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Chromosomal Fragile Site Wikipedia

For detailed information regarding each characterized fragile site, please visit HumCFS: a database of fragile sites in human chromosomes, published in BMC Genomics. ... "Heritable fragile sites on human chromosomes. X. New folate-sensitive fragile sites: 6p23, 9p21, 9q32, and 11q23" . ... "An AT-Rich Sequence in Human Common Fragile Site FRA16D Causes Fork Stalling and Chromosome Breakage in S. cerevisiae" . ... PMID 17360458 . ^ Calin, GA; Sevignani, C; Dumitru, CD; Hyslop, T; Noch, E; Yendamuri, S; Shimizu, M; Rattan, S; Bullrich, F; Negrini, M; Croce, CM (Mar 2, 2004). ... "FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites" .
Placental Site Nodule Wikipedia

Placental site nodule Micrograph of a placental site nodule (top of image). H&E stain . A placental site nodule ( PSN ) is benign remnant from a previous pregnancy . [1] Contents 1 Presentation 2 Pathology 3 Diagnosis 4 Prognosis 5 See also 6 References 7 External links Presentation [ edit ] They are typically asymptomatic and found incidentally. [1] Pathology [ edit ] PSNs are intermediate trophoblastic remnants. ... The differential diagnosis includes ( cervical ) squamous cell carcinoma , gestational trophoblastic disease , and exaggerated placental site. Prognosis [ edit ] PSN are benign. ... See also [ edit ] Gestational trophoblastic disease Placental site trophoblastic tumour References [ edit ] ^ a b Jacob, S.; Mohapatra, D. (2009). "Placental site nodule: a tumor-like trophoblastic lesion" .
Vaccine-Associated Sarcoma Wikipedia

Several of the tumors were located in common injection sites and had similar histologic features to VAS in cats. [5] Also in 2003, a study in Italy compared fibrosarcomas in dogs from injection sites and non-injection sites to VAS in cats, and found distinct similarities between the injection site tumors in dogs and VAS in cats. ... Retrieved 2006-08-27 . ^ Hendrick M, Goldschmidt M (1991). "Do injection site reactions induce fibrosarcomas in cats?". ... PMID 12724570 . ^ Vascellari M, Melchiotti E, Bozza M, Mutinelli F (2003). "Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas" . ... PMC 340241 . PMID 13677599 . ^ Chang H, Ho S, Lo H, Tu Y, Jeng C, Liu C, Wang F, Pang V (2006). ... PMID 16407487 . S2CID 23721821 . ^ Couto S, Griffey S, Duarte P, Madewell B (2002).
Adenylosuccinate Lyase Deficiency Wikipedia

In the severely affected individuals, the concentration levels of SAICA riboside and S-Ado are comparable, whereas in people with milder forms of the disease, the ratio of S-Ado is more than double that of those more severely affected, while SAICA riboside concentration levels remain comparable. [ medical citation needed ] Lysine Adenylosuccinate lyase Biochemical studies of the enzyme have focused on proteins of ADSL from nonhuman species, the ADSL structure from the crystallized protein of Thermotoga maritime has been used, along with DNA sequencing data, to construct homology models for a variety of other organisms, including human ADSL. ... Homology models overlaid on each other show a high degree of overlap between the enzymes. [8] The family of enzymes to which ADSL belongs and that catalyze β-eliminations in which fumarate is one of the products are homotetramers with four active sites composed of amino acid residues from three distinct subunits. Much is known about the active site of human ADSL due to studies of the active site in the B. subtilis ADSL through affinity labeling and site-directed mutagenesis . While there is some variability among species in the sequencing of ADSL, the active site of the enzyme contains many residues that are conserved across species and have been shown to be critical to the enzyme's function. ... Additionally the following options include: [5] S-adenosylmethionine D-ribose and uridine administration Ketogenic diet S-adenosyl-l-methionine Prognosis [ edit ] The prognosis of this condition in childhood usually has a stable outcome, whereas in neonatal is almost always fatal, according to Jurecka, et al. [5] See also [ edit ] Adenylosuccinate Adenylosuccinate lyase List of genetic disorders References [ edit ] ^ Online Mendelian Inheritance in Man (OMIM): 103050 ^ a b c "Adenylosuccinase deficiency" . rarediseases.info.nih.gov .

ADSL, ATIC
- Adenylosuccinase Deficiency OMIM
  
  ADSL deficiency leads to the accumulation of toxic intermediates, including succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) in body fluids. There are 3 major phenotypic forms of the disorder that correlate with different values of the S-Ado and SAICAr concentration ratios (S-Ado/SAICAr) in the cerebrospinal fluid. These include the most severe fatal neonatal encephalopathy (S-Ado/SAICAr ratio less than 1); childhood form (type I) with severe psychomotor retardation (S-Ado/SAICAr ratio close to 1), and a milder form (type II) with psychomotor retardation or hypotonia (S-Ado/SAICAr ratio greater than 2) (summary by Baresova et al., 2012). ... This disorder is characterized by the presence in urine and cerebrospinal fluid of succinyl-5-amino-4-imidazolecarboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado), the nucleosides corresponding to SAICA-ribotide (SARCAR) and adenylosuccinate (S-AMP), respectively, the 2 substrates of ADSL. In patients with ADSL deficiency, the lower the S-Ado:SAICAr ratio in CSF, the more severe the phenotype.
- Adenylosuccinate Lyase Deficiency Orphanet
  
  Biochemically, this defect manifests by the presence in the biologic fluids of two dephosphorylated substrates of ADSL enzyme: succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). The underlying defect is associated with mutations in the ADSL gene (22q13.1).
- Adenylosuccinate Lyase Deficiency MedlinePlus
  
  A characteristic feature that can help with diagnosis of this condition is the presence of chemicals called succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. Adenylosuccinate lyase deficiency is classified into three forms based on the severity of the signs and symptoms. ... Reduced function of this enzyme leads to buildup of SAICAR and SAMP, which are converted through a different reaction to succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). Researchers believe that SAICAr and S-Ado are toxic; damage to brain tissue caused by one or both of these substances likely underlies the neurological problems that occur in adenylosuccinate lyase deficiency. Studies suggest that the amount of SAICAr relative to S-Ado reflects the severity of adenylosuccinate lyase deficiency. Individuals with more SAICAr than S-Ado have more severe encephalopathy and psychomotor delay.
- Adenylosuccinase Deficiency GARD
  
  Adenylosuccinase deficiency impacts the way the body breaks down certain chemicals and results in damage to the nervous system. There are several types of adenylosuccinase deficiency. Symptoms vary greatly from person to person. In general, adenylosuccinase deficiency causes intellectual and movement disabilities, autistic features , epilepsy, low muscle tone, and feeding problems. In the most severe form of this condition, symptoms begin in infancy and death usually occurs in early childhood. Adenylosuccinase deficiency occurs due to a ADSL gene that is not working correctly and is inherited in an autosomal recessive fashion.
Fibrin-Associated Diffuse Large B-Cell Lymphoma Wikipedia

DLBCL-CI is an aggressive malignancy that develops in sites of chronic inflammation that are walled off from the immune system . ... Since the EBV-infected cells are subject to immune attack when they leave these sites, FA-DLBCL remains, it is thought, an otherwise non-invasive, non-metastasizing, site-limited disease. [2] Unlike most other forms of DLBCL, including DLBCL-CI, the neoplastic cells in FA-DLBCL have relatively few gene abnormalities, [2] or abnormal expressions of genes such as MYC [3] and p53 [7] which are implicated in the development of malignancy. ... Local recurrences of the disease in non-pseudocyst sites did occur but responded to further treatment. ... PMID 31519155 . ^ a b c d King RL, Goodlad JR, Calaminici M, Dotlic S, Montes-Moreno S, Oschlies I, Ponzoni M, Traverse-Glehen A, Ott G, Ferry JA (December 2019). "Lymphomas arising in immune-privileged sites: insights into biology, diagnosis, and pathogenesis".
Activated Protein C Resistance Wikipedia

