia of secondary cilia". Differentiation of cilia into primary (or solitary) and secondary types was first described by Sorokin.7 The ciliogenetic material exists only in the first stages of ciliogenesis; the maturation of procentrioles and ciliary centrioles is interrupted. Jahrsdoerfer et al8 mentioned two brothers in one of whom no cilia could be demonstrated despite biopsy at three different sites. Unfortunately, no further information on ciliogenesis was available.
Fig
1-Pseudostratitied
Apical
region contains
epithelium with superficial cytofila. secretory granules and mitochondna
numerous
Some
elongated mitochondna form vesicles with electronlucent material. Lysosomes and aggregates of granular material are found in the supranuclear region. (Insert: Higher magnification of fibrogranular complexes, the 1 pm. precursor material for ciliogenesis.) Bar =
cytoplasm of the epithelial cells differed in electron density, sometimes being electronlucent, with numerous mitochondria, Golgi complexes, profiles of rough endoplasmic reticulum, and free ribosomes and lysosomes. In the supranuclear region occasional aggregates of dense granules and fibrogranular complexes (centriolar precursor material, fig lb) but neither procentrioles nor ciliary centrioles were seen. Irregular complexes of striated 1 Afzelius BA A human syndrome caused by immotile cilia. Science 1976, 193: 317-19 2. Rossmann CM, Forrest JB, Lee RMKW, Newhouse MT The dyskinetic cilia syndrome Chest 1980; 78: 580-82 3 Eliasson R, Mossberg B, Camner P, Afzelius BA. The immotile cilia syndrome. N Engl 4 5
J Med 1977; 297: 1-6 Turner JAP, Corkey CWB, Lee JYC, Levison H, Sturgess J. Clinical expressions of immotile cilia syndrome. Pediatrics 1981; 67: 805-10.
Stockinger L. Die Ultrastruktur Zellforsch 1963; 59: 443-66.
des
Flimmerepithels
des
Nasenseptums der
Ratte. Z
Such a defect is clearly compatible with life. All four patients had respiratory problems, manifest by repeated episodes of coughing, soon after birth, and they are now at various stages of a common underlying disease process progressing to chronic infiltrative lung damage and atelectasis. Coughing was largely ineffective and nonproductive, which may reflect diminution of goblet cells. A fifth girl, the third sister in one of the sibships, was also seen by us and had the same clinical features. Biopsy specimens could not be obtained but we assume that she too had ciliary aplasia. This girl is now very short of breath and intolerant of exercise. Of the parents of these children only one (a mother) has had ciliary morphology studied: posterior nasal brushing revealed no structural abnormalities of cilia.
We suggest
an
autosomal recessive mode of inheritance for this
ciliary aplasia. University Children’s Hospital, Vienna, Austria
A1090
MANFRED GOTZ
Institute of Micromorphology and Electron Microscopy,
University of
Vienna
6 Afzelius BA
"Immotile-cilia" syndrome and ciliary abnormalities induced by infection injury. Am Rev Resp Dis 1981, 124: 107-09 Sorokin SP Reconstruction of centriole formation and ciliogenesis in mammalian lungs J Cell Sci 1968, 3: 207-30. Jahrsdoerfer R. Feldman PS, Rubel EW, Guerrant JL, Eggleston PA, Selden RF. Otitis media and the immotile cilia syndrome Laryngoscope 1979; 89: 769-77 and
7
8.
LEOPOLD STOCKINGER
APLASIA OF RESPIRATORY TRACT CILIA
SIR,-Ultrastructurall
and
functional2
disturbances of cilia
or
combinations of both have been found to cause syndromes, characterised by chronic airway obstruction3and expressing themselves in a variety of clinical manifestations.We describe here the first cases of total aplasia of secondary cilia in the upper and lower airways in four children, all girls, aged between 3 months and 9 years. The four girls represent two sibships, the two mothers being sisters. The fathers are also consanguineous. All patients had been seen many times for chronic obstructive lung disease leading to cough in all and to irreversible atelectasis in one. All of them had diffuse peribronchial thickening on radiography: some segmental lung changes suggested bronchiectasis.
