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Cancer of the throat
Human papillomavirus-positive oropharyngeal cancer
Other namesHPV16+ oropharyngeal cancer, HPV16+OPC
Microscope image of tumour showing HPV positivity by in situ hybridization
SpecialtyOncology
SymptomsSore or blister in back of mouth, difficulty with speech, swallowing or breathing, swelling in neck, loss of appetite, loss of weight, and weakness
CausesHuman papilloma virus
Risk factorsoral sexual contact
Diagnostic methodEndoscopy, Biopsy, Staining for p16, CT Scan,
Differential diagnosisTobacco associated oropharyngeal cancer
PreventionVaccination
TreatmentSurgery, radiation, chemotherapy
Frequency22,000 cases globally (2008)[1][2]
Human papillomavirus-positive oropharyngeal cancer (HPV-positive OPC or HPV+OPC), is a cancer (squamous cell carcinoma) of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was associated with the use of alcohol or tobacco or both, but the majority of cases are now associated with the HPV virus, acquired by having oral contact with the genitals (oral-genital sex) of a person who has a genital HPV infection. Risk factors include having a large number of sexual partners, a history of oral-genital sex or anal–oral sex, having a female partner with a history of either an abnormal Pap smear or cervical dysplasia, having chronic periodontitis, and, among men, younger age at first intercourse and a history of genital warts. HPV-positive OPC is considered a separate disease from HPV-negative oropharyngeal cancer (also called HPV negative-OPC and HPV-OPC).
HPV-positive OPC presents in one of four ways: as an asymptomatic abnormality in the mouth found by the patient or a health professional such as a dentist; with local symptoms such as pain or infection at the site of the tumor; with difficulties of speech, swallowing, and/or breathing; or as a swelling in the neck if the cancer has spread to local lymph nodes. Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, based on the T stage (size and extent of tumor), N stage (extent of involvement of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not), and combined into an overall stage from I–IV. In 2016, a separate staging system was developed for HPV+OPC, distinct from HPV-OPC.
Whereas most head and neck cancers have been declining as reduced smoking rates have declined, HPV-positive OPC has been increasing. Compared to HPV-OPC patients, HPV-positive patients tend to be younger, have a higher socioeconomic status and are less likely to smoke. In addition, they tend to have smaller tumours, but are more likely to have involvement of the cervical lymph nodes. In the United States and other countries, the number of cases of oropharyngeal cancer has been increasing steadily, with the incidence of HPV-positive OPC increasing faster than the decline in HPV-negative OPC. The increase is seen particularly in young men in developed countries, and HPV-positive OPC now accounts for the majority of all OPC cases. Efforts are being made to reduce the incidence of HPV-positive OPC by introducing vaccination that includes HPV types 16 and 18, found in 95% of these cancers, prior to exposure to the virus. Early data suggest a reduction in infection rates.
In the past, the treatment of OPC was radical surgery, with an approach through the neck and splitting of the jaw bone, which resulted in morbidity and poor survival rates. Later, radiotherapy with or without the addition of chemotherapy, provided a less disfiguring alternative, but with comparable poor outcomes. Now, newer minimally invasive surgical techniques through the mouth have improved outcomes; in high risk cases, this surgery is often followed by radiation and/or chemotherapy. In the absence of high quality evidence regarding which treatment provides the best outcomes, management decisions are often based on one or more of the following: technical factors, likely functional loss, and patient preference. The presence of HPV in the tumour is associated with a better response to treatment and a better outcome, independent of the treatment methods used, and a nearly 60% reduced risk of dying from the cancer. Most recurrence occurs locally and within the first year after treatment. The use of tobacco decreases the chances of survival.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Risk factors
* 4 Pathology
* 4.1 Anatomy
* 4.2 Patterns of spread
* 4.3 Mechanism
* 4.3.1 Virology
* 4.3.2 Oncogenesis
* 5 Diagnosis
* 5.1 Biopsy
* 5.2 Differentiating HPV+OPC from HPV-OPC
* 6 Staging
* 7 Prevention
* 7.1 Avoiding exposure
* 7.2 Vaccination
* 8 Treatment
* 8.1 Surgery
* 8.1.1 Pathological staging
* 8.1.2 Adjuvant postoperative therapy
* 8.1.2.1 Deintensification
* 8.2 Radiotherapy
* 8.2.1 Dosimetry
* 8.2.2 Deintensification
* 8.3 Chemotherapy
* 8.4 Choice of treatment approach
* 8.5 Patient preferences
* 8.6 Carcinoma of unknown primary
* 9 Prognosis
* 9.1 Comparison with HPV-negative oropharyngeal cancer
* 9.2 Determinants of survival
* 9.3 Determinants of disease progression
* 9.4 Determinants of metastasis rates
* 9.5 Predictors of survival
* 9.5.1 After chemoradiation
* 9.5.2 After surgery
* 9.6 Development of other cancers
* 9.7 Regional recurrence after surgery
* 10 Epidemiology
* 10.1 Trends
* 11 See also
* 12 Notes
* 13 References
* 14 Bibliography
* 14.1 Articles
* 14.1.1 Human Papilloma Virus (HPV) and molecular biology
* 14.1.2 Diagnosis and staging
* 14.1.3 Treatment
* 14.1.3.1 Surgery
* 14.1.3.2 Radiation
* 14.1.3.3 Chemotherapy and chemoradiation
* 14.1.3.4 Deintensification
* 14.1.4 Prognosis
* 14.1.5 Epidemiology
* 14.2 Books and conference proceedings
* 14.3 Chapters, monographs, reports and theses
* 14.4 Websites
* 14.4.1 Treatment guidelines
* 15 External links
## Signs and symptoms[edit]
HPV+OPC presents in one of four ways: as an asymptomatic abnormality in the mouth found by the patient or a health professional such as a dentist; with local symptoms such as pain or infection at the site of the tumor; with difficulties of speech, swallowing, and/or breathing; or as a swelling in the neck (if the cancer has spread to lymph nodes). These may be accompanied by more general symptoms such as loss of appetite, weight loss, and weakness.[3]
## Cause[edit]
Electron micrograph of Human Papilloma Viruses
Most mucosal squamous cell head and neck cancers, including oropharyngeal cancer (OPC), have historically been attributed to tobacco and alcohol use. However this pattern has changed considerably since the 1980s. It was realised that some cancers occur in the absence of these risk factors and an association between human papilloma virus (HPV) and various squamous cell cancers, including OPC, was first described in 1983.[4][5] Since then both molecular and epidemiological evidence has been accumulating, with the International Agency for Research on Cancer (IARC) stating that high-risk HPV types 16 and 18 are carcinogenic in humans, in 1995,[6] and In 2007 that HPV was a cause for oral cancers.[7][8] Human papillomavirus (HPV)-positive cancer (HPV+OPC) incidence has been increasing while HPV-negative (HPV-OPC) cancer incidence is declining, a trend that is estimated to increase further in coming years.[9] Since there are marked differences in clinical presentation and treatment relative to HPV status, HPV+OPC is now viewed as a distinct biologic and clinical condition.[10][11][12]
Human HPV has long been implicated in the pathogenesis of several anogenital cancers including those of the anus, vulva, vagina, cervix, and penis.[13] In 2007 it was also implicated by both molecular and epidemiological evidence in cancers arising outside of the anogenital tract, namely oral cancers. HPV infection is common among healthy individuals, and is acquired through oral sex. Although less data is available, prevalence of HPV infection is at least as common among men as among women, with 2004 estimates of about 27% among US women aged 14–59.[8]
HPV oral infection precedes the development of HPV+OPC.[8][5] Slight injuries in the mucous membrane serve as an entry gate for HPV, which thus works into the basal layer of the epithelium.[14][15] People testing positive for HPV type 16 virus (HPV16) oral infection have a 14 times increased risk of developing HPV+OPC.[14] Immunosuppression seems to be an increased risk factor for HPV+OPC.[5] Individuals with TGF-β1 genetic variations, specially T869C, are more likely to have HPV16+OPC.[16] TGF-β1 plays an important role in controlling the immune system. In 1993 it was noted that patients with human papillomavirus (HPV)-associated anogenital cancers had a 4-fold increased risk of tonsillar squamous-cell carcinoma.[17] Although evidence suggests that HPV16 is the main cause of OPC in humans not exposed to smoking and alcohol, the degree to which tobacco and/or alcohol use may contribute to increase the risk of HPV+OPC has not always been clear[5] but it appears that both smoking and HPV infection are independent and additive risk factors for developing OPC.[18] The connection between HPV-infection and oropharyngeal cancer is stronger in regions of lymphoepithelial tissue (base of tongue and palatine tonsils) than in regions of stratified squamous epithelium (soft palate and uvula).[19] Human herpesvirus-8 infection can potentiate the effects of HPV-16.[20]
## Risk factors[edit]
Risk factors include a high number of sexual partners (25% increase >= 6 partners), a history of oral-genital sex (125% >= 4 partners), or anal–oral sex, a female partner with a history of either an abnormal Pap smear or cervical dysplasia,[21] chronic periodontitis,[22][23] and, among men, decreasing age at first intercourse and history of genital warts.[24][25][26][27]
## Pathology[edit]
Basaloid pattern of squamous cell cancer
Cancers of the oropharynx primarily arise in lingual and palatine tonsil lymphoid tissue that is lined by respiratory squamous mucosal epithelium, which may be invaginated within the lymphoid tissue. Therefore, the tumour first arises in hidden crypts. OPC is graded on the basis of the degree of squamous and keratin differentiation into well, moderate or poorly (high) differentiated grades. Other pathological features include the presence of finger-like invasion, perineural invasion, depth of invasion and distance of the tumour from resection margins. Phenotypic variants include basaloid squamous carcinoma, a high grade form (see Chung Fig. 35-3(C)[28] and illustration here). They are most commonly non-keratinising. HPV+OPC also differs from HPV-OPC in being focal rather than multifocal and not being associated with pre-malignant dysplasia. HPV+OPC patients are therefore at less risk of developing other malignancies in the head and neck region, unlike other head and neck primary tumours that may have associated second neoplasms, that may occur at the same time (synchronous) or a distant time (metachronous), both within the head and neck region or more distantly. This suggests that the oncogenic alterations produced by the virus are spatially limited rather than related to a field defect.[29][28][30]
### Anatomy[edit]
Anatomy of oropharynx and surrounding structures
The oropharynx, at the back of the mouth, forms a circle and includes the base of the tongue (posterior third) below, the tonsils on each side, and the soft palate above, together with the walls of the pharynx, including the anterior epiglottis, epiglottic valleculae and branchial cleft at its base. The oropharynx is one of three divisions of the interior of the pharynx based on their relation to adjacent structures (nasal pharynx (nasopharynx), oral pharynx (oropharynx) and laryngeal pharynx (laryngopharynx \- also referred to as the hypopharynx), from top to bottom). The pharynx is a semicircular fibromuscular tube joining the nasal cavities above to the larynx (voice box) and oesophagus (gullet), below, where the larynx is situated in front of the oesophagus.[31]
The oropharynx lies between the mouth (oral cavity) to the front, and the laryngopharynx below, which separates it from the larynx. The upper limit of the oropharynx is marked by the soft palate, and its lower limit by the epiglottis and root of the tongue. The oropharynx communicates with the mouth, in front through what is known as the oropharyngeal isthmus, or isthmus of the fauces. The isthmus (i.e. connection) is formed above by the soft palate, below by the posterior third of the tongue, and at the sides by the palatoglossal arches. The posterior third of the tongue, or tongue base contains numerous follicles of lymphatic tissue that form the lingual tonsils. Adjacent to the tongue base, the lingual surface of the epiglottis, which curves forward, is attached to the tongue by median and lateral glossoepiglottic folds. The folds form small troughs known as the epiglottic valleculae. The lateral walls are marked by two vertical pillars on each side, the pillars of the fauces, or palatoglossal arches. More properly they are separately named the palatoglossal arch anteriorly and the palatopharyngeal arch posteriorly. The anterior arch is named from the palatoglossal muscle within, running from the soft palate to the tongue (glossus), while the posterior arch similarly contains the palatopharyngeal muscle running from the soft palate to the lateral pharynx. Between the arches lies a triangular space, the tonsillar fossa in which lies the palatine tonsil, another lymphoid organ. [32]
The external pharyngeal walls consisting of the four constrictor muscles form part of the mechanism of swallowing. The microscopic anatomy is composed of four layers, being from the lumen outwards, the mucosa, submucosa, muscles and the fibrosa, or fibrous layer. The mucosa consists of stratified squamous epithelium, that is generally non-keratinised, except when exposed to chronic irritants such as tobacco smoke. The submucosa contains aggregates of lymphoid tissue.[32][33]
### Patterns of spread[edit]
Cancers arising in the tonsillar fossa spread to the cervical lymph nodes, primarily the subdigastric (upper jugular) lymph nodes (level II), with secondary involvement of the mid (level III) and low (level IV) jugular nodes and sometimes the posterior cervical nodes (level V). Base of tongue cancers spread to the subdigastric and mid jugular nodes, and occasionally posterior cervical nodes but being closer to the midline are more likely to have bilateral nodal disease. Tonsillar cancers rarely spread to the contralateral side unless involving the midline.[34]
### Mechanism[edit]
Genomic structure of HPV
#### Virology[edit]
HPV associated cancers are caused by high-risk strains of HPV, mainly HPV-16 and HPV-18.[35] HPV is a small non-enveloped DNA virus of the papillomavirus family. Its genome encodes the early (E) oncoproteins E5, E6 and E7 and the late (L) capsid proteins L1 and L2. The virus gains access to the mucosa through microlesions, where it infects the basal layer of cells, which are still able to proliferate. While the virus does not replicate in these cells, expression of its early genes stimulates proliferation and lateral expansion of the basal cells. As this moves the virus particles into the overlying suprabasal layers, late viral gene expression occurs, enabling replication of the circular viral genome (see figure) and structural proteins. As these are pushed into the most superficial mucosal layers, complete viral particles are assembled and released.[36]
#### Oncogenesis[edit]
An increased risk of HPV+OPC is observed more than 15 years after HPV exposure,[8] pointing to a slow development of the disease, similar to that seen in cervical cancer. Relative to HPV-OPC, the oncogenic molecular progression of HPV+OPC is poorly understood.[28] The two main viral oncoproteins of the high risk HPV types are E6 and E7. These are consistently expressed in malignant cell lines, and if their expression is inhibited the malignant phenotype of the cancer cells is blocked. Either of these oncoproteins can immortalise cell lines,[37] but are more efficient when both are expressed, since their separate molecular roles are synergistic.[35][36] The E6 and E7 oncogenes become integrated into host-cell DNA, and the oncoproteins they express interfere with a variety of predominantly antiproliferative cellular regulatory mechanisms. They bind to and inactivate the best known of these mechanisms, the tumor suppressor proteins p53 and retinoblastoma protein pRB (pRb) leading to genomic instability and then cell cycle deregulation (see Chung et al., 2016 Fig. 35.2).[28] Further, yet to be elicited, mechanisms are required for the final steps of malignant transformation of HPV infected cells.[28]
HPV- and HPV+OPC are distinguishable at the molecular level. The naturally occurring (wild type) p53 is widely involved in cellular processes, including autophagy, response to DNA damage, cell cycle regulation and senescence, apoptosis and the generation of adenosine triphosphate (ATP) through oxidative phosphorylation.[38] The gene encoding p53 is inactivated by E6 at the protein level and is found as the wild type in HPV+OPC but mutated in HPV-OPC. In HPV+OPC p53 protein undergoes accelerated degradation by E6, drastically reducing its levels, while in HPV-OPC it undergoes genetic mutation, which may result in synthesis of an abnormal p53 protein, that may not only be inactive as a tumour suppressor, but can also bind and inactivate any non-mutated wild type p53, with an increase in oncogenic activity.[39] Although p53 mutations occur in HPV+OPC, they are far less common than in HPV-OPC (26% vs 48%), and do not appear to affect clinical outcome.[40]
The pRb protein is inactivated by E7 in HPV+OPC, but in HPV-OPC it is the p16 tumour suppressor part of the pRb tumour suppressor network that is inactivated. Also the pRb pathway is inactivated by E7 instead of Cyclin D1 amplification.[8][41] CDKN2A is a tumour suppressor gene that encodes a tumor suppressor protein, p16 (cyclin-dependent kinase inhibitor 2A) and inhibits the kinase activity of the cyclin-dependent kinases CDK4 and CDK6, which in turn induce cell cycle arrest.[38] p16 expression is cell cycle dependent and is expressed focally in only about 5–10% of normal squamous epithelium. Like most HPV+ cancers, HPV+OPC express p16 but the latter does not function as a tumour-suppressor, because the mechanism by which this is achieved, pRb, has been inactivated by E7. p16 is upregulated (over-expressed) due to E7-related loss of pRB with reduced negative feedback,[39][42] whereas it is downregulated in up to 90% of HPV-OPC.[43] This diffuse over-expression in the tumour cells provides a diagnostic marker for HPV involvement.[44][45] Although HPV E6 and E7 reduce tumour suppressor activity, they do so less than genetic and epigenetic processes do in HPV-OPC.[46][47][11]
The tonsillar epithelia (palatine and lingual) share similar nonkeratinization characteristics with the cervix, where HPV infection plays the major role in cases of cervical cancer.[14][48] Also E6 and E7 may make HPV+OPC more immunogenic than HPV-OPC, since anti-E6 and E7 antibodies may be detected in these patients. This in turn could restrict the malignant behaviour of HPV+OPC and the presence of antibodies has been associated with a better prognosis, while treatment may enhance the immunogenicity of the tumour, and hence improve response, although to what extent is not clear.[49][11] Outcomes are also associated with improved adaptive immunity.[50]
## Diagnosis[edit]
Rhinoscope used in diagnosis and surveillance
CT scan in transverse plane, viewed from below, showing a contrast enhancing right tonsil mass due to HPV+OPC
### Biopsy[edit]
Initial diagnosis requires visualisation of the tumour either through the mouth or endoscopically through the nose using a rhinoscope, illustrated to the right, followed by biopsy.[citation needed]
### Differentiating HPV+OPC from HPV-OPC[edit]
HPV+OPC is usually diagnosed at a more advanced stage than HPV-OPC,[8] with 75–90% having involvement of regional lymph nodes.[51] Furthermore, nonkeratinizing squamous cell carcinoma is strongly associated with HPV-OPC.[52][53]
Genetic signatures of HPV+ and HPV- OPC are different.[54][55][56][57][58] HPV+OPC is associated with expression level of the E6/E7 mRNAs and of p16.[59] HPV16 E6/E7-positive cases are histopathologically characterized by their verrucous or papillary (nipple like) structure and koilocytosis of the adjacent mucosa. Approximately 15% of HNSCCs are caused by HPV16 infection and the subsequent constitutive expression of E6 and E7, and some HPV-initiated tumors may lose their original characteristics during tumor progression.[60] High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B.[61]
HPV+OPC is not merely characterized by the presence of HPV-16: only the expression of viral oncogenes within the tumor cells plus the serum presence of E6 or E7 antibodies is unambiguously conclusive for HPV+OPC.[14]
There is not a standard HPV testing method in head and neck cancers,[62] both in situ hybridization (ISH) and polymerase chain reaction (PCR) are commonly used.[44][63] Both methods have comparable performance for HPV detection, however it is important to use appropriate sensitivity controls.[64] Immunohistochemistry (IHC) staining of the tissue for p16 is frequently used as a cost-effective surrogate for HPV in OPC, compared to ISH or PCR[65][66][67] but there is a small incidence of HPV-negative p16-positive disease accounting for about 5% of HPV-OPC.[65]
## Staging[edit]
Staging is generally by the UICC/AJCC TNM (Tumour, Nodes, Metastases) system.[67] Staging is based on clinical examination, diagnostic imaging, and pathology. On imaging, involved lymph nodes may appear cystic, a characteristic of HPV+OPC.[68]
HPV+OPC has been treated similarly to stage-matched and site-matched HPV unrelated OPC, but its unique features, which contrast smoking-related HPV-OPC head and neck cancers, for which patients' demographics, comorbidities, risk factors, and carcinogenesis differ markedly, suggest that a distinct staging system be developed to more appropriately represent the severity of the disease and its prognosis.[69] Standard AJCC TNM staging, such as the seventh edition (2009)[70] while predictive for HPV-OPC has no prognostic value in HPV+OPC.[71][72][66][69] The 8th edition of the AJCC TNM Staging Manual (2016)[73] incorporates this specific staging for HPV+OPC.[74] As of 2018, treatment guidelines are evolving to account for the different outcomes observed in HPV+OPC. Consequently, less intensive (de-intensification) use of radiotherapy or chemotherapy,[75] as well as specific therapy, is under investigation, enrolling HPV+OPC in clinical trials to preserve disease control and minimise morbidity in selected groups based on modified TNM staging and smoking status.[76][77][78][79][80]
HPV+ cancer of the oropharynx are staged as (AJCC 8th ed. 2016):[74] Tumour stage
* T0 no primary identified
* T1 2 cm or less in greatest dimension
* T2 2–4 cm
* T3 >4 cm, or extension to lingual surface of epiglottis
* T4 moderately advanced local disease, invading larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond
Nodal stage
* Nx regional lymph nodes cannot be assessed
* N0 no regional lymph nodes involved
* N1 one or more ipsilateral nodes involved, less than 6 cm
* N2 contralateral or bilateral lymph nodes, less than 6 cm
* N3 lymph node(s) larger than 6 cm
Clinical stage
* Stage I: T0N1, T1–2N0–1
* Stage II: T0N2, T1–3N2, T3N0–2
* Stage III: T0–3N3, T4N0-3
* Stage IV: any metastases (M1)
However, the published literature and ongoing clinical trials use the older seventh edition that does not distinguish between HPV+OPC and HPV-OPC - see Oropharyngeal Cancer - Stages.[81][82] The T stages are essentially similar between AJCC 7 and AJCC 8. with two exceptions. Tis (carcinoma in situ) has been eliminated and the division of T4 into substages (e.g. T4a) has been removed. The major changes are in the N stages, and hence the overall clinical stage. N0 remains the same, but as with the T stage, substages such as N2a have been eliminated. Extracapsular extension (ECE), also referred to as extranodal extension (ENE), which is invasion by the tumour beyond the capsule of the lymph node has been eliminated as a staging criterion.[a]
This results in a HPV+OPC tumour being given a lower stage than if it were HPV-OPC. For instance, a 5 cm tumour with one ipsilateral node involved that is 5 cm in size but has ECE would be considered T3N3bM0 Stage IVB if HPV- but T3N1M0 Stage II if HPV+.[74]
## Prevention[edit]
Vial of HPV vaccine
### Avoiding exposure[edit]
Main article: HPV-associated oropharyngeal cancer awareness and prevention
Prevention of HPV+OPC involves avoiding or reducing exposure to risk factors where possible.
### Vaccination[edit]
About 90% of HPV+OPC carry HPV 16, and another 5% type 18. These two types are both targets of available vaccines. HPV vaccines given prior to exposure can prevent persistent genital infection and the consequent precancerous state.[11] Therefore, they have a theoretical potential to prevent oral HPV infection.[8] A 2010 review study has found that HPV16 oral infection was rare (1.3%) among the 3,977 healthy subjects analyzed.[83]
## Treatment[edit]
The goals of treatment are to optimise survival and locoregional disease control, and prevent spread to distant areas of the body (metastasis), while minimising short and long term morbidity.[84] There is no high quality Level I evidence from prospective clinical trials in HPV+OPC, therefore treatment guidelines must rely on data from treatment of OPC in general and from some retrospective unplanned subsetting of those studies, together with data for head and neck cancer in general.[67] Treatment for OPC has traditionally relied on radiotherapy, chemotherapy and/or other systemic treatments, and surgical resection. Depending on stage and other factors treatment may include a combination of modalities.[85] The mainstay has been radiotherapy in most cases.[66] a pooled analysis of published studies suggested comparable disease control between radiation and surgery, but higher complication rates for surgery +/- radiation.[85][86] Ideally a single modality approach is preferred, since triple modality is associated with much more toxicity, and a multidisciplinary team in a large centre with high patient volumes is recommended.[67][87][12]
Differences in response to treatment between HPV-OPC and HPV+OPC may include differences in the extent and manner in which cellular growth-regulatory pathways are altered in the two forms of OPC. For instance in HPV+OPC the HPV E6 and E7 oncogenes merely render the p53 and pRb pathways dormant, leaving open the possibility of reactivation of these pathways by down-regulating (reducing) expression of the oncogenes. This is in contrast to the mutant form of p53 found in HPV-OPC that is associated with treatment resistance.[11] Furthermore, it is suggested that the effects of E6 and E7 on these pathways renders the tumour more radiosensitive, possibly by interference with mechanisms such as DNA repair, repopulation signalling, and cell-cycle redistribution.[88][89] The microenvironment is also important, with radiation increasing host immune response to viral antigens expressed on the tumour.[50][49] Also, there is an association between an increase in tumour-infiltrating lymphocytes and in circulating white blood cells in HPV+OPC patients and better prognosis. This implies a role for an adaptive immune system in suppressing tumour progression.[90][91][89]
### Surgery[edit]
Historically, surgery provided the single approach to head and neck cancer. Surgical management of OPC carried significant morbidity with a transcervical (through the neck) approach, often involving mandibulotomy, in which the jawbone (mandible) is split. This is referred to as an open surgical technique. Consequently, surgical approaches declined in favour of radiation. In the United States, the use of surgery declined from 41% of cases in 1998 to 30% by 2009, the year that the Food and Drug Administration approved the use of the newer techniques.[92]
These improvements in surgical techniques have allowed many tumours to be resected (removed) by transoral (through the mouth) surgical approaches (TOS), using transoral endoscopic head and neck surgery (HNS).[93] Consequently, surgery became used more, increasing to 35% of cases by 2012.[92] This approach has proven safety, efficacy and tolerability, and includes two main minimally invasive techniques, transoral robotic surgery (TORS)[94][95][96][97][98][99] and transoral laser microsurgery (TLM).[100][101][102] No direct comparisons of these two techniques have been conducted, and clinical trials in head and neck cancer such as ECOG 3311 allow either. They are associated with substantial postoperative morbidity, depending on extent of resection but compared to older techniques have shorter hospital stay, faster recovery, less pain, and less need for gastrostomy or tracheostomy, and less long term effects, which are minimal in the absence of postoperative radiation (RT), or chemoradiation (CRT).[103][104] TORS has the practical advantage that angled telescopes and rotating robotic surgical arms provide better line of sight. Outcomes of minimally invasive procedures also compare favourably with more invasive ones. In early stage disease, including involvement of neck nodes, TORS produces a 2-year survival of 80–90%.[105] TLM similarly, is reported to have a five-year survival of 78% and local control rates of 85–97%.[106][107] In addition to early disease, minimally invasive surgery has been used in advanced cases, with up to 90% local control and disease specific survival.[94][107] Postoperative swallowing was excellent in 87%, but long term dysphagia was associated with larger (T4) cancers, especially if involving the base of the tongue.[107] [12]
The details of the surgical approach depend on the location and size of the primary tumour and its N stage. Neck dissection to examine the draining lymph nodes may be carried out simultaneously or as a second staging procedure. For tumours of the tonsil and lateral pharyngeal wall, and clinically node negative (N0) disease, dissection of the neck typically involves levels 2–4 (see diagram in Dubner 2017) ipsilaterally. Where nodes are involved clinically, dissection will depend on the location and size of the node or nodes. In the case of tongue base primaries, close to the midline, bilateral dissection is recommended.[12]
#### Pathological staging[edit]
An advantage of a primary surgical approach is the amount of pathological information made available, including grade, margin status, and degree of involvement of lymph nodes. This may change the staging, as up to 40% of patients may have a different postoperative pathological stage compared to their preoperative clinical stage. In one study, 24% had their stage reduced (downstaged), which may impact subsequent decision making, including reduction in intensity and morbidity.[108][12] In the United Kingdom, the Royal College of Pathologists (1998)[109][b] has standardised the reporting of surgical margins, with two categories, "mucosal" and "deep", and for each created groups based on the microscopic distance from invasive cancer to the margin, as follows: more than 5 mm (clear), 1–5 mm (close) and less than 1 mm (involved).[110]
#### Adjuvant postoperative therapy[edit]
Data on the use of postoperative radiation therapy (PORT) is largely confined to historical or retrospective studies rather than high quality randomized clinical trials and are based on the overall population of patients with head and neck cancer, rather than specific studies of HPV+OPC, which would have formed a very small proportion of the population studied.[12] Despite surgical excision, in the more advanced cases local and regional recurrence of the cancer, together with spread outside of the head and neck region (metastases) are frequent. The risk of subsequent recurrent disease has been considered highest in those tumours where the pathology shows tumour at the margins of the resection (positive margins), multiple involved regional lymph nodes and extension of the tumour outside of the capsule of the lymph node (extracapsular extension), based on historical experience with head and neck cancer.[111] PORT was introduced in the 1950s in an attempt to reduce treatment failure from surgery alone.[112] Although never tested in a controlled setting, PORT has been widely adopted for this purpose.[113] In an analysis of surgical treatment failure at Memorial Sloan-Kettering Cancer Center, patients treated with surgery alone between 1960–1970 had failure rates of 39 and 73% for those with negative and positive surgical margins respectively. These were compared to those who received PORT (with or without chemotherapy) from 1975–1980. The latter group had lower failure rates of 2% and 11% respectively.[114] In addition, one randomised study from the 1970s (RTOG 73-03) compared preoperative radiation to PORT, and found lower failure rates with the latter.[113][115]
The addition of another modality of treatment is referred to as adjuvant (literally helping) therapy, compared to its use as the initial (primary) therapy, also referred to as radical therapy. Consequently, many of these patients have been treated with adjuvant radiation, with or without chemotherapy. In the above series of reports of minimally invasive surgery, many (30–80%) patients received adjuvant radiation. However, functional outcomes were worse if radiation was added to surgery and worst if both radiation and chemotherapy were used.[12] Radiation dosage has largely followed that derived for all head and neck cancers, in this setting, based on risk. Historically only one randomised clinical trial has addressed optimal dosage, allocated patients to two dosage levels, stratified by risk, but showed no difference in cancer control between the low and high doses (63 and 68.4 Gy), but a higher incidence of complications at the higher doses. Consequently, the lower dose of 57.6 Gy was recommended.[116][117] Because the authors used a fractionation scheme of 1.8 Gy per treatment, this dosage was not widely adopted, practitioners preferring a larger fraction of 2 Gy to produce a shorter treatment time, and a slightly higher dose of 60 Gy in 2 Gy fractions (30 daily treatments).[41] Yet 57.6 Gy in 1.8 Gy fractions is equivalent (iso-effective dose) to only 56 Gy in 2 Gy fractions.[118] 60 Gy corresponds to the 63 Gy used as the low dose in the high risk group. 60 Gy was also the dose used in RTOG 73-03. Subsequently, there was a tendency to intensify treatment in head and neck cancer, and a number of centres adopted a dose of 66 Gy, at least for those patients with adverse tumour features.[119] The effectiveness of PORT in HPV+OPC receives some support from a cohort study (Level 2b), although the number of patients was low, and the number of events (recurrent disease or death) only 7%.[120] Another retrospective population-level study (Level 4) of the SEER database (1998–2011) concluded that there was an overall survival but not disease-specific survival effect of radiation in 410 patients with a single lymph node involved, but used only univariate statistical analysis and contained no information on HPV status.[121] A subsequent much larger study on a similar population in the National Cancer Database (2004–2013) of over 9,000 patients found a survival advantage but this was only in HPV-OPC, not in 410 HPV+OPC patients,[122] and a subsequent study of 2,500 low and intermediate risk HPV+OPC patients showed similar overall survival whether PORT was given or not.[123]
##### Deintensification[edit]
While less studies have been completed examining deintensification (de-escalation) in this setting, than in primary radical radiation for this cancer (see below), it is an area of active investigation.[124] In one single institution study, a decision was made to reduce the radiation dose in high risk patients with HPV+OPC from 66 to 60 Gy, corresponding to the actual evidence, and follow up has shown no decrease in cancer control.[119] Current trials, both in North America and Europe (such as ECOG 3311[c] and PATHOS[d]) use 50 Gy as the comparison arm.[126] The comparator of 50 Gy was chosen on the grounds of (i) the exquisite sensitivity of HPV+OPC to radiation, both in vitro and in vivo; ECOG 1308 showing excellent disease control at 54 Gy; and data[127] suggesting that 50 Gy in 1.43 Gy (iso-effective dose 43 Gy in 2.0 Gy) was sufficient to electively treat the neck.[125] Other studies, such as MC1273 and DART-HPV have evaluated doses as low as 30–36 Gy.[128] Lowering the radiation dose to 54 Gy was identified as one of the important Clinical Cancer Advances of 2018 by the American Society of Clinical Oncology, under the general theme of "Less Is More: Preserving Quality of Life With Less Treatment".[129] Chemotherapy has been used concurrently with radiation in this setting, as in primary treatment with radical radiation, particularly where pathological features indicated a higher risk of cancer recurrence. A number of studies have suggested that this does not improve local control, although adding toxicity.[130]
### Radiotherapy[edit]
Transverse radiation contours used in treating cancer seen on above CT scan and in machine set up below
Person with HPV+OPC receiving IMRT PORT on Varian TruBeam linear accelerator with detail of restraining mask
Concerns over the morbidity associated with traditional open surgical en-bloc resection, led to exploring alternative approaches using radiation.[120] Intensity modulated radiation therapy (IMRT) can provide good control of primary tumours while preserving excellent control rates, with reduced toxicity to salivary and pharyngeal structures relative to earlier technology. HPV+OPC has shown increased sensitivity to radiation with more rapid regression, compared to HPV-OPC.[131] Generally, radiation can safely be delivered to the involved side alone (ipsilateral), due to the low rate of recurrent cancer on the opposite side (contralateral), and significantly less toxicity compared to bilateral treatment.[e][133][132] IMRT has a two-year disease free survival between 82 and 90%, and a two-year disease specific survival up to 97% for stage I and II.[134][135]
Reported toxicities include dry mouth (xerostomia) from salivary gland damage, 18% (grade 2);[f] difficulty swallowing (dysphagia) from damage to the constrictor muscles, larynx and oesophageal sphincter, 15% (grade 2); subclinical aspiration up to 50% (reported incidence of aspiration pneumonia approximately 14%); hypothyroidism 28–38% at three years (may be up to 55% depending on amount of the thyroid gland exposed to over 45 Gy radiation; esophageal stenosis 5%; osteonecrosis of the mandible 2.5%; and need for a gastrostomy tube to be placed at some point during or up to one year after treatment 4% (up to 16% with longer follow up).[12][137][135][138][139] Concerns have been expressed regarding excessive short and long term toxicity, especially dysphagia and xerostomia,[140][141][142] and hence whether standard doses expose patients with better prognoses are being exposed to overtreatment and unnecessary side effects.[143][89]
#### Dosimetry[edit]
The probability of xerostomia at one year increases by 5% for every 1Gy increase in dose to the parotid gland. Doses above 25–30 Gy are associated with moderate to severe xerostomia. Similar considerations apply to the submandibular gland, but xerostomia is less common if only one parotid gland is included in the radiated field[144] and the contralateral submandibular gland is spared (less than 39 Gy)[145] In the same manner, radiation dose to the pharyngeal constrictor muscles, larynx, and cricopharyngeal inlet determine the risk of dysphagia (and hence dependence on gastrostomy tube feeds). The threshold for this toxicity is volume-dependent at 55–60 Gy,[146][147][148][89] with moderate to severe impairment of swallowing, including aspiration, stricture and feeding tube dependence above a mean dose of 47 Gy, with a recommended dose to the inferior constrictor of less than 41 Gy.[149][150] Dose-toxicity relationships for the superior and middle constrictors are steep, with a 20% increase in the probability of dysphagia for each 10 Gy.[151] For late dysphagia, threshold mean total constrictor doses, to limit rates of greater than or equal to grade 2 and 3 below 5% were 58 and 61 Gy respectively. For grade 2 dysphagia, the rate increased by 3.4% per Gy.[152] Doses above 30 Gy to the thyroid are associated with moderate to severe hypothyroidism.[153] Subjective, patient-reported outcomes of quality of life also correlate with radiation dose received.[141]
Altered fractionation schemes, such as RTOG 9003 [g][140] and RTOG 0129[h] have not conferred additional benefit.[154][155] Radiation dose recommendations were largely determined empirically in clinical studies with few HPV+OPC patients, and have remained unchanged for half a century,[89] making it difficult to determine the optimum dose for this subgroup. A common approach uses 70 Gy bilaterally and anteriorly, such as RTOG 9003 (1991–1997)[140][154] and RTOG 0129 (2002–2005).[156][155] For lateralized tonsil cancer unilateral neck radiation is usually prescribed, but for tongue base primaries bilateral neck radiation is more common, but unilateral radiation may be used where tongue base lesions are lateralised.[12]
#### Deintensification[edit]
Concerns have been expressed regarding excessive short and long term toxicity, especially dysphagia and xerostomia,[140][141][142] and hence whether standard doses expose patients with better prognoses to overtreatment and unnecessary side effects.[143][89] Current toxicities have been described as "not tolerable",[157] and hence an intense interest in de-escalation.[126]
While comparison with historical controls has limited value compared to randomised clinical trials (phase III), phase II studies using reduced doses of radiation compared to the historical standard of 70 Gy have been carried out. A study using 54–60 Gy (a 15–20% reduction, stratified by response to initial induction chemotherapy) demonstrated comparable levels of disease control with much lower complication rates,[89] when compared to similar studies, using 70 Gy, such as ECOG 2399.[158][159] The percentage of patients alive after 2 years were 95% at the higher dose and 98% at the lower dose. Similarly for the percentage free of disease (86 and 92%). Toxicities were greatly reduced from an incidence of grade 3 or greater dysphagia and mucositis of 54 and 53% respectively, to 9%. A lower incidence and severity of dysphagia also means that less patients require gastrostomy feeding.[89] A similar comparison can be made with the pooled data from two RTOG studies which utilized 70 Gy (0129 and 0522).[160]
No new guidelines dealing specifically with HPV+OPC have yet been developed, outside of clinical trials. Indirect data suggests the efficacy of less intense treatment. A retrospective analysis of advanced (N+) HPV+OPC suggested 96% 5 year local control with de-intensified radiation of 54 Gy and concurrent cisplatin based chemotherapy.[161] The conclusions of the above pair of similar phase II trials have been supported by several other phase II trials. A prospective trial (ECOG 1308) demonstrated similar locoregional control with 54 Gy,[143] and another study, a high pathological complete response rate at 60 Gy.[162] The Quarterback trial[i] showed comparable outcomes between 56 and 70 Gy.[163] and was followed by Quarterback 2, comparing 50 to 56 Gy.[j] Similarly, the Optima trial showed good disease control with doses between 45 and 50 Gy.[164] Ongoing studies, following the experience of the Mayo Clinic trial (MC1273),[128] such as that the Memorial Sloan Kettering Cancer Center are exploring doses as low as 30Gy.[k] These studies all used well below the previous standard dose of 70 Gy. Since long term toxicity is associated with radiation dose, determining the efficacy of lower and hence less morbid doses of radiation is a priority, since many HPV+ patients can be expected to have long term survival.[12]
Radiation is commonly utilised in combination with chemotherapy, but also may be used as a single modality, especially in earlier stages, e.g. T1-T2, N0-1, and its use in later stages is being explored in clinical trials such as RTOG 1333 which compares radiation alone to radiation with reduced chemotherapy, in non or light smokers.[12]
### Chemotherapy[edit]
As with the radiotherapy data, most of the available knowledge on the efficacy of chemotherapy derives from the treatment of advanced head and neck cancer rather than specific studies of HPV+OPC. Since 1976, many clinical studies have compared CRT to RT alone in the primary management of locally advanced head and neck cancers and have demonstrated an advantage to CRT in both survival and locoregional control.[165][166] Cisplatin is considered the standard agent, and a survival advantage was seen for those patients who received radiation with concurrent cisplatin.[167] Despite this no trials directly comparing cisplatin with other agents in this context have been conducted. The other agent that is widely used is Cetuximab, a monoclonal antibody directed at the epidermal growth factor receptor (EGFR). A 10% survival advantage at three years was noted when cetuximab was given concurrently with radiation (bioradiation).[168] Cetuximab trials were completed prior to knowledge of HPV status.[169] Laboratory and clinical studies on the utility of cetuximab in this context are conflicting. The main toxicity is an acneiform rash, but it had not been compared directly to cisplatin in HPV+OPC, till RTOG 1016 (see Talk) addressed this question.[12][163] Analysis of the results three years after the trial was completed demonstrate that cetuximab is inferior to cisplatin.[170] Concurrent chemotherapy is also superior to chemotherapy alone (induction chemotherapy) followed by radiation.[165][12] Cetuximab shows no advantage when added to cisplatin in combination with radiation.[142] Although chemoradiation became a treatment standard based on clinical trials and in particular, meta-analyses, a subsequent population based study of patients with OPC, indicated no advantage to the addition of chemotherapy to radiation in either HPV+OPC or HPV-OPC,[171] and significant concerns about added toxicity.[172]
Chemotherapy also has a role, combined with radiation, in the postoperative setting (adjuvant therapy).[173] Generally it is used where the pathology of the resected specimen indicates features associated with high risk of locoregional recurrence (e.g. extracapsular extension through involved lymph nodes or very close margins). It has shown improved disease-free survival and locoregional control in two very similar clinical trials in such high risk patients, EORTC 22931 (1994–2000)[111] and RTOG 9501 (1995–2000).[l][m][n][174][175][176] However, for HPV+OPC patients, such extracapsular spread does not appear to be an adverse factor[177][178][179] and the addition of chemotherapy to radiation in this group provided no further advantage.[178] Since the sample size to detect a survival advantage is large, given the small number of events in this group, these studies may have been underpowered and the question of the utility of adding chemotherapy is being addressed in a randomized clinical trial (ADEPT) with two year locoregional control and disease free survival as the endpoint.[o] The addition of chemotherapy to radiation increases acute and late toxicity. In the GORTEC trial, chemotherapy with docetaxel provided improved survival and locoregional control in locally advanced OPC, but was associated with increased mucositis and need for feeding by gastrostomy.[180] Chemotherapy and radiation are associated with a risk of death of 3–4% in this context.[181] It is unclear whether the added toxicity of adding chemotherapy to radiation is offset by significant clinical benefit in disease control and survival.[12]
It is thought that HPV+OPC patients benefit better from radiotherapy and concurrent cetuximab treatment than HPV-OPC patients receiving the same treatment,[182] and that radiation and cisplatin induce an immune response against an antigenic tumour which enhances their effect on the cancer cells.[49] Although the incidence of HPV positivity is low (10–20%), an advantage for HPV+OPC was seen in trials of both cetuximab and panitumumab, a similar anti-EGFR agent, but not a consistent interaction with treatment, although HPV+OPC appears not to benefit to the same extent as HPV-OPC to second line anti-EGFR therapy, possibly due to lower EGFR expression in HPV+OPC.[169]
### Choice of treatment approach[edit]
In the absence of high quality evidence comparing a primary surgical approach to other modalities, decisions are based on consideration of factors such as adequate surgical exposure and anatomically favourable features for adequate resection, post treatment function and quality of life. Such patient selection may enable them to avoid the morbidity of additional adjuvant treatment. In the absence of favourable surgical features the primary treatment of choice remains radiation with or without chemotherapy. Tumor characteristics which favour a non-surgical approach include invasion of the base of the tongue to the extent of requiring resection of 50% or more of the tongue, pterygoid muscle involvement, extension into the parapharyngeal fat abutting the carotid, involvement of the mandible or maxilla or invasion of the prevertebral space.[12]
The adequacy of surgical resection is a major factor in determining the role of postoperative adjuvant therapy. In the presence of a positive margin on pathological examination, most radiation oncologists recommend radiation to the primary site, and concurrent chemotherapy. A negative margin is more likely to be treated with lower doses and a smaller treatment volume. Also the removal of a bulky tumour may allow reduced dosage to adjacent uninvolved pharyngeal structures and hence less effect on normal swallowing.[75][12]
The cancer outcomes (local control, regional control, and survival) for transoral resection followed by adjuvant therapy are comparable to primary chemoradiation,[101][97][138] so that treatment decisions depend more on treatment-related morbidity, functional outcome, and quality of life. Patient factors also need to be taken into account, including general baseline functionality, smoking history, anesthesia risk, oropharyngeal function, swallowing and airway protection and potential for rehabilitation. Patient preference is equally important. Many clinical trials are under way focussing on deintensification, often with risk stratification, e.g. Low, Intermediate and High risk (see Fundakowski and Lango, Table I).[12][p]
Clinical decisions also take into account morbidities, particularly if cancer outcomes are comparable for instance surgery is associated with a risk of bleeding between 5–10%, and a 0.3% risk of fatal postoperative haemorrhage.[102][183][98][99] Surgery may also be complicated by dysphagia, and while most patients can tolerate a diet on the first postoperative day, long term use of a feeding tube has been reported as high as 10%.[107][98][99] Patients with larger tumours, involvement of base of tongue and requiring postoperative adjuvant therapy are more likely to require a long term feeding tube.[184][185] Overall, function and quality of life appear relatively similar between surgery with postoperative radiation, and primary chemoradiation,[186][187][12] but HPV+OPC patients tend to have better quality of life at diagnosis than HPV-OPC but may sustain greater loss following treatment.[188]
Anatomical considerations may also dictate preference for surgical or non-surgical approaches. For instance trismus, a bulky tongue, limited extension of the neck, prominent teeth, torus mandibularis (a bony growth on the mandible) or limited width of the mandible would all be relative contraindications to surgery.[100] Tumour related considerations include invasion of the mandible, base of skull and extensive involvement of the larynx or more than half of the base of tongue.[101] Technical considerations in offering surgery as a primary modality include the presumed ability to achieve adequate margins in the resected specimen and the degree of resulting defect, since close or positive margins are likely to result in subsequent adjuvant therapy to achieve disease control, with resultant increased morbidity. Costs are difficult to estimate but one US study, based on estimates of 25% of all OPC patients receiving surgery alone and 75% surgery followed by adjuvant therapy, using the criteria of the NCCN, found that this approach was less expensive than primary chemoradiation.[189][190][191]
Early stage disease[q] is associated with a relatively favourable outcome, for which single modality therapy is recommended, the choice depending on tumour location and accessibility. For instance unilateral tonsil or tongue base tumours will generally be treated with transoral resection and selective ipsilateral neck dissection. On the other hand, a large midline tongue lesion would require bilateral neck dissection, but in the absence of what are considered adverse pathology (positive margins, extracapsular extension) will likely be treated by surgery alone or radiation including ipsilateral or bilateral neck radiation fields, with surgery for those instances where the likelihood of adjuvant therapy is low.[12]
But many HPV+OPC present with involvement of the lymph nodes in the neck, and hence a higher stage of disease, generally referred to as locally advanced disease. This group is mostly treated with multimodality therapy, with the exception of one of the more favourable subgroups with small primary tumours and lymph node involvement confined to a single node no larger than 3 cm in size, which as noted are considered early stage disease. The three main options for locally advanced but operable disease are resection, neck dissection and adjuvant therapy; chemoradiation (with possible salvage surgery); induction chemotherapy followed by radiation or chemoradiation. However the last option has not been supported in clinical trials that tested it.[r] The primary consideration of surgery for locally advanced disease is to obtain adequate negative margins and spare the patient postoperative chemoradiation. But this must be balanced against the morbidity and functional loss from extensive resection, particularly where the tongue base is involved. To avoid such morbidity, primary chemoradiation is preferred. The management of disease within the cervical lymph nodes has to be taken into account in treating locally advanced disease. Guidelines for all OPC dictate that ectracapsular extension be given postoperative chemoradiation. Where gross neck disease is evident initially primary chemoradiation is usually given.[12]
### Patient preferences[edit]
Current guidelines are based on data for OPC as a whole, so that patients are generally being treated regardless of HPV status, yet many clinicians and researchers are considering deintensification.[194] It is likely that treatment of this condition will continue to evolve in the direction of deintensification, in order to minimize loss of function but maintain disease control.[195] In the absence of specific clinical trials and guidelines, patient preferences need to be taken into consideration to minimise short and long term toxicity and functional loss and optimize quality of life, given the prolonged survival frequently seen.[12] This may involve exploring patients' values regarding trade-offs of disease control against adverse effects of treatment. Patients who have received CRT as primary treatment for OPC place a high value on survival, and although agreeing that deintensification is desirable, were reluctant to trade off much survival advantage for lower toxicity, though would be more likely to forgo chemotherapy than accept reduced radiation.[196]
### Carcinoma of unknown primary[edit]
In some situations HPV+OPC may present with cervical lymph nodes but no evident disease of a primary tumour (T0 N1-3) and is therefore classed as Squamous Cell Carcinoma of Unknown Primary Origin. The occurs in 2-4% of patients presenting with metastatic cancer in the cervical nodes. The incidence of HPV positivity is increasing at a similar rate to that seen in OPC. In such situations, resection of the lingual and palatine tonsils together with neck dissection may be diagnostic and constitute sufficient intervention, since recurrence rates are low.[197][198][199][200][201][12]
## Prognosis[edit]
The presence of HPV within the tumour has been realised to be an important factor for predicting survival since the 1990s.[202]
### Comparison with HPV-negative oropharyngeal cancer[edit]
Tumor HPV status is strongly associated with positive therapeutic response and survival compared with HPV-negative cancer, independent of the treatment modality chosen and even after adjustment for stage.[203] While HPV+OPC patients have a number of favourable demographic features compared to HPV-OPC patients, such differences account for only about ten per cent of the survival difference seen between the two groups.[11] Response rates of over 80% are reported in HPV+ cancer and three-year progression free survival has been reported as 75–82% and 45–57%, respectively, for HPV+ and HPV- cancer, and improving over increasing time.[12][204][205][206] It is likely that HPV+OPC is inherently less malignant than HPV-OPC, since patients treated by surgery alone have a better survival after adjustment for stage.[11]
### Determinants of survival[edit]
In RTOG clinical trial 0129,[s] in which all patients with advanced disease received radiation and chemotherapy, a retrospective analysis (recursive-partitioning analysis, or RPA) at three years identified three risk groups for survival (low, intermediate, and high) based on HPV status, smoking, T stage and N stage (see Ang et al., Fig. 2).[156] HPV status was the major determinant of survival, followed by smoking history and stage. 64% were HPV+ and all were in the low and intermediate risk group, with all non-smoking HPV+ patients in the low risk group. 82% of the HPV+ patients were alive at three years compared to 57% of the HPV- patients, a 58% reduction in the risk of death.[t][156] Locoregional failure is also lower in HPV+, being 14% compared to 35% for HPV-.[159]
### Determinants of disease progression[edit]
HPV positivity confers a 50–60% lower risk of disease progression and death, but the use of tobacco is an independently negative prognostic factor.[156][207] A pooled analysis of HPV+OPC and HPV-OPC patients with disease progression in RTOG trials 0129 and 0522 showed that although less HPV+OPC experienced disease progression (23 v. 40%), the median time to disease progression following treatment was similar (8 months). The majority (65%) of recurrences in both groups occurred within the first year after treatment and were locoregional. Although the rate of failure in the opposite neck following treatment of only one side, is 2.4%, the rate of an isolated recurrence in the opposite neck is 1.7%, and these were mainly where the primary tumour involved the midline. However the rate of failure in the contralateral neck is also greater for HPV+.[208] Of those that recur in this site, nearly all were successfully treated (salvaged) by further local treatment to the opposite neck.[132]
### Determinants of metastasis rates[edit]
HPV+ did not reduce the rate of metastases (about 45% of patients experiencing progression), which are predominantly to the lungs (70%), although some studies have reported a lower rate.[209][160] with 3-year distant recurrence rates of about 10% for patients treated with primary radiation or chemoradiation.[210] Even if recurrence or metastases occur, HPV positivity still confers an advantage.[12][209][211] By contrast tobacco usage is an independently negative prognostic factor, with decreased response to therapy,[156][207] increased disease recurrence rates and decreased survival.[212] The negative effects of smoking, increases with amount smoked, particularly if greater than 10 pack-years.[156][207]
### Predictors of survival[edit]
#### After chemoradiation[edit]
For patients such as those treated on RTOG 0129 with primary chemoradiation, detailed nomograms have been derived from that dataset combined with RTOG 0522, enabling prediction of outcome based on a large number of variables. For instance, a 71 year old married non-smoking high school graduate with a performance status (PS) of 0, and no weight loss or anaemia and a T3N1 HPV+OPC would expect to have a progression-free survival of 92% at 2 years and 88% at 5 years. A 60 year old unmarried nonsmoking high school graduate with a PS of 1, weight loss and anaemia and a T4N2 HPV+OPC would expect to have a survival of 70% at two years and 48% at five years.[213]
#### After surgery[edit]
Less detailed information is available for those treated primarily with surgery, for whom less patients are available,[120] as well as low rates of recurrence (7–10%), but features that have traditionally been useful in predicting prognosis in other head and neck cancers, appear to be less useful in HPV+OPC.[51] These patients are frequently stratified into three risk groups:[92]
* Low risk: No adverse pathological features
* Intermediate risk: T3–T4 primary, perineural or lymphovascular invasion, N2 (AJCC 7)[a]
* High risk: Positive margins, ECE
### Development of other cancers[edit]
HPV+OPC patients are less likely to develop other cancers, compared to other head and neck cancer patients.[30] A possible explanation for the favourable impact of HPV+ is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease"[14] Presence of TP53 mutations, a marker for HPV- OPC, is associated with worse prognosis.[8] High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response.[63]
### Regional recurrence after surgery[edit]
The risk of regional cancer recurrence after neck dissection is often estimated[163] from a large series based on all upper aerodigestive squamous cell cancers. In this series, the overall risks at three years by pathological stage (AJCC 7) were:[214]
* pN0 4.7%
* pN1 4.9%
* pN2 12.1%
## Epidemiology[edit]
In 2015, squamous cell cancer of the head and neck region was the fifth most common cancer other than skin cancer, globally, with an annual incidence of 600,000 cases and about 60,000 cases annually in the United States and Europe.[215] The global incidence of pharyngeal cancer in 2013 was estimated at 136,000 cases.[12][216][217] For 2008 the Global Burden of Disease for OPC in 2008 is estimated at 85,000 cases, of which 22,000 were attributable to HPV, a population attributable fraction (PAF) of 26%. Of these, 17,000 were males and 4,400 females, 13,000 (60%) were aged between 50 and 69 years of age, and the majority of cases (15,000) were in developed regions compared to developing regions (6,400).[218][2] Age Standardised Incidence Rates (ASR) differ considerably by region and country (see de Martel et al., 2017 Fig. 2b).[218] ASRs for 2012 were highest in Europe (Hungary 3.0) and North America (United States 1.7) but much lower in Africa (≤ 0.3), Asia (≤ 0.6), Latin America (≤ 0.4) and Oceania (≤ 0.2) (other than Australasia, Australia 0.9).[219][218] Estimated average numbers of cases and ASR for the US in the period 2008–2012 were 15,738 and 4.5 respectively. HPV+OPC was much more common in males than females (12,638, 7.6 and 3,100, 1.7). The highest incidence age group was 60–69, and was higher in Caucasians than in other races.[220]
HPV+OPC patients tend to be younger than HPV- patients in general.[221] The clinical presentation is also changing from the “typical” head and neck cancer patient with advanced age and major substance usage.[12] By contrast patients with HPV+ cancer are younger (4th–6th decades), male (ratio 8:1) with no or only a minimum history of smoking, generally Caucasian, reached higher education levels, are married, and have higher income.[222] The risk factors for HPV-OPC and HPV+OPC tend to be independent, with the exception of smoking which has an adverse effect on both.[11] The presenting features are also different between HPV+ and HPV- OPC. HPV+ tumours have smaller primary lesions (less than 4 cm) but more advanced nodal disease resulting in higher TNM staging. This in turn may overestimate the severity of the disease status.[223][224]
### Trends[edit]
There has been a global trend in increasing OPC incidence, particularly in North America and northern Europe, but even in Taiwan, which has a very high rate for all cancers of the head and neck region, OPC rates increased more rapidly between 1995 and 2009 than any other cancer site.[225][226] The Global Burden of HPV+OPC increased from 22,000 in 2008 to 29,000 by 2012, and the PAF from 26% to 31%,[218] and is considered an epidemic.[44] In the United States the estimated number of cases was 12,410 in 2008,[227] 13,930 in 2013[228] and 17,000 for 2017.[229] Of these cases, HPV+ cancer has been increasing compared to HPV- cancer, but the increase in HPV+OPC exceeds the decline in HPV-OPC resulting an overall increase in OPC.[11] The rise in pharyngeal cancer incidence contrasts with a marginal decline in other head and neck cancers.[230] As a result, the commonest head and neck cancer has shifted from larynx to oropharynx.[120] A survey of 23 countries between 1983 and 2002 showed an increase in oropharyngeal squamous cell carcinoma that was particularly noticeable in young men in economically developed countries.[217][12] In the United Kingdom the incidence of oral and oropharyngeal cancer in men rose 51%, from 7/100,000 to 11/100,000 between 1989 and 2006.[230] In the US there is a growing incidence of HPV associated oropharyngeal cancers,[231] In the early 1980s HPV+ accounted for only 7.5% of cases in the US but by 2016 this was 70%,[12][232][233][234] perhaps as a result of changing sexual behaviors, decreased popularity of tonsillectomies, improved radiologic and pathologic evaluation, and changes in classification.[235][236][237] Tonsil and oropharyngeal cancers increased in male predominance between 1975 and 2004, despite reductions in smoking.[238] HPV-OPC decreased with decreasing smoking rates from 1988 to 2004, while HPV+OPC increased by almost 7.5% per year from about 16% of all cases of OPC in the early 1980s to almost 70% in 2004.[222][239] The decline in smoking may be linked to the decreasing proportion of HPV negative cancers, while changes in sexual activity may be reflected in increasing proportion of HPV positive cancers.[222] Recently, in the US, HPV associated OPC represent about 60% of OPC cases[159][240] compared with 40% in the previous decade.[230] By 2007, in the US, incidence of general OPC, including non-HPV associated, is 3.2 cases per 100,000 males/year and 1.9 per 100,000 all-sexes/year.[241] This makes HPV+OPC one of only five cancers that have increased in incidence in the US since 1975.[242] The largest increase in incidence has occurred in patients under age 50.[243]
The increase in incidence of HPV associated OPC is also seen in other countries, like Sweden, with a 2007 incidence of over 80% for cancer in the tonsils,[244][245] Finland[246] and the Czech Republic.[247] Partners of patients with HPV positive oropharyngeal cancer do not seem to have elevated oral HPV infection compared with the general population.[248] In Australia the incidence of HPV associated OPC was 1.56 cases per 100,000 males/year (2001–2005), rising from 19% (1987–90), to 47% (2001–05) and 63.5% (2006–2010).[249][40] In Canada the percentage of cases of OPC attributable to HPV increased from 47% in 2000 to 74% in 2012.[250]
## See also[edit]
* HPV-associated oropharyngeal cancer awareness and prevention
## Notes[edit]
1. ^ a b N stage, AJCC 7th ed.[74]
N1: one ipsilateral node involved, 3 cm or smaller, ECE negative (ECE-)
N2a: one ipsilateral node 3–6 cm, ECE-
N2b: more than one ipsilateral node, less than 6 cm, ECE-
N2c: bilateral nodes, less than 6 cm, ECE-
N3a: any lymph node larger than 6 cm, ECE-
N3b: any lymph node ECE+
2. ^ Revised 3rd edition, 2013
3. ^ ECOG 3311 (NCT01706939) was activated in 2013 and completed accrual of 511 patients and is now in follow up - see Talk
4. ^ Planned accrual of 242 patients to PATHOS commenced in late 2014 - see Talk[125]
5. ^ Contralteral recurrence after unilateral treatment has been reported in only 2.4% of cases[132]
6. ^ Adverse effects are usually reported as grades 0–5, where 0 represents none and 5 represents death, corresponding to 1. mild, 2. moderate, 3. severe and 4. life-threatening. These are standardised as the Common Terminology Criteria for Adverse Events (CTCAE)[136]
7. ^ RTOG 9003 - see Talk
8. ^ RTOG0129 - see Talk
9. ^ NCT01706939 - see Talk
10. ^ NCT02945631 - see Talk
11. ^ NCT03323463 - see Talk
12. ^ RTOG 9501 randomized 459 patients with head and neck cancer and any or all of the following high risk features identified on the basis of previous trials: histologic evidence of invasion of two or more regional lymph nodes, extracapsular extension of nodal disease, and microscopically involved mucosal resection margins, between radiation and chemoradiation with cisplatin postoperatively. At five years, locoregional control was improved with chemotherapy but adverse events were greater. Distant metastases were not affected. Longer follow up to ten years showed that these differences were only seen in two high risk subgroups, those with positive margins and those with extracapsular extension
13. ^ :EORC 22931, also published in 2004, used a similar design but differing definition of high risk. It showed a similar early advantage for combined therapy
14. ^ RTOG 9501 - see Talk
15. ^ ADEPT - see Talk
16. ^ For instance ECOG 3311 stratifies HPV+OPC with AJCC 7 Stages III and IV 1-2, N1-2b into three risk groups postoperatively. Low risk is T1-T2 N0-N1 with negative margins. Intermediate risk is clear or close margins with the presence of adverse features on pathology such as perineural invasion or lymphovascular invasion, <1 mm ECE or 2–4 nodes involved. High risk is positive margins or greater than 1 mm ECE or at least 5 nodes involved.
