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Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome(CANDF7; IMD31C)

MedGen UID:
481620
Concept ID:
C3279990
Disease or Syndrome
Synonyms: Candidiasis, familial, 7; Immunodeficiency 31C
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): STAT1 (2q32.2)
 
Monarch Initiative: MONDO:0013599
OMIM®: 614162
Orphanet: ORPHA391487

Definition

IMD31C is a disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1 (600555). Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis (CMC). Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation (summary by Uzel et al., 2013 and Sampaio et al., 2013). [from OMIM]

Additional description

From NCBI curation
Immunodeficiency-31C is an autosomal dominant disorder of immunologic dysregulation with highly variable manifestations. Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis. Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation (summary by Uzel et al., 2013 and Sampaio et al., 2013).

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Intussusception
MedGen UID:
43940
Concept ID:
C0021933
Disease or Syndrome
An abnormality of the intestine in which part of the intestine invaginates (telescopes) into another part of the intestine.
Protein-losing enteropathy
MedGen UID:
19522
Concept ID:
C0033680
Disease or Syndrome
Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption. Some patients also exhibit bowel inflammation, recurrent infections associated with hypogammaglobulinemia, and/or angiopathic thromboembolic disease. Patient T lymphocytes show increased complement activation, causing surface deposition of complement and generating soluble C5a (Ozen et al., 2017).
Villous atrophy
MedGen UID:
154306
Concept ID:
C0554101
Finding
The enteric villi are atrophic or absent.
Eosinophilic gastroenteritis
MedGen UID:
220382
Concept ID:
C1262481
Disease or Syndrome
Eosinophilic infiltration of one or more gastrointestinal organs. Gastrointestinal eosinophilia is a broad term for abnormal eosinophil accumulation in the GI tract, involving many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in HES and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
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.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Pulmonary nodule
MedGen UID:
883842
Concept ID:
C0034079
Finding
Focal rounded or ovoid opacity, not more than 3 cm in diameter. Pulmonary nodules are typically observed by chest radiography or computer tomography imaging.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory 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.
Coccidioidomycosis
MedGen UID:
3137
Concept ID:
C0009186
Disease or Syndrome
Infection by a Coccidioides species fungus. These are dimorphic, soil-dwelling, fungi known to cause a broad spectrum of disease, ranging from a mild febrile illness to severe pulmonary manifestations or disseminated disease. The genus Coccidioides is comprised of two genetically distinct species
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
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.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Onychomycosis
MedGen UID:
11825
Concept ID:
C0040261
Disease or Syndrome
A fungal infection of the toenails or fingernails that tends to cause the nails to thicken, discolor, disfigure, and split.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Disseminated histoplasmosis
MedGen UID:
575913
Concept ID:
C0343900
Disease or Syndrome
Histoplasmosis infection involving multiple sites of the body. Disseminated histoplasmosis can involve various organs, including reticuloendothelial organs, gastrointestinal tract, adrenal glands, central nervous system, endovascular structures, kidney, and skin. It typically presents with systemic symptoms like fever, generalized fatigue, night sweats, weight loss, and the symptoms related to the specific organ involved. Severe disseminated disease can manifest as septic shock, multi organ failure, and ARDS.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Immune dysregulation
MedGen UID:
335001
Concept ID:
C1844666
Finding
Altered immune function characterized by lymphoid proliferation, immune activation, and excessive autoreactivity often leading to autoimmune/inflammatory complications.
Recurrent vulvovaginal candidiasis
MedGen UID:
868604
Concept ID:
C4023003
Finding
Recurrent infection involving the vulva, vagina, and adjacent crural areas, whereby the causative agent belongs to the genus Candida.
Chronic oral candidiasis
MedGen UID:
870166
Concept ID:
C4024599
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
Impaired lymphocyte transformation with phytohemagglutinin
MedGen UID:
871152
Concept ID:
C4025625
Finding
Normal peripheral blood lymphocytes, when stimulated by phytohemagglutinin (PHA) are cytotoxic for homologous and heterologous cells but not for autologous cells in monolayer culture. The cytotoxic effect is thought to be indicative of the immunological competence of the lymphocytes.
Decreased lymphocyte proliferation in response to anti-CD3
MedGen UID:
1614554
Concept ID:
C4531165
Finding
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with an anti-CD3 antibody against the T-cell co-receptor, CD3.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

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