Blau Syndrome (BLAUS)

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Disease Ontology 12 DOID:0050678 OMIM 56 186580 KEGG 36 H00285 H01309 MeSH 43 D007592 D014605 NCIt 49 C116794

UMLS via Orphanet 72 C1861303 Orphanet 58 ORPHA90340 MedGen 41 C1861303 SNOMED-CT via HPO 68 10890000 112625008 11399002 128306009 128473001 16294009 16386004 165397008 16553002 188251003 193093009 193387007 193570009 202281000 20255002 230145002 230507009 235856003 238810007 23986001 24184005 246622003 247053007 247441003 254915003 25694009 263681008 267036007 271737000 271771009 271807003 271811009 275259005 281104002 29555009 300268000 30746006 3238004 32861005 35055000 3723001 38341003 386661006 409668002 41607009 416209007 416956002 417373000 43116000 433146000 43363007 443871003 444827008 46742003 4830009 49765009 50177009 56893005 57676002 5888003 65074000 67362008 697898008 70819003 70995007 77971008 7973008 86735004 87715008 90708001 95666008 more UMLS 71 C1836122 C1861303

Genetics Home Reference : ²⁵ Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4. A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs. Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of the joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can involve additional joints and restrict movement by decreasing the range of motion in many joints. In people with Blau syndrome, the tendons as well as the joints can be inflamed, causing tenosynovitis. Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). While individuals with Blau syndrome may have normal vision, inflammation of any of these structures can lead to severe vision impairment or blindness. Some individuals with Blau syndrome develop kidney disease (nephritis) due to inflammation. They may also have deposits of calcium in the kidneys (nephrocalcinosis) and often develop chronic kidney failure. Inflammation of blood vessels (vasculitis) can cause scarring and tissue death in the vessels and impedes blood flow to tissues and organs. Less commonly, Blau syndrome can affect other parts of the body, including the liver, spleen, lymph nodes, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can impair their function and cause life-threatening complications. Rarely, affected individuals have disturbances in nerve function (neuropathy), episodes of fever, or high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension).

MalaCards based summary : Blau Syndrome, also known as arthrocutaneouveal granulomatosis, is related to uveitis and sarcoidosis 1. An important gene associated with Blau Syndrome is NOD2 (Nucleotide Binding Oligomerization Domain Containing 2), and among its related pathways/superpathways are NOD-like receptor signaling pathway and Innate Immune System. Affiliated tissues include skin, eye and liver, and related phenotypes are skin rash and arthralgia

Disease Ontology : ¹² A syndrome characterized by familial granulomatous arthritis, uveitis and skin granulomas. It has material basis in heterozygous mutations in the NOD2 gene.

NIH Rare Diseases : ⁵² Blau syndrome is a rare condition characterized mainly by skin rash, arthritis and uveitis . It has variable expressivity and usually affects preschool age children younger than four years of age. Characteristic findings include synovial effusions (fluid in the joints due to inflammation) and cysts, anterior uveitis (swelling and irritation of the uvea ) and focal posterior synechiae (adhesion of the iris to the cornea). Permanent bending of the fingers and toes (camptodactyly) and other findings have also been reported. It is caused by mutations in the NOD2 gene and is inherited in an autosomal dominant manner. Blau syndrome and early-onset sarcoidosis have the same symptoms and genetic cause, but early-onset sarcoidosis is caused by de novo (new) mutations and occurs sporadically (in individuals with no history of the disorder in the family).

OMIM : ⁵⁶ Blau syndrome is characterized by the triad of granulomatous arthritis, uveitis, and dermatitis. First described in 1985, it was considered to be distinct from sarcoidosis due to the early age of onset and autosomal dominant inheritance pattern. Published reports of sporadic cases of children with 'early-onset sarcoidosis' (EOS) with granulomatous involvement of different organs, primarily affecting joints, eyes, and skin, were suspected to represent the same disorder because the patients' characteristics were nearly identical. Subsequently, identical NOD2 mutations were identified in patients with Blau syndrome as well as in patients diagnosed with EOS, confirming earlier suspicions that they represented the same disease (summary by Borzutzky et al., 2010). Unlike older children diagnosed with sarcoidosis, these patients have no apparent pulmonary involvement; however, the disease is progressive and may result in severe complications such as blindness and/or joint destruction (Shetty and Gedalia, 1998). (186580)

KEGG : ³⁶ Blau syndrome is an autosomal dominantly-inherited disease which is presented with triad of juvenile-onset granulomatous arthritis, uveitis, and skin rashes. Inflammation of the eyes, camptodactyly and lymphaedenopathy are additional feature of the disease. Missense mutations in the NOD region of NOD2 underlie Blau syndrome, augmenting NOD2 activity even in the absence of pathogenic stimuli. Inflammation seen in patients with Blau syndrome might be due to an aberrant activation of NOD2 and constitutive NF-kappaB activation. Blau syndrome usually occurs in children younger than age 4 years.

UniProtKB/Swiss-Prot : ⁷³ Blau syndrome: An autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases.

Wikipedia : ⁷⁴ Blau Syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and... more...

Clinical features from OMIM:

186580

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.7	NOD2 RIPK2
2	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.7	IL10 IL1B NLRC4 NLRP1 NLRP3 NOD1
3	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.44	IL10 IL1B NLRP1 NLRP3 NOD1 TNF
4	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.44	IL10 IL1B NLRP1 NLRP3 NOD1 NOD2

Search Clinical Trials , NIH Clinical Center for Blau Syndrome

Search GEO for disease gene expression data for Blau Syndrome.