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Autoinflammatory disease, multisystem, with immune dysregulation, X-linked(ADMIDX)

MedGen UID:
1840213
Concept ID:
C5829577
Disease or Syndrome
Synonym: ADMIDX
 
Gene (location): DOCK11 (Xq24)
 
Monarch Initiative: MONDO:0957494
OMIM®: 301109

Definition

X-linked multisystem autoinflammatory disease with immune dysregulation (ADMIDX) is an X-linked recessive disorder with onset of symptoms in infancy or early childhood. Affected individuals may present with variable cytopenias, including anemia, thrombocytopenia, neutropenia, lymphopenia, or hypogammaglobulinemia, and systemic or organ-specific autoinflammatory manifestations. These include skin lesions, panniculitis, inflammatory bowel disease, pulmonary disease, or arthritis associated with recurrent fever, leukocytosis, lymphoproliferation, and hepatosplenomegaly in the absence of an infectious agent. Some patients have circulating autoantibodies that underlie the cytopenias or systemic features, whereas others do not have circulating autoantibodies. In addition, some patients have recurrent infections, whereas others do not show signs of an immunodeficiency. Laboratory studies are consistent with immune dysregulation, including altered B-cell subsets and variably elevated proinflammatory cytokines. Detailed functional studies of platelets, red cells, and T lymphocytes suggest that abnormal actin cytoskeleton remodeling is a basic defect, indicating that this disorder can be classified as an immune-related actinopathy. Severe complications of the disease may result in death in childhood (Boussard et al., 2023; Block et al., 2023). [from OMIM]