17. ^ Early stage disease is considered as AJCC 7 as T1–22 N0–1 M0, approximately equivalent to T1–2 N0–2 M0 by AJCC 8
18. ^ Clinical trials, such as PARADIGM[192] and DeCIDE[193]
19. ^ RTOG 0129 - see Talk
20. ^ In RTOG 0129 the three prognostic groups were;
* Low risk: HPV-, and had either less than 10 pack years of smoking, or more than 10 pack years but low nodal status (confined to a single node, >3 cm but ≤6 cm in greatest dimension)
* Intermediate risk: HPV+ with >10 pack year smoking and more advanced nodal status, or HPV-, <10 pack years and tumour stage T2–T3
* High risk: All others (including remainder of HPV-, <10 pack years with T4 tumours, and all with >10 pack years)
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## Bibliography[edit]
### Articles[edit]
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#### Human Papilloma Virus (HPV) and molecular biology[edit]
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#### Diagnosis and staging[edit]
* Chenevert, J; Seethala, RR; Barnes, EL; Chiosea, SI (April 2012). "Squamous cell carcinoma metastatic to neck from an unknown primary: the potential impact of modern pathologic evaluation on perceived incidence of human papillomavirus-positive oropharyngeal carcinoma prior to 1970". The Laryngoscope. 122 (4): 793–796. doi:10.1002/lary.21899. PMID 22252715. S2CID 25749527.
* Goldenberg, David; Begum, Shahnaz; Westra, William H.; Khan, Zubair; Sciubba, James; Pai, Sara I.; Califano, Joseph A.; Tufano, Ralph P.; Koch, Wayne M. (July 2008). "Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon" (PDF). Head & Neck. 30 (7): 898–903. doi:10.1002/hed.20796. PMID 18383529. S2CID 32614424.
* Huang, Shao Hui; Xu, Wei; Waldron, John; et al. (10 March 2015). "Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas". Journal of Clinical Oncology. 33 (8): 836–845. doi:10.1200/JCO.2014.58.6412. PMID 25667292.
* Keane, Florence K.; Chen, Yui-Hui; Neville, Bridget A.; Tishler, Roy B.; Schoenfeld, Jonathan D.; Catalano, Paul J.; Margalit, Danielle N. (1 August 2015). "Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era". Cancer. 121 (15): 2594–2602. doi:10.1002/cncr.29402. PMID 25873094. S2CID 205670627.
* Lydiatt, William M.; Patel, Snehal G.; O'Sullivan, Brian; Brandwein, Margaret S.; Ridge, John A.; Migliacci, Jocelyn C.; Loomis, Ashley M.; Shah, Jatin P. (March 2017). "Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual". CA: A Cancer Journal for Clinicians. 67 (2): 122–137. doi:10.3322/caac.21389. PMID 28128848.
* O'Sullivan, Brian; Huang, Shao Hui; Su, Jie; et al. (April 2016). "Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study". The Lancet Oncology. 17 (4): 440–451. doi:10.1016/S1470-2045(15)00560-4. PMID 26936027.
* Porceddu, Sandro V (April 2016). "A TNM classification for HPV+ oropharyngeal cancer". The Lancet Oncology (Editorial). 17 (4): 403–404. doi:10.1016/S1470-2045(15)00611-7. PMID 26936026.
#### Treatment[edit]
* Brockstein, Bruce E.; Vokes, Everett E. (February 2011). "Head and neck cancer in 2010: Maximizing survival and minimizing toxicity". Nature Reviews Clinical Oncology. 8 (2): 72–74. doi:10.1038/nrclinonc.2010.226. PMID 21278773. S2CID 1347226.
* Corry, June; Peters, Lester J.; Rischin, Danny (10 January 2015). "Impact of Center Size and Experience on Outcomes in Head and Neck Cancer". Journal of Clinical Oncology. 33 (2): 138–140. doi:10.1200/JCO.2014.58.2239. PMID 25488964.
* Fakhry, C.; Westra, W.; Li, S.; Cmelak, A.; Ridge, J.; Pinto, H.; Forastiere, A.; Gillison, M. (Feb 2008). "Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial". Journal of the National Cancer Institute. 100 (4): 261–269. doi:10.1093/jnci/djn011. ISSN 0027-8874. PMID 18270337.
* Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; et al. (20 October 2014). "Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma". Journal of Clinical Oncology. 32 (30): 3365–3373. doi:10.1200/JCO.2014.55.1937. PMC 4195851. PMID 24958820.
* Fundakowski, Christopher E.; Lango, Miriam (11 July 2016). "Considerations in surgical versus non-surgical management of HPV positive oropharyngeal cancer". Cancers of the Head & Neck (Review). 1 (1): 6. doi:10.1186/s41199-016-0007-8. PMC 6457136. PMID 31093336.
* Galloway, TJ; Ridge, JA (10 October 2015). "Management of Squamous Cancer Metastatic to Cervical Nodes With an Unknown Primary Site". Journal of Clinical Oncology (Review). 33 (29): 3328–3337. CiteSeerX 10.1.1.1029.7347. doi:10.1200/JCO.2015.61.0063. PMID 26351351.
* Maxwell, Jessica H.; Mehta, Vikas; Wang, Hong; Cunningham, Diana; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas; Ferris, Robert L. (July 2014). "Quality of life in head and neck cancer patients: Impact of HPV and primary treatment modality". The Laryngoscope. 124 (7): 1592–1597. doi:10.1002/lary.24508. PMID 24353066. S2CID 8040452.
* Mehanna, H; Evans, M; Beasley, M; Chatterjee, S; Dilkes, M; Homer, J; O'Hara, J; Robinson, M; Shaw, R; Sloan, P (12 May 2016). "Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines". The Journal of Laryngology & Otology. 130 (S2): S90–S96. doi:10.1017/S0022215116000505. PMC 4873902. PMID 27841123.
* More, Yogesh I.; Tsue, Terance T.; Girod, Douglas A.; Harbison, John; Sykes, Kevin J.; Williams, Carson; Shnayder, Yelizaveta (1 January 2013). "Functional Swallowing Outcomes Following Transoral Robotic Surgery vs Primary Chemoradiotherapy in Patients With Advanced-Stage Oropharynx and Supraglottis Cancers". JAMA Otolaryngology–Head & Neck Surgery. 139 (1): 43–8. doi:10.1001/jamaoto.2013.1074. PMID 23247974.
* Sharma, Arun; Méndez, Eduardo; Yueh, Bevan; Lohavanichbutr, Pawadee; Houck, John; Doody, David R.; Futran, Neal D.; Upton, Melissa P.; Schwartz, Stephen M.; Chen, Chu (24 January 2012). "Human Papillomavirus–Positive Oral Cavity and Oropharyngeal Cancer Patients Do Not Have Better Quality-of-Life Trajectories". Otolaryngology–Head and Neck Surgery. 146 (5): 739–745. doi:10.1177/0194599811434707. PMC 3535430. PMID 22275190.
* Spanos, William C.; Nowicki, Paul; Lee, Dong Wook; Hoover, Andrew; Hostager, Bruce; Gupta, Anjali; Anderson, Mary E.; Lee, John H. (1 November 2009). "Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head and Neck Cancer". Archives of Otolaryngology–Head & Neck Surgery. 135 (11): 1137–46. doi:10.1001/archoto.2009.159. PMID 19917928.
* Wansom, Derrick; Light, Emily; Worden, Frank; et al. (20 December 2010). "Correlation of Cellular Immunity With Human Papillomavirus 16 Status and Outcome in Patients With Advanced Oropharyngeal Cancer". Archives of Otolaryngology–Head & Neck Surgery. 136 (12): 1267–73. doi:10.1001/archoto.2010.211. PMC 3342998. PMID 21173378.
##### Surgery[edit]
* Adelstein, David J.; Ridge, John A.; Brizel, David M.; et al. (December 2012). "Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia". Head & Neck. 34 (12): 1681–1703. doi:10.1002/hed.23136. hdl:2027.42/94490. PMID 23015475. S2CID 542440.
* de Almeida, John R.; Byrd, James K.; Wu, Rebecca; Stucken, Chaz L.; Duvvuri, Uma; Goldstein, David P.; Miles, Brett A.; Teng, Marita S.; Gupta, Vishal; Genden, Eric M. (September 2014). "A systematic review of transoral robotic surgery and radiotherapy for early oropharynx cancer: A systematic review". The Laryngoscope. 124 (9): 2096–2102. doi:10.1002/lary.24712. PMID 24729006. S2CID 20283441.
* Ambrosch, Petra; Kron, Martina; Pradier, O.; Steiner, W. (2001). "Efficacy of Selective Neck Dissection: A Review of 503 Cases of Elective and Therapeutic Treatment of the Neck in Squamous Cell Carcinoma of the Upper Aerodigestive Tract". Otolaryngology–Head and Neck Surgery. 124 (2): 180–187. doi:10.1067/mhn.2001.111598. PMID 11226954. S2CID 25298496.
* Canis, Martin; Martin, Alexios; Kron, Martina; Konstantinou, Alexandra; Ihler, Friedrich; Wolff, Hendrik A.; Matthias, Christoph; Steiner, Wolfgang (29 December 2012). "Results of transoral laser microsurgery in 102 patients with squamous cell carcinoma of the tonsil". European Archives of Oto-Rhino-Laryngology. 270 (8): 2299–2306. doi:10.1007/s00405-012-2335-6. PMC 3699702. PMID 23274878.
* Chen, Allen M.; Daly, Megan E.; Luu, Quang; Donald, Paul J.; Farwell, D. Gregory (March 2015). "Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer". Head & Neck. 37 (3): 381–385. doi:10.1002/hed.23610. PMID 24431059. S2CID 28264800.
* Chia, Stanley H.; Gross, Neil D.; Richmon, Jeremy D. (December 2013). "Surgeon Experience and Complications with Transoral Robotic Surgery (TORS)". Otolaryngology–Head and Neck Surgery. 149 (6): 885–892. doi:10.1177/0194599813503446. PMID 24013139. S2CID 3339804.
* Choby, Garret W.; Kim, Jeehong; Ling, Diane C.; Abberbock, Shira; Mandal, Rajarsi; Kim, Seungwon; Ferris, Robert L.; Duvvuri, Umamaheswar (1 June 2015). "Transoral Robotic Surgery Alone for Oropharyngeal Cancer". JAMA Otolaryngology–Head & Neck Surgery. 141 (6): 499–504. doi:10.1001/jamaoto.2015.0347. PMID 25834991.
* Cohen, Marc A.; Weinstein, Gregory S.; O'Malley, Bert W.; Feldman, Michael; Quon, Harry (April 2011). "Transoral robotic surgery and human papillomavirus status: Oncologic results". Head & Neck. 33 (4): 573–580. doi:10.1002/hed.21500. PMID 21425382. S2CID 24704123.
* Durmus, K; Rangarajan, SV; Old, MO; Agrawal, A; Teknos, TN; Ozer, E (June 2014). "Transoral robotic approach to carcinoma of unknown primary". Head & Neck. 36 (6): 848–52. doi:10.1002/hed.23385. PMC 4266274. PMID 23720223.
* Dziegielewski, Peter T.; Teknos, Theodoros N.; Durmus, Kasim; Old, Matthew; Agrawal, Amit; Kakarala, Kiran; Marcinow, Anna; Ozer, Enver (1 November 2013). "Transoral Robotic Surgery for Oropharyngeal Cancer". JAMA Otolaryngology–Head & Neck Surgery. 139 (11): 1099–108. doi:10.1001/jamaoto.2013.2747. PMC 4274181. PMID 23576186.
* Dowthwaite, Samuel A.; Franklin, Jason H.; Palma, David A.; Fung, Kevin; Yoo, John; Nichols, Anthony C. (2012). "The Role of Transoral Robotic Surgery in the Management of Oropharyngeal Cancer: A Review of the Literature". ISRN Oncology. 2012: 945162. doi:10.5402/2012/945162. PMC 3347745. PMID 22606380.
* Genden, Eric M.; Kotz, Tamar; Tong, Charles C. L.; Smith, Claris; Sikora, Andrew G.; Teng, Marita S.; Packer, Stuart H.; Lawson, William L.; Kao, Johnny (August 2011). "Transoral robotic resection and reconstruction for head and neck cancer". The Laryngoscope. 121 (8): 1668–1674. doi:10.1002/lary.21845. PMID 21792953. S2CID 25175486.
* Graboyes, EM; Sinha, P; Thorstad, WL; Rich, JT; Haughey, BH (November 2015). "Management of human papillomavirus-related unknown primaries of the head and neck with a transoral surgical approach". Head & Neck. 37 (11): 1603–11. doi:10.1002/hed.23800. PMID 24931847. S2CID 33000811.
* Haughey, Bruce H.; Hinni, Michael L.; Salassa, John R.; Hayden, Richard E.; Grant, David G.; Rich, Jason T.; Milov, Simon; Lewis, James S.; Krishna, Murli (December 2011). "Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: A united states multicenter study". Head & Neck. 33 (12): 1683–1694. doi:10.1002/hed.21669. PMID 21284056. S2CID 10611085.
* Mehta, V; Johnson, P; Tassler, A; Kim, S; Ferris, RL; Nance, M; Johnson, JT; Duvvuri, U (January 2013). "A new paradigm for the diagnosis and management of unknown primary tumors of the head and neck: a role for transoral robotic surgery". The Laryngoscope. 123 (1): 146–151. doi:10.1002/lary.23562. PMID 23154813. S2CID 321364.
* Moore, Eric J.; Hinni, Michael L.; Olsen, Kerry D.; Price, Daniel L.; Laborde, Rebecca R.; Inman, Jared C. (June 2012). "Cost Considerations in the Treatment of Oropharyngeal Squamous Cell Carcinoma". Otolaryngology–Head and Neck Surgery. 146 (6): 946–951. doi:10.1177/0194599812437534. PMID 22344182. S2CID 40004254.
* Moore, Eric J.; Henstrom, Doug K.; Olsen, Kerry D.; Kasperbauer, Jan L.; McGree, Michaela E. (March 2009). "Transoral resection of tonsillar squamous cell carcinoma". The Laryngoscope. 119 (3): 508–515. doi:10.1002/lary.20124. PMID 19235742. S2CID 26256802.
* Moore, Eric J.; Olsen, Kerry D.; Kasperbauer, Jan L. (November 2009). "Transoral robotic surgery for oropharyngeal squamous cell carcinoma: A prospective study of feasibility and functional outcomes". The Laryngoscope. 119 (11): 2156–2164. doi:10.1002/lary.20647. PMID 19824067. S2CID 20097467.
* Moore, Eric J.; Olsen, Steven M.; Laborde, Rebecca R.; García, Joaquín J.; Walsh, Francis J.; Price, Daniel L.; Janus, Jeffrey R.; Kasperbauer, Jan L.; Olsen, Kerry D. (March 2012). "Long-term Functional and Oncologic Results of Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma". Mayo Clinic Proceedings. 87 (3): 219–225. doi:10.1016/j.mayocp.2011.10.007. PMC 3538408. PMID 22386176.
* Moore, Eric J.; Hinni, Michael L. (April 2013). "Critical Review: Transoral Laser Microsurgery and Robotic-Assisted Surgery for Oropharynx Cancer Including Human Papillomavirus Related Cancer". International Journal of Radiation Oncology Biology Physics (Review). 85 (5): 1163–1167. doi:10.1016/j.ijrobp.2012.08.033. PMID 23182390.
* Patel, SA; Magnuson, JS; Holsinger, FC; et al. (November 2013). "Robotic surgery for primary head and neck squamous cell carcinoma of unknown site". JAMA Otolaryngology–Head & Neck Surgery. 139 (11): 1203–1211. doi:10.1001/Jamaoto.2013.5189. PMID 24136446.
* Pollei, Taylor R.; Hinni, Michael L.; Moore, Eric J.; Hayden, Richard E.; Olsen, Kerry D.; Casler, John D.; Walter, Logan C. (1 November 2013). "Analysis of Postoperative Bleeding and Risk Factors in Transoral Surgery of the Oropharynx". JAMA Otolaryngology–Head & Neck Surgery. 139 (11): 1212–8. doi:10.1001/jamaoto.2013.5097. PMID 24113922.
* Rinaldi, V; Pagani, D; Torretta, S; Pignataro, L (26 September 2013). "Transoral robotic surgery in the management of head and neck tumours". Ecancermedicalscience. 7: 359. doi:10.3332/ecancer.2013.359. PMC 3782590. PMID 24073017.
* Sinclair, CF; McColloch, NL; Carroll, WR; Rosenthal, EL; Desmond, RA; Magnuson, JS (November 2011). "Patient-perceived and objective functional outcomes following transoral robotic surgery for early oropharyngeal carcinoma". Archives of Otolaryngology–Head & Neck Surgery. 137 (11): 1112–6. doi:10.1001/archoto.2011.172. PMID 22106235.
* Steiner, Wolfgang; Fierek, Oliver; Ambrosch, Petra; Hommerich, Christian P.; Kron, Martina (1 January 2003). "Transoral Laser Microsurgery for Squamous Cell Carcinoma of the Base of the Tongue". Archives of Otolaryngology–Head & Neck Surgery. 129 (1): 36–43. doi:10.1001/archotol.129.1.36. PMID 12525192.
* Walvekar, Rohan R.; Li, Ryan J.; Gooding, William E.; Gibson, Michael K.; Heron, Dwight; Johnson, Jonas T.; Ferris, Robert L. (December 2008). "Role of Surgery in Limited (T1-2, N0-1) Cancers of the Oropharynx". The Laryngoscope. 118 (12): 2129–2134. doi:10.1097/MLG.0b013e3181857950. PMID 18948826. S2CID 8072424.
* Weinstein, Gregory S.; O'Malley, Bert W.; Magnuson, J. Scott; Carroll, William R.; Olsen, Kerry D.; Daio, Lixia; Moore, Eric J.; Holsinger, F. Christopher (August 2012). "Transoral robotic surgery: A multicenter study to assess feasibility, safety, and surgical margins". The Laryngoscope. 122 (8): 1701–1707. doi:10.1002/lary.23294. PMID 22752997. S2CID 30048884.
* White, Hilliary N.; Moore, Eric J.; Rosenthal, Eben L.; Carroll, William R.; Olsen, Kerry D.; Desmond, Reneé A.; Magnuson, J. Scott (20 December 2010). "Transoral Robotic-Assisted Surgery for Head and Neck Squamous Cell Carcinoma". Archives of Otolaryngology–Head & Neck Surgery. 136 (12): 1248–52. doi:10.1001/archoto.2010.216. PMID 21173375.
* Woolgar, Julia Anne; Triantafyllou, Asterios (November 2005). "A histopathological appraisal of surgical margins in oral and oropharyngeal cancer resection specimens". Oral Oncology. 41 (10): 1034–1043. doi:10.1016/j.oraloncology.2005.06.008. PMID 16129652.
##### Radiation[edit]
* Adelstein, David J.; Li, Yi; Adams, George L.; Wagner, Henry; Kish, Julie A.; Ensley, John F.; Schuller, David E.; Forastiere, Arlene A. (January 2003). "An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer". Journal of Clinical Oncology. 21 (1): 92–98. doi:10.1200/JCO.2003.01.008. PMID 12506176.
* Al-Mamgani, Abrahim; van Rooij, Peter; Verduijn, Gerda M.; Mehilal, Robert; Kerrebijn, Jeroen D.; Levendag, Peter C. (February 2013). "The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer". The Laryngoscope. 123 (2): 386–393. doi:10.1002/lary.23699. PMID 23404489. S2CID 37351159.
* Bedi, Meena; Firat, Selim; Semenenko, Vladimir A.; Schultz, Christopher; Tripp, Patrick; Byhardt, Roger; Wang, Dian (May 2012). "Elective Lymph Node Irradiation With Intensity-Modulated Radiotherapy: Is Conventional Dose Fractionation Necessary?". International Journal of Radiation Oncology*Biology*Physics. 83 (1): e87–e92. doi:10.1016/j.ijrobp.2011.12.016. PMID 22516389.
* Beitler, Jonathan J.; Zhang, Qiang; Fu, Karen K.; Trotti, Andy; Spencer, Sharon A.; Jones, Christopher U.; Garden, Adam S.; Shenouda, George; Harris, Jonathan; Ang, Kian K. (May 2014). "Final Results of Local-Regional Control and Late Toxicity of RTOG 9003: A Randomized Trial of Altered Fractionation Radiation for Locally Advanced Head and Neck Cancer". International Journal of Radiation Oncology Biology Physics. 89 (1): 13–20. doi:10.1016/j.ijrobp.2013.12.027. PMC 4664465. PMID 24613816.
* Bourhis, Jean; Overgaard, Jens; Audry, Hélène; et al. (September 2006). "Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis". The Lancet. 368 (9538): 843–854. doi:10.1016/S0140-6736(06)69121-6. PMID 16950362. S2CID 20670949.
* Caudell, Jimmy J.; Schaner, Philip E.; Desmond, Renee A.; Meredith, Ruby F.; Spencer, Sharon A.; Bonner, James A. (February 2010). "Dosimetric Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Squamous Cell Carcinoma of the Head and Neck". International Journal of Radiation Oncology*Biology*Physics. 76 (2): 403–409. doi:10.1016/j.ijrobp.2009.02.017. PMID 19467801.
* Chen, Allen M.; Li, Judy; Beckett, Laurel A.; Zhara, Talia; Farwell, Gregory; Lau, Derick H.; Gandour-Edwards, Regina; Vaughan, Andrew T.; Purdy, James A. (January 2013). "Differential response rates to irradiation among patients with human papillomavirus positive and negative oropharyngeal cancer". The Laryngoscope. 123 (1): 152–157. doi:10.1002/lary.23570. PMID 23008061. S2CID 5106261.
* Chin, Re-I; Spencer, Christopher R.; DeWees, Todd; et al. (November 2016). "Reevaluation of postoperative radiation dose in the management of human papillomavirus-positive oropharyngeal cancer". Head & Neck. 38 (11): 1643–1649. doi:10.1002/hed.24486. PMID 27152851. S2CID 3577182.
* Cramer, John David; Ferris, Robert L.; Duvvuri, Umamaheswar (20 May 2018). "Treatment deintensification to surgery only for stage I human papillomavirus-associated oropharyngeal cancer". Journal of Clinical Oncology. 36 (15 supplement): 6003. doi:10.1200/JCO.2018.36.15_suppl.6003.
* Daly, Megan E.; Le, Quynh-Thu; Maxim, Peter G.; Loo, Billy W.; Kaplan, Michael J.; Fischbein, Nancy J.; Pinto, Harlan; Chang, Daniel T. (April 2010). "Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: Clinical Outcomes and Patterns of Failure". International Journal of Radiation Oncology*Biology*Physics. 76 (5): 1339–1346. doi:10.1016/j.ijrobp.2009.04.006. PMID 19540068.
* Deasy, Joseph O.; Moiseenko, Vitali; Marks, Lawrence; Chao, K.S. Clifford; Nam, Jiho; Eisbruch, Avraham (March 2010). "Radiotherapy Dose–Volume Effects on Salivary Gland Function". International Journal of Radiation Oncology*Biology*Physics. 76 (3): S58–S63. doi:10.1016/j.ijrobp.2009.06.090. PMC 4041494. PMID 20171519.
* Dok, Rüveyda; Kalev, Peter; Van Limbergen, Evert Jan; Asbagh, Layka Abbasi; Vázquez, Iria; Hauben, Esther; Sablina, Anna; Nuyts, Sandra (15 March 2014). "p16INK4a Impairs Homologous Recombination–Mediated DNA Repair in Human Papillomavirus–Positive Head and Neck Tumors". Cancer Research. 74 (6): 1739–1751. doi:10.1158/0008-5472.CAN-13-2479. PMID 24473065.
* Feng, Felix Y.; Kim, Hyungjin M.; Lyden, Teresa H.; Haxer, Marc J.; Feng, Mary; Worden, Frank P.; Chepeha, Douglas B.; Eisbruch, Avraham (August 2007). "Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose–Effect Relationships for the Swallowing Structures". International Journal of Radiation Oncology*Biology*Physics. 68 (5): 1289–1298. doi:10.1016/j.ijrobp.2007.02.049. PMID 17560051.
* Forastiere, Arlene A.; Zhang, Qiang; Weber, Randal S.; et al. (March 2013). "Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer". Journal of Clinical Oncology. 31 (7): 845–852. doi:10.1200/JCO.2012.43.6097. PMC 3577950. PMID 23182993.
* Fu, Karen K.; Pajak, Thomas F.; Trotti, Andy; Jones, Christopher U.; Spencer, Sharon A.; Phillips, Theodore L.; Garden, Adam S.; Ridge, John A.; Cooper, Jay S.; Ang, K.Kian (August 2000). "A radiation therapy oncology group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003". International Journal of Radiation Oncology*Biology*Physics. 48 (1): 7–16. doi:10.1016/S0360-3016(00)00663-5. PMID 10924966.
* Garden, Adam S.; Dong, Lei; Morrison, William H.; et al. (March 2013). "Patterns of Disease Recurrence Following Treatment of Oropharyngeal Cancer With Intensity Modulated Radiation Therapy". International Journal of Radiation Oncology*Biology*Physics. 85 (4): 941–947. doi:10.1016/j.ijrobp.2012.08.004. PMID 22975604.
* Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan B.; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S.; Dreicer, Robert; Epstein, Andrew S.; Gillison, Maura L.; Graham, David L.; Jones, Joshua; Ko, Andrew H.; Lopez, Ana Maria; Maki, Robert G.; Rodriguez-Galindo, Carlos; Schilsky, Richard L.; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold (April 2018). "Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology". Journal of Clinical Oncology. 36 (10): 1020–1044. doi:10.1200/JCO.2017.77.0446. PMID 29380678.
* Kramer, Simon; Gelber, Richard D.; Snow, James B.; Marcial, Victor A.; Lowry, Louis D.; Davis, Lawrence W.; Chandler, Richard (September 1987). "Combined radiation therapy and surgery in the management of advanced head and neck cancer: Final report of study 73-03 of the radiation therapy oncology group". Head & Neck Surgery. 10 (1): 19–30. doi:10.1002/hed.2890100105. PMID 3449477.
* Langendijk, Johannes A.; Doornaert, Patricia; Verdonck-de Leeuw, Irma M.; Leemans, Charles R.; Aaronson, Neil K.; Slotman, Ben J. (August 2008). "Impact of Late Treatment-Related Toxicity on Quality of Life Among Patients With Head and Neck Cancer Treated With Radiotherapy". Journal of Clinical Oncology. 26 (22): 3770–3776. doi:10.1200/JCO.2007.14.6647. PMID 18669465.
* Levendag, Peter C.; Teguh, David N.; Voet, Peter; et al. (October 2007). "Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: A dose-effect relationship". Radiotherapy and Oncology. 85 (1): 64–73. doi:10.1016/j.radonc.2007.07.009. PMID 17714815.
* Li, Baoqing; Li, Dan; Lau, Derick H; Farwell, D Gregory; Luu, Quang; Rocke, David M; Newman, Kathleen; Courquin, Jean; Purdy, James A; Chen, Allen M (2009). "Clinical-dosimetric analysis of measures of dysphagia including gastrostomy-tube dependence among head and neck cancer patients treated definitively by intensity-modulated radiotherapy with concurrent chemotherapy". Radiation Oncology. 4 (1): 52. doi:10.1186/1748-717X-4-52. PMC 2785826. PMID 19909531.
* Maccomb, WS; Fletcher, GH (March 1957). "Planned combination of surgery and radiation in treatment of advanced primary head and neck cancers". The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. 77 (3): 397–414. PMID 13403033.
* Monroe, Marcus M.; Buchmann, Luke O.; Hunt, Jason P.; Hitchcock, Ying J.; Lloyd, Shane; Hashibe, Mia (April 2017). "The Benefit of Adjuvant Radiation in Surgically-Treated T1-2 N1 Oropharyngeal Squamous Cell Carcinoma". Laryngoscope Investigative Otolaryngology. 2 (2): 57–62. doi:10.1002/lio2.64. PMC 5527368. PMID 28894823.
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* Parsons, James T.; Mendenhall, William M.; Stringer, Scott P.; et al. (1 June 2002). "Squamous cell carcinoma of the oropharynx: Surgery, radiation therapy, or both". Cancer. 94 (11): 2967–2980. doi:10.1002/cncr.10567. PMID 12115386. S2CID 34438428.
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* Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H. (September 2009). "Transoral laser microsurgery (TLM) ± adjuvant therapy for advanced stage oropharyngeal cancer". The Laryngoscope. 119 (9): 1709–1719. doi:10.1002/lary.20552. PMC 3877921. PMID 19572271.
* Robin, Tyler P.; Gan, Gregory N.; Tam, Moses; Westerly, David; Riaz, Nadeem; Karam, Sana D.; Lee, Nancy; Raben, David (April 2016). "Safety of contralateral submandibular gland sparing in locally advanced oropharyngeal cancers: A multicenter review". Head & Neck. 38 (4): 506–511. doi:10.1002/hed.23928. PMID 25482748. S2CID 2317606.
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##### Chemotherapy and chemoradiation[edit]
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* Calais, Gilles; Bardet, Etienne; Sire, Christian; Alfonsi, Marc; Bourhis, Jean; Rhein, Béatrix; Tortochaux, Jacques; Man, Yooye Tao Kong; Auvray, Hugues; Garaud, Pascal (January 2004). "Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial". International Journal of Radiation Oncology Biology Physics. 58 (1): 161–166. doi:10.1016/S0360-3016(03)01370-1. PMID 14697434.
* Chen, Allen M; Felix, Carol; Wang, Pin-Chieh; et al. (June 2017). "Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study". The Lancet Oncology (Submitted manuscript). 18 (6): 803–811. doi:10.1016/S1470-2045(17)30246-2. PMC 6488353. PMID 28434660.
* Chera, Bhishamjit S.; Amdur, Robert J.; Tepper, Joel; et al. (December 2015). "Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma". International Journal of Radiation Oncology*Biology*Physics. 93 (5): 976–985. doi:10.1016/j.ijrobp.2015.08.033. PMID 26581135.
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* Cohen, EE; Karrison, TG; Kocherginsky, M; et al. (1 September 2014). "Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer". Journal of Clinical Oncology. 32 (25): 2735–43. doi:10.1200/JCO.2013.54.6309. PMC 4876357. PMID 25049329.
* Cooper, Jay S.; Pajak, Thomas F.; Forastiere, Arlene A.; et al. (6 May 2004). "Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck". New England Journal of Medicine. 350 (19): 1937–1944. doi:10.1056/NEJMoa032646. PMID 15128893.
* Cooper, Jay S.; Zhang, Qiang; Pajak, Thomas F.; et al. (December 2012). "Long-term Follow-up of the RTOG 9501/Intergroup Phase III Trial: Postoperative Concurrent Radiation Therapy and Chemotherapy in High-Risk Squamous Cell Carcinoma of the Head and Neck". International Journal of Radiation Oncology Biology Physics. 84 (5): 1198–1205. doi:10.1016/j.ijrobp.2012.05.008. PMC 3465463. PMID 22749632.
* Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel; et al. (June 2010). "Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer". International Journal of Radiation Oncology*Biology*Physics. 77 (2): 468–476. doi:10.1016/j.ijrobp.2009.05.018. PMID 19577867.
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* Eriksen, J. G.; Lassen, P.; Overgaard, J. (2010). "Do all patients with head and neck cancer benefit from radiotherapy and concurrent cetuximab?". The Lancet Oncology. 11 (4): 312–313. doi:10.1016/S1470-2045(10)70035-8. PMID 20359659.
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* Haddad, R; O'Neill, A; Rabinowits, G; et al. (March 2013). "Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial". The Lancet Oncology. 14 (3): 257–64. doi:10.1016/S1470-2045(13)70011-1. PMID 23414589.
* Hall, S.F.; Irish, J.C.; Gregg, R.W.; Groome, P.A.; Rohland, S. (8 January 2015). "Adherence to and uptake of clinical practice guidelines: lessons learned from a clinical practice guideline on chemotherapy concomitant with radiotherapy in head-and-neck cancer". Current Oncology. 22 (2): e61–8. doi:10.3747/co.22.2235. PMC 4399625. PMID 25908922.
* Hall, Stephen F; Liu, Fei-Fei; O'Sullivan, Brian; Shi, Willa; Rohland, Susan; Griffiths, Rebecca; Groome, Patti (22 August 2017). "Did the addition of concurrent chemotherapy to conventional radiotherapy improve survival for patients with HPV+ve and HPV−ve Oropharynx cancer? A population-based study". British Journal of Cancer. 117 (8): 1105–1112. doi:10.1038/bjc.2017.275. PMC 5674099. PMID 28829763.
* Hunter, Klaudia U.; Schipper, Matthew; Feng, Felix Y.; Lyden, Teresa; Haxer, Mark; Murdoch-Kinch, Carol-Anne; Cornwall, Benjamin; Lee, Connie S.Y.; Chepeha, Douglas B.; Eisbruch, Avraham (March 2013). "Toxicities Affecting Quality of Life After Chemo-IMRT of Oropharyngeal Cancer: Prospective Study of Patient-Reported, Observer-Rated, and Objective Outcomes". International Journal of Radiation Oncology Biology Physics. 85 (4): 935–940. doi:10.1016/j.ijrobp.2012.08.030. PMC 3556374. PMID 23040224.
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* Seiwert, T.; Melotek, J.M.; Foster, C.C.; Blair, E.A.; Karrison, T.G.; Agrawal, N.; Portugal, L.; Gooi, Z.; Stenson, K.M.; Brisson, R.J.; Arshad, S.; Dekker, A.; Kochanny, S.; Saloura, V.; Spiotto, M.T.; Villaflor, V.M.; Haraf, D.J.; Vokes, E.E. (April 2018). "OPTIMA—A Phase 2 Trial of Induction Chemotherapy Response-Stratified Radiation Therapy Dose and Volume De-escalation for HPV+ Oropharyngeal Cancer: Efficacy, Toxicity, and HPV Subtype Analysis". International Journal of Radiation Oncology Biology Physics. 100 (5): 1309. doi:10.1016/j.ijrobp.2017.12.025.
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##### Deintensification[edit]
* An, Yi; Holsinger, F. Christopher; Husain, Zain A. (20 December 2016). "De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer". Cancers of the Head & Neck (Review). 1 (1): 18. doi:10.1186/s41199-016-0016-7. PMC 6460758. PMID 31093347.
* Arnaoutakis, Demetri; Sumer, Baran D. (10 August 2017). "Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer". Annals of Surgical Oncology. 24 (12): 3463–3465. doi:10.1245/s10434-017-6045-6. PMID 28799138.
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#### Prognosis[edit]
* Al-Mamgani, Abrahim; van Werkhoven, Erik; Navran, Arash; Karakullukcu, Baris; Hamming-Vrieze, Olga; Machiels, Melanie; van der Velden, Lilly-Ann; Vogel, Wouter V.; Klop, W. Martin (September 2017). "Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review". Cancer Treatment Reviews. 59: 102–108. doi:10.1016/j.ctrv.2017.07.004. PMID 28779635.
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* Fakhry, Carole; Zhang, Qiang; Nguyen-Tân, Phuc Felix; et al. (4 August 2017). "Development and Validation of Nomograms Predictive of Overall and Progression-Free Survival in Patients With Oropharyngeal Cancer". Journal of Clinical Oncology. 35 (36): 4057–4065. doi:10.1200/JCO.2016.72.0748. PMC 5736236. PMID 28777690.
* Fischer, C. A.; Kampmann, M.; Zlobec, I.; Green, E.; Tornillo, L.; Lugli, A.; Wolfensberger, M.; Terracciano, L. M. (27 April 2010). "p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters" (PDF). Annals of Oncology. 21 (10): 1961–1966. doi:10.1093/annonc/mdq210. PMID 20423915.
* Gillison, Maura L. (20 December 2006). "Human Papillomavirus and Prognosis of Oropharyngeal Squamous Cell Carcinoma: Implications for Clinical Research in Head and Neck Cancers". Journal of Clinical Oncology (Editorial). 24 (36): 5623–5625. doi:10.1200/JCO.2006.07.1829. PMID 17179099.
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* Huang, K.; Banerjee, R.N.; Debenham, B.; Patel, A.; Sabiq, F.; Harold, L.; Skarsgard, D.P.; Lysack, J.; Ghosh, S.; Quon, H.C. (April 2018). "What's the Matter With Matted Nodes? Significance of Matted Lymph Nodes in HPV-Related Oropharyngeal Squamous Cell Carcinoma: A Multi-institutional Population-Based Cohort Study". International Journal of Radiation Oncology Biology Physics. 100 (5): 1328. doi:10.1016/j.ijrobp.2017.12.059.
* de Jong, M. C.; Pramana, J.; Knegjens, J. L.; Balm, A. J. M.; Van Den Brekel, M. W. M.; Hauptmann, M.; Begg, A. C.; Rasch, C. R. N. (24 March 2010). "HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors". Radiotherapy and Oncology. 95 (3): 365–370. doi:10.1016/j.radonc.2010.02.001. ISSN 1879-0887. PMID 20346528.
* Kato, Masanari G.; Ellis, Mark A.; Nguyen, Shaun A.; Day, Terry A. (February 2018). "Predictors of contralateral-bilateral nodal disease in oropharyngeal cancer: A National Cancer Data Base Study". Head & Neck. 40 (2): 338–348. doi:10.1002/hed.24964. PMID 28963823. S2CID 10627950.
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* Lowy, D.; Munger, K. (2010). "Prognostic Implications of HPV in Oropharyngeal Cancer". The New England Journal of Medicine (Editorial). 363 (1): 82–84. doi:10.1056/NEJMe1003607. PMID 20530315.
* Martel, María; Alemany, Laia; Taberna, Miren; Mena, Marisa; Tous, Sara; Bagué, Silvia; Castellsagué, Xavier; Quer, Miquel; León, Xavier (January 2017). "The role of HPV on the risk of second primary neoplasia in patients with oropharyngeal carcinoma". Oral Oncology. 64: 37–43. doi:10.1016/j.oraloncology.2016.11.011. PMID 28024722.
* Maxwell, J. H.; Kumar, B.; Feng, F. Y.; et al. (9 February 2010). "Tobacco Use in Human Papillomavirus-Positive Advanced Oropharynx Cancer Patients Related to Increased Risk of Distant Metastases and Tumor Recurrence". Clinical Cancer Research. 16 (4): 1226–1235. doi:10.1158/1078-0432.CCR-09-2350. PMC 2822887. PMID 20145161.
* Maxwell, Jessica H.; Ferris, Robert L.; Gooding, William; Cunningham, Diana; Mehta, Vikas; Kim, Seungwon; Myers, Eugene N.; Johnson, Jonas; Chiosea, Simion (September 2013). "Extracapsular spread in head and neck carcinoma: Impact of site and human papillomavirus status". Cancer. 119 (18): 3302–3308. CiteSeerX 10.1.1.663.564. doi:10.1002/cncr.28169. PMID 23797868. S2CID 32595866.
* Nguyen, Nam P.; Ly, Bevan Hong; Betz, Michael; Vinh-Hung, Vincent (18 June 2010). "Importance of Age as a Prognostic Factor for Tonsillar Carcinoma". Annals of Surgical Oncology. 17 (10): 2570–2577. doi:10.1245/s10434-010-1167-0. PMID 20559738. S2CID 8833627.
* O'Sullivan, Brian; Huang, Shao Hui; Siu, Lillian L.; et al. (10 February 2013). "Deintensification Candidate Subgroups in Human Papillomavirus–Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis". Journal of Clinical Oncology. 31 (5): 543–550. doi:10.1200/JCO.2012.44.0164. PMID 23295795.
* Ragin, Camille C. R.; Taioli, Emanuela (15 October 2007). "Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta-analysis". International Journal of Cancer. 121 (8): 1813–1820. doi:10.1002/ijc.22851. PMID 17546592. S2CID 23657353.
* Rischin, Danny; Young, Richard J.; Fisher, Richard; et al. (20 September 2010). "Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial". Journal of Clinical Oncology. 28 (27): 4142–4148. doi:10.1200/JCO.2010.29.2904. PMC 2953971. PMID 20697079.
* Routman, David M.; Funk, Ryan K.; Tangsriwong, Kanograt; et al. (June 2017). "Relapse Rates With Surgery Alone in Human Papillomavirus–Related Intermediate- and High-Risk Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review". International Journal of Radiation Oncology*Biology*Physics. 99 (4): 938–946. doi:10.1016/j.ijrobp.2017.06.2453. PMID 28847412.
* Sinha, Parul; Lewis, James S.; Piccirillo, Jay F.; Kallogjeri, Dorina; Haughey, Bruce H. (15 July 2012). "Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma". Cancer. 118 (14): 3519–3530. doi:10.1002/cncr.26671. PMID 22086669. S2CID 28111538.
* Sinha, P.; Thorstad, W.T.; Nussenbaum, B.; Haughey, B.H.; Adkins, D.R.; Kallogjeri, D.; Lewis Jr., J.S. (January 2014). "Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: A critical analysis of patterns and outcomes". Oral Oncology. 50 (1): 45–51. doi:10.1016/j.oraloncology.2013.10.007. PMC 3942323. PMID 24211084.
* Sinha, Parul; Kallogjeri, Dorina; Gay, Hiram; Thorstad, Wade L.; Lewis, James S.; Chernock, Rebecca; Nussenbaum, Brian; Haughey, Bruce H. (May 2015). "High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer". Oral Oncology. 51 (5): 514–520. doi:10.1016/j.oraloncology.2015.02.098. PMID 25771076.
* Trosman, Samuel J.; Koyfman, Shlomo A.; Ward, Matthew C.; et al. (1 May 2015). "Effect of Human Papillomavirus on Patterns of Distant Metastatic Failure in Oropharyngeal Squamous Cell Carcinoma Treated With Chemoradiotherapy". JAMA Otolaryngology–Head & Neck Surgery. 141 (5): 457–62. doi:10.1001/jamaoto.2015.136. PMID 25742025.
* Ward, M J; Thirdborough, S M; Mellows, T; et al. (29 October 2013). "Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer". British Journal of Cancer. 110 (2): 489–500. doi:10.1038/bjc.2013.639. PMC 3899750. PMID 24169344.
#### Epidemiology[edit]
* Anantharaman, Devasena; Muller, David C; Lagiou, Pagona; et al. (June 2016). "Combined effects of smoking and HPV16 in oropharyngeal cancer". International Journal of Epidemiology. 45 (3): 752–761. doi:10.1093/ije/dyw069. PMC 5841602. PMID 27197530.
* Chaturvedi, A.; Engels, E.; Anderson, W.; Gillison, M. (Feb 2008). "Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States". Journal of Clinical Oncology. 26 (4): 612–619. doi:10.1200/JCO.2007.14.1713. PMID 18235120.
* Chaturvedi, Anil K.; Engels, Eric A.; Pfeiffer, Ruth M.; et al. (10 November 2011). "Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States". Journal of Clinical Oncology. 29 (32): 4294–4301. doi:10.1200/JCO.2011.36.4596. PMC 3221528. PMID 21969503.
* Chaturvedi, Anil K.; Anderson, William F.; Lortet-Tieulent, Joannie; Curado, Maria Paula; Ferlay, Jacques; Franceschi, Silvia; Rosenberg, Philip S.; Bray, Freddie; Gillison, Maura L. (20 December 2013). "Worldwide Trends in Incidence Rates for Oral Cavity and Oropharyngeal Cancers". Journal of Clinical Oncology. 31 (36): 4550–4559. doi:10.1200/JCO.2013.50.3870. PMC 3865341. PMID 24248688.
* Chenevert, J; Chiosea, S (January 2012). "Incidence of human papillomavirus in oropharyngeal squamous cell carcinomas: now and 50 years ago". Human Pathology. 43 (1): 17–22. doi:10.1016/j.humpath.2011.03.009. PMID 21777945.
* Cook, M.; Dawsey, S.; Freedman, N.; Inskip, P.; Wichner, S.; Quraishi, S.; Devesa, S.; McGlynn, K. (2009). "Sex disparities in cancer incidence by time period and age". Cancer Epidemiology, Biomarkers & Prevention. 18 (4): 1174–1182. doi:10.1158/1055-9965.EPI-08-1118. PMC 2793271. PMID 19293308.
* Dayyani, Farshid; Etzel, Carol J; Liu, Mei; Ho, Chung-Han; Lippman, Scott M; Tsao, Anne S (2010). "Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC)". Head & Neck Oncology. 2 (1): 15. doi:10.1186/1758-3284-2-15. PMC 2908081. PMID 20587061.
* D'Souza, G.; Kreimer, A.; Viscidi, R.; Pawlita, M.; Fakhry, C.; Koch, W.; Westra, W.; Gillison, M. (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine. 356 (19): 1944–1956. doi:10.1056/NEJMoa065497. ISSN 0028-4793. PMID 17494927. S2CID 18819678.
* de Martel, Catherine; Ferlay, Jacques; Franceschi, Silvia; Vignat, Jérôme; Bray, Freddie; Forman, David; Plummer, Martyn (June 2012). "Global burden of cancers attributable to infections in 2008: a review and synthetic analysis". The Lancet Oncology. 13 (6): 607–615. doi:10.1016/S1470-2045(12)70137-7. PMID 22575588.
* de Martel, Catherine; Plummer, Martyn; Vignat, Jerome; Franceschi, Silvia (15 August 2017). "Worldwide burden of cancer attributable to HPV by site, country and HPV type". International Journal of Cancer. 141 (4): 664–670. doi:10.1002/ijc.30716. PMC 5520228. PMID 28369882.
* Ernster, J.; Sciotto, C.; O'Brien, M.; Finch, J.; Robinson, L.; Willson, T.; Mathews, M. (Dec 2007). "Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus". The Laryngoscope. 117 (12): 2115–2128. doi:10.1097/MLG.0b013e31813e5fbb. ISSN 0023-852X. PMID 17891052. S2CID 38017888.
* Forman, David; de Martel, Catherine; Lacey, Charles J.; et al. (November 2012). "Global Burden of Human Papillomavirus and Related Diseases". Vaccine. 30: F12–F23. doi:10.1016/j.vaccine.2012.07.055. PMID 23199955.
* Gillison, Maura L.; Chaturvedi, Anil K.; Anderson, William F.; Fakhry, Carole (10 October 2015). "Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma". Journal of Clinical Oncology. 33 (29): 3235–3242. doi:10.1200/JCO.2015.61.6995. PMC 4979086. PMID 26351338.
* Habbous, Steven; Chu, Karen P.; Lau, Harold; et al. (13 August 2017). "Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation". Canadian Medical Association Journal. 189 (32): E1030–E1040. doi:10.1503/cmaj.161379. PMC 5555753. PMID 28808115.
* Hammarstedt, L.; Lindquist, D.; Dahlstrand, H.; et al. (Dec 2006). "Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer". International Journal of Cancer. 119 (11): 2620–2623. doi:10.1002/ijc.22177. ISSN 0020-7136. PMID 16991119. S2CID 20541360.
* Heck, Julia E; Berthiller, Julien; Vaccarella, Salvatore; et al. (February 2010). "Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium". International Journal of Epidemiology. 39 (1): 166–181. doi:10.1093/ije/dyp350. PMC 2817092. PMID 20022926.
* Hemminki, K; Dong, C; Frisch, M (December 2000). "Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands". European Journal of Cancer Prevention. 9 (6): 433–437. doi:10.1097/00008469-200012000-00010. PMID 11201683. S2CID 10517792.
* Hong, Angela M.; Grulich, Andrew E.; Jones, Deanna; Lee, C. Soon; Garland, Suzanne M.; Dobbins, Timothy A.; Clark, Jonathan R.; Harnett, Gerald B.; Milross, Christopher G.; O’Brien, Christopher J.; Rose, Barbara R. (April 2010). "Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets". Vaccine. 28 (19): 3269–3272. doi:10.1016/j.vaccine.2010.02.098. PMID 20226244.
* Hong, Angela; Lee, C. Soon; Jones, Deanna; et al. (May 2016). "Rising prevalence of human papillomavirus-related oropharyngeal cancer in Australia over the last 2 decades". Head & Neck. 38 (5): 743–750. doi:10.1002/hed.23942. PMID 25521312. S2CID 1974978.
* Hwang, Tzer-Zen; Hsiao, Jenn-Ren; Tsai, Chia-Rung; Chang, Jeffrey S. (15 July 2015). "Incidence trends of human papillomavirus-related head and neck cancer in Taiwan, 1995-2009". International Journal of Cancer. 137 (2): 395–408. doi:10.1002/ijc.29330. PMID 25395239. S2CID 20551422.
* Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Murray, T.; Thun, M. J. (28 January 2008). "Cancer Statistics, 2008". CA: A Cancer Journal for Clinicians. 58 (2): 71–96. doi:10.3322/CA.2007.0010. PMID 18287387. S2CID 43737426.
* Marur, S.; D'souza, G.; Westra, W. H.; Forastiere, A. A. (2010). "HPV-associated head and neck cancer: a virus-related cancer epidemic". The Lancet Oncology. 11 (8): 781–789. doi:10.1016/S1470-2045(10)70017-6. PMC 5242182. PMID 20451455.* Näsman, A.; Attner, P.; Hammarstedt, L.; et al. (July 2009). "Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?". International Journal of Cancer. 125 (2): 362–366. doi:10.1002/ijc.24339. PMID 19330833. S2CID 36268685.
* Salem, A. (2010). "Dismissing links between HPV and aggressive tongue cancer in young patients". Annals of Oncology. 21 (1): 13–17. doi:10.1093/annonc/mdp380. PMID 19825879.
* Schwartz, S. M.; Daling, J. R.; Madeleine, M. M.; et al. (4 November 1998). "Oral Cancer Risk in Relation to Sexual History and Evidence of Human Papillomavirus Infection". JNCI Journal of the National Cancer Institute. 90 (21): 1626–1636. doi:10.1093/jnci/90.21.1626. PMID 9811312.
* Siegel, Rebecca; Naishadham, Deepa; Jemal, Ahmedin (January 2013). "Cancer statistics, 2013". CA: A Cancer Journal for Clinicians. 63 (1): 11–30. doi:10.3322/caac.21166. PMID 23335087. S2CID 24926725.
* Siegel, Rebecca L.; Miller, Kimberly D.; Jemal, Ahmedin (January 2015). "Cancer statistics, 2015". CA: A Cancer Journal for Clinicians. 65 (1): 5–29. doi:10.3322/caac.21254. PMID 25559415. S2CID 10193624.
* Siegel, Rebecca L.; Miller, Kimberly D.; Jemal, Ahmedin (January 2017). "Cancer statistics, 2017". CA: A Cancer Journal for Clinicians. 67 (1): 7–30. doi:10.3322/caac.21387. PMID 28055103.
* Smith, E.; Ritchie, J.; Summersgill, K.; Klussmann, J.; Lee, J.; Wang, D.; Haugen, T.; Turek, L. (Feb 2004). "Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers". International Journal of Cancer. 108 (5): 766–772. doi:10.1002/ijc.11633. ISSN 0020-7136. PMID 14696105. S2CID 25146008.
* Sturgis, E.; Cinciripini, P. (Oct 2007). "Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers?". Cancer. 110 (7): 1429–1435. doi:10.1002/cncr.22963. ISSN 0008-543X. PMID 17724670. S2CID 20189903.
* Sturgis, EM; Ang, KK (1 June 2011). "The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms?". Journal of the National Comprehensive Cancer Network. 9 (6): 665–73. doi:10.6004/jnccn.2011.0055. PMID 21636538.
* Tachezy, R (May 2005). "HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic". Oral Diseases. 11 (3): 181–185. doi:10.1111/j.1601-0825.2005.01112.x. PMID 15888110.
* Tezal, Mine; Sullivan Nasca, Maureen; Stoler, Daniel L.; Melendy, Thomas; Hyland, Andrew; Smaldino, Philip J.; Rigual, Nestor R.; Loree, Thom R. (1 April 2009). "Chronic Periodontitis−Human Papillomavirus Synergy in Base of Tongue Cancers". Archives of Otolaryngology–Head & Neck Surgery. 135 (4): 391–6. doi:10.1001/archoto.2009.6. PMID 19380363.
* Tezal, M.; Sullivan, M. A.; Hyland, A.; et al. (10 September 2009). "Chronic Periodontitis and the Incidence of Head and Neck Squamous Cell Carcinoma". Cancer Epidemiology, Biomarkers & Prevention. 18 (9): 2406–2412. doi:10.1158/1055-9965.EPI-09-0334. PMID 19745222.
* Viens, Laura J.; Henley, S. Jane; Watson, Meg; Markowitz, Lauri E.; Thomas, Cheryll C.; Thompson, Trevor D.; Razzaghi, Hilda; Saraiya, Mona (8 July 2016). "Human Papillomavirus–Associated Cancers — United States, 2008–2012". MMWR. Morbidity and Mortality Weekly Report. 65 (26): 661–666. doi:10.15585/mmwr.mm6526a1. PMID 27387669.
### Books and conference proceedings[edit]
* Bernier, Jacques, ed. (2016). Head and Neck Cancer: Multimodality Management. Springer International Publishing. ISBN 978-3-319-27601-4.
* Brierley, J.D.; Gospodarowicz, M.K.; Wittekind, Ch., eds. (2017). TNM classification of malignant tumours (8th ed.). Chichester, West Sussex, UK: Wiley-Blackwell. ISBN 978-1-4443-3241-4.
* Cardesa, Antonio; Slootweg, Pieter J.; Gale, Nina; Franchi, Alessandro, eds. (2017). Pathology of the Head and Neck (2nd ed.). Springer. ISBN 978-3-662-49672-5.
* Golusiński, Wojciech; Leemans, C René; Dietz, Andreas, eds. (2016). HPV Infection in Head and Neck Cancer. Springer. ISBN 978-3-319-43580-0.
* DeVita, Vincent T.; Lawrence, Theodore S.; Rosenberg, Steven A., eds. (2008) [1982]. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology (8th ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0-7817-7207-5.
* Hayat, M. A., ed. (2010). Methods of Cancer Diagnosis, Therapy, and Prognosis: Volume 7 - General Overviews, Head and Neck Cancer and Thyroid Cancer. Springer Science & Business Media. ISBN 978-90-481-3186-0.
* Kerr, David J.; Haller, Daniel G.; van de Velde, Cornelis J.H.; Baumann, Michael, eds. (2016) [1995]. Oxford Textbook of Oncology (3rd ed.). Oxford University Press. ISBN 978-0-19-965610-3.
* Myers, Jeffrey N.; Sturgis, Erich M., eds. (2013). Oral Cavity and Oropharyngeal Cancer, An Issue of Otolaryngologic Clinics, E-Book. Elsevier Health Sciences. ISBN 978-0-323-18632-2.
* Olshan, Andrew F., ed. (2010). Epidemiology, Pathogenesis, and Prevention of Head and Neck Cancer. Springer Science & Business Media. ISBN 978-1-4419-1471-2.
* Sobin, L.H.; Gospodarowicz, M.K.; Wittekind, Ch., eds. (2010). TNM classification of malignant tumours (7th ed.). Chichester, West Sussex, UK: Wiley-Blackwell. ISBN 978-1-4443-3241-4.
* Standring, Susan, ed. (2015). Gray's Anatomy: The Anatomical Basis of Clinical Practice (41st ed.). Elsevier Health Sciences. ISBN 978-0-7020-6851-5., see also Gray's Anatomy
* "Annual Meeting of the American Academy of Otolaryngology, Chicago, September 10-13, 2017: Oral presentations". Otolaryngology–Head and Neck Surgery. 157 (1 suppl): P40–P173. 30 August 2017. doi:10.1177/0194599817717251. PMID 28854028.
### Chapters, monographs, reports and theses[edit]
* Bruni, L; Barrionuevo-Rosas, L; Albero, G; Serrano, B; Mena, M; Gómez, D; Muñoz, J; Bosch, FX; de Sanjosé, S (7 July 2017). Human Papillomavirus and Related Diseases in the World (PDF). HPVIC. Retrieved 11 August 2017., in HPVIC (2017)
* Chaturvedi, Anil; Gillison, Maura L. (2010-03-04). Human Papillomavirus and Head and Neck Cancer. pp. 87–116. ISBN 978-1-4419-1471-2., in Olshan (2010)
* Chung, Christine H; Dietz, Andreas; Gregoire, Vincent; et al. (2016). Head and neck cancer. pp. 329–364. ISBN 9780199656103., in Kerr et al (2016)
* Hammarstedt, Lalle (25 April 2008), Tonsillar Cancer - Incidence, Prevalence of HPV and Survival (PhD thesis), Stockholm: Department of Clinical Neuroscience, Karolinska Institutet, ISBN 978-91-7357-587-4, retrieved 3 June 2017
* McHanwell, Stephen (2015-08-07). Pharynx. pp. 571–585. ISBN 9780702068515., in Standring (2015)
* Helliwell, T; Woolgar, JA (1998). Standards and minimum datasets for reporting common cancers. Minimum dataset for head and neck histopathology reports. London: The Royal College of Pathologists.
* Johnson, Newell; Chaturvedi, Anil (2016). Global burden of oral cavity and pharyngeal cancers (PDF) (Conference white paper). Retrieved 12 August 2017., in GOCF (2016)
* Mehanna, H (2017). "Update on De-intensification and Intensification Studies in HPV". HPV Infection in Head and Neck Cancer. Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 206. pp. 251–256. doi:10.1007/978-3-319-43580-0_20. ISBN 978-3-319-43578-7. PMID 27699545., in Golusiński et al (2016) excerpt here
* Munck-Wikland, Eva; Hammarstedt, Lalle; Dahlstrand, Hanna (2010-04-07). Role of Human Papillomavirus in Tonsillar Cancer. pp. 271–283. ISBN 9789048131860., in Hayat (2010) (additional extract here)
* IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1995). "Human papillomaviruses". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 64: 1–378. PMC 5366848. PMID 16755705.
* IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2007). "Human papillomaviruses". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 90: 1–636. PMC 4781057. PMID 18354839.
* IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2012). "Human Papilloviruses". Biological Agents. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 100B. Lyon: International Agency for Research on Cancer. pp. 255–314. ISBN 978-9283213192.
### Websites[edit]
* Bath, Charlotte (25 April 2017). "Deintensifiying Treatment of HPV-Positive Oropharyngeal Cancer Could Reduce Toxicity While Maintaining Function and Survival". ASCO Post (Report of 2016 Multidisciplinary Head & Neck Symposium). ASCO. Retrieved 3 August 2017.
* Hunt, Jennifer L (21 March 2010). "Molecular Assessment of HPV in Patients with Head and Neck Tumors" (PDF). Association for Molecular Pathology. United States and Canadian Academy of Pathology. Archived from the original (PDF) on 16 July 2011. Retrieved 30 May 2017.
* "Cancer of the Oral Cavity and Pharynx by Subsite" (PDF). SEER Cancer Statistics Review 1975-2007. Surveillance, Epidemiology, and End Results (SEER) Program. 15 April 2010. Retrieved 3 June 2017.
* "The Pharynx". TeachMeAnatomy. TeachMe. 29 April 2017. Retrieved 20 June 2017.
* Dubner, Sanford (19 June 2017). "Head and Neck Cancer - Resection and Neck Dissection: Relevant Anatomy". Medscape. WebMD. Retrieved 17 July 2017.
* Joshi, Arjun S; Vashishta, Rishi; George, Philip E (18 November 2013). "Pharynx Anatomy". Medscape. WebMD. Retrieved 20 June 2017.
* "Oropharyngeal Cancer Treatment". Head and neck Cancer - Patient version. National Institutes of Health - National Cancer Institute. December 2016. Retrieved 12 June 2017.
* "Oropharyngeal Cancer Treatment (Adult) (PDQ®): Health Professional Version". Oropharyngeal Cancer Treatment (Adult) (PDQ®). Head and Neck Cancer. Health professional version. National Institutes of Health - National Cancer Institute. 28 March 2018. Retrieved 1 July 2018.
* "Oropharyngeal Cancer Treatment". emedicinehealth. WebMD. 1 August 2017. Retrieved 6 August 2017.
* Is Oral Sex Safe? (Television production). England: BBC Three. 10 January 2011.
* "HPV Information Centre". Lyon: International Agency for Research on Cancer & Catalan Institute of Oncology. Retrieved 11 August 2017.
* "The Global Oral Cancer Forum 2016" (Conference proceedings). Henry Schein Cares Foundation. 2017. Retrieved 12 August 2017.
* "Cetuximab with radiation found to be inferior to standard treatment in HPV-positive oropharyngeal cancer". News releases. National Institutes of Health. 14 August 2018. Retrieved 15 August 2018.
#### Treatment guidelines[edit]
* "Head and Neck Cancer Evidence-based Series (EBS) and Practice Guidelines (PG)". Evidence Based Guidelines. Cancer Care Ontario. 31 March 2017. Retrieved 22 May 2017.
* "The Management of Head and Neck Cancer in Ontario. EBS 5-3". December 2009. Retrieved 22 May 2017., in CCO (2017)
* "Routine HPV Testing in Head and Neck Squamous Cell Carcinoma. EBS 5-9". May 2013. Retrieved 22 May 2017., in CCO (2017)
* "Head and Neck Cancers" (PDF). NCCN Guidelines 2.2018. National Comprehensive Cancer Network. 20 June 2018. Retrieved 22 June 2018.
* "Head & Neck". Cancer Management Guidelines. British Columbia: BC Cancer Agency. 2017. Retrieved 30 June 2017.
## External links[edit]
Classification
D
* ICD-10: C01, C02.4, C09, C10, C14.2
* ICD-9-CM: 146
* ICD-O: M8070/3
* OMIM: 275355
* DiseasesDB: 9288
External resources
* MedlinePlus: 001042
* eMedicine: article/1289474 article/2047780 article/847955
* "Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03)" (PDF). CTCAE. National Cancer Institute. 14 June 2010. Archived from the original (PDF) on 30 August 2017. Retrieved 3 August 2017.
* v
* t
* e
Tumors of lip, oral cavity and pharynx / head and neck cancer
Oral cancer
Salivary gland
malignant epithelial tumors
* Acinic cell carcinoma
* Mucoepidermoid carcinoma
* Adenoid cystic carcinoma
* Salivary duct carcinoma
* Epithelial-myoepithelial carcinoma
* Polymorphous low-grade adenocarcinoma
* Hyalinizing clear cell carcinoma
benign epithelial tumors
* Pleomorphic adenoma
* Warthin's tumor
ungrouped:
* Oncocytoma
Tongue
* Leukoplakia
* Rhabdomyoma
* Oropharynx
* v
* t
* e
Human papillomavirus
Related
diseases
Cancers
* Cervical cancer
* cancers
* Anal
* Vaginal
* Vulvar
* Penile
* Head and neck cancer (HPV-positive oropharyngeal cancer)
Warts
* * genital
* plantar
* flat
* Laryngeal papillomatosis
* Epidermodysplasia verruciformis
* Focal epithelial hyperplasia
* Papilloma
Others
Acrochordon (skin tags)
Vaccine
* HPV vaccines
* Cervarix
* Gardasil
Screening
* Pap test:
* stain
* Bethesda system
* Cytopathology
* Cytotechnology
* Experimental techniques:
* Speculoscopy
* Cervicography
Colposcopy
Biopsy histology
* Cervical intraepithelial neoplasia (CIN)
* Koilocyte
* Vaginal intraepithelial neoplasia (VAIN)
* Vulvar intraepithelial neoplasia (VIN)
Treatment
* Cervical conization
* Loop electrical excision procedure (LEEP)
History
* Georgios Papanikolaou
* Harald zur Hausen
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| HPV-positive oropharyngeal cancer | None | 6,600 | wikipedia | https://en.wikipedia.org/wiki/HPV-positive_oropharyngeal_cancer | 2021-01-18T18:49:41 | {"icd-10": ["C02.4", "C01", "C14.2", "C09.0", "C10.9"], "wikidata": ["Q5635621"]} |
Gaucher's disease
Acid beta-glucosidase
SpecialtyEndocrinology, neurology
Gaucher's disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.
The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females. About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is one in 450.[1]
Gaucher's disease is the most common of the lysosomal storage diseases.[2] It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids.[3]
The disease is named after the French physician Philippe Gaucher, who originally described it in 1882.[4]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 6 Epidemiology
* 7 History
* 8 Prominent people with disease
* 9 Gallery
* 10 See also
* 11 References
* 12 External links
## Signs and symptoms[edit]
* Painless hepatomegaly and splenomegaly: the size of the spleen can be 1500–3000 g, as opposed to the normal size of 50–200 g. Splenomegaly may decrease the affected individual's capacity for eating by exerting pressure on the stomach. While painless, enlargement of spleen increases the risk of splenic rupture.
* Hypersplenism and pancytopenia, the rapid and premature destruction of blood cells, leads to anemia, neutropenia, leukopenia, and thrombocytopenia (with an increased risk of infection and bleeding).
* Cirrhosis of the liver is rare.
* Severe pain associated with joints and bones occurs, frequently presenting in hips and knees.
* Neurological symptoms occur only in some types of Gaucher's (see below):
* Type I: impaired olfaction and cognition
* Type II: serious convulsions, hypertonia, intellectual disability, and apnea
* Type III: muscle twitches known as myoclonus, convulsions, dementia, and ocular muscle apraxia
* Parkinson's disease is recognized as being more common in Gaucher's disease patients and their heterozygous carrier relatives.[5]
* Osteoporosis: 75% of patients develop visible bony abnormalities due to the accumulated glucosylceramide. A deformity of the distal femur in the shape of an Erlenmeyer flask is commonly described.
* Yellowish-brown skin pigmentation
## Genetics[edit]
The three types of Gaucher's disease are autosomal recessive. Both parents must be carriers for a child to be affected. If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Genetic counseling and genetic testing are recommended for families who may be carriers of mutations.
Each type has been linked to particular mutations. In all, about 80 known GBA gene mutations are grouped into three main types:[6]
* Type I (N370S homozygote), the most common, also called the "non-neuropathic" type occurs mainly in Ashkenazi Jews, at 100 times the occurrence in the general populace. The median age at diagnosis is 28 years of age,[7] and life expectancy is mildly decreased.[8]
* Type II (one or two alleles L444P) is characterized by neurological problems in small children. The enzyme is hardly released into the lysosomes. Prognosis is poor: most die before the age of three.
* Type III (also one or two copies of L444P, possibly delayed by protective polymorphisms) occurs in Swedish patients from the Norrbotten region.[9] This group develops the disease somewhat later, but most die before their 30th birthday.
The Gaucher-causing mutations may have entered the Ashkenazi Jewish gene pool in the early Middle Ages (48–55 generations ago).[10]
## Pathophysiology[edit]
The disease is caused by a defect in housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, EC 3.2.1.45, PDB: 1OGS) on the first chromosome (1q22). The enzyme is a 55.6-kilodalton, 497-amino acid-long protein that catalyses the breakdown of glucocerebroside, a cell membrane constituent of red and white blood cells. In Gaucher disease, the enzyme is unable to function correctly and glucocerebroside accumulates. The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into 'Gaucher cells', which appear on light microscopy to resemble crumpled-up paper.[3]
The exact mechanism of neurotoxicity is not understood, but it is thought to involve a reaction to glucosylsphingosine.[3]
Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type.[3] Although there is some correlation between genotype and phenotype, neither the amount of stored lipids, nor the residual enzyme activity correlates well with disease symptoms.[11] This circumstance has called for alternative explanations accounting for disease symptoms including
* jamming of the endo/lysosomal system[12]
* ER stress[13]
* altered lipid composition of membranes throughout the cell, including the plasma membrane,[14] and consequent changes in the dynamic and signaling properties of the cell membrane[15]
* inflammation caused by cytokine secretion as a result of sphingolipid accumulation, and neurodegeneration caused by the accumulation of glucosylsphingosine, a neurotoxin[16]
Heterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinson's disease, making this the most common known genetic risk factor for Parkinson's.[17][18]
Cancer risk may be increased, particularly myeloma.[19][20][21] This is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids.[22]
The role of inflammatory processes in Gaucher disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and apoptosis, and markers of macrophage activation are elevated in people with Gaucher disease. These markers include angiotensin-converting enzyme, cathepsin S, chitotriosidase, and CCL18 in the blood plasma; and tumor necrosis factor alpha in splenic Gaucher cells (engorged macrophages).[3]
## Diagnosis[edit]
Micrograph showing crinkled paper macrophages in the marrow space in a case of Gaucher disease, H&E stain.
Gaucher disease is suggested based on the overall clinical picture. Initial laboratory testing may include enzyme testing. As a result, lower than 15% of mean normal activity is considered to be diagnostic.[23] Decreased enzyme levels will often be confirmed by genetic testing. Numerous different mutations occur; sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available and is useful when a known genetic risk factor is present.
A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase, angiotensin-converting enzyme, and immunoglobulin levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages.
Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher's disease activity in response to treatment, and may reflect the severity of the disease
### Classification[edit]
Gaucher's disease (GD) has four common clinical subtypes.[24][25] These subtypes have come under some criticism for not taking account of the full spectrum of observable symptoms (the phenotypes[26]). Also, compound heterozygous variations occur which considerably increase the complexity of predicting disease course.
GD type I (non-neuropathic) is the most common and least severe form of the disease. Symptoms may begin early in life or in adulthood and mainly affect the liver, spleen, and bone. Enlarged liver and grossly enlarged spleen (together hepatosplenomegaly) are common;[3] the spleen can rupture and cause additional complications. Skeletal weakness and bone disease may be extensive.[3] Spleen enlargement and bone marrow replacement cause anemia, thrombocytopenia, and leukopenia. The brain and nervous system are not affected pathologically,[3] but lung and, rarely, kidney impairment may occur. Patients in this group usually bruise easily (due to low levels of platelets) and experience fatigue due to low numbers of red blood cells. Depending on disease onset and severity, type I patients may live well into adulthood. The range and severity of symptoms can vary dramatically between patients.
GD type II (acute infantile neuropathic) typically begins within 6 months of birth and has an incidence rate around one 1 in 100,000 live births. Symptoms include an enlarged liver and spleen, extensive and progressive brain damage, eye movement disorders, spasticity, seizures, limb rigidity, and a poor ability to suck and swallow. Affected children usually die by age two.
GD type III (chronic neuropathic) can begin at any time in childhood or even in adulthood, and occurs in about one in 100,000 live births. It is characterized by slowly progressive, but milder neurologic symptoms compared to the acute or type II version. Major symptoms include an enlarged spleen and/or liver, seizures, poor coordination, skeletal irregularities, eye movement disorders, blood disorders including anemia, and respiratory problems. Patients often live into their early teen years and adulthood.[27]
## Treatment[edit]
For those with type-I and most type-III, enzyme replacement treatment with intravenous recombinant glucocerebrosidase can decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations.[16][28] This treatment costs about US$200,000 annually for a single person and should be continued for life. The rarity of the disease means dose-finding studies have been difficult to conduct, so controversy remains over the optimal dose and dosing frequency.[7] Due to the low incidence, this has become an orphan drug in many countries, meaning a government recognizes and accommodates the financial constraints that limit research into drugs that address a small population.
The first drug for Gaucher's was alglucerase (Ceredase), which was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes.[29] It was approved by the FDA in 1991[30] and has been withdrawn from the market[31][32] due to the approval of similar drugs made with recombinant DNA technology instead of being harvested from tissue; drugs made recombinantly are preferable, since there is no concern about diseases being transmitted from the tissue used in harvesting, there are fewer risks of variations in enzyme structure from batch to batch, and they are less expensive to manufacture.[29]
Available recombinant glucocerebrosidases are:[16]
* Imiglucerase (approved in 1995)[29]
* Velaglucerase (approved in 2010)[33]
* Taliglucerase alfa (Elelyso) (approved in 2012)[34]
Miglustat is a small molecule, orally available drug that was first approved for Gaucher's Disease in Europe in 2002.[35] It works by preventing the formation of glucocerebroside, the substance that builds up and causes harm in Gaucher's. This approach is called substrate reduction therapy.[36]
Eliglustat (Cerdelga) (approved in 2014) [37] is also a small molecule. The compound is believed to work by inhibition of glucosylceramide synthase.
## Epidemiology[edit]
The National Gaucher Foundation (United States) states the incidence of Gaucher's disease is about one in 20,000 live births.[38] Around one in 100 people in the general US population is a carrier for type I Gaucher's disease, giving a prevalence of one in 40,000.[39] Among Ashkenazi Jews, the rate of carriers is considerably higher, at roughly one in 15.[39]
Type II Gaucher's disease shows no particular preference for any ethnic group.
Type III Gaucher's disease is especially common in the population of the northern Swedish region of Norrbotten, where the incidence of the disease is one in 50,000.[40]
## History[edit]
The disease was first recognized by the French doctor Philippe Gaucher, who originally described it in 1882 and lent his name to the condition.[4] In 1902, its mode of inheritance was discovered by Nathan Brill.[3] The neuronal damage associated with the disease was discovered in the 1920s, and the biochemical basis for the disease was elucidated in the 1960s by Roscoe Brady.[3][41] The first effective treatment for the disease, the drug alglucerase (Ceredase), was approved by the FDA in April 1991. An improved drug, imiglucerase (Cerezyme), was approved by the FDA in May 1994 and has replaced the use of Ceredase.
October is National Gaucher's Disease Awareness Month in the United States.[citation needed]
## Prominent people with disease[edit]
* Wallace Chapman; New Zealand radio and television personality[42]
## Gallery[edit]
* Sphingolipidoses
## See also[edit]
* Niemann–Pick disease
* Fabry disease
* Tay–Sachs disease
* Krabbe disease
* Metachromatic leukodystrophy
* Medical genetics of Ashkenazi Jews
* List of radiographic findings associated with cutaneous conditions
## References[edit]
1. ^ Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E (October 1991). "High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews". American Journal of Human Genetics. 49 (4): 855–9. PMC 1683177. PMID 1897529.
2. ^ James WD, Elston DM, Berger TG, Andrews GC (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 536. ISBN 978-0-7216-2921-6. OCLC 663444979.
3. ^ a b c d e f g h i j Dandana A, Ben Khelifa S, Chahed H, Miled A, Ferchichi S (2016). "Gaucher Disease: Clinical, Biological and Therapeutic Aspects". Pathobiology. 83 (1): 13–23. doi:10.1159/000440865. PMID 26588331.
4. ^ a b Gaucher PCE (1882). De l'epithelioma primitif de la rate, hypertrophie idiopathique de la rate sans leucemie [Primary epithelioma of the spleen, idiopathic hypertrophy of the spleen without leukemia] (academic thesis) (in French). Paris, France.[page needed]
5. ^ McNeill A, Duran R, Hughes DA, Mehta A, Schapira AH (August 2012). "A clinical and family history study of Parkinson's disease in heterozygous glucocerebrosidase mutation carriers". Journal of Neurology, Neurosurgery, and Psychiatry. 83 (8): 853–4. doi:10.1136/jnnp-2012-302402. PMC 3927562. PMID 22577228.
6. ^ Online Mendelian Inheritance in Man (OMIM): Gluosidase, beta, acid; GBA - 606463
7. ^ a b Grabowski GA (October 2008). "Phenotype, diagnosis, and treatment of Gaucher's disease". Lancet. 372 (9645): 1263–71. doi:10.1016/S0140-6736(08)61522-6. PMID 19094956. S2CID 25221799.
8. ^ Weinreb NJ, Deegan P, Kacena KA, Mistry P, Pastores GM, Velentgas P, vom Dahl S (December 2008). "Life expectancy in Gaucher disease type 1". American Journal of Hematology. 83 (12): 896–900. doi:10.1002/ajh.21305. PMC 3743399. PMID 18980271.
9. ^ Dahl N, Lagerström M, Erikson A, Pettersson U (August 1990). "Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene". American Journal of Human Genetics. 47 (2): 275–8. PMC 1683716. PMID 2378352.
10. ^ Diaz GA, Gelb BD, Risch N, Nygaard TG, Frisch A, Cohen IJ, Miranda CS, Amaral O, Maire I, Poenaru L, Caillaud C, Weizberg M, Mistry P, Desnick RJ (June 2000). "Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations". American Journal of Human Genetics. 66 (6): 1821–32. doi:10.1086/302946. PMC 1378046. PMID 10777718.
11. ^ Sidransky E (October 2012). "Gaucher disease: insights from a rare Mendelian disorder". Discovery Medicine. 14 (77): 273–81. PMC 4141347. PMID 23114583.
12. ^ Simons K, Gruenberg J (November 2000). "Jamming the endosomal system: lipid rafts and lysosomal storage diseases". Trends in Cell Biology. 10 (11): 459–62. doi:10.1016/S0962-8924(00)01847-X. PMID 11050411.
13. ^ Westbroek W, Gustafson AM, Sidransky E (September 2011). "Exploring the link between glucocerebrosidase mutations and parkinsonism". Trends in Molecular Medicine. 17 (9): 485–93. doi:10.1016/j.molmed.2011.05.003. PMC 3351003. PMID 21723784.
14. ^ Hein LK, Meikle PJ, Hopwood JJ, Fuller M (December 2007). "Secondary sphingolipid accumulation in a macrophage model of Gaucher disease". Molecular Genetics and Metabolism. 92 (4): 336–45. doi:10.1016/j.ymgme.2007.08.001. PMID 17881272.
15. ^ Batta G, Soltész L, Kovács T, Bozó T, Mészár Z, Kellermayer M, Szöllősi J, Nagy P (January 2018). "Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease". Scientific Reports. 8 (1): 157. Bibcode:2018NatSR...8..157B. doi:10.1038/s41598-017-18405-8. PMC 5760709. PMID 29317695.
16. ^ a b c Grabowski GA (2012). "Gaucher disease and other storage disorders". Hematology. American Society of Hematology. Education Program. 2012: 13–8. doi:10.1182/asheducation.v2012.1.13.3797921. PMID 23233555.
17. ^ Beals JK (November 19, 2008). "ASHG 2008: Gaucher Disease Mutation Carriers at Higher Risk for Parkinson's Disease". Medscape Medical News.
18. ^ Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R (November 2004). "Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews". The New England Journal of Medicine. 351 (19): 1972–7. doi:10.1056/NEJMoa033277. PMID 15525722.
19. ^ Arends M, van Dussen L, Biegstraaten M, Hollak CE (June 2013). "Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature". British Journal of Haematology. 161 (6): 832–42. doi:10.1111/bjh.12335. PMID 23594419.
20. ^ Thomas AS, Mehta A, Hughes DA (May 2014). "Gaucher disease: haematological presentations and complications". British Journal of Haematology. 165 (4): 427–40. doi:10.1111/bjh.12804. PMID 24588457.
21. ^ Ayto R, Hughes DA (2013). "Gaucher disease and myeloma". Critical Reviews in Oncogenesis. 18 (3): 247–68. doi:10.1615/critrevoncog.2013006061. PMID 23510067.
22. ^ Barth BM, Shanmugavelandy SS, Tacelosky DM, Kester M, Morad SA, Cabot MC (2013). "Gaucher's disease and cancer: a sphingolipid perspective". Critical Reviews in Oncogenesis. 18 (3): 221–34. doi:10.1615/critrevoncog.2013005814. PMC 3604879. PMID 23510065.
23. ^ "Gaucher Disease". symptoma. Retrieved 2015-12-07.
24. ^ Nagral A (March 2014). "Gaucher disease". Journal of Clinical and Experimental Hepatology. 4 (1): 37–50. doi:10.1016/j.jceh.2014.02.005. PMC 4017182. PMID 25755533.
25. ^ Bennett LL, Mohan D (September 2013). "Gaucher disease and its treatment options". The Annals of Pharmacotherapy. 47 (9): 1182–93. doi:10.1177/1060028013500469. PMID 24259734. S2CID 10092272.
26. ^ [1] Archived September 24, 2006, at the Wayback Machine
27. ^ Dreborg S, Erikson A, Hagberg B (March 1980). "Gaucher disease--Norrbottnian type. I. General clinical description". European Journal of Pediatrics. 133 (2): 107–18. doi:10.1007/BF00441578. PMID 7363908. S2CID 12375149.
28. ^ Shemesh E, Deroma L, Bembi B, Deegan P, Hollak C, Weinreb NJ, Cox TM (March 2015). "Enzyme replacement and substrate reduction therapy for Gaucher disease". The Cochrane Database of Systematic Reviews (3): CD010324. doi:10.1002/14651858.CD010324.pub2. PMID 25812601.
29. ^ a b c Deegan PB, Cox TM (2012). "Imiglucerase in the treatment of Gaucher disease: a history and perspective". Drug Design, Development and Therapy. 6: 81–106. doi:10.2147/DDDT.S14395. PMC 3340106. PMID 22563238.
30. ^ World Health Organization. Regulatory Matters WHO Drug Information 5:3 1991. p 123
31. ^ Aetna. Last reviewed 8 August 2014 Clinical Policy Bulletin Number: 0442: Enzyme-replacement Therapy for Lysosomal Storage Disorders
32. ^ FDA Prescription and Over-the-Counter Drug Product List. 32ND Edition Cumulative Supplement Number 3: March 2012. Additions/Deletions for Prescription Drug Product List
33. ^ "Shire Announces FDA Approval Of VPRIV(TM) (velaglucerase Alfa For Injection) For The Treatment Of Type I Gaucher Disease". Medicalnewstoday.com. Archived from the original on June 13, 2011. Retrieved 2012-08-13.
34. ^ Yukhananov A (1 May 2012). "U.S. FDA approves Pfizer/Protalix drug for Gaucher". Chicago Tribune. Reuters. Retrieved 2 May 2012.[permanent dead link]
35. ^ European Medicines Agency. Human Medicines Database. Zavesca (miglustat) Page Accessed 1 September 2014.
36. ^ European Medicines Agency 1 April 2003 Scientific discussion related to approval of Zavesca.
37. ^ "Center Watch: Cerdelga (eliglustat)".
38. ^ Gaucher Disease at National Gaucher Foundation. Retrieved June 2012
39. ^ a b "Gaucher Disease Genetics | About Gaucher Disease | National Gaucher Foundation". National Gaucher Foundation. Retrieved 2016-11-16.
40. ^ "Gaucher disease - Affected population". NORD - National Organization for Rare Disorders. Archived from the original on 25 September 2013. Retrieved 21 September 2013.
41. ^ Brady RO, Kanfer JN, Shapiro D (January 1965). "Metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher's disease". Biochemical and Biophysical Research Communications. 18 (2): 221–5. doi:10.1016/0006-291X(65)90743-6. PMID 14282020.
42. ^ "Eating Fried Chicken - Cold is Gold". RNZ. 2019-08-01. Retrieved 2019-08-08.
## External links[edit]
Classification
D
* ICD-10: E75.2 (ILDS E75.220)
* ICD-9-CM: 272.7
* OMIM: 230800 230900 231000
* MeSH: D005776
* DiseasesDB: 5124
External resources
* MedlinePlus: 000564
* eMedicine: ped/837 derm/709
* Patient UK: Gaucher's disease
* GeneReviews: Gaucher disease
* Orphanet: 355
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* Gaucher Disease at NINDS
* v
* t
* e
Lysosomal storage diseases: Inborn errors of lipid metabolism (Lipid storage disorders)
Sphingolipidoses
(to ceramide)
From ganglioside
(gangliosidoses)
* Ganglioside: GM1 gangliosidoses
* GM2 gangliosidoses (Sandhoff disease
* Tay–Sachs disease
* AB variant)
From globoside
* Globotriaosylceramide: Fabry's disease
From sphingomyelin
* Sphingomyelin: phospholipid: Niemann–Pick disease (SMPD1-associated
* type C)
* Glucocerebroside: Gaucher's disease
From sulfatide
(sulfatidoses
* leukodystrophy)
* Sulfatide: Metachromatic leukodystrophy
* Multiple sulfatase deficiency
* Galactocerebroside: Krabbe disease
To sphingosine
* Ceramide: Farber disease
NCL
* Infantile
* Jansky–Bielschowsky disease
* Batten disease
Other
* Cerebrotendineous xanthomatosis
* Cholesteryl ester storage disease (Lysosomal acid lipase deficiency/Wolman disease)
* Sea-blue histiocytosis
Authority control
* LCCN: sh85053526
* NDL: 00576302
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Gaucher's disease | c0017205 | 6,601 | wikipedia | https://en.wikipedia.org/wiki/Gaucher%27s_disease | 2021-01-18T18:55:19 | {"gard": ["8233"], "mesh": ["D005776"], "umls": ["C0017205"], "orphanet": ["355"], "wikidata": ["Q861645"]} |
Chromium toxicity
Chromium
SpecialtyToxicology
Chromium toxicity refers to any poisonous toxic effect in an organism or cell that results from exposure to specific forms of chromium—especially hexavalent chromium. Hexavalent chromium and its compounds are toxic when inhaled or ingested. Trivalent chromium is a trace mineral that is essential to human nutrition. There is a hypothetical risk of genotoxicity in humans if large amounts of trivalent chromium were somehow able to enter living cells, but normal metabolism and cell function prevent this.
## Contents
* 1 Forms of chromium
* 1.1 Hexavalent chromium
* 1.1.1 Chromate
* 1.1.2 Genotoxicity
* 1.2 Trivalent chromium
* 2 References
* 3 External links
## Forms of chromium[edit]
Hexavalent chromium and trivalent chromium are chromium ions—they have different numbers of electrons and, therefore, different properties. Trivalent chromium, or chromium(III), is the form of chromium that is essential to human health.[1] Hexavalent chromium, or chromium(VI), is an unequivocally toxic form.
### Hexavalent chromium[edit]
Main article: Hexavalent chromium § Toxicity
Hexavalent chromium, also called chromium(VI), is hemotoxic, genotoxic, and carcinogenic.[2] When hexavalent chromium enters the bloodstream, it damages blood cells by causing oxidation reactions. This oxidative damage can lead to hemolysis and, ultimately, kidney and liver failure. Patients might be treated with dialysis.[3]
The median lethal dose of hexavalent chromium is 50–150 mg/kg.[4] The World Health Organization recommends a maximum allowable concentration of 0.05 milligrams per litre of chromium(VI) in drinking water.[5] In Europe, the use of hexavalent chromium is regulated by the Restriction of Hazardous Substances Directive.
Hexavalent chromium can be found in some dyes and paints, as well as in some leather tanning products. Primer paint containing hexavalent chromium is widely used in aerospace and automobile refinishing applications. Metal workers (such as welders)—as well as people with a surgical implant made from cobalt-chromium alloy—may also be exposed to hexavalent chromium.[6] Chromium concentrations in whole blood, plasma, serum, or urine may be measured to monitor for safety in exposed workers, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdosage.[7]
In the U.S. state of California, an epidemic of hexavalent chromium exposure led to a class-action lawsuit in 1993: Anderson, et al. v. Pacific Gas and Electric. The Pacific Gas and Electric Company had dumped more than 1.4 billion litres (370 million gallons) of wastewater tainted with hexavalent chromium into the Mojave Desert. This contaminated the groundwater, and caused widespread illness among the people of Hinkley, California, a small community nearby. As of May 2017, the mandated environmental remediation measures are ongoing.[8]
#### Chromate[edit]
See also: Chromate and dichromate § Toxicity
Chromates (chromium salts) formed from hexavalent chromium are used to manufacture leather products, paints, cement, mortar, anti-corrosives, and other things. They are carcinogenic and allergenic. The carcinogenity of chromate dust has been documented since the late 19th century, when workers in a chromate dye company were found to exhibit high incidence of cancer.[9][10] Chromate enters cells by means of the same transport mechanism that carries sulfate and phosphate ions into cells.
Contact with products containing chromates can lead to allergic contact dermatitis and irritant dermatitis, resulting in ulceration of the skin—a condition sometimes called chrome ulcers. Workers that have been exposed to strong chromate solutions in electroplating, tanning, and chrome-producing manufacturers may also develop chrome ulcers.[11][12][13]
#### Genotoxicity[edit]
This section needs to be updated. Please update this article to reflect recent events or newly available information. (June 2018)
Hexavalent chromium is genotoxic: it damages genetic information in living cells, which results in DNA mutations, and possibly the formation of cancerous tumors. One hypothesis asserts that the genotoxicity is caused by free radicals such as hydroxyl radicals, produced by the reduction of chromium(VI) to chromium(III). Another proposed mechanism supposes that chromium binds to DNA at the end of the reduction to chromium(III).[14]
A third hypothesis proposes that two other forms of chromium—Chromium(IV) compounds, along with chromium(V) produced by redox reactions in the cell—bind to DNA.[citation needed]
### Trivalent chromium[edit]
See also: Chromium deficiency
Trivalent chromium, or chromium(III), is an essential trace mineral in the human diet.[1] In some nutritional supplements, chromium(III) occurs as chromium(III) picolinate (in which chromium is bound to picolinic acid) or chromium(III) nicotinate (in which chromium is bound to nicotinic acid). Nicotinic acid is also known as the B vitamin niacin.
Chromium(III) is poorly absorbed in humans; most dietary chromium is excreted in the urine.[15] The threshold for acute oral toxicity is 1900–3300 mg/kg.[4] In rats, nonsteroidal anti-inflammatory drugs such as aspirin and indometacin can increase chromium absorption.[16]
Ordinarily, cellular transport mechanisms in humans and some other animals limit the amount of chromium(III) that enters a cell. Hypothetically, if an excessive amount was able to enter a cell, free radical damage to DNA might result.[17]
## References[edit]
1. ^ a b Bogden, John D.; Klevay, Leslie M., eds. (2000). "Trace Elements and Minerals in the Elderly § Chromium". Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals. Springer Science+Business Media. p. 189. ISBN 978-1-61737-090-8 – via Google Books.
2. ^ Barceloux, Donald G.; Barceloux, Donald (1999). "Chromium". Clinical Toxicology. 37 (2): 173–194. doi:10.1081/CLT-100102418. PMID 10382554.
3. ^ Dayan, A. D.; Paine, A. J. (2001). "Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000". Human & Experimental Toxicology. 20 (9): 439–451. doi:10.1191/096032701682693062. PMID 11776406. S2CID 31351037.
4. ^ a b Katz, Sidney A.; Salem, H (1992). "The toxicology of chromium with respect to its chemical speciation: A review". Journal of Applied Toxicology. 13 (3): 217–224. doi:10.1002/jat.2550130314. PMID 8326093. S2CID 31117557.
5. ^ "WHO Guidelines on Drinking-Water Quality" (PDF). WHO.int. World Health Organisation. Section 12.30: Chromium.
6. ^ Merritt, Katharine; Brown, Stanley A. (May 1995). "Release of hexavalent chromium from corrosion of stainless steel and cobalt—chromium alloys". Journal of Biomedical Materials Research. 29 (5): 627–633. doi:10.1002/jbm.820290510. PMID 7622548.
7. ^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City: Biomedical Publications. pp. 305–7. ISBN 978-0962652370.
8. ^ Izbicki, John A.; Groover, Krishangi. "Natural and Man-Made Hexavalent Chromium, Cr(VI), in Groundwater near a Mapped Plume, Hinkley, California—Study Progress as of May 2017, and a Summative-Scale Approach to Estimate Background Cr(VI) Concentrations" (PDF). Open-file Report. United States Geological Survey. ISSN 2331-1258. Retrieved 2018-05-15.
9. ^ Newman, D. (1890). "A case of adeno-carcinoma of the left inferior turbinated body, and perforation of the nasal septum, in the person of a worker in chrome pigments". Glasgow Medical Journal. 33: 469–470.
10. ^ Langard, Sverre (1990). "One Hundred Years of Chromium and Cancer: A Review of Epidemiological Evidence and Selected Case Reports". American Journal of Industrial Medicine. 17 (2): 189–215. doi:10.1002/ajim.4700170205. PMID 2405656.
11. ^ "Chrome Contact Allergy". DermNet NZ.
12. ^ Basketter, David; Horev, L.; Slodovnik, D.; Merimes, S.; Trattner, A.; Ingber, A. (2000). "Investigation of the threshold for allergic reactivity to chromium". Contact Dermatitis. 44 (2): 70–74. doi:10.1034/j.1600-0536.2001.440202.x. PMID 11205406. S2CID 45426346.
13. ^ Basketter, D. A.; Briatico-Vangosa, G.; Kaestner, W.; Lally, C.; Bontinck, W. J. (1992). "Nickel, cobalt and chromium in consumer products: A role in allergic contact dermatitis?". Contact Dermatitis. 28 (1): 15–25. doi:10.1111/j.1600-0536.1993.tb03318.x. PMID 8428439. S2CID 35966310.
14. ^ M. D., Cohen; Kargacin, B.; Klein, C. B.; Costa, M. (1993). "Mechanisms of chromium carcinogenicity and toxicity". Critical Reviews in Toxicology. 23 (3): 255–81. doi:10.3109/10408449309105012. PMID 8260068.
15. ^ "Chromium § Toxicity". Micronutrient Information Center. Oregon State University. Retrieved 2018-04-15.
16. ^ "Chromium § Drug interactions". Micronutrient Information Center. Oregon State University. Retrieved 2018-04-15.
17. ^ Eastmond, David A.; MacGregor, JT; Slesinski, RS (2008). "Trivalent Chromium: Assessing the Genotoxic Risk of an Essential Trace Element and Widely Used Human and Animal Nutritional Supplement". Critical Reviews in Toxicology. 38 (3): 173–190. doi:10.1080/10408440701845401. PMID 18324515. S2CID 21033504.
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*[mRNA]: messenger RNA
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| Chromium toxicity | c0161708 | 6,602 | wikipedia | https://en.wikipedia.org/wiki/Chromium_toxicity | 2021-01-18T18:33:39 | {"umls": ["C0161708"], "icd-9": ["985.6"], "icd-10": ["T56.2"], "wikidata": ["Q5113833"]} |
Glycogen storage disease due to LAMP-2 (Lysosomal-Associated Membrane Protein 2) deficiency is a lysosomal glycogen storage disease characterised by severe cardiomyopathy and variable degrees of muscle weakness, frequently associated with intellectual deficit.
## Epidemiology
More than 20 families have been described in the literature so far.
## Clinical description
The disease classically manifests in males over 10 years of age. The clinical picture may be severe in both sexes, but onset generally occurs later in females.
## Etiology
The disease is caused by mutations in the LAMP2 gene, localised to Xq24. The LAMP2 protein is an essential component of the lysosomal membrane and appears to play a role in autophagosome-lysosome fusion.
## Diagnostic methods
Biological diagnosis revolves around demonstration of normal or high acid maltase activity in combination with muscle biopsies showing large vacuoles (filled with glycogen and products of cytoplasmic degradation) and an absence of the LAMP-2 protein on immunohistochemical analysis. The diagnosis can be confirmed by molecular analysis of the LAMP2 gene. Identification of LAMP2 mutations allows diagnosis of both female and male carriers in affected families.
## Differential diagnosis
The differential diagnosis should include X-linked myopathy with excessive autophagia (XMEA) and glycogen storage disease type 2 (see these terms).
## Antenatal diagnosis
Prenatal diagnosis is feasible for affected families once the disease-causing mutation has been identified.
## Genetic counseling
The disease is transmitted as an X-linked recessive trait. Genetic counselling is complicated by the heterogeneous nature of the disease, even in males from the same family.
## Management and treatment
There is no specific treatment for this disease. Symptomatic treatment is required for the cardiac manifestations and patients may require a heart transplant.
## Prognosis
Patients are at risk of sudden death due to arrhythmia during early adulthood.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
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*[nM]: nanomolars
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*[DOR]: δ-opioid receptor
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*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
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*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
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*[MAOIs]: Monoamine oxidase inhibitors
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
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*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
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*[Percent]: Percent of total in category
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*[GER]: Germany
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*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Glycogen storage disease due to LAMP-2 deficiency | c0878677 | 6,603 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=34587 | 2021-01-23T19:03:30 | {"gard": ["9730"], "mesh": ["D052120"], "omim": ["300257"], "umls": ["C0878677"], "icd-10": ["E74.0"], "synonyms": ["Danon disease", "GSD due to LAMP-2 deficiency", "Glycogenosis due to LAMP-2 deficiency", "Lysosomal glycogen storage disease with normal acid maltase activity"]} |
A rare congenital malformation syndrome characterized by a typical facial dysmorphism, macrodontia of the permanent upper central incisors, short stature, skeletal anomalies, developmental delay and behavioral abnormalities.
## Epidemiology
The prevalence is unknown. More than 150 cases have been reported to date. ANKRD11 is one of the most frequently muted gene in patients with neurodevelopmental disorders diagnosed by whole exome sequencing.
## Clinical description
BG syndrome (KBGS) manifests in childhood with global developmental delay with short stature, mild-to-moderate intellectual disability, characteristic facies, macrodontia of the permanent upper central incisors and skeletal anomalies. Behavioral disturbances including hyperactivity, aggressiveness, attention deficit and autism spectrum disorders are recognized as constant clinical features. Developmental delay includes delayed motor milestones and markedly delayed speech and is almost always present in all patients. Characteristic facial dysmorphism is prominent in about half of the patients, consisting of triangular face, wide eyebrows with mild synophrys, hypertelorism, prominent ears and nasal bridge with bulbous nasal tip, long flat philtrum and thin upper lip. The hallmark feature, macrodontia, is observed in about 80% of cases; additional dental findings include oligo- or hypodontia, premature teeth loss in adults and enamel hypoplasia. Height below the 10th centile is observed in about two-thirds of cases. The most frequent skeletal anomalies are brachydactyly and fifth finger clinodactyly. Seizures, feeding difficulties, recurrent otitis media/hearing loss, palatal abnormalities and precocious puberty are notable additional features associated with KBGS.
## Etiology
KBGS is caused by loss-of function alterations (pathogenic variants and copy number variations) affecting the ANKRD11 gene (16q24.3) which encodes ankyrin repeat domain-containing protein 11. The extent of ANKRD11 functions is yet to be determined, but it has been shown to be a crucial chromatin regulator that controls histone acetylation and gene expression during neural development.
## Diagnostic methods
Diagnosis is based on clinical evaluation; there is no consensus on diagnostic criteria. The diagnosis is established by cytogenetic and molecular studies including a-CGH (array-comparative genome hybridization), targeted sequencing, gene panel, whole exome or genome sequencing.
## Differential diagnosis
Differential diagnosis includes Cornelia de Lange syndrome, cleidocranial dysplasia, Robinow syndrome and 22q11.2 deletion syndrome.
## Genetic counseling
The pattern of inheritance is autosomal dominant. Most cases occur sporadically due to de novo mutations. Intra-familial variability of the phenotype has been noted in familial cases.
## Management and treatment
Management is symptom-based and requires a multidisciplinary approach. At diagnosis, systematic echocardiogram, palatal assessment, vision, hearing and dental assessment, pediatric assessment for developmental delay, autism spectrum disorders and behavioral anomalies are recommended. Additional investigations depends on the clinical presentation. Management and follow-up include educational support, surveillance of growth and puberty, screening for hearing loss (otitis media), educational and speech therapy, and treatment of seizures when needed.
## Prognosis
Despite the history of developmental delay, many patients grow into autonomous adults.
* European Reference Network
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| KBG syndrome | c0220687 | 6,604 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2332 | 2021-01-23T18:34:42 | {"gard": ["82"], "mesh": ["C537015"], "omim": ["148050"], "umls": ["C0220687"], "icd-10": ["Q87.8"], "synonyms": ["Short stature-facial and skeletal anomalies-intellectual disability-macrodontia syndrome"]} |
Granuloma faciale
Other namesGF
SpecialtyDermatology
Granuloma faciale is an uncommon benign chronic skin disease of unknown origin characterized by single or multiple cutaneous nodules, usually occurring over the face.[1]:836 Occasionally, extrafacial involvement is noted, most often on sun-exposed areas.
## Contents
* 1 Diagnosis
* 1.1 Differential diagnosis
* 2 Treatment
* 3 History
* 4 See also
* 5 References
* 6 External links
## Diagnosis[edit]
Skin biopsy for histopathology: Focal LCV, diffuse dermal neutrophilia with leukocytoclasia, tissue eosinophilia & perivascular fibrosis.
### Differential diagnosis[edit]
The disease mimics many other dermatoses and can be confused with conditions, such as sarcoidosis, discoid lupus erythematosus, mycosis fungoides, and fixed drug eruption.[citation needed]
## Treatment[edit]
Topical corticosteriod, Intralesional corticosteroid, Dapsone, Colchicine, Antimalarial, Pulse dye laser, Carbon dioxide laser.
## History[edit]
GF was first described in 1945 by John Edwin Mackonochie Wigley (1892–1962).[2]
## See also[edit]
* Cutaneous small-vessel vasculitis
* List of cutaneous conditions
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
2. ^ Wigley, J. E. (1945). "Eosinophilic Granuloma. ? Sarcoid of Boeck". Proceedings of the Royal Society of Medicine. 38 (3): 125–126. PMC 2181658. PMID 19992999.
## External links[edit]
Classification
D
* ICD-10: L92.2
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* DiseasesDB: 33779
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* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
* v
* t
* e
Neutrophilic and eosinophilic dermatoses
Eosinophilic dermatosis
With vasculitis
* Eosinophilic vasculitis
* Eosinophilic granulomatosis with polyangiitis
Without vasculitis
* Arthropod assault
* Eosinophilic cellulitis
* Hypereosinophilic syndrome
* Papuloerythroderma of Ofuji
* Granuloma faciale
* Eosinophilic folliculitis
Ungrouped
* Angiolymphoid hyperplasia with eosinophilia/Kimura's disease
* Annular erythema of infancy
* Eosinophilic fasciitis
* Eosinophilic granuloma
* Eosinophilic ulcer of the oral mucosa
* Erythema toxicum neonatorum
* Incontinentia pigmenti
* Itchy red bump disease
* Juvenile xanthogranuloma
* Pachydermatous eosinophilic dermatitis
* Papular eruption of blacks
* Pruritic papular eruption of HIV disease
Reactive neutrophilic dermatoses
Epidermis
* Keratoderma blennorrhagicum
* Subcorneal pustular dermatosis
Dermis
without vasculitis:
* Sweet's syndrome
* Pyoderma gangrenosum
* Bowel-associated dermatosis–arthritis syndrome
with vasculitis:
* Neutrophilic dermatosis of the dorsal hands
Ungrouped
* Acute erythema nodosum
* Marshall syndrome
* Neutrophilic eccrine hidradenitis
* Pyogenic arthritis–pyoderma gangrenosum–acne syndrome
* Rheumatoid neutrophilic dermatitis
* Superficial granulomatous pyoderma
* Sweet's syndrome-like dermatosis
* Vesicopustular dermatosis
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Granuloma faciale | c0239495 | 6,605 | wikipedia | https://en.wikipedia.org/wiki/Granuloma_faciale | 2021-01-18T18:39:43 | {"icd-9": ["701.8"], "icd-10": ["L92.2"], "wikidata": ["Q186488"]} |
Waardenburg-Shah syndrome (WSS), also known as Waardenburg syndrome type 4 (WS4) is characterized by the association of Waardenburg syndrome (sensorineural hearing loss and pigmentary abnormalities) and Hirschsprung disease (aganglionic megacolon).
## Epidemiology
Prevalence is unknown. So far, less than 100 cases have been reported in the literature worldwide.
## Clinical description
Patients usually present in the neonatal period with pigmentary anomalies (including white forelock, eyebrows and eyelashes, heterochromia of the irides, possibly retinal pigment abnormalities and/or hypopigmented patches on the skin), neurosensory deafness (frequently bilateral, but can be unilateral) and intestinal obstruction presenting as bilious vomiting, inability to pass meconium and abdominal distension since birth. Depending on the gene involved, morphological abnormalities of the temporal bone (especially utricle and semi-circular canals), anosmia (with or without agenesis of the olfactory bulbs) and hypogonadotropic hypogonadism can be associated. ABCD syndrome is a rare variant expression of WSS, characterized by albinism, black lock, cell migration disorder of the gut neurocytes and deafness.
## Etiology
WSS is caused by abnormal migration or differentiation of neural crest cells during embryonic development. This syndrome is genetically heterogeneous, composed of three etiological subtypes: WS4-A, WS4-B and WS4-C, caused by mutations in the EDNRB (13q22.3, coding for the endothelin-B receptor), EDN3 (20q13.32, coding for an endothelin receptor ligand) and SOX10 (22q13.1, coding for the SOX10 transcription factor) genes, respectively. These genes are involved in melanocyte development and nerve cells development in the intestine. Heterozygous mutations in EDNRB and EDN3 are often asymptomatic although patients may also present with less severe phenotypes (isolated Hirschsprung disease, isolated deafness, less extended hypopigmentation, or Waardenburg syndrome type 2). Specific mutations in SOX10 (particularly those predicted to truncate the protein at the level of the terminal coding exons) result in a more severe WSS variant with neurologic findings (neurologic Waardenburg-Shah syndrome, also called PCWH).
## Diagnostic methods
Diagnosis is determined by the presence of major and minor characteristic clinical features according to the Waardenburg Consortium criteria, as well as history and physical examination for Hirschsprung disease utilizing plain abdominal X-ray, barium enema, anorectal manometry and rectal biopsy. Genetic molecular analysis confirms the diagnosis.
## Differential diagnosis
The differential diagnosis includes other forms of Waardenburg syndrome, piebaldism and ermine phenotype, as well as other causes of hearing loss or Hirschsprung disease.
## Antenatal diagnosis
Molecular prenatal diagnosis may be proposed to families in which the disease-causing mutation has been identified.
## Genetic counseling
Genetic counseling should be adapted according to the mode of inheritance associated with the detected mutation. SOX10 mutations are inherited in an autosomal dominant manner. EDNRB and EDN3 mutations are inherited in an autosomal recessive manner in most families but are semi-dominant in some (with the index case usually carrying bi-allelic mutations, while heterozygous affected relatives present with isolated or milder signs of the disease).
## Management and treatment
Management is only symptomatic. Surgical treatment is required for Hirschsprung disease. Hearing aids are recommended to ameliorate hearing impairment, as well as to improve language, communication and cognitive skills. Associated manifestations are treated as appropriate (e.g., cosmetics to manage the pigmentation defects, sunblock and sunglasses to protect skin and eyes from the sun).
## Prognosis
The prognosis is often good, however, significant morbidity and mortality may be associated due to complications resulting from Hirschsprung disease (related to the size of the aganglionic intestinal segment).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Waardenburg-Shah syndrome | c1848519 | 6,606 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=897 | 2021-01-23T17:08:21 | {"gard": ["5524"], "mesh": ["C536467"], "omim": ["277580", "613265", "613266"], "umls": ["C1848519", "C3266898"], "icd-10": ["Q87.8"], "synonyms": ["Shah-Waardenburg syndrome", "WS4", "Waardenburg syndrome type 4", "Waardenburg-Hirschsprung syndrome"]} |
Main article: Speech and language pathology
Speech and language impairment are basic categories that might be drawn in issues of communication involve hearing, speech, language, and fluency.
A speech impairment is characterized by difficulty in articulation of words. Examples include stuttering or problems producing particular sounds. Articulation refers to the sounds, syllables, and phonology produced by the individual. Voice, however, may refer to the characteristics of the sounds produced—specifically, the pitch, quality, and intensity of the sound. Often, fluency will also be considered a category under speech, encompassing the characteristics of rhythm, rate, and emphasis of the sound produced.[1]
A language impairment is a specific impairment in understanding and sharing thoughts and ideas, i.e. a disorder that involves the processing of linguistic information. Problems that may be experienced can involve the form of language, including grammar, morphology, syntax; and the functional aspects of language, including semantics and pragmatics.[1]
An individual can have one or both types of impairment. These impairments/disorders are identified by a speech and language pathologist.
## Contents
* 1 Speech disorders
* 1.1 Apraxia of speech
* 1.2 Developmental verbal dyspraxia
* 1.3 Dysarthria
* 1.4 Orofacial myofunctional disorders
* 1.5 Speech sound disorder
* 1.6 Stuttering
* 1.7 Voice disorders
* 2 Language disorders
* 2.1 Specific language impairment
* 2.2 Selective mutism
* 2.3 Aphasia
* 2.4 Language-based learning disabilities
* 3 Diagnostic criteria
* 3.1 Developmental disorders
* 3.2 Acquired disorders
* 3.3 Speech and language assessment
* 3.4 In the United States of America
* 4 Management
* 4.1 Speech-language pathology
* 4.2 Interventions
* 4.3 Adaptability and limitations
* 4.4 Assistive technology
* 4.5 Inclusion vs. exclusion
* 5 Prevalence
* 6 Discrimination
* 7 Terminology
* 8 History
* 9 See also
* 10 References
* 11 Further reading
* 12 External links
## Speech disorders[edit]
Main article: Speech disorder
The following are brief definitions of several of the more prominent speech disorders:
### Apraxia of speech[edit]
Main article: Apraxia of speech
Apraxia of speech is the acquired form of motor speech disorder caused by brain injury, stroke or dementia.
### Developmental verbal dyspraxia[edit]
Main article: Developmental verbal dyspraxia
Developmental verbal dyspraxia refers specifically to a motor speech disorder. This is a neurological disorder. Individuals suffering from developmental verbal apraxia encounter difficulty saying sounds, syllables, and words. The difficulties are not due to weakness of muscles, but rather on coordination between the brain and the specific parts of the body.[2][3] Apraxia of speech is the acquired form of this disorder caused by brain injury, stroke or dementia.
Interventions are more effective when they occur individually at first, and between three and five times per week. With improvements, children with apraxia may be transitioned into group therapy settings. Therapeutic exercises must focus on planning, sequencing, and coordinating the muscle movements involved in speech production. Children with developmental verbal dyspraxia must practice the strategies and techniques that they learn in order to improve. In addition to practice, feedback can be helpful to improve apraxia of speech. Tactile feedback (touch), visual feedback (watching self in mirror), and verbal feedback are all important additions.[4] Biofeedback has also been cited as a possible therapy. Functional training involves placing the individual in more speech situations, while providing him/her with a speech model, such as the SLP.[5] Because the cause is neurological, however, some patients do not progress. In these cases, AAC may be more appropriate.
### Dysarthria[edit]
Main article: Dysarthria
Dysarthria is a motor speech disorder that results from a neurological injury. Some stem from central damage, while other stem from peripheral nerve damage. Difficulties may be encountered in respiratory problems, vocal fold function, or velopharyngeal closure, for example.[5]
### Orofacial myofunctional disorders[edit]
Main article: Orofacial myological disorders
Orofacial myofunctional disorders refers to problems encountered when the tongue thrusts forward inappropriately during speech. While this is typical in infants, most children outgrow this. Children that continue to exaggerate the tongue movement may incorrectly produce speech sounds, such as /s/, /z/, /ʃ/, /tʃ/, and /dʒ/. For example, the word, "some," might be pronounced as "thumb".[3]
The treatment of OMD will be based upon the professional's evaluation.[6] Each child will present a unique oral posture that must be corrected. Thus, the individual interventions will vary. Some examples include:
* increasing awareness of muscles around the mouth
* increasing awareness of oral postures
* improving muscle strength and coordination
* improving speech sound productions
* improving swallowing patterns
### Speech sound disorder[edit]
Main article: Speech sound disorder
Speech sound disorders may be of two varieties: articulation (the production of sounds) or phonological processes (sound patterns). An articulation disorder may take the form of substitution, omission, addition, or distortion of normal speech sounds. Phonological process disorders may involve more systematic difficulties with the production of particular types of sounds, such as those made in the back of the mouth, like "k" and "g".[3]
Naturally, abnormalities in speech mechanisms would need to be ruled out by a medical professional. Therapies for articulation problems must be individualized to fit the individual case. The placement approach—instructing the individual on the location in which the tongue should be and how to blow air correctly—could be helpful in difficulties with certain speech sounds. Another individual might benefit more from developing auditory discrimination skills, since he/she has not learned to identify error sounds in his/her speech. Generalization of these learned speech techniques will need to be generalized to everyday situations.[5] Phonological process treatment, on the other hand, can involve making syntactical errors, such as omissions in words. In cases such as these, explicit teaching of the linguistic rules may be sufficient.[7]
Some cases of speech sound disorders, for example, may involve difficulties articulating speech sounds. Educating a child on the appropriate ways to produce a speech sound and encouraging the child to practice this articulation over time may produce natural speech, Speech sound disorder. Likewise, stuttering does not have a single, known cause, but has been shown to be effectively reduced or eliminated by fluency shaping (based on behavioral principles) and stuttering modification techniques.
### Stuttering[edit]
Main article: Stuttering
Stuttering is a disruption in the fluency of an individual's speech, which begins in childhood and may persist over a lifetime. Stuttering is a form of disfluency; disfluency becomes a problem insofar as it impedes successful communication between two parties. Disfluencies may be due to unwanted repetitions of sounds, or extension of speech sounds, syllables, or words. Disfluencies also incorporate unintentional pauses in speech, in which the individual is unable to produce speech sounds.[3]
While the effectiveness is debated, most treatment programs for stuttering are behavioral. In such cases, the individual learns skills that improve oral communication abilities, such as controlling and monitoring the rate of speech. SLPs may also help these individuals to speak more slowly and to manage the physical tension involved in the communication process. Fluency may be developed by selecting a slow rate of speech, and making use of short phrases and sentences. With success, the speed may be increased until a natural rate of smooth speech is achieved.[8] Additionally, punishment for incorrect speech production should be eliminated, and a permissive speaking environment encouraged. Electronic fluency devices, which alter the auditory input and provide modified auditory feedback to the individual, have shown mixed results in research reviews.
Because stuttering is such a common phenomenon, and because it is not entirely understood, various opposing schools of thought emerge to describe its etiology. The Breakdown theories maintain that stuttering is the result of a weakening or breakdown in physical systems that are necessary for smooth speech production. Cerebral dominance theories (in the stutterer, no cerebral hemisphere takes the neurological lead) and theories of perseveration (neurological "skipping record" of sorts) are both Breakdown theories. Auditory Monitoring theories suggest that stutters hear themselves differently from how other people hear them. Since speakers adjust their communication based upon the auditory feedback they hear (their own speech), this creates conflict between the input and the output process. Psychoneurotic theories posit repressed needs as the source of stuttering. Lastly, Learning theories are straightforward—children learn to stutter. It should be clear that each etiological position would suggest a different intervention, leading to controversy with the field.[5]
### Voice disorders[edit]
Voice disorders range from aphonia (loss of phonation) to dysphonia, which may be phonatory and/or resonance disorders. Phonatory characteristics could include breathiness, hoarseness, harshness, intermittency, pitch, etc. Resonance characteristics refer to overuse or underuse of the resonance chambers resulting in hypernasality or hyponasality.[5] Several examples of voice problems are vocal cord nodules or polyps, vocal cord paralysis, paradoxical vocal fold movement, and spasmodic dysphonia. Vocal cord nodules and polyps are different phenomena, but both may be caused by vocal abuse, and both may take the form of growths, bumps, or swelling on the vocal cords. Vocal fold paralysis is the inability to move one or both of the vocal cords, which results in difficulties with voice and perhaps swallowing. Paradoxical vocal fold movement occurs when the vocal cords close when they should actually be open. Spasmodic dysphonia is caused by strained vocal cord movement, which results in awkward voice problems, such as jerkiness or quavering.[3]
If nodules or polyps are present, and are large, surgery may be the appropriate choice for removal. Surgery is not recommended for children, however. Other medical treatment may suffice for slighter problems, such as those induced by gastroesophageal reflux disease, allergies, or thyroid problems. Outside of medical and surgical interventions, professional behavioral interventions can be useful in teaching good vocal habits and minimizing abuse of vocal cords. This voice therapy may instruct in attention to pitch, loudness, and breathing exercises. Additionally, the individual may be instructed on the optimal position to produce the maximum vocal quality. Bilateral paralysis is another disorder that may require medical or surgical interventions to return vocal cords to normalcy; unilateral paralysis may be treated medically or behaviorally.[9]
Paradoxical vocal fold movement (PVFM) is also treated medically and behaviorally. Behavioral interventions will focus on voice exercises, relaxation strategies, and techniques that can be used to support breath. More generally, however, PVFM interventions focus on helping an individual to understand what triggers the episode, and how to deal with it when it does occur.[9]
While there is no cure for spasmodic dysphonia, medical and psychological interventions can alleviate some of the symptoms. Medical interventions involve repeated injections of Botox into one or both of the vocal cords. This weakens the laryngeal muscles, and results in a smoother voice.[9]
## Language disorders[edit]
Main article: Language disorder
A language disorder is an impairment in the ability to understand and/or use words in context, both verbally and nonverbally. Some characteristics of language disorders include improper use of words and their meanings, inability to express ideas, inappropriate grammatical patterns, reduced vocabulary and inability to follow directions. One or a combination of these characteristics may occur in children who are affected by language learning disabilities or developmental language delay. Children may hear or see a word but not be able to understand its meaning. They may have trouble getting others to understand what they are trying to communicate.
