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Ciliary dyskinesia, primary, 44(CILD44)

MedGen UID:
1716408
Concept ID:
C5394063
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 44, WITHOUT SITUS INVERSUS
 
Gene (location): NEK10 (3p24.1)
 
Monarch Initiative: MONDO:0032914
OMIM®: 618781

Definition

Primary ciliary dyskinesia-44 (CILD44) is an autosomal recessive disorder characterized by recurrent sinopulmonary infections resulting from defective mucociliary clearance. Affected individuals have onset of symptoms in infancy or early childhood, and the repetitive nature of the disorder results in bronchiectasis. Although respiratory epithelial cell motile cilia are shorter than normal and overall ciliary motion is decreased, nasal nitric oxide, radial ciliary structure, and ciliary beat frequency are normal. In addition, patients do not have situs inversus (summary by Chivukula et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Clinical features

From HPO
Heterotaxy
MedGen UID:
75620
Concept ID:
C0266642
Congenital Abnormality
An abnormality in which the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Decreased nasal nitric oxide
MedGen UID:
767344
Concept ID:
C3554430
Finding
Reduced level of nasal nitric oxide (nNO). Current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines for nNO measurements recommend air aspiration via a nasal probe while the subject exhales through the mouth against resistance in order to maintain velum closure.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Reduced forced expiratory volume in one second
MedGen UID:
1687063
Concept ID:
C5139283
Finding
An abnormal reduction in the amount of air a person can forcefully expel in one second.
Otitis media
MedGen UID:
45253
Concept ID:
C0029882
Disease or Syndrome
Inflammation or infection of the middle ear.
Abnormal sweat electrolytes
MedGen UID:
868031
Concept ID:
C4022422
Finding

Professional guidelines

PubMed

Schreck LD, Goutaki M, Jörger P, Dexter K, Manion M, Christin-Maitre S, Maitre B; COVID-PCD Patient Advisory Group, Kuehni CE, Pedersen ESL
Pediatr Pulmonol 2024 Feb;59(2):281-290. Epub 2023 Nov 7 doi: 10.1002/ppul.26743. PMID: 37933800
Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Pensabene M, Gambazza S, Carta F, Rocchi A, Lelii M, Madini B, Hassan V, Piotto M, Patria MF
Pediatr Pulmonol 2023 Apr;58(4):1051-1058. Epub 2022 Dec 29 doi: 10.1002/ppul.26293. PMID: 36571235

Recent clinical studies

Etiology

Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Fein V, Maier C, Schlegtendal A, Denz R, Koerner-Rettberg C, Brinkmann F
Pediatr Pulmonol 2023 Jul;58(7):1950-1958. Epub 2023 Apr 25 doi: 10.1002/ppul.26417. PMID: 37096790
Güney E, Emiralioğlu N, Cinel G, Yalçın E, Doğru D, Kiper N, Özçelik HU
Turk J Pediatr 2019;61(1):20-25. doi: 10.24953/turkjped.2019.01.004. PMID: 31559717
Keniş Coşkun Ö, Gençer Atalay K, Erdem E, Karadag-Saygi E, Gökdemir Y, Karadağ B
Pediatr Pulmonol 2019 Dec;54(12):1936-1940. Epub 2019 Aug 29 doi: 10.1002/ppul.24503. PMID: 31468736
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article

Diagnosis

Rezaei M, Soheili A, Ziai SA, Fakharian A, Toreyhi H, Pourabdollah M, Ghorbani J, Karimi-Galougahi M, Mahdaviani SA, Hasanzad M, Eslaminejad A, Ghaffaripour HA, Mahmoudian S, Rodafshani Z, Mirenayat MS, Varahram M, Marjani M, Tabarsi P, Mansouri D, Jamaati HR, Velayati AA
Sci Rep 2022 Feb 11;12(1):2375. doi: 10.1038/s41598-022-06370-w. PMID: 35149751Free PMC Article
Baz-Redón N, Rovira-Amigo S, Paramonov I, Castillo-Corullón S, Cols Roig M, Antolín M, García Arumí E, Torrent-Vernetta A, de Mir Messa I, Gartner S, Iglesias Serrano I, Caballero-Rabasco MA, Asensio de la Cruz Ó, Vizmanos-Lamotte G, Martín de Vicente C, Martínez-Colls MDM, Reula A, Escribano A, Dasí F, Armengot-Carceller M, Polverino E, Amengual Pieras E, Amaro-Rodríguez R, Garrido-Pontnou M, Tizzano E, Camats-Tarruella N, Fernández-Cancio M, Moreno-Galdó A
Arch Bronconeumol (Engl Ed) 2021 Mar;57(3):186-194. Epub 2020 Apr 3 doi: 10.1016/j.arbres.2020.02.010. PMID: 32253119
Güney E, Emiralioğlu N, Cinel G, Yalçın E, Doğru D, Kiper N, Özçelik HU
Turk J Pediatr 2019;61(1):20-25. doi: 10.24953/turkjped.2019.01.004. PMID: 31559717
Collins SA, Gove K, Walker W, Lucas JS
Eur Respir J 2014 Dec;44(6):1589-99. Epub 2014 Oct 16 doi: 10.1183/09031936.00088614. PMID: 25323224
Hogg C
Paediatr Respir Rev 2009 Jun;10(2):44-50. Epub 2009 Apr 9 doi: 10.1016/j.prrv.2008.10.001. PMID: 19410200

