Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome

Margaret W. Leigh, Jessica E. Pittman, Johnny L. Carson, Thomas W. Ferkol, Sharon D. Dell, Stephanie Davis, Michael R. Knowles, Maimoona A. Zariwala

Research output: Contribution to journalArticle

218 Citations (Scopus)

Abstract

Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate (dynein axonemal intermediate chain 1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for primary ciliary dyskinesia is available for the most common mutations. The respiratory manifestations of primary ciliary dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with primary ciliary dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with primary ciliary dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with primary ciliary dyskinesia.

Original languageEnglish (US)
Pages (from-to)473-487
Number of pages15
JournalGenetics in Medicine
Volume11
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Kartagener Syndrome
Movement Disorders
Dyneins
Cilia
Bronchiectasis
Mutation
Alstrom Syndrome
Autosomal Recessive Polycystic Kidney
Bardet-Biedl Syndrome
Sperm Tail
Axoneme
Situs Inversus
Mucociliary Clearance
Autosomal Dominant Polycystic Kidney
Male Infertility
Chronic Bronchitis
Sinusitis
Otitis Media
Genetic Testing
Genes

Keywords

  • Dynein
  • Kartagener syndrome
  • PCD
  • Primary ciliary dyskinesia
  • Situs inversus

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Leigh, M. W., Pittman, J. E., Carson, J. L., Ferkol, T. W., Dell, S. D., Davis, S., ... Zariwala, M. A. (2009). Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome. Genetics in Medicine, 11(7), 473-487. https://doi.org/10.1097/GIM.0b013e3181a53562

Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome. / Leigh, Margaret W.; Pittman, Jessica E.; Carson, Johnny L.; Ferkol, Thomas W.; Dell, Sharon D.; Davis, Stephanie; Knowles, Michael R.; Zariwala, Maimoona A.

In: Genetics in Medicine, Vol. 11, No. 7, 07.2009, p. 473-487.

Research output: Contribution to journalArticle

Leigh, MW, Pittman, JE, Carson, JL, Ferkol, TW, Dell, SD, Davis, S, Knowles, MR & Zariwala, MA 2009, 'Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome', Genetics in Medicine, vol. 11, no. 7, pp. 473-487. https://doi.org/10.1097/GIM.0b013e3181a53562
Leigh, Margaret W. ; Pittman, Jessica E. ; Carson, Johnny L. ; Ferkol, Thomas W. ; Dell, Sharon D. ; Davis, Stephanie ; Knowles, Michael R. ; Zariwala, Maimoona A. / Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome. In: Genetics in Medicine. 2009 ; Vol. 11, No. 7. pp. 473-487.
@article{00fd239fcfc04e00b57f0d7bcd1e4a4d,
title = "Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome",
abstract = "Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate (dynein axonemal intermediate chain 1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for primary ciliary dyskinesia is available for the most common mutations. The respiratory manifestations of primary ciliary dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80{\%}) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50{\%} of patients with primary ciliary dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with primary ciliary dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with primary ciliary dyskinesia.",
keywords = "Dynein, Kartagener syndrome, PCD, Primary ciliary dyskinesia, Situs inversus",
author = "Leigh, {Margaret W.} and Pittman, {Jessica E.} and Carson, {Johnny L.} and Ferkol, {Thomas W.} and Dell, {Sharon D.} and Stephanie Davis and Knowles, {Michael R.} and Zariwala, {Maimoona A.}",
year = "2009",
month = "7",
doi = "10.1097/GIM.0b013e3181a53562",
language = "English (US)",
volume = "11",
pages = "473--487",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Clinical and genetic aspects of primary ciliary dyskinesia/kartagener syndrome

AU - Leigh, Margaret W.

AU - Pittman, Jessica E.

AU - Carson, Johnny L.

AU - Ferkol, Thomas W.

AU - Dell, Sharon D.

AU - Davis, Stephanie

AU - Knowles, Michael R.

AU - Zariwala, Maimoona A.

PY - 2009/7

Y1 - 2009/7

N2 - Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate (dynein axonemal intermediate chain 1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for primary ciliary dyskinesia is available for the most common mutations. The respiratory manifestations of primary ciliary dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with primary ciliary dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with primary ciliary dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with primary ciliary dyskinesia.

AB - Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate (dynein axonemal intermediate chain 1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for primary ciliary dyskinesia is available for the most common mutations. The respiratory manifestations of primary ciliary dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with primary ciliary dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with primary ciliary dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with primary ciliary dyskinesia.

KW - Dynein

KW - Kartagener syndrome

KW - PCD

KW - Primary ciliary dyskinesia

KW - Situs inversus

UR - http://www.scopus.com/inward/record.url?scp=68749097262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68749097262&partnerID=8YFLogxK

U2 - 10.1097/GIM.0b013e3181a53562

DO - 10.1097/GIM.0b013e3181a53562

M3 - Article

C2 - 19606528

AN - SCOPUS:68749097262

VL - 11

SP - 473

EP - 487

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 7

ER -