Activated protein C resistance (APCR) Protein C Anticoagulant Pathway : Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. ... This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S Specialty Hematology Activated protein C resistance (APCR) is a hypercoagulability (an increased tendency of the blood to clot) characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis (blood clots in veins), which resulting in medical conditions such as deep vein thrombosis (usually in the leg) and pulmonary embolism (in the lung, which can cause death). [1] Contents 1 Presentation 1.1 Associated conditions 2 Genetics 3 Pathophysiology 4 Diagnosis 5 Treatment 6 References 7 External links Presentation [ edit ] Associated conditions [ edit ] An estimated 64 percent of patients with venous thromboembolism may have activated protein C resistance. [2] [ needs update ] Genetics [ edit ] The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern. [3] Pathophysiology [ edit ] Activated protein C (with protein S as a cofactor) degrades Factor Va and Factor VIIIa . ... Semin Vasc Med . 3 (1): 33–46. doi : 10.1055/s-2003-38331 . PMID 15199491 . External links [ edit ] Classification D ICD - 10 : D68.51 OMIM : 188055 MeSH : D020016 v t e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause Clotting factors Antithrombin III deficiency Protein C deficiency Activated protein C resistance Protein S deficiency Factor V Leiden Prothrombin G20210A Platelets Sticky platelet syndrome Thrombocytosis Essential thrombocythemia DIC Purpura fulminans Antiphospholipid syndrome Clots Thrombophilia Thrombus Thrombosis Virchow's triad Trousseau sign of malignancy By site Deep vein thrombosis Bancroft's sign Homans sign Lisker's sign Louvel's sign Lowenberg's sign Peabody's sign Pratt's sign Rose's sign Pulmonary embolism Renal vein thrombosis Bleeding By cause Thrombocytopenia Thrombocytopenic purpura : ITP Evans syndrome TM TTP Upshaw–Schulman syndrome Heparin-induced thrombocytopenia May–Hegglin anomaly Platelet function adhesion Bernard–Soulier syndrome aggregation Glanzmann's thrombasthenia platelet storage pool deficiency Hermansky–Pudlak syndrome Gray platelet syndrome Clotting factor Hemophilia A/VIII B/IX C/XI von Willebrand disease Hypoprothrombinemia/II Factor VII deficiency Factor X deficiency Factor XII deficiency Factor XIII deficiency Dysfibrinogenemia Congenital afibrinogenemia Signs and symptoms Bleeding Bruise Hematoma Petechia Purpura Nonthrombocytopenic purpura By site head Epistaxis Hemoptysis Intracranial hemorrhage Hyphema Subconjunctival hemorrhage torso Hemothorax Hemopericardium Pulmonary hematoma abdomen Gastrointestinal bleeding Hemobilia Hemoperitoneum Hematocele Hematosalpinx joint Hemarthrosis

F5, PROC
- Factor V Leiden Thrombophilia MedlinePlus
  
  Factor V Leiden thrombophilia also increases the risk that clots will break away from their original site and travel through the bloodstream.
- Factor V Leiden Thrombophilia GeneReviews
  
  Deep vein thrombosis (DVT) is the most common VTE, with the legs being the most common site. Thrombosis in unusual locations is less common. ... Deep vein thrombosis (DVT) is the most common VTE. The most common site for DVT is the legs, but upper-extremity thrombosis also occurs. ... The combination of Leiden variant heterozygosity and most other thrombophilic disorders (including protein C deficiency, protein S deficiency, antithrombin deficiency, and the F2 thrombophilia variant [c.*97G>A, commonly known as 20210G>A]) has a supra-additive effect on overall thrombotic risk [Ridker et al 1997a] (see Differential Diagnosis). ... Inherited abnormalities or deficiencies of the natural anticoagulant proteins C, S, and antithrombin are approximately tenfold less common than the Leiden variant, with a combined prevalence of less than 1%-2% of the population. ... Management Evaluations Following Initial Diagnosis To assess the risk for thrombosis in an individual found to have the factor V Leiden variant, the following evaluations are recommended: For individuals heterozygous for the Leiden variant: the following testing for other inherited or acquired thrombophilic disorders is recommended by experts (but is not a hard-and-fast rule) given that double heterozygosity for the Leiden variant and F2 thrombophilia variant 20210G>A occurs more commonly than protein C, S, and AT deficiencies (which are rare and unlikely to be found except in those with "high risk features" such as a strong family history) and antiphospholipid antibody (APLA) syndrome can occur at any age in anyone: DNA testing F2 thrombophilia variant (c.*97G>A, commonly known as 20210G>A) Multiple phospholipid-dependent coagulation assays for a lupus inhibitor Serologic assays for anticardiolipin antibodies and anti-beta 2 -glycoprotein 1 antibodies For high-risk individuals (i.e., those with a history of recurrent VTE, especially at young age, or those with strong family history of VTE at young age) evaluation should also include assays of: Protein C activity Antithrombin activity Protein S activity or free protein S antigen Note: Measurement of the following is NOT recommended: Plasma concentration of homocysteine since no data support a change in duration of anticoagulation or the use of vitamin supplementation in individuals with hyperhomocysteinemia and a history of VTE MTHFR variants as no clinical rationale for this testing exists Factor VIII and other clotting factor levels [Moll 2015] Treatment of Manifestations Treatment of VTE in Adults The management of individuals with factor V Leiden thrombophilia depends on the clinical circumstances.
- Thrombophilia Due To Activated Protein C Resistance OMIM
  
  Anticardiolipin antibodies or deficiency of protein S, protein C, or antithrombin III were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (p less than 0.001). ... Two of these also had familial raised Lp(a) levels (152200) and 1 child also had protein S deficiency (612336). An additional 10 children had protein C deficiency, protein S deficiency, or familial raised Lp(a) levels. ... The I359T allele was predicted to create an additional consensus site for N-linked glycosylation in factor V, which may have resulted in abnormal N-linked glycosylation within the factor V A2 domain and and reduced susceptibility of factor Va to proteolysis. ... Cui et al. (2000) suggested that these results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within factor V among mammalian species.
Rhabdomyosarcoma Wikipedia

A.; Beltangady, M.; Crist, W.; Dickman, P. S.; Donaldson, S. S.; Fryer, C.; Hammond, D.; Hays, D. ... PMID 1614537 . S2CID 1056405 . ^ Weber-Hall, S.; Anderson, J.; McManus, A.; Abe, S.; Nojima, T.; Pinkerton, R.; Pritchard-Jones, K.; Shipley, J. (1996-07-15). ... PMID 10337369 . ^ Cessna, M. H.; Zhou, H.; Perkins, S. L.; Tripp, S. R.; Layfield, L.; Daines, C.; Coffin, C. ... PMID 9305719 . ^ Pedrick, T. J.; Donaldson, S. S.; Cox, R. S. (1986-03-01). "Rhabdomyosarcoma: the Stanford experience using a TNM staging system". ... PMC 3925355 . PMID 24467821 . Saboo, S. S.; Krajewski, K. M.; Zukotynski, K.; Howard, S.; Jagannathan, J.

