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Osteomyelitis

MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Synonym: Osteomyelitis (disease)
SNOMED CT: OSTM - Osteomyelitis (60168000); OM - Osteomyelitis (60168000); Osteomyelitis (60168000); Pyogenic inflammation of bone (60168000)
 
HPO: HP:0002754
Monarch Initiative: MONDO:0005246

Definition

Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism. [from HPO]

Conditions with this feature

Hereditary insensitivity to pain with anhidrosis
MedGen UID:
6915
Concept ID:
C0020074
Disease or Syndrome
NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of NTRK1-CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Congenital sensory neuropathy with selective loss of small myelinated fibers
MedGen UID:
6916
Concept ID:
C0020075
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.\n\nThe signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
Fanconi-like syndrome
MedGen UID:
56237
Concept ID:
C0151638
Disease or Syndrome
A syndrome characterized by pancytopenia, immune deficiency and cutaneous malignancies.
Leukocyte adhesion deficiency 1
MedGen UID:
98310
Concept ID:
C0398738
Disease or Syndrome
Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder of neutrophil function resulting from a deficiency of the beta-2 integrin subunit of the leukocyte cell adhesion molecule. The leukocyte cell adhesion molecule is present on the surface of peripheral blood mononuclear leukocytes and granulocytes and mediates cell-cell and cell-extracellular matrix adhesion. LAD is characterized by recurrent bacterial infections; impaired pus formation and wound healing; abnormalities of a wide variety of adhesion-dependent functions of granulocytes, monocytes, and lymphocytes; and a lack of beta-2/alpha-L, beta-2/alpha-M, and beta-2/alpha-X expression. Genetic Heterogeneity of Leukocyte Adhesion Deficiency Also see LAD2 (266265), caused by mutation in the SLC35C1 gene (605881), and LAD3 (612840), caused by mutation in the FERMT3 gene (607901).
Chronic multifocal osteomyelitis
MedGen UID:
140822
Concept ID:
C0410422
Disease or Syndrome
Chronic recurrent multifocal osteomyelitis-3 (CRMO3) is an autosomal dominant autoinflammatory bone disease characterized by early childhood onset of bone pain and arthritis caused by sterile osteomyelitis. The disorder results from constitutive activation of the IL1-mediated inflammatory pathway due to loss of IL1 receptor sensitivity to its antagonist IL1RN (147679). et al. (2023) suggested the term 'Loss of IL1R1 Sensitivity to IL1RA (IL1RN)' or 'LIRSA' as a designation for this disorder. For a discussion of genetic heterogeneity of CRMO, see 609628.
Gnathodiaphyseal dysplasia
MedGen UID:
331575
Concept ID:
C1833736
Disease or Syndrome
Gnathodiaphyseal dysplasia (GDD) is an autosomal dominant generalized skeletal syndrome characterized by cementoosseous lesions of the jawbones, in conjunction with bone fragility, bowing/cortical thickening of tubular bones, and diaphyseal sclerosis of long bones (summary by Marconi et al., 2013).
Hyper-IgM syndrome type 4
MedGen UID:
330847
Concept ID:
C1842413
Disease or Syndrome
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process (summary by Imai et al., 2003). For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Granulomatous disease, chronic, X-linked
MedGen UID:
336165
Concept ID:
C1844376
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Autosomal recessive osteopetrosis 2
MedGen UID:
342420
Concept ID:
C1850126
Disease or Syndrome
Osteopetrosis is a bone disease that makes bone tissue abnormally compact and dense and also prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant or autosomal recessive. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.\n\nAutosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In affected people with no symptoms, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. \n\nIn individuals with ADO who develop signs and symptoms, the major features of the condition include multiple bone fractures after minor injury, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.\n\nAutosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.\n\nOther features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).\n\nA few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.
Autosomal recessive osteopetrosis 1
MedGen UID:
376708
Concept ID:
C1850127
Disease or Syndrome
