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Ciliary dyskinesia, primary, 15(CILD15)

MedGen UID:
462487
Concept ID:
C3151137
Disease or Syndrome
Synonyms: CILD15; CILIARY DYSKINESIA, PRIMARY, 15, WITH OR WITHOUT SITUS INVERSUS; Primary Ciliary Dyskinesia; Primary Ciliary Dyskinesia15: CCDC40-Related Primary Ciliary Dyskinesia; Sperm flagellum with disorganization of outer dense fibres and fibrous sheath
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Gene: CCDC40
Cytogenetic location: 17q25.3
OMIM®: 613808

Disease characteristics

Excerpted from the GeneReview: Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic oto-sino-pulmonary disease. More than 75% of full-term neonates with PCD have 'neonatal respiratory distress' requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 6%. Approximately 50% of males with PCD are infertile as a result of abnormal sperm motility.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Maimoona A Zariwala  |  Michael R Knowles  |  Margaret W Leigh   view full author information

Additional descriptions

From OMIM
Primary ciliary dyskinesia-15 is an autosomal recessive disorder characterized by recurrent respiratory infections associated with defects in ciliary inner dynein arms and axonemal disorganization (summary by Becker-Heck et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).  http://www.omim.org/entry/613808
From GHR
Primary ciliary dyskinesia is a disorder characterized by chronic respiratory tract infections, abnormally positioned internal organs, and the inability to have children (infertility). The signs and symptoms of this condition are caused by abnormal cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. They are found in the linings of the airway, the reproductive system, and other organs and tissues. Flagella are tail-like structures, similar to cilia, that propel sperm cells forward. In the respiratory tract, cilia move back and forth in a coordinated way to move mucus towards the throat. This movement of mucus helps to eliminate fluid, bacteria, and particles from the lungs. Most babies with primary ciliary dyskinesia experience breathing problems at birth, which suggests that cilia play an important role in clearing fetal fluid from the lungs. Beginning in early childhood, affected individuals develop frequent respiratory tract infections. Without properly functioning cilia in the airway, bacteria remain in the respiratory tract and cause infection. People with primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections can result in a condition called bronchiectasis, which damages the passages, called bronchi, leading from the windpipe to the lungs and can cause life-threatening breathing problems. Some individuals with primary ciliary dyskinesia have abnormally placed organs within their chest and abdomen. These abnormalities arise early in embryonic development when the differences between the left and right sides of the body are established. About 50 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus totalis). For example, in these individuals the heart is on the right side of the body instead of on the left. Situs inversus totalis does not cause any apparent health problems. When someone with primary ciliary dyskinesia has situs inversus totalis, they are often said to have Kartagener syndrome. Approximately 12 percent of people with primary ciliary dyskinesia have a condition known as heterotaxy or situs ambiguus, which is characterized by abnormalities of the heart, liver, intestines, or spleen. These organs may be structurally abnormal or improperly positioned. In addition, affected individuals may lack a spleen (asplenia) or have multiple spleens (polysplenia). Heterotaxy results from problems establishing the left and right sides of the body during embryonic development. The severity of heterotaxy varies widely among affected individuals. Primary ciliary dyskinesia can also lead to infertility. Vigorous movements of the flagella are necessary to propel the sperm cells forward to the female egg cell. Because their sperm do not move properly, males with primary ciliary dyskinesia are usually unable to father children. Infertility occurs in some affected females and is likely due to abnormal cilia in the fallopian tubes. Another feature of primary ciliary dyskinesia is recurrent ear infections (otitis media), especially in young children. Otitis media can lead to permanent hearing loss if untreated. The ear infections are likely related to abnormal cilia within the inner ear. Rarely, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus), likely due to abnormal cilia in the brain.  http://ghr.nlm.nih.gov/condition/primary-ciliary-dyskinesia