After exclusion of cystic fibrosis and immunodeficiency posterior nasal and bronchial mucosal specimens were obtained by brushing or by biopsy. Electron microscopy revealed, in all patients, epithelia, both of the nasal cavity and of the tracheobronchial tree, with columnar or pseudostratified pattern. Mostly in the apical region of the epithelial cells some secretory granules were seen. Normal goblet cells were rare. From the free cell surface only numerous cytofila (elongated branched microvilli with central filaments5 projected into the superficial mucous layer (fig 1). The
2-In apical part of cytofila-bearing cells numerous mitochondria and irregularly orientated rootlet material are seen.
Fig
Broken lines enclose
complexes
of striated filaments. Bar= = 11"
m.
filaments, similar to rootlets, also occurred (fig 2). Normal primary were detected in only one epithelial and in one
centrioles
mesenchymal
cell.
Thus, besides the "immotile cilia syndrome" with ciliary abnormalities due to infection and injury or as an inborn disorder,6 we now have a hereditary form of "aplasia of secondary cilia". Differentiation of cilia into primary (or solitary) and secondary types was first described by Sorokin.7 The ciliogenetic material exists only in the first stages of ciliogenesis; the maturation of procentrioles and ciliary centrioles is interrupted. Jahrsdoerfer et al8 mentioned two brothers in one of whom no cilia could be demonstrated despite biopsy at three different sites. Unfortunately, no further information on ciliogenesis was available.
Fig
1-Pseudostratitied
Apical
region contains
epithelium with superficial cytofila. secretory granules and mitochondna
numerous
Some
elongated mitochondna form vesicles with electronlucent material. Lysosomes and aggregates of granular material are found in the supranuclear region. (Insert: Higher magnification of fibrogranular complexes, the 1 pm. precursor material for ciliogenesis.) Bar =
cytoplasm of the epithelial cells differed in electron density, sometimes being electronlucent, with numerous mitochondria, Golgi complexes, profiles of rough endoplasmic reticulum, and free ribosomes and lysosomes. In the supranuclear region occasional aggregates of dense granules and fibrogranular complexes (centriolar precursor material, fig lb) but neither procentrioles nor ciliary centrioles were seen. Irregular complexes of striated 1 Afzelius BA A human syndrome caused by immotile cilia. Science 1976, 193: 317-19 2. Rossmann CM, Forrest JB, Lee RMKW, Newhouse MT The dyskinetic cilia syndrome Chest 1980; 78: 580-82 3 Eliasson R, Mossberg B, Camner P, Afzelius BA. The immotile cilia syndrome. N Engl 4 5
J Med 1977; 297: 1-6 Turner JAP, Corkey CWB, Lee JYC, Levison H, Sturgess J. Clinical expressions of immotile cilia syndrome. Pediatrics 1981; 67: 805-10.
Stockinger L. Die Ultrastruktur Zellforsch 1963; 59: 443-66.
des
Flimmerepithels
des
Nasenseptums der
Ratte. Z
Such a defect is clearly compatible with life. All four patients had respiratory problems, manifest by repeated episodes of coughing, soon after birth, and they are now at various stages of a common underlying disease process progressing to chronic infiltrative lung damage and atelectasis. Coughing was largely ineffective and nonproductive, which may reflect diminution of goblet cells. A fifth girl, the third sister in one of the sibships, was also seen by us and had the same clinical features. Biopsy specimens could not be obtained but we assume that she too had ciliary aplasia. This girl is now very short of breath and intolerant of exercise. Of the parents of these children only one (a mother) has had ciliary morphology studied: posterior nasal brushing revealed no structural abnormalities of cilia.
We suggest
an
autosomal recessive mode of inheritance for this
ciliary aplasia. University Children’s Hospital, Vienna, Austria
A1090
MANFRED GOTZ
Institute of Micromorphology and Electron Microscopy,
University of
Vienna
6 Afzelius BA
"Immotile-cilia" syndrome and ciliary abnormalities induced by infection injury. Am Rev Resp Dis 1981, 124: 107-09 Sorokin SP Reconstruction of centriole formation and ciliogenesis in mammalian lungs J Cell Sci 1968, 3: 207-30. Jahrsdoerfer R. Feldman PS, Rubel EW, Guerrant JL, Eggleston PA, Selden RF. Otitis media and the immotile cilia syndrome Laryngoscope 1979; 89: 769-77 and
7
8.
LEOPOLD STOCKINGER