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Ectodermal dysplasia and immunodeficiency 1(EDAID1)

MedGen UID:
375787
Concept ID:
C1846008
Disease or Syndrome
Synonyms: ECTODERMAL DYSPLASIA AND IMMUNE DEFICIENCY 1; ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH IMMUNE DEFICIENCY; Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema; EDAID1; Hyper-IgM immunodeficiency, X-linked, with hypohidrotic ectodermal dysplasia
 
Gene (location): IKBKG (Xq28)
 
Monarch Initiative: MONDO:0020740
OMIM®: 300291

Definition

Ectodermal dysplasia with immunodeficiency-1 (EDAID1) is an X-linked recessive disorder that characteristically affects only males. Affected individuals have onset of recurrent severe infections due to immunodeficiency in early infancy or in the first years of life. There is increased susceptibility to bacterial, pneumococcal, mycobacterial, and fungal infections. Laboratory studies usually show dysgammaglobulinemia with low IgG subsets and normal or increased IgA and IgM, consistent with impaired 'class-switching' of B cells, although immunologic abnormalities may be subtle compared to the clinical picture, and B- and T-cell numbers are usually normal. There is a poor antibody response to polysaccharide vaccinations, particularly pneumococcus; response to other vaccinations is variable. Patients also have features of ectodermal dysplasia, including conical incisors, hypo/anhidrosis, and thin skin or hair. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, likely due to different hypomorphic mutations, and may be fatal in childhood. Intravenous immunoglobulins and prophylactic antibiotics are used as treatment; some patients may benefit from bone marrow transplantation. Although only males tend to be affected with immunodeficiency, many patients inherit a mutation from a mother who has mild features of IP or conical teeth (summary by Doffinger et al., 2001, Orange et al., 2004, Roberts et al., 2010, Heller et al., 2020). Genetic Heterogeneity of Ectodermal Dysplasia and Immune Deficiency Also see EDAID2 (612132), caused by mutation in the NFKBIA gene (164008). [from OMIM]

Clinical features

From HPO
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Dysgammaglobulinemia
MedGen UID:
41679
Concept ID:
C0013374
Disease or Syndrome
Selective deficiency of one or more, but not all, classes of immunoglobulins.
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.
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.
Increased circulating IgA concentration
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Reduced natural killer cell activity
MedGen UID:
333452
Concept ID:
C1839969
Finding
Reduced ability of the natural killer cell to function in the adaptive immune response.
Increased circulating IgM level
MedGen UID:
333454
Concept ID:
C1839972
Finding
An abnormally increased level of immunoglobulin M in blood.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Severe cytomegalovirus infection
MedGen UID:
1634535
Concept ID:
C4703481
Disease or Syndrome
An unusually severe infection by cytomegalovirus.
Abnormal circulating IgG concentration
MedGen UID:
1687987
Concept ID:
C5139422
Finding
An abnormal deviation from normal levels of IgG immunoglobulin in blood.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Conical incisor
MedGen UID:
341076
Concept ID:
C1856136
Finding
An abnormal conical morphology of the incisor tooth.
Ectodermal dysplasia
MedGen UID:
8544
Concept ID:
C0013575
Disease or Syndrome
Ectodermal dysplasia is a group of conditions in which there is abnormal development of the skin, hair, nails, teeth, or sweat glands.
Aplasia of the eccrine sweat glands
MedGen UID:
868084
Concept ID:
C4022475
Finding
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Butcher C, Abbott BM, Grange D, Fete M, Meyer B, Spinka C, Fete T
Am J Med Genet A 2024 Dec;194(12):e63832. Epub 2024 Aug 9 doi: 10.1002/ajmg.a.63832. PMID: 39126172

Diagnosis

Butcher C, Abbott BM, Grange D, Fete M, Meyer B, Spinka C, Fete T
Am J Med Genet A 2024 Dec;194(12):e63832. Epub 2024 Aug 9 doi: 10.1002/ajmg.a.63832. PMID: 39126172

Therapy

Martuszewski A, Paluszkiewicz P, Sierżęga-Staykov K, Wawrzyniak-Dzierżek E, Salamonowicz-Bodzioch M, Frączkiewicz J, Janeczko-Czarnecka M, Mielcarek-Siedziuk M, Nowak M, Dąbrowska-Leonik N, Wolska-Kuśnierz B, Gul K, Bąbol-Pokora K, Młynarski W, Kałwak K, Ussowicz M
Transplant Proc 2020 Mar;52(2):647-652. Epub 2020 Feb 6 doi: 10.1016/j.transproceed.2019.11.033. PMID: 32035679

Prognosis

Martuszewski A, Paluszkiewicz P, Sierżęga-Staykov K, Wawrzyniak-Dzierżek E, Salamonowicz-Bodzioch M, Frączkiewicz J, Janeczko-Czarnecka M, Mielcarek-Siedziuk M, Nowak M, Dąbrowska-Leonik N, Wolska-Kuśnierz B, Gul K, Bąbol-Pokora K, Młynarski W, Kałwak K, Ussowicz M
Transplant Proc 2020 Mar;52(2):647-652. Epub 2020 Feb 6 doi: 10.1016/j.transproceed.2019.11.033. PMID: 32035679

Clinical prediction guides

Martuszewski A, Paluszkiewicz P, Sierżęga-Staykov K, Wawrzyniak-Dzierżek E, Salamonowicz-Bodzioch M, Frączkiewicz J, Janeczko-Czarnecka M, Mielcarek-Siedziuk M, Nowak M, Dąbrowska-Leonik N, Wolska-Kuśnierz B, Gul K, Bąbol-Pokora K, Młynarski W, Kałwak K, Ussowicz M
Transplant Proc 2020 Mar;52(2):647-652. Epub 2020 Feb 6 doi: 10.1016/j.transproceed.2019.11.033. PMID: 32035679

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