NBN, ALK, PTCH1, FGFR4, HRAS, DICER1, BUB1B, PMS2, IGF2, MYOD1, VEGFA, CNR1, SLC22A18, PTMA, TIMM10, CDKN2A, ANGPT2, NF1, NRAS, RHD, GLI1, IGF1R, DES, MSH6, BUB1, TRIP13, BUB3, MC1R, MDM2, EPHB2, MAPK1, CEP57, FOXO1, PAX3, BRCA1, PIK3CA, PIK3CG, MYCN, PIK3CD, MSH2, PIK3CB, TP53, MYOG, MLH1, PAX7, IGF1, AKT1, MET, MIR206, TGFB1, EWSR1, FSD1, FSD1L, EGFR, CXCR4, ABCB1, DMD, CDK4, MYC, CAV1, TNF, KRAS, HDAC9, TBC1D9, SIX1, EGR1, CDKN1A, CXCL12, ACTB, MTOR, MAP2K7, EZR, STIM1, PLK1, MAPK8, EZH2, NES, PLAT, SLC2A1, MMP2, GLI2, IGFBP6, HGF, KIDINS220, NCOA2, ACKR3, YAP1, NR4A1, TDP1, HES1, PTGS2, IL15, RB1, IFNG, PTPN11, RPE65, CD274, MAPK14, VIM, H19, DUX4, CASP3, ARHGEF25, PROM1, DYRK1B, CTNNB1, CCND1, MIR27A, PARP1, BCL2, TFCP2, ILK, HDAC3, TBX2, BIRC2, KAT2B, RAG2, RASGRF1, IGFBP2, FGFR1, COL11A2, CRK, CRKL, TRA, MSTN, TNFRSF10B, ITGA2, MMP9, BMP4, BRAF, RNF19A, EIF3K, PLG, CASP8, AHSA1, MIR203A, CCK, CCND2, SMUG1, DLK1, KIF22, KIT, OBP2A, ABCC1, PTEN, POLDIP2, NFE2L2, GRAP2, PDGFRB, MIR450B, GPC3, GABPA, PHB2, SP1, ABCG2, FN1, SMARCA4, IL24, ORAI1, FOXM1, SMARCB1, FOXF1, FHL2, AIMP2, GPC5, SMO, ERBB2, PDGFRA, DNER, MBD2, SYT1, NHS, STAT3, WEE1, UTS2, NOTCH3, CCN3, SLC12A9, EGF, MIB1, EPHB4, EPHA3, HPSE, HMGA2, BFSP2, RGS5, COIL, TP63, CHEK2, TFPI2, LMO4, TAM, CKAP4, CLTCL1, MTMR11, ST8SIA2, NOG, PTCH2, HDAC4, PHOX2B, OLIG2, LRPPRC, ARPC5, HDAC6, MAML1, WASF1, NR1I2, RGN, BAG3, ZHX2, SLC16A4, SLC16A3, LARGE1, SYNJ1, SPRY1, NCOA1, FADD, TNFSF13B, IGF2BP1, PDLIM5, TNFSF14, CIB2, TNFSF10, CARM1, SPRY2, MERTK, OLFM1, MYCNOS, DLEU2, TUBA1B, EFS, ENOX2, AADAC, CEP164, WNT3A, CAVIN1, PGP, NUTM1, FNDC5, VGLL2, SMYD1, PDIK1L, PWAR1, TWIST2, TNFRSF13C, SLFN11, BMF, TANC1, IL21, RITA1, MAGT1, ARHGAP24, SPRY4, MINDY3, WLS, DHDDS, SLC52A2, GGCT, WNK1, MARCKSL1, GORASP1, CAVIN4, PRSS57, MIRLET7C, MIR145, LOC110806263, HBB-LCR, MTCO2P12, DUX4L9, MIR874, MIR605, MIR411, MIR545, MIR486-1, MIR410, MIR431, MIR378A, XRCC6P5, PLIN5, MIR17HG, MIR92A1, MIR29A, MIR223, MIR22, MIR214, MIR20A, MIR19B1, MIR19A, MIR197, MIR18A, GOLPH3, CXCL16, MMRN1, BRD1, SETD2, TRAC, TRAJ60, TRAV29DV5, DLL1, IGHV1-12, EML4, ANKRD1, DUX1, ANKRD2, PTPN22, PANX1, ZNF281, WDR48, SUZ12, HEY1, SIRT1, SATB2, VPS13A, CIC, PPRC1, CMTR1, ZNF609, KDM1A, HMGXB3, SIRT2, TRPM5, MRM2, IL22, SDF4, VANGL2, PNPLA2, CHPT1, XAB2, PARD3, PCDHA4, PDGFC, DEPDC1B, CCDC88A, NLRP2, FEM1A, HES6, ZNF331, MEG3, PACC1, GOLPH3L, MSTO1, FEV, P4HTM, FAM193B, NANS, LUC7L3, SUFU, ETV7, LEF1, ST8SIA4, RRM2, ZBTB16, HLA-DMA, HIF1A, HIC1, CFHR1, CFH, H2AX, GSK3B, GPT, UTS2R, GLI3, GLB1, G6PD, FUS, FOLH1, FLT1, FOXO3, FOXS1, FOXF2, FGFR3, FGF2, FCGRT, FABP2, F3, F2RL2, HLA-A, HMGB1, ETV4, HMOX1, LGALS3, JARID2, ITGAM, IRS1, INSRR, INSR, INSM1, CXCR2, CXCL8, IL6ST, IL6, IL4, IL1R1, RBPJ, ICAM1, IAPP, TNC, HTC2, HSP90AA1, HSPA4, HRG, HOXB6, HNRNPH1, F2R, ESR2, YES1, CAV2, CA5A, SERPING1, BMP2, BCL2L1, BAGE, ATP2B1, ATM, ARRB1, RHOA, APP, XIAP, APEX1, ANPEP, ALPP, ALPI, ALB, NR0B1, JAG1, AGER, AP2B1, AP2A1, ACVRL1, ACTL6A, CA8, CAV3, ESR1, CD47, ERG, ERBB3, EPOR, EPO, ENO2, ENG, EDN3, DNMT3B, DMPK, DCC, DAG1, CYP2B6, CLTC, CHRNG, CEACAM7, CEACAM3, CETN1, CEACAM5, CDKN2C, CDKN2B, CDKN1C, CDH15, CDC42, LIF, LTK, SMAD4, SSX1, SPP1, SP3, SOX11, SOX2, SOS1, SNRPF, SNAI1, SMARCA1, SLPI, SHH, FBXW4, SGK1, SGCA, MAP2K4, CCL11, CCL5, CCL2, TSPAN31, RPS6KA2, ROCK1, RELA, RBBP7, RAF1, SRMS, SSX2, MB, SS18, WT1, WNT2, UVRAG, UTRN, UCHL3, TXN, TTN, TP73, TNNT1, TH, TGFBR1, TFRC, TFE3, TFAP2B, TERT, TEAD1, TRBV20OR9-2, TBX3, TBP, TAZ, TAT, SYP, STAT6, MOK, PVALB, PTPRC, PTHLH, NM, NGF, NFKB1, NEU2, NELL1, NACA, PPP1R12A, MYL1, MYF6, MYF5, COX2, MPST, MMP14, MAP3K10, MKI67, CD99, CIITA, MGMT, KITLG, MEF2D, MEF2C, MDM4, MCL1, NOS1, NOS2, NOTCH1, ABCB4, PTH, PTBP1, PSG2, MAPK3, PKN1, PRKCI, PPARA, POU4F1, PLAU, PLAG1, SERPINF1, NPM1, PDPK1, PCNA, PAX9, PAX5, PAM, PAK1, SERPINE1, ODC1, NTRK1, YBX1, H3P10
- Rhabdomyosarcoma, Embryonal, 1 OMIM
  