### Specific language impairment[edit]
Main article: Specific language impairment
Interventions for specific language impairment will be based upon the individual difficulties in which the impairment manifests. For example, if the child is incapable of separating individual morphemes, or units of sound, in speech, then the interventions may take the form of rhyming, or of tapping on each syllable. If comprehension is the trouble, the intervention may focus on developing metacognitive strategies to evaluate his/her knowledge while reading, and after reading is complete. It is important that whatever intervention is employed, it must be generalized to the general education classroom.[10]
### Selective mutism[edit]
Main article: Selective mutism
Selective mutism is a disorder that manifests as a child that does not speak in at least one social setting, despite being able to speak in other situations. Selective mutism is normally discovered when the child first starts school.[3]
Behavioral treatment plans can be effective in bringing about the desired communication across settings. Stimulus fading involves a gradual desensitization, in which the individual is placed in a comfortable situation and the environment is gradually modified to increase the stress levels without creating a large change in stress level. Shaping relies on behavioral modification techniques, in which successive attempts to produce speech is reinforced. Self-modeling techniques may also be helpful; for example, self-modeling video tapes, in which the child watches a video of him/herself performing the desired action, can be useful.
If additional confounding speech problems exist, a SLP may work with the student to identify what factors are complicating speech production and what factors might be increasing the mute behaviors. Additionally, he/she might work with the individual to become more comfortable with social situations, and with the qualities of their own voice. If voice training is required, they might offer this as well.[11]
### Aphasia[edit]
Main article: Aphasia
Aphasia refers to a family of language disorders that usually stem from injury, lesion, or atrophy to the left side of the brain that result in reception, perception, and recall of language; in addition, language formation and expressive capacities may be inhibited.[5]
### Language-based learning disabilities[edit]
Language-based learning disabilities, which refer to difficulties with reading, spelling, and/or writing that are evidenced in a significant lag behind the individual's same-age peers. Most children with these disabilities are at least of average intelligence, ruling out intellectual impairments as the causal factor.[3]
## Diagnostic criteria[edit]
The DSM-5 and the ICD-10 are both used to make specific diagnostic decisions. Speech and language disorders commonly include communication issues, but also extend into various areas such as oral-motor function—sucking, swallowing, drinking, or eating. In some cases, a child's communication is delayed considerably behind his/her same-aged peers. The effects of these disorders can range from basic difficulties in the production of certain letter sounds to more comprehensive inabilities to generate (expressive) or understand (receptive) language. In most cases, the causal factors that create these speech and language difficulties are unknown. There are a wide variety of biological and environmental causal factors that can create them, ranging from drug abuse to neurological issues. For more information on causal hypotheses, refer to the section on models.[12]
### Developmental disorders[edit]
Developmental disorders tend to have a genetic origin, such as mutations of FOXP2, which has been linked to developmental verbal dyspraxia and specific language impairment. Some of these impairments are caused by genetics. Case histories often reveal a positive family history of communication disorders. Between 28% and 60% of children with a speech and language deficit have a sibling and/or parent who is also affected.[13] Down syndrome is another example of a genetic causal factor that may result in speech and/or language impairments. Stuttering is a disorder that is hypothesized to have a strong genetic component as well.
Some speech and language impairments have environmental causes. A specific language impairment, for example, may be caused by insufficient language stimulation in the environment. If a child does not have access to an adequate role model, or is not spoken to with much frequency, the child may not develop strong language skills. Furthermore, if a child has little stimulating experiences, or is not encouraged to develop speech, that child may have little incentive to speak at all and may not develop speech and language skills at an average pace.[14]
Developmental disabilities such as autism and neurological disorders such as cerebral palsy may also result in impaired communicative abilities. Similarly, malformation or malfunctioning of the respiratory system or speech mechanisms may result in speech impairments. For example, a cleft palate will allow too much air to pass through the nasal cavity and a cleft lip will not allow the individual to correctly form sounds that require the upper lip.[14] The development of vocal fold nodules represents another issue of biological causation. In some cases of biological origin, medical interventions such as surgery or medication may be required. Other cases may require speech therapy or behavioral training.
### Acquired disorders[edit]
Acquired disorders result from brain injury, stroke or atrophy, many of these issues are included under the Aphasia umbrella. Brain damage, for example, may result in various forms of aphasia if critical areas of the brain such as Broca's or Wernicke's area are damaged by lesions or atrophy as part of a dementia.
An acquired language disorder occurs after the person is injured or ill, it is neurological. One of the most commonly known acquired language disorder is aphasia.[15] Everyday activities are easily affected because of a language disorder.[15] Communication impacts how understanding the person is of this disorder.[15]
There is a sender and receiver to communication, the receiver needs to be able to understand the communication process.[15] The receiver should also be able to understand, so that they can respond and communicate back to the sender.[15] The person needs to be careful how the sender/ receiver interprets the messages being sent.[15] There are 4 types of barriers to communication for the sender/receivers, Process barriers, Physical barriers, Semantic barriers, and Psychosocial barriers.[15] Process barriers are the sender and receiver of communication.[15] Physical barriers, one of the biggest and major barriers to communication, are caused by distractions.[15] The semantic barriers of communication are the words and meaning of the words and how they are used.[15] Psychosocial barriers are the mental and emotional factors of communication.[15] These barriers are important because of how to treat and an acquired language disorder.[15] Noise plays a big role in the communication process, by helping to interpret the message and bringing out emotions and attitude.[15]
### Speech and language assessment[edit]
Main article: Speech and language assessment
What follows are a list of frequently used measures of speech and language skills, and the age-ranges for which they are appropriate.[1]
* Clinical Evaluation of Language Fundamentals – Preschool (3–6 years)
* Clinical Evaluation of Language Fundamentals (6–21 years)
* MacArthur Communicative Development Inventories (0–12 months)
* The Rossetti Infant-Toddler Language Scale (0–36 months)
* Preschool Language Scale (0–6 years)
* Expressive One-word Picture Vocabulary Test (2–15 years)
* Bankson-Bernthal Phonological Process Survey Test (2–16 years)
* Goldman-Fristoe Test of Articulation 2 (2–21 years)
* Peabody Picture Vocabulary Test (2.5–40 years)
### In the United States of America[edit]
Under the Individuals with Disabilities Education Act (IDEA) 2004, the federal government has defined a speech or language impairment as "a communication disorder such as stuttering, impaired articulation, a language impairment, or a voice impairment, which adversely affects a child's learning". In order to qualify in the educational system as having a speech or language impairment, the child's speech must be either unintelligible much of the time or he/she must have been professionally diagnosed as having either a speech impairment or language delay which requires intervention. Additionally, IDEA 2004 contains an exclusionary clause that stipulates that a speech or language impairment may not be either cultural, ethnic, bilingual, or dialectical differences in language, temporary disorders (such as those induced by dental problems), or delayed abilities in producing the most difficult linguistic sounds in a child's age range.[14]
## Management[edit]
Speech-language pathologists (SLPs) offer many services to children with speech or language disabilities.
### Speech-language pathology[edit]
Main article: Speech-language pathology
Speech-language pathologists (SLPs) may provide individual therapy for the child to assist with speech production problems such as stuttering. They may consult with the child's teacher about ways in which the child might be accommodated in the classroom, or modifications that might be made in instruction or environment. The SLP can also make crucial connections with the family, and help them to establish goals and techniques to be used in the home. Other service providers, such as counselors or vocational instructors may also be included in the development of goals as the child transitions into adulthood.[12]
The individual services that the child receives will depend upon the needs of that child. Simpler problems of speech, such as hoarseness or vocal fatigue (voicing problems) may be solved with basic instruction on how to modulate one's voice. Articulation problems could be remediated by simple practice in sound pronunciation. Fluency problems may be remediated with coaching and practice under the guidance of trained professionals, and may disappear with age. However, more complicated problems, such as those accompanying autism or strokes, may require many years of one-on-one therapy with a variety of service providers. In most cases, it is imperative that the families be included in the treatment plans since they can help to implement the treatment plans. The educators are also a critical link in the implementation of the child's treatment plan.[16]
For children with language disorders, professionals often relate the treatment plans to classroom content, such as classroom textbooks or presentation assignments. The professional teaches various strategies to the child, and the child works to apply them effectively in the classroom. For success in the educational environment, it is imperative that the SLP or other speech-language professional have a strong, positive rapport with the teacher(s).[10]
Speech-language pathologists create plans that cater to the individual needs of the patient. If speech is not practical for a patient, the SLP will work with the patient to decide upon an augmentative and alternative communication (AAC) method or device to facilitate communication. They may work with other patients to help them make sounds, improve voices, or teach general communication strategies. They also work with individuals who have difficulties swallowing. In addition to offering these types of communication training services, SLPs also keep records of evaluation, progress, and eventual discharge of patients, and work with families to overcome and cope with communication impairments (Bureau of Labor Statistics, 2009).
In many cases, SLPs provide direct clinical services to individuals with communication or swallowing disorders. SLPs work with physicians, psychologists, and social workers to provide services in the medical domain, and collaborate with educational professionals to offer additional services for students to facilitate the educational process. Thus, speech-language services may be found in schools, hospitals, outpatient clinics, and nursing homes, among other settings.[17]
The setting in which therapy is provided to the individual depends upon the age, type, and severity of the individual's impairment. An infant/toddler may engage in an early intervention program, in which services are delivered in a naturalistic environment in which the child is most comfortable—probably his/her home. If the child is school-aged, he/she may receive speech-language services at an outpatient clinic, or even at his/her home school as part of a weekly program. The type of setting in which therapy is offered depends largely upon characteristics of the individual and his/her disability.
As with any professional practice that is informed by ongoing research, controversies exist in the fields that deal with speech and language disorders. One such current debate relates to the efficacy of oral motor exercises and the expectations surrounding them. According to Lof,[18] non-speech oral motor exercises (NS-OME) includes "any technique that does not require the child to produce a speech sound but is used to influence the development of speaking abilities". These sorts of exercises would include blowing, tongue push-ups, pucker-smile, tongue wags, big smile, tongue-to-nose-to-chin, cheek puffing, blowing kisses, and tongue curling, among others. Lof continues, indicating that 85% of SLPs are currently using NS-OME. Additionally, these exercises are used for dysarthria, apraxia, late talkers, structural anomalies, phonological impairments, hearing impairments, and other disorders. Practitioners assume that these exercises will strengthen articulatory structures and generalize to speech acts. Lof reviews 10 studies, and concludes that only one of the studies shows benefits to these exercises (it also suffered serious methodological flaws). Lof ultimately concludes that the exercises employ the same structures, but are used for different functions.[19] The NS-OME position is not without its supporters, however, and the proponents are numerous.
### Interventions[edit]
Intervention services will be guided by the strengths and needs determined by the speech and language evaluation. The areas of need may be addressed individually until each one is functional; alternatively, multiple needs may be addressed simultaneously through the intervention techniques. If possible, all interventions will be geared towards the goal of developing typical communicative interaction. To this end, interventions typically follow either a preventive, remedial, or compensatory model. The preventive service model is common as an early intervention technique, especially for children whose other disorders place them at a higher risk for developing later communication problems. This model works to lessen the probability or severity of the issues that could later emerge. The remedial model is used when an individual already has a speech or language impairment that he/she wishes to have corrected. Compensatory models would be used if a professional determines that it is best for the child to bypass the communication limitation; often, this relies on AAC.
Language intervention activities are used in some therapy sessions. In these exercises, an SLP or other trained professional will interact with a child by working with the child through play and other forms of interaction to talk to the child and model language use. The professional will make use of various stimuli, such as books, objects, or simple pictures to stimulate the emerging language. In these activities, the professional will model correct pronunciation, and will encourage the child to practice these skills. Articulation therapy may be used during play therapy as well, but involves modeling specific aspects of language—the production of sound. The specific sounds will be modeled for the child by the professional (often the SLP), and the specific processes involved in creating those sounds will be taught as well. For example, the professional might instruct the child in the placement of the tongue or lips in order to produce certain consonant sounds.[20]
Technology is another avenue of intervention, and can help children whose physical conditions make communication difficult. The use of electronic communication systems allow nonspeaking people and people with severe physical disabilities to engage in the give and take of shared thought.
### Adaptability and limitations[edit]
While some speech problems, such as certain voice problems, require medical interventions, many speech problems can be alleviated through effective behavioral interventions and practice. In these cases, instruction in speech techniques or speaking strategies, coupled with regular practice, can help the individual to overcome his/her speaking difficulties. In other, more severe cases, the individual with speech problems may compensate with AAC devices.[14]
Speech impairments can seriously limit the manner in which an individual interacts with others in work, school, social, and even home environments. Inability to correctly form speech sounds might create stress, embarrassment, and frustration in both the speaker and the listener. Over time, this could create aggressive responses on the part of the listener for being misunderstood, or out of embarrassment. Alternatively, it could generate an avoidance of social situations that create these stressful situations. Language impairments create similar difficulties in communicating with others, but may also include difficulties in understanding what others are trying to say (receptive language). Because of the pervasive nature of language impairments, communicating, reading, writing, and academic success may all be compromised in these students. Similar to individuals with speech impairments, individuals with language impairments may encounter long-term difficulties associated with work, school, social, and home environments.[14]
### Assistive technology[edit]
Augmentative and alternative communication (AAC) includes all forms of communication other than oral communication that an individual might employ to make known his/her thoughts. AAC work to compensate for impairments that an individual might have with expressive language abilities. Each system works to maintain a natural and functional level of communication. There is no one best type of AAC for all individuals; rather, the best type of AAC will be determined by the strengths and weaknesses of a specific individual. While there are a large number of types of AAC, there are fundamentally two categories: aided and unaided.
Unaided systems of communication are those that require both communication parties to be physically present in the same location. Examples of unaided systems include gestures, body language, sign language, and communication boards. Communication boards are devices upon which letters, words, or pictorial symbols might be displayed; the individual may interface with the communication board to express him/herself to the other individual.
Aided systems of communication do not require both individuals to be physically present in the same location, though they might be. Aided systems are often electronic devices, and they may or may not provide some form of voice output. If a device does create a voice output, it is referred to as a speech generating device. While the message may take the form of speech output, it may also be printed as a visual display of speech. Many of these devices can be connected to a computer, and in some cases, they may even be adapted to produce a variety of different languages.[14][21]
### Inclusion vs. exclusion[edit]
Students identified with a speech and language disability often qualify for an Individualized Education Plan as well as particular services. These include one-on-one services with a speech and language pathologist. Examples used in a session include reading vocabulary words, identifying particular vowel sounds and then changing the context, noting the difference. School districts in the United States often have speech and language pathologists within a special education staff to work with students. Additionally, school districts can place students with speech and language disabilities in a resource room for individualized instruction. A combination of early intervention and individualized support has shown promise increasing long-term academic achievement with students with this disability.[22]
Students might work individually with a specialist, or with a specialist in a group setting. In some cases, the services provided to these individuals may even be provided in the regular education classroom. Regardless of where these services are provided, most of these students spend small amounts of time in therapy and the large majority of their time in the regular education classroom with their typically developing peers.[23]
Therapy often occurs in small groups of three or four students with similar needs. Meeting either in the office of the speech-language pathologist or in the classroom, sessions may take from 30 minutes to one hour. They may occur several times per week. After introductory conversations, the session is focused on a particular therapeutic activity, such as coordination and strengthening exercises of speech muscles or improving fluency through breathing techniques. These activities may take the form of games, songs, skits, and other activities that deliver the needed therapy. Aids, such as mirrors, tape recorders, and tongue depressors may be utilized to help the children to become aware of their speech sounds and to work toward more natural speech production.
## Prevalence[edit]
In 2006, the U.S. Department of Education indicated that more than 1.4 million students were served in the public schools' special education programs under the speech or language impairment category of IDEA 2004.[14] This estimate does not include children who have speech/language problems secondary to other conditions such as deafness; this means that if all cases of speech or language impairments were included in the estimates, this category of impairment would be the largest. Another source has estimated that communication disorders—a larger category, which also includes hearing disorders—affect one of every 10 people in the United States.[12]
ASHA has cited that 24.1% of children in school in the fall of 2003 received services for speech or language disorders—this amounts to a total of 1,460,583 children between 3 –21 years of age.[13] Again, this estimate does not include children who have speech/language problems secondary to other conditions. Additional ASHA prevalence figures have suggested the following:
* Stuttering affects approximately 4% to 5% of children between the ages of 2 and 4.
* ASHA has indicated that in 2006:
* Almost 69% of SLPs served individuals with fluency problems.
* Almost 29% of SLPs served individuals with voice or resonance disorders.
* Approximately 61% of speech-language pathologists in schools indicated that they served individuals with SLI
* Almost 91% of SLPs in schools indicated that they servedindividuals with phonological/articulation disorder
* Estimates for language difficulty in preschool children range from 2% to 19%.
* Specific Language Impairment (SLI) is extremely common in children, and affects about 7% of the childhood population.[13]
## Discrimination[edit]
While more common in childhood, speech impairments can result in a child being bullied. Bullying is a harmful activity that often takes place at school, though may be present in adult life. Bullying involves the consistent and intentional harassment of another individual, and may be physical or verbal in nature.[24]
Speech impairments (e.g., stuttering) and language impairments (e.g., dyslexia, auditory processing disorder) may also result in discrimination in the workplace. For example, an employer would be discriminatory if he/she chose to not make reasonable accommodations for the affected individual, such as allowing the individual to miss work for medical appointments or not making onsite-accommodations needed because of the speech impairment. In addition to making such appropriate accommodations, the Americans with Disabilities Act (1990) protects against discrimination in "job application procedures, hiring, advancement, discharge, compensation, job training, and other terms, conditions, and privileges of employment".[25]
## Terminology[edit]
Smith[14] offers the following definitions of major terms that are important in the world of speech and language disorders.
* Alternative and augmentative communication (AAC): Assistive technology that helps individuals to communicate; may be low-tech or high-tech
* Articulation disorder: Atypical generation of speech sounds
* Cleft lip: Upper lip is not connected, resulting in abnormal speech
* Cleft palate: An opening in the roof of the mouth that allows too much air to pass through nasal cavity, resulting in abnormal speech
* Communication: Transfer of knowledge, ideas, opinions, and feelings
* Communication board: Low-tech AAC device that displays pictures or words to which an individual points to communicate
* Communication disorder: Disorders in speech, language, hearing, or listening that create difficulties in effective communication
* Disfluency: Interruptions in the flow of an individual's speech
* Expressive language: Ability to express one's thoughts, feelings, or information
* Language: Rule-based method used for communication
* Language delays: Slowed development of language skills
* Language disorder: Difficulty/inability to comprehend/make use of the various rules of language
* Loudness: A characteristic of voice; refers to intensity of sound
* Morphology: Rules that determine structure and form of words
* Otitis media: Middle ear infection that can interrupt normal language development
* Pitch: A characteristic of voice; usually either high or low
* Phonological awareness: Understanding, identifying, and applying the relationships between sound and symbol
* Phonology: Rules of a language that determine how speech sounds work together to create words and sentences
* Pragmatics: Appropriate use of language in context
* Receptive language: Ability to comprehend information that is received
* Semantics: System of language that determines content, intent, and meaning of language
* Speech: Vocal production of language
* Speech impairment: Abnormal speech is unintelligible, unpleasant, or creates an ineffective communication process
* Speech/language pathologist: Professionals who help individuals to maximize their communication skills.
* Speech synthesizer: Assistive technology that creates voice
* Stuttering: Hesitation or repetition contributes to dysfluent speech
* Syntax: Rules that determine word endings and word orders
* Voice problem: Abnormal oral speech, often including atypical pitch, loudness, or quality
## History[edit]
In the mid 19th century, the scientific endeavors of such individuals as Charles Darwin gave rise to more systematic and scientific consideration of physical phenomenon, and the work of others, such as Paul Broca and Carl Wernicke, also lent scientific rigor to the study of speech and language disorders. The late 19th century saw an increase in "pre-professionals," those who offered speech and language services based upon personal experiences or insights. Several trends were exhibited even in the 19th century, some have indicated the importance of elocution training in the early 19th century, through which individuals would seek out those with training to improve their vocal qualities. By 1925 in the USA interest in these trends lead to the forming of the organization that would become American Speech-Language-Hearing Association (ASHA) and the birth of speech-language pathology.[26]
The twentieth century has been proposed to be composed of four major periods: Formative Years, Processing Period, Linguistic Era, and Pragmatics Revolution. The Formative Years, which began around 1900 and ended around WWII, was a time during which the scientific rigor extended and professionalism entered the picture. During this period, the first school-based program began in the U.S. (1910). The Processing Period, from roughly 1945-1965, further developed the assessment and interventions available for general communication disorders; much of these focused on the internal, psychological transactions involved in the communication process. During the Linguistic Era, from about 1965-1975, professionals began to separate language deficits from speech deficits, which had major implications for diagnosis and treatment of these communication disorders. Lastly, the Pragmatics Revolution has continued to shape the professional practice by considering major ecological factors, such as culture, in relation to speech and language impairments. It was during this period that IDEA was passed, and this allowed professionals to begin working with a greater scope and to increase the diversity of problems with which they concerned themselves.[14][26]
## See also[edit]
* Auditory processing disorder
* Broca's area
* Communication disorder
* Dyslexia
* FOXP2
* Language delay
* Origin of speech
* Speech and language assessment
* Speech and language pathology
* Speech and language pathology in school settings
* Speech perception
* Speech processing
* Speech repetition
## References[edit]
1. ^ a b c Batshaw, Mark L (2002). Children with disabilities. 5. Baltimore: Paul H. Brookes. ISBN 978-0-86433-137-3. OCLC 608999305.
2. ^ Souza TN, Payão Mda C, Costa RC (2009). "Childhood speech apraxia in focus: theoretical perspectives and present tendencies". Pro Fono. 21 (1): 76–80. doi:10.1590/S0104-56872009000100013. PMID 19360263.
3. ^ a b c d e f g "Child Speech and Language". American Speech-Language-Hearing Association. Retrieved 2009-07-05.
4. ^ "Childhood Apraxia of Speech". American Speech-Language-Hearing Association.
5. ^ a b c d e f Palmer, John; Yantis, Phillip A. (1990). Survey of communication disorders. Baltimore: Williams & Wilkins. ISBN 978-0-683-06743-9. OCLC 20168213.
6. ^ "Sorry! That Page Cannot Be Found". American Speech-Language-Hearing Association.
7. ^ "Speech Sound Disorders". American Speech-Language-Hearing Association.
8. ^ "Stuttering". American Speech-Language-Hearing Association.
9. ^ a b c "Voice Disorders". American Speech-Language-Hearing Association.
10. ^ a b "Learning Disabilities". American Speech-Language-Hearing Association.
11. ^ "Selective Mutism". American Speech-Language-Hearing Association.
12. ^ a b c "Speech and Language Impairments". National Dissemination Center for Children with Disabilities (NICHCY). Retrieved 2009-07-05.
13. ^ a b c "Sorry! That Page Cannot Be Found". American Speech-Language-Hearing Association.
14. ^ a b c d e f g h i Smith, Deborah D.; Tyler, Naomi Chodhuri (2009). Introduction to Special Education: Making A Difference (7th ed.). Englewood Cliffs, N.J: Prentice Hall. ISBN 978-0-205-60056-4. OCLC 268789042.
15. ^ a b c d e f g h i j k l m Ondondo, Emily (July 2015). "Acquired Language Disorders as Barriers to Effective Communication". Theory and Practice in Language Studies. 5 (7): 1324. doi:10.17507/tpls.0507.02.
16. ^ "Morales, S. (2009). The mechanics of speech and language. Retrieved July 10, 2009".
17. ^ "Bureau of Labor Statistics. (2009). Speech-language pathologist. Retrieved July 10, 2009".
18. ^ Lof, G.L. (2006). Logic, theory, and evidence against the use of non-speech oral motor exercises to change speech sound production. ASHA Convention 2006, 1-11.
19. ^ Lof, G.L. (2003). Oral motor exercises and treatment outcomes. Language Learning and Education, April 2003, 7-11.
20. ^ "Speech-Language Therapy (for Parents) - KidsHealth". kidshealth.org.
21. ^ "Augmentative and Alternative Communication (AAC)". American Speech-Language-Hearing Association.
22. ^ Reynolds, Arthur J.; Judy A. Temple; Dylan L. Robertson; Emily A. Mann (2001). "Long-term Effects of an Early Childhood Intervention on Educational Achievement and Juvenile Arrest". Journal of the American Medical Association. 285 (18): 2339–2346. doi:10.1001/jama.285.18.2339. PMID 11343481.
23. ^ Mastropieri, Margo A.; Scruggs, Thomas E. (2009). The Inclusive Classroom: Strategies for Effective Instruction (4th ed.). Englewood Cliffs, N.J: Prentice Hall. ISBN 978-0-13-500170-7. OCLC 268789048.
24. ^ IStutter. (2005). Teasing and bullying: Facts and support. Retrieved July 22, 2009
25. ^ "Parry, W.D. (2009). Being your own best advocate. Retrieved July 26, 2009".
26. ^ a b "Judy Duchan's History of Speech - Language Pathology". www.acsu.buffalo.edu.
## Further reading[edit]
* American Journal of Speech-Language Pathology - Articles in Press
* Journal of Communication Disorders - Articles in Press
* DeThorne, Laura S.; Cynthia J. Johnson; Louise Walder; Jamie Mahurin-Smith (May 2009). "When "Simon Says" Doesn't Work: Alternatives to Imitation for Facilitating Early Speech Development". American Journal of Speech-Language Pathology. 18 (2): 133–145. doi:10.1044/1058-0360(2008/07-0090). PMID 18930909. S2CID 46499568.
* Maas, Edwin; Donald A. Robin; Shannon N. Austermann Hula; Skott E. Freedman; Gabriele Wulf; Kirrie J. Ballard; Richard A. Schmidt (August 2008). "Principles of Motor Learning in Treatment of Motor Speech Disorders". American Journal of Speech-Language Pathology. 17 (3): 277–298. doi:10.1044/1058-0360(2008/025). PMID 18663111. S2CID 2981254.
* DeBonis, David A.; Deborah Moncrieff (February 2008). "Auditory Processing Disorders: An Update for Speech-Language Pathologists". American Journal of Speech-Language Pathology. 17 (1): 4–18. doi:10.1044/1058-0360(2008/002). PMID 18230810. S2CID 1520146.
* "Discussion Meeting Issue 'Language in developmental and acquired disorders: converging evidence for models of language representation in the brain' - Table of Contents". Royal Society Publishing. 2014. Retrieved 31 December 2013.
* Schlosser, Ralf W.; Oliver Wendt (August 2008). "Effects of Augmentative and Alternative Communication Intervention on Speech Production in Children With Autism: A Systematic Review". American Journal of Speech-Language Pathology. 17 (3): 212–230. doi:10.1044/1058-0360(2008/021). PMID 18663107. S2CID 25959320.
* Clark, Heather M. (November 2003). "Neuromuscular Treatments for Speech and Swallowing". American Journal of Speech-Language Pathology. 12 (4): 400–415. doi:10.1044/1058-0360(2003/086). PMID 14658992.
## External links[edit]
Wikimedia Commons has media related to Speech and language impairment.
* American Speech-Language-Hearing Association
* American Academy of Audiology
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* Canadian Association of Speech-Language Pathologists & Audiologists
* Controversial Practices in Children's Speech Sound Disorders - Oral Motor Exercises, Dietary Supplements, Auditory Integration Training
* Apraxia-Kids Glossary of Common Acronyms and Abbreviations
* National Aphasia Association
* National Association of Special Education Teachers: Speech and Language Impairment
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*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Speech and language impairment | None | 6,607 | wikipedia | https://en.wikipedia.org/wiki/Speech_and_language_impairment | 2021-01-18T19:01:59 | {"wikidata": ["Q5356302"]} |
Baller-Gerold syndrome is characterized by the association of coronal craniosynostosis with radial ray anomalies (oligodactyly, aplasia or hypoplasia of the thumb, aplasia or hypoplasia of the radius).
## Epidemiology
Around 30 cases have been reported but the prevalence of the syndrome is unknown.
## Clinical description
Craniosynostosis and radial ray anomalies present at birth and are associated with facial dysmorphism (brachycephaly, ocular exophthalmia, frontal bossing, nasal hypoplasia, small mouth, ogival palate). An inconstant poikiloderma can appear during the first months of life. Delayed growth is nearly always present, usually around -4SD. Patellar aplasia or hypoplasia can be observed during childhood. Intelligence is usually normal. Patients have a predisposition to cancer, in particular osteosarcoma.
## Etiology
Baller-Gerold syndrome is secondary to mutations of the RECQL4 gene (8q24.3). RECQL4 is a member of the RecQ helicase gene family which cause other diseases predisposing to cancer. The proportion of patients with mutations in this gene has not been determined.
## Diagnostic methods
Diagnosis of Baller-Gerold syndrome relies on clinical criteria. Given the numerous differential diagnoses, finding a mutation of the RECQL4 gene can help clarify the diagnosis spectrum, genetic counseling and management.
## Differential diagnosis
The principal differential diagnoses include Rothmund-Thomson syndrome (RTS) and RAPADILINO syndrome, also secondary to mutations of the RECQL4 gene (see these terms). A phenotypic continuum between these diseases has been suggested by numerous authors: it is possible that they represent different expressions of the same pathology. Other differential diagnoses include Roberts syndrome and Fanconi anemia, which are frequently associated with radial ray anomalies but rarely with craniosynostosis, and Saethre-Chotzen syndrome which is characterized by coronal craniosynostosis usually without radial ray anomalies (see these terms). The combinationof craniosynostosis and radial ray hypoplasia is also associated with fetal valproic syndrome (see this term). The presence of poikiloderma allows other pathologies to be excluded.
## Antenatal diagnosis
Prenatal diagnosis by chorionic villus sampling (CVS) is suggested when pathogenic mutations of the RECQL4 gene are found in an index case (homozygous or heterozygous). Ultrasound can be used to identify limb anomalies and an abnormally shaped cranium.
## Genetic counseling
Baller-Gerold syndrome is inherited in an autosomal recessive manner.
## Management and treatment
Treatment consists of surgery of the bilateral craniosynostosis in the first 6 months of life and, if necessary, pollicization of the index finger for thumb reconstruction. When monitoring patients particular clinical attention should be paid to bone pain, limpness or fractures, because of the risk of osteosarcoma. Exposure to the sun should be avoided because of a risk of skin cancer and photosensitivity.
## Prognosis
The prognosis for patients with mutations of the RECQL4 gene, homozygous or heterozygous, is related to an increased risk of cancer.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Baller-Gerold syndrome | c0265308 | 6,608 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1225 | 2021-01-23T19:08:37 | {"gard": ["1602"], "mesh": ["C536788"], "omim": ["218600"], "umls": ["C0265308"], "icd-10": ["Q75.0"]} |
Meckel syndrome
Other namesMeckel–Gruber syndrome, Gruber syndrome, Dysencephalia splanchnocystica
Embryos with mutation in MKS1KRC, a cause of Meckel syndrome.
SpecialtyMedical genetics
Meckel-Gruber syndrome is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (post axial), hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.
Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber.[1][2][3]
## Contents
* 1 Pathophysiology
* 1.1 Relation to other rare genetic disorders
* 2 Diagnosis
* 3 Management
* 4 Prognosis
* 5 Incidence
* 6 References
* 7 External links
## Pathophysiology[edit]
Meckel–Gruber syndrome (MKS) is an autosomal recessive lethal malformation. Recently, two MKS genes, MKS1 and MKS3, have been identified. A study done recently has described the cellular, sub-cellular and functional characterization of the novel proteins, MKS1 and meckelin, encoded by these genes.[4] The malfunction of this protein production is mainly responsible for this lethal disorder.[citation needed]
Type OMIM Gene
MKS1 609883 MKS1
MKS2 603194 TMEM216
MKS3 607361 TMEM67
MKS4 611134 CEP290
MKS5 611561 RPGRIP1L
MKS6 612284 CC2D2A
MKS7 608002 NPHP3
MKS8 613846 TCTN2
MKS9 614144 B9D1
MKS10 611951 B9D2
### Relation to other rare genetic disorders[edit]
Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Meckel–Gruber syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, and some forms of retinal degeneration.[5] The MKS1 gene has been identified as being associated with a ciliopathy.[6]
## Diagnosis[edit]
Dysplastic kidneys are prevalent in over 95% of all identified cases. When this occurs, microscopic cysts develop within the kidney and slowly destroy it, causing it to enlarge to 10 to 20 times its original size. The level of amniotic fluid within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.[citation needed]
Occipital encephalocele is present in 60% to 80% of all cases, and post-axial polydactyly is present in 55% to 75% of the total number of identified cases. Bowing or shortening of the limbs are also common.[citation needed]
Finding at least two of the three phenotypic features of the classical triad, in the presence of normal karyotype, makes the diagnosis solid. Regular ultrasounds and pro-active prenatal care can usually detect symptoms early on in a pregnancy.[citation needed]
## Management[edit]
There is no cure to the disease. Treatment is symptomatic and to make the baby as comfortable as possible.[7]
## Prognosis[edit]
The disease is lethal. Most infants that are not stillborn with Meckel syndrome die within hours to days of birth.[8] The longest survival time reported in medical literature is 28 months.[9]
## Incidence[edit]
While not precisely known, it is estimated that the general rate of incidence, according to Bergsma,[10] for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births.[11]
This syndrome is a Finnish heritage disease. Its frequency is much higher in Finland, where the incidence is as high as 1.1 per 10,000 births. It is estimated that Meckel syndrome accounts for 5% of all neural tube defects there.[12]The Leicestershire Perinatal Mortality Survey for the years 1976 to 1982 had found high incidences of Meckel syndrome in Gujarati Indian immigrants.[13]
## References[edit]
1. ^ synd/2055 at Who Named It?
2. ^ J. F. Meckel. Beschreibung zweier durch sehr ähnliche Bildungsabweichungen entstellter Geschwister. Deutsches Archiv für Physiologie, 1822, 7: 99–172.
3. ^ G. B. Gruber. Beiträge zur Frage "gekoppelter" Missbildungen (Akrocephalossyndactylie und Dysencephalia splancnocystica. Beitr path Anat, 1934, 93: 459–476.
4. ^ Dawe HR, Smith UM, Cullinane AR, Gerrelli D, Cox P, Badano JL, Blair-Reid S, Sriram N, Katsanis N, Attie-Bitach T, Afford SC, Copp AJ, Kelly DA, Gull K, Johnson CA (2007). "The Meckel–Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation". Human Molecular Genetics. 16 (2): 173–186. doi:10.1093/hmg/ddl459. PMID 17185389.
5. ^ Badano, Jose L.; Norimasa Mitsuma; Phil L. Beales; Nicholas Katsanis (Sep 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics. 7: 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803.
6. ^ Kyttälä, Mira (May 2006). "Identification of the Meckel Syndrome Gene (MKS1) Exposes a Novel Ciliopathy" (PDF). National Public Health Institute, Helsinki. Archived from the original (PDF) on 2006-07-21. Retrieved 2008-07-06. Cite journal requires `|journal=` (help)
7. ^ "Meckel Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2019-12-02.
8. ^ Kheir, Abdelmoneim E. M.; Imam, Abdelmutalab; Omer, Ilham M.; Hassan, Ibtsama M.A.; Elamin, Sara A.; Awadalla, Esra A.; Gadalla, Mohammed H.; Hamdoon, Tagwa A. (2012). "Meckel-Gruber syndrome: A rare and lethal anomaly". Sudanese Journal of Paediatrics. 12 (1): 93–96. ISSN 0256-4408. PMC 4949827. PMID 27493335.
9. ^ Barisic, Ingeborg; Boban, Ljubica; Loane, Maria; Garne, Ester; Wellesley, Diana; Calzolari, Elisa; Dolk, Helen; Addor, Marie-Claude; Bergman, Jorieke EH; Braz, Paula; Draper, Elizabeth S (June 2015). "Meckel–Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe". European Journal of Human Genetics. 23 (6): 746–752. doi:10.1038/ejhg.2014.174. ISSN 1018-4813. PMC 4795048. PMID 25182137.
10. ^ Bergsma, D. (1979). "Birth Defects". Atlas and Compendium. London: Macmillan Press.
11. ^ Salonen, R.; Norio, R.; Reynolds, James F. (1984). "The Meckel syndrome: Clinicopathological Findings in 67 Patients". American Journal of Medical Genetics. 18 (4): 671–689. doi:10.1002/ajmg.1320180414. PMID 6486167.
12. ^ Nyberg, D. A.; et al. (1990). "Meckel–Gruber syndrome; Importance of Prenatal Diagnosis". Journal of Ultrasound in Medicine. 9 (12): 691–696. doi:10.7863/jum.1990.9.12.691. PMID 2277397. S2CID 25658017.
13. ^ Young, I. D.; Rickett, A. B.; Clarke, M. (1985-08-01). "High incidence of Meckel's syndrome in Gujarati Indians". Journal of Medical Genetics. 22 (4): 301–304. doi:10.1136/jmg.22.4.301. ISSN 0022-2593. PMC 1049454. PMID 4045959.
## External links[edit]
Classification
D
* ICD-10: Q61.9
* OMIM: 249000
* DiseasesDB: 31662
External resources
* eMedicine: ped/1390
* v
* t
* e
Congenital malformations and deformations of urinary system
Abdominal
Kidney
* Renal agenesis/Potter sequence, Papillorenal syndrome
* cystic
* Polycystic kidney disease
* Meckel syndrome
* Multicystic dysplastic kidney
* Medullary sponge kidney
* Horseshoe kidney
* Renal ectopia
* Nephronophthisis
* Supernumerary kidney
* Pelvic kidney
* Dent's disease
* Alport syndrome
Ureter
* Ectopic ureter
* Megaureter
* Duplicated ureter
Pelvic
Bladder
* Bladder exstrophy
Urethra
* Epispadias
* Hypospadias
* Posterior urethral valves
* Penoscrotal transposition
Vestigial
Urachus
* Urachal cyst
* Urachal fistula
* Urachal sinus
* v
* t
* e
Diseases of cilia
Structural
* receptor: Polycystic kidney disease
* cargo: Asphyxiating thoracic dysplasia
* basal body: Bardet–Biedl syndrome
* mitotic spindle: Meckel syndrome
* centrosome: Joubert syndrome
Signaling
* Nephronophthisis
Other/ungrouped
* Alström syndrome
* Primary ciliary dyskinesia
* Senior–Løken syndrome
* Orofaciodigital syndrome 1
* McKusick–Kaufman syndrome
* Autosomal recessive polycystic kidney
See also: ciliary proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Meckel–Gruber syndrome | c0311245 | 6,609 | wikipedia | https://en.wikipedia.org/wiki/Meckel%E2%80%93Gruber_syndrome | 2021-01-18T18:59:12 | {"gard": ["3436"], "umls": ["C0311245"], "orphanet": ["564"], "wikidata": ["Q1915681"]} |
A number sign (#) is used with this entry because of evidence that epidermolysis bullosa simplex (EBS) with migratory circinate erythema can be caused by mutation in the keratin-5 gene (KRT5; 148040).
Clinical Features
Gu et al. (2003) described a form of epidermolysis bullosa simplex that was milder than the Dowling-Meara phenotype (131760) but involved an unusual migratory circinate erythema with multiple vesicles on the area affected by the erythema. The lesions, which appeared from birth primarily on the hands, feet, and legs but spared the nails, ocular epithelia, and mucosae, healed with brown pigmentation but no scarring. Electron microscopy findings were distinct from those seen in the Dowling-Meara type of EBS, with no evidence of tonofilament clumping.
Molecular Genetics
In an affected Japanese girl and affected members of an unrelated Korean family, Gu et al. (2003) identified heterozygosity for a 1649delG mutation in the KRT5 gene (148040.0017). The mutation was assumed to have arisen de novo in the Japanese girl. When a younger sister with EBS was born and was found to have the same 1649delG mutation as her older sib, Nagao-Watanabe et al. (2004) reinvestigated the familial segregation of the mutation and identified heterozygosity for the deletion in the mother's DNA from hair bulb and buccal cell samples. Closer scrutiny of the mother's history revealed that she had migratory circinate pigmentation of the skin in childhood, and Nagao-Watanabe et al. (2004) concluded that this represented maternal somatic and germline mosaicism.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| EPIDERMOLYSIS BULLOSA SIMPLEX WITH MIGRATORY CIRCINATE ERYTHEMA | c1836284 | 6,610 | omim | https://www.omim.org/entry/609352 | 2019-09-22T16:06:16 | {"mesh": ["C563730"], "omim": ["609352"], "orphanet": ["158681"]} |
Olfactory reference syndrome (ORS) is a psychiatric condition in which there is a persistent false belief and preoccupation with the idea of emitting abnormal body odors which the patient thinks are foul and offensive to other individuals.[1][2] People with this condition often misinterpret others' behaviors, e.g. sniffing, touching nose or opening a window, as being referential to an unpleasant body odor which in reality is non-existent and can not be detected by other people.[3]
This disorder is often accompanied by shame, embarrassment, significant distress, avoidance behavior, social phobia and social isolation.[4]
## Contents
* 1 Signs and symptoms
* 1.1 Odor complaint
* 1.2 Referential ideas
* 1.3 Repetitive behavior
* 1.4 Functional impairment
* 1.5 Psychiatric co-morbidity
* 2 Causes
* 3 Diagnosis
* 3.1 Classification
* 3.2 Diagnostic criteria
* 3.3 Differential diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 History
* 8 Society
* 9 Etymology
* 10 References
## Signs and symptoms[edit]
The onset of ORS may be sudden, where it usually follows after a precipitating event, or gradual.[1]
### Odor complaint[edit]
The defining feature of ORS is excessive thoughts of having offensive body odor(s) which are detectable to others. The individual may report that the odor comes from: the nose and/or mouth, i.e. halitosis (bad breath); the anus; the genitals; the skin generally; or specifically the groin, armpits or feet. The source(s) of the supposed odor may also change over time.[1] There are also some who are unsure of the exact origin of the odor.[1] The odor is typically reported to be continuously present.[1] The character of the odor may be reported as similar to bodily substances, e.g. feces, flatus, urine, sweat, vomitus, semen, vaginal secretions; or alternatively it may be an unnatural, non-human or chemical odor, e.g. ammonia,[5] detergent,[5] rotten onions,[5] burnt rags,[1] candles,[1] garbage,[2] burning fish,[2] medicines,[2] old cheese.[2] Again, the reported character of the odor complaint may change over time.[1] Halitosis appears to be the most common manifestation of ORS,[6] with 75% complaining of bad breath, alone or in combination with other odors.[7] The next most common complaint was sweat (60%).[7]
Although all individuals with ORS believe they have an odor, in some cases the individual reports they cannot perceive the odor themselves. In the latter cases, the belief arises via misinterpretation of the behavior of others or with the rationale that a disorder of smell which prevents self detection of the odor (i.e. anosmia) exists. In the cases where the non-existent odor can be detected, this is usually considered as phantosmia (olfactory hallucination). Olfactory hallucination can be considered the result of the belief in an odor delusion, or the belief a result of the olfactory hallucination.[1] In one review, the individual with ORS was unreservedly convinced that he or she could detect the odor themselves in 22% of cases, whilst in 19% there was occasional or intermittent detection and in 59% lack of self-detection was present.[2]
Some distinguish delusional and non-delusional forms of ORS. In the delusional type, there is complete conviction that the odor is real. In the non-delusional type, the individual is capable of some insight into the condition, and can recognize that the odor might not be real, and that their level of concern is excessive.[5] Others argue that reported cases of ORS present a spectrum of different levels of insight.[2] Since sometimes the core belief of ORS is not of delusional intensity, it is argued that considering the condition as a form of delusional disorder, as seems to occur in the DSM, is inappropriate.[2] In one review, in 57% of cases the beliefs were fixed, held with complete conviction, and the individual could not be reassured that the odor was non existent. In 43% of cases the individual held the beliefs with less than complete conviction, and was able to varying degrees to consider the possibility that the odor was not existent.[2]
Other symptoms may be reported and are claimed to be related to the cause of the odor, such as malfunction of the anal sphincter, a skin disease, "diseased womb", stomach problems or other unknown organic disease.[1] Excessive washing in ORS has been reported to cause the development of eczema.[1]
### Referential ideas[edit]
People with ORS misinterpret the behavior of others to be related to the imagined odor (thoughts of reference). In one review, ideas of reference were present in 74% of cases.[2] Usually, these involve misinterpretations of comments, gestures and actions of other people such that it is believed that an offensive smell from the individual is being referred to.[2] These thoughts of reference are more pronounced in social situations which the individual with ORS may find stressful, such as public transport, crowded lift, workplace, classroom, etc.[2] Example behaviors which are misinterpreted include coughing, sneezing, turning of the head, opening a window, facial expressions, sniffing, touching nose, scratching head, gestures, moving away, avoiding the person, whistling.[2] Commonly, when being in proximity to others who are talking among themselves, persons with ORS will be convinced that the conversation is about his or her odor. Even the actions of animals (e.g. barking of dogs) can be interpreted as referential to an odor.[2] Persons with ORS may have trouble concentrating at a given task or in particular situations due to obsessive thoughts concerning body odor.
### Repetitive behavior[edit]
95% of persons with ORS engage in at least one excessive hygiene, grooming or other related repetitive practice in an attempt to alleviate, mask and monitor the perceived odor.[8][9] This has been described as a contrite reaction,[2] and repetitive, counterphobic, "safety", ritual or compulsive behaviors.[1][8] Despite these measures, the odor symptom is reported to still offend other people.[1] Example ORS behaviors include: repetitive showering and other grooming behaviors,[9] excessive tooth brushing,[9] or tongue scraping (a treatment for halitosis), repeated smelling of oneself to check for any odor,[5] over-frequent bathroom use,[1] attempts to mask the odor,[5] with excessive use of deodorants, perfumes, mouthwash, mint, chewing gum, scented candles, and soap;[1] changing clothes (e.g. underwear),[10] multiple times per day,[2] frequent washing of clothes, wearing several layers of clothing, wrapping feet in plastic,[1] wearing garments marketed as odor-reducing,[1] eating special diets, dietary supplements (e.g. intended to reduce flatulence odor),[1][10] repeatedly seeking reassurance from others that there is no odor, although the negative response is usually interpreted instead as politeness rather than truth,[1] and avoidance behaviors such habitually sitting at a distance from others, minimizing movement in an attempt "not to spread the odor", keeping the mouth closed and avoiding talking or talking with a hand in front of the mouth.[1]
### Functional impairment[edit]
Persons with ORS tend to develop a behavior pattern of avoidance of social activities and progressive social withdrawal. They often avoid travel, dating, relationships, break off engagements and avoid family activities.[8] Due to shame and embarrassment, they may avoid school or work, or repeatedly change jobs and move to another town.[8] Significant developments may occur such as loss of employment,[10] divorce, becoming housebound, psychiatric hospitalization, and suicide attempts.[8] According to some reports, 74% of persons with ORS avoid social situations,[5] 47% avoid work, academic or other important activities,[5] 40% had been housebound for at least once week because of ORS,[5] and 31.6% had experienced psychiatric hospitalization.[5] With regards suicide, reports range from 43-68% with suicidal ideation, and 32% with a history of at least one suicide attempt. 5.6% died by suicide.[5][8]
### Psychiatric co-morbidity[edit]
Psychiatric co-morbidity in ORS is reported. Depression, which is often severe, may be a result of ORS, or may be pre-existing.[1] Personality disorders, especially cluster C, and predominantly the avoidant type, may exist with ORS.[10] Bipolar disorder, schizophrenia, hypochondriasis, alcohol or drug abuse and obsessive compulsive disorder may also be co-morbid with ORS.[1]
## Causes[edit]
The causes of ORS are unknown.[10] It is thought that significant negative experiences may trigger the development of ORS. These have been considered as two types: key traumatic experiences related to smell, and life stressors present when the condition developed but which were unrelated to smell.[2] In one review, 85% of reported cases had traumatic, smell-related experiences, and 17% of cases had stress factors unrelated to smell.[2] Reported smell-related experiences usually revolve around family members, friends, co-workers, peers or other people making comments about an odor from the person, which causes embarrassment and shame.[2] Examples include accusation of flatulence during a religious ceremony,[10] or being bullied for flatulence such at school,[2] accidental urination in class,[10] announcements about a passenger needing to use deodorant over speaker by a driver on public transport,[10] sinusitis which caused a bad taste in the mouth,[2] mockery about a fish odor from a finger which had been inserted into the person's vagina in the context of a sexual assault,[10] and revulsion about menarche and brother's sexual intimacy.[2] It has been suggested that a proportion of such reported experiences may not have been real, but rather early symptom of ORS (i.e. referential thoughts).[11] Examples of non smell-related stressful periods include guilt due to a romantic affair,[2] being left by a partner,[2] violence in school,[2] family illness when growing up (e.g. cancer),[2] and bullying.[2]
The importance of a family history of mental illness or other conditions in ORS is unclear,[1] because most reported cases have lacked this information.[2] In some cases, there has been reported psychiatric and medical conditions in first degree relatives such as schizophrenia,[1] psychosis,[2] alcoholism,[1] suicide,[1] affective disorders,[1] obsessive compulsive disorder,[1] anxiety,[2] paranoia,[1] neurosis,[2] sociopathy,[2] and epilepsy.[1] Sometimes more than one family member had a noteworthy condition.[2]
Neuroimaging has been used to investigate ORS. Hexamethylpropyleneamine oxime single-photon emission computed tomography (HMPAO SPECT) demonstrated hypoperfusion of the frontotemporal lobe in one case.[10] That is to say, part of the brain was receiving insufficient blood flow. In another, functional magnetic resonance imaging was carried out while the person with ORS listened to both neutral words and emotive words. Compared to an age and sex matched healthy control subject under the same conditions, the individual with ORS showed more activation areas in the brain when listening to emotionally loaded words. This difference was described as abnormal, but less pronounced as would be observed in the brain of a person with a psychotic disorder.[10]
## Diagnosis[edit]
### Classification[edit]
Although the existence of ORS is generally accepted,[2][10] there is some controversy as to whether it is a distinct condition or merely a part or manifestation of other psychiatric conditions, mainly due to the overlapping similarities.[4] Similarly, there is controversy with regards how the disorder should be classified.[2][5] As ORS has obsessive and compulsive features, some consider it as a type of obsessive compulsive spectrum disorder, while others consider it an anxiety disorder due to the strong anxiety component. It is also suggested to be a type of body dysmorphic disorder or, as it involves a single delusional belief, some suggest that ORS is a monosymptomatic hypochondriacal psychosis (hypochondriacal type of delusional disorder, see monothematic delusion).[2][5]
The World Health Organization's 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) does not have a specific entry for ORS,[5] or use the term, but in the "persistent delusional disorders" section, states delusions can "express a conviction that others think that they smell."[5]
ORS has also never been allocated a dedicated entry in any edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders.[5] In the third edition (DSM-III), ORS was mentioned under "atypical somatoform disorders".[2] The revised third edition (DSM-III-R) mentions ORS in the text, stating: "convictions that the person emits a foul odor are one of the most common types of delusion disorder, somatic type."[5] The fourth edition (DSM-IV), does not use the term ORS[5] but again mentions such a condition under "delusional disorder, somatic type",[2] stating "somatic delusions can occur in several forms. Most common are the person's conviction that he or she emits a foul odor from the skin, mouth, rectum or vagina."[5] In the fifth edition (DSM-5), ORS again does not appear as a distinct diagnosis, but it is mentioned in relation to taijin kyōfushō (対人恐怖症, "disorder of fear of personal interaction").[12] The variants of taijin kyōfushō (shubo-kyofu "the phobia of a deformed body" and jikoshu-kyofu "fear of foul body odor") are listed under 300.3 (F42) "other specified obsessive compulsive and related disorders",[12] and is about someone's fear that his or her body, or its functions, is offensive to other people.[4] There are four subtypes of taijin kyōfushō.[13] 17% of these individuals suffer from "the phobia of having foul body odor", the subtype termed jikoshu-kyofu.[5][13] Although taijin kyōfushō has been described as a culture-bound syndrome confined to east Asia (e.g. Japan and Korea),[4][5] it has been suggested that the jikoshu-kyofu variant of taijin kyōfushō is closely related or identical to ORS,[4][10] and that such a condition occurs in other cultures.[12] However, some Western sources state that jikoshu-kyofu and ORS are distinguishable because of cultural differences, i.e. Western culture being primarily concerned with individual needs, and Japanese culture primarily with the needs of the many. Hence, it is claimed that ORS mainly focuses on the affected individual's embarrassment, and jikoshu-kyofu is focused on the fear of creating embarrassment in others. In this article, jikoshu-kyofu and ORS are considered as one condition.
Synonyms for ORS, many historical, include bromidrosiphobia,[2] olfactory phobic syndrome,[2] chronic olfactory paranoid syndrome,[2] autodysomophobia,[2] delusions of bromosis,[5] hallucinations of smell[5] and olfactory delusional syndrome.[citation needed] By definition, the many terms which have been suggested in the dental literature to refer to subjective halitosis complaints (i.e. where a person complains of halitosis yet no odor is detectable clinically) can also be considered under the umbrella of ORS. Examples include halitophobia,[11] non-genuine halitosis, delusional halitosis,[11] pseudo-halitosis, imaginary halitosis,[8] psychosomatic halitosis, and self halitosis.[citation needed]
### Diagnostic criteria[edit]
Diagnostic criteria have been proposed for ORS:[2][10][11]
* Persistent (> six months), false belief that one emits an offensive odor, which is not perceived by others. There may be degrees of insight (i.e. the belief may or may not be of delusional intensity).
* This pre-occupation causes clinically significant distress (depression, anxiety, shame), social and occupational disability, or may be time-consuming (i.e. preoccupies the individual at least one hour per day).
* The belief is not a symptom of schizophrenia or other psychotic disorder, and not due to the effects of medication or recreational drug abuse, or any other general medical condition.
### Differential diagnosis[edit]
The differential diagnosis for ORS may be complicated as the disorder shares features with other conditions. Consequently, ORS may be misdiagnosed as another medical or psychiatric condition and vice versa.
The typical history of ORS involves a long delay while the person continues to believe there is a genuine odor. On average, a patient with ORS goes undiagnosed for about eight years.[10] Repeated consultation with multiple different non-psychiatric medical specialists ("doctor shopping") in an attempt to have their non-existent body odor treated is frequently reported.[2] Individuals with ORS may present to dermatologists,[14] gastroentrologists,[1] otolaryngologists,[10] dentists,[10] proctologists,[8] and gynecologists. Despite the absence of any clinically detectable odor, physicians and surgeons may embark on unnecessary investigations (e.g. gastroscopy),[11] and treatments, including surgery such as thoracic sympathectomy, tonsillectomy, etc. Such treatments generally have no long-term effect on the individual's belief in an odor symptom.[1] If non-psychiatric clinicians refuse to carry out treatment on the basis that there is no real odor and offer to refer them to a psychologist or psychiatrist, persons with ORS typically refuse and instead seek "a better" doctor/dentist.[1][15]
Conversely, some have suggested that medical conditions which cause genuine odor may sometimes be misdiagnosed as ORS.[16] There are a great many different medical conditions which are reported to potentially cause a genuine odor, and these are usually considered according to the origin of the odor, e.g. halitosis (bad breath), bromhidrosis (body odor), etc.[17][18][19][20][21][22][23] These conditions are excluded before a diagnosis of ORS is made.[4] Although there are a multitude of different publications on topics like halitosis, the symptom is still poorly understood and managed in practice.[24] It is recognized that symptoms such as halitosis can be intermittent, and therefore may not be present at the time of the consultation, leading to misdiagnosis.[6] Individuals with genuine odor symptoms may present with similar mindset and behavior to persons with ORS. For example, one otolaryngologist researcher noted "behavioral problems such as continuous occupation with oral hygiene issues, obsessive use of cosmetic breath freshening products such as mouthwashes, candies, chewing gums, and sprays, avoiding close contact with other people, and turning the head away during conversation" as part of what was termed "skunk syndrome" in patients with genuine halitosis secondary to chronic tonsillitis.[25] Another author, writing about halitosis, noted that there are generally three types of persons that complain of halitosis: those with above average odor, those with average or near-average odor who are oversensitive, and those with below average or no odor who believe they have offensive breath. Therefore, in persons with genuine odor complaints, the distress and concern may typically be out of proportion to the reality of the problem.[6] Genuine halitosis has been described as a social barrier between the individual and friends, relatives, partners and colleagues, and may negatively alter self-esteem and quality of life.[26] Similar psychosocial problems are reported in other conditions which cause genuine odor symptoms.[27][28] In the literature on halitosis, emphasis is frequently placed on multiple consultations to reduce the risk of misdiagnosis, and also asking the individual to have a reliable confidant accompany them to the consultation who can confirm the reality of the reported symptom. ORS patients are unable to provide such confidants as they have no objective odor.[6][15]
Various organic diseases may cause parosmias (distortion of the sense of smell). Also, since smell and taste are intimately linked senses, disorders of gustation (e.g. dysgeusia\- taste dysfunction) can present as a complaint related to smell, and vice versa. These conditions, collectively termed chemosensory dysfunctions, are many and varied, and they may trigger a person to complain of an odor than is not present,[29] however the diagnostic criteria for ORS require the exclusion of any such causes.[4] They include pathology of the right hemisphere of the brain,[4] substance abuse,[10] arteriovenous malformations in the brain,[10] and temporal lobe epilepsy.[10]
Social anxiety disorder (SAD) and ORS have some demographic and clinical similarities.[10] Where the social anxiety and avoidance behavior is primarily focussed on concern about body odors, ORS is a more appropriate diagnosis than avoidant personality disorder or SAD.[4] Body dismorphic disorder (BDD) has been described as the closest diagnosis in DSM-IV to ORS as both primarily focus on bodily symptoms.[4] The defining difference between the two is that in BDD the preoccupation is with physical appearance not body odors.[4] Similarly, where obsessive behaviors are directly and consistently related to body odors rather than anything else, ORS is a more appropriate diagnosis than obsessive compulsive disorder, in which obsessions are different and multiple over time.[4]
ORS may be misdiagnosed as schizophrenia.[2][5] About 13% of schizophrenics have olfactory hallucinations.[10] Generally, schizophrenic hallucinations are perceived as having an imposed, external origin, while in ORS they are recognized as originating from the individual.[10] The suggested diagnostic criteria mean that the possibility of ORS is negated by a diagnosis of schizophrenia in which persistent delusions of an offensive body odor and olfactory hallucinations are contributing features for criterion A.[7] However, some reported ORS cases were presented as co-morbid.[1] Indeed, some have suggested that ORS may in time transform into schizophrenia, but others state there is little evidence for this.[1] Persons with ORS have none of the other criteria to qualify for a diagnosis of schizophrenia.[4]
It has been suggested that various special investigations may be indicated to help rule out some of the above conditions. Depending upon the case, this might include neuroimaging, thyroid and adrenal hormone tests, and analysis of body fluids (e.g. blood) with gas chromatography.[4]
## Treatment[edit]
There is no agreed treatment protocol.[10] In most reported cases of ORS the attempted treatment was antidepressants, followed by antipsychotics and various psychotherapies.[10] Little data are available regarding the efficacy of these treatments in ORS, but some suggest that psychotherapy yields the highest rate of response to treatment, and that antidepressants are more efficacious than antipsychotics (response rates 78%, 55% and 33% respectively).[1] According to one review, 43% of cases which showed overall improvement required more than one treatment approach, and in only 31% did the first administered treatment lead to some improvement.[10]
Pharmacotherapies that have been used for ORS include antidepressants,[10] (e.g. selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors), antipsychotics, (e.g. blonanserin,[10] lithium,[10] chlorpromazine),[6] and benzodiazepines.[10] The most common treatment used for ORS is SSRIs. Specific antidepressants that have been used include clomipramine.[4]
Psychotherapies that have been used for ORS include cognitive behavioral therapy, eye movement desensitization and reprocessing.[4] Dunne (2015) reported a Case Study treatment of ORS using EMDR which was successful using a trauma model formulation rather than an OCD approach.
