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Neutropenia, severe congenital, 11, autosomal dominant(SCN11)

MedGen UID:
1846394
Concept ID:
C5882742
Disease or Syndrome
Synonym: SCN11
 
Gene (location): SEC61A1 (3q21.3)
 
Monarch Initiative: MONDO:0958017
OMIM®: 620674

Definition

Autosomal dominant severe congenital neutropenia-11 (SCN11) is characterized by the onset of recurrent infections, mainly bacterial, in early childhood. Laboratory studies show severe neutropenia due to maturation arrest and impaired development of myeloid cells. Other leukocyte subsets, including B cells and NK cells, may also be subtly affected. Patients should be followed for possible renal dysfunction (Van Nieuwenhove et al., 2020). For discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). [from OMIM]

Clinical features

From HPO
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.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Perianal abscess
MedGen UID:
14677
Concept ID:
C0031019
Disease or Syndrome
The presence of an abscess located around the anus.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bone marrow maturation arrest
MedGen UID:
549798
Concept ID:
C0302173
Cell or Molecular Dysfunction
Interruption of the procecss of diffferentiation of hematopoietic cells in the bone marrow, manifested by an increased proportion of immature cells in the bone marrow.
Pleural empyema
MedGen UID:
4928
Concept ID:
C0014013
Disease or Syndrome
Accumulation of pus in the pleural cavity.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Monocytosis
MedGen UID:
39091
Concept ID:
C0085702
Disease or Syndrome
An increased number of circulating monocytes.
Increased circulating IgA concentration
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Recurrent tonsillitis
MedGen UID:
1781351
Concept ID:
C0740402
Disease or Syndrome
Inflammation of the tonsils that has occurred repeatedly. The definition of recurrent may vary somewhat, but the criteria used recently as a measure of severity were five or more episodes of true tonsillitis per year, symptoms recurring for at least a year, and episodes that are disabling and that prevent normal functioning. In some cases recurrent tonsillitis may be related to immunosusceptibility. Evidence exists for a genetic predisposition for recurrent tonsillitis.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Increased proportion of plasmablasts
MedGen UID:
1693971
Concept ID:
C5139148
Finding
An elevation above the normal proportion of plasmablasts in circulation relative to total number of B cells.
Increased circulating IgG2 level
MedGen UID:
1704424
Concept ID:
C5139256
Finding
An abnormally increased concentration of the IgG2 subtype in the blood circulation.
Recurrent gingivitis
MedGen UID:
1814411
Concept ID:
C5676847
Disease or Syndrome
Repeated occurrences of inflammatory condition of the gums (gingival tissue), most commonly caused by bacterial infection.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Aphthous stomatitis
MedGen UID:
20959
Concept ID:
C0038363
Disease or Syndrome
Oral aphthous ulcers typically present as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.
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.
Poor wound healing
MedGen UID:
377525
Concept ID:
C1851789
Finding
A reduced ability to heal cutaneous wounds.

Recent clinical studies

Etiology

Dobrewa W, Bielska M, Bąbol-Pokora K, Janczar S, Młynarski W
Mutat Res Rev Mutat Res 2024 Jan-Jun;793:108476. Epub 2023 Nov 19 doi: 10.1016/j.mrrev.2023.108476. PMID: 37989463
Dale DC, Dick E, Kelley M, Makaryan V, Connelly J, Bolyard AA
Curr Opin Hematol 2020 Jan;27(1):11-17. doi: 10.1097/MOH.0000000000000554. PMID: 31652152Free PMC Article

Diagnosis

Erdős M, Boyarchuk O, Maródi L
Front Immunol 2022;13:975017. Epub 2022 Sep 8 doi: 10.3389/fimmu.2022.975017. PMID: 36159802Free PMC Article
Dale DC, Dick E, Kelley M, Makaryan V, Connelly J, Bolyard AA
Curr Opin Hematol 2020 Jan;27(1):11-17. doi: 10.1097/MOH.0000000000000554. PMID: 31652152Free PMC Article
Makaryan V, Rosenthal EA, Bolyard AA, Kelley ML, Below JE, Bamshad MJ, Bofferding KM, Smith JD, Buckingham K, Boxer LA, Skokowa J, Welte K, Nickerson DA, Jarvik GP, Dale DC; UW Center for Mendelian Genomics
Hum Mutat 2014 Jul;35(7):824-7. Epub 2014 May 21 doi: 10.1002/humu.22563. PMID: 24753205Free PMC Article

Therapy

Erdős M, Boyarchuk O, Maródi L
Front Immunol 2022;13:975017. Epub 2022 Sep 8 doi: 10.3389/fimmu.2022.975017. PMID: 36159802Free PMC Article

Prognosis

Dobrewa W, Bielska M, Bąbol-Pokora K, Janczar S, Młynarski W
Mutat Res Rev Mutat Res 2024 Jan-Jun;793:108476. Epub 2023 Nov 19 doi: 10.1016/j.mrrev.2023.108476. PMID: 37989463

Clinical prediction guides

Dobrewa W, Bielska M, Bąbol-Pokora K, Janczar S, Młynarski W
Mutat Res Rev Mutat Res 2024 Jan-Jun;793:108476. Epub 2023 Nov 19 doi: 10.1016/j.mrrev.2023.108476. PMID: 37989463
Dale DC, Dick E, Kelley M, Makaryan V, Connelly J, Bolyard AA
Curr Opin Hematol 2020 Jan;27(1):11-17. doi: 10.1097/MOH.0000000000000554. PMID: 31652152Free PMC Article
Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, Yang Y, Bergstrom KL, Mahoney DH, Shardy DL, Alsaleh G, Naegely L, Kolmer A, Paul N, Hanauer A, Rolli V, Müller JS, Alghisi E, Sauteur L, Macquin C, Morlon A, Sancho CS, Amati-Bonneau P, Procaccio V, Mosca-Boidron AL, Marle N, Osmani N, Lefebvre O, Goetz JG, Unal S, Akarsu NA, Radosavljevic M, Chenard MP, Rialland F, Grain A, Béné MC, Eveillard M, Vincent M, Guy J, Faivre L, Thauvin-Robinet C, Thevenon J, Myers K, Fleming MD, Shimamura A, Bottollier-Lemallaz E, Westhof E, Lengerke C, Isidor B, Bahram S
J Clin Invest 2017 Nov 1;127(11):4090-4103. Epub 2017 Oct 3 doi: 10.1172/JCI92876. PMID: 28972538Free PMC Article

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