Clinical features

Infertility
MedGen UID:
504598
Concept ID:
CN000737
Finding
Sinusitis
MedGen UID:
504406
Concept ID:
CN000238
Finding
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Recurrent otitis media
MedGen UID:
332967
Concept ID:
C1837887
Finding
Sinusitis
MedGen UID:
504406
Concept ID:
CN000238
Finding
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Situs inversus totalis
MedGen UID:
504917
Concept ID:
CN001542
Finding
A left-right reversal (or \
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Bronchiectasis
MedGen UID:
505109
Concept ID:
CN001911
Finding
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Abnormal axonemal organization of respiratory motile cilia
MedGen UID:
489873
Concept ID:
CN168778
Finding
Abnormal arrangement of the structures of the axoneme, which is the cytoskeletal structure that forms the inner core of the motile cilium and displays a canonical 9 + 2 microtubular pattern of motile cilia studded with dynein arms.
Ciliary dyskinesia
MedGen UID:
506719
Concept ID:
CN168785
Finding
A deviation from the normally well coordinated pattern of intracellular and intercellular synchrony of motile cilia. Dyskinetic cilia usually beat out of synchrony relative to neighboring cilia.
Recurrent otitis media
MedGen UID:
332967
Concept ID:
C1837887
Finding
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding

Recent clinical studies

Etiology

Harris A, Bhullar E, Gove K, Joslin R, Pelling J, Evans HJ, Walker WT, Lucas JS
BMC Pulm Med 2014 Feb 10;14:18. doi: 10.1186/1471-2466-14-18. [Epub ahead of print] PMID: 24507708Free PMC Article
Gokdemir Y, Karadag-Saygi E, Erdem E, Bayindir O, Ersu R, Karadag B, Sekban N, Akyuz G, Karakoc F
Pediatr Pulmonol 2014 Jun;49(6):611-6. Epub 2013 Aug 30 doi: 10.1002/ppul.22861. [Epub ahead of print] PMID: 24039238
Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, Lavange LM, Horton BJ, Qaqish B, Carson JL, Davis SD, Dell SD, Ferkol TW, Atkinson JJ, Olivier KN, Sagel SD, Rosenfeld M, Milla C, Lee HS, Krischer J, Zariwala MA, Knowles MR
Ann Am Thorac Soc 2013 Dec;10(6):574-81. doi: 10.1513/AnnalsATS.201305-110OC. PMID: 24024753Free PMC Article
Papon JF, Bassinet L, Cariou-Patron G, Zerah-Lancner F, Vojtek AM, Blanchon S, Crestani B, Amselem S, Coste A, Housset B, Escudier E, Louis B
Orphanet J Rare Dis 2012 Oct 11;7:78. doi: 10.1186/1750-1172-7-78. [Epub ahead of print] PMID: 23057704Free PMC Article
Magnin ML, Cros P, Beydon N, Mahloul M, Tamalet A, Escudier E, Clément A, Le Pointe HD, Blanchon S
Pediatr Pulmonol 2012 Aug;47(8):816-25. Epub 2012 May 8 doi: 10.1002/ppul.22577. [Epub ahead of print] PMID: 22570319

Diagnosis

Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article
Mata M, Milian L, Armengot M, Carda C
Curr Allergy Asthma Rep 2014 Mar;14(3):420. doi: 10.1007/s11882-014-0420-1. PMID: 24459089
Leigh MW, Hazucha MJ, Chawla KK, Baker BR, Shapiro AJ, Brown DE, Lavange LM, Horton BJ, Qaqish B, Carson JL, Davis SD, Dell SD, Ferkol TW, Atkinson JJ, Olivier KN, Sagel SD, Rosenfeld M, Milla C, Lee HS, Krischer J, Zariwala MA, Knowles MR
Ann Am Thorac Soc 2013 Dec;10(6):574-81. doi: 10.1513/AnnalsATS.201305-110OC. PMID: 24024753Free PMC Article
Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW
Am J Respir Crit Care Med 2013 Oct 15;188(8):913-22. doi: 10.1164/rccm.201301-0059CI. PMID: 23796196Free PMC Article
Türkoğlu K, Orhan K, Demir P, Karabulut B, Can-Karabulut DC
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010 Oct;110(4):e49-56. doi: 10.1016/j.tripleo.2010.05.054. PMID: 20868986