## Prognosis[edit]
When untreated, the prognosis for ORS is generally poor. It is chronic, lasting many years or even decades with worsening of symptoms rather than spontaneous remission.[1] Transformation to another psychiatric condition is unlikely, although very rarely what appears to be ORS may later manifest into schizophrenia,[1] psychosis,[2] mania,[2] or major depressive disorder.[2] The most significant risk is suicide.
When treated, the prognosis is better. In one review, the proportion of treated ORS cases which reported various outcomes were assessed. On average, the patients were followed for 21 months (range: two weeks to ten years). With treatment, 30% recovered (i.e. no longer experienced ORS odor beliefs and thoughts of reference), 37% improved and in 33% there was a deterioration in the condition (including suicide) or no change from the pre-treatment status.[2]
## Epidemiology[edit]
Cases have been reported from many different countries around the world. It is difficult to estimate the prevalence of ORS in the general population because data are limited and unreliable,[10] and due to the delusional nature of the condition and the characteristic secrecy and shame.[1]
For unknown reasons, males appear to be affected twice as commonly as females.[1] High proportions of ORS patients are unemployed, single,[1] and not socially active.[11] The average age reported is around 20–21 years,[2][8] with almost 60% of cases occurring in subjects under 20 in one report,[2] although another review reported an older average age for both males (29) and females (40).[10]
## History[edit]
The term olfactory reference syndrome was first proposed in 1971 by William Pryse-Phillips.[30] Prior to this, published descriptions of what is now thought to be ORS appear from the late 1800s,[5] with the first being Potts 1891.[2] Often the condition was incorrectly described as other conditions, e.g. schizophrenia.[5]
## Society[edit]
In modern times, commercial advertising pressures have altered the public's attitude towards problems such as halitosis,[6] which have taken on greater negative psychosocial sequelae as a result. For example, in the United States, a poll reported that 55–75 million citizens consider bad breath a "principal concern" during social encounters.[6]
## Etymology[edit]
The term olfactory reference syndrome comes from:
* Olfactory, pertaining to the sense of smell.
* Reference, because of the belief that the behavior of others is referential to a supposed odor.
* Syndrome, because it is a recognizable set of features that occur together.
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao Phillips KA, Gunderson C, Gruber U, Castle D (2006). "Delusions of body malodour: the olfactory reference syndrome." (PDF). In Brewer WJ, Castle D, Pantelis C (eds.). Olfaction and the brain. Cambridge: Cambridge University Press. pp. 334–353. ISBN 978-0-521-84922-7. Archived from the original (PDF) on 2014-01-08.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az Begum, M; McKenna, PJ (Mar 2011). "Olfactory reference syndrome: a systematic review of the world literature". Psychological Medicine. 41 (3): 453–61. doi:10.1017/S0033291710001091. PMID 20529415.
3. ^ Feusner, Jamie D.; Phillips, Katharine A.; Stein, Dan J. (2010). "Olfactory Reference Syndrome: Issues for DSM-V". Depression and Anxiety. 27 (6): 592–599. doi:10.1002/da.20688. ISSN 1091-4269. PMC 4247225. PMID 20533369.
4. ^ a b c d e f g h i j k l m n o p Lochner, C; Stein, DJ (Oct–Dec 2003). "Olfactory reference syndrome: diagnostic criteria and differential diagnosis". Journal of Postgraduate Medicine. 49 (4): 328–31. PMID 14699232.
5. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Feusner, JD; Phillips, KA; Stein, DJ (Jun 2010). "Olfactory reference syndrome: issues for DSM-V" (PDF). Depression and Anxiety. 27 (6): 592–9. doi:10.1002/da.20688. PMC 4247225. PMID 20533369.
6. ^ a b c d e f g Richter, JL (Apr 1996). "Diagnosis and treatment of halitosis". Compendium of Continuing Education in Dentistry. 17 (4): 370–2, 374–6 passim, quiz 388. PMID 9051972.
7. ^ a b c Phillips, KA; Menard, W (Jul–Aug 2011). "Olfactory reference syndrome: demographic and clinical features of imagined body odor". General Hospital Psychiatry. 33 (4): 398–406. doi:10.1016/j.genhosppsych.2011.04.004. PMC 3139109. PMID 21762838.
8. ^ a b c d e f g h i Phillips KA, Castle DJ (2007). "How to help patients with olfactory reference syndrome" (PDF). Current Psychiatry. 6 (3). Archived from the original (PDF) on 2015-05-11.
9. ^ a b c Feusner, JD; Hembacher, E; Phillips, KA (Sep 2009). "The mouse who couldn't stop washing: pathologic grooming in animals and humans". CNS Spectrums. 14 (9): 503–13. doi:10.1017/S1092852900023567. PMC 2853748. PMID 19890232.
10. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af Arenas, B; Garcia, G; Gómez, J; Renovell, M; García, V; Olucha-Bordonau, FE; Sanjuán, J (Jan 16, 2013). "[Olfactory reference syndrome: a systematic review]". Revista de Neurología. 56 (2): 65–71. doi:10.33588/rn.5602.2012555. PMID 23307351.
11. ^ a b c d e f Nir Sterer; Mel Rosenberg (2011). Breath odors origin, diagnosis, and management. Berlin: Springer. pp. 89–90. ISBN 978-3-642-19312-5.
12. ^ a b c Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA: Amer. Psychiatric Pub. Incorporated. 2013. pp. 263–264, 837. ISBN 978-0-89042-554-1.
13. ^ a b Sajatovic M, Loue S, eds. (2012-02-29). Encyclopedia of immigrant health. New York: Springer. ISBN 978-1-4419-5659-0.
14. ^ Robles, DT; Romm, S; Combs, H; Olson, J; Kirby, P (Jun 15, 2008). "Delusional disorders in dermatology: a brief review". Dermatology Online Journal. 14 (6): 2. PMID 18713583.
15. ^ a b (editors) Newman MG, Takei HH, Klokkevold PR, Carranza FA (2012). Carranza's clinical periodontology (11th ed.). St. Louis, Mo.: Elsevier/Saunders. pp. 1333, 1334. ISBN 978-1-4377-0416-7.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)
16. ^ Wise, PM; Eades, J; Tjoa, S; Fennessey, PV; Preti, G (Nov 2011). "Individuals reporting idiopathic malodor production: demographics and incidence of trimethylaminuria". The American Journal of Medicine. 124 (11): 1058–63. doi:10.1016/j.amjmed.2011.05.030. PMID 21851918.
17. ^ Brent, A (2010). "Chapter 46, Odor - unusual". In Gary R. Fleisher; Stephen Ludwig; et al. (eds.). Textbook of pediatric emergency medicine (6th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health. ISBN 978-1-60547-159-4.
18. ^ Shirasu, M; Touhara, K (Sep 2011). "The scent of disease: volatile organic compounds of the human body related to disease and disorder". Journal of Biochemistry. 150 (3): 257–66. doi:10.1093/jb/mvr090. PMID 21771869.
19. ^ Stitt, WZ; Goldsmith, A (Sep 1995). "Scratch and sniff. The dynamic duo". Archives of Dermatology. 131 (9): 997–9. doi:10.1001/archderm.131.9.997. PMID 7661625.
20. ^ Pausch, NC; Reiss, M; Reiss, G (Feb 2001). "[Malodor from the nose. Causes, diagnosis and therapy]". Medizinische Monatsschrift für Pharmazeuten. 24 (2): 48–50. PMID 11255985.
21. ^ Reiss, M; Reiss, G (Nov 23, 2000). "[Nasal odors]". Praxis. 89 (47): 1953–5. PMID 11143967.
22. ^ Sobel, JD (Jun 2012). "Genital malodour in women: an unmet therapeutic challenge". Sexually Transmitted Infections. 88 (4): 238. doi:10.1136/sextrans-2011-050440. PMID 22383853. S2CID 207027103.
23. ^ Subramanian, C; Nyirjesy, P; Sobel, JD (Jan 2012). "Genital malodor in women: a modern reappraisal". Journal of Lower Genital Tract Disease. 16 (1): 49–55. doi:10.1097/LGT.0b013e31822b7512. PMID 21964208. S2CID 21530432.
24. ^ Coil, JM; Yaegaki, K; Matsuo, T; Miyazaki, H (Jun 2002). "Treatment needs (TN) and practical remedies for halitosis". International Dental Journal. 52 Suppl 3: 187–91. doi:10.1002/j.1875-595x.2002.tb00922.x. PMID 12090450.
25. ^ Finkelstein, Y; Talmi, YP; Ophir, D; Berger, G (Oct 2004). "Laser cryptolysis for the treatment of halitosis". Otolaryngology–Head and Neck Surgery. 131 (4): 372–7. doi:10.1016/j.otohns.2004.02.044. PMID 15467602. S2CID 25036981.
26. ^ Elias, MS; Ferriani, Md (Sep–Oct 2006). "Historical and social aspects of halitosis". Revista Latino-americana de Enfermagem. 14 (5): 821–3. CiteSeerX 10.1.1.586.5603. doi:10.1590/s0104-11692006000500026. PMID 17117270.
27. ^ Mountain, H; Brisbane, JM; Hooper, AJ; Burnett, JR; Goldblatt, J (Oct 20, 2008). "Trimethylaminuria (fish malodour syndrome): a "benign" genetic condition with major psychosocial sequelae". The Medical Journal of Australia. 189 (8): 468. doi:10.5694/j.1326-5377.2008.tb02126.x. PMID 18928446. S2CID 35200507.
28. ^ Scarff, CE (Sep 2009). "Sweaty, smelly hands and feet" (PDF). Australian Family Physician. 38 (9): 666–9. PMID 19893792.
29. ^ Falcão, DP; Vieira, CN; Batista de Amorim, RF (Mar 2012). "Breaking paradigms: a new definition for halitosis in the context of pseudo-halitosis and halitophobia". Journal of Breath Research. 6 (1): 017105. Bibcode:2012JBR.....6a7105P. doi:10.1088/1752-7155/6/1/017105. PMID 22368258.
30. ^ Munro, Alistair (1999). Delusional Disorder: Paranoia and Related Illnesses. Concepts in clinical psychiatry. Cambridge University Press. pp. 79, 91, 92. ISBN 978-1-139-42732-6.
30em Dunne, T.P. (2015). "EMDR: An Effective and Less Stigmatising Treatment for Olfactory Reference Syndrome", EMDR Now, Vol. 7, No.1, Jan, pp 6–7.
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* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Olfactory reference syndrome | None | 6,611 | wikipedia | https://en.wikipedia.org/wiki/Olfactory_reference_syndrome | 2021-01-18T18:57:42 | {"wikidata": ["Q4386741"]} |
A rare ectodermal dysplasia syndrome characterized by hypotrichosis of scalp and eyebrows, finger syndactyly, intellectual disability and early eruption of teeth. Facial dysmorphism (i.e. round face with prominent forehead, cheeks and ears, and upward-slanting palpebral fissures), hypoplasia of median and distal phalanges, and kyphosis are additionally observed features. There have been no further descriptions in the literature since 1996.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Hypotrichosis-intellectual disability, Lopes type | None | 6,612 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2266 | 2021-01-23T17:33:33 | {"synonyms": ["Lopes-Marques de Faria syndrome"]} |
The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted.
Find sources: "Zeism" – news · newspapers · books · scholar · JSTOR (July 2020) (Learn how and when to remove this template message)
Zeism is any condition attributed to excessive use of maize (corn) in the diet, such as pellagra. Maize is low in zinc, niacin, and tryptophan, and the limited niacin found in maize is not absorbed in the digestive tract unless it has been treated with alkalis, as in the preparation of tortillas. A type of pellagra attributed to amino acid imbalance is common in India among people who eat a millet with a high leucine content. The deficiencies are usually seasonal.
The (now confirmed) zeist hypotheses that pellagra might be a deficiency disease related to corn consumption was stated in 1810 by the Italian Giovanni Battista Marzari.[1]
## See also[edit]
* Vitamin deficiency
## Sources[edit]
Primary sources
* Dorland's Illustrated Medical Dictionary
* The Merck Manuals Online Medical Library - Niacin Deficiency
* Encyclopedia of Neurological Disorders: Vitamin/Nutritional Deficiency
Secondary sources
* Wilson, Jean D. "Deficiency States". In Harrison's Principles of Internal Medicine, ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.
* Garrison, Robert H., Jr. and Elizabeth Somer. The Nutrition Desk Reference. Keats Publishing, Inc., 1985.
## References[edit]
1. ^ Bryan CS, Mull SR (2015). "Pellagra Pre-Goldberger: Rupert Blue, Fleming Sandwith, and The "Vitamine Hypothesis"". Trans Am Clin Climatol Assoc. 126: 20–45. PMC 4530670. PMID 26330657.
This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Zeism | None | 6,613 | wikipedia | https://en.wikipedia.org/wiki/Zeism | 2021-01-18T19:00:04 | {"wikidata": ["Q8068594"]} |
## Clinical Features
Reardon et al. (1993) reported a brother and sister, the offspring of second-cousin Pakistani parents, with an apparently new form of mesomelic limb shortening and bowing with associated skin dimpling, retrognathia, mandibular hypoplasia, cleft palate, and camptodactyly. The sister died a few hours after birth from cardiorespiratory arrest and the brother was alive at age 4 years. Radiologic findings were incompatible with the diagnosis of campomelic dysplasia (114290). Differences from Langer mesomelic dysplasia (249700) were also noted.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| MESOMELIC LIMB SHORTENING AND BOWING | c2930871 | 6,614 | omim | https://www.omim.org/entry/249710 | 2019-09-22T16:25:25 | {"mesh": ["C535294"], "omim": ["249710"], "orphanet": ["2631"]} |
A rare disorder characterized by early-onset progressive encephalopathy with migrant, continuous myoclonus. Three cases have been reported. The focal continuous myoclonus appeared during the first months of life. Prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occurred later. Subsequently, a progressive encephalopathy with hypotonia and ataxia appeared. Cortical atrophy was revealed by computed tomography (CT) scan and magnetic resonance imaging (MRI). The aetiology is unknown.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Early-onset progressive encephalopathy with migrant continuous myoclonus | None | 6,615 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1943 | 2021-01-23T19:06:00 | {"gard": ["2995"], "icd-10": ["G40.4"]} |
Melioidosis is an infectious disease caused by the bacteria Burkholderia pseudomallei that are commonly found in the soil and water. Melioidosis is a rare disease in the United States, but it is common in tropical or subtropical areas of the world, including Southeast Asia, Africa, and Australia. The signs and symptoms of the disease can vary greatly and may mimic those of tuberculosis or common forms of pneumonia. Signs and symptoms may include pain or swelling, fever, abscess, cough, high fever, headache, trouble breathing, and more. Although healthy people can also experience signs and symptoms of the disease, people with certain conditions like diabetes, liver disease, kidney disease, lung disease, thalassemia, cancer, or certain autoimmune diseases are more severely affected. Diagnosis is made by collecting blood, sputum, urine, or pus samples and growing the bacteria. Current treatment is divided into two stages: an intravenous (IV) antibiotic stage and oral antibiotic maintenance stage to prevent recurrence.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Melioidosis | c0025229 | 6,616 | gard | https://rarediseases.info.nih.gov/diseases/9546/melioidosis | 2021-01-18T17:59:09 | {"mesh": ["D008554"], "umls": ["C0025229"], "synonyms": ["Burkholderia pseudomallei infection", "B pseudomallei infection", "Whitmore disease", "Nightcliff gardener's disease"]} |
Sturge-Weber syndrome (SWS) is a rare disorder affecting the skin and nervous system. Babies with SWS are born with a birthmark on their face known as a port-wine stain. Port-wine birthmarks are caused by enlarged blood vessels right underneath the skin. People with Sturge-Weber syndrome also have clusters of abnormal blood vessels between the layers of tissue that cover the brain and spine known as leptomeningeal angiomas. They may also have increased pressure in the eyes known as glaucoma. Other symptoms of SWS may include seizures, muscle weakness, developmental and intellectual disability. SWS is caused by a mutation in the GNAQ gene. The gene mutation is not inherited, but occurs by chance in cells of the developing embryo. SWS is diagnosed based on the symptoms. Imaging studies, such as an MRI or CT-scan, are also used to aid in the diagnosis. There is no one treatment for SWS, so management involves treating the specific symptoms that are present. This may include anti-seizure medications, medications and/or surgery for glaucoma, and low-dose aspirin to reduce the pressure in the eyes and brain. The port-wine birthmark may be treated with various types of laser treatments. The long-term outlook for people with SWS is dependent on the severity of symptoms and varies from person to person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Sturge-Weber syndrome | c0038505 | 6,617 | gard | https://rarediseases.info.nih.gov/diseases/7706/sturge-weber-syndrome | 2021-01-18T17:57:30 | {"mesh": ["D013341"], "omim": ["185300"], "orphanet": ["3205"], "synonyms": ["SWS", "Sturge Weber syndrome", "Encephalotrigeminal angiomatosis", "Fourth phacomatosis", "Meningeal capillary angiomatosis", "Leptomeningeal angiomatosis", "Encephalofacial angiomatosis", "SWS type I - Facial and leptomeningeal angiomas", "SWS type II - Facial angioma alone, no CNS involvement", "SWS type III - Isolated leptomeningeal angiomas"]} |
Urethral stricture
Urethra is tube at center.
SpecialtyUrology
A urethral stricture is a narrowing of the urethra caused by injury, instrumentation, infection, and certain non-infectious forms of urethritis.[1]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 4.1 Dilation and other endoscopic approaches
* 4.2 Cell therapy approach through endoscopy
* 4.3 Urethroplasty
* 4.4 Urethral stent
* 4.5 Emergency treatment
* 4.6 Ongoing care
* 5 Research
* 6 References
* 7 External links
## Signs and symptoms[edit]
The hallmark sign of urethral stricture is a weak urinary stream. Other symptoms include:
* Splaying of the urinary stream
* Urinary frequency
* Urinary urgency
* Straining to urinate
* Pain during urination
* Urinary tract infection
* Prostatitis
* Inability to completely empty the bladder.
Some people with severe urethral strictures are completely unable to urinate. This is referred to as acute urinary retention, and is a medical emergency. Hydronephrosis and kidney failure may also occur.
### Complications[edit]
* Urinary retention
* Prostatitis
* Bladder dysfunction
* Urethral diverticulum
* Periurethral abscess
* Fournier's gangrene
* Urethral fistula
* Bilateral hydronephrosis
* Urinary infections
* Urinary calculus
## Causes[edit]
Urethral strictures most commonly result from injury, urethral instrumentation, infection, non-infectious inflammatory conditions of the urethra, and after prior hypospadias surgery. Less common causes include congenital urethral strictures and those resulting from malignancy.
Urethral strictures after blunt trauma can generally be divided into two sub-types;
* Pelvic fracture-associated urethral disruption occurs in as many as 15% of severe pelvic fractures.[2] These injuries are typically managed with suprapubic tube placement and delayed urethroplasty 3 months later. Early endoscopic realignment may be used in select cases instead of a suprapubic tube, but these patients should be monitored closely as vast majority of them will require urethroplasty.[3]
* Blunt trauma to the perineum compresses the bulbar urethra against the pubic symphysis, causing a "crush" injury. These patients are typically treated with suprapubic tube and delayed urethroplasty.
Other specific causes of urethral stricture include:
* Instrumentation (e.g., after transurethral resection of prostate, transurethral resection of bladder tumor, or endoscopic kidney surgery)
* Infection (typically with Gonorrhea)
* Lichen sclerosus[4]
* Surgery to address hypospadias can result in a delayed urethral stricture, even decades after the original surgery.
## Diagnosis[edit]
Urethrography showing urethral stricture in man (labeled Verengung which translates to "Narrowing").
* Cystoscopy
* Urethrography
## Treatment[edit]
### Dilation and other endoscopic approaches[edit]
Urethral dilation and other endoscopic approaches such as direct vision internal urethrotomy (DVIU), laser urethrotomy, and self intermittent dilation are the most commonly used treatments for urethral stricture. However, these approaches are associated with low success rates[5] and may worsen the stricture, making future attempts to surgically repair the urethra more difficult.[6]
A Cochrane review found that performing intermittent self-dilatation may confer a reduced risk of recurrent urethral stricture after endoscopic treatment, but the evidence is weak.[7]
### Cell therapy approach through endoscopy[edit]
Buccal mucosal tissue harvested under local anesthesia after culturing in the lab when applied through endoscopy after urethrotomy in a pilot study has yielded encouraging results. This method named as BEES-HAUS procedure needs to be validated through a larger multicentric study before becoming a routine application.[8]
### Urethroplasty[edit]
Urethroplasty refers to any open reconstruction of the urethra. Success rates range from 85% to 95% and depend on a variety of clinical factors, such as stricture as the cause, length, location, and caliber.[9][10][11][12] Urethroplasty can be performed safely on men of all ages.[13]
In the posterior urethra, anastomotic urethroplasty (with or without preservation of bulbar arteries) is typically performed after removing scar tissue.
In the bulbar urethra,[9][10][11] the most common types of urethroplasty are anastomotic (with or without preservation of corpus spongiosum and bulbar arteries) and substitution with buccal mucosa graft, full-thickness skin graft, or split thickness skin graft. These are nearly always done in a single setting (or stage).
In the penile urethra, anastomotic urethroplasties are rare because they can lead to chordee (penile curvature due to a shortened urethra). Instead, most penile urethroplasties are substitution procedures utilizing buccal mucosa graft, full-thickness skin graft, or split thickness skin graft. These can be done in one or more setting, depending on stricture location, severity, cause and patient or surgeon preference.
The first reported cases using umbilical vein as urethral graft in urethral stricture yielded good results 85% , Al-Naieb in 1985 . the first 10 cases were reported in his PhD thesis submitted to Johannes Gutenberg university in Mainz Germany. after this successful results, 25 cases operated and published in Jordanian medical Journal in the nineties . with excellent results mainly posterior urethra. published as Editorial in 2019:.EC Gynaecology 8.1 (21019): 01-12.
### Urethral stent[edit]
3D Medical Animation still shot of Urethral Stent
A permanent urethral stent[14] was approved for use in men with bulbar urethral strictures in 1996, but was recently removed from the market.
A temporary thermoexpandable urethral stent (Memotherm) is available in Europe, but is not currently approved for use in the United States.
### Emergency treatment[edit]
When in acute urinary retention, treatment of the urethral stricture or diversion is an emergency. Options include:
* Urethral dilatation and catheter placement. This can be performed in the Emergency Department, a practitioner's office or an operating room. The advantage of this approach is that the urethra may remain patent for a period of time after the dilation, though long-term success rates are low.
* Insertion of a suprapubic catheter with catheter drainage system. This procedure is performed in an Operating Room, Emergency Department or practitioner's office. The advantage of this approach is that it does not disrupt the scar and interfere with future definitive surgery.
### Ongoing care[edit]
Following urethroplasty, patients should be monitored for a minimum of 1 year, since the vast majority of recurrences occur within 1 year.
Because of the high rate of recurrence following dilation and other endoscopic approaches, the provider must maintain a high index of suspicion for recurrence when the patient presents with obstructive voiding symptoms or urinary tract infection.
## Research[edit]
The use of bioengineered urethral tissue is promising, but still in the early stages. The Wake Forest Institute of Regenerative Medicine has pioneered the first bioengineered human urethra, and in 2006 implanted urethral tissue grown on bioabsorbable scaffolding (approximating the size and shape of the affected areas) in five young (human) males who suffered from congenital defects, physical trauma, or an unspecified disorder necessitating urethral reconstruction. As of March, 2011, all five recipients report the transplants have functioned well.[15]
## References[edit]
1. ^ "Urethral stricture: What causes it? - MayoClinic.com". MayoClinic.com. Archived from the original on November 26, 2007. Retrieved December 13, 2007.
2. ^ Figler, B. D.; Hoffler, C. E.; Reisman, W.; Carney, K. J.; Moore, T.; Feliciano, D.; Master, V. (2012). "Multi-disciplinary update on pelvic fracture associated bladder and urethral injuries". 43 (81): 242–249. Cite journal requires `|journal=` (help)
3. ^ "American Urological Association - Urotrauma". www.auanet.org. Retrieved 21 April 2018.
4. ^ Palminteri, E.; Brandes, S. B.; Djordjevic, M. (2012). "Urethral reconstruction in lichen sclerosus". Curr Opin Urol. 22 (6): 478–483. doi:10.1097/MOU.0b013e328358191c.
5. ^ Santucci R and Eisenberg L: Urethrotomy has a much lower success rate than previously reported. J Urol 2010; 183: 1859.
6. ^ Hudak SJ, Atkinson TH, Morey AF. Repeat transurethral manipulation of bulbar urethral strictures is associated with increased stricture complexity and prolonged disease duration. J Urol. 2012 May;187(5):1691-5
7. ^ Jackson, MJ; Veeratterapillay, R; Harding, CK; Dorkin, TJ (19 December 2014). "Intermittent self-dilatation for urethral stricture disease in males". The Cochrane Database of Systematic Reviews. 12: CD010258. doi:10.1002/14651858.CD010258.pub2. PMID 25523166.
8. ^ Vaddi, Suryaprakash; Vijayabaskar, Reddy; Abraham, Samuel JK (22 November 2018). "Buccal epithelium Expanded and Encapsulated in Scaffold‐Hybrid Approach to Urethral Stricture (BEES‐HAUS) procedure: A novel cell therapy‐based pilot study". International Journal of Urology. 26 (2): 253–257. doi:10.1111/iju.13852. PMID 30468021.
9. ^ a b Santucci RA, Mario LA, McAninch JW. Anastomotic urethroplasty for bulbar urethral stricture: analysis of 168 patients. J Urol. 2002 Apr;167(4):1715-9.
10. ^ a b Figler BD, Malaeb BS, Dy GW, Voelzke BB, Wessells H. Impact of graft position on failure of single-stage bulbar urethroplasties with buccal mucosa graft. Urology. 2013 Nov;82(5):1166-70.
11. ^ a b Barbagli G1, Sansalone S, Romano G, Lazzeri M. Bulbar urethroplasty: transecting vs. nontransecting techniques. Curr Opin Urol. 2012 Nov;22(6):474-7.
12. ^ Bello JO. Impact of preoperative patient characteristics on posturethroplasty recurrence: the significance of stricture length and prior treatments. Niger J Surg. 2016; 22(2):86-89
13. ^ Santucci RA, McAninch JW, Mario LA et al. (July 2004). "Urethroplasty in patients older than 65 years: indications, results, outcomes and suggested treatment modifications". J Urol. 172 (1): 201–3.
14. ^ "Urolume Endoprosthesis". americanmedicalsystems.com. Archived from the original on 13 March 2006. Retrieved 21 April 2018.
15. ^ Alice Park (8 March 2011). "Scientists Grow New Body Parts in the Lab". Time.
## External links[edit]
Classification
D
* ICD-10: N35
* ICD-9-CM: 598
* MeSH: D014525
* DiseasesDB: 13562
External resources
* MedlinePlus: 001271
* eMedicine: med/3075
* v
* t
* e
Diseases of the urinary tract
Ureter
* Ureteritis
* Ureterocele
* Megaureter
Bladder
* Cystitis
* Interstitial cystitis
* Hunner's ulcer
* Trigonitis
* Hemorrhagic cystitis
* Neurogenic bladder dysfunction
* Bladder sphincter dyssynergia
* Vesicointestinal fistula
* Vesicoureteral reflux
Urethra
* Urethritis
* Non-gonococcal urethritis
* Urethral syndrome
* Urethral stricture
* Meatal stenosis
* Urethral caruncle
Any/all
* Obstructive uropathy
* Urinary tract infection
* Retroperitoneal fibrosis
* Urolithiasis
* Bladder stone
* Kidney stone
* Renal colic
* Malakoplakia
* Urinary incontinence
* Stress
* Urge
* Overflow
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Urethral stricture | c0041974 | 6,618 | wikipedia | https://en.wikipedia.org/wiki/Urethral_stricture | 2021-01-18T19:09:43 | {"mesh": ["D014525"], "umls": ["C0029752", "C0041974"], "icd-10": ["N35"], "wikidata": ["Q1585753"]} |
A rare ophthalmic disorder with cranial nerve involvement characterized by dysfunction of the superior oblique muscle with typical eye motility patterns including elevation in adduction, V-pattern related to reduced abduction force in downgaze with unopposed adduction by the inferior rectus muscle, and excyclotorsion. Patients may present with contralateral head tilt to compensate for vertical binocular misalignment and diplopia.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Congenital trochlear nerve palsy | None | 6,619 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98686 | 2021-01-23T17:09:11 | {"icd-10": ["H49.1"], "synonyms": ["Congenital CNIV palsy", "Congenital fourth cranial nerve palsy", "Congenital superior oblique palsy"]} |
Interdigital dermatitis in cattle is caused by the anaerobic bacterium Dichelobacter nodosus. This is also the agent of footrot in sheep, but strains appear to be different and there is no cross-infection.
Interdigital dermatitis is different from footrot in cattle and both conditions may occur concurrently.
The condition most commonly occurs in farms with a high stocking density or where cattle traffic is high and is most prevalent in Winter.
## Clinical signs and diagnosis[edit]
Interdigital dermatitis appears as an infections of the skin between the claws and is usually very mild. There may be fluid or a scab in that area, and there is rarely lameness. There is then progression to the heels which become raw and cattle will experience pain. Chronic cases will show changes of the hoof including hyperplasia of the interdigital tissues and muscle atrophy in the affected limb. The horn may become underrun.[1]
Diagnosis is principally based on history and clinical signs. It is very rare that attempts are made to isolate the bacteria.[1]
## Treatment and control[edit]
The skin should be cleaned and kept dry, and topical antibiotics can be applied to the area. Systemic antibiotics are not needed.[1]
Control relies on prompt detection, isolation and treatment of affected cattle. Footpaths should be kept as dry as possible and slurry build-up should be avoided. Regular footbaths should be organised, using formalin, copper sulphate[1] or a thymol-based disinfectant.[2] In 2013, a safer and alternative to chemicals for hoof baths called Thymox Technology was proven, through field testing, to kill the main bacteria causing digital dermatitis.[2]
## References[edit]
1. ^ a b c d Interdigital Dermatitis - Cattle reviewed and published by WikiVet, accessed 11 October 2011.
2. ^ a b "Vet Med Scientists Find Better, Safer Treatments for Hoof Disease". University of Wisconsin School of Veterinary Medicine. 8 November 2013. Retrieved 3 September 2014.
This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Interdigital dermatitis in cattle | None | 6,620 | wikipedia | https://en.wikipedia.org/wiki/Interdigital_dermatitis_in_cattle | 2021-01-18T18:35:00 | {"wikidata": ["Q6046090"]} |
Ascher's syndrome
Other namesLaffer-Ascher Syndrome
Ascher's syndrome, is a rare disorder first described in 1920.[1] It is characterized by repeated episodes of lip and eyelid edema and occasionally euthyroid goiter. The syndrome generally occurs within the first 20 years of life.[2] About 100 cases had been described by 1998.[3]
## Contents
* 1 Signs and Symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Signs and Symptoms[edit]
* Blepharochalasis : Recurrent episodes of swelling cause stretching and atrophy of the upper eyelid skin. This results in the relaxation of the tarsal fold allowing tissue to slack over the palpebral fissure. In severe cases, the lower eyelid is also involved.
* Double Upper Lip : Swelling causes duplication between the inner and outer parts of the upper lip. Occasionally the lower lip is involved.[1]
* Euthyroid Goiter : Occurs in 10% of cases.[2] It is not usually associated with toxic symptoms. Goiter usually presents several years after initial eyelid and lip edema.[1]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (April 2018)
## Treatment[edit]
Cosmetic surgery is generally the treatment of choice.[4]
## References[edit]
1. ^ a b c Gorlin RJ, Pindborg JJ, CohenMM.Syndromes of the head and neck, 4th ed.New York:McGraw-Hill, 1976: 500-501.
2. ^ a b Sanchez MR, Lee M, Moy JA et al. Ascher syndrome: a mimicker of acquired angioedema. J Am Acad Dermatol 1993;29:650–651.
3. ^ U. Beinhoff; H. Piza-Katzer (1998). "Double lip in a patient with Ascher's syndrome". European Journal of Plastic Surgery. 21 (7): 370–373. doi:10.1007/s002380050120.
4. ^ Atzeni M, et al. Surgical correction and MR imaging of double lip in Ascher syndrome: record of a case and a review of the literature. Eur Rev Med Pharmacol Sci 2009;13:309-311.
## External links[edit]
Classification
D
* OMIM: 109900
* MeSH: C562742
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Ascher's syndrome | c0339085 | 6,621 | wikipedia | https://en.wikipedia.org/wiki/Ascher%27s_syndrome | 2021-01-18T18:56:56 | {"gard": ["201"], "mesh": ["C562742"], "umls": ["C0339085"], "orphanet": ["1253"], "wikidata": ["Q4803881"]} |
Benign hereditary chorea (BHC)
Other namesBenign familial chorea
Benign hereditary chorea (BHC), also known as benign familial chorea, is a rare autosomal dominant neurogenetic syndrome. It typically presents in childhood with isolated chorea, with or without dull normal intelligence. Unlike other neurogenetic causes of chorea such as Huntington's disease, BHC is not progressive, and not associated with cognitive decline or psychiatric problems in the vast majority of cases.[1]
BHC is caused by a single-nucleotide insertion mutation in TITF1, which encodes thyroid transcription factor 1 (TTF-1). This gene is also known as NK2 homeobox 1 (NKX2-1)[1]
In some cases, additional developmental abnormalities of lung and thyroid tissue are found in BHC, leading to the suggested alternative name brain-lung-thyroid syndrome.[2]
## See also[edit]
* Chorea
* Huntington's disease
## References[edit]
1. ^ a b Kleiner-Fisman, G; Rogaeva, E; Halliday, W; Houle, S; Kawarai, T; Sato, C; Medeiros, H; St George-Hyslop, PH; Lang, AE (August 2003). "Benign hereditary chorea: clinical, genetic, and pathological findings". Annals of Neurology. 54 (2): 244–7. doi:10.1002/ana.10637. PMID 12891678. S2CID 10793142.
2. ^ Peall, KJ; Kurian, MA (2015). "Benign Hereditary Chorea: An Update". Tremor and Other Hyperkinetic Movements. 5: 314. doi:10.7916/D8RJ4HM5. PMC 4502401. PMID 26196025.
## External links[edit]
Classification
D
* OMIM: 118700
* MeSH: C565851
External resources
* GeneReviews: NKX2-1-Related Disorders
* Orphanet: 1429
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Benign hereditary chorea | c1859098 | 6,622 | wikipedia | https://en.wikipedia.org/wiki/Benign_hereditary_chorea | 2021-01-18T18:33:45 | {"gard": ["1305"], "mesh": ["C565851"], "umls": ["C1859098"], "orphanet": ["1429"], "wikidata": ["Q24977061"]} |
Pyoderma gangrenosum is a rare, destructive inflammatory skin disease of which a painful nodule or pustule breaks down to form a progressively enlarging ulcer. Lesions may occur either in the absence of any apparent underlying disorder or in association with other diseases, such as ulcerative colitis, Crohn's disease, polyarthritis (an inflammation of several joints together), gammopathy, vasculitis, leukemia, and other conditions. Each year in the United States, pyoderma gangrenosum occurs in about 1 person per 100,000 people.
Pyoderma gangrenosum belongs to a group of autoinflammatory skin diseases called neutrophilic dermatoses. Neutrophils are a type of white blood cell or leukocyte which form an early line of defense against bacterial infections. Ulcerations associated with pyoderma gangrenosum may occur after trauma or injury to the skin, a process called pathergy. Treatment involves wound care and the use of anti-inflammatory agents, including antibiotics, corticosteroids, immunosuppressants, and biologics.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Pyoderma gangrenosum | c0085652 | 6,623 | gard | https://rarediseases.info.nih.gov/diseases/7510/pyoderma-gangrenosum | 2021-01-18T17:58:02 | {"mesh": ["D017511"], "umls": ["C0085652"], "orphanet": ["48104"], "synonyms": []} |
Galli–Galli disease
SpecialtyDermatology
Galli–Galli disease is a rare inherited condition that has close resemblance clinically to Dowling-Degos' disease, but is histologically distinct, characterized by skin lesions that are 1- to 2-mm slightly keratotic red to dark brown papules which are focally confluent in a reticulate pattern.[1]:856 The disease is also characterized by slowly progressive and disfiguring reticulate hyperpigmentation of the flexures, clinically and histopathologically diagnostic for Dowling-Degos disease but also associated with suprabasal, nondyskeratotic acantholysis.[2][3]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Journal of the American Academy of Dermatology ISSN 0190-9622 CODEN JAADDB
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| Galli–Galli disease | None | 6,624 | wikipedia | https://en.wikipedia.org/wiki/Galli%E2%80%93Galli_disease | 2021-01-18T18:42:48 | {"wikidata": ["Q5519115"]} |
## Description
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008).
Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008).
For a general description and a discussion of genetic heterogeneity of Hirschsprung disease (HSCR), see 142623.
Mapping
Brooks et al. (2006) described a multigenerational Dutch family with isolated HSCR. Five patients were affected by either short-segment or long-segment HSCR. The family consisted of 2 main branches: 1 with 4 patients (3 sibs and 1 maternal uncle) and 1 with 1 patient. Analysis of the RET gene (164761), the major gene involved in HSCR susceptibility, revealed neither linkage or mutations. A genomewide linkage analysis showed suggestive linkage to 4q31-q32 with a maximum parametric multipoint lod score of 2.7 between markers D4S1585 and D4S3351. Nonparametric linkage (NPL) analysis of the genomewide scan data showed an NPL score of 2.54 (P = 0.003) for the same region on 4q. The minimum linkage interval of 11.7 cM (12.2 Mb) between markers D4S3049 and D4S1566 on 4q31.3-q32.3 contained no genes that had previously been implicated in HSCR. The 3 affected sibs were heterozygous for a common risk haplotype defined by SNPs located in the 5-prime region of the RET locus reported in Dutch patients (Burzynski et al., 2004, Burzynski et al., 2005). However, their affected maternal uncle and cousin did not carry the 5-prime RET common risk haplotype. Brooks et al. (2006) concluded that, considering the low penetrance of the disease in this family, the 4q locus may be necessary but not sufficient to cause HSCR in the absence of modifying loci elsewhere in the genome.
Cytogenetics
In a mother and 3 sons with delayed development, dysmorphic facial features, and variable expression of Hirschsprung disease, Wang et al. (2009) identified a 4.3-Mb triplication at chromosome 4q32.1-q32.2 (613603), which included the HSCR9 locus mapped within this region.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
| HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 9 | c0019569 | 6,625 | omim | https://www.omim.org/entry/611644 | 2019-09-22T16:03:03 | {"doid": ["10487"], "mesh": ["D006627"], "omim": ["611644"], "orphanet": ["388"]} |
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Major side effects of bicalutamide[1][2][3][4][5][6][7] Frequency Class of effect Effect
Very common (≥10%) Reproductive system and breast disorders • Breast tenderness[a]
• Gynecomastia[a]
Common (1-10%) General and psychiatric disorders • Asthenia
• Decreased libido
• Erectile dysfunction
• Hot flashes
Skin and subcutaneous
tissue disorders • Decreased body hair
Hepato-biliary disorders • Elevated liver enzymes[b]
Uncommon (0.1-1%) Immune system disorders and hypersensitivity reactions • Angioedema
• Hives
Rare (<0.1%) or unknown Respiratory disorders • Lung disease[c]
Skin and subcutaneous tissue disorders • Sensitivity to light
Hepato-biliary disorders • Liver toxicity[c]
1. ^ a b May occur as often as 90% of those taking bicalutamide, but is mild-to-moderate in 90% of occurrences. Incidence greatly decreased in combination with castration.
2. ^ Usually transient, rarely severe. Resolves or improves with continued therapy or on discontinuation.
3. ^ a b Reported in single cases, but not observed in any large, randomized trial.
The side effects of bicalutamide, a nonsteroidal antiandrogen (NSAA), including its frequent and rare side effects, have been well-studied and characterized. The most common side effects of bicalutamide monotherapy in men include breast tenderness, gynecomastia, feminization, demasculinization, and hot flashes. Less common side effects of bicalutamide monotherapy in men include sexual dysfunction, depression, fatigue, weakness, and anemia. Bicalutamide is well tolerated and has few side effects in women. General side effects of bicalutamide that may occur in either sex include diarrhea, constipation, abdominal pain, nausea, dry skin, itching, and rash.
In men with prostate cancer, bicalutamide monotherapy has been associated with an increased risk of non-cancer death, in part due to an increased incidence of heart failure. This is thought to be a consequence of androgen deprivation. Bicalutamide monotherapy has been found to cause unfavorable liver changes in around 3% of men, with such changes necessitating discontinuation in about 0.3 to 1% of men. Very rarely, bicalutamide has been associated with liver damage, lung disease, and sensitivity to light. It has also uncommonly been associated with hypersensitivity reactions. Bicalutamide has a theoretical risk of birth defects in male fetuses.
## Contents
* 1 Central nervous system
* 1.1 Hot flashes
* 1.2 Sexual dysfunction
* 1.3 Psychiatric conditions
* 2 Breasts and reproductive system
* 2.1 Breast changes
* 2.1.1 Management of breast changes
* 2.1.2 Male breast cancer
* 2.2 Lower reproductive system
* 2.2.1 Male birth defects
* 3 Skin, fat, and bone
* 3.1 Skin changes
* 3.1.1 Sensitivity to light
* 3.2 Fat distribution
* 3.3 Bone density and fractures
* 4 Gastrointestinal system
* 5 Heart, liver, kidneys, and lungs
* 5.1 Cardiovascular system
* 5.1.1 Coagulation
* 5.2 Kidney function
* 5.2.1 Anemia
* 5.3 Liver toxicity
* 5.4 Lung toxicity
* 6 Modification of side effects by castration
* 7 References
## Central nervous system[edit]
### Hot flashes[edit]
In the EPC trial, at 7.4 years follow-up, the rate of hot flashes was 9.2% for bicalutamide monotherapy relative to 5.4% for placebo, which was regarded as relatively low.[8] In the LAPC subgroup of the EPC trial, the rate of hot flashes with bicalutamide monotherapy was 13.1% (relative to 50.0% for castration).[8][9]
### Sexual dysfunction[edit]
Bicalutamide may cause sexual dysfunction, including decreased sex drive and erectile dysfunction.[8] However, the rates of these side effects with bicalutamide monotherapy are very low.[8] In the EPC trial, at 7.4 years follow-up, the rates of decreased libido and impotence were only 3.6% and 9.3% in the 150 mg/day bicalutamide monotherapy group relative to 1.2% and 6.5% for placebo, respectively.[8] Similarly, in the trials of 150 mg/day bicalutamide monotherapy for advanced prostate cancer, fewer than 10% of men reported decreased sex drive or reduced erectile function as a side effect.[9] About two-thirds of men in these trials, who had advanced prostate cancer and were of almost invariably advanced age,[10] maintained sexual interest, while sexual function was slightly reduced by 18%.[9] Most men experience sexual dysfunction only moderately or not at all with bicalutamide monotherapy, and the same is true during monotherapy with other NSAAs.[11] Bicalutamide monotherapy at a dosage of 50 mg/day had no effect on nocturnal erections in men with prostate cancer.[12][13]
Similarly to in men, bicalutamide has been associated with minimal or no sexual dysfunction in women.[14] A phase III clinical study of 50 mg/day bicalutamide in conjunction with a combined oral contraceptive in women with severe hirsutism due to polycystic ovary syndrome (PCOS) carefully assessed the side effect of decreased libido and found that the incidence with bicalutamide did not differ from the control group.[14] Minimal rates of reduced sex drive have also been associated with the related NSAA flutamide.[15][16] These findings are in accordance with the fact that women with complete androgen insensitivity syndrome (CAIS) show normal sexual function in spite of complete loss of androgen receptor (AR) signaling.[17] They are also in accordance with a variety of findings concerning testosterone levels and sexual function in premenopausal women, in which no change in parameters of sexual function, including libido, have been observed in association with increases or decreases in testosterone levels.[17] It appears that testosterone levels within the normal physiological range are not importantly involved in sexual desire or function in women.[18]
### Psychiatric conditions[edit]
At 5.3 years follow-up, the incidence of depression was 5.5% for bicalutamide monotherapy relative to 3.0% for placebo in the EPC trial, and the incidence of asthenia (weakness or fatigue) was 10.2% for bicalutamide monotherapy relative to 5.1% for placebo.[19] Rarely, bicalutamide has been associated with hallucinations.[20] This is thought to be secondary to AR antagonism.[20]
## Breasts and reproductive system[edit]
Bicalutamide monotherapy and breast side effects in dose-ranging studies in men Study N Dosage Gynecomastia Breast tenderness Ref
Tyrrell et al. (1998)a 386 10 mg/day 9% 11% [21]
30 mg/day 26% 42%
50 mg/day 36% 48%
100 mg/day 79% 86%
150 mg/day 78% 89%
200 mg/day 79% 79%
Kennealey & Furr (1991)b 210 10 mg/day 29% 38% [22]
30 mg/day 60% 64%
50 mg/day 52% 60%
Zanardi et al. (2006)c 66 0 mg/week (controls) 0% 0% [23][24][25]
50 mg/week (~7 mg/day) 44% 32%
100 mg/week (~14 mg/day) 50% 64%
Footnotes: a = Testosterone levels increased to ~460–610 ng/dL and estradiol levels to ~32–51 pg/mL. b = Testosterone levels increased to ~505–715 ng/dL and estradiol levels to ~32–53 pg/mL. c = Testosterone levels increased to ~540–600 ng/dL and estradiol levels to ~29–34 pg/mL.
### Breast changes[edit]
Gynecomastia in a 60-year-old man treated with 150 mg/day bicalutamide for prostate cancer.[26]
The most common side effects of bicalutamide monotherapy in men are breast pain/tenderness and gynecomastia.[11] These side effects may occur in as many as 90% of men treated with bicalutamide monotherapy,[27] but gynecomastia is generally reported to occur in 70 to 80% of patients.[28] In the EPC trial, at a median follow-up of 7.4 years, breast pain and gynecomastia respectively occurred in 73.6% and 68.8% of men treated with 150 mg/day bicalutamide monotherapy.[8][9] Gynecomastia associated with NSAA monotherapy usually develops within the first 6 to 9 months following initiation of treatment.[26] In more than 90% of affected men, bicalutamide-related breast changes are mild-to-moderate in severity.[9][29] It is only rarely and in severe and extreme cases of gynecomastia that the proportions of the male breasts become so marked that they are comparable to those of women.[30] In addition, bicalutamide-associated breast changes improve or resolve in most men upon discontinuation of therapy.[9] In the EPC trial, 16.8% of bicalutamide patients relative to 0.7% of controls withdrew from the study due to breast pain and/or gynecomastia.[29] The incidence and severity of gynecomastia are reportedly higher with estrogens (e.g., diethylstilbestrol) than with NSAAs like bicalutamide in the treatment of men with prostate cancer.[31]
#### Management of breast changes[edit]
Severe gynecomastia with 150 mg/day bicalutamide monotherapy in a 64-year-old man with prostate cancer. Before (left) and after (right) surgical breast reduction.[32]
Tamoxifen, a selective estrogen receptor modulator (SERM) with antiestrogenic actions in breast tissue and estrogenic actions in bone, has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men.[33][34] Moreover, in contrast to GnRH analogues (which also alleviate bicalutamide-induced gynecomastia), tamoxifen poses minimal risk of accelerated bone loss and osteoporosis.[33][34] For reasons that are unclear, anastrozole, an aromatase inhibitor (or an inhibitor of estrogen biosynthesis), has been found to be much less effective in comparison to tamoxifen for treating bicalutamide-induced gynecomastia.[33][34] A 2015 systematic review of NSAA-induced gynecomastia and breast tenderness concluded that tamoxifen (10–20 mg/day) and radiotherapy could effectively manage the side effect without relevant adverse effects, though with tamoxifen showing superior effectiveness.[35] A 2019 network meta-analysis likewise concluded that tamoxifen was more effective than radiotherapy or anastrozole for preventing bicalutamide-induced gynecomastia.[36] Surgical breast reduction may also be employed to correct bicalutamide-induced gynecomastia.[37]
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Tamoxifen doses and rates of bicalutamide-induced breast symptoms in men Follow-up
timepoint Tamoxifen dosage
Placebo 1 mg/day 2.5 mg/day 5 mg/day 10 mg/day 20 mg/day
0 months
–
6 months 98% 90% 80% 54% 22% 10%
12 months 99% 95% 84% 56% 38% 19%
Notes: Prevention of breast symptoms—specifically gynecomastia and breast pain—induced by 150 mg/day bicalutamide monotherapy with tamoxifen in 282 men with prostate cancer. Bicalutamide and tamoxifen were initiated at the same time (0 months). Sources: [38][39] Estradiol levels were in the range of about 22 to 47 pg/mL in the treated group.[39]
#### Male breast cancer[edit]
A case report of male breast cancer subsequent to bicalutamide-induced gynecomastia has been published.[40] According to the authors, "this is the second confirmed case of breast cancer in association with bicalutamide-induced gynaecomastia (correspondence AstraZeneca)."[40] It is notable, however, that gynecomastia does not seem to increase the risk of breast cancer in men.[40][41] Moreover, the lifetime incidence of breast cancer in men is approximately 0.1%,[42] the average age of diagnosis of prostate cancer and male breast cancer are similar (around 70 years),[10][43] and millions of men have been treated with bicalutamide for prostate cancer,[44] all of which are potentially in support of the notion of chance co-occurrences.[40] In accordance, the authors concluded that "causality cannot be established" and that it was "probable that the association is entirely coincidental and sporadic."[40]
### Lower reproductive system[edit]
Bicalutamide reduces the size of the prostate gland and seminal vesicles,[45] though not of the testes.[46] Slightly but significantly reduced penile length is also a recognized adverse effect of ADT.[47][48] Reversible hypospermia or aspermia (that is, reduced or absent semen/ejaculate production) may occur.[49][50] However, bicalutamide does not appear to adversely affect spermatogenesis, and thus may not necessarily abolish the capacity/potential for fertility in men.[46][51] Due to the induction of chronic overproduction of LH and testosterone, there was concern that long-term bicalutamide monotherapy might induce Leydig cell hyperplasia and tumors (usually benign),[52] but clinical studies indicate that Leydig cell hyperplasia does not occur to a clinically important extent.[53][51][54]
#### Male birth defects[edit]
Because bicalutamide blocks the AR, like all antiandrogens, it can interfere with the androgen-mediated sexual differentiation of the genitalia (and brain) during prenatal development.[55][56][57][58] In pregnant rats given bicalutamide at a dosage of 10 mg/kg/day (resulting in circulating drug levels approximately equivalent to two-thirds of human therapeutic concentrations) and above, feminization of male offspring, such as reduced anogenital distance and hypospadias, as well as impotence, were observed.[59] No other teratogenic effects were observed in rats or rabbits receiving up to very high dosages of bicalutamide (that corresponded to up to approximately two times human therapeutic levels), and no teratogenic effects of any sort were observed in female rat offspring at any dosage.[59] As such, bicalutamide is a selective reproductive teratogen in males, and may have the potential to produce undervirilization/sexually ambiguous genitalia in male fetuses.[55][56]
## Skin, fat, and bone[edit]
### Skin changes[edit]
Antiandrogen therapy and estrogen therapy are known to produce demasculinizing and feminizing effects in the skin and on hair follicle distribution in people assigned male at birth.[60] Androgens are involved in regulation of the skin (e.g., sebum production), and antiandrogens are known to be associated with skin changes.[53] Skin-related side effects, which included dry skin, itching, and rash, were reported at a rate of 2% in both monotherapy and CAB clinical studies of bicalutamide in men.[53]
#### Sensitivity to light[edit]
A few cases of photosensitivity (hypersensitivity to ultraviolet light-induced skin redness and/or lesions) associated with bicalutamide have been reported.[61][62][63] In one of the cases, bicalutamide was continued due to effectiveness in treating prostate cancer in the patient, and in combination with strict photoprotection (in the form of avoidance/prevention of ultraviolet light exposure). Eventually, the symptoms disappeared and did not recur.[61] Flutamide is also associated with photosensitivity, but much more frequently in comparison to bicalutamide.[61][63]
### Fat distribution[edit]
Antiandrogen therapy and estrogen therapy are known to produce demasculinizing and feminizing effects on fat distribution in people assigned male at birth.[60]
### Bone density and fractures[edit]
Bicalutamide monotherapy preserves bone mineral density in men with prostate cancer relative to surgical or medical castration.[7][64][65][66][67] This is considered to be due to preservation of gonadal estradiol production with bicalutamide monotherapy, in contrast to castration which greatly reduces estradiol levels.[7] The risk of osteoporosis and serious bone fractures with bicalutamide monotherapy appears to be no different than with non-use in men with prostate cancer.[68]
## Gastrointestinal system[edit]
The incidence of diarrhea with bicalutamide monotherapy in the EPC trial was comparable to placebo (6.3% vs. 6.4%, respectively).[9] In phase III studies of bicalutamide monotherapy for LAPC, the rates of diarrhea for bicalutamide and castration were 6.4% and 12.5%, respectively, the rates of constipation were 13.7% and 14.4%, respectively, and the rates of abdominal pain were 10.5% and 5.6%, respectively.[69]
## Heart, liver, kidneys, and lungs[edit]
### Cardiovascular system[edit]
See also: Testosterone and the cardiovascular system
In the LPC group of the EPC study, although 150 mg/day bicalutamide monotherapy had reduced mortality due to prostate cancer relative to placebo, there was a trend toward significantly increased overall mortality for bicalutamide relative to placebo at 5.4-year follow-up (25.2% vs. 20.5%).[19][70][71] This was because more bicalutamide than placebo recipients had died due to causes unrelated to prostate cancer in this group (16.8% vs. 9.5% at 5.4-year follow-up; 10.2% vs. 9.2% at 7.4-year follow-up).[19][71][8] At 7.4-year follow-up, there were numerically more deaths from heart failure (1.2% vs. 0.6%; 49 vs. 25 patients) and gastrointestinal cancer (1.3% vs. 0.9%) in the bicalutamide group relative to placebo recipients, although cardiovascular morbidity was similar between the two groups and there was no consistent pattern suggestive of drug-related toxicity for bicalutamide.[8][72] In any case, although the reason for the increased overall mortality with 150 mg/day bicalutamide monotherapy has not been fully elucidated,[28] it has been said that the finding that heart failure was twice as frequent in the bicalutamide group warrants further investigation.[73] In this regard, it is notable that low testosterone levels in men have been associated in epidemiological studies with cardiovascular disease as well as with a variety of other disease states (including hypertension, hypercholesterolemia, diabetes, obesity, Alzheimer's disease, osteoporosis, and frailty).[74]
According to Iversen et al. (2006), the increased non-prostate cancer mortality with bicalutamide monotherapy in LPC patients has also been seen with castration (via orchiectomy or GnRH analogue monotherapy) and is likely a consequence of androgen deprivation in men rather than a specific drug toxicity of bicalutamide:[75]
> The increased number of deaths in patients with localized disease receiving bicalutamide was meticulously investigated and they appeared to be due to a number of small imbalances rather than a specific cause. In addition, no direct toxic effect on any organ system could be identified. From this it may be speculated that the excess deaths in patients who are at low risk from prostate cancer mortality reflect the impact of endocrine therapy (rather than bicalutamide in particular). [...] The increased number of non-prostate cancer deaths in the early castration therapy arm [(via orchiectomy or GnRH monotherapy)] in the [Medical Research Council] study suggests that the trend towards an increased number of deaths in patients with localized disease in the present study is a reflection of early endocrine therapy as a concept rather than a bicalutamide-related phenomenon.[75]
A study of 300 to 600 mg/day bicalutamide monotherapy in 248 men with LAPC or metastatic prostate cancer found that there were no effects of bicalutamide on heart rate, blood pressure, or electrocardiogram parameters.[76][77] In addition, at 5-year follow-up, the incidence of cardiovascular events was low, with no differences between the bicalutamide and castration groups.[76][77] There were also no differences in the incidences of arrhythmia, myocardial infarction, or other ischemic cardiac or cerebrovascular conditions.[76][77] These findings suggest that bicalutamide does not cause an excess in cardiovascular events or conditions.[76][77]
A meta-analysis of prospective randomized clinical trials of GnRH agonist-based ADT for the treatment of non-metastatic prostate cancer that included over 4,000 patients found no evidence of increased cardiovascular mortality or overall mortality.[78] Non-prostate cancer mortality was not specifically assessed.[78]
A case report in which bicalutamide was described as a probable cause of heart failure in an elderly man with prostate cancer has been published.[79]
Cardiovascular risks have been reviewed and subjected to meta-analysis.[80][81]
#### Coagulation[edit]
NSAA monotherapy is associated with a greater risk of venous thromboembolism (VTE) than non-use, although not to the same extent as surgical or medical castration or particularly high-dose estrogen therapy.[82][83][84][85][86]
### Kidney function[edit]
Androgens and anabolic steroids, including testosterone, have trophic and anabolic effects in the kidneys.[87][88][89][90] Androgen deprivation therapy, including with GnRH agonists and bicalutamide monotherapy, may increase the risk of kidney failure in men.[91][92][93] A large randomized controlled trial in men with prostate cancer found that the incidence of kidney failure was 1 to 2% with combined androgen blockade using bicalutamide or flutamide.[94][95][96]
#### Anemia[edit]
Androgens including testosterone are known to stimulate erythropoiesis (formation of red blood cells) and increase hematocrit (red blood cell levels).[97][98] These effects are mediated by increasing production and secretion of erythropoietin from the kidneys.[98] Erythropoietin in turn stimulates erythropoiesis in hematopoietic tissues such as bone marrow.[99] The high levels of testosterone in males are why hematocrit and hemoglobin levels are higher in men than in women.[100] Due to stimulation of erythropoiesis, anabolic–androgenic steroids (AAS) such as oxymetholone and nandrolone decanoate are effective for and used in the treatment of severe anemia (very low hematocrit).[98][101] High doses or levels of AAS, including testosterone, can cause polycythemia—high red blood cell and/or hemoglobin levels that increase the risk of stroke—as an adverse effect.[97][98] Conversely, whether via castration, NSAA monotherapy, or CAB, decreased erythropoiesis resulting in mild anemia is a common side effect of ADT in men.[53][102] The incidence of anemia with bicalutamide as a monotherapy or with castration was about 7.4% in clinical trials.[53] A decrease of hemoglobin levels of 1 to 2 g/dL after approximately six months of treatment may be observed.[102]
### Liver toxicity[edit]
Bicalutamide may cause liver changes rarely, such as elevated transaminases and jaundice.[103] In the EPC study of 4,052 prostate cancer patients who received 150 mg/day bicalutamide as a monotherapy, the incidence of abnormal liver function tests was 3.4% for bicalutamide and 1.9% for standard care (a 1.5% difference potentially attributable to bicalutamide) at 3-year median follow-up.[8][104] For comparison, the incidences of abnormal liver function tests are 42 to 62% for flutamide, 2 to 3% for nilutamide,[103][105] and (dose-dependently) between 10% and 28% for CPA,[106][107][108] whereas there appears to be no risk with enzalutamide.[109][110] In the EPC trial, bicalutamide-induced liver changes were usually transient and rarely severe.[8] The medication was discontinued due to liver changes (manifested as hepatitis or marked increases in liver enzymes) in approximately 0.3% to 1% of patients treated with it for prostate cancer in clinical trials.[59][111]
The risk of liver changes with bicalutamide is considered to be small but significant, and monitoring of liver function is recommended.[8][112] Elevation of transaminases above twice the normal range or jaundice may be an indication that bicalutamide should be discontinued.[113] Liver changes with bicalutamide usually occur within the first 3 or 4 months of treatment, and it is recommended that liver function be monitored regularly for the first 4 months of treatment and periodically thereafter.[59] Symptoms that may indicate liver dysfunction include nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, dark urine, and jaundice.[59]
A total of 7 case reports of bicalutamide-associated hepatotoxicity or liver failure, two of which were fatal, have been published in the literature as of 2018.[114][103][115] One of these cases occurred after two doses of bicalutamide, and has been said to more likely to have been caused by prolonged prior exposure of the patient to flutamide and CPA.[103][105][116][117][118] In the reported cases of bicalutamide-associated hepatotoxicity, the dosages of the drug were 50 mg/day (three), 80 mg/day (one), 100 mg/day (one), and 150 mg/day (two).[114][115] Relative to flutamide (which has an estimated incidence rate of 0.03% or 3 per 10,000), hepatotoxicity is far rarer with bicalutamide and nilutamide, and bicalutamide is regarded as having the lowest risk of the three medications.[119][116][120] For comparison, by 1996, 46 cases of severe cholestatic hepatitis associated with flutamide had been reported, with 20 of the cases resulting in death.[106] Moreover, a 2002 review reported that there were 18 reports of hepatotoxicity associated with CPA in the medical literature, with 6 of the reported cases resulting in death, and the review also cited a report of an additional 96 instances of hepatotoxicity that were attributed to CPA, 33 of which resulted in death.[106]
The clinical studies that have found elevated liver enzymes and the case reports of hepatotoxicity with bicalutamide have all specifically pertained to men of advanced age with prostate cancer.[8][104][103][115] It is notable that older age, for a variety of reasons, appears to be an important risk factor for drug-induced hepatotoxicity.[121][122] As such, the risk of liver changes with bicalutamide may be less in younger patients, for instance young hirsute women and transgender women.[121][122] However, it has been reported on the basis of very limited evidence that this may not be the case with flutamide.[123] There is no evidence of greater liver function changes with higher doses of bicalutamide.[124]
From a theoretical standpoint (on the basis of structure–activity relationships), it has been suggested that flutamide, bicalutamide, and nilutamide, to varying extents, all have the potential to cause liver toxicity.[125] However, in contrast to flutamide, hydroxyflutamide, and nilutamide, bicalutamide exhibits much less or no mitochondrial toxicity and inhibition of enzymes in the electron transport chain such as respiratory complex I (NADH ubiquinone oxidoreductase), and this may be the reason for its much lower risk of hepatotoxicity in comparison.[126][127][128][129] The activity difference may be related to the fact that flutamide, hydroxyflutamide, and nilutamide all possess a nitroaromatic group, whereas in bicalutamide, a cyano group is present in place of this nitro group, potentially reducing toxicity.[116][126][129][130]
* v
* t
* e
Published case reports of bicalutamide-associated liver injury # Age Sex Dosage Use Onset Outcome Source
1 60 years Male 50 mg/day Prostate cancer 2 days Survived Dawson et al. (1997)
2 79 years Male 80 mg/day Prostate cancer 1.5 months Survived Ikemoto et al. (2000)
3 59 years Male 50 mg/day Prostate cancer 4 days Death O'Bryant et al. (2008)
4 61 years Male 50 mg/day Prostate cancer 3.5 months Death Castro Beza et al. (2008)
5 81 years Male 150 mg/day Prostate cancer 3 weeks Survived Hussain et al. (2014)
6 62 years Male 100 mg/day Prostate cancer 4.5 months Survived Yun et al. (2016)
7 67 years Male 150 mg/day Prostate cancer 3 weeks Survived Gretarsdottir et al. (2018)
8 74 years Male 80 mg/day Prostate cancer 1.5 months Survived Kotoh et al. (2018)
9 79 years Male ? Prostate cancer 15 days Survived Saito (2020)
Notes: Additional cases of bicalutamide-associated adverse liver changes have been reported. These include 11 cases in a 2006 Spanish pharmacovigilance system report (including 1 case of hepatitis, 2 cases of cholestatic hepatitis, 1 case of jaundice, 4 cases of elevated liver enzymes, and 1 case of elevated bilirubin; no deaths) and a number of cases in the FDA Adverse Event Reporting System (FAERS). Also 5 cases of jaundice (including 1 death) were reported out of ~3,700 men in clinical trials. Sources: Main: [131][132]
### Lung toxicity[edit]
Case reports of interstitial pneumonitis associated with bicalutamide treatment have been published in the medical literature.[133][134][135][136] Interstitial pneumonitis can progress to pulmonary fibrosis and can be fatal. Interstitial pneumonitis with bicalutamide is said to be an extremely rare event.[137] The risk is much lower than that with nilutamide (which has an incidence rate of 0.5–2% of patients).[138]:81[134][139] In a large cohort of prostate cancer patients, the incidence of interstitial pneumonitis with NSAAs was 0.77% for nilutamide, 0.04% (4 per 10,000) for flutamide, and 0.01% (1 per 10,000) for bicalutamide.[3] An assessment done prior to the publication of the aforementioned study estimated the rates of pulmonary toxicity with flutamide, bicalutamide, and nilutamide as 1 case, 5 cases, and 303 cases per million, respectively.[140] A Japanese study reported a reporting odds ratio (ROR) of 9.2 for bicalutamide and interstitial pneumonitis.[141] In addition to interstitial pneumonitis, there is a smaller number of published case reports of eosinophilic lung disease associated with bicalutamide.[142][143] Side effects associated with the rare lung toxicity of bicalutamide may include dyspnea (difficult breathing or shortness of breath), cough, and pharyngitis (inflammation of the pharynx, resulting in sore throat).[144]
* v
* t
* e
Published case reports of bicalutamide-associated lung toxicity # Age Sex Dosage Onset Type of injury Outcome Ref
1 69 years Male 200 mg/day 6 months Eosinophilic lung disease Recovered Wong et al. (1998)
2 ~76 years Male 200 mg/day 8 months Interstitial pneumonitis Recovered McCaffrey & Scher (1998)
3 ~82 years Male 80 mg/day 4 weeks Interstitial pneumonitis Recovered Shioi et al. (2003)
4 ~72 years Male 80 mg/day 2.5 months Interstitial pneumonitis Recovered, then deatha Shioi et al. (2005)
5 84 years Male ? 8 months Interstitial pneumonitis Recovered Kobayashi et al. (2006)
6 76 years Male ? ? Interstitial pneumonitis ? Gifford & DeLong (2008)
7 85 years Male ? 4 months Interstitial pneumonitis Death Kawahara et al. (2009)
8 78 years Male 80 mg/day 8 months Interstitial pneumonitis Recovered Masago et al. (2011)
9 77 years Male ? 7 months Interstitial pneumonitis Death Song et al. (2014)
10 77 years Male >50 mg/day ~12 months Interstitial pneumonitis Death Molina Mancero et al. (2016)
11 79 years Male ? 1 month Interstitial pneumonitis Death Polatoglu et al. (2017)
12 66 years Male ? ? Interstitial pneumonitis Recovered Kim et al. (2018)
13 66 years Male ? ? Interstitial pneumonitis Recovered Derichs et al. (2018)
14 86 years Male 150 mg/day 6 years Eosinophilic pneumonitis Recovered Umeojiako & James (2019)
15 75 years Male ? 2 weeks Interstitial pneumonitis Death Maeda et al. (2019)
16 79 years Male ? 1.5 months Interstitial pneumonitis Recovered Saito (2020)
17 66 years Male 50 mg/day 6 months Interstitial pneumonitis Recovered Smith & Antonarakis (2020)
Footnotes: a = Died of pneumothorax followed by spontaneous rupture of bulla induced by previous interstitial pneumonitis 14 months after discontinuation of bicalutamide and recovery from interstitial pneumonitis. Notes: Twelve additional cases of bicalutamide-associated interstitial pneumonitis, three of which resulted in death, were observed in an 87,000-patient cohort from MedWatch (U.S. FDA passive adverse-event reporting database) between 1998 and 2000 (0.01% incidence). The median age of the patients was 73.5 years (range 59 to 91 years), and median duration of bicalutamide exposure was 7.5 weeks (range 1 to 312 weeks). Cases of interstitial pneumonitis have also been reported in association with flutamide, nilutamide, and gonadotropin-releasing hormone (GnRH) agonists.