Osteopetrosis (OPT) is a life-threatening disease caused by subnormal osteoclast function, with an incidence of 1 in 250,000 births. The disease usually manifests in the first few months of life with macrocephaly and frontal bossing, resulting in a characteristic facial appearance. Defective bone remodeling of the skull results in choanal stenosis with concomitant respiratory problems and feeding difficulties, which are the first clinical manifestation of disease. The expanding bone encroaches on neural foramina, leading to blindness, deafness, and facial palsy. Complete visual loss invariably occurs in all untreated patients, and hearing loss is estimated to affect 78% of patients with OPT. Tooth eruption defects and severe dental caries are common. Calcium feedback hemostasis is impaired, and children with OPT are at risk of developing hypocalcemia with attendant tetanic seizures and secondary hyperparathyroidism. The most severe complication of OPT, limiting survival, is bone marrow insufficiency. The abnormal expansion of cortical and trabecular bone physically limits the availability of medullary space for hematopoietic activity, leading to life-threatening cytopenia and secondary expansion of extramedullary hematopoiesis at sites such as the liver and spleen (summary by Aker et al., 2012). Genetic Heterogeneity of Autosomal Recessive Osteopetrosis Other forms of autosomal recessive infantile malignant osteopetrosis include OPTB4 (611490), which is caused by mutation in the CLCN7 gene (602727) on chromosome 16p13, and OPTB5 (259720), which is caused by mutation in the OSTM1 gene (607649) on chromosome 6q21. A milder, osteoclast-poor form of autosomal recessive osteopetrosis (OPTB2; 259710) is caused by mutation in the TNFSF11 gene (602642) on chromosome 13q14, an intermediate form (OPTB6; 611497) is caused by mutation in the PLEKHM1 gene (611466) on chromosome 17q21, and a severe osteoclast-poor form associated with hypogammaglobulinemia (OPTB7; 612301) is caused by mutation in the TNFRSF11A gene (603499) on chromosome 18q22. Another form of autosomal recessive osteopetrosis (OPTB8; 615085) is caused by mutation in the SNX10 gene (614780) on chromosome 7p15. A form of autosomal recessive osteopetrosis associated with renal tubular acidosis (OPTB3; 259730) is caused by mutation in the CA2 gene (611492) on chromosome 8q21. OPTB9 (620366) is caused by mutation in the SLC4A2 gene (109280) on chromosome 7q36. Autosomal dominant forms of osteopetrosis are more benign (see OPTA1, 607634).
Cervical hypertrichosis-peripheral neuropathy syndrome
MedGen UID:
341004
Concept ID:
C1855902
Disease or Syndrome
A rare genetic syndrome characterized by the association of congenital hypertrichosis in the anterior cervical region with peripheral sensory and motor neuropathy. Associated features may include retinal anomalies, spina bifida, kyphoscoliosis and hallux valgus, and developmental delay (one case). There have been no further descriptions in the literature since 1993.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2
MedGen UID:
383869
Concept ID:
C1856245
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1
MedGen UID:
341102
Concept ID:
C1856251
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative
MedGen UID:
383872
Concept ID:
C1856255
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Majeed syndrome
MedGen UID:
351273
Concept ID:
C1864997
Disease or Syndrome
Majeed syndrome (MJDS) is an autosomal recessive pediatric multisystem autoinflammatory disorder characterized by chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia; some patients may also develop neutrophilic dermatosis. Additional features may include fever, failure to thrive, and neutropenia. Laboratory studies show elevated inflammatory markers consistent with activation of the proinflammatory IL1 (147760) pathway (summary by Ferguson and El-Shanti, 2021). Genetic Heterogeneity of Chronic Recurrent Multifocal Osteomyelitis See also CRMO2 (612852), caused by mutation in the IL1RN gene (147679) on chromosome 2q14; and CRMO3 (259680), caused by mutation in the IL1R1 gene (147810) on chromosome 2q12.
Sterile multifocal osteomyelitis with periostitis and pustulosis
MedGen UID:
411230
Concept ID:
C2748507
Disease or Syndrome
Chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2) is an autosomal recessive multisystemic autoinflammatory disorder characterized by onset of symptoms in early infancy. Affected individuals present with joint swelling and pain, pustular rash, oral mucosal lesions, and fetal distress. The disorder progresses in severity to generalized severe pustulosis or ichthyosiform lesions and diffuse bone lesions. Radiographic studies show widening of the anterior rib ends, periosteal elevation along multiple long bones, multifocal osteolytic lesions, heterotopic ossification, and metaphyseal erosions of the long bones. Laboratory studies show elevation of inflammatory markers. The disorder results from unopposed activation of the IL1 inflammatory signaling pathway. Treatment with the interleukin-1 receptor antagonist anakinra may result in clinical improvement (Aksentijevich et al., 2009). For a discussion of genetic heterogeneity of CRMO, see 609628.
Neuropathy, hereditary sensory and autonomic, type 2B
MedGen UID:
413474
Concept ID:
C2751092
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease.
Neuropathy, hereditary sensory and autonomic, type 1C
MedGen UID:
462246
Concept ID:
C3150896