Clinical features

From HPO
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Ulcerative colitis
MedGen UID:
3532
Concept ID:
C0009324
Disease or Syndrome
A chronic inflammatory bowel disease that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset and intermittent periods of exacerbated symptoms contrasting with periods that are relatively symptom-free. In contrast to Crohn's disease this special form of colitis begins in the distal parts of the rectum, spreads continually upwards and affects only mucose and submucose tissue of the colon.
Crohn disease
MedGen UID:
3664
Concept ID:
C0010346
Disease or Syndrome
A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.
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.
Ileitis
MedGen UID:
9410
Concept ID:
C0020877
Disease or Syndrome
Inflammation of the ileum.
Recurrent gastroenteritis
MedGen UID:
815158
Concept ID:
C3808828
Finding
Increased susceptibility to gastroenteritis, an infectious inflammationof the stomach and small intestines manifested by signs and symptoms such as diarheas and abdominal pain, as manifested by recurrent episodes of gastroenteritis.
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
Abnormally increased variability in the size of erythrocytes.
Coombs-positive hemolytic anemia
MedGen UID:
105458
Concept ID:
C0520736
Disease or Syndrome
A type of hemolytic anemia in which the Coombs test is positive.
Mastoiditis
MedGen UID:
7480
Concept ID:
C0024904
Disease or Syndrome
Inflammation of the mucosal lining of the mastoid antrum and mastoid air cell system of the mastoid process.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Polyarticular arthritis
MedGen UID:
56408
Concept ID:
C0162323
Disease or Syndrome
Pain and inflammation in more than five joints.
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 bronchitis
MedGen UID:
148159
Concept ID:
C0741796
Disease or Syndrome
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Acute respiratory distress syndrome
MedGen UID:
1812214
Concept ID:
C2887484
Disease or Syndrome
Acute respiratory distress syndrome (ARDS) is defined as an acute disorder that starts within seven days of the inciting event and is characterized by bilateral lung infiltrates and severe progressive hypoxemia in the absence of any evidence of cardiogenic pulmonary edema. ARDS is defined by the patient's oxygen in arterial blood (PaO2) to the fraction of the oxygen in the inspired air (FiO2). These patients have a PaO2/FiO2 ratio of less than 300.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Systemic lupus erythematosus
MedGen UID:
6146
Concept ID:
C0024141
Disease or Syndrome
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by production of autoantibodies against nuclear, cytoplasmic, and cell surface molecules that transcend organ-specific boundaries. Tissue deposition of antibodies or immune complexes induces inflammation and subsequent injury of multiple organs and finally results in clinical manifestations of SLE, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, and arthritis. Evidence strongly suggests the involvement of genetic components in SLE susceptibility (summary by Oishi et al., 2008). Genetic Heterogeneity of Systemic Lupus Erythematosus An autosomal recessive form of systemic lupus erythematosus (SLEB16; 614420) is caused by mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3. An X-linked dominant form of SLE (SLEB17; 301080) is caused by heterozygous mutation in the TLR7 gene (300365) on chromosome Xp22. See MAPPING and MOLECULAR GENETICS sections for a discussion of genetic heterogeneity of susceptibility to SLE.
Panniculitis
MedGen UID:
45301
Concept ID:
C0030326
Disease or Syndrome
Inflammation of subcutaneous adipose tissue.
Pericarditis
MedGen UID:
18377
Concept ID:
C0031046
Disease or Syndrome
Inflammation of the sac-like covering around the heart (pericardium).
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Rheumatoid factor positive
MedGen UID:
56226
Concept ID:
C0151379
Laboratory or Test Result
The presence in the serum of an autoantibody directed against the Fc portion of IgG.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Decreased circulating IgA concentration
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Anti-smooth muscle antibody positivity
MedGen UID:
116117
Concept ID:
C0241185
Laboratory or Test Result
The presence in serum of antibodies against smooth muscle.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Neutropenia in presence of anti-neutropil antibodies
MedGen UID:
137947
Concept ID:
C0340971
Disease or Syndrome
A type of neutropenia that is observed in the presence of granulocyte-specific antibodies.
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.
Anti-thyroid peroxidase antibody positivity
MedGen UID:
1392952
Concept ID:
C4476743
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against thyroid peroxidase.
Neutrophilic infiltration of the skin
MedGen UID:
1620481
Concept ID:
C4531258
Anatomical Abnormality
A predominantly neutrophilic infiltrate of the dermis and or epidermis (i.e., a large number of neutrophils inferred to have migrated into the skin).
Anti-thyroglobulin antibody positivity
MedGen UID:
1670955
Concept ID:
C4732836
Finding
The presence of autoantibodies (immunoglobulins) in the serum that react to thyroglobulin.
BCGitis
MedGen UID:
1684722
Concept ID:
C5139070
Disease or Syndrome
Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination.
Cytoplasmic antineutrophil antibody positivity
MedGen UID:
1690999
Concept ID:
C5139210
Finding
The presence of autoantibodies in the serum that react against proteins predominantly expressed in cytoplasmic granules of neutrophils.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Anti-U1 ribonucleoprotein antibody positivity
MedGen UID:
1770556
Concept ID:
C5421559
Laboratory or Test Result
The presence autoantibodies in the serum that react to proteins (70 Kd, A, C) that are associated with U1 RNA and form U1snRNP.
Anti-integrin antibody positivity
MedGen UID:
1784328
Concept ID:
C5539874
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against an integrin. Integrins are a family of cell adhesion molecules with 24 known integrin heterodimers. Integrins transduce mechanical and biochemical signals from fibrotic extracellular matrix into the cell, activate latent TGFbeta, and subsequently modulate fibroblast adhesion, migration, and growth.
Anti-type VII collagen antibody
MedGen UID:
1778335
Concept ID:
C5539880
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against collagen type VII.
Discoid lupus erythematosus
MedGen UID:
1811126
Concept ID:
C5574816
Disease or Syndrome
Cutaneous lesion that develops as a dry, scaly, red patch that evolves to an indurated and hyperpigmented plaque with adherent scale. Scarring may result in central white patches (loss of pigmentation) and skin atrophy.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
Thickened nuchal skin fold
MedGen UID:
324644
Concept ID:
C1836940
Finding
A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome.

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