## Modification of side effects by castration[edit]
Combination of bicalutamide with medical (i.e., a GnRH analogue) or surgical castration modifies the side-effect profile of bicalutamide. Some of its side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when the drug is combined with a GnRH analogue,[145] while certain other side effects, including hot flashes, depression, fatigue, and sexual dysfunction,[146] occur much more frequently in combination with a GnRH analogue.[12][147][148] It is thought that this is due to the suppression of estrogen levels (in addition to androgen levels) by GnRH analogues, as estrogens may compensate for various negative central effects of androgen deprivation.[12] If bicalutamide is combined with a GnRH analogue or surgical castration, the elevation of androgen and estrogen levels in men caused by bicalutamide will be prevented and the side effects of excessive estrogens, namely gynecomastia, will be reduced.[145] However, due to the loss of estrogen, bone loss will accelerate and the risk of osteoporosis developing with long-term therapy will increase.[149]
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127. ^ Marroquin LD, Hynes J, Dykens JA, Jamieson JD, Will Y (June 2007). "Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants". Toxicological Sciences. 97 (2): 539–47. doi:10.1093/toxsci/kfm052. PMID 17361016. "Apoptosis induced by the androgen antagonist bicalutamide is receptor mediated (Lin et al., 2006), and hence a dominant effect at low concentrations, and hepatoxicity is a rare event (Dawson et al., 1997), in accord with its relative lack of toxicity to galactose-grown cells."
128. ^ Kashimshetty R, Desai VG, Kale VM, Lee T, Moland CL, Branham WS, New LS, Chan EC, Younis H, Boelsterli UA (July 2009). "Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity". Toxicology and Applied Pharmacology. 238 (2): 150–9. doi:10.1016/j.taap.2009.05.007. PMID 19442681.
129. ^ a b Ball AL, Kamalian L, Alfirevic A, Lyon JJ, Chadwick AE (July 2016). "Identification of the Additional Mitochondrial Liabilities of 2-Hydroxyflutamide When Compared With its Parent Compound, Flutamide in HepG2 Cells". Toxicological Sciences. 153 (2): 341–351. doi:10.1093/toxsci/kfw126. PMC 5036617. PMID 27413113.
130. ^ Boelsterli UA, Ho HK, Zhou S, Leow KY (October 2006). "Bioactivation and hepatotoxicity of nitroaromatic drugs". Current Drug Metabolism. 7 (7): 715–27. doi:10.2174/138920006778520606. PMID 17073576.
131. ^ Gretarsdottir, Helga M.; Bjornsdottir, Elin; Bjornsson, Einar S. (2018). "Bicalutamide-Associated Acute Liver Injury and Migratory Arthralgia: A Rare but Clinically Important Adverse Effect". Case Reports in Gastroenterology. 12 (2): 266–270. doi:10.1159/000485175. ISSN 1662-0631.
132. ^ "Drug Record: Bicalutamide - LiverTox". National Library of Medicine. National Institutes of Health. Retrieved 13 November 2018.
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134. ^ a b Masago T, Watanabe T, Nemoto R, Motoda K (December 2011). "Interstitial pneumonitis induced by bicalutamide given for prostate cancer". International Journal of Clinical Oncology. 16 (6): 763–5. doi:10.1007/s10147-011-0239-x. PMID 21537882. S2CID 24068787.
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136. ^ Umeojiako WI, James M (2019). "Bicalutamide-induced Eosinophilic Pneumonitis-A Serendipitous Diagnosis". Journal of Case Reports in Medicine. 8 (1): 6. doi:10.25149/case-reports.v8i1.164. ISSN 2090-5351.
137. ^ Ricci F, Buzzatti G, Rubagotti A, Boccardo F (November 2014). "Safety of antiandrogen therapy for treating prostate cancer". Expert Opinion on Drug Safety. 13 (11): 1483–99. doi:10.1517/14740338.2014.966686. PMID 25270521. S2CID 207488100.
138. ^ Gulley JL (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7. Archived from the original on 25 April 2016.
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141. ^ Matsumoto K, Nakao S, Hasegawa S, Matsui T, Shimada K, Mukai R, Tanaka M, Uranishi H, Nakamura M (2020). "Analysis of drug-induced interstitial lung disease using the Japanese Adverse Drug Event Report database". SAGE Open Med. 8: 2050312120918264. doi:10.1177/2050312120918264. PMC 7262990. PMID 32528682.
142. ^ Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 497, 521. ISBN 978-0-7817-2845-4. Archived from the original on 11 May 2016.
143. ^ Wong PW, Macris N, DiFabrizio L, Seriff NS (February 1998). "Eosinophilic lung disease induced by bicalutamide: a case report and review of the medical literature". Chest. 113 (2): 548–50. doi:10.1378/chest.113.2.548. PMID 9498983.
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149. ^ Vanderschueren D, Gaytant J, Boonen S, Venken K (June 2008). "Androgens and bone". Current Opinion in Endocrinology, Diabetes and Obesity. 15 (3): 250–4. doi:10.1097/MED.0b013e3282fe6ca9. PMID 18438173. S2CID 23851080.
* v
* t
* e
Bicalutamide
Topics
* Medical uses of bicalutamide
* Side effects of bicalutamide
* Pharmacology of bicalutamide
* Comparison of bicalutamide with other antiandrogens
Related drugs
* Nonsteroidal antiandrogens: First-generation: Flutamide
* Nilutamide
* Topilutamide; Second-generation: Apalutamide
* Enzalutamide
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Side effects of bicalutamide | c0570242 | 6,626 | wikipedia | https://en.wikipedia.org/wiki/Side_effects_of_bicalutamide | 2021-01-18T18:28:21 | {"umls": ["C0570242"], "wikidata": ["Q48841275"]} |
A number sign (#) is used with this entry because of evidence that ring dermoid of the cornea can be caused by heterozygous mutation in the PITX2 gene (601542) on chromosome 4q25.
Clinical Features
Mattos et al. (1980) reported a Peruvian family in which the grandmother, all 3 of her children (daughters), and 1 of the 2 sons of a daughter had bilateral annular limbal dermoids with corneal and conjunctival extensions. There were no associated extraocular anomalies. The choristomas (mass of tissue histologically normal for another site) involved the limbus for 360 degrees, and extended anteriorly onto the cornea and posteriorly about 5 mm. (Conjunctival and limbal dermoids occur with the Goldenhar syndrome (164210).) Each patient had hairs growing from the tumor mass.
Xia et al. (2004) studied a large Chinese family in which 21 individuals were affected by RDC. Patients showed yellow-white tumor-like apophyses on the corneal border of both eyes. The apophyses were clinically detectable at birth and progressively impaired the patients' vision with aging. Some affected individuals also had glaucoma, unilateral cataracts, or involuntary oscillation of the eyes. The only clinical manifestation in the affected individuals was in the eyes. Affected cases were found in both males and females in each of 4 generations, with instances of male-to-male transmission.
Mapping
In a large Chinese family segregating RDC, Xia et al. (2004) found linkage of the disorder to chromosome 4q24-q26.
Molecular Genetics
In affected members of a large Chinese family segregating RDC, Xia et al. (2004) identified heterozygosity for an R62H mutation in the PITX2 gene (601542.0012); the mutation was not found in 8 unaffected members of the family.
Eyes \- Annular limbal dermoids extending onto cornea and conjunctiva Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| RING DERMOID OF CORNEA | c1867155 | 6,627 | omim | https://www.omim.org/entry/180550 | 2019-09-22T16:35:07 | {"mesh": ["C535684"], "omim": ["180550"], "orphanet": ["91481"]} |
Kallmann syndrome is a condition characterized by delayed or absent puberty and an impaired sense of smell.
This disorder is a form of hypogonadotropic hypogonadism, which is a condition resulting from a lack of production of certain hormones that direct sexual development. These hormones are normally made in a part of the brain called the hypothalamus. Males born with hypogonadotropic hypogonadism often have an unusually small penis (micropenis) and undescended testes (cryptorchidism). At puberty, most affected individuals do not develop secondary sex characteristics, such as the growth of facial hair and deepening of the voice in males, the start of monthly periods (menstruation) and breast development in females, and a growth spurt in both sexes. Without treatment, most affected men and women are unable to have biological children (infertile).
In Kallmann syndrome, the sense of smell is either diminished (hyposmia) or completely absent (anosmia). This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. Many people with Kallmann syndrome are not aware that they are unable to detect odors until the impairment is discovered through testing.
Kallmann syndrome can have a wide variety of additional signs and symptoms. These include a failure of one kidney to develop (unilateral renal agenesis), abnormalities of bones in the fingers or toes, a cleft lip with or without an opening in the roof of the mouth (a cleft palate), abnormal eye movements, hearing loss, and abnormalities of tooth development. Some affected individuals have a feature called bimanual synkinesis, in which the movements of one hand are mirrored by the other hand. Bimanual synkinesis can make it difficult to do tasks that require the hands to move separately, such as playing a musical instrument.
## Frequency
Kallmann syndrome occurs more often in males than in females, with an estimated prevalence of 1 in 30,000 males and 1 in 120,000 females.
## Causes
Changes in more than 20 genes have been associated with Kallmann syndrome. Among the most common causes of the condition are mutations in the ANOS1, CHD7, FGF8, FGFR1, PROK2, or PROKR2 gene. In some cases, affected individuals have mutations in more than one of these genes. Additionally, researchers have identified mutations in other genes that may contribute to the development and features of Kallmann syndrome, but are unlikely to cause the disease on their own.
The genes associated with Kallmann syndrome play roles in the development of certain areas of the brain before birth. Although some of their specific functions are unclear, these genes appear to be involved in the formation and movement (migration) of a group of nerve cells that are specialized to process the sense of smell (olfactory neurons). These nerve cells originate in the developing nose and then migrate together to a structure in the front of the brain called the olfactory bulb, which is critical for the perception of odors. Studies suggest that the genes associated with Kallmann syndrome are also involved in the migration of neurons that produce a hormone called gonadotropin-releasing hormone (GnRH). Like olfactory neurons, GnRH-producing neurons migrate from the developing nose to the front of the brain. GnRH controls the production of several hormones that direct sexual development before birth and during puberty. These hormones are important for the normal function of the ovaries in women and testes in men.
Studies suggest that mutations in genes associated with Kallmann syndrome disrupt the migration of olfactory nerve cells and GnRH-producing nerve cells in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired or absent. Misplacement of GnRH-producing neurons in the brain prevents the production of other sex hormones, which interferes with normal sexual development and causes the characteristic features of hypogonadotropic hypogonadism. It is unclear how gene mutations lead to the other signs and symptoms that can occur in Kallmann syndrome. Because the features of this condition vary among individuals, additional genetic and environmental factors likely contribute to this disease.
Together, mutations in known genes account for about 30 percent of all cases of Kallmann syndrome. In cases without a mutation in one of the identified genes, the cause of the condition is unknown. Researchers are looking for additional genetic changes that can cause this disorder.
### Learn more about the genes associated with Kallmann syndrome
* ANOS1
* CHD7
* FGF8
* FGFR1
* PROK2
* PROKR2
* SOX10
Additional Information from NCBI Gene:
* AXL
* CCDC141
* DUSP6
* FEZF1
* FGF17
* FLRT3
* HS6ST1
* IL17RD
* NSMF
* SEMA3A
* SEMA7A
* SPRY4
* WDR11
## Inheritance Pattern
When Kallmann syndrome is caused by ANOS1 gene mutations, the condition has an X-linked recessive pattern of inheritance. The ANOS1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to be present in both copies of the gene to cause the disorder. No females with two ANOS1 gene mutations have been reported in the medical literature. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Most of the time, people with Kallmann syndrome resulting from an ANOS1 gene mutation inherit the mutation from their mothers, who carry a single altered copy of the gene in each cell (and generally do not have any signs or symptoms of the condition). Other people have Kallmann syndrome as a result of a new mutation in the ANOS1 gene.
When Kallmann syndrome results from mutations in other genes, it often has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from an affected mother or father. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
In several families, Kallmann syndrome has shown an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Kallmann syndrome | c0162809 | 6,628 | medlineplus | https://medlineplus.gov/genetics/condition/kallmann-syndrome/ | 2021-01-27T08:25:19 | {"gard": ["10771", "3071", "3070", "3073", "10772", "10773", "10774"], "mesh": ["D017436"], "omim": ["308700", "147950", "244200", "610628", "308750"], "synonyms": []} |
In a mother and her 4 children, Goldstein et al. (1985) described a previously unreported syndrome of distichiasis with congenital heart defects and mixed peripheral vascular anomalies. The 52-year-old mother had ventricular septal defect. Two daughters had surgery for patent ductus arteriosus (see 607411). Sinus bradycardia alone (elder son), with stress-induced asystole (younger son), and with wandering atrial pacemaker (both daughters) were documented electrocardiographically. Of the 5, 3 had edema, 2 had visible varicosities, 3 had symptoms of chronic venous disease of the legs, and the older daughter, aged 19, had complaints suggesting arterial disease in the legs.
Hair \- Double rows of eyelashes Cardiac \- Congenital heart defect \- Ventricular septal defect \- Patent ductus arteriosus \- Sinus bradycardia \- Stress-induced asystole \- Wandering atrial pacemaker Limbs \- Leg edema \- Varicose veins \- Arterial disease of legs Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| DISTICHIASIS WITH CONGENITAL ANOMALIES OF THE HEART AND PERIPHERAL VASCULATURE | c1852062 | 6,629 | omim | https://www.omim.org/entry/126320 | 2019-09-22T16:42:12 | {"mesh": ["C565092"], "omim": ["126320"], "orphanet": ["1683"]} |
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-36 (MRD36) is caused by heterozygous mutation in the PPP2R1A gene (605983) on chromosome 19q13.
Clinical Features
The Deciphering Developmental Disorders Study (2015) identified 3 patients with intellectual disability who carried heterozygous mutations in the PPP2R1A gene. All 3 patients had hypoplasia of the corpus callosum. The first patient also had joint hypermobility, deviation of the fifth finger, pectus excavatum, and seizures. The second patient had plagiocephaly, anteverted nares, muscular hypotonia, broad hallux, abnormal hair whorl, ocular abnormalities, hydrocephalus, and seizures. The third patient had plagiocephaly, delayed gross motor development, congenital visual impairment, facial asymmetry, and prominent metopic ridge.
Houge et al. (2015) reported 2 additional unrelated patients with MRD36. Common features included hypotonia, severely delayed psychomotor development with absent or very poor speech, agenesis of the corpus callosum, enlarged ventricles, hypotonic facies with open mouth, and mild hypertelorism.
Molecular Genetics
The Deciphering Developmental Disorders Study (2015) examined 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements. The authors discovered 12 novel genes associated with developmental disorders. The PPP2R1A gene was implicated in a gene-specific analysis (p = 2.03 x 10(-8)). The Deciphering Developmental Disorders Study (2015) identified 3 patients with intellectual disability who had heterozygous de novo missense mutations in the PPP2R1A gene. Two patients carried the same mutation (R182W; 605983.0001), and the third carried a different mutation (P179L; 605983.0002).
In 2 unrelated patients with MRD36, Houge et al. (2015) identified 2 different de novo heterozygous missense mutations in the PPP2R1A gene (605983.0001 and 605983.0003). The mutations were found by parent-child trio exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies showed that all 3 reported PPP2R1A mutations affected PP2A holoenzyme formation by variably interfering with interaction of the A-alpha subunit with the C subunit. All mutations resulted in decreased phosphatase activity, consistent with a dominant-negative effect.
INHERITANCE \- Autosomal dominant GROWTH Height \- Increased height (in some patients) HEAD & NECK Head \- Microcephaly (in some patients) Face \- Hypotonic facies Eyes \- Downslanting palpebral fissures \- Hypertelorism, mild Mouth \- Open mouth \- Tented upper lip MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Poor or absent speech \- Inability to walk (in some patients) \- Seizures (in some patients) \- Hypoplasia or agenesis of the corpus callosum \- Enlarged ventricles \- Delayed myelination MISCELLANEOUS \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the protein phosphatase 2, structural/regulatory subunit A, alpha gene (PPP2R1A, 605983.0001 ) ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| MENTAL RETARDATION, AUTOSOMAL DOMINANT 36 | c4225352 | 6,630 | omim | https://www.omim.org/entry/616362 | 2019-09-22T15:49:06 | {"doid": ["0070066"], "omim": ["616362"], "orphanet": ["457284"], "synonyms": []} |
A group of variants of mendelian susceptibility to mycobacterial diseases (MSMD) due to dominantly inherited partial deficiencies in interferon gamma receptor 1 (IFN-gammaR1), IFN-gammaR2, signal transducer and activator of transcription 1 (STAT1) or interferon regulator factor 8 (IRF8).
## Epidemiology
Prevalence is unknown.
## Clinical description
The clinical disease seen in all of these variants is relatively mild. Weakly virulent bacillus Calmette-Guérin (BCG) and Mycobacterium avium complex infections are most commonly seen in patients with these diseases.
## Etiology
AD MSMD due to a partial deficiency is caused by a mutation in one of the following genes: IFNGR1, IFNGR2, STAT1 or IRF8, depending on the variant. These mutations affect the IFN-gamma pathway and lead to susceptibility to infections with BCG and other environmental mycobacteria.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiency | None | 6,631 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319543 | 2021-01-23T17:05:12 | {"icd-10": ["D84.8"], "synonyms": ["Autosomal dominant MSMD due to a partial deficiency"]} |
## Clinical Features
Albumin (103600) is the major transport protein in blood for zinc. On the basis of a detailed comparison of the 18 x-ray crystal structures of human albumin available in a protein database, together with competitive zinc/cadmium-binding studies using cadmium NMR, mutagenesis, and molecular modeling, Stewart et al. (2003) proposed a model for the high-affinity Zn(2+) site and a mechanism for fatty acid-induced switching of its ligand environment.
In 2 generations of a family with male-to-male transmission, Smith et al. (1976) found elevated plasma zinc due apparently to increased binding to albumin. No ill effects were noted.
Failla et al. (1982) showed that albumin is not increased in these cases but that excess zinc is bound to albumin. They did not identify the molecular change in albumin responsible for the increased binding. (Copper and iron were not increased.)
Familial hyperzincemia may be a 'nondisease' caused by abnormal binding by a mutant albumin, comparable to familial dysalbuminemic hyperthyroxinemia.
Hambidge et al. (1985) observed very high plasma zinc in an 18-year-old Pakistani man with recurrent arthritis and pyoderma gangrenosa from an early age. The authors thought the genetic form of hyperzincemia was excluded by normal values in all close relatives. He could, of course, be the victim of a new mutation. Alternatively, there may have been unknown dosing with zinc.
Sampson et al. (1997) reported a patient with very high concentrations of zinc in plasma but with clinical features of zinc deficiency. Biochemical analysis showed that the patient had high concentrations of an unidentified zinc-binding protein which was subsequently identified by Richmond et al. (1999) as calprotectin, a complex of S100A8 (123885) and S100A9 (123886).
### Hyperzincemia and Hypercalprotectinemia
Sampson et al. (2002) reported 5 patients with hyperzincemia in whom hypercalprotectinemia was also present: an 18-year-old male (previously reported by Sampson et al., 1997), a 9-year-old girl and a 14-year-old boy with similar clinical features, the 35-year-old mother of the 18 year old (previously reported by Saito et al. (2002)), and a 21-year-old man with a milder phenotype than the other patients. All patients presented with recurrent infections, hepatosplenomegaly, anemia, and evidence of systemic inflammation. Three had cutaneous inflammation and 3 presented in infancy with severe growth failure. Size exclusion chromatography showed that zinc and calprotectin were associated in a broad fraction with a molecular mass range of 100 to 300 kD. Analysis by electrophoresis and mass spectrometry showed that the calprotectin in the patients' protein, although raised in quantity, contained normal S100A8 and S100A9 subunits.
Lab \- Elevated plasma zinc \- Increased zinc binding to albumin \- Copper and iron not increased Inheritance \- Autosomal dominant \- ? albumin gene (103600) mutation ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| ZINC, ELEVATED PLASMA | c1860229 | 6,632 | omim | https://www.omim.org/entry/194470 | 2019-09-22T16:31:43 | {"mesh": ["C565988"], "omim": ["194470"], "orphanet": ["251523"], "synonyms": ["Alternative titles", "ALBUMIN BINDING OF ZINC, ELEVATED", "HYPERZINCEMIA, FAMILIAL DYSALBUMINEMIC"]} |
Tachylalia or tachylogia[1] is extremely rapid speech.[2] Tachylalia by itself is not considered a speech disorder. Tachylalia occurs in many clutterers and many people who have speech disorders.
Tachylalia is a generic term for speaking fast, and does not need to coincide with other speech problems.
Tachylalia may be exhibited as a single stream of rapid speech without prosody, and can be delivered quietly or mumbled. Tachylalia can be simulated by stimulating the brain electronically.[3]
## Occurrences[edit]
Tachylalia can occur with the following:
* Normal speech
* Cluttering
* Parkinson's disease[4]
* Pressure of speech
## References[edit]
1. ^ Tachylalia[permanent dead link]
2. ^ Tachylalia
3. ^ BÉRUBÉ, Louise. Terminologie de neuropsychologie et de neurologie du comportement, Montréal, Les Éditions de la Chenelière Inc.,1991, 176 p., p.58.
4. ^ Tachylalia: clinical and acoustic study of 149 subjects
This speech and debate-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Tachylalia | None | 6,633 | wikipedia | https://en.wikipedia.org/wiki/Tachylalia | 2021-01-18T18:39:32 | {"wikidata": ["Q4452818"]} |
Gaucher disease - ophthalmoplegia - cardiovascular calcification is a variant of Gaucher disease, also known as a Gaucher-like disease that is characterized by cardiac involvement.
## Epidemiology
This syndrome is rare with less than 30 cases reported in the literature.
## Clinical description
The principle manifestation is progressive calcification of the aorta, and of the aortic and/or mitral valves. Other common features include mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia.
## Etiology
The disease is caused by homozygous D409H (1342G to C) mutations in the GBA gene (1q21) that encodes the lysosomal membrane-associated glycoprotein, glucosylceramidase. The enzyme deficiency resulting from the mutation leads to accumulation of glucosylceramide (GL1) and other glycolipids in the cells of the reticuloendothelial system.
## Diagnostic methods
The diagnosis can be made by measuring glucosylceramidaseactivity and is confirmed by identification of the D409H GBA gene mutation.
## Antenatal diagnosis
Prenatal diagnosis is possible through detection of the glucosylceramidase deficiency in amniocytes or chorionic villus samples, or through screening for the GBA gene mutation in families in which the D409H allele has been identified in both parents or an affected brother or sister.
## Genetic counseling
The syndrome is transmitted in an autosomal recessive manner.
## Management and treatment
Patients with this syndrome require close monitoring by echocardiography as the cardiac complications require aortic and mitral valve replacement. Enzyme substitution therapy, involving regular intravenous infusions of the recombinant glucosylceramidase enzyme, imiglucerase, has been used successfully in the treatment of this disorder following surgery.
## Prognosis
The prognosis for patients depends on the outcome of the heart surgery.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome | c1856476 | 6,634 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2072 | 2021-01-23T18:59:01 | {"gard": ["12504", "2445"], "mesh": ["C565553"], "omim": ["231005"], "umls": ["C1856476", "C2931585"], "icd-10": ["E75.2"], "synonyms": ["Cardiovascular Gaucher disease", "Gaucher disease type 3C", "Gaucher-like disease"]} |
A number sign (#) is used with this entry because of evidence that childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy (NADGP) is caused by homozygous mutation in the SQSTM1 gene (601530) on chromosome 5q35.
Description
Childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy is an autosomal recessive progressive disorder characterized by onset of gait ataxia, cognitive decline, and gaze palsy in the first or second decades. Additional features include dysarthria, dystonia, and athetoid movements. Some patients may become wheelchair-bound as young adults (summary by Haack et al., 2016).
Clinical Features
Haack et al. (2016) reported 9 patients from 4 unrelated families with onset of a neurodegenerative disorder between 7 and 15 years of age. The patients presented with progressively unsteady gait and ataxia. More variable presenting symptoms included upper limb ataxia, urinary incontinence, and cognitive decline. Many of the patients became wheelchair-bound in young adulthood. The patients had variable cerebellar and pyramidal symptoms, such as dysdiadochokinesis, dysmetria, nystagmus, and hyperreflexia, as well as dysarthria, dystonia, athetotic movements, vertical gaze palsy, and oculomotor apraxia. A few had parkinsonism, tremor, or mild hearing loss. None had seizures. Muscle biopsies, when performed, were normal, although some patients showed mildly decreased mitochondrial complex IV activity. Brain imaging showed cerebellar atrophy in 2 families, iron deposition in the basal ganglia without cerebellar atrophy in a third family, and no abnormalities in the fourth family.
Inheritance
The transmission pattern of NADGP in the families reported by Haack et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 9 patients from 4 unrelated families with NADGP, Haack et al. (2016) identified 3 different homozygous loss-of-function mutations in the SQSTM1 gene (601530.0008-601530.0010). The mutations were found by exome sequencing and segregated with the disorder in the families; none of the heterozygous carriers had skeletal or neurologic abnormalities. Patient fibroblasts showed absence of the SQSTM1 protein as well as abnormalities in the early response to mitochondrial depolarization and autophagosome formation, as demonstrated by decreased perinuclear clustering of mitochondria after depolarization treatment. However, overall clearance of mitochondria was similar to controls after 24 hours, indicating redundant cellular mechanisms for mitochondrial removal.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, mild (in some patients) Eyes \- Vertical gaze palsy \- Oculomotor apraxia \- Nystagmus \- Saccadic eye pursuit GENITOURINARY Bladder \- Urinary incontinence (in some patients) NEUROLOGIC Central Nervous System \- Gait abnormalities \- Gait ataxia \- Limb ataxia \- Tremor \- Dystonia \- Dysarthria \- Dysmetria \- Dysdiadochokinesis \- Cognitive decline \- Cognitive impairment \- Pyramidal signs \- Hyperreflexia \- Cerebellar signs \- Cerebellar atrophy (in some patients) \- Iron deposition in the basal ganglia (in one family) MISCELLANEOUS \- Onset between 7 and 15 years of age \- Progressive disorder \- Many patients become wheelchair-bound as young adults MOLECULAR BASIS \- Caused by mutation in the sequestosome 1 gene (SQSTM1, 601530.0008 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| NEURODEGENERATION WITH ATAXIA, DYSTONIA, AND GAZE PALSY, CHILDHOOD-ONSET | c4310693 | 6,635 | omim | https://www.omim.org/entry/617145 | 2019-09-22T15:46:42 | {"omim": ["617145"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive cornea plana-2 (CNA2) is caused by homozygous or compound heterozygous mutation in the KERA gene (603288) on chromosome 12q21.
Description
Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. CNA2 is a severe form of the disorder, which is frequently associated with additional ocular manifestations (summary by Tahvanainen et al., 1996).
For discussion of genetic heterogeneity of CNA, see CNA1 (121400).
Clinical Features
Eriksson et al. (1973) pointed out that the autosomal recessive form of CNA has more severe manifestations than the dominant form (CNA1; 121400) in terms of reduced visual activity, extreme hyperopia (usually +10 diopters (D) or more), hazy corneal limbus, opacities in the corneal parenchyma, and marked arcus senilis (often detected at an early age).
Tahvanainen et al. (1996) noted that a round and opaque thickening, approximately 5 mm wide and located centrally, occurs in most cases of the recessive form but never in the dominant form. Additional anomalies such as malformations of the iris, a slit-like pupil, and adhesions between the iris and cornea are more prevalent in the recessive form.
Tahvanainen et al. (1996) compared dominant and recessive forms of cornea plana in the Finnish population by measuring horizontal corneal refraction values in diopters. A control population of 473 individuals had a mean value of 43.4 (SD = 1.5 D) for men and 43.7 (SD = 1.6 D) for women, whereas in 51 subjects affected with CNA2, the mean value was 29.9 (SD = 5.1 D), and in 5 subjects affected with CNA1, the mean value was 37.8 (SD = 1.6 D).
Al Hazimi and Khan (2015) noted that flat keratometry contributes to the hyperopia and associated refractive accommodative esotropia in recessive CNA. They compared the axial length of the right eye of 8 children, aged 10 to 12 years, from 7 families with CNA2 with the axial length of 50 control right eyes from children aged 4 to 12 years. Axial lengths were longer in the affected eyes despite greater hyperopia, providing evidence that axial length is not shortened by the disease.
Inheritance
Felix (1925) described 2 brothers with CNA from an uncle-niece mating. Forsius (1961) reported a study in Finland in which 19 cases were found in 9 families in patterns consistent with autosomal recessive inheritance.
Population Genetics
Cornea plana has a high prevalence in Finland. An extensive pedigree with 27 affected persons in 13 sibships was presented by Forsius et al. (1980).
Mapping
Tahvanainen et al. (1995) mapped the CNA2 locus to chromosome 12 by linkage to an interval of approximately 10 cM between markers D12S82 and D12S327. They tentatively assigned the locus to 12q21. Tahvanainen et al. (1995) extended the mapping studies by exploiting the haplotype and linkage disequilibrium information that could be derived from the Finnish population. By testing 32 independent families with 10 polymorphic markers in the CNA2 interval, they demonstrated strong allelic association between CNA2 and a set of markers with a peak at marker D12S351. The critical region for CNA2 could be narrowed to 0.04-0.3 cM from marker D12S351, thus defining a critical interval of 0.08-0.60 cM.
Although the 12q region was excluded as the site of the mutation in 2 Finnish families with autosomal dominant cornea plana (CNA1) by Tahvanainen et al. (1996), Tahvanainen et al. (1996) described a Cuban pedigree in which dominantly inherited cornea plana was linked to the same region of 12q in which the recessive form is located.
Molecular Genetics
Pellegata et al. (2000) cloned the human KERA gene as a candidate gene for CNA2 and identified mutations in 47 CNA2 patients. Forty-six Finnish patients were homozygous for a founder missense mutation leading to the substitution of a highly conserved amino acid (603288.0001), and 1 Chinese American patient was homozygous for a mutation leading to a premature stop codon that truncates the KERA protein (603288.0002).
In a consanguineous pedigree in which corneal plana cosegregated with microphthalmia, Lehmann et al. (2001) identified a homozygous thr215-to-lys substitution (603288.0003) at the start of a highly conserved leucine-rich repeat motif in keratocan. Structural modeling predicted that this mutation altered the length and position of 1 of these motifs on the beta-sheet array of keratocan. The authors concluded that normal corneal function is dependent on the regular spacing of collagen fibrils, and the predicted alteration of the tertiary structure of KERA is the probable mechanism of the cornea plana phenotype.
Khan et al. (2004) described the ophthalmic phenotype of a family with autosomal recessive cornea plana due to a novel KERA mutation. Five of 6 sibs were affected and had small, flat corneas with arcus juvenilis and variable degrees of corneal clouding, variable anterior chamber depth, and severe hyperopia due to decreased axial length. Genetic testing revealed a novel homozygous nonsense mutation in exon 3 (603288.0004) of the keratocan gene in affected individuals. The clinically unaffected parents were confirmed as carriers; the clinically unaffected sib had no KERA mutation. The authors stated that this novel point mutation in the KERA gene was the fourth described to that time.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Cornea plana \- Reduced visual activity \- Extreme hyperopia \- Hazy corneal limbus \- Corneal parenchymal opacities \- Early onset corneal arcus \- Thin cornea \- Indistinct sclerocorneal boundary \- Flattened corneal curvature (reduced keratometry) \- Normal axial length MOLECULAR BASIS \- Caused by mutation in the keratocan gene (KERA, 603288.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| CORNEA PLANA 2, AUTOSOMAL RECESSIVE | c1857574 | 6,636 | omim | https://www.omim.org/entry/217300 | 2019-09-22T16:29:24 | {"doid": ["0060287"], "mesh": ["C565677"], "omim": ["217300"], "orphanet": ["53691"], "synonyms": []} |
Alopecia areata is a common disorder that causes hair loss. "Alopecia" is a Latin term that means baldness, and "areata" refers to the patchy nature of the hair loss that is typically seen with this condition.
In most people with alopecia areata, hair falls out in small, round patches, leaving coin-sized areas of bare skin. This patchy hair loss occurs most often on the scalp but can affect other parts of the body as well. Uncommonly, the hair loss involves the entire scalp (in which case the condition is known as alopecia totalis) or the whole body (alopecia universalis). Other rare forms of alopecia areata, which have different patterns of hair loss, have also been reported.
Alopecia areata affects people of all ages, although it most commonly appears in adolescence or early adulthood. Hair loss occurs over a period of weeks. The hair usually grows back after several months, although it may fall out again. In some cases, unpredictable cycles of hair loss followed by regrowth can last for years. In addition to hair loss, some affected individuals have fingernail and toenail abnormalities, such as pits on the surface of the nails.
The hair loss associated with alopecia areata is not painful or disabling. However, it causes changes in a person's appearance that can profoundly affect quality of life and self-esteem. In some people, the condition can lead to depression, anxiety, and other emotional or psychological issues.
## Frequency
Alopecia areata affects 1 in every 500 to 1,000 people in the United States. It is one of many recognized forms of alopecia; alopecia areata is the second most common form after androgenetic alopecia (male-pattern baldness in men and female-pattern baldness in women). Alopecia areata affects men and women equally, and it can occur in people of any ethnic background.
## Causes
The causes of alopecia areata are complex and not well understood. A combination of factors likely underlies the disorder, including changes in many genes that function in the hair and skin and in the immune system.
Alopecia areata is one of a large group of immune system diseases classified as autoimmune disorders. Normally, the immune system protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. In autoimmune disorders, the immune system malfunctions and attacks the body's own tissues instead. For reasons that are unclear, in alopecia areata the immune system targets hair follicles, stopping hair growth. However, the condition does not permanently damage the follicles, which is why hair may later regrow.
Many of the genes that have been associated with alopecia areata participate in the body's immune response. These include several genes belonging to a gene family called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders. Each HLA gene has many different variations, allowing each person's immune system to react to a wide range of foreign proteins. Certain variations in HLA genes likely contribute to the inappropriate immune response targeting hair follicles that leads to alopecia areata. Immune system genes outside the HLA complex, such as several genes involved in inflammation, have also been associated with alopecia areata.
Some of the genetic variations associated with alopecia areata have been identified in people with other autoimmune disorders, which suggests that this group of diseases may share some genetic risk factors. People with alopecia areata have an increased risk of developing other autoimmune disorders, including vitiligo, systemic lupus erythematosus, atopic dermatitis, allergic asthma, and autoimmune thyroid diseases (such as Hashimoto thyroiditis and Graves disease). Similarly, people with those autoimmune disorders have an increased risk of developing alopecia areata.
In many cases, it is unknown what triggers hair loss in people with alopecia areata. It is possible that environmental factors, such as emotional stress, physical injury, or illness, provoke an abnormal immune response in people who are at risk. However, in most affected people, the onset of hair loss has no clear explanation.
### Learn more about the genes associated with Alopecia areata
* AIRE
* FLG
* HLA-DQA1
* HLA-DQB1
* HLA-DRB1
* MTHFR
* PMS2
* PTPN22
* VDR
Additional Information from NCBI Gene:
* BTNL2
* CCL2
* CLEC16A
* CTLA4
* ERBB3
* HLA-A
* HLA-C
* HLA-DMB
* HLA-DQA2
* HLA-DQB2
* HLA-DRA
* HLA-DRB5
* HSPA1B
* ICOS
* IFNG
* IKZF4
* IL13
* IL16
* IL1B
* IL1RN
* IL2
* IL2RA
* IL4
* KLRK1
* LTA
* MICA
* MIF
* NOS3
* NOTCH4
* PRDX5
* RAET1L
* SPATA5
* STX17
* TLR1
* TNF
* TRAF1
* TSBP1
* ULBP3
## Inheritance Pattern
The inheritance pattern of alopecia areata is unclear because multiple genetic and environmental factors appear to be involved. Overall, the risk of developing the condition is greater for first-degree relatives (such as siblings or children) of affected individuals than it is in the general population. People with alopecia areata are also more likely to have family members with other autoimmune disorders.
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Alopecia areata | c0263505 | 6,637 | medlineplus | https://medlineplus.gov/genetics/condition/alopecia-areata/ | 2021-01-27T08:24:48 | {"gard": ["5782", "614"], "mesh": ["C537055"], "omim": ["104000", "610753"], "synonyms": []} |
Arachnoid cysts are sacs filled with cerebrospinal fluid (CSF) that are located between the brain or spinal cord and the arachnoid membrane, one of the three membranes that cover the brain and spinal cord. Arachnoid cysts can be primary or secondary. Primary arachnoid cysts are congenital (present at birth), resulting from abnormal development of the brain and spinal cord during early pregnancy. Secondary arachnoid cysts are less common, and result from head injuries, meningitis, tumors, or as a complication of brain surgery. Signs and symptoms depend on the location and size of the cyst and may include headache, nausea and vomiting, seizures, hearing and visual disturbances, vertigo, and difficulties with balance and walking. Although many affected individuals develop symptoms in the first year of life, some never develop symptoms. Whether and how to treat the condition depends on the location and size of the cyst. In some cases, arachnoid cysts are part of a genetic syndrome such as Chudley-McCullough syndrome, mucopolysaccharidosis, or Marfan syndrome, where there are many other associated signs and symptoms. When treatment is recommended, it may include placing a shunt to drain the fluid; surgically removing the cyst membranes; or opening the cyst so the fluid can drain into the CSF.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Arachnoid cysts | c0078981 | 6,638 | gard | https://rarediseases.info.nih.gov/diseases/17/arachnoid-cysts | 2021-01-18T18:02:03 | {"mesh": ["D016080"], "omim": ["207790"], "orphanet": ["2356"], "synonyms": ["Arachnoid cysts, intracranial", "Intracranial arachnoid cysts"]} |
A number sign (#) is used with this entry because Lujan-Fryns syndrome is caused by mutation in the MED12 gene (300188) on chromosome Xq13.
Opitz-Kaveggia syndrome (OKS; 305450) is an allelic disorder with an overlapping phenotype.
Clinical Features
Lujan et al. (1984) described 4 mentally retarded males in a large kindred with marfanoid habitus and similar craniofacial changes: long, narrow face, small mandible, high-arched palate, and hypernasal voice. Fryns and Buttiens (1987) described 2 pairs of mildly to moderately mentally retarded brothers with these same features. Lalatta et al. (1991) reported 4 sporadic cases and suggested that psychotic behavior may be a manifestation. Fryns (1991) gave a brief report of 2 affected brothers and 2 sporadic males with this disorder, varying in age from 14 to 24 years. All were referred to the genetics clinic with the diagnosis of Marfan syndrome (154700). Gurrieri and Neri (1991) observed the syndrome in brother and sister. They thought that the affected sister was a manifesting heterozygote. They suggested that the Lujan-Fryns syndrome is an X-linked dominant condition with higher penetrance and greater expressivity in males. Rivera et al. (1992) reported a case, raising to 19 (18M:1F) the total reported. Rivera et al. (1992) stated that 7 of the 19 cases were isolated (i.e., nonfamilial). Fryns (1993) found 18 cases of this disorder among 682 cases of syndromic mental retardation; the fragile X syndrome (300624), the Aarskog syndrome (305400), and the Coffin-Lowry syndrome (303600) represented 560, 60, and 20 cases, respectively. Leroy et al. (1993) reviewed the disorder in 8 young adults, including 2 pairs of brothers and 1 set of 3 sibs. Lacombe et al. (1993) reported 3 additional cases with useful photographs.
Wittine et al. (1999) reported a male patient and his maternal uncle, both of whom had features consistent with the diagnosis of Lujan-Fryns syndrome. Both patients also had a ventricular septal defect and aortic root dilation, neither of which had been described previously in Lujan-Fryns syndrome. The authors suggested that the similarity of Lujan-Fryns syndrome to Marfan syndrome and the presence of aortic root dilation in their patients may implicate a mutation in a structural connective tissue gene in the etiology of this condition.
Williams (2006) provided a detailed neuropsychologic evaluation of the patient reported by Wittine et al. (1999). His speech and language development was delayed by 1 year at age 3 years. He subsequently had severe learning disabilities and trouble with short-term memory despite normal IQ measurements. He had attention-deficit hyperactivity disorder (ADHD; see 143465), oppositional defiant disorder, poor impulse control, obsessive compulsive disorder (see 164230), and low frustration tolerance. He was shy and seldom socialized with peers. Williams (2006) emphasized that the patient would not be classified as having mental retardation because of his normal IQ, although he had severe social and cognitive impairment. Williams (2006) noted that the patient was exposed to prenatal alcohol, but did not have physical characteristics of fetal alcohol syndrome.
Stathopulu et al. (2003) described a 16-year-old male with phenotypic features of Lujan-Fryns syndrome and terminal deletion of chromosome 5p. He had the behavior of an autistic spectrum disorder. Symmetrical intrauterine growth retardation was evident upon delivery at 37 weeks' gestation. In the early neonatal period he had a 'shrill, cat-like cry' and micrognathia, resulting in feeding difficulties severe enough to require tube feeding. He had hypotonia during the first year and significant feeding difficulties. At the age of 16 years he was tall (height in the 75th centile) and slim (weight in the 50th centile). He had a very nasal voice which the authors thought was different from the voice of teenagers with velopharyngeal incompetence. The uvula and soft palate did not reach the back wall of the pharynx during speech, suggesting the presence of a submucous cleft palate, which was treated by surgical pharynoplasty.
Lerma-Carrillo et al. (2006) reported a 23-year-old man with Lujan-Fryns syndrome admitted to a psychiatric hospital by judicial order for behavioral misconduct and aggressive behavior, including pyromania. He had a marfanoid habitus with long narrow face, hypernasal speech, high-arched palate, low-set ears, pectus excavatum, and long thin fingers and toes. He had a borderline IQ, a long history of hyperactivity and behavioral disorders, and complete agenesis of the corpus callosum on MRI. Psychiatric evaluation showed low insight and concrete thought pattern. A maternal uncle was similarly affected and also had ascending aortic aneurysm and a double row of teeth; a sister was diagnosed with anorexia nervosa (see 606788). A review of 32 published cases of Lujan-Fryns syndrome indicated a high frequency of psychopathology, most commonly an autistic-like disorder.
Molecular Genetics
In affected members of the family reported by Lujan et al. (1984), Schwartz et al. (2007) identified a mutation in the MED12 gene (N1007S; 300188.0002). Schwartz et al. (2007) noted that 1 of the family members originally thought to be affected was later found not to be affected with the same disorder and did not carry the MED12 mutation. Schwartz et al. (2007) identified the N1007S mutation in affected members of an unrelated family. The findings indicated that Lujan-Fryns syndrome and Opitz-Kaveggia syndrome are allelic disorders. Clinically, Lujan-Fryns syndrome could be distinguished by tall stature, hypernasal voice, hyperextensible digits, and high nasal root. Schwartz et al. (2007) suggested that the Lujan-Fryns syndrome designation be used only for those cases with a compatible clinical phenotype and mutations in the MED12 gene.
INHERITANCE \- X-linked recessive GROWTH Height \- Tall stature Other \- Marfanoid habitus HEAD & NECK Head \- Macrocephaly Face \- Prominent forehead \- Long face \- Narrow face \- Maxillary hypoplasia \- Micrognathia \- Short philtrum \- Deep philtrum Ears \- Low-set ears \- Abnormally folded helix Nose \- Long nose \- High nasal bridge \- Narrow nasal bridge Mouth \- High-arched palate \- Thin upper lip \- Open mouth Teeth \- Double row of teeth \- Crowded teeth CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect Vascular \- Ascending aortic aneurysm CHEST External Features \- Pectus excavatum GENITOURINARY Internal Genitalia (Male) \- Borderline to large testes SKELETAL \- Joint laxity \- Joint contractures Skull \- Small mandible Hands \- Long fingers \- Thin fingers \- Broad thumbs NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Hypotonia, generalized \- Seizures \- Agenesis of the corpus callosum Behavioral Psychiatric Manifestations \- Aggressive behavior \- Autistic-like behavior \- Poor social interactions \- Hyperactivity \- Emotional instability \- Obsessive compulsive disorder \- Poor impulse control \- Low frustration tolerance \- Psychosis VOICE \- Hypernasal voice MISCELLANEOUS \- Allelic disorder to Opitz-Kaveggia syndrome ( 305450 ) MOLECULAR BASIS \- Caused by mutation in the S. cerevisiae homolog of mediator of RNA polymerase II transcription, subunit 12 gene (MED12, 300188.0002 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| LUJAN-FRYNS SYNDROME | c0796022 | 6,639 | omim | https://www.omim.org/entry/309520 | 2019-09-22T16:17:52 | {"mesh": ["C537724"], "omim": ["309520"], "orphanet": ["776"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED, WITH MARFANOID HABITUS"], "genereviews": ["NBK1676"]} |
A rare genetic dystonia characterized by focal or segmental isolated dystonia involving the face, neck, upper limbs (commonly writing dystonia), larynx, or trunk, with an onset from childhood to early adulthood. Dystonia may be tremulous, giving rise to head or hand tremor. Mode of inheritance is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Primary dystonia, DYT27 type | c4225336 | 6,640 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=464440 | 2021-01-23T16:58:43 | {"omim": ["616411"], "icd-10": ["G24.1"]} |
An internalizing disorder (or internalising disorder) is one type of emotional and behavioral disorder, along with externalizing disorders, and low incidence disorders.[1] One who has an internalizing disorder will keep their problems to themselves, or internalize the problems.
## Contents
* 1 Signs and symptoms
* 2 DSM-5
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Signs and symptoms[edit]
Behaviors that are apparent in those with internalizing disorders include depression, withdrawal, anxiety, and loneliness.[1] There are also behavioral characteristics involved with internalizing disorders. Some behavioral abnormalities include poor self-esteem, suicidal behaviors, decreased academic progress, and social withdrawal.[2] Internalizing one's problems, like sadness, can cause the problems to grow into larger burdens such as social withdrawal, suicidal behaviors or thoughts, and other unexplained physical symptoms.[3]
## DSM-5[edit]
The internalizing disorders, with high levels of negative affectivity, include depressive disorders, anxiety disorders, obsessive-compulsive and related disorders, trauma and stressor-related disorders, and dissociative disorders.[4][5] Others like bulimia, and anorexia also come under this category.[1]
## Treatment[edit]
Some treatments for internalizing disorders include antidepressants, electroconvulsive therapy, and psychotherapy.[6]
## See also[edit]
* Anxiety
* Depression
* Emotional and behavioral disorders
* Externalizing disorders
* Obsessive-compulsive disorders
## References[edit]
1. ^ a b c Smith, D.D. "Emotional or Behavioral Disorders Defined". education.com. Archived from the original on 31 March 2018. Retrieved 17 March 2014.
2. ^ "Internalizing Symptoms and Affect of Children with Emotional and Behavioral Disorders". studymode.com. Retrieved 17 March 2014.
3. ^ DiMaria, Lauren. "Internalizing Behaviors and Depression". about.com. Retrieved 17 March 2014.
4. ^ Regier, Darrel A.; Kuhl, Emily A.; Kupfer, David J. (June 2013). "The DSM-5: Classification and criteria changes". World Psychiatry. 12 (2): 92–98. doi:10.1002/wps.20050. PMC 3683251. PMID 23737408.
5. ^ Turygin, Nicole C.; Matson, Johnny L.; Adams, Hilary; Belva, Brian (August 2013). "The effect of DSM-5 criteria on externalizing, internalizing, behavioral and adaptive symptoms in children diagnosed with autism". Developmental Neurorehabilitation. 16 (4): 277–282. doi:10.3109/17518423.2013.769281. PMID 23617257.
6. ^ "Depression". helpguide.org. Archived from the original on 14 March 2014. Retrieved 17 March 2014.
## External links[edit]
* Depression at National Institute of Mental Health website
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Internalizing disorder | None | 6,641 | wikipedia | https://en.wikipedia.org/wiki/Internalizing_disorder | 2021-01-18T18:58:33 | {"wikidata": ["Q17126447"]} |
Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air (0.04% carbon dioxide and 21% oxygen); facultatively anaerobic bacteria can grow in the presence or absence of air. Microaerophilic bacteria do not grow at all aerobically or grow poorly, but grow better under 10% carbon dioxide or anaerobically. Anaerobic bacteria can be divided into strict anaerobes that can not grow in the presence of more than 0.5% oxygen and moderate anaerobic bacteria that are able of growing between 2 and 8% oxygen.[1] Anaerobic bacteria usually do not possess catalase, but some can generate superoxide dismutase which protects them from oxygen.
The clinically important anaerobes in decreasing frequency are:[2] 1\. Six genera of Gram-negative rods (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Bilophila and Sutterella spp.); 2\. Gram-positive cocci (primarily Peptostreptococcus spp.); 3\. Gram-positive spore-forming (Clostridium spp.) and non-spore-forming bacilli (Actinomyces, Propionibacterium, Eubacterium, Lactobacillus and Bifidobacterium spp.); and 4\. Gram-negative cocci (mainly Veillonella spp.) .
The frequency of isolation of anaerobic bacterial strains varies in different infectious sites.[3] Mixed infections caused by numerous aerobic and anaerobic bacteria are often observed in clinical situations.
Anaerobic bacteria are a common cause of infections, some of which can be serious and life-threatening. Because anaerobes are the predominant components of the normal flora of the skin and mucous membranes, they are a common cause of infections of endogenous origin.[4] Because of their fastidious nature, anaerobes are hard to culture and isolate and are often not recovered from infected sites. The administration of delayed or inappropriate therapy against these organisms may lead to failures in eradication of these infections. The isolation of anaerobic bacteria requires adequate methods for collection, transportation and cultivation of clinical specimens.[5] The management of anaerobic infection is often difficult because of the slow growth of anaerobic organisms, which can delay their identification by the frequent polymicrobial nature of these infections and by the increasing resistance of anaerobic bacteria to antimicrobials.[6]
## Contents
* 1 Signs and symptoms
* 1.1 Central nervous system
* 1.2 Upper respiratory tract and head and neck infections
* 1.3 Lung infections
* 1.4 Abdominal infections
* 1.5 Female genital infections
* 1.6 Skin and soft-tissue infections
* 1.7 Osteomyelitis and septic arthritis
* 1.8 Bacteremia
* 1.9 Neonatal infection
* 2 Causes
* 3 Management
* 4 References
* 5 Further reading
* 6 External links
## Signs and symptoms[edit]
Anaerobes have been found in infections throughout the human body.[7] The frequency of the host or patient's recovery depends on the employment of proper methods of collection of specimen, their transportation to the microbiology laboratory and cultivation. The recovery of organisms depends on the site of infection and is related to the adjacent mucous membranes microbial flora.
### Central nervous system[edit]
Anaerobes are able to cause all types of intracranial infections. These often cause subdural empyema, and brain abscess, and rarely cause epidural abscess and meningitis. The origin of brain abscess is generally an adjacent chronic ear, mastoid, or sinus infection [8] oropharynx, teeth [9] or lungs.[10] Mastoid and ear or infections generally progress to the temporal lobe or cerebellum, while facial sinusitis commonly causes frontal lobe abscess. Hematogenous spread of the infection into the CNS often occurs after oropharyngeal, dental, or pulmonary infection. Infrequently bacteremia originating of another location or endocarditis can also cause intracranial infection.