Therapy

Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Güney E, Emiralioğlu N, Cinel G, Yalçın E, Doğru D, Kiper N, Özçelik HU
Turk J Pediatr 2019;61(1):20-25. doi: 10.24953/turkjped.2019.01.004. PMID: 31559717
Stewart E, Adams PS, Tian X, Khalifa O, Wearden P, Zahid M, Lo CW
J Thorac Cardiovasc Surg 2018 Feb;155(2):755-763.e7. Epub 2017 Sep 20 doi: 10.1016/j.jtcvs.2017.09.050. PMID: 29056267Free PMC Article
Boon M, Vermeulen FL, Gysemans W, Proesmans M, Jorissen M, De Boeck K
Thorax 2015 Apr;70(4):339-45. Epub 2015 Feb 11 doi: 10.1136/thoraxjnl-2014-206578. PMID: 25673230
Phillips GE, Thomas S, Heather S, Bush A
Eur Respir J 1998 Jun;11(6):1389-91. doi: 10.1183/09031936.98.11061389. PMID: 9657584

Prognosis

Shi Y, Lei Q, Han Q
Medicine (Baltimore) 2023 Dec 29;102(52):e36271. doi: 10.1097/MD.0000000000036271. PMID: 38206729Free PMC Article
Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Fein V, Maier C, Schlegtendal A, Denz R, Koerner-Rettberg C, Brinkmann F
Pediatr Pulmonol 2023 Jul;58(7):1950-1958. Epub 2023 Apr 25 doi: 10.1002/ppul.26417. PMID: 37096790
Pensabene M, Gambazza S, Carta F, Rocchi A, Lelii M, Madini B, Hassan V, Piotto M, Patria MF
Pediatr Pulmonol 2023 Apr;58(4):1051-1058. Epub 2022 Dec 29 doi: 10.1002/ppul.26293. PMID: 36571235
Coren ME, Meeks M, Morrison I, Buchdahl RM, Bush A
Acta Paediatr 2002;91(6):667-9. doi: 10.1080/080352502760069089. PMID: 12162599

Clinical prediction guides

Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Fein V, Maier C, Schlegtendal A, Denz R, Koerner-Rettberg C, Brinkmann F
Pediatr Pulmonol 2023 Jul;58(7):1950-1958. Epub 2023 Apr 25 doi: 10.1002/ppul.26417. PMID: 37096790
Asfuroglu P, Ramasli Gursoy T, Sismanlar Eyuboglu T, Aslan AT
Pediatr Pulmonol 2021 Aug;56(8):2717-2723. Epub 2021 Jun 21 doi: 10.1002/ppul.25533. PMID: 34133086
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article
Hoffmann MB, Wolynski B, Bach M, Meltendorf S, Behrens-Baumann W, Golla F
Invest Ophthalmol Vis Sci 2011 Jun 28;52(7):4617-25. doi: 10.1167/iovs.11-7194. PMID: 21508109

Recent systematic reviews

Zhang Y, Song A, Liu J, Dai J, Lin J
J Investig Med 2021 Mar;69(3):742-748. Epub 2020 Dec 3 doi: 10.1136/jim-2020-001479. PMID: 33272932
Collins SA, Gove K, Walker W, Lucas JS
Eur Respir J 2014 Dec;44(6):1589-99. Epub 2014 Oct 16 doi: 10.1183/09031936.00088614. PMID: 25323224

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