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Combined immunodeficiency due to STK4 deficiency(IMD110)

MedGen UID:
766857
Concept ID:
C3553943
Disease or Syndrome
Synonyms: IMD110; MST1 DEFICIENCY; STK4 DEFICIENCY; T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): STK4 (20q13.12)
 
Monarch Initiative: MONDO:0013934
OMIM®: 614868
Orphanet: ORPHA314689

Definition

Immunodeficiency-110 (IMD110) is an autosomal recessive primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, and autoimmune manifestations. Patients are at risk for developing lymphoproliferative disorders or lymphoma, particularly associated with EBV. Some patients may show cardiac malformations, including atrial septal defect (Abdollahpour et al., 2012; Nehme et al., 2012). [from OMIM]

Clinical features

From HPO
Classic Hodgkin lymphoma
MedGen UID:
9283
Concept ID:
C0019829
Neoplastic Process
Classic Hodgkin lymphoma is a lymph node cancer of germinal center B-cell origin. Hodgkin lymphoma tumors consist of a minority of malignant cells, known as 'Reed-Sternberg' (RS) cells, mixed with reactive lymphocytes and other benign inflammatory cells. A defining feature of RS cells is the presence of 2 nuclei (summary by Salipante et al., 2009).
Lymphoproliferative disorder
MedGen UID:
6162
Concept ID:
C0024314
Neoplastic Process
A disorder characterized by proliferation of lymphocytes at various stages of differentiation. Lymphoproliferative disorders can be neoplastic (clonal, as in lymphomas and leukemias) or reactive (polyclonal, as in infectious mononucleosis).
Verrucae
MedGen UID:
777120
Concept ID:
C3665596
Finding
Warts, benign growths on the skin or mucous membranes that cause cosmetic problems as well as pain and discomfort. Warts most often occur on the hands, feet, and genital areas.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
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.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Chronic mucocutaneous candidiasis
MedGen UID:
2426
Concept ID:
C0006845
Disease or Syndrome
Recurrent or persistent superficial Candida infections of the skin, mucous membranes, and nails.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Molluscum contagiosum
MedGen UID:
10081
Concept ID:
C0026393
Disease or Syndrome
Molluscum contagiosum is a cutaneous viral infection that is commonly observed in both healthy and immunocompromised children. The infection is caused by a member of the Poxviridae family, the molluscum contagiosum virus. Molluscum contagiosum presents as single or multiple small white or flesh-colored papules that typically have a central umbilication. The central umbilication may be difficult to observe in young children and, instead, may bear an appearance similar to an acneiform eruption. The lesions vary in size (from 1 mm to 1 cm in diameter) and are painless, although a subset of patients report pruritus in the area of infection. On average, 11-20 papules appear on the body during the course of infection and generally remains a self-limiting disease. However, in immunosuppressed patients, molluscum contagiosum can be a severe infection with hundreds of lesions developing on the body. Extensive eruption is indicative of an advanced immunodeficiency state.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Recurrent fungal infections
MedGen UID:
336166
Concept ID:
C1844384
Disease or Syndrome
Increased susceptibility to fungal infections, as manifested by multiple episodes of fungal infection.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Persistent EBV viremia
MedGen UID:
767466
Concept ID:
C3554552
Finding
Persistent presence of Epstein-Barr virus in the blood.
Disseminated molluscum contagiosum
MedGen UID:
1693458
Concept ID:
C5139182
Disease or Syndrome
The presense of molluscum contagiosum lesions across multiple areas of the body.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Recurrent aphthous stomatitis
MedGen UID:
445425
Concept ID:
C2937365
Disease or Syndrome
Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCombined immunodeficiency due to STK4 deficiency
Follow this link to review classifications for Combined immunodeficiency due to STK4 deficiency in Orphanet.

Professional guidelines

PubMed

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article

Recent clinical studies

Etiology

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Abolnezhadian F, Iranparast S, Ahmadpour F
Iran J Immunol 2020 Dec;17(4):333-340. doi: 10.22034/iji.2020.83003.1607. PMID: 33382390
Ashrafi F, Klein C, Poorpooneh M, Sherkat R, Khoshnevisan R
Medicine (Baltimore) 2020 Feb;99(9):e18601. doi: 10.1097/MD.0000000000018601. PMID: 32118703Free PMC Article
Cohen JI
Curr Top Microbiol Immunol 2015;390(Pt 1):241-65. doi: 10.1007/978-3-319-22822-8_10. PMID: 26424649Free PMC Article
Halacli SO, Ayvaz DC, Sun-Tan C, Erman B, Uz E, Yilmaz DY, Ozgul K, Tezcan İ, Sanal O
Clin Immunol 2015 Dec;161(2):316-23. Epub 2015 Jun 25 doi: 10.1016/j.clim.2015.06.010. PMID: 26117625