Meningitis due to anaerobic bacteria is infrequent and may follow respiratory tract infection or complicate a cerebrospinal fluid shunt.[11] Neurological shunt infections are often caused by skin bacteria such as Cutibacterium acnes,[12] or in instances of ventriculoperitoneal shunts that perforate the gut, by anaerobes of enteric origin (i.e. Bacteroides fragilis).[13]Clostridium perfringens can cause of brain abscesses and meningitis following intracranial surgery or head trauma.
The anaerobes often isolated from brain abscesses complicating respiratory and dental infections are anaerobic Gram-negative bacilli (AGNB, including Prevotella, Porphyromonas, Bacteroides), Fusobacterium and Peptostreptococcus spp. Microaerophilic and other streptococci are also often isolated. Actinomyces are rarely isolated.
At the stage of encephalitis, antimicrobial therapy and utilization of measures to lower the increase in the intracranial pressure can prevent the formation of an intracranial abscess However, after an abscess has emerged, surgical removal or drainage may be necessary, along with an extended course of antimicrobial therapy (4–8 weeks). Some advocate complete drainage of intracranial abscess, while others use repeated aspirations of the abscess.,[14] Repeated aspirations of an abscess are preferable in those with multiple abscesses or when the abscess is located in a predominate brain site. Administration of antimicrobials in a high-dose for an extended period of time can offer an alternative treatment strategy in this type of patients and may substitute for surgical evacuation of an abscess.[15]
Because of the poor penetration of many antimicrobial agents through the blood–brain barrier, there are few agents available for the treatment of intracranial infections. The antimicrobials with good intracranial penetration are metronidazole, chloramphenicol, penicillins, and meropenem. Optimally, the selection of antimicrobial is done according to the recovered isolates and their antimicrobial susceptibilities. A substantial improvement in patients' survival rate has occurred after the introduction of computed tomography (CT) and other scans and utilization of metronidazole therapy.
### Upper respiratory tract and head and neck infections[edit]
Anaerobes can be isolated from most types of upper respiratory tract and head and neck infection, and are especially common in chronic ones. These include tonsillar,[16] peritonsillar and retropharyngeal abscesses, chronic otitis media, sinusitis and mastoiditis, eye ocular) infections,[17] all deep neck space infections, parotitis, sialadenitis, thyroiditis, odontogenic infections, and postsurgical and nonsurgical head and neck wounds and abscesses.,[18] The predominant organisms are of oropharyngeal flora origin and include AGNB, Fusobacterium[19] and Peptostreptococcus spp.
Anaerobes involve almost all dental infections. These include dental abscesses,[20] endodontal pulpitis and periodontal (gingivitis and periodontitis) infections, and perimandibular space infection.[21][22] Pulpitis can lead to abscess formation and eventually spread to the mandible and other neck spaces. In addition to strict anaerobic bacteria, microaerophilic streptococci and Streptococcus salivarius can also be present.
Fusobacterium spp. and anaerobic spirochetes are often the cause of acute necrotizing ulcerative gingivitis (or Vincent's angina) which is a distinct form of ulcerative gingivitis.
Deep neck infections that develop as a consequence of oral, dental and pharyngeal infections are generally polymicrobial in nature. These include extension of retropharyngeal cellulitis or abscess, mediastinitis following esophagus perforation, and dental or periodontal abscess.[23]
### Lung infections[edit]
In adults the most common source of aspiration pneumonia is aspiration of oropharyngeal secretions or gastric contents. In children the most common cause is aspiration of infected amniotic fluid, or vaginal secretions. Severe periodontal or gingival diseases are important risk factors for establishment of an anaerobic pleuropulmonary infection. Progression of the infection from pneumonitis into necrotizing pneumonia and pulmonary abscess can occur, with or without the development of empyema.,[24][25] The infection is often polymicrobial in nature and isolates of community-acquired infection (in 60–80% of cases) are aerobic and anaerobic belonging to the individual's oropharyngeal flora. The anaerobic bacteria commonly recovered are Prevotella, Porphyromonas, Fusobacterium and Peptostreptococcus spp., and the aerobic bacteria are beta-hemolytic and microaerophilic streptococci.[26] Anaerobic bacteria can also be isolated in about 35% of individuals who suffer from nosocomial-acquired aspiration pneumonia [27] and pneumonia associated with tracheostomy with and without mechanical ventilation,[28] where they are often isolated along with Enterobacteriaceae, Pseudomonas spp. and Staphylococcus aureus. It is important that specimens are obtained in a method that avoids their contamination by the oral micro flora.
### Abdominal infections[edit]
Secondary peritonitis and intra-abdominal abscesses including splenic and hepatic abscesses generally occur because of the entry of enteric micro-organisms into the peritoneal cavity through a defect in the wall of the intestine or other viscus as a result of obstruction, infarction or direct trauma. Perforated appendicitis, diverticulitis, inflammatory bowel disease with perforation and gastrointestinal surgery are often associated with polymicrobial infections caused by aerobic and anaerobic bacteria, where the number of isolates can average 12 (two-thirds are generally anaerobes).[29] The most common aerobic and facultative bacteria are Escherichia coli, Streptococcus spp. (including Enterococcus spp.), and the most frequently isolated anaerobic bacteria are the B. fragilis group, Peptostreptococcus spp., and Clostridium spp.[30]
Abdominal infections are characteristically biphasic: an initial stages of generalized peritonitis associated with Escherichia coli sepsis, and a later stages, in which intra abdominal abscesses harboring anaerobic bacteria ( including B. fragilis group ) emerge.
The clinical manifestations of secondary peritonitis are a reflection of the underlying disease process. Fever, diffuse abdominal pain, nausea and vomiting are common. Physical examination generally show signs of peritoneal inflammation, isuch as rebound tenderness, abdominal wall rigidity and decrease in bowel sounds. These early findings may be followed by signs and symptoms of shock.
Biliary tract infection is usually caused by E. coli, Klebsiella and Enterococcus spp. Anaerobes (mostly B. fragilis group, and rarely C. perfringens) can be recovered in complicated infections associated with carcinoma, recurrent infection, obstruction, bile tract surgery or manipulation.[31]
Laboratory studies show elevated blood leukocyte count and predominance of polymorphonuclear forms. Radiographs studies may show free air in the peritoneal cavity, evidence of ileus or obstruction and obliteration of the psoas shadow. Diagnostic ultrasound, gallium and CT scanning may detect appendiceal or other intra-abdominal abscesses. Polymicrobial postoperative wound infections can occur.
Treatment of mixed aerobic and anaerobic abdominal infections requires the utilization of antimicrobials effective against both components of the infection as well as surgical correction and drainage of pus. Single and easily accessible abscesses can be drained percutaneously.[32]
### Female genital infections[edit]
Female genital tract infections caused by anaerobic bacteria are polymicrobial and include: soft-tissue perineal, vulvar and Bartholin gland abscesses; bacterial vaginosis; endometritis; pyometra; salpingitis; adnexal abscess; tubo-ovarian abscesses; intrauterine contraceptive device-associated infection; pelvic inflammatory disease,[33] which may include pelvic cellulitis and abscess; amnionitis; septic pelvic thrombophlebitis; septic abortion; and postsurgical obstetric and gynecologic infections.,[34][35] Getting adequate microbiological cultures is essential. It is important to avoid contaminating the culture with the normal genital flora. Methods that can ensure adequate cultures are laparoscopy, culdocentesis, or obtaining quantitative endometrial cultures employing a telescoping catheter.
The anaerobes often recovered include Prevotella bivia, Prevotella disiens, and Peptostreptococcus, Porphyromonas and Clostridium spp. Bacteroides fragilis group is rarely recovered in these infections compared to intra-abdominal infection.[36] Actinomyces spp. and Eubacterium nodatum are often recovered in infections associated with intrauterine devices. Mobiluncus spp. can be associated with bacterial vaginosis.[37] The aerobic bacteria also found mixed with these anaerobic bacteria include Enterobacteriaceae, Streptococcus spp. (including groups A and B), Neisseria gonorrhoeae, Chlamydia spp. and Mycoplasma hominis. Free gas in the tissues, abscess formation and foul-smelling discharge is commonly associated with the presence of anaerobic bacteria. Treatment of these infections includes the use of antimicrobials active against all of the potential aerobic and anaerobic bacterial pathogens. Antimicrobials against sexually transmissible pathogens should also be administered.[speculation?][citation needed]
### Skin and soft-tissue infections[edit]
The infections that frequently involve anaerobic bacteria include superficial infections, including infected paronychia, infected human or animal bites, cutaneous ulcers, cellulitis, pyoderma, and hidradenitis suppurativa.[38] Secondary infected sites include secondary infected diaper rash, gastrostomy or tracheostomy site wounds, scabies or kerion infections, eczema, psoriasis, poison ivy, atopic dermatitis, eczema herpeticum, infected subcutaneous sebaceous or inclusion cysts, and postsurgical wound infection.[39]
Skin involvement in subcutaneous tissue infections includes: cutaneous and subcutaneous abscesses,[40] breast abscess, decubitus ulcers, infected pilonidal cyst or sinus, Meleney's ulcer infected diabetic (vascular or trophic) ulcers, bite wound,[41] anaerobic cellulitis and gas gangrene, bacterial synergistic gangrene, and burn wound infection.[42] Deeper anaerobic soft-tissue infections are necrotizing fasciitis, necrotizing synergistic cellulitis, gas gangrene and crepitus cellulitis. These can involve the fascia as well as the muscle surrounded by the fascia, and may also induce myositis and myonecrosis.
The isolates found in soft-tissue infections can vary depending on the type of infection. The infection's location and the circumstances causing the infection can also influence the nature of the microorganisms recovered. Bacteria that are members of the 'normal flora' of the region of the infection are often also isolated from lesions involving anaerobic bacteria.
Specimens obtained from wounds and subcutaneous tissue infections and abscesses in the rectal area (perirectal abscess, decubitus ulcer) or that are of gut flora origin(i.e. diabetic foot infection) often to yield colonic flora organisms.[43] These are generally B. fragilis group, Clostridium spp., Enterobacteriaceae and Enterococcus spp. On the other hand, infections in and around the oropharynx, or infections that originate from that location, frequently contain oral flora organisms (i.e. paronychia, bites, breast abscess). These bacteria include pigmented Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp. Skin flora organisms such as S. aureus and Streptococcus spp., or nosocomially acquired microorganisms can be recovered at all body locations. Human bite infections often contain Eikenella spp. and animal bites harbor Pasteurella multocida in addition to oral flora,
Anaerobes infections are often polymicrobial in nature, and sometimes (i.e. decubitus ulcers, diabetic foot ulcer) they are complicated by bacteremia and or osteomyelitis .[44] Infections which are in the deep tissues ( necrotizing cellulitis, fasciitis and myositis) often include Clostridium spp., S. pyogenes or polymicrobic combinations of both aerobic and anaerobic bacteria. Gas in the tissues and putrid-like pus with a gray thin quality are often found in these infections, and they are frequently associated with a bacteremia and high mortality rate.
Treatment of deep-seated soft-tissue infections includes: vigorous surgical management that includes surgical debridement and drainage. Even though there are no controlled studies that support this approach improvement of the involved tissues oxygenation by enhancement of blood supply and administration of hyperbaric oxygen, especially in clostridial infection, may be helpful.
### Osteomyelitis and septic arthritis[edit]
Anaerobic bacteria are often found in oesteomyelitis of the long bones especially after trauma and fracture, osteomyelitis associated with peripheral vascular disease, and decubitus ulcers and osteomyelitis of the facial and cranial bones.[45] Many of these bone infections are polymicrobial in nature.
Cranial and facial bones anaerobic osteomyelitis often originates by the spread of the infection from a contiguous soft-tissue source or from dental, sinus, or ear infection. The high concentration of anaerobic bacteria in the oral cavity explains their importance in cranial and facial bone infections. The high number of gut anaerobes in pelvic osteomyelitis is generally caused by their spread from decubitus ulcers sites. The anaerobic organisms in osteomyelitis associated with peripheral vascular disease generally reach the bone from adjacent soft-tissue ulcers. Long bones osteomyelitis is often caused by trauma, hematogenic spread, or the presence of a prosthetic device.
Peptostreptococcus and Bacteroides spp. are the most frequently recovered isolates at all bone infections, including those caused by bites and cranial infection. Pigmented Prevotella and Porphyromonas spp. are especially common in bite and skull bone infections, whereas members of the B. fragilis group are often found in vascular disease or neuropathy. Fusobacterium spp., which belongs to the oral microflora, are most often isolated from bites and from cranial and facial bone infections. Clostridium spp. are frequently recovered in long bones infections, mostly in association with traumatic wounds. Because Clostridium spp. colonize the lower gastrointestinal tract, they can contaminate compound lower extremities fractures.
Septic arthritis due to anaerobic bacteria is frequently associated with contiguous or hematogenous infection spread, prosthetic joints and trauma. Most septic arthritis cases caused by anaerobic bacteria are monomicrobial. The predominant anaerobic bacteria isolated are Peptostreptococcus spp. and P. acnes (frequently found in prosthetic joint infection), B. fragilis and Fusobacterium spp. (frequently found in infections of hematogenic origin), and Clostridium spp. (frequently found in infections after trauma).
### Bacteremia[edit]
The incidence of anaerobic bacteria in bacteremia varies between 5% to 15%,[46] The incidence of anaerobic bacteremia in the 1990s declined to about 4% (0.5–12%) of all cases of bacteremias. A resurgence in bacteremia due to anaerobic bacteria was observed recently.[47] This is explained by a greater number of anaerobic bacteremia in patients with complex underlying disease or those that are immunosuppressed. The commonest isolates are B. fragilis group (over 75% of anaerobic isolates), Clostridium spp. (10–20%), Peptostreptococcus spp. (10–15%), Fusobacterium spp. (10–15%) and P. acnes (2–5%).
The type of bacteria involved in bacteremia is greatly influenced by the infection's portal of entry and the underlying disease. The isolation of B. fragilis group and Clostridium spp. is often associated with a gastrointestinal source, pigmented Prevotella and Porphyromonas spp. and Fusobacterium spp.with oropharynx and pulmonary sites, Fusobacterium spp. with the female genital tract locations, P. acnes with a foreign body,[48] and Peptostreptococcus spp. with all infection sources, but mostly with oropharyngeal, pulmonary and female genital tract locations. The association of these organisms is related to the origin of the initial infection and the endogenous bacterial flora at that site.
The main factors which predispose to anaerobic bacteremia are: hematologic disorders; organ transplant; recent gastrointestinal, obstetric, or gynecologic surgery; malignant neoplasms intestinal obstruction; decubitus ulcers; dental extraction; sickle cell disease; diabetes mellitus; postsplenectomy; the newborn; and the administration of cytotoxic agents or corticosteroids.,[49][50]
The clinical presentations of anaerobic bacteremia are not different from those observed in aerobic bacteremia, except for the infection's signs observed at the portal of entry of the infection. It often includes fever, chills, hypotension, shock, leukocytosis, anemia and disseminated intravascular coagulation. Clinical features that are characteristic of anaerobicbacteremia include hyperbilirubinemia, metastatic lesions, and suppurative thrombophlebitis. The mortality rate varies between 15% and 30% and can be improved in those who are diagnosed early and receive appropriate antimicrobial therapy and their primary infection when present is resolved.
### Neonatal infection[edit]
The newborn's exposure to the maternal vaginal bacterial flora which contains aerobic and anaerobic bacterial flora can lead to the development of anaerobic bacterial infection. These infections include cellulitis of the site of fetal monitoring (caused by Bacterodes spp.), bacteremia, aspiration pneumonia (caused by Bacterodes spp.), conjunctivitis (caused by clostridia,) omphalitis (caused by mixed flora), and infant botulism.[51][52] Clostridial species may play a role in necrotizing enterocolitis.[53] Management of these infection necessitates treating of the underlying condition(s) when present, and administration of proper antimicrobial therapy
## Causes[edit]
Condition predisposing to anaerobic infections include: exposure of a sterile body location to a high inoculum of indigenous bacteria of mucous membrane flora origin, inadequate blood supply and tissue necrosis which lower the oxidation and reduction potential which support the growth of anaerobes. Conditions which can lower the blood supply and can predispose to anaerobic infection are: trauma, foreign body, malignancy, surgery, edema, shock, colitis and vascular disease. Other predisposing conditions include splenectomy, neutropenia, immunosuppression, hypogammaglobinemia, leukemia, collagen vascular disease and cytotoxic drugs and diabetes mellitus. A preexisting infection caused by aerobic or facultative organisms can alter the local tissue conditions and make them more favorable for the growth of anaerobes. Impairment in defense mechanisms due to anaerobic conditions can also favor anaerobic infection. These include production of leukotoxins (by Fusobacterium spp.), phagocytosis intracellular killing impairments (often caused by encapsulated anaerobes)[54] and by succinic acid ( produced by Bacteroides spp.), chemotaxis inhibition (by Fusobacterium, Prevotella and Porphyromonas spp.), and proteases degradation of serum proteins (by Bacteroides spp.) and production of leukotoxins (by Fusobacterium spp.).[55]
The hallmarks of anaerobic infection include suppuration, establishment of an abscess, thrombophlebitis and gangrenous destruction of tissue with gas generation. Anaerobic bacteria are very commonly recovered in chronic infections, and are often found following the failure of therapy with antimicrobials that are ineffective against them, such as trimethoprim–sulfamethoxazole (co-trimoxazole), aminoglycosides, and the earlier quinolones.
Some infections are more likely to be caused by anaerobic bacteria, and they should be suspected in most instances. These infections include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia and lung abscesses, amnionitis, endometritis, septic abortions, tubo-ovarian abscess, peritonitis and abdominal abscesses following viscus perforation, abscesses in and around the oral and rectal areas, pus-forming necrotizing infections of soft tissue or muscle and postsurgical infections that emerge following procedures on the oral or gastrointestinal tract or female pelvic area.[56] Some solid malignant tumors, ( colonic, uterine and bronchogenic, and head and neck necrotic tumors, are more likely to become secondarily infected with anaerobes.[57] The lack of oxygen within the tumor that are proximal to the endogenous adjacent mucosal flora can predispose such infections.
## Management[edit]
Recovery from an anaerobic infection depends on adequate and rapid management. The main principles of managing anaerobic infections are neutralizing the toxins produced by anaerobic bacteria, preventing the local proliferation of these organisms by altering the environment and preventing their dissemination and spread to healthy tissues.
Toxin can be neutralized by specific antitoxins, mainly in infections caused by Clostridia (tetanus and botulism). Controlling the environment can be attained by draining the pus, surgical debriding of necrotic tissue, improving blood circulation, alleviating any obstruction and by improving tissue oxygenation. Therapy with hyperbaric oxygen (HBO) may also be useful. The main goal of antimicrobials is in restricting the local and systemic spread of the microorganisms.
The available parenteral antimicrobials for most infections are metronidazole, clindamycin, chloramphenicol, cefoxitin, a penicillin (i.e. ticarcillin, ampicillin, piperacillin) and a beta-lactamase inhibitor (i.e. clavulanic acid, sulbactam, tazobactam), and a carbapenem (imipenem, meropenem, doripenem, ertapenem).[58] An antimicrobial effective against Gram-negative enteric bacilli (i.e. aminoglycoside) or an anti-pseudomonal cephalosporin (i.e. cefepime ) are generally added to metronidazole, and occasionally cefoxitin when treating intra-abdominal infections to provide coverage for these organisms. Clindamycin should not be used as a single agent as empiric therapy for abdominal infections. Penicillin can be added to metronidazole in treating of intracranial, pulmonary and dental infections to provide coverage against microaerophilic streptococci, and Actinomyces.[59]
Oral agents adequate for polymicrobial oral infections include the combinations of amoxicillin plus clavulanate, clindamycin and metronidazole plus a macrolide. Penicillin can be added to metronidazole in the treating dental and intracranial infections to cover Actinomyces spp., microaerophilic streptococci, and Arachnia spp. A macrolide can be added to metronidazole in treating upper respiratory infections to cover S. aureus and aerobic streptococci. Penicillin can be added to clindamycin to supplement its coverage against Peptostreptococcus spp. and other Gram-positive anaerobic organisms.[60]
Doxycycline is added to most regimens in the treatment of pelvic infections to cover chlamydia and mycoplasma. Penicillin is effective for bacteremia caused by non-beta lactamase producing bacteria. However, other agents should be used for the therapy of bacteremia caused by beta-lactamase producing bacteria.
Because the length of therapy for anaerobic infections is generally longer than for infections due to aerobic and facultative anaerobic bacteria, oral therapy is often substituted for parenteral treatment. The agents available for oral therapy are limited and include amoxacillin plus clavulanate, clindamycin, chloramphenicol and metronidazole.
In 2010 the Surgical Infection Society and Infectious Diseases Society of America updated joint guidelines for the treatment of abdominal infections.[61] The recommendations suggest the following:
For mild-to-moderate community-acquired infections in adults, the agents recommended for empiric regimens are: ticarcillin- clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin. Agents no longer recommended are: cefotetan and clindamycin ( Bacteroides fragilis group resistance) and ampicillin-sulbactam (E. coli resistance) and ainoglycosides (toxicity).
For high risk community-acquired infections in adults, the agents recommended for empiric regimens are: meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin in combination with metronidazole, or ceftazidime or cefepime in combination with metronidazole. Quinolones should not be used unless hospital surveys indicate >90% susceptibility of E. coli to quinolones.
Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive cocci is recommended. The routine use of an aminoglycoside or another second agent effective against gram-negative facultative and aerobic bacilli is not recommended in the absence of evidence that the infection is caused by resistant organisms that require such therapy. Empiric use of agents effective against enterococci is recommended and agents effective against methicillin-resistant S. aureus (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms.
Empiric antibiotic therapy for health care-associated intra-abdominal should be driven by local microbiologic results. Empiric coverage of likely pathogens may require multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli. These include meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required.
Antimicrobial regimens for children include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a beta-lactam/beta-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole.
Clinical judgment, personal experience, safety and patient compliance should direct the physician in the choice of the appropriate antimicrobial agents. The length of therapy generally ranges between 2 and 4 weeks, but should be individualized depending on the response. In some instances treatment may be required for as long as 6–8 weeks, but can often be shortened with proper surgical drainage.
## References[edit]
1. ^ Jousimies-Somer HR, Summanen P, Baron EJ, Citron DM, Wexler HM, Finegold SM. Wadsworth-KTL anaerobic bacteriology manual. 6th ed. Belmont, CA: Star Publishing, 2002.
2. ^ Brook, I.: "Anaerobic Infections Diagnosis and Management". A Textbook. Informa Healthcare USA, Inc. New York. 2007.
3. ^ Nagy E. Anaerobic infections: update on treatment considerations. Drugs. 2010; 70:841–58
4. ^ Hentges DJ. The anaerobic microflora of the human body . Clin Infect Dis 1993; 164:S175–80.
5. ^ Brook, I.: "Anaerobic Infections Diagnosis and Management". A Textbook. Informa Healthcare USA, Inc. New York. 2007.
6. ^ Jousimies-Somer HR, Summanen P, Baron EJ, Citron DM, Wexler HM, Finegold SM. Wadsworth-KTL anaerobic bacteriology manual. 6th ed. Belmont, CA: Star Publishing, 2002.
7. ^ Nagy E. Anaerobic infections: update on treatment considerations.Drugs. 2010; 70:841–58
8. ^ Brook I. Microbiology and antimicrobial treatment of orbital and intracranial complications of sinusitis in children and their management. Int J Pediatr Otorhinolaryngol. 2009; 73:1183–6.
9. ^ Brook I, Microbiology of intracranial abscesses associated with sinusitis of odontogenic origin. Ann Otol Rhinol Laryngol. 2006; 115:917–20.
10. ^ Le Moal G, Landron C, Grollier G, Bataille B, Roblot F, Nassans P, Becq-Giraudon B. Characteristics of brain abscess with isolation of anaerobic bacteria. Scand J Infect Dis. 2003; 35:318–211.
11. ^ Brook I. Meningitis and shunt infection caused by anaerobic bacteria in children. Pediatr Neurol.; 26:99–105. 2002.
12. ^ Brook I, Infection caused by Propionibacterium in children. Clin Pediatr (Phila). 1994; 33:485–90.
13. ^ Brook I, Johnson N, Overturf GD, Wilkins J. Mixed bacterial meningitis: a complication of ventriculo- and lumbo-peritoneal shunts. J Neurosurg 1977; 47:961–4.
14. ^ Bernardini GL. Diagnosis and management of brain abscess and subdural empyema. Curr Neurol Neurosci Rep. 2004; 4:448–56.
15. ^ Bernardini GL. Diagnosis and management of brain abscess, and subdural empyema. Curr Neurol Neurosci Rep. 2004; 4:448–56..
16. ^ Brook I/ The role of anaerobic bacteria in tonsillitis. Int J Pediatr Otorhinolaryngol. 2005; 69:9–1.
17. ^ Brook I. Ocular infections due to anaerobic bacteria in children. J Pediatr Ophthalmol Strabismus. 2008; 45:78–84.
18. ^ Brook I. The role of anaerobic bacteria in upper respiratory tract and other head and neck infections. Curr Infect Dis Rep. 2007; 9:208–17.
19. ^ Le Monnier A, Jamet A, Carbonnelle E, Barthod G, Moumile K, Lesage F, Zahar JR, Mannach Y, Berche P, Couloigner V. Fusobacterium necrophorum middle ear infections in children and related complications: report of 25 cases and literature review. Pediatr Infect Dis J. 2008; 27:613–7.
20. ^ Robertson D, Smith AJ. The microbiology of the acute dental abscess. J Med Microbiol. 2009; 58:155-62. Archived April 17, 2009, at the Wayback Machine
21. ^ Brook I, Frazier EH, Gher ME. Aerobic nd anaerobic microbiology of periodontal abscess. Oral Microbiol Immunol 1991; 6:123–5.
22. ^ Tatakis DN, Kumar PS. Etiology and pathogenesis of periodontal diseases. Dent Clin North Am. 2005; 49:491–516,.
23. ^ Brook I, Frazier EH. Microbiology of mediastinitis. Arch Intern Med 1996; 156:333–6.
24. ^ Brook I, Microbiology of empyema in children and adolescents. Pediatrics. 1990; 85:722–6.
25. ^ Brook, I.: Frazier, E.H. Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals. Chest. 1993; 103:1502–7.
26. ^ Bartlett JG. Anaerobic bacterial infections of the lung and pleural space.Clin Infect Dis. 1993 Suppl 4:S248–55.
27. ^ Brook I, Finegold SM. Bacteriology of aspiration pneumonia in children. Pediatrics. 1980; 65:1115–20.
28. ^ Brook I. Bacterial colonization tracheobronchitis and pneumonia, following tracheostomy and long-term intubation in pediatric patients. Chest 1979; 70:420–4.
29. ^ Brook I. Microbiology and management of abdominal infections. Dig Dis Sci. 2008:53:2585–91.
30. ^ Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50:133–64
31. ^ Brook I. Microbiology and management of abdominal infections. Dig Dis Sci. 2008:53:2585–91.
32. ^ Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50:133–64
33. ^ pelvic Inflammatory Disease (PID)—CDC Fact Sheet
34. ^ Barrett S, Taylor C..A review on pelvic inflammatory disease. Int J STD AIDS. 2005; 16:715–20.
35. ^ Sobel JD. What's new in bacterial vaginosis and trichomoniasis? Infect Dis Clin North Am. 2005; 19:387–406.
36. ^ Soper DE. Pelvic inflammatory disease. Obstet Gynecol. 2010; 116(2 Pt 1):419–28.
37. ^ Donders G. Diagnosis and management of bacterial vaginosis and other types of abnormal vaginal bacterial flora: a review. Obstet Gynecol Surv. 2010; 65:462–73.
38. ^ Brook I, Frazier EH.Aerobic and anaerobic microbiology of axillary hidradenitis suppurativa. J Med Microbiol. 1999 48:103–5.
39. ^ Brook I. Secondary bacterial infections complicating skin lesions. J Med Microbiol. 2002; 51:808–12.
40. ^ Meislin HW, Lerner SA, Graves MH, et al. Cutaneous abscesses: anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 1977; 97:145–50.
41. ^ Brook I. Management of human and animal bite wound infection: an overview. Curr Infect Dis Rep. 2009; 11:389–95.
42. ^ Brook I.The role of anaerobic bacteria in cutaneous and soft tissue abscesses and infected cysts. Anaerobe. 2007; 13:171–7
43. ^ Brook I. The role of anaerobic bacteria in cutaneous and soft tissue abscesses and infected cysts. Anaerobe. 2007; 13:171–7
44. ^ Brook I. The role of anaerobic bacteria in bacteremia. Anaerobe. 2010; 16:183–9.
45. ^ Brook I. Microbiology and management of joint and bone infections due to anaerobic bacteria. J Orthop Sci. 2008; 13:160–9.
46. ^ Brook I. The role of anaerobic bacteria in bacteremia. Anaerobe. 2010; 16:183–9.
47. ^ Lassmann B, Gustafson DR, Wood C M, Rosenblatt J E, Reemergence of Anaerobic Bacteremia. Clin. Infec. Dis. 2007; 44:895–900.
48. ^ Brook, I., Frazier, E.H.: Infections Caused by Propionibacterium species. Reviews of Infectious Disease. 13: 819–822; 1991.
49. ^ Finegold SM. Anaerobic bacteria in human disease. Orlando: Academic Press Inc.; 1977.
50. ^ Brook, I.: "Anaerobic Infections Diagnosis and Management". A Textbook. Informa Healthcare USA, Inc. New York. 2007.
51. ^ Brook I. Infant botulism. J Perinatol. 2007; 27:175–80.
52. ^ Botulism-CDC General Information
53. ^ Brook I. Anaerobic infections in children. Adv Exp Med Biol. 2011; 697:117–52.
54. ^ Brook I, Myhal LA, Dorsey HC. Encapsulation and pilus formation of Bacteroides spp. J Infect 1991; 25:251–7.
55. ^ Hofstad T. Virulence determinants in non-spore-forming anaerobic bacteria. Scand J Infect Dis 1989; (Suppl.62):15–24.
56. ^ Brook, I. Long S.: "Anaerobic bacteria: Classification, normal flora, and clinical concept,"(Chapter 202, pg. 946–956); In Principles and Practice of Pediatric Infectious Diseases, Eds. Long, S.S., Pickering, L.K., and Prober, C.G. Churchill Livingstone, New York, 3rd ed, 2008.
57. ^ Brook I, Frazier EH. Aerobic and anaerobic infection associated with malignancy. Support Care Cancer 1998; 6:125–31.
58. ^ Nagy E. Anaerobic infections: update on treatment considerations.Drugs. 2010; 70:841–58
59. ^ Brook I. Treatment of anaerobic infection. Expert Rev Anti Infect Ther. 2007; 5:991–1006
60. ^ Brook I. Treatment of anaerobic infection. Expert Rev Anti Infect Ther. 2007; 5:991–1006
61. ^ Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010 ,15; 50:133–6.
## Further reading[edit]
* Brook, I.: "Anaerobic Infections Diagnosis and Management". A Textbook. Informa Healthcare USA, Inc. New York. 2007.
## External links[edit]
* Bacteroides infections in E Medicine
* Peptostreptococcus infections in E Medicine
*[v]: View this template
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*[e]: Edit this template
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| Anaerobic infection | c0854328 | 6,642 | wikipedia | https://en.wikipedia.org/wiki/Anaerobic_infection | 2021-01-18T18:36:14 | {"umls": ["C0854328"], "wikidata": ["Q4065009"]} |
Rare form of tertiary hypothyroidism
Pickardt–Fahlbusch syndrome
Other namesPickardt's syndrome or Pickardt–Fahlbusch syndrome
An interupption of the hypophyseal portal system causes Pickardt's syndrome
SpecialtyEndocrinology
Pickardt syndrome denotes a rare form of tertiary hypothyroidism that is caused by interruption of the portal veins connecting hypothalamus and pituitary.
It was characterized in 1972 and 1973 by Renate Pickardt and Rudolf Fahlbusch.[1][2]
## Contents
* 1 Cause
* 1.1 Endocrine consequences
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Cause[edit]
Interruption of the portal system may be caused by tumors compressing the infundibulum. Other causes for Pickardt's syndrome are inflammatory disorders and traumatic brain injury. An inborn variant of Pickardt's syndrome that is associated with certain mutations (HESX1[3] or LHX4) is referred to as pituitary stalk interruption syndrome (PSIS).
### Endocrine consequences[edit]
Typical manifestations of Pickardt–Fahlbusch syndrome are hypothyroidism with reduced TSH values and functional hyperprolactinemia (which is caused by disinhibition of prolactin release). Other endocrine disorders that are usually associated with Pickardt syndrome are suprasellar failures like secondary hypogonadism, reduced levels of growth hormone and, in more severe cases, secondary adrenal insufficiency.[citation needed]
## Diagnosis[edit]
Pickardt's syndrome may cause difficulties in differential diagnosis of pituitary adenomas, as both suprasellar hormone-inactive adenomas and prolactinomas may be associated with increased prolactin levels, central hypogonadism and central hypothyroidism. Usually, the prolactin levels are higher in case of a true prolactinoma, but the concentration ranges overlap.[citation needed]
## Treatment[edit]
Treatment modality depends on the cause. Tumors may be removed surgically, but pituitary stalk interruption may persist. Usually, replacement of those hormones that are reduced due to failed feedback control systems will be necessary.[citation needed]
## References[edit]
1. ^ Pickardt C, Fahlbusch R (1972). "Chronic hyperosmolality, adipsia and secondary insufficiency of the anterior pituitary gland in hypothalamic lesions". Internist (Berl). 13 (2): 45–51. PMID 4554749.
2. ^ Pickardt, C. R.; Erhardt, F.; Fahlbusch, R. & Scriba, P. C. (1973). "Portal Vessels Occlusion. A Cause for Pituitary Insufficiency in Patiens with Pituitary Tumors". European Journal of Clinical Investigation. 3 (3): 262. doi:10.1111/j.1365-2362.1973.tb00351.x. ISSN 0014-2972. Archived from the original on 2013-01-05.
3. ^ Reynaud R, Albarel F, Saveanu A, Kaffel N, Castinetti F, Lecomte P, Brauner R, Simonin G, Gaudart J, Carmona E, Enjalbert A, Barlier A, Brue T (April 2011). "Pituitary Stalk Interruption Syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms". Eur J Endocrinol. 164 (4): 457–65. doi:10.1530/EJE-10-0892. PMID 21270112.CS1 maint: multiple names: authors list (link)
## External links[edit]
Classification
D
* ICD-10: E23
* ICD-9-CM: 253.7
* MeSH: 68006966
* DiseasesDB: 6314
* v
* t
* e
Thyroid disease
Hypothyroidism
* Iodine deficiency
* Cretinism
* Congenital hypothyroidism
* Myxedema
* Myxedema coma
* Euthyroid sick syndrome
* Signs and symptoms
* Queen Anne's sign
* Woltman sign
* Thyroid dyshormonogenesis
* Pickardt syndrome
Hyperthyroidism
* Hyperthyroxinemia
* Thyroid hormone resistance
* Familial dysalbuminemic hyperthyroxinemia
* Hashitoxicosis
* Thyrotoxicosis factitia
* Thyroid storm
Graves' disease
* Signs and symptoms
* Abadie's sign of exophthalmic goiter
* Boston's sign
* Dalrymple's sign
* Stellwag's sign
* lid lag
* Griffith's sign
* Möbius sign
* Pretibial myxedema
* Graves' ophthalmopathy
Thyroiditis
* Acute infectious
* Subacute
* De Quervain's
* Subacute lymphocytic
* Palpation
* Autoimmune/chronic
* Hashimoto's
* Postpartum
* Riedel's
Enlargement
* Goitre
* Endemic goitre
* Toxic nodular goitre
* Toxic multinodular goiter
* Thyroid nodule
* Colloid nodule
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Pickardt syndrome | c4053775 | 6,643 | wikipedia | https://en.wikipedia.org/wiki/Pickardt_syndrome | 2021-01-18T18:37:27 | {"gard": ["13209"], "umls": ["C4053775"], "icd-9": ["253.7"], "icd-10": ["E23"], "orphanet": ["95496"], "wikidata": ["Q2092226"]} |
## Summary
### Clinical characteristics.
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
### Diagnosis/testing.
The diagnosis is established in a proband by detection of the 1.4-megabase (Mb) heterozygous recurrent deletion at chromosome 17q12 by chromosomal microarray testing or other genomic methods.
### Management.
Treatment of manifestations: Treatment of kidney anomalies, neurodevelopmental and neuropsychiatric disorders, MODY5, genital tract abnormalities, liver abnormalities, eye abnormalities, congenital heart defects, seizures and sensorineural hearing loss should follow standard practice.
Surveillance: Kidneys and urinary tract: In the absence of known structural abnormalities, kidney and bladder ultrasound examination 12 months after establishing the diagnosis, then every 2-3 years in childhood/adolescence, then every 3-5 years in adulthood; presence of an abnormality may warrant more frequent monitoring. Annual monitoring of kidney function in individuals with abnormalities detected on kidney ultrasound examination; more frequent monitoring may be advised in those taking potentially nephrotoxic medications and/or known to have impaired kidney function. Routine monitoring of neurodevelopment through early childhood; full neuropsychological evaluation for children who experience difficulty with school. HbA1C annually to monitor for MODY5; self-monitoring by individuals and their families for clinical signs and symptoms of diabetes mellitus, such as polydipsia and polyuria. Consider reevaluation for uterine and vaginal abnormalities related to müllerian duct aplasia in pubertal females with primary amenorrhea. Consider annual hepatic function panel (or comprehensive metabolic panel), GGT, and lipid panel. Annual ophthalmologic evaluation during early childhood. Monitor those with seizures as clinically indicated. Hearing screening throughout childhood.
Agents/circumstances to avoid: Because kidney transplantation increases the risk for post-transplant diabetes mellitus, an immunosuppressive regimen that avoids tacrolimus and mammalian target of rapamycin (mTOR) inhibitors and reduces corticosteroid exposure may benefit those without preexisting diabetes mellitus. Nephrotoxic and hepatotoxic drugs should be avoided by individuals with kidney or liver abnormalities. For individuals with mental health conditions such as autism, schizophrenia, or bipolar disorder, careful consideration of antipsychotic agents that may lead to weight gain is recommended, as this potential increase has been associated with metabolic syndrome and the later development of diabetes mellitus, for which people with 17q12 deletions are at baseline increased risk. Likewise, the use of mood stabilizers that affect kidney function in the long term, such as lithium, should be carefully considered in the setting of potential underlying anatomic and functional abnormalities in people with 17q12 deletions.
Evaluation of relatives at risk: If one of the proband's parents has the 17q12 recurrent deletion, it is appropriate to test older and younger sibs of the proband and other relatives at risk in order to identify those who would benefit from close assessment/monitoring for evidence of genitourinary structural or functional defects, MODY5, and developmental delays / intellectual disability.
### Genetic counseling.
The 17q12 recurrent deletion is inherited in an autosomal dominant manner, with approximately 75% of deletions occurring de novo and approximately 25% inherited from a parent. If the 17q12 recurrent deletion identified in the proband is not found in one of the parents, the risk to sibs is presumed to be lower than 1% (but slightly greater than that of the general population because of the theoretic possibility of parental germline mosaicism for the deletion). Offspring of an individual with the 17q12 recurrent deletion have a 50% chance of inheriting the deletion. Prenatal testing or preimplantation genetic testing using genomic testing that will detect the 17q12 recurrent deletion is possible.
## Diagnosis
### Suggestive Findings
17q12 recurrent deletion syndrome should be suspected in individuals with any of the following clinical and laboratory findings.
Clinical findings
* Kidney abnormalities
* Congenital abnormalities of the kidney and urinary tract (CAKUT), including the following:
* Abnormalities on prenatal imaging including hyperechogenicity or poor corticomedullary differentiation
* Abnormalities of kidney parenchyma including hypoplasia, dysplasia, multicystic dysplastic kidney (MCDK), or agenesis
* Fusion anomalies (e.g., horseshoe kidney)
* Collecting system abnormalities, including duplicated collecting systems, ureteropelvic junction obstruction, isolated hydronephrosis, or hydroureter
* Tubulointerstitial disease, characterized by reduced urine concentrating ability with bland urinary sediment, absent-to-minimal albuminuria/proteinuria, hyperuricemia, hypomagnesemia, hypokalemia, and tubulointerstitial fibrosis on kidney histology. In some cases, hypomagnesemia is the initial and predominant symptom of kidney disease [van der Made et al 2015].
* Maturity-onset diabetes of the young (MODY), a type of monogenic diabetes resulting from beta-cell dysfunction
* Neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder)
* Müllerian aplasia / Mayer-Rokitansky-Küster-Hauser syndrome in females
Note: The combination of kidney or urogenital anomalies with MODY has been referred to as renal cysts and diabetes (RCAD) syndrome.
Laboratory findings. The 17q12 recurrent deletion syndrome should be suspected in individuals with a deletion of HNF1B identified on gene-targeted deletion/duplication analysis (i.e., testing that detects deletion of HNF1B, but cannot reliably detect the diagnostic recurrent 17q12 deletion), as virtually all whole-gene deletions have been found to be the 17q12 recurrent deletion [Laffargue et al 2015].
Note that identification of an intragenic HNF1B pathogenic variant on sequence analysis establishes the diagnosis of an HNF1B-related disorder (see Genetically Related Disorders) and excludes the diagnosis of the 17q12 recurrent deletion syndrome.
### Establishing the Diagnosis
The diagnosis of the 17q12 recurrent deletion syndrome is established in a proband by detection of the 1.4-Mb heterozygous recurrent deletion at chromosome 17q12 (see Table 1 and Molecular Genetics).
For this GeneReview, the 17q12 recurrent deletion is defined as the presence of a recurrent 1.4-Mb deletion at the approximate position of 36,458,167-37,854,616 in the reference genome (NCBI Build GRCh38/hg38).
ISCN nomenclature for this deletion is: seq[GRCh37] del(17)(q12) chr17:g. 36,458,16737,854,616del. Note: Since this deletion is recurrent and mediated by segmental duplications, the unique genetic sequence that is deleted is the same in all individuals with the syndrome; however, the reported size of the deletion may: (1) be larger if adjacent segmental duplications are included in the size and (2) vary based on the design of the microarray used to detect it.
For information on the 15 known genes in the 17q12 region see Molecular Genetics.
Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA), exome sequencing with CNV calling, genome sequencing, or targeted deletion analysis. Note: The 17q12 recurrent deletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques.
CMA using oligonucleotide or SNP arrays can detect the recurrent deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 17q12 region.
Note: (1) Most individuals with the 17q12 recurrent deletion are identified by CMA performed in the context of evaluation for developmental delay, intellectual disability, or autism spectrum disorder. (2) Prior to 2007, many CMA platforms did not include coverage for this region and thus may not have detected this deletion.
Exome and genome sequencing analyses are next-generation sequencing technologies that generate DNA sequence either for all coding regions (exome) or the entire genome. Copy number variant-calling algorithms need to be utilized to detect the 17q12 recurrent deletion.
Targeted deletion analysis. FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA), or other targeted quantitative methods may be used to test relatives of a proband who is known to have the 17q12 recurrent deletion. Virtually all whole-gene deletions of HNF1B identified by gene-targeted deletion/duplication analysis have been shown to include the entire 17q12 recurrent deletion region [Laffargue et al 2015], which can be confirmed using CMA.
Note: (1) Targeted deletion testing is not appropriate for an individual in whom the 17q12 recurrent deletion was not detected by CMA designed to target this region. (2) It is not possible to size the deletion routinely by use of targeted methods.
### Table 1.
Genomic Testing Used in 17q12 Recurrent Deletion Syndrome
View in own window
Deletion 1MethodSensitivity
ProbandAt-risk family
members
1.4-Mb heterozygous deletion at 17q12
ISCN: seq[GRCh38] del(17)(q12)
chr17:g. 36,458,167-37,854,616del 2
ClinGen ID: ISCA-37432CMA 3100%100%
Exome & genome
sequencing 4100%100%
Targeted deletion
analysis 5NA 6100% 7
1\.
See Molecular Genetics for details of the deletion and genes of interest included in the region.
2\.
Standardized ISCN annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium). The region is identified in dbVar (www.ncbi.nlm.nih.gov/dbvar) as nsv491563. Genomic coordinates represent the minimum deletion size associated with the 17q12 recurrent deletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the deletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the recurrent 17q12 deletion (see Genetically Related Disorders).
3\.
Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 17q12 region. Note: The 17q12 recurrent deletion may not have been detectable by older oligonucleotide or BAC platforms.
4\.
Copy number variant-calling algorithms need to be utilized to detect the 17q12 recurrent deletion.
5\.
Targeted deletion analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA), as well as other targeted quantitative methods.
6\.
Targeted deletion analysis is not appropriate for an individual in whom the 17q12 recurrent deletion was not detected by CMA designed to target this region.
7\.
Targeted deletion analysis may be used to test at-risk relatives of a proband known to have the 17q12 recurrent deletion.
Evaluating at-risk relatives. FISH, qPCR, or other quantitative methods of targeted deletion analysis can be used to identify the 17q12 recurrent deletion in at-risk relatives of the proband. Testing of parental samples is important in determining recurrence risk (see Genetic Counseling).
## Clinical Characteristics
### Clinical Description
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the following three most common findings: kidney abnormalities including congenital abnormalities of the kidney and urinary tract (CAKUT) and tubulointerstitial disease, maturity-onset diabetes of the young (MODY), and neurodevelopmental/neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder).
To calculate the frequency rates for these features reported in 17q12 recurrent deletion syndrome, the authors reviewed phenotypic information for 282 individuals on whom sufficiently detailed phenotypic information was reported in 42 studies (Table 2) using the following criteria:
* To minimize ascertainment bias, studies involving disease-specific cohorts were not included in the prevalence calculations of that particular phenotypic manifestation (e.g., kidney anomalies).
* Individuals with HNF1B pathogenic sequence variants were not included; however, individuals with whole-gene HNF1B deletions were included, as virtually all whole-gene deletions have been found to be the 17q12 recurrent deletion [Laffargue et al 2015].
### Table 2.
17q12 Recurrent Deletion Syndrome: Frequency of Select Features
View in own window
FrequencyFeatures
Most common (>50%)
* Kidney structural or functional defects
* Neurodevelopmental/neuropsychiatric disorders
* Mild dysmorphic features
* Hyperparathyroidism
Common (25%-50%)
* Maturity-onset diabetes of the young type 5
* Female & male genital abnormalities
* Structural & functional liver abnormalities
* Eye abnormalities
* Structural &exocrine abnormalities of the pancreas
* Nonspecific structural brain findings
* Prematurity
Less common (<25%)
* Congenital cardiac anomalies
* Musculoskeletal features
* Other gastrointestinal features
* Seizures
Clinical data summarized from 42 studies, including 282 individuals in whom the 17q12 recurrent deletion was identified [Bellanné-Chantelot et al 2005, Faguer et al 2007, Mefford et al 2007, Cheroki et al 2008, Edghill et al 2008, Bernardini et al 2009, Raile et al 2009, Loirat et al 2010, Moreno-De-Luca et al 2010, Nagamani et al 2010, Oram et al 2010, Kasperavičiūtė et al 2011, Nik-Zainal et al 2011, Dixit et al 2012, George et al 2012, Grozeva et al 2012, Hendrix et al 2012, Hinkes et al 2012, Sanna-Cherchi et al 2012, Ferrè et al 2013, Palumbo et al 2014, Quintero-Rivera et al 2014, Roberts et al 2014, Stefansson et al 2014, Goumy et al 2015, Laffargue et al 2015, Verbitsky et al 2015, Rasmussen et al 2016, Dubois-Laforgue et al 2017a, Madariaga et al 2018, Roehlen et al 2018, Stiles et al 2018, Dotto et al 2019, Li et al 2019, Okorn et al 2019, Vasileiou et al 2019, Berberich et al 2020, Bustamante et al 2020, Du et al 2020, Kołbuc et al 2020, Lim et al 2020, Sztromwasser et al 2020]
#### Most Common Features (>50%)
Kidney disease. Structural kidney abnormalities and unspecified chronic kidney disease have been described in 257 individuals (Table 2). Cystic dysplastic kidneys and other structural kidney anomalies are reported in 130/148 (88%) individuals who were not ascertained through cohorts with kidney disease, making this feature the most commonly reported manifestation of the 17q12 recurrent deletion syndrome.
Cystic dysplasia is the most common kidney finding; other kidney and urinary tract abnormalities include poor cortico-medullary differentiation, collecting system abnormalities (duplicated collecting system, hydronephrosis, pyelectasis, vesicoureteral reflux, dilated ureter), single kidney (due to unilateral agenesis or involution of a cystic dysplastic kidney), and horseshoe kidney.
Individuals may also present with tubulointerstitial disease, which is characterized by reduced urine concentrating ability, bland urinary sediment, absent-to-minimal albuminuria/proteinuria, hyperuricemia, hypomagnesemia, hypokalemia, and slowly progressive kidney disease; interstitial fibrosis and tubular atrophy are seen on biopsy (although biopsy is not routinely indicated) [Eckardt et al 2015, Verhave et al 2016]. Of note, autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by HNF1B haploinsufficiency (frequently due to 17q12 deletion) is designated ADTKD-HNF1B [Eckardt et al 2015].
Tubular wasting of magnesium resulting in hypomagnesemia is common and can be the initial and predominant manifestation of kidney disease in individuals with HNF1B haploinsufficiency, including those with the 17q12 recurrent deletion [Clissold et al 2015, Raaijmakers et al 2015, van der Made et al 2015]. Hypomagnesemia is reported in 36/81 (44%) individuals with 17q12 recurrent deletion and can be severe [Ferrè et al 2013, Madariaga et al 2018, Dotto et al 2019, Li et al 2019, Okorn et al 2019, Berberich et al 2020]. Some studies suggest that hypomagnesemia may be underdiagnosed among children with HNF1B-related disorders, including 17q12 recurrent deletion [Kołbuc et al 2020]. Tubular magnesium wasting can be diagnosed through an elevated fractional excretion of magnesium (FEMg >2%) in individuals with normal kidney function.
The spectrum of severity and range in age of detection of HNF1B-associated kidney disease are broad, including prenatal severe kidney failure, slow progression to end-stage renal disease (ESRD) in adulthood, and normal kidney function never requiring kidney replacement therapy [Madariaga et al 2013, Clissold et al 2015, Verhave et al 2016]. While initial evidence suggested that the cause of HNF1B haploinsufficiency – 17q12 deletion, a HNF1B missense variant, or a HNF1B truncating variant (nonsense, frameshift, or splice site) – did not predict the type and severity of kidney involvement [Raaijmakers et al 2015], more recent evidence indicates that intragenic HNF1B pathogenic variants may be associated with worse kidney function and higher risk of progression to ESRD compared to 17q12 deletions [Dubois-Laforgue et al 2017b, Clissold et al 2018]. The reason for this finding is unknown, but the authors speculate a possible dominant-negative effect of certain HNF1B variants resulting in a more severe phenotype, or a protective effect conferred by the loss of one or more genes in the 17q12 recurrent deletion region.
Progression to ESRD in childhood appears to be uncommon among individuals with HNF1B haploinsufficiency, including those with the 17q12 recurrent deletion [Bockenhauer & Jaureguiberry 2016]. In a large retrospective cohort study, progression to ESRD was less common among adults with 17q12 deletion at follow-up (51%) compared with those with HNF1B intragenic mutations (78%) [Dubois-Laforgue et al 2017b].
Neurodevelopmental/neuropsychiatric disorders. Several studies have identified an increased risk for neurodevelopmental and neuropsychiatric disorders, such as developmental delay, intellectual disability (mild to severe), autism spectrum disorder (ASD), and schizophrenia [Moreno-De-Luca et al 2010, Laliève et al 2020].
In a case-control study, Moreno-De-Luca et al [2010] identified the following number of individuals with the 17q12 recurrent deletion:
* Eighteen of 15,749 individuals referred for developmental delay, intellectual disability, and/or ASD. Detailed phenotypic information for nine individuals revealed six with anxiety and/or phobias, one of whom was diagnosed with bipolar disorder. Because the 17q12 recurrent deletion was not detected in 4,519 controls, the authors concluded that the deletion confers a high risk for developmental brain disorders.
* Four of 6,340 individuals from two large schizophrenia cohorts. Because the 17q12 recurrent deletion was not detected in 43,076 controls, the authors concluded that deletion also confers a high risk for schizophrenia.
Overall, about half (37/79) of individuals with the 17q12 recurrent deletion are reported to have some degree of learning disability, although phenotypic information about cognitive skills was limited in most studies. Speech and motor delay are common findings, reported in 78% and 68% of individuals, respectively. While not routinely assessed, autism or autistic features are described in 9% of individuals ascertained for other clinical findings [Raile et al 2009, Loirat et al 2010, Dixit et al 2012, Palumbo et al 2014, Roberts et al 2014, Goumy et al 2015, Laffargue et al 2015, Rasmussen et al 2016, Li et al 2019, Vasileiou et al 2019, Lim et al 2020]. Learning difficulties, when noted, are most often described as mild. One study found that only 14/110 (12.7%) children with the 17q12 recurrent deletion required special school placement, which the researchers used as a proxy for severe neuropsychiatric disorder [Laliève et al 2020].
Some studies suggest that genes other than HNF1B in the 17q12 region could be responsible for neurodevelopmental and neuropsychiatric features, although evidence is mixed. One study found that individuals with the recurrent 17q12 deletion, but not an HNF1B intragenic pathogenic variant, exhibited neurodevelopmental disorders, psychopathology, and autistic traits [Clissold et al 2016]; however, other studies have found that both groups of HNF1B-related disorders are associated with an increased risk of intellectual disability [Dubois-Laforgue et al 2017a, Laliève et al 2020]. While haploinsufficiency of HNF1B alone may not be sufficient to result in the cognitive and behavioral features associated with the 17q12 recurrent deletion, the role of HNF1B in neurologic impairment cannot be ruled out.
Dysmorphic features. Subtle but highly variable dysmorphic features are described for most individuals for whom this information is available. The most commonly described features include high forehead, frontal bossing, depressed nasal bridge, deep-set eyes, full cheeks, downslanting palpebral fissures, high palate, and high-arched eyebrows [Moreno-De-Luca et al 2010, Laffargue et al 2015, Rasmussen et al 2016, Roehlen et al 2018, Vasileiou et al 2019].
Hypoplastic nails, 2-3 finger/toe syndactyly, and clinodactyly of the fifth finger are also frequently reported [Moreno-De-Luca et al 2010, Kasperavičiūtė et al 2011, Palumbo et al 2014].
Hyperparathyroidism. Nineteen of 36 (53%) individuals who had parathyroid hormone plasma levels tested were found to have hyperparathyroidism [Ferrè et al 2013, Li et al 2019, Berberich et al 2020, Kołbuc et al 2020, Lim et al 2020]. Furthermore, one study reported transient neonatal hypercalcemia and hypophosphatemia, the combination of which is suggestive of hyperparathyroidism, although PTH levels were not specifically measured to confirm [Dixit et al 2012]. Another study demonstrated that HNF1B is expressed in the parathyroid gland and acts as a transcriptional repressor of PTH [Ferrè et al 2013]. Additionally, this study found that PTH levels remained increased even after kidney transplantation and normalized magnesium levels in some patients. Although hyperparathyroidism is persistent in 20%-50% of individuals who are post-transplant independent of genetics, the authors concluded that the weight of the evidence suggests that HNF1B haploinsufficiency causes hyperparathyroidism independent of associated kidney failure.
#### Common Features (25%-50%)
Maturity-onset diabetes of the young type 5 (MODY5) is most often diagnosed before age 25 years (range: 10-50 years) [Bellanné-Chantelot et al 2005].
Overt diabetes mellitus and abnormal blood glucose levels and/or insulin response are reported in 49/125 (39%) individuals with the 17q12 recurrent deletion not ascertained from cohorts with diabetes mellitus; however, this is almost certainly an underestimate of the lifetime prevalence, since many individuals described in the literature are children and young adults who may not yet have developed manifestations of diabetes. When cohorts with diabetes mellitus are considered, prevalence of MODY5 among individuals with the 17q12 recurrent deletion is 50%.
While many individuals with 17q12 deletion with MODY5 have some residual insulin secretion at the time of diagnosis, one study found that 79% required insulin therapy by ten-year follow up [Dubois-Laforgue et al 2017b].
Genital abnormalities. About one third of females and one quarter of males have genital abnormalities.
In females, the most commonly reported finding is partial or complete absence of the upper part of the vagina, cervix, and uterus, often referred to as müllerian aplasia or Mayer-Rokitansky-Küster-Hauser syndrome [Bernardini et al 2009]. Other reported uterine abnormalities include bicornuate uterus, uterus didelphys, hypoplastic uterus, and ovarian cysts [Oram et al 2010, Stiles et al 2018, Vasileiou et al 2019].
In males, genital abnormalities include cryptorchidism, shawl scrotum, phimosis, urethral stenosis or obstruction, hypospadias, and epydidimary cysts [Nagamani et al 2010, Madariaga et al 2018, Lim et al 2020].
Structural and functional abnormalities of the liver. Elevated liver enzymes were reported in 64/133 (48%) individuals in cohorts ascertained for kidney involvement, diabetes mellitus, and uterine malformations [Rasmussen et al 2016, Dubois-Laforgue et al 2017a, Okorn et al 2019]. Liver involvement ranges from asymptomatic elevation of hepatic transaminase enzyme levels to neonatal and adult-onset cholestasis [Kotalova et al 2015, Pinon et al 2019]. Neonatal cholestasis with paucity of interlobular bile ducts and variable periportal fibrosis has also been reported in several infants with 17q12 recurrent deletion, including one who required portoenterostomy and one who developed hepatocellular carcinoma requiring liver transplantation [Pinon et al 2019]. Additional reported liver abnormalities include choledochal and common bile duct cysts, hepatomegaly, and steatohepatitis [Roehlen et al 2018, Lim et al 2020]. One study reported an even higher frequency of abnormal liver function tests (71%) in a large cohort that included both intragenic HNF1B variants and 17q12 deletions [Dubois-Laforgue et al 2017b]. While the study’s authors did not differentiate between genotypes, no statistically significant genotype/phenotype correlations were reported, suggesting that elevated LFTs may be even more common (>50%).
Eye abnormalities. Fifteen of 37 (41%) reported individuals had eye findings that included strabismus [Vasileiou et al 2019], horizontal nystagmus [Cheroki et al 2008], posterior embryotoxon [Dixit et al 2012], hypermetropia [Moreno-De-Luca et al 2010], cataracts [Nagamani et al 2010], and coloboma [Raile et al 2009].
Structural and exocrine abnormalities of the pancreas. About one third (32/105) of individuals with imaging results were found to have some morphologic abnormality of the pancreas, most often hypoplasia, atrophy, and/or agenesis of the body and tail [Madariaga et al 2018, Roehlen et al 2018, Dotto et al 2019, Kołbuc et al 2020].