  A number sign (#) is used with this entry because of evidence that rhabdomyosarcoma can be caused by somatic mutation in the SLC22A18 gene (602631) on chromosome 11p15. Mapping Scrable et al. (1987) generalized the hypothesis of somatic chromosomal interchanges at mitosis as the basis of retinoblastoma (180200). To the study of other tumors, the proposed model suggests that predisposing recessive mutations are revealed by exchanges that result in homozygous (or hemizygous) defect at the tumor locus. This would suggest that for tumors with no known cytogenetic aberrations, one could find the location of these genes by delineating the smallest overlapping region of genetic homozygosity shared among tumors of the same type. They applied this rationale to rhabdomyosarcoma, a 'pediatric tumor.'
- Rhabdomyosarcoma Orphanet
  
  Rhabdomyosarcoma can develop anywhere in the body, including in sites where striated muscle does not normally occur.
- Rhabdomyosarcoma Mayo Clinic
  
  Overview Rhabdomyosarcoma (RMS) is a rare type of cancer that forms in soft tissue — specifically skeletal muscle tissue or sometimes hollow organs such as the bladder or uterus. RMS can occur at any age, but it most often affects children. Although RMS can arise anywhere in the body, it's more likely to start in the: Head and neck area Urinary system, such as the bladder Reproductive system, such as the vagina, uterus and testes Arms and legs The outlook (prognosis) and treatment decisions depend on the type of rhabdomyosarcoma, where it starts, tumor size and whether the cancer has spread. Treatment is usually with a combination of surgery, chemotherapy and radiation therapy. Major advancements in the treatment of rhabdomyosarcoma have significantly improved outcomes. After completion of treatment, people need lifelong monitoring for potential late effects of intense chemotherapy and radiation.
Osteoblastoma Wikipedia

Although the tumor is usually considered benign , a controversial aggressive variant has been described in the literature, with histologic features similar to those of malignant tumors such as an osteosarcoma . [ citation needed ] Diagnosis [ edit ] When diagnosing osteoblastoma, the preliminary radiologic workup should consist of radiography of the site of the patient's pain. However, computed tomography ( CT ) is often necessary to support clinical and plain radiographic findings suggestive of osteoblastoma and to better define the margins of the lesion for potential surgery. ... Bone scintigraphy (bone scan) demonstrates abnormal radiotracer accumulation at the affected site, substantiating clinical suspicion, but this finding is not specific for osteoblastoma. ... The long tubular bones are another common site of involvement, with a lower extremity preponderance. ... Epiphyseal involvement is extremely rare. Although other sites are rarely affected, several bones in the abdomen and extremities have been reported as sites of osteoblastoma tumors. [ citation needed ] References [ edit ] ^ " osteoblastoma " at Dorland's Medical Dictionary ^ George, Timothy; Daniel H. ... Minim Invasive Neurosurg . 51 (5): 310–2. doi : 10.1055/s-0028-1083816 . PMID 18855299 . ^ Mortazavi SM, Wenger D, Asadollahi S, Shariat Torbaghan S, Unni KK, Saberi S (March 2007).

FOS, FOSB, APRT, RPE65, MIR135B, MIR210, PPM1E, CKAP4, TP63, UVRAG, TP53, SOX9, PCNA, RUNX2, MFAP1, SMAD2, SMAD1, IL6, FYN, CTNNB1, CHI3L1, MIR486-1
- Osteoblastoma Orphanet
  
  A rare, neoplastic disease characterized by a typically benign, locally aggressive, non self-limiting, osteoblastic bone tumor, usually located on the spine, proximal humerus and hip (although any bone may be involved), generally manifesting with slowly progressive, dull aching pain which is difficult to localize and is not relieved by nonsteroidal anti-inflammatory drugs or aspirin. Neurologic symptoms, such as cranial nerve palsies, myelopathy, neuralgia, radiculopathy, paraparesis or paraplegia, may be associated if the spine is involved. Imaging reveals a lytic (or mixed lytic and blastic) lesion with a radiolucent nidus (> 2 cm) associated with reactive sclerotic bone.
Mouse Models Of Breast Cancer Metastasis Wikipedia

PMID 4512654 . ^ Martins, F. C.; De, S; Almendro, V; Gönen, M; Park, S. Y.; Blum, J. ... PMID 19308069 . ^ Weng, D; Penzner, J. H.; Song, B; Koido, S; Calderwood, S. K.; Gong, J (2012). ... PMID 22277639 . ^ Liu, W; Laitinen, S; Khan, S; Vihinen, M; Kowalski, J; Yu, G; Chen, L; Ewing, C. ... PMID 15358632 . ^ Behbod, F; Kittrell, F. S.; Lamarca, H; Edwards, D; Kerbawy, S; Heestand, J. ... Nature Biotechnology 34, 192-198. doi: 10.1038/nbt.3450 ^ Srinivas, S; Watanabe, T; Lin, C. S.; William, C.
Thrombophilia Due To Protein S Deficiency, Autosomal Dominant OMIM

Type I refers to deficiency of both free and total protein S as well as decreased protein S activity; type II shows normal plasma values, but decreased protein S activity; and type III shows decreased free protein S levels and activity, but normal total protein S levels. ... Thus, free protein S is the molar surplus of protein S over C4BPA. Mild protein S deficiency will thus present with selective deficiency of free protein S, whereas more pronounced protein S deficiency will also decrease the complexed protein S and consequently the total protein S level. ... Crossed immunoelectrophoresis using anti-protein S antibodies revealed no free protein S. ... Other Features Pan et al. (1990) reported 2 children with typical inherited protein S deficiency which resulted in serious episodes of thrombosis at multiple sites.

PROS1
- Severe Hereditary Thrombophilia Due To Congenital Protein S Deficiency Orphanet
  
  An inherited coagulation disorder characterized by recurrent venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein S. Epidemiology Prevalence of partial protein S deficiency (heterozygous individuals) is estimated at 0.16-0.21% in the general population. ... Arterial thrombosis may also occur. Etiology Protein S deficiency is caused by mutations in the PROS1 gene (3q11-q11.2). Diagnostic methods Diagnosis is based on the measurement of protein S antigen levels (total protein S or free protein S) and anticoagulant activity. ... Type I and type III are quantitative deficiencies with low free antigen levels (with normal total protein S levels in type III and decreased total protein S levels in type I deficiency). Type II is a qualitative deficiency with normal total and free protein S levels. Molecular testing is available, but is unnecessary for diagnosis.
- Protein S Deficiency MedlinePlus
  
  Protein S deficiency is a disorder of blood clotting. ... Causes Protein S deficiency is caused by mutations in the PROS1 gene. ... Most mutations that cause protein S deficiency change single protein building blocks (amino acids) in protein S, which disrupts its ability to control blood clotting. ... Protein S deficiency can be divided into types I, II and III based on how mutations in the PROS1 gene affect protein S. Learn more about the gene associated with Protein S deficiency PROS1 Inheritance Pattern Protein S deficiency is inherited in an autosomal dominant pattern , which means one altered copy of the PROS1 gene in each cell is sufficient to cause mild protein S deficiency.
Cancer Of Unknown Primary Origin Wikipedia

Stem cells can migrate from their natural tissue and initiate a cancer in the new site before generating a detectable tumor in their natural tissue. ... In patients in whom the primary cancer is eventually found, the lung and pancreas are the most common primary cancer sites. CUP also may be traced to the breast, prostate, colon, or rectum as the primary site. [ medical citation needed ] Sometimes, however, even when doctors use very sophisticated methods to try to identify the primary site, the part of the body the cancer cells came from cannot be determined. About 2 to 4 percent of all cancer patients have a cancer whose primary site is never found. Identifying the primary tumor site is important because knowing its location and type often helps doctors plan the best treatment. ... PMID 25140961 . ^ a b c d e Ettinger, David S.; Agulnik, Mark; Cates, Justin M. ... PMC 4145520 . PMID 25184090 . ^ Lee, J.; Hahn, S.; Kim, D.-W.; Kim, J.; Kang, S. N.; Rha, S.
Frasier Syndrome Wikipedia