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type IC (HSAN1C) is an autosomal dominant neurologic disorder characterized by sensory neuropathy with variable autonomic and motor involvement. Most patients have adult onset of slowly progressive distal sensory impairment manifest as numbness, tingling, or pain, as well as distal muscle atrophy. Complications include ulceration and osteomyelitis. Some patients may have a more severe phenotype with onset in childhood. Electrophysiologic studies show a predominantly axonal neuropathy with some demyelinating features. Some patients may have evidence of central nervous system involvement, including macular telangiectasia type 2 and/or pyramidal signs. Affected individuals have increased levels of plasma 1-deoxysphingolipids (1-deoxySLs), which are thought to be neurotoxic. (summary by Rotthier et al., 2010, Gantner et al., 2019, and Triplett et al., 2019). Oral supplementation with serine decreases 1-deoxySL and may offer some clinical benefits (Fridman et al., 2019). For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400).
Neuropathy, hereditary sensory, type 1D
MedGen UID:
462322
Concept ID:
C3150972
Disease or Syndrome
Spastic paraplegia 3A (SPG3A; also known as ATL1-HSP) is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. Compared to other forms of autosomal dominant hereditary spastic paraplegia (HSP), in which diminished vibration sense (caused by degeneration of the corticospinal tracts and dorsal columns) and urinary bladder hyperactivity are present in all affected individuals, these findings occur in a minority of individuals with SPG3A. The average age of onset is four years. More than 80% of reported individuals manifest spastic gait before the end of the first decade of life. Most persons with early-onset ATL1-HSP have a "pure" ("uncomplicated") HSP; however, complicated HSP with axonal motor neuropathy and/or distal amyotrophy with lower motor neuron involvement (Silver syndrome phenotype) has been observed. The rate of progression in ATL1-HSP is slow, and wheelchair dependency or need for a walking aid (cane, walker, or wheelchair) is relatively rare.
Hereditary sensory neuropathy-deafness-dementia syndrome
MedGen UID:
481515
Concept ID:
C3279885
Disease or Syndrome
DNMT1-related disorder is a degenerative disorder of the central and peripheral nervous systems comprising a phenotypic spectrum that includes hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). DNMT1 disorder is often characterized by moderate-to-severe sensorineural hearing loss beginning in the teens or early 20s, sensory impairment, sudomotor dysfunction (loss of sweating), and dementia usually beginning in the mid-40s. In some affected individuals, narcolepsy/cataplexy syndrome and ataxia are predominant findings.
Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
MedGen UID:
481620
Concept ID:
C3279990
Disease or Syndrome
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).
Monocytopenia with susceptibility to infections
MedGen UID:
481660
Concept ID:
C3280030
Disease or Syndrome
This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Some patients may have an increased risk of miscarriage. Both autosomal dominant transmission and sporadic cases occur. Less common manifestations of GATA2 deficiency include lymphedema and sensorineural hearing loss, a phenotype usually termed 'Emberger syndrome' (614038) (summary by Bigley et al. (2011), Hsu et al. (2011), and Spinner et al. (2014)).
Neuropathy, hereditary sensory, type 1F
MedGen UID:
816524
Concept ID:
C3810194
Disease or Syndrome
Hereditary sensory neuropathy type IF is an autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment (summary by Kornak et al., 2014). For a discussion of genetic heterogeneity of HSN, see HSAN1A (162400).
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
MedGen UID:
863300
Concept ID:
C4014863
Disease or Syndrome
Immunodeficiency-27B (IMD27B) results from autosomal dominant (AD) IFNGR1 deficiency. Patients with AD IFNGR1 deficiency commonly present with recurrent, moderately severe infections with environmental mycobacteria or bacillus Calmette-Guerin (BCG). In contrast with patients with complete autosomal recessive (AR) IFNGR1 deficiency (IMD27A), cells from patients with AD IFNGR1 deficiency display residual responses to IFNG in vitro, indicating that the deficiency in IFNGR1 is partial. The clinical features of AD IFNGR1 deficiency are usually less severe than those in children with complete AR IFNGR1 deficiency, and mycobacterial infection often occurs later (mean age of 13.4 years vs 1.3 years), with patients having longer mean disease-free survival. In patients with AD IFNGR1 deficiency, M. avium tends to cause unifocal or multifocal osteomyelitis. Salmonellosis is present in about 5% of patients with AR or AD IFNGR1 deficiency, and other infections have been reported in single patients (review by Al-Muhsen and Casanova, 2008).
Combined immunodeficiency due to DOCK8 deficiency
MedGen UID:
1648410
Concept ID:
C4722305
Disease or Syndrome