One retrospective cohort study involving both 17q12 deletions and HNF1B sequence variants found pancreatic exocrine insufficiency in 29/38 cases (76%) and structural pancreatic abnormalities in 62% of 95 patients who had imaging [Dubois-Laforgue et al 2017b]. The study’s authors did not differentiate between the groups of patients, but reported no significant genotype/phenotype differences for this feature. Most other studies did not measure fecal elastase, but those that did reported a lower frequency of pancreatic exocrine insufficiency (2 of 8 cases) [Raile et al 2009, Quintero-Rivera et al 2014, Roehlen et al 2018].
Prematurity. Among 16 studies that reported premature birth (gestational age <37 weeks), 13 of 47 individuals (28%) were affected.
Nonspecific structural brain findings. No systematic neuroimaging studies of cohorts with 17q12 recurrent deletion syndrome have been published. Among publications describing neuroimaging findings, structural brain anomalies were reported in eight of 31 (26%) individuals. These abnormalities, which appeared to be nonspecific and to vary widely, included the following:
* Ventricular dilatation [Vasileiou et al 2019]
* Mild cerebellar atrophy [Kasperavičiūtė et al 2011]
* Abnormal signal intensity of subcortical white matter [Moreno-De-Luca et al 2010]
* Atrophy of the hippocampus [Nagamani et al 2010]
#### Less Common Features (<25%)
Congenital cardiac anomalies. Congenital heart defects are reported in nine of 45 (20%) individuals, ranging from mild to severe. Cardiac anomalies include right heart failure with tricuspid valve insufficiency, increased aortic root size, aortic insufficiency, coarctation of the aorta, ventricular septal defect, transposition of the great arteries, pulmonary valve defect, tricuspid regurgitation, and patent ductus arteriosus [Hinkes et al 2012, Palumbo et al 2014, Roberts et al 2014, Vasileiou et al 2019, Du et al 2020].
Musculoskeletal. Nine of 39 (23%) individuals were reported to have short stature. Other musculoskeletal differences include joint laxity (5 persons), long/slender hands and feet (4), pectus deformity (3), fifth finger clinodactyly (3), single transverse palmar crease (1), and hip dysplasia (1).
Other gastrointestinal features. Gastroesophageal reflux disease was reported in three individuals [Moreno-De-Luca et al 2010, Goumy et al 2015, Rasmussen et al 2016]. One individual had duodenal atresia [Quintero-Rivera et al 2014] and two had esophageal abnormalities, including hiatus hernia caused by a short esophagus and dysphagia [Rasmussen et al 2016].
Seizures. Seven out of 50 cases (14%) reported seizure activity, including febrile seizures [Moreno-De-Luca et al 2010], partial complex seizures [Nagamani et al 2010], and mesial temporal lobe epilepsy requiring lobectomy [Kasperavičiūtė et al 2011].
#### Case Reports
Other reported physical findings include hypotonia (6 persons), prenatal oligohydramnios (4), macrocephaly (4), sensorineural hearing loss (3), deep vein thrombosis/vascular calcifications (2) and congenital diaphragmatic hernia (2).
### Intrafamilial Variability
While the recurrent 17q12 deletion most often occurs de novo, there have been several reports of familial inheritance [Moreno-De-Luca et al 2010, George et al 2012, Quintero-Rivera et al 2014, Dotto et al 2019, Okorn et al 2019, Kołbuc et al 2020]. Although the size of the deletion did not differ between parents and children in these reports, significant variability in clinical presentation has been reported both between and within phenotype categories.
### Penetrance
The 17q12 recurrent deletion is highly pathogenic and penetrant, but expressivity is variable.
Because population-based studies with evaluation of all individuals with a 17q12 recurrent deletion are lacking, the exact penetrance is unknown both for individual phenotypic categories (e.g., kidney anomalies, neurodevelopmental disorders, diabetes) and for the presence of any associated pathologic phenotype (e.g., kidney anomaly OR neurodevelopmental disorder OR diabetes).
However, high pathogenicity and penetrance is supported by several lines of evidence:
* High rate of structural kidney anomalies among individuals who were not ascertained as part of kidney disease cohorts (130/148; 88%) (Table 2)
* Preliminary evidence suggesting a high rate of neurodevelopmental and neuropsychiatric disorders among individuals who were not ascertained as part of NDD/NPD cohorts (3/4; 75%) [Martin et al 2020]
* Very low frequency of the deletion in control populations (e.g., none in ~48,000 controls in one study [Moreno-De-Luca et al 2010])
* High de novo ratio (percentage of cases that are de novo) [Kirov et al 2014]
These studies suggest that penetrance is virtually 100%, with missing data and variable expressivity accounting for the very rare presence of the 17q12 deletion in control populations.
### Nomenclature
In 1997, heterozygous pathogenic variants in HNF1B were described as a cause of MODY in one family [Horikawa et al 1997]; shortly thereafter the same family was found to have kidney involvement [Iwasaki et al 1998]. In 2001, the combination of congenital anomalies of the kidney and urinary tract and MODY5 became known as "renal cysts and diabetes (RCAD) syndrome" [Bingham et al 2001].
### Prevalence
The reported prevalence of the 17q12 recurrent deletion in large populations not selected on the basis of disease ranges from 0.002% (1:50,000) to 0.007% (1:14,000) – 0.002% in healthy European volunteers (UK Biobank; n = ~421K), 0.004% in a US health care system-based population (DiscovEHR; n = ~90K), and 0.007% in a large Icelandic control sample (deCODE; n = ~101K) [Martin et al 2020]. A higher prevalence estimate of 0.025% (1:4,000) was described in a population-based pregnancy cohort study of 12,252 mother-father-newborn trios [Smajlagić et al 2020].
Among individuals undergoing clinical postnatal chromosomal microarray analysis, the prevalence of the 17q12 recurrent deletion is much higher: approximately 0.1% (1:1000) [Moreno-De-Luca et al 2010, Rosenfeld et al 2013, Kirov et al 2014, Rasmussen et al 2016]. The main indications for clinical CMA in these studies were neurodevelopmental disorders (global developmental delay, intellectual disability, ASD) and congenital malformations.
It may be useful to consider the estimated prevalence of the 17q12 recurrent deletion in certain clinical populations:
* Congenital anomalies of the kidney. 1.9% (~1:53); when considering CAKUT more broadly, 0.8% (~1:123) have 17q12 deletion [Verbitsky et al 2019].
* Chronic kidney disease. 0.03%-2.2% (~1:3000 - 1:46) [Lata et al 2018, Connaughton et al 2019, Groopman et al 2019]
* Neurodevelopmental disorders. 0.09% (~1:1,150) [Kirov et al 2014]
* Schizophrenia. 0.036% (~1:2,800) [Kirov et al 2014]
* Müllerian aplasia. 3%-6% (~1:33 - 1:17) [Nik-Zainal et al 2011, Williams et al 2017]. Among women with both uterine and kidney anomalies, 18% (~1:6) had a 17q12 deletion or pathogenic HNF1B sequence variant [Oram et al 2010].
## Differential Diagnosis
Kidney anomalies. The differential diagnosis of kidneys cysts is age dependent (see Table 3).
### Table 3.
Genetic Disorders with Kidney Cysts in the Differential Diagnosis of 17q12 Recurrent Deletion Syndrome
View in own window
Gene(s)DisorderMOIKidney PhenotypeExtrarenal Phenotype
DNAJB11
GANAB
PKD1
PKD2ADPKDADNumerous bilateral cysts; kidney enlargement; hypertension; nephrolithiasis; progressive CKD, w/ESRD in mid- to late-adulthood. DNAJB11\- & GANAB-assoc disease have milder phenotypes w/normal-sized kidneys, smaller cysts, & less progression to ESRD.Liver cysts; intracranial aneurysms; cardiac valve abnormalities; diverticular disease; hernias
ALG8
GANAB 1
LRP5
PRKCSH
SEC63
SEC61B 2ADPLD (OMIM PS174050)ADFew cysts occasionally reportedPolycystic liver disease
MUC1ADTKD-MUC1 (previously known as MCKD1)ADTubulointerstitial disease; few small corticomedullary cysts in 50%; normal or small-sized kidneys; CKD, highly variable progression to ESRDHyperuricemia, gout
RENADTKD-REN (previously known as FJHN2)ADTubulointerstitial disease, cysts, slowly progressive CKDAnemia, hyperuricemia, gout
SEC61A1ADTKD-SEC61A1 3 (also referred to as FJHN4)ADBilateral small cysts in 50%; normal or small-sized kidneys; CKDIUGR, congenital anemia
UMODADTKD-UMOD (previously known as FJHN1 or MCKD2)ADTubulointerstitial disease; normal or small kidneys; few unilateral or bilateral cysts in 1/3; variable progression of CKD to ESRDHyperuricemia, gout
JAG1
NOTCH2Alagille syndromeADRenal dysplasia, renal tubular acidosis, CAKUTCholestatic liver disease, cardiac anomalies, characteristic facies, skeletal anomalies, ophthalmic anomalies
PKHD1
(DZIP1L) 4ARPKDAREnlarged, hyperechogenic kidneys in utero; multiple small bilateral cysts in childhood; ESRD in 1st decade in 50%Congenital hepatic fibrosis, Caroli syndrome, pulmonary hypoplasia, prenatal oligoanhydramnios
EYA1
SIX1
SIX5Branchiootorenal spectrum disorderADRenal agenesis, hypoplasia, or dysplasia; ureteropelvic junction obstruction; calyceal cyst/diverticulum; calyectasis, pelviectasis, hydronephrosis, VUREar abnormalities (deafness, outer ear anomalies, middle ear anomalies, preauriular pits); 2nd branchial arch anomalies (sinus tract, cyst)
BICC1Cystic renal dysplasia, susceptibility to (OMIM 601331)ADCystic renal dysplasia, VURNone
BMPERDiaphanospondylo-dysostosis (OMIM 608022)ARNephroblastomatosis w/cystic kidneysSkeletal anomalies (small chest, abnormal vertebral segmentation, & posterior rib gaps); craniofacial anomalies (ocular hypertelorism, epicanthal folds, depressed nasal bridge w/short nose, & low-set ears)
PMM2HIPKD 5ARAntenatal or childhood onset enlarged hyperechogenic kidneys w/multiple cysts; variable progression of CKD to ESRD from infancy to early adulthoodInfantile hyperinsulinemic hypoglycemia; liver cysts
CEP290
INVS
IQCB1
NPHP1
NPHP3
NPHP4
TMEM67
(≥19 genes) 6NephronophthisisARCorticomedullary cysts; normal or small-sized kidneys (but often moderately enlarged in infantile onset type); urinary concentrating & sodium reabsorption defect; progressive CKDNephronophthisis may be isolated or part of a syndrome, such as Joubert, Bardet-Biedl, Jeune, Meckel-Gruber, Senior-Loken, Leber congenital amaurosis, Cogan, or COACH.
OFD1Oral-facial-digital syndrome type IXLPolycystic kidneys in women; progressive kidney dysfunction in adulthoodCleft palate, dental anomalies, facial dysmorphology, digital anomalies, ID
PAX2Renal coloboma syndrome (See PAX2-Related Disorder.)ADHypoplasia, hypodysplasia, multicystic dysplastic kidney, VUR, other CAKUT, FSGS, uric acid nephrolithiasisOptic nerve dysplasia, retinal coloboma, other eye malformations
TSC1
TSC2Tuberous sclerosis complexADMultiple & bilateral cysts & angiomyolipomas, oncocytomas, renal cell carcinomaCortical tubers, astrocytomas; epilepsy, ID; cutaneous angiofibromas, hypopigmented patches; retinal hamartoma; cardiac rhabdomyoma; pulmonary LAM;
VHLvon Hippel-Lindau syndromeADBilateral cysts, renal cell carcinomaretinal hemangiomas; hemangioblastomas of the cerebellum, spine, retina; pheochromocytoma; pancreatic neuroendocrine tumors
CRB2Ventriculomegaly w/cystic kidney disease (OMIM 219730)ARMicroscopic renal tubular cystsDilated cerebral ventricles, postaxial polydactyly, ventricular septal defect
Adapted from: Cornec-Le Gall et al [2019]; Lanktree et al [2019]; Armstrong & Thomas [2019]; Polycystic Kidney Disease, Autosomal Dominant; Polycystic Kidney Disease, Autosomal Recessive; and Nephronophthisis
AD = autosomal dominant; ADPKD = autosomal dominant polycystic kidney disease; ADPLD = autosomal dominant polycystic liver disease; ADTKD = autosomal dominant tubulointerstitial kidney disease; AR = autosomal recessive; ARPKD = autosomal recessive polycystic kidney disease; CAKUT = congenital anomalies of the kidney and urinary tract; CKD = chronic kidney disease; COACH = cerebellar vermis hypo/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis; ESRD = end-stage renal disease; FJHN = familial juvenile hyperuricemic nephropathy; FSGS = focal segmental glomerulonephritis; HIPKD = hyperinsulinemia with hypoglycemia and polycystic kidney disease; ID = intellectual disability; IUGR = intrauterine growth restriction; LAM = lymphangioleiomyomatosis; MCKD = medullary cystic kidney disease; MOI = mode of inheritance; VUR = vesicoureteric reflux
1\.
Porath et al [2016]
2\.
Besse et al [2017]
3\.
Bolar et al [2016]
4\.
DZIP1L has not yet been definitively proven to be a second locus for ARPKD (see ARPKD).
5\.
Soares et al [2020]
6\.
Listed genes represent the most common genetic causes of nephronophthisis; for other genes associated with this phenotype, see Nephronophthisis.
The differential diagnosis of kidney cysts also includes, in children: idiopathic cystic dysplasia and obstructive dysplasia; and in adults: acquired kidney cysts (related to chronic kidney disease and/or dialysis) or simple cortical cysts [Clissold et al 2015].
Maturity-Onset Diabetes of the Young (MODY) is a group of inherited disorders of non-autoimmune diabetes mellitus which usually present in adolescence or young adulthood (typically age <35 years). MODY is generally inherited in an autosomal dominant manner.
The clinical findings are either:
* An atypical type 2 diabetes-like condition that occurs in the absence of the usual predisposing factors (obesity, hypertension, dyslipidemia, and acanthosis nigricans); OR
* An atypical type 1 diabetes-like condition that occurs in the absence of the usual clinical and laboratory manifestations (islet cell autoantibodies, persistence of measurable C-peptide levels, and diabetic ketoacidosis) [American Diabetes Association 2010, Fajans & Bell 2011, Carroll & Murphy 2013].
### Table 4.
Maturity-Onset Diabetes of the Young (MODY): Genes and Associated Clinical Features
View in own window
GeneLocus NameClinical Features
ABCC8MODY12Similar to HNF1A\- & HNF4A-MODY
APPL1MODY14Overweight/obesity in some
BLKMODY11Overweight/obesity in some
CELMODY8Pancreatic atrophy → exocrine pancreatic insufficiency. Fibrosis & lipomatosis → diabetes.
GCKMODY2Stable, mild fasting hyperglycemia at birth. Typically asymptomatic; diagnosis often incidental.
HNF1AMODY3Transient neonatal hyperinsulinemic hypoglycemia in some. Progressive insulin secretory defect. OGTT frequently needed to make an early diagnosis. Renal glycosuria.
HNF1BMODY5IUGR, kidney anomalies, urogenital tract anomalies, pancreatic hypoplasia
HNF4AMODY1Birth weight >800 g above normal. Transient neonatal hyperinsulinemic hypoglycemia common. Progressive insulin secretory defect.
INSMODY10
KCNJ11MODY13Similar to HNF1A-MODY & HNF4A-MODY
KLF11MODY7
NEUROD1MODY6Overweight/obesity in some
PAX4MODY9
PDX1MODY4Overweight/obesity in some
Adapted from the MODY Overview.
IUGR = intrauterine growth restriction; OGTT = oral glucose tolerance test
Other genetic causes of müllerian aplasia. Six percent of women in a large cohort with müllerian aplasia had the 17q12 recurrent deletion; an additional 8% had other recurrent copy number variants, including the 16p11.2 recurrent deletion and the distal 22q11.2 recurrent deletion [Nik-Zainal et al 2011]. Additional case reports of women with uterine malformations have identified intragenic pathogenic variants in LHX1, a gene found within the recurrent 17q12 deletion region that encodes a transcription factor required for the formation of müllerian ducts [Ledig et al 2012, Sandbacka et al 2013].
Other genetic causes of neurodevelopmental or neuropsychiatric disorders. The differential diagnosis for developmental delay, intellectual disability, schizophrenia, and autism spectrum disorder includes hundreds of known copy number and single-nucleotide variants and is too broad for discussion here. (See OMIM Phenotypic Series: Autosomal dominant ID; Autosomal recessive ID; Nonsyndromic X-linked ID; Syndromic X-linked ID; and Susceptibility to autism.)
## Management
No clinical practice guidelines for 17q12 recurrent deletion syndrome have been published.
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with the 17q12 recurrent deletion syndrome, the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 5.
Recommended Evaluations Following Initial Diagnosis in Individuals with 17q12 Recurrent Deletion Syndrome
View in own window
System/ConcernEvaluationComment
Kidney structural or
functional defectsBlood pressure; kidney & bladder ultrasound examination; serum BUN, creatinine, electrolytes (incl calcium, Mg, phosphorus) & uric acid; urine protein, Mg, & creatinine; consultation w/nephrologistRandom urine Mg/creatinine is needed to calculate fractional excretion of Mg.
↑ FEMg (>2%) is diagnostic of tubular Mg wasting in those w/normal kidney function.
Neurodevelopmental/
neuropsychiatric
disordersAssessment of speech & language; cognitive, motor, & social development; perceptual anomalies; mood; behavior
Maturity-onset
diabetes of the
young type 5Fasting glucose & hemoglobin A1C levels; consultation w/endocrinologist
Genital tract
abnormalities
* Males: clinical exam
* Females: pelvic ultrasound exam & gynecologic exam to evaluate for possible müllerian abnormalities
Liver abnormalitiesLiver function tests (hepatic function panel, GGT)
Eye abnormalitiesOphthalmologic exam
Congenital heart
defectsClinical assessment; consultation w/cardiologist & echocardiography if warranted
SeizuresNeurology consultation if seizures are suspected clinically
Sensorineural
hearing lossAudiologic eval
Genetic counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of 17q12 recurrent deletion syndrome in order to facilitate medical & personal decision-making
Family support/
resourcesAssess:
* Use of community or online resources such as Parent to Parent;
* Need for social work involvement for parental support;
* Need for home nursing referral;
* Need for home psychotherapy or behavioral support.
GGT = gamma-glutamyl transferase; Mg = magnesium; MOI = mode of inheritance
1\.
Medical geneticist, certified genetic counselor, certified advanced genetic nurse
### Treatment of Manifestations
Treatment is symptomatic and depends on an individual's specific needs.
### Table 6.
Treatment of Manifestations in Individuals with 17q12 Recurrent Deletion Syndrome
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
Kidney diseaseTreatment should follow standard practice. Established guidelines for the management of chronic kidney disease, incl that related to CAKUT or ADTKD, are available for children & adults [KDIGO CKD Work Group 2013].
* Some persons have normal kidney function; others may progress to ESRD & require dialysis or kidney transplantation.
* Mg depletion is common & often requires replacement. Oral Mg supplements in organic salt forms (e.g., aspartate, citrate, gluconate) may be more bioavailable than inorganic salt forms (e.g., oxide, sulfate, glycerophosphate) [NIH 2018]
* In those developing ESRD, transplantation is a good option, as kidney disease is not expected to recur. For those who also have diabetes mellitus, simultaneous pancreas & kidney transplantation has been successful & should be considered [Poitou et al 2012].
Neurodevelopmental/
neuropsychiatric disorders
* Provide specialized instruction, OT, PT, & speech/behavioral therapies if indicated.
* Treatment of developmental disabilities involves a multimodal approach to educational needs, social & recreational activities, & assoc impairments incl behavior problems & coexisting diagnoses.
* Management of ASD should follow AAP [Hyman et al 2020] & AACAP [Volkmar et al 2014] guidelines.
* Psychiatric consultation & therapy for those w/mental health concerns incl mood disorders, anxiety, &/or psychosis. The AACAP has published guidelines for assessment & treatment of psychiatric disorders in children & adolescents w/ID [Siegel et al 2020].
Early identification & intervention for neurodevelopmental or neuropsychiatric disorders is important for optimal outcomes.
Maturity-onset diabetes of the young type 5Treatment should follow standard practice.Initial response to oral antihyperglycemic agents is common, but clinical course tends to be progressive, & most ultimately require treatment w/insulin [Dubois-Laforgue et al 2017b].
Genital tract
abnormalities
* Nonsurgical & surgical intervention may be considered for those w/genital tract anomalies, incl müllerian agenesis.
* All individuals w/müllerian agenesis should be offered counseling & encouraged to connect w/peer support groups.
Primary vaginal dilation is successful for >90%-96% of patients w/müllerian agenesis [Committee on Adolescent Health Care 2018]
Liver abnormalitiesStandard treatment(s) as recommended by gastroenterologist.A minority of persons w/neonatal cholestasis have required surgical intervention [Kotalova et al 2015, Pinon et al 2019].
Eye abnormalitiesStandard treatment(s) as recommended by ophthalmologist, incl refractory eye exam & corrective lenses as needed
Congenital heart
defectsMedical & surgical management per cardiologist & cardiothoracic surgery
SeizuresStandardized treatment w/AEDs by experienced neurologist
* Many AEDs may be effective (none demonstrated effective specifically for this disorder).
* Education of parents/caregivers 1
Sensorineural
hearing lossHearing aids may be helpful; per audiologist.Community hearing services through early intervention or school district
AACAP = American Academy of Child & Adolescent Psychiatrists; AAP = American Academy of Pediatrics; ADTKD = autosomal dominant tubulointerstitial kidney disease; AED = antiepileptic drug; ASD = autism spectrum disorder; ESRD = end-stage renal disease; OT = occupational therapy; PT = physical therapy
1\.
Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit.
### Surveillance
### Table 7.
Recommended Surveillance for Individuals with 17q12 Recurrent Deletion Syndrome
View in own window
System/ConcernEvaluationFrequency
Kidney structure/
functionKidney & bladder ultrasound exam to monitor for kidney cysts or other structural abnormalitiesIn those without known structural defects, 12 months after establishing the diagnosis, then every 2-3 years in childhood/adolescence and every 3-5 years in adulthood. If an abnormality is detected, more frequent ultrasound examinations may be warranted
Monitoring of:
* Blood pressure
* Kidney function
* Serum concentration of Mg, potassium, uric acid
* Urine protein:creatinine ratio
* Urine Mg & creatinine
Periodic, preferably under guidance of nephrologist. Annual or more frequent monitoring may be advised for those who:
* Have lab findings suggestive of kidney disease,
* Are taking potentially nephrotoxic medications (e.g., NSAIDs)
* Have genitourinary structural abnormalities
[Verbitsky et al 2015]
Neurodevelopment
* Monitor developmental progress & educational needs.
* A full psychoeducational eval incl assessment of speech, cognitive, social/emotional, adaptive, & motor skills is indicated for children who experience difficulty w/school or behavioral challenges.
* Surveillance for autism symptoms in early childhood & prodromal psychotic symptoms in teenage years is warranted (although autism & schizophrenia occur less frequently than intellectual & learning disabilities).
At each visit
Maturity-onset
diabetes of the
young type 5HgbA1CAnnually
Individuals & families should be educated on how to monitor for clinical signs/symptoms of diabetes mellitus (e.g., polyuria, polydipsia, weight loss [sometimes w/polyphagia], fatigue, nausea, vomiting, blurred vision) in order to promote early diagnosis & treatment.Referral to endocrinologist as indicated depending on clinical manifestations
Genital tract
abnormalitiesConsider reevaluation for uterine & vaginal abnormalities related to müllerian duct aplasia in pubertal females w/primary amenorrhea.Rudimentary müllerian structures are commonly found on MRI. On US, these rudimentary structures are difficult to interpret & may be particularly misleading before puberty [Committee on Adolescent Health Care 2018].
Liver abnormalitiesHepatic function panel (or comprehensive metabolic panel) & GGT. Consider lipid panel given case reports of hepatic steatosis. Ultrasound may be indicated if labs are abnormal.Periodic; consider annually w/kidney function tests & electrolytes as described above.
EyesOphthalmologic evalAnnually during early childhood
NeurologyMonitor those w/seizures as clinically indicated.
HearingHearing screeningThroughout childhood, per established guildelines of Bright Futures/American Academy of Pediatrics [Hagan et al 2017]
GGT = gamma-glutamyl transferase; NSAIDs = nonsteroidal anti-inflammatory drugs; US = ultrasound
### Agents/Circumstances to Avoid
Individuals with HNF1B-associated kidney disease (including the 17q12 recurrent deletion) who develop ESRD and require kidney transplantation are at increased risk for developing post-transplant diabetes mellitus; therefore, use of an immunosuppressive regimen that avoids tacrolimus and mammalian target of rapamycin (mTOR) inhibitors and reduces corticosteroid exposure may be beneficial, including for those who do not have preexisting diabetes [Zuber et al 2009, Faguer et al 2011, Clissold et al 2015].
Nephrotoxic drugs (e.g., NSAIDs) should be avoided by those with kidney abnormalities. Hepatotoxic medications and alcohol should be avoided by those with liver abnormalities.
For individuals with mental health conditions such as autism, schizophrenia, or bipolar disorder, the authors recommend careful consideration of antipsychotic agents that may lead to weight gain, as this potential increase has been associated with metabolic syndrome and the later development of diabetes mellitus, for which people with 17q12 deletions are at baseline increased risk. Likewise, the use of mood stabilizers that affect kidney function in the long term, such as lithium, should be carefully considered in the setting of potential underlying anatomic and functional abnormalities in people with 17q12 deletions. These recommedations stem from empirically grounded clinical reasoning based on the underlying phenotypes associated with 17q12 deletions, as large studies assessing the efficacy of these interventions have not yet been performed.
### Evaluation of Relatives at Risk
If genomic testing detects the 17q12 recurrent deletion in one of the proband's parents, it is appropriate to clarify the genetic status of older and younger sibs of the proband and other relatives at risk in order to identify those who would benefit from close assessment/monitoring for evidence of kidney structural or functional defects, maturity-onset diabetes of the young, and developmental delays / intellectual disability.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| 17q12 Recurrent Deletion Syndrome | None | 6,644 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK401562/ | 2021-01-18T21:45:46 | {"synonyms": []} |
Unicentric Castleman disease (UCD) is a rare condition that affects the lymph nodes and related tissues. It is a form of Castleman disease that is "localized" to a single set of lymph nodes (as opposed to multicentric Castleman disease which has more widespread effects). UCD often starts as an enlarged lymph node. Depending on the location of this enlarged node, some people will have no additional features of the condition, while others will develop symptoms when it pushes on nearby organs and/or tissues. The exact underlying cause of UCD is currently unknown. Treatment typically includes surgical removal of the affected lymph node.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Unicentric Castleman disease | c0017531 | 6,645 | gard | https://rarediseases.info.nih.gov/diseases/6005/unicentric-castleman-disease | 2021-01-18T17:57:14 | {"mesh": ["D005871"], "umls": ["C0017531"], "orphanet": ["93685"], "synonyms": ["Unicentric angiofollicular ganglionic hyperplasia", "Unicentric angiofollicular lymph hyperplasia", "Localized Castleman disease"]} |
A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth disease type 2Q (CMT2Q) is caused by a heterozygous loss-of-function mutation in the DHTKD1 gene (614984) on chromosome 10p14. One such family has been reported.
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Clinical Features
Xu et al. (2012) reported a 5-generation Chinese family from the Shandong Province of China affected by an autosomal dominant form of CMT2. This family was ascertained through a 40-year-old male proband. There were 8 affected individuals, 5 males and 3 females, among 5 generations who had symmetrical muscle wasting and a predominating weakness of the distal parts of the lower limbs, decreased or absent deep tendon reflex, and mild to moderate deep sensory impairment. The initial complaints of the proband included difficulty walking and tripping due to foot and distal leg weakness at the age of 15 years. Neurologic exam at that time revealed muscle atrophy in the distal parts of the forearms and inner osseous muscles of the hands. The lower legs developed severe muscle atrophy, which presented as 'crane-leg-like' malformations. Motor neuron and sensory neuron conduction velocities were normal in the upper limbs but reduced in the lower limbs. Muscle biopsy from the proband showed small angulated muscle fibers, and electron microscopy showed sarcomere disappearance, disorganized microfilaments, and mitochondrial vacuolization. Among the other individuals who were examined, ranging in age from 13 to 71 years, all had symptom onset between ages 13 to 25 years. All exhibited pes cavus and had some degree of motor and sensory deficits, more severe in lower than in upper extremities.
Mapping
Xu et al. (2012) performed linkage analysis in a Chinese family segregating axonal CMT and found that the phenotype was linked to chromosome 10p14-p13, spanning a 5.41-Mb region between D10S585 and D10S1477.
Molecular Genetics
In all 8 affected members of a Chinese family segregating axonal CMT, Xu et al. (2012) identified a heterozygous nonsense mutation (Y485X; 614984.0004) in the DHTKD1 gene. The mutation was not found in unaffected individuals in the family or in 250 unrelated control individuals. Knockdown of DHTKD1 resulted in decreased ATP, total NAD(+), and NADH, and NADH in vitro.
Animal Model
Xu et al. (2018) found that homozygous Dhtkd1-knockout mice exhibited a CMT2Q-like phenotype characterized by anatomic and functional development of peripheral neuropathy with signs of motor and sensory impairment, axonal nerve degeneration, and muscle atrophy. Examination of Dhtkd1-knockout sciatic nerve showed decreased density of nerve fibers, irregular myelin sheath that dissociated from axons, and abnormal expression levels of major myelin genes. Moreover, Dhtkd1 knockout caused severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Increased 2-KAA and 2-AAA stimulated insulin biosynthesis and secretion, causing elevated insulin in knockout mice. Subsequently, elevated insulin regulated myelin protein zero (MPZ; 159440) transcription in Schwann cells via upregulation of Egr2 (129010), leading to myelin structure damage and axonal degeneration. Mice fed 2-AAA did reproduce phenotypes similar to CMT2Q.
INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Small, angulated muscle fibers seen on muscle biopsy \- Sarcomere disappearance seen on muscle biopsy \- Disorganized myofilaments seen on muscle biopsy \- Mitochondrial vacuolization seen on muscle biopsy \- Symmetrical muscle wasting \- Muscle atrophy NEUROLOGIC Peripheral Nervous System \- Weakness of distal lower limbs \- Muscle atrophy in distal forearm and hands \- Decreased or absent deep tendon reflexes \- Deep sensory impairment, mild to moderate \- Difficulty walking MISCELLANEOUS \- One 5-generation Chinese family reported (last curated November 2014) MOLECULAR BASIS \- Caused by mutation in the dehydrogenase E1 and transketolase domains-containing protein 1 (DHTKD1, 614984.0004 ) ▲ Close
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*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2Q | c3554366 | 6,646 | omim | https://www.omim.org/entry/615025 | 2019-09-22T15:53:25 | {"doid": ["0110170"], "omim": ["615025"], "orphanet": ["329258"], "synonyms": ["CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2Q", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2Q", "Alternative titles", "CMT2Q"]} |
A number sign (#) is used with this entry because this form of susceptibility to leprosy (LPRS3) is associated with a polymorphism in the TLR2 gene (603028) on chromosome 4q32.
See 609888 for a discussion of leprosy susceptibility in general and information on genetic heterogeneity.
Mapping
LPRS3 is associated with a polymorphism in the TLR2 gene, which Rock et al. (1998) mapped to chromosome 4q32.
Molecular Genetics
Kang and Chae (2001) identified an arg677-to-trp polymorphism (R677W; 603028.0001) in the intracellular domain of TLR2 in 10 (22%) of 45 Korean lepromatous leprosy patients, but not in any of 41 Korean tuberculoid patients or 45 Korean controls. They concluded that the R677W polymorphism in TLR2 has a role in susceptibility to lepromatous leprosy.
Bochud et al. (2003) found that wildtype TLR2 mediated CD14 (158120)-enhanced Mycobacterium leprae-dependent activation of NFKB (see 164011), but TLR2 containing R677W did not. They concluded that the impaired function of the R677W variant provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy.
Malhotra et al. (2005) used a case control study to investigate whether the R677W SNP in TLR2 reported by Kang and Chae (2001) was associated with leprosy susceptibility in 286 Indian leprosy patients and 183 ethnically matched controls. Genotyping results after direct PCR sequencing led Malhotra et al. (2005) to conclude that the R677W polymorphism is not a true polymorphism of TLR2, but rather resulted from variation present in a duplicated region 23 kb upstream of TLR2 that shares 93% identity with TLR2 exon 3. Malhotra et al. (2005) also failed to detect variation in the TLR2 promoter region.
Mikita et al. (2009) investigated the R677W polymorphism in 99 Japanese leprosy patients, whose genetic background is close to that of the Korean patients studied by Kang and Chae (2001). They found that R677W was undetectable in the Japanese patients, similar to the findings in Indian patients reported by Malhotra et al. (2005). Moreover, they failed to detect any of 7 additional nonsynonymous SNPs in the TLR2 gene in the Japanese patients.
Bochud et al. (2008) analyzed 3 TLR2 polymorphisms for associations with risk of developing leprosy, leprosy type, or leprosy reactions in 441 patients and 187 controls belonging to 3 Ethiopian ethnic groups. They found that a synonymous 597C-T SNP was associated with reduced susceptibility to reversal reaction (OR of 0.34), whereas patients homozygous for a 280-bp microsatellite marker had an increased risk of reversal reaction (OR of 5.83).
INHERITANCE \- Autosomal dominant IMMUNOLOGY \- Susceptibility to infection by Mycobacterium leprae causing leprosy MISCELLANEOUS \- See 609888 for a discussion on leprosy susceptibility MOLECULAR BASIS \- Susceptibility conferred by mutation in the toll-like receptor-2 gene (TLR2, 603028.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| LEPROSY, SUSCEPTIBILITY TO, 3 | c0023343 | 6,647 | omim | https://www.omim.org/entry/246300 | 2019-09-22T16:25:55 | {"mesh": ["D007918"], "omim": ["246300"], "orphanet": ["548"]} |
Ishikawa et al. (2000) reported a Japanese family with an autosomal dominant neurodegenerative disorder with mild chromosome instability and radiation sensitivity. Clinical manifestations included short stature, mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated calcification of bilateral basal ganglia, markedly atrophic spinal cord, and degeneration of the white matter. Cytogenetic studies demonstrated several spontaneous chromosome rearrangements at 14q11.2. Pretreatment with radiation or bleomycin resulted in a high rate of chromatid breaks. The patients showed no evidence of immunodeficiency. Ishikawa et al. (2000) suggested that this family may represent a new autosomal dominant degenerative disorder, possibly due to a mutation in a gene responsible for DNA double-strand breakage repair.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| RADIATION SENSITIVITY/CHROMOSOME INSTABILITY SYNDROME, AUTOSOMAL DOMINANT | c1854244 | 6,648 | omim | https://www.omim.org/entry/605463 | 2019-09-22T16:11:21 | {"mesh": ["C565326"], "omim": ["605463"]} |
Central centrifugal cicatricial alopecia
Other namesHot comb alopecia and Follicular degeneration syndrome
SpecialtyDermatology
Central centrifugal cicatricial alopecia (CCCA), is a type of alopecia first noticed in African Americans in the 1950s and reported by LoPresti et al. in 1968 as a result of application of petrolatum followed by a stove-heated iron comb. The original theory was that the hot petrolatum would travel down to the hair root, burn the follicle, and after repetitive injury scarring would result.[1] Later CCCA was realized to affect men and women without a history significant for use of such styling techniques. Consequently, the terms "follicular degeneration syndrome" per Sperling and Sau in 1992 and then CCCA per Olsent et al. in 2003 were evolved. Plausible contributing factors may include other African-American styling techniques such as relaxers, tight braids, heavy extensions, certain oils, gels or pomades.
## Contents
* 1 Presentation
* 2 Cause
* 3 Histopathologic features
* 4 Treatment
* 5 Epidemiology
* 6 Terminology
* 7 See also
* 8 References
## Presentation[edit]
CCCA usually begins at the central (sagittal) midline of the scalp. It is symmetric and exhibits scarring as the name suggests. It involves solely the top of the scalp or may progress to Hamilton–Norwood scale Type VI or VII. Early symptoms may include pruritus, dysesthesias and tenderness. On examination the skin is thin with few follicular ostia and later in the disease the scalp may appear shiny.[citation needed]
## Cause[edit]
The mechanism of pathology of CCCA has only been postulated and not proven. However, one theory involves pressure exerted on the internal root sheath leading to damage, which leads to the recruitment of inflammatory cells and the end result of scarring. African Americans are found to be at increased risk either because of the curled hair shaft, distinct styling practices, moisturizing hair products, or chemical processing techniques (especially in the youth population). Some have hypothesized that CCCA represents an end stage of traction alopecia. However, this theory does not ring true as many patients lack a report of traction hairstyling.
## Histopathologic features[edit]
Histopathologic features include a perifollicular lymphocytic infiltrate, concentric lamellar fibrosis (layers of fibroblasts in the papillary dermis), sebaceous gland loss and premature disintegration of the internal root sheath. Additionally, granulomatous inflammation secondary to follicular rupture has been noted.[2] Perifollicular erythema and follicular keratosis is usually absent.[1]
## Treatment[edit]
Treatments for CCCA remain investigational. Altering hair care practices has not been proven to assist in hair rejuvenation. High-dose topical steroids, antibiotics, immunomodulators such as tacrolimus (Protopic) and pimecrolimus (Elidel), and anti-androgen/5alpha Reductase inhibitors have been used with unknown efficacy.[1][3]:648–9[4]:760[5]
## Epidemiology[edit]
CCCA tends to present itself in the 20s and progresses over 20–30 years. One should consider this diagnosis in African Americans with what appears to be a female-pattern hair loss.[1]
## Terminology[edit]
The terminology of CCCA has been a source of regular confusion. Recent clarifications have been made, with the term "central centrifugal cicatritial alopecia" adopted as a diagnostic category by the North American Hair Research Society. It has also been referred to as:[6][7]
* Hot comb alopecia
* Follicular degeneration syndrome
* Pseudopelade in African Americans
* Central elliptical pseudopelade in Caucasians
Also in this category is cicatricial pattern hair loss (CPHL). This CCCA pattern is a potential alopecia mimic that can be confused for androgenetic alopecia. Alopecia mimics have proven a problem in establishing diagnosis of alopecia when using only clinical evaluation.[8]
A similarly sounding term is central centrifugal scarring alopecia (CCSA). (L.C. Sperling, Central, centrifugal scarring alopecia. In: L.C. Sperling, Editor, An atlas of hair pathology with clinical correlations, Parthenon Publishing Group, New York (2003), pp. 91–100). This is a clinical finding that describes the diagnosis of some primary cicatricial alopecias as noted mainly in the central scalp, and includes CCCA, folliculitis decalvans, and any other potential centrally presenting cicatricial alopecia. This term is not often used in the literature to signify diagnostic terminology.
## See also[edit]
* Cicatricial alopecia
* List of cutaneous conditions
* Hot comb
## References[edit]
1. ^ a b c d Woolery-lloyd, Heather. Central Centrigugal Scarring Alopecia. www.Skinandaging.com, volume 11. (2003)
2. ^ Sperling and Sau, 1992
3. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
4. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
5. ^ Female Pattern Hair Loss and its Relationship to Permanent/Cicatricial Alopecia: A New Perspective. Journal of Investigative Dermatology (2007) 127, 1827-1828
6. ^ Ross EK, Tan E, Shapiro J. J Am Acad Dermatol. 2005 Jul;53(1):1-37;
7. ^ "Archived copy". Archived from the original on 2010-08-06. Retrieved 2010-06-24.CS1 maint: archived copy as title (link)
8. ^ Androgenic pattern presentation of scarring and inflammatory alopecia. J Eur Acad Dermatol Venereol. 2010 Jan 6. Rashid RM, Thomas V.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Central centrifugal cicatricial alopecia | c1274708 | 6,649 | wikipedia | https://en.wikipedia.org/wiki/Central_centrifugal_cicatricial_alopecia | 2021-01-18T18:52:49 | {"gard": ["10826"], "wikidata": ["Q5062079"]} |
Severe protein malnutrition
Kwashiorkor
One of many children with kwashiorkor in relief camps during the Biafra War (Image courtesy of U.S. Centers for Disease Control and Prevention)
Pronunciation
* /kwɑːʃiˈɔːrkər/
SpecialtyPediatrics
Deaths18
Kwashiorkor is a form of severe protein malnutrition characterized by edema and an enlarged liver with fatty infiltrates.[1] It is caused by sufficient calorie intake, but with insufficient protein consumption, which distinguishes it from marasmus. Kwashiorkor cases occur in areas of famine or poor food supply.[2] Cases in the developed world are rare.[3]
Jamaican pediatrician Cicely Williams introduced the term in 1935, two years after she published the disease's first formal description.[4][5] The name is derived from the Ga language of coastal Ghana, translated as "the sickness the baby gets when the new baby comes" or "the disease of the deposed child",[6] and reflecting the development of the condition in an older child who has been weaned from the breast when a younger sibling comes.[7] Breast milk contains amino acids vital to a child's growth. In at-risk populations, kwashiorkor may develop after a mother weans her child from breast milk, replacing it with a diet high in carbohydrates, such as a maize diet.[4]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Low protein intake
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Prognosis
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
The defining sign of kwashiorkor in a malnourished child is pitting edema (swelling of the ankles and feet). Other signs include a distended abdomen, an enlarged liver with fatty infiltrates, thinning of hair, loss of teeth, skin depigmentation, and dermatitis. Children with kwashiorkor often develop irritability and anorexia. Generally, the disease can be treated by adding protein to the diet; however, it can have a long-term impact on a child's physical and mental development, and in severe cases may lead to death.
In dry climates, marasmus is the more frequent disease associated with malnutrition. Another malnutrition syndrome includes cachexia, although it is often caused by underlying illnesses. These are important considerations in the treatment of the patients.
## Causes[edit]
The precise etiology of kwashiorkor remains unclear.[8][9][10][11][12] Several hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor. They include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes.[8][12][13]
### Low protein intake[edit]
Disability-adjusted life years per 100,000 inhabitants for protein–energy malnutrition in 2002.[14]
no data
fewer than 10
10–100
100–200
200–300
300–400
400–500
500–600
600–700
700–800
800–1000
1000–1350
more than 1350
Kwashiorkor is a severe form of malnutrition associated with a deficiency in dietary protein.[9] The extreme lack of protein causes an osmotic imbalance in the gastro-intestinal system causing swelling of the gut diagnosed as an edema or retention of water.[5]
Extreme fluid retention observed in individuals suffering from kwashiorkor is a direct result of irregularities in the lymphatic system and an indication of capillary exchange. The lymphatic system serves three major purposes: fluid recovery, immunity, and lipid absorption. Victims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption, all of which result from a state of severe undernourishment. Fluid recovery in the lymphatic system is accomplished by re-absorption of water and proteins which are then returned to the blood. Compromised fluid recovery results in the characteristic belly distension observed in highly malnourished children.[15]
Capillary exchange between the lymphatic system and the bloodstream is stunted due to the inability of the body to effectively overcome the hydrostatic pressure gradient. Proteins, mainly albumin, are responsible for creating the colloid osmotic pressure (COP) observed in the blood and tissue fluids. The difference in the COP of the blood and tissue is called the oncotic pressure. The oncotic pressure is in direct opposition with the hydrostatic pressure and tends to draw water back into the capillary by osmosis. However, due to the lack of proteins, no substantial pressure gradient can be established to draw fluids from the tissue back into the blood stream. This results in the pooling of fluids, causing the swelling and distention of the abdomen.[16]
The low protein intake leads to some specific signs: edema of the hands and feet, irritability, anorexia, a desquamative rash, hair discolouration, and a large fatty liver. The typical swollen abdomen is due to two causes: ascites because of hypoalbuminemia (low oncotic pressure), and enlarged fatty liver.[17]
Ignorance of nutrition can be a cause. A case was described where parents who fed their child cassava failed to recognize malnutrition because of the edema caused by the syndrome and believed the child was well-nourished despite the lack of dietary protein.[18]
Protein should be supplied only for anabolic purposes. The catabolic needs should be satisfied with carbohydrate and fat. Protein catabolism involves the urea cycle, which is located in the liver and can easily overwhelm the capacity of an already damaged organ. The resulting liver failure can be fatal. This means in patients suffering from kwashiorkor, protein must be introduced back into the diet gradually. Clinical solutions include weaning the affected with milk products and increasing the intake of proteinaceous material progressively to daily recommended amounts.[19]
## Diagnosis[edit]
Kwashiorkor, also known as “edematous malnutrition” because of its association with edema (fluid retention), is a nutritional disorder in regions experiencing famine.[20] Kwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema, low mid-upper arm circumference (MUAC < 115 mm), and a low weight-for-height Z-score (WHZ, Z < -3).[21][22][9] Additional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.[9][23] Kwashiorkor is distinguished from marasmus by the presence of edema.
WHO criteria for clinical assessment of malnutrition are based on the degree of wasting (MUAC), stunting (weight-for-height Z-score), and the presence of edema (mild to severe).[24]
## Prevention[edit]
In order to avoid refeeding syndrome, the person must be rehabilitated with small but frequent rations, given every two to four hours. During week one, a diet high in sugar and carbs is gradually enriched in protein as well as essential elements: sweet milk with mineral salts and vitamins. The diet may include lactases—so that children who have developed lactose intolerance can ingest dairy products—and antibiotics—to compensate for immunodeficiency. After two to three weeks, the milk is replaced by boiled cereals fortified with minerals and vitamins until the person's mass is at least 80% of normal weight. Traditional food can then be reintroduced. The child is considered healed when their mass reaches 85% of normal.[citation needed]
## Treatment[edit]
WHO guidelines outline 10 general principles for the inpatient management of severely malnourished children.[24][25]
1. Treat/prevent hypoglycemia
2. Treat/prevent hypothermia
3. Treat/prevent dehydration
4. Correct electrolyte imbalance
5. Treat/prevent infection
6. Correct micronutrient deficiencies
7. Start cautious feeding
8. Achieve catch-up growth
9. Provide sensory stimulation and emotional support
10. Prepare for follow-up after recovery
Both clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly.[12][24]
## Prognosis[edit]
Disorders usually resolve after early treatment. If the treatment is delayed, the overall health of the child is improved but physical (reduced) and intellectual (mental disabilities) sequelae are feared. Without treatment or if treatment occurs too late, death is inevitable.[citation needed]
A high risk of death is identified by a brachial perimeter < 11 cm or by a weight-to-height threshold[when defined as?] < −3 SD. In practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition.[citation needed]
## See also[edit]
* Anemia
* Emaciation
* Starvation and Edema
*
## References[edit]
1. ^ Benjamin O, Lappin SL (2020), "Kwashiorkor", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29939653, retrieved 27 July 2020
2. ^ Krebs NF, Primak LE, Hambridge KM. Normal childhood nutrition & its disorders. In: Current Pediatric Diagnosis & Treatment. McGraw-Hill.
3. ^ Liu T, Howard RM, Mancini AJ, Weston WL, Paller AS, Drolet BA, et al. (May 2001). "Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance". Archives of Dermatology. 137 (5): 630–6. PMID 11346341.[permanent dead link]
4. ^ a b Williams CD (July 1983) [1933]. "Fifty years ago. Archives of Diseases in Childhood 1933. A nutritional disease of childhood associated with a maize diet". Archives of Disease in Childhood. 58 (7): 550–60. doi:10.1136/adc.58.7.550. PMC 1628206. PMID 6347092.
5. ^ a b Williams CD, Oxon BM, Lond H (1935). "Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935". Bulletin of the World Health Organization. 81 (12): 912–3. doi:10.1016/S0140-6736(00)94666-X. PMC 2572388. PMID 14997245. Reprint: Williams CD, Oxon BM, Lond H (2003). "Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935". Bulletin of the World Health Organization. 81 (12): 912–3. doi:10.1016/S0140-6736(00)94666-X. PMC 2572388. PMID 14997245.
6. ^ Stanton J (2001). "Listening to the Ga: Cicely Williams' discovery of kwashiorkor on the Gold Coast". Clio Medica. 61: 149–71. doi:10.1163/9789004333390_008. ISBN 9789004333390. PMID 11603151.
7. ^ "Merriam Webster Dictionary". Retrieved 5 April 2009.
8. ^ a b Briend A (2014). "Kwashiorkor: still an enigma – the search must go on" (PDF). Emergency Nutrition Network. Retrieved 2 August 2019.
9. ^ a b c d Benjamin O, Lappin SL (2019). "Kwashiorkor". StatPearls. StatPearls Publishing. PMID 29939653. Retrieved 1 August 2019.
10. ^ Coulthard MG (May 2015). "Oedema in kwashiorkor is caused by hypoalbuminaemia". Paediatrics and International Child Health. 35 (2): 83–9. doi:10.1179/2046905514Y.0000000154. PMC 4462841. PMID 25223408.
11. ^ Pham TP, Tidjani Alou M, Bachar D, Levasseur A, Brah S, Alhousseini D, et al. (June 2019). "Gut Microbiota Alteration is Characterized by a Proteobacteria and Fusobacteria Bloom in Kwashiorkor and a Bacteroidetes Paucity in Marasmus". Scientific Reports. 9 (1): 9084. Bibcode:2019NatSR...9.9084P. doi:10.1038/s41598-019-45611-3. PMC 6591176. PMID 31235833.
12. ^ a b c Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, et al. (February 2013). "Gut microbiomes of Malawian twin pairs discordant for kwashiorkor". Science. 339 (6119): 548–54. Bibcode:2013Sci...339..548S. doi:10.1126/science.1229000. PMC 3667500. PMID 23363771.
13. ^ Velly H, Britton RA, Preidis GA (March 2017). "Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host". Gut Microbes. 8 (2): 98–112. doi:10.1080/19490976.2016.1267888. PMC 5390823. PMID 27918230.
14. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.
15. ^ "Nova et Vetera". The British Medical Journal. 2 (4673): 284. 1950. doi:10.1136/bmj.2.4673.267.
16. ^ Saladin K (2012). Anatomy and Physiology (6th ed.). New York: McGraw Hill. pp. 766–767, 809–811. ISBN 978-0-07-337825-1.
17. ^ Tierney EP, Sage RJ, Shwayder T (May 2010). "Kwashiorkor from a severe dietary restriction in an 8-month infant in suburban Detroit, Michigan: case report and review of the literature". International Journal of Dermatology. 49 (5): 500–6. doi:10.1111/j.1365-4632.2010.04253.x. PMID 20534082.
18. ^ "Malnutrition in Third World Countries". www.religion-online.org. Archived from the original on 19 September 2015. Retrieved 2 March 2017.
19. ^ https://www.embibe.com/study/examples-on-kwashiorkar-concept
20. ^ "Kwashiorkor".
21. ^ "UpToDate". www.uptodate.com. Retrieved 1 August 2019.
22. ^ Roberfroid D, Hammami N, Mehta P, Lachat C, Verstraeten R, Weise Prinzo Z, Huybregts L, Kolsteren P. "Management of oedematous malnutrition in infants and children aged >6 months: a systematic review of the evidence" (PDF).
23. ^ Heilskov S, Rytter MJ, Vestergaard C, Briend A, Babirekere E, Deleuran MS (August 2014). "Dermatosis in children with oedematous malnutrition (Kwashiorkor): a review of the literature". Journal of the European Academy of Dermatology and Venereology. 28 (8): 995–1001. doi:10.1111/jdv.12452. PMID 24661336.
24. ^ a b c "Updates on the Management of Severe Acute Malnutrition in Infants and Children" (PDF). WHO. 2013.
25. ^ Ashworth A (2003). "Guidelines for the inpatient treatment of severely malnourished children" (PDF). WHO.
## External links[edit]
* Media related to Kwashiorkor at Wikimedia Commons
Classification
D
* ICD-10: E40
* MeSH: D007732
* v
* t
* e
Malnutrition
Protein-energy
malnutrition
* Kwashiorkor
* Marasmus
* Catabolysis
Vitamin deficiency
B vitamins
* B1
* Beriberi
* Wernicke–Korsakoff syndrome
* Wernicke's encephalopathy
* Korsakoff's syndrome
* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
* Potassium
* Magnesium
* Calcium
* Iron
* Zinc
* Manganese
* Copper
* Iodine
* Chromium
* Molybdenum
* Selenium
* Keshan disease
Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
* Weight loss
* Cachexia
* Underweight
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Kwashiorkor | c0022806 | 6,650 | wikipedia | https://en.wikipedia.org/wiki/Kwashiorkor | 2021-01-18T19:05:58 | {"mesh": ["D007732"], "umls": ["C0022806"], "icd-9": ["260"], "icd-10": ["E40"], "wikidata": ["Q213151"]} |
A number sign (#) is used with this entry because supravalvular aortic stenosis (SVAS) is caused by heterozygous mutation in the gene encoding elastin (ELN; 130160) on chromosome 7q11.
SVAS is a frequent feature of Williams-Beuren syndrome (WBS; 194050), a contiguous gene deletion syndrome that includes hemizygous deletion of the ELN gene.
Clinical Features
Eisenberg et al. (1964) reported 22 cases of supravalvular aortic stenosis involving 3 generations of each of 2 families. Some had associated pulmonary valvular or peripheral arterial stenosis. None had unusual facies.
Gyllensward et al. (1957) reported pulmonary artery stenosis in mother and son.
Lewis et al. (1969) described a sibship in which 5 of 9 sibs had supravalvar aortic stenosis with peculiar facies but normal intelligence. Schmidt et al. (1989) reevaluated this family and provided examinations of the parents, additional sibs, and offspring of the original 5 patients. Echocardiographic examinations added to the completeness of the survey. The SVAS showed marked variability of expression and was not associated with mental retardation. It also was said not to be associated with the facial manifestations of Williams syndrome, but the photographs seem to belie that conclusion: the configuration of the mouth in patients III-16 and III-18 who had SVAS documented by echocardiogram is very suggestive of the Williams syndrome and is quite different from that in their brother, III-17, who had a normal echocardiogram. Schmidt et al. (1989) concluded that isolated SVAS and Williams syndrome represent 'clinically distinct entities.' They did not commit themselves as to whether there was any genetic relationship between the two.
Antia et al. (1967) commented on a lack of clear distinction between the familial supravalvular aortic stenosis with normal facies and mentality and the nonfamilial type with abnormal facies and mental retardation.
McDonald et al. (1969) described an arteriopathy, with multiple pulmonary and systemic arterial stenoses, in a mother and 3 daughters. Two had supravalvular aortic stenosis. The familial occurrence of pulmonary arterial stenoses is documented (McCue et al., 1965) and their occurrence after maternal rubella is well established (Rowe, 1963). It can be argued that supravalvular aortic stenosis is an inadequate or inappropriate designation.
Strong et al. (1970) observed sudden death following premedication for cardiac catheterization in an 11-month-old male. Postmortem showed severe fibromuscular dysplasia of both systemic and pulmonary arteries. A sister had signs of mild pulmonary artery and supravalvular aortic stenosis. The mother had signs of mild aortic stenosis.
Wooley et al. (1961) described sibs with supravalvular aortic stenosis.
McKusick (1978) saw a family in which a man, his son and daughter, and his paternal uncle had well-confirmed signs of supravalvular aortic stenosis and/or peripheral pulmonary stenoses. None had manifestations of Williams syndrome.
O'Connor et al. (1985) studied 6 patients with supravalvular aortic stenosis; 3 had Williams syndrome, 2 had familial SVAS (presumably without evidence of Williams syndrome), and 1 had sporadic SVAS.
The existence of a familial form of SVAS, which might be called the Eisenberg form, separate from the SVAS in the Williams-Beuren syndrome appeared to be established by a study of an extensive kindred with 36 affected persons in 5 generations (Chiarella et al., 1989). The unique study was made possible by the fact that the family had lived in relative isolation on a small island in the Sardinian archipelago for over 200 years and also by the availability of echocardiography, including portable equipment usable in the home, for noninvasive diagnosis. Penetrance was estimated to be 86%. In 5 of 8 patients who underwent cardiac catheterization, multiple pulmonary stenoses were observed. Surgical correction was performed in 4 cases. None of the affected family members had unusual facies or mental retardation.
A similar family with the Eisenberg form of SVAS was reported by Ensing et al. (1989). Three members of that family had supravalvular aortic stenosis requiring surgery. Of 22 members examined echocardiographically who had not had prior surgical repair, 13 had supravalvular aortic stenosis. The echocardiographic findings varied widely, from calcification of the ascending aorta in a 71-year-old man with minimally increased flow velocity, to mild narrowing with mildly increased flow velocity in 6 members, to significant narrowing with impressively increased flow velocity in 7. In addition, 4 patients had mild narrowing of pulmonary artery branches and 8 had peak pulmonary artery flow velocities above normal. The family was of Irish-Native American-English descent living in the United States.
Kumar et al. (1993) observed 5 affected persons in 1 family; 3 had isolated SVAS, 1 had isolated peripheral pulmonary stenosis (PPS), and 1 had SVAS and PPS.
Mapping
In a family with autosomal dominant SVAS, Curran et al. (1993) found that a translocation t(6;7)(p21.1;q11.23) that cosegregated with the disease also disrupted the elastin gene (130160). The breakpoint was localized to exon 28 of the gene. Combined with studies indicating linkage of SVAS to the elastin gene (Ewart et al., 1993), the data suggested that mutations in the elastin gene are the cause of SVAS. Ewart et al. (1993) found a combined lod score of 5.90 for linkage of SVAS with the ELN gene, which has been mapped to 7q11.2. In a large 3-generation family, Olson et al. (1993) found linkage to a highly informative (CA)n repeat marker at locus D7S440 which had been localized to 7q. The findings are entirely consistent with the evidence implicating the elastin gene in the causation of this abnormality.
Kumar et al. (1994) confirmed the linkage of supravalvular aortic stenosis to the elastin gene. In the family they studied, individuals in 4 sibships in 3 generations and, by inference, a patient in an earlier generation were affected. Three individuals had supravalvular aortic stenosis; one had peripheral pulmonary stenosis; and one had both.
### Exclusion Studies
Bennett et al. (1988) excluded the calcitonin gene (114130) as the site of the mutation in SVAS by use of a gene-specific probe which failed to show concordant segregation. In a family with many affected members with SVAS previously reported by Schmidt et al. (1989), Pastores et al. (1992) also excluded the calcitonin gene as the site of the mutation. Linkage was ruled out.
Cytogenetics
Morris et al. (1993) reported on the family in which SVAS cosegregated with a familial 6;7 translocation that disrupted the elastin gene at exon 28 (Curran et al., 1993). They pointed out that main pulmonary artery hypoplasia, preductal coarctation of the aorta, and pulmonic stenosis are frequently noted in patients with deletions involving the 7q11 region. Some of the patients have facial features such as wide mouth, long and prominent philtrum, and full lips like those in Williams syndrome.
Von Dadelszen et al. (2000) reported a patient with a de novo translocation 46,XX,t(6;7)(q27;q11.23). Since the Williams syndrome critical region probe showed 3 signals on FISH analysis (1 on the normal chromosome 7, 1 on the derivative 7 at 7q11.23, and a smaller signal on the derivative 6 chromosome at the translocation breakpoint), it appeared that the translocation may have disrupted the elastin gene. The patient presented prenatally with hydrops fetalis and severe supravalvular aortic and pulmonary stenosis, and died shortly after delivery at 32 weeks' gestation. Given the degree of body edema and prematurity, the authors were unable to distinguish between isolated SVAS and Williams syndrome in this patient.
Molecular Genetics
In a family with SVAS, Ewart et al