Results of various investigations identified the loss of function of WT1 to be a prerequisite of Wilms' tumour development, and also a key trait of individuals with genital abnormalities. [8] Mutations responsible for Frasier syndrome predominantly occur in intron 9 of the WT1 gene, specifically nucleotide substitutions that influence an intron splice site . Mutations in this region proved for the absence of three amino acids— K T S —between the third and fourth WT1 zinc fingers. [9] Referring to the autosomal dominant expressive nature of this disease, it is only necessary for an individual to have one complement of the mutated intronic sequence to appear affected. [10] Differing from the similar Denys-Drash syndrome, where a mutated form of the WT1 protein exists, Frasier syndrome expression works solely on the existence of a changed ratio of KTS isoforms : normal WT1 proteins including the KTS site (+KTS), and mutated, shortened proteins lacking the KTS site (–KTS). [1] Through alternative splicing , a specific ratio of the two isoforms normally exists, though the mutation in the intron 9 splice site severely lowers levels of the +KTS isoform; this leads to Frasier syndrome. [9] Inheritance pattern [ edit ] Frasier syndrome is inherited in an autosomal dominant fashion, indicating the need for only one mutated allele in a cell to lead to expression of the disease. ... Hum Mol Genet . 1 (5): 293–5. doi : 10.1093/hmg/1.5.293 . PMID 1338905 . ^ a b Barbaux S.; Niaudet P.; Gubler MC.; et al. (Dec 1997). "Donor splice-site mutations in WT1 are responsible for Frasier syndrome".

WT1, KTWS, PAX6, SOX9, SRY, DEL11P13
- Frasier Syndrome MedlinePlus
  
  Frasier syndrome is a condition that affects the kidneys and genitalia. Frasier syndrome is characterized by kidney disease that begins in early childhood. Affected individuals have a condition called focal segmental glomerulosclerosis, in which scar tissue forms in some glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood . In people with Frasier syndrome, this condition often leads to kidney failure by adolescence. Although males with Frasier syndrome have the typical male chromosome pattern (46,XY ), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female.
- Frasier Syndrome OMIM
  
  In 3 patients with Frasier syndrome, Barbaux et al. (1997) identified mutations in the donor splice site of intron 9 of the WT1 gene (607102.0018; 607102.0019) with a predicted loss of the so-called +KTS isoform. Normally, an alternative splice site in intron 9 allows the addition of 3 amino acids (KTS) between the third and fourth zinc fingers of the WT1 protein. ... Melo et al. (2002) reported a 19-year-old male with Frasier syndrome who had the IVS9+4C-T mutation (607102.0018), which predicts a change in splice site utilization. He had an unusual phenotype.
- Frasier Syndrome Orphanet
  
  A rare genetic, syndromic glomerular disorder characterized by the association of progressive glomerular nephropathy and 46,XY complete gonadal dysgenesis with a high risk of developing gonadoblastoma. Epidemiology To date, less than 150 cases have been described. Clinical description Nephropathy is the hallmark of the disease. It develops during childhood presenting as persistent proteinuria and subsequently steroid-resistant nephrotic syndrome (SRNS) and progresses to end-stage renal disease (ESRD) in the second or third decade of life. On renal biopsy, focal segmental glomeruloscrelosis (FSGS) is the most common histopathological finding. Individuals have a 46, XY karyotype and present with female external genitalia, complete gonadal dysgenesis and have a higher risk of gonadoblastoma.
Kohlschütter-Tönz Syndrome Wikipedia

This mutation destroys the splice acceptor and donor sites resulting in an in-frame deletion. ... PMID 4372200 . ^ a b c d e f g h i j Tucci A, Kara E, Schossig A, Wolf NI, Plagnol V, Fawcett K, Paisán-Ruiz C, Moore M, Hernandez D, Musumeci S, Tennison M, Hennekam R, Palmeri S, Malandrini A, Raskin S, Donnai D, Hennig C, Tzschach A, Hordijk R, Bast T, Wimmer K, Lo CN, Shorvon S, Mefford H, Eichler EE, Hall R, Hayes I, Hardy J, Singleton A, Zschocke J, Houlden H (19 October 2012). ... PMID 22424600 . ^ a b c d e f g Mory, A; Dagan E; Illi B; Duquesnoy P; Mordechai S; Shahor I; Romani S; Hawash-Moustafa N; Mandel H; Valente EM; Amselem S; Gershoni-Baruch R (6 April 2012). ... PMID 26384929 . ^ a b c d Haberlandt E., Svejda C., Felber S., Baumgartner S., Gunther B., Utermann G., Kotzot D. (2006). ... Helv Paediatr Acta, 29(4), 283-294. ^ Parry D.; Brookes S.; Logan C.; Poulter J.; El-Sayed W.; Al-Bahlani S.; Mighell A. (2012).

ROGDI, SLC13A5, ACADSB, AUH, DHCR7, HSD17B10, ACAD8, FKBP14
- Kohlschutter-Tonz Syndrome OMIM
  
  A number sign (#) is used with this entry because Kohlschutter-Tonz syndrome (KTZS) is caused by homozygous or compound heterozygous mutation in the ROGDI gene (614574) on chromosome 16p13. Description Kohlschutter-Tonz syndrome is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discoloration of the teeth. Although the phenotype is consistent, there is variability. Intellectual disability is related to the severity of seizures, and the disorder can thus be considered an epileptic encephalopathy. Some infants show normal development until seizure onset, whereas others are delayed from birth. The most severely affected individuals have profound mental retardation, never acquire speech, and become bedridden early in life (summary by Schossig et al., 2012 and Mory et al., 2012).
- Amelocerebrohypohidrotic Syndrome Orphanet
  
  Kohlschütter-Tönz syndrome (KTS) is a genetically heterogeneous autosomal recessive syndrome characterized by the triad of amelogenesis imperfect, infantile onset epilepsy, intellectual disability with or without regression and dementia.
Mucous Membrane Pemphigoid GARD

Mucous membrane pemphigoid is a rare, chronic, blistering and scarring disease that affects the oral and ocular mucosa . Other mucosal sites that might be affected include the nasopharnyx, larynx, genitalia, rectum, and esophagus. The condition usually begins in late adulthood (e.g. 50's or 60's), affects more women than men, and has a variable prognosis.

PTGER3, COL17A1, HLA-DQB1, TGFB1, IL4, IL5, CXCL8, RBM45, CD274, LAD1, CXCR1, C5AR1, SERPINH1, IL1RN, IL1B, IL1A, IFNG, HLA-DRB1, HT
- Mucous Membrane Pemphigoid Orphanet
  
  The disease manifests as fragile bullous lesions that give way to superficial erosions. The principle sites affected are the oral (80-90% of cases), ocular (50-70% of cases), pharyngolaryngeal (8-20% of cases), genital (15% of cases) and esophageal mucous membranes.
- Ocular Cicatricial Pemphigoid OMIM
  
  Clinical Features Ocular cicatricial pemphigoid is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. If not treated or treated inappropriately, it can cause blindness. Like pemphigus vulgaris (169610), it is a disease associated with antibodies to components of the skin and mucous membranes. Antibody in pemphigus vulgaris is directed against a protein of the epidermal intercellular cement substance (169615), whereas the antigen involved in OCP has not been definitively characterized. Although both diseases are associated with HLA-DR4 in some patients, in other respects the major histocompatibility complex (MHC) associations are quite different. Ahmed et al. (1991) showed that OCP patients have an increased frequency of DQB1*0301 (see HLA-DQB1, 604305).
Male Breast Cancer Wikipedia

A.; Zujewski, J. A.; Kamin, L.; Giordano, S.; Domchek, S. ; Anderson, W. F.; Bartlett, J. ... PMID 20308661 . . ^ a b c d Liukkonen, S.; Saarto, T.; Mäenpää, H.; Sjöström-Mattson, J. (2010). ... Retrieved 2010-05-20 . ^ Fentiman, Ian S. (1 August 2018). "Unmet needs of men with breast cancer" . ... PMID 20193984 . ^ Ottini, L.; Palli, D.; Rizzo, S.; Federico, Mario; Bazan, Viviana; Russo, Antonio; et al. (2009). ... PMID 19427229 . . ^ Kalyani, R.; Days, S.; Bindra Singh, M. S.; Kumar, H. (2010).