Hyper-IgE syndrome-2 with recurrent infections (HIES2) is an autosomal recessive immunologic disorder characterized by recurrent staphylococcal infections of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. It is distinguished from autosomal dominant HIES1 (147060) by the lack of connective tissue and skeletal involvement (Renner et al., 2004). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see 147060. See also TYK2 deficiency (611521), a clinically distinct disease entity that includes characteristic features of both autosomal recessive HIES2 and mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006).
Glycosylphosphatidylinositol biosynthesis defect 17
MedGen UID:
1648437
Concept ID:
C4747891
Disease or Syndrome
Glycosylphosphatidylinositol biosynthesis defect-17 (GPIBD17) is an autosomal recessive disorder characterized by variable neurologic deficits that become apparent in infancy or early childhood. Patients may present with early-onset febrile or afebrile seizures that tend to be mild or controllable. Other features may include learning disabilities, autism, behavioral abnormalities, hypotonia, and motor deficits. The phenotype is relatively mild compared to that of other GPIBDs (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Hyper-IgE recurrent infection syndrome 3, autosomal recessive
MedGen UID:
1648483
Concept ID:
C4748969
Disease or Syndrome
Hyper-IgE syndrome-3 with recurrent infections (HIES3) is an autosomal recessive immunologic disorder characterized by childhood onset of atopic dermatitis, skin infections particularly with Staphylococcus aureus, recurrent sinopulmonary infections, and increased serum IgE and IgG. Patients are susceptible to bacterial and fungal infections, including chronic mucocutaneous candidiasis. Immunologic workup shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells (summary by Beziat et al., 2018). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060).
Neuropathy, hereditary sensory and autonomic, type 1A
MedGen UID:
1716450
Concept ID:
C5235211
Disease or Syndrome
SPTLC1-related hereditary sensory neuropathy (HSN) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic "lightning" or "shooting" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles, possibly leading to wheelchair dependency by the seventh or eighth decade. Sensorineural hearing loss is variable.
Endove syndrome, limb-brain type
MedGen UID:
1782954
Concept ID:
C5543142
Disease or Syndrome
Limb-brain ENDOVE syndrome (ENDOVESLB) is characterized by marked mesomelic shortening of the lower limbs due to severe hypoplasia of the tibia and fibula. The talus is absent and foot bones are rudimentary. Hands show short and malformed fingers with a missing digit, and nails are absent on some fingers. In addition, there is cerebellar aplasia with hypoplasia of the brainstem (Allou et al., 2021).
Immunodeficiency 82 with systemic inflammation
MedGen UID:
1781752
Concept ID:
C5543581
Disease or Syndrome
Immunodeficiency-82 with systemic inflammation (IMD82) is a complex autosomal dominant immunologic disorder characterized by recurrent infections with various organisms, as well as noninfectious inflammation manifest as lymphocytic organ infiltration with gastritis, colitis, and lung, liver, CNS, or skin disease. One of the more common features is inflammation of the stomach and bowel. Most patients develop symptoms in infancy or early childhood; the severity is variable. There may be accompanying fever, elevated white blood cell count, decreased B cells, hypogammaglobulinemia, increased C-reactive protein (CRP; 123260), and a generalized hyperinflammatory state. Immunologic workup shows variable B- and T-cell abnormalities such as skewed subgroups. Patients have a propensity for the development of lymphoma, usually in adulthood. At the molecular level, the disorder results from a gain-of-function mutation that leads to constitutive and enhanced activation of the intracellular inflammatory signaling pathway. Treatment with SYK inhibitors rescued human cell abnormalities and resulted in clinical improvement in mice (Wang et al., 2021).
Combined oxidative phosphorylation deficiency 53
MedGen UID:
1779083
Concept ID:
C5543631
Disease or Syndrome
Combined oxidative phosphorylation deficiency-53 (COXPD53) is an autosomal recessive disorder characterized by hypomyelination, microcephaly, liver dysfunction, and recurrent autoinflammation (summary by Lausberg et al., 2021). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
1794167
Concept ID:
C5561957
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).
Immunodeficiency 92
MedGen UID:
1794249
Concept ID:
C5562039
Disease or Syndrome
Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets. Hematopoietic stem cell transplantation may be curative (summary by Beaussant-Cohen et al., 2019 and Levy et al., 2021).
Autoinflammatory disease, X-linked
MedGen UID:
1811268
Concept ID:
C5676885
Disease or Syndrome
X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature (de Jesus et al., 2020 and Lee et al., 2022).