Therapy

Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article
Olivier KN, Shaw PA, Glaser TS, Bhattacharyya D, Fleshner M, Brewer CC, Zalewski CK, Folio LR, Siegelman JR, Shallom S, Park IK, Sampaio EP, Zelazny AM, Holland SM, Prevots DR
Ann Am Thorac Soc 2014 Jan;11(1):30-5. doi: 10.1513/AnnalsATS.201307-231OC. PMID: 24460437Free PMC Article
Gokdemir Y, Karadag-Saygi E, Erdem E, Bayindir O, Ersu R, Karadag B, Sekban N, Akyuz G, Karakoc F
Pediatr Pulmonol 2014 Jun;49(6):611-6. Epub 2013 Aug 30 doi: 10.1002/ppul.22861. [Epub ahead of print] PMID: 24039238
Failly M, Bartoloni L, Letourneau A, Munoz A, Falconnet E, Rossier C, de Santi MM, Santamaria F, Sacco O, DeLozier-Blanchet CD, Lazor R, Blouin JL
J Med Genet 2009 Apr;46(4):281-6. doi: 10.1136/jmg.2008.061176. PMID: 19357118
Geremek M, Schoenmaker F, Zietkiewicz E, Pogorzelski A, Diehl S, Wijmenga C, Witt M
Eur J Hum Genet 2008 Jun;16(6):688-95. Epub 2008 Feb 13 doi: 10.1038/ejhg.2008.5. [Epub ahead of print] PMID: 18270537

Prognosis

Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article
Gokdemir Y, Karadag-Saygi E, Erdem E, Bayindir O, Ersu R, Karadag B, Sekban N, Akyuz G, Karakoc F
Pediatr Pulmonol 2014 Jun;49(6):611-6. Epub 2013 Aug 30 doi: 10.1002/ppul.22861. [Epub ahead of print] PMID: 24039238
Magnin ML, Cros P, Beydon N, Mahloul M, Tamalet A, Escudier E, Clément A, Le Pointe HD, Blanchon S
Pediatr Pulmonol 2012 Aug;47(8):816-25. Epub 2012 May 8 doi: 10.1002/ppul.22577. [Epub ahead of print] PMID: 22570319
Marthin JK, Mortensen J, Pressler T, Nielsen KG
Chest 2007 Sep;132(3):966-76. Epub 2007 Jul 23 doi: 10.1378/chest.06-2951. [Epub ahead of print] PMID: 17646235
Mahut B, Escudier E, de Blic J, Zerah-Lancner F, Coste A, Harf A, Delclaux C
Pediatr Pulmonol 2006 Feb;41(2):158-63. doi: 10.1002/ppul.20329. PMID: 16353174

Clinical prediction guides

Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article
Olivier KN, Shaw PA, Glaser TS, Bhattacharyya D, Fleshner M, Brewer CC, Zalewski CK, Folio LR, Siegelman JR, Shallom S, Park IK, Sampaio EP, Zelazny AM, Holland SM, Prevots DR
Ann Am Thorac Soc 2014 Jan;11(1):30-5. doi: 10.1513/AnnalsATS.201307-231OC. PMID: 24460437Free PMC Article
Gokdemir Y, Karadag-Saygi E, Erdem E, Bayindir O, Ersu R, Karadag B, Sekban N, Akyuz G, Karakoc F
Pediatr Pulmonol 2014 Jun;49(6):611-6. Epub 2013 Aug 30 doi: 10.1002/ppul.22861. [Epub ahead of print] PMID: 24039238
Magnin ML, Cros P, Beydon N, Mahloul M, Tamalet A, Escudier E, Clément A, Le Pointe HD, Blanchon S
Pediatr Pulmonol 2012 Aug;47(8):816-25. Epub 2012 May 8 doi: 10.1002/ppul.22577. [Epub ahead of print] PMID: 22570319
Piacentini GL, Bodini A, Peroni D, Rigotti E, Pigozzi R, Pradal U, Boner AL
Respir Med 2008 Apr;102(4):541-7. Epub 2008 Jan 9 doi: 10.1016/j.rmed.2007.11.013. [Epub ahead of print] PMID: 18187313

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