CHEK2, AR, RAD51B, TOX3, BRCA2, BRCA1, ESR1, LHCGR, MEN1, PRLR, SULT1A1, TP53, TMSB4Y, EMSY
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Wikipedia

In consequence, these cells progressively acquire increased rates of proliferation, prolonged survival, the ability to spread to other tissues, the ability to avoid attack by the immune system, and other malignant behaviors that characterize this disease. [7] Presentation [ edit ] Afflicted individuals (median age 76 years; range 49–92 years; more common in females [3] ) typically present with one or more rapidly growing red to bluish-red, firm tumors located on the leg(s) at some site(s) below the knees. [5] Occasionally the lesions are ulcerated. [3] About 10% of cases do not have lesions on the legs but rather present with one or more skin lesions outside of the legs; ~20% of individuals present with cutaneous lesion(s) but on further or later investigation are found to have disease in non-cutaneous sites such as the lymph nodes, visceral organs, [1] bone marrow , and/or, rarely, central nervous system . [5] Some individuals, particularly those with widespread disease, complain of having the B symptoms of fever, night sweats , and/or weight loss. [1] DLBCL cases that have cutaneous lesions in association with widespread disease may be advanced PCDLBCL, LT but without evidence that the disease began in the skin are diagnosed as having and treated for some other variant or subtype of the Diffuse large B-cell lymphomas that has spread to the skin. [7] Diagnosis [ edit ] The diagnosis of PCDLBCL, LT depends on analyzing skin biopsies of the involved sites microscopically. ... PMID 30380402 . ^ a b c d e f g h i j k l Selva R, Violetti SA, Delfino C, Grandi V, Cicchelli S, Tomasini C, Fierro MT, Berti E, Pimpinelli N, Quaglino P (2017). ... PMID 29909914 . ^ Gravelle P, Burroni B, Péricart S, Rossi C, Bezombes C, Tosolini M, Damotte D, Brousset P, Fournié JJ, Laurent C (July 2017). ... PMID 28402953 . ^ Heyman M, Einhorn S (October 1996). "Inactivation of the p15INK4B and p16INK4 genes in hematologic malignancies". ... PMC 6294323 . PMID 29931605 . ^ Li S, Young KH, Medeiros LJ (January 2018).

BCL2, MYD88, MYC, BCL6, PWWP3A, IRF4, IGKV1-5, IGLL5, MIR214, BMS1P20, PDCD1LG2, FOXP3, IGKV2-29, CCND1, PIM1, MME, IL3RA, IGLV@, IGKV@, CDKN2A, CD79B, TNFRSF8, H3P10
- Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Orphanet
  
  A rare, aggressive, primary cutaneous B-cell lymphoma characterized by rapidly progressive, red to bluish, often ulcerating, nodular tumors predominantly involving the lower legs. Histology shows sheets of centroblasts and immunoblasts that spare the epidermis, but infiltrate the dermis and subcutaneous tissues, and often disseminate extracutaneously. The neoplastic cells typically express CD20, CD79a, Bcl-2, MUM-1, and FOXP1, but are negative for CD10.
Global Aphasia Wikipedia

PMID 20438263 . ^ Pai A.R., Krishnan G, Prashanth S, Rao S. (2011). Global aphasia without hemiparesis: A case series. ... PMID 8976318 . ^ a b c d e f g Christman, S. S.; Boutsen, F. R. (2006). "Recovery of Language after Stroke or Trauma in Adults". ... PMID 21395923 . ^ Bakheit, A.M.; Shaw, S.; Carrington, S.; Griffiths, S. (2007). ... PMID 728786 . ^ Bakheit, A.; Shaw, S.; Carrington, S.; Griffiths, S. (2007). ... PMID 17981853 . ^ a b Smania, N.; Gandolfi, M.; Aglioti, S.; Girardi, P.; Fiaschi, A.; Girardi, F. (2010).

L1CAM, PLAT
Clinically Isolated Syndrome Wikipedia

An episode may be monofocal , in which symptoms present at a single site in the central nervous system , or multifocal , in which multiple sites exhibit symptoms. ... In order for such a diagnosis , multiple sites in the central nervous system must present lesions, typically over multiple episodes, and for which no other diagnosis is likely. ... PMID 11456302 . ^ a b Lublin, F. D; Reingold, S. C; Cohen, J. A; Cutter, G. R; Sorensen, P. S; Thompson, A. J; Wolinsky, J. S; Balcer, L. ... A; Clanet, M; Comi, G; Fox, R. J; Freedman, M. S; Goodman, A. D; Inglese, M; Kappos, L; Kieseier, B.

IFNB1, NEFL, CISH, MS, CSF2, LAMC2, CHI3L1, IL10, MIR181C, MARCHF11, CX3CL1, SMPD1, SPP1, STAT3, SYN1, TGFBI, THBD, TNFRSF1A, TP53BP1, IL17F, VDR, PRB1, TCL1B, TOB1, CXCL13, LDB3, CSAD, HRH4, MIR20A, NR4A3, AQP4, PLXNA2, H2AX, SERPING1, CD1C, CD27, CD38, CCR6, DDT, GH1, GLA, GRN, NR4A1, NCAM1, HRH1, HRH2, IFNG, IGHG3, IL17A, KIR2DL2, KIR2DL3, MOG, ARG2, KIR2DS2
Neurapraxia Wikipedia

Wallerian degeneration often occurs in the near the proximity of the injury site. [7] Neurapraxia is least serious form of nerve injury. [7] There are two different forms of mechanical nerve injury involving neurapraxia. ... If joints are kept mobile, the limb has the best possible chance of benefit from the return of nervous function. [7] Non-steroidal anti-inflammatory medications can also help to reduce swelling at the injury site. In addition to these non-operative remedies, it is suggested that muscles affected by neurapraxia be kept warm at all times. ... Cases of neurapraxia in the National Football League were first described in 1986 by Joseph S. Torg, M.D., founder of the National Football Head and Neck Injury Registry (established in 1975). ... In popular culture [ edit ] In M*A*S*H Season 4 Episode one , Hawkeye Pierce claims that Radar O'Reilly has neurapraxia as an excuse for driving past a military checkpoint. ... Retrieved 5 April 2011 . ^ a b Torg J. S., Genuario S. E., Sennett B., Wisneski R.
Congenital Myasthenic Syndrome Wikipedia

The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic properties of the receptor. ... S.; Lochmüller, H. (2012). "Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients". ... PMID 22678886 . ^ Shen, X. -M.; Brengman, J. M.; Edvardson, S.; Sine, S. M.; Engel, A. G. (2012). "Highly fatal fast-channel syndrome caused by AChR subunit mutation at the agonist binding site" . Neurology . 79 (5): 449–454. doi : 10.1212/WNL.0b013e31825b5bda . PMC 3405251 . PMID 22592360 . ^ Muller, J. S.; Baumeister, S. K.; Rasic, V. M.; Krause, S.; Todorovic, S.; Kugler, K.; Müller-Felber, W.; Abicht, A.; Lochmüller, H. (2006).