Professional guidelines

PubMed

Masters EA, Ricciardi BF, Bentley KLM, Moriarty TF, Schwarz EM, Muthukrishnan G
Nat Rev Microbiol 2022 Jul;20(7):385-400. Epub 2022 Feb 15 doi: 10.1038/s41579-022-00686-0. PMID: 35169289Free PMC Article
Bury DC, Rogers TS, Dickman MM
Am Fam Physician 2021 Oct 1;104(4):395-402. PMID: 34652112
Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, Hendershot EF, Holtom PD, Huddleston PM 3rd, Petermann GW, Osmon DR, Infectious Diseases Society of America
Clin Infect Dis 2015 Sep 15;61(6):e26-46. Epub 2015 Jul 29 doi: 10.1093/cid/civ482. PMID: 26229122

Recent clinical studies

Etiology

Aydingoz U
Rofo 2023 Apr;195(4):297-308. Epub 2023 Feb 1 doi: 10.1055/a-1949-7641. PMID: 36724804
Sergi CM, Miller E, Demellawy DE, Shen F, Zhang M
Front Immunol 2022;13:959575. Epub 2022 Aug 22 doi: 10.3389/fimmu.2022.959575. PMID: 36072576Free PMC Article
Bury DC, Rogers TS, Dickman MM
Am Fam Physician 2021 Oct 1;104(4):395-402. PMID: 34652112
Lima AL, Oliveira PR, Carvalho VC, Cimerman S, Savio E; Diretrizes Panamericanas para el Tratamiento de las Osteomielitis e Infecciones de Tejidos Blandos Group
Braz J Infect Dis 2014 Sep-Oct;18(5):526-34. Epub 2014 Apr 1 doi: 10.1016/j.bjid.2013.12.005. PMID: 24698709Free PMC Article
Spellberg B, Lipsky BA
Clin Infect Dis 2012 Feb 1;54(3):393-407. Epub 2011 Dec 12 doi: 10.1093/cid/cir842. PMID: 22157324Free PMC Article

Diagnosis

Aydingoz U
Rofo 2023 Apr;195(4):297-308. Epub 2023 Feb 1 doi: 10.1055/a-1949-7641. PMID: 36724804
Moreno-Mateo F, Perea SH, Onel KB
Curr Opin Pediatr 2021 Feb 1;33(1):90-96. doi: 10.1097/MOP.0000000000000970. PMID: 33278106
Maffulli N, Papalia R, Zampogna B, Torre G, Albo E, Denaro V
Surgeon 2016 Dec;14(6):345-360. Epub 2016 Jan 21 doi: 10.1016/j.surge.2015.12.005. PMID: 26805473
Lindbloom BJ, James ER, McGarvey WC
Foot Ankle Clin 2014 Sep;19(3):569-88. Epub 2014 Jul 3 doi: 10.1016/j.fcl.2014.06.012. PMID: 25129362
Lew DP, Waldvogel FA
Lancet 2004 Jul 24-30;364(9431):369-79. doi: 10.1016/S0140-6736(04)16727-5. PMID: 15276398