Diagnosis

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Cagdas D, Halacli SO, Tan C, Esenboga S, Karaatmaca B, Cetinkaya PG, Balcı-Hayta B, Ayhan A, Uner A, Orhan D, Boztug K, Ozen S, Topaloglu R, Sanal O, Tezcan I
J Allergy Clin Immunol Pract 2021 Oct;9(10):3752-3766.e4. Epub 2021 Jun 17 doi: 10.1016/j.jaip.2021.05.032. PMID: 34146746
Vignesh P, Rawat A, Kumrah R, Singh A, Gummadi A, Sharma M, Kaur A, Nameirakpam J, Jindal A, Suri D, Gupta A, Khadwal A, Saikia B, Minz RW, Sharma K, Desai M, Taur P, Gowri V, Pandrowala A, Dalvi A, Jodhawat N, Kambli P, Madkaikar MR, Bhattad S, Ramprakash S, Cp R, Jayaram A, Sivasankaran M, Munirathnam D, Balaji S, Rajendran A, Aggarwal A, Singh K, Na F, George B, Mehta A, Lashkari HP, Uppuluri R, Raj R, Bartakke S, Gupta K, Sreedharanunni S, Ogura Y, Kato T, Imai K, Chan KW, Leung D, Ohara O, Nonoyama S, Hershfield M, Lau YL, Singh S
Front Immunol 2020;11:619146. Epub 2021 Feb 8 doi: 10.3389/fimmu.2020.619146. PMID: 33628209Free PMC Article
Halacli SO, Ayvaz DC, Sun-Tan C, Erman B, Uz E, Yilmaz DY, Ozgul K, Tezcan İ, Sanal O
Clin Immunol 2015 Dec;161(2):316-23. Epub 2015 Jun 25 doi: 10.1016/j.clim.2015.06.010. PMID: 26117625
Dotta L, Badolato R
Immunol Lett 2014 Oct;161(2):222-5. Epub 2013 Dec 4 doi: 10.1016/j.imlet.2013.11.018. PMID: 24316408

Therapy

Uygun V, Keleş S, Daloğlu H, Öztürkmen S, Yalçın K, Karasu G, Yeşilipek A
Pediatr Transplant 2023 Mar;27(2):e14439. Epub 2022 Nov 16 doi: 10.1111/petr.14439. PMID: 36394186
Sherkat R, Sabri MR, Dehghan B, Bigdelian H, Reisi N, Afsharmoghadam N, Rahimi H, Rahmanian N, Klein C
Medicine (Baltimore) 2017 Dec;96(48):e8852. doi: 10.1097/MD.0000000000008852. PMID: 29310365Free PMC Article

Prognosis

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article
Ashrafi F, Klein C, Poorpooneh M, Sherkat R, Khoshnevisan R
Medicine (Baltimore) 2020 Feb;99(9):e18601. doi: 10.1097/MD.0000000000018601. PMID: 32118703Free PMC Article
Sherkat R, Sabri MR, Dehghan B, Bigdelian H, Reisi N, Afsharmoghadam N, Rahimi H, Rahmanian N, Klein C
Medicine (Baltimore) 2017 Dec;96(48):e8852. doi: 10.1097/MD.0000000000008852. PMID: 29310365Free PMC Article

Clinical prediction guides

Delavari S, Rasouli SE, Fekrvand S, Chavoshzade Z, Mahdaviani SA, Shirmast P, Sharafian S, Sherkat R, Momen T, Aleyasin S, Ahanchian H, Sadeghi-Shabestari M, Esmaeilzadeh H, Barzamini S, Tarighatmonfared F, Salehi H, Esmaeili M, Marzani Z, Fathi N, Abolnezhadian F, Rad MK, Saeedi-Boroujeni A, Shirkani A, Bagheri Z, Salami F, Shad TM, Marzbali MY, Mojtahedi H, Razavi A, Tavakolinia N, Cheraghi T, Tavakol M, Shafiei A, Behniafard N, Ebrahimi SS, Sepahi N, Ghaneimoghadam A, Rezaei A, Kalantari A, Abolhassani H, Rezaei N
Clin Immunol 2024 Feb;259:109896. Epub 2024 Jan 4 doi: 10.1016/j.clim.2024.109896. PMID: 38184287
Dang TS, Willet JD, Griffin HR, Morgan NV, O'Boyle G, Arkwright PD, Hughes SM, Abinun M, Tee LJ, Barge D, Engelhardt KR, Jackson M, Cant AJ, Maher ER, Koref MS, Reynard LN, Ali S, Hambleton S
J Clin Immunol 2016 Feb;36(2):117-22. Epub 2016 Jan 22 doi: 10.1007/s10875-016-0232-2. PMID: 26801501Free PMC Article

Recent systematic reviews

López-Nevado M, González-Granado LI, Ruiz-García R, Pleguezuelo D, Cabrera-Marante O, Salmón N, Blanco-Lobo P, Domínguez-Pinilla N, Rodríguez-Pena R, Sebastián E, Cruz-Rojo J, Olbrich P, Ruiz-Contreras J, Paz-Artal E, Neth O, Allende LM
Front Immunol 2021;12:671755. Epub 2021 Aug 10 doi: 10.3389/fimmu.2021.671755. PMID: 34447369Free PMC Article

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