GFPT1, AGRN, SCN4A, SLC18A3, SLC5A7, ALG2, LRP4, CHRND, ALG14, COLQ, RAPSN, DOK7, GMPPB, VAMP1, DPAGT1, MUSK, COL13A1, PLEC, LAMB2, PREPL, SNAP25, SYT2, CHRNG, CHRNB1, CHRNE, CHAT, TAPBPL, ACHE, C17orf107, CHRNA1, CD2AP, BCHE, HNRNPH1, HNRNPH2, MYO9A, DAP, EIF3K, SRSF1, UTRN, NGFR, NTRK1, CAV1, SMN1, SMN2, DES, ERBB3, SEA, CHD7, LAMA5, SEMA7A, TPM3, B3GAT1, SLC25A1, RPH3A, VCP, DNAJA3, MACF1
- Congenital Myasthenic Syndromes GeneReviews
  
  Prenatal testing and preimplantation genetic testing are possible if the pathogenic variant(s) have been identified in an affected family member. ... Establishing the Diagnosis The diagnosis of CMS is established in a proband with the findings above in combination with the identification of a heterozygous or biallelic pathogenic variant(s) in one of the genes listed in Table 1a and Table 1b; these genes, encoding different proteins expressed at the neuromuscular junction, are currently known to be associated with CMS [Hantaï et al 2013, Rodríguez Cruz et al 2014, Engel et al 2015]. ... Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. ... CMS Subtypes by Gene Involved View in own window Gene(s) Associated with Disease CMS Subtype Clinical Findings 1 Response to AChE Inhibitors 2 CHAT CMS w/episodic apnea Hypotonia, respiratory failure at birth Episodic apnea Improvement w/age Improvement AChR subunit genes: CHRNE CHRNA1 CHRNB1 CHRND Acetylcholine receptor deficiency Early onset Varies from mild to severe Ptosis, EOP; 3 bulbar, arm, leg weakness Improvement Slow-channel CMS Selective severe neck, wrist, finger extensor weakness Childhood to adult onset Varies from mild to severe Progressive ventilatory insufficiency; may require assisted ventilation Often deterioration Fast-channel CMS Varies from mild to severe Improvement COLQ Endplate AChE deficiency Often severe In some w/C-terminal missense pathogenic variants: later presentation, milder clinical course EOP General muscle weakness / severe involvement of axial muscles Slow pupillary light response Deterioration or no response DOK7 DOK7-associated limb-girdle-myasthenia Limb-girdle pattern of weakness w/predominantly proximal weakness, waddling gait, & ptosis but no EOP Deterioration or no response RAPSN Endplate rapsyn deficiency Early onset: Hypotonia, respiratory failure at birth Episodic apnea Arthrogryposis multiplex congenita Varies from mild to severe Late onset: Limb weakness in adolescence or adulthood resembling seronegative myasthenia gravis Improvement GFPT1 , DPAGT1 , ALG2 , ALG14 , GMPPB , PREPL Limb-girdle-myasthenia w/glycosylation deficiency "Limb-girdle" pattern of weakness w/predominantly proximal weakness but usually no ptosis or EOP; sometimes tubular aggregates in muscle biopsy 4 Improvement Includes only those genes for which more than a few individuals/families have been reported 1.
- Congenital Myasthenic Syndromes GARD
  
  Congenital myasthenic syndromes (CMS) are a group of genetic conditions that all include muscle weakness that gets worse with physical activity. There are many subtypes of CMS with different symptoms, severity, and treatments. Most people with CMS develop symptoms in infancy or by early childhood, but the age at which symptoms begin can vary. Symptoms range from mild to severe muscle weakness and may get worse over time or only occur periodically. The muscles of the face, neck, throat, eyes and limbs are most affected.
- Myasthenic Syndrome, Congenital, 3c, Associated With Acetylcholine Receptor Deficiency OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-3C (CMS3C) associated with acetylcholine receptor (AChR) deficiency is caused by compound heterozygous mutation in the CHRND gene (100720) on chromosome 2q37. One such patient has been reported. Mutation in the CHRND gene can also cause slow-channel congenital myasthenic syndrome (CMS3A; 616321) and fast-channel congenital myasthenic syndrome (CMS3B; 616322). Description Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with acetylcholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 9, Associated With Acetylcholine Receptor Deficiency OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-9 (CMS9) associated with acetylcholine receptor (AChR) deficiency is caused by homozygous or compound heterozygous mutation in the MUSK gene (601296), which is critical for synaptic differentiation, on chromosome 9q31. Description Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Patients may show a favorable response to amifampridine (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
- Myasthenic Syndrome, Congenital, 4b, Fast-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that fast-channel congenital myasthenic syndrome-4B (CMS4B) is caused by homozygous or compound heterozygous mutation in the CHRNE gene (100725) on chromosome 17p13. Mutation in the CHRNE gene can also cause slow-channel myasthenic syndrome (CMS4A; 605809) and CMS with acetylcholine receptor (AChR) deficiency (CMS4C; 608931). Description Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 15 OMIM
  
  INHERITANCE - Autosomal recessive SKELETAL - Joint contractures (1 patient) MUSCLE, SOFT TISSUES - Myasthenic syndrome - Muscle weakness, proximal greater than distal - Difficulty walking - Decrement of compound action muscle potentials (CMAP) seen on repetitive nerve stimulation MISCELLANEOUS - Onset in first decade - Slowly progressive - Favorable response to anticholinesterase medication - Two sisters have been reported (last curated February 2015) MOLECULAR BASIS - Caused by mutation in the homolog of the S. cerevisiae ALG14 gene (ALG14, 612866.0001 ) ▲ Close
- Myasthenic Syndrome, Congenital, 22 OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-22 (CMS22) is caused by homozygous or compound heterozygous mutation in the PREPL gene (609557) on chromosome 2p21. Homozygous deletion of both PREPL and the neighboring gene SLC3A1 (104614) causes hypotonia-cystinuria syndrome (606407). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Regal et al. (2014) reported a female infant who presented with marked neonatal hypotonia, eyelid ptosis, tented upper lip, and feeding difficulties. She was treated with a feeding tube and showed a favorable response to the acetylcholinesterase (AChE) inhibitor pyridostigmine, from which she was weaned at age 12 months without deterioration, suggesting spontaneous improvement with age.
- Myasthenic Syndrome, Congenital, 13 OMIM
  
  Muscle biopsy showed structural and functional abnormalities of the neuromuscular junction, including decreased acetylcholine receptor binding sites and decreased postsynaptic folding, consistent with a loss of endplate AChR.
- Myasthenic Syndrome, Congenital, 4c, Associated With Acetylcholine Receptor Deficiency OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-4C (CMS4C) associated with acetylcholine receptor (AChR) deficiency is caused by homozygous or compound heterozygous mutation in the CHRNE gene (100725) on chromosome 17p13. Mutation in the CHRNE gene can also cause slow-channel CMS (CMS4A; 605809) and fast-channel CMS (CMS4B; 616324). Description Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Patients with mutations in the CHRNE gene may have compensatory increased expression of the fetal subunit CHRNG (100730) and may respond to treatment with cholinergic agents, pyridostigmine, or amifampridine (summary by Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 2a, Slow-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-2A (CMS2A) is caused by heterozygous mutation in the CHRNB1 gene (100710) on chromosome 17p13. Mutation in the CHRNB1 gene can also cause congenital myasthenic syndrome-2C associated with acetylcholine receptor (AChR) deficiency (CMS2C; 616314). Description Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
- Myasthenic Syndrome, Congenital, 12 OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-12 (CMS12) is caused by homozygous or compound heterozygous mutation in the GFPT1 gene (138292) on chromosome 2p13. Description Congenital myasthenic syndrome-12 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. EMG classically shows a decremental response to repeated nerve stimulation. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors (summary by Senderek et al., 2011). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
- Myasthenic Syndrome, Congenital, 1b, Fast-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that fast-channel congenital myasthenic syndrome-1B (CMS1B) is caused by mutation in the CHRNA1 gene (100690) on chromosome 2q31. Most patients have compound heterozygous mutations, although heterozygous mutations have rarely been reported. Mutation in the CHRNA1 gene can also cause slow-channel myasthenic syndrome (CMS1A; 601462). Description Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor (AChR) channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization.
- Myasthenic Syndrome, Congenital, 4a, Slow-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-4A (CMS4A) is caused by heterozygous mutation in the CHRNE gene (100725) on chromosome 17p13. Biallelic CHRNE mutations have rarely been reported. Mutation in the CHRNE gene can also cause fast-channel CMS (CMS4B; 616324) and CMS with acetylcholine receptor (AChR) deficiency (CMS4C; 608931). Description Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
- Myasthenic Syndrome, Congenital, 5 OMIM
  