Therapy

Lee RA, Stripling JT, Spellberg B, Centor RM
Clin Microbiol Infect 2023 Feb;29(2):150-159. Epub 2022 Sep 6 doi: 10.1016/j.cmi.2022.08.024. PMID: 36075498
Korang SK, Safi S, Nava C, Greisen G, Gupta M, Lausten-Thomsen U, Jakobsen JC
Cochrane Database Syst Rev 2021 May 8;5(5):CD013836. doi: 10.1002/14651858.CD013836.pub2. PMID: 33998665Free PMC Article
Wiegand S, Berner R, Schneider A, Lundershausen E, Dietz A
Dtsch Arztebl Int 2019 Mar 29;116(13):224-234. doi: 10.3238/arztebl.2019.0224. PMID: 31064650Free PMC Article
Maffulli N, Papalia R, Zampogna B, Torre G, Albo E, Denaro V
Surgeon 2016 Dec;14(6):345-360. Epub 2016 Jan 21 doi: 10.1016/j.surge.2015.12.005. PMID: 26805473
Spellberg B, Lipsky BA
Clin Infect Dis 2012 Feb 1;54(3):393-407. Epub 2011 Dec 12 doi: 10.1093/cid/cir842. PMID: 22157324Free PMC Article

Prognosis

Zhao Y, Ferguson PJ
Pediatr Clin North Am 2018 Aug;65(4):783-800. doi: 10.1016/j.pcl.2018.04.003. PMID: 30031498
Kumar S, Basu S, Bhartiya SK, Shukla VK
Int J Low Extrem Wounds 2015 Sep;14(3):217-23. Epub 2015 Aug 18 doi: 10.1177/1534734615599653. PMID: 26286931
Christenson JC
Pediatr Rev 2013 Sep;34(9):375-83. doi: 10.1542/pir.34-9-375. PMID: 24000341
Cheung WY, Luk KD
Int Orthop 2012 Feb;36(2):397-404. Epub 2011 Oct 28 doi: 10.1007/s00264-011-1384-6. PMID: 22033610Free PMC Article
Floyed RL, Steele RW
Pediatr Infect Dis J 2003 Aug;22(8):731-6. doi: 10.1097/01.inf.0000078901.26909.cf. PMID: 12913776

Clinical prediction guides

Singhal S, Landes C, Shukla R, McCann LJ, Hedrich CM
Expert Rev Clin Immunol 2023 Jul-Dec;19(9):1101-1116. Epub 2023 Jun 7 doi: 10.1080/1744666X.2023.2218088. PMID: 37224535
Macias D, Jeong SS, Van Swol JM, Moore JD, Brennan EA, Raymond M, Nguyen SA, Rizk HG
Otol Neurotol 2022 Dec 1;43(10):1095-1107. doi: 10.1097/MAO.0000000000003714. PMID: 36351221
Massel DH, Jenkins NW, Rush AJ 3rd, Trapana JE, Foremny GB, Donnally CJ 3rd, Subhawong T, Aiyer A
Foot Ankle Spec 2021 Oct;14(5):415-426. Epub 2020 May 16 doi: 10.1177/1938640020921572. PMID: 32418456
Palestro CJ
Semin Nucl Med 2015 Jan;45(1):32-46. doi: 10.1053/j.semnuclmed.2014.07.005. PMID: 25475377
Leone A, Dell'Atti C, Magarelli N, Colelli P, Balanika A, Casale R, Bonomo L
Eur Rev Med Pharmacol Sci 2012 Apr;16 Suppl 2:8-19. PMID: 22655479

Recent systematic reviews

Wald-Dickler N, Holtom PD, Phillips MC, Centor RM, Lee RA, Baden R, Spellberg B
Am J Med 2022 Mar;135(3):369-379.e1. Epub 2021 Oct 27 doi: 10.1016/j.amjmed.2021.10.007. PMID: 34715060Free PMC Article
Korang SK, Safi S, Nava C, Greisen G, Gupta M, Lausten-Thomsen U, Jakobsen JC
Cochrane Database Syst Rev 2021 May 8;5(5):CD013836. doi: 10.1002/14651858.CD013836.pub2. PMID: 33998665Free PMC Article
Fantoni M, Taccari F, Giovannenze F
Eur Rev Med Pharmacol Sci 2019 Apr;23(2 Suppl):258-270. doi: 10.26355/eurrev_201904_17500. PMID: 30977893
Gigante A, Coppa V, Marinelli M, Giampaolini N, Falcioni D, Specchia N
Eur Rev Med Pharmacol Sci 2019 Apr;23(2 Suppl):145-158. doi: 10.26355/eurrev_201904_17484. PMID: 30977881
Buchbinder R, Johnston RV, Rischin KJ, Homik J, Jones CA, Golmohammadi K, Kallmes DF
Cochrane Database Syst Rev 2018 Apr 4;4(4):CD006349. doi: 10.1002/14651858.CD006349.pub3. PMID: 29618171Free PMC Article

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