  A number sign (#) is used with this entry because congenital myasthenic syndrome-5 (CMS5), also known as endplate acetylcholinesterase deficiency (EAD), is caused by homozygous or compound heterozygous mutation in the COLQ gene (603033) on chromosome 3p25. Description Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction. Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. Endplate acetylcholinesterase deficiency is an autosomal recessive congenital myasthenic syndrome characterized by a defect within the synapse at the neuromuscular junction (NMJ).
- Myasthenic Syndrome, Congenital, 1a, Slow-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-1A (CMS1A) is caused by heterozygous mutation in the CHRNA1 gene (100690) on chromosome 2q31. There are rare reports of recessive inheritance. Mutation in the CHRNA1 gene can also cause fast-channel CMS1B (608930). Description Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic, as well as by pathologic mechanism and electrophysiologic studies (i.e., acetylcholine receptor (AChR) deficiency, slow-channel or fast-channel kinetic defects at the AChR) (summary by Engel et al., 2003; Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 14 OMIM
  
  INHERITANCE - Autosomal recessive HEAD & NECK Mouth - High-arched palate (in some patients) CHEST Ribs Sternum Clavicles & Scapulae - Scapular winging (in some patients) SKELETAL - Joint contractures (in some patients) - Distal joint laxity (in some patients) Spine - Lordosis (in some patients) - Scoliosis (in some patients) Feet - Pes planus (in some patients) MUSCLE, SOFT TISSUES - Myasthenia - Limb-girdle muscle weakness - Muscle weakness, proximal greater than distal - Gower sign - Lower and upper limbs affected - Hypotonia (in some patients) - Decremental response of compound muscle action potential on repetitive nerve stimulation - Jitter - Muscle biopsy shows type 1 fiber predominance - Ragged-red fibers (in some patients) - Subsarcolemmal accumulation of normal mitochondria (in some patients) - Tubular aggregates (in some patients) NEUROLOGIC Central Nervous System - Delayed motor development (in some patients) - Waddling gait - Learning difficulties, mild (1 family) LABORATORY ABNORMALITIES - Mildly increased serum creatine kinase (in some patients) - Serum transferrin shows normal or mild hypo-glycosylation MISCELLANEOUS - Onset in first decade - Slowly progressive - Some patients may become wheelchair-bound - Favorable response to anticholinesterase medication - Three unrelated families have been reported (last curated February 2015) MOLECULAR BASIS - Cause by mutation in the homolog of the S. cerevisiae ALG2 gene (ALG2, 607905.0003 ) ▲ Close
- Myasthenic Syndrome, Congenital, 11, Associated With Acetylcholine Receptor Deficiency OMIM
  
  Of note, in 2 asymptomatic N88K homozygous individuals, a second haplotype was present that differed at 3 SNP sites downstream from the N88K mutation.
- Congenital Myasthenic Syndrome Orphanet
  
  Congenital myasthenic syndrome (CMS) is a group of genetic disorders of impaired neuromuscular transmission at the motor endplate characterized by fatigable muscle weakness.
- Myasthenic Syndrome, Congenital, 2c, Associated With Acetylcholine Receptor Deficiency OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome associated with acetylcholine receptor (AChR) deficiency-2C (CMS2C) is caused by compound heterozygous mutation in the CHRNB1 gene (100710) on chromosome 17p13. One such family has been reported. Mutation in the CHRNB1 gene can also cause slow-channel congenital myasthenic syndrome-2A (CMS2A; 616313). Description Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized clinically by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 17 OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-17 (CMS17) is caused by compound heterozygous mutation in the LRP4 gene (604270) on chromosome 11p11. One such family has been reported. For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Ohkawara et al. (2014) reported a young woman with a congenital myasthenic syndrome who presented soon after birth with respiratory and feeding difficulties. She started to walk at age 18 months, but fatigued easily during childhood and was partially wheelchair-bound. Examination at age 9 and 14 years showed mild ptosis, slight limitation of lateral eye movements, moderately severe proximal greater than distal weakness, and hyporeflexia.
- Myasthenia, Congenital, Refractory To Acetylcholinesterase Inhibitors OMIM
  
  Triggs et al. (1992) reported the cases of 3 brothers and a sister, aged 22-43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness, and fatigability unresponsive to acetylcholinesterase inhibitors. Repetitive nerve stimulation showed a significant compound muscle action potential area decrement at 2 or 3 Hz. Nerve conduction studies and concentric needle electromyography were normal. Assessment of individual endplates using single fiber electromyography (SFEMG) with intramuscular axonal microstimulation showed a pattern consistent with a postsynaptic defect of neuromuscular transmission. Edrophonium, an acetylcholinesterase inhibitor, eliminated the decremental response to repetitive nerve stimulation but caused no significant clinical improvement.
- Myasthenic Syndrome, Congenital, 10 OMIM
  
  In 3 additional patients, a frameshift mutation was identified in combination with a nonsense mutation, a splice site mutation, and a missense change of a conserved residue.
- Congenital Myasthenic Syndromes Mayo Clinic
  
  Overview Congenital myasthenic syndromes are rare hereditary (genetic) conditions resulting from a defect at the junction where your nerve stimulates muscle activity. That defect causes muscle weakness. Congenital myasthenic syndromes may affect your nerve cells (presynaptic), your muscle cells (postsynaptic), or the space between your nerve and muscle cells (synaptic).
- Myasthenic Syndrome, Congenital, 3b, Fast-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that fast-channel congenital myasthenic syndrome-3B (CMS3B) is caused by homozygous or compound heterozygous mutation in the CHRND gene (100720) on chromosome 2q37. Mutation in the CHRND gene can also cause slow-channel congenital myasthenic syndrome (CMS3A; 616321) and congenital myasthenic syndrome associated with acetylcholine receptor (AChR) deficiency (CMS3C; 616323). Description Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015).
- Myasthenic Syndrome, Congenital, 3a, Slow-Channel OMIM
  
  A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-3A (CMS3A) is caused by heterozygous mutation in the CHRND gene (100720) on chromosome 2q37. One such patient has been reported. Mutation in the CHRND gene can also cause fast-channel congenital myasthenic syndrome (CMS3B; 616322) and CMS with acetylcholine receptor (AChR) deficiency (CMS3C; 616323). Description Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
- Myasthenic Syndrome, Congenital, 16 OMIM
  
  A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-16 (CMS16) is caused by compound heterozygous or homozygous mutation in the SCN4A gene (603967) on chromosome 17q23. Description Congenital myasthenic syndrome is a disorder characterized by variable degrees of muscle fatigability caused by impaired transmission of electrical signals at the neuromuscular junction (NMJ) (summary by Arnold et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Tsujino et al. (2003) reported a 20-year-old woman with delayed motor development and severe generalized muscle weakness. She also had recurrent attacks of respiratory and bulbar paralysis a few times a month since birth, resulting in cerebral anoxia and secondary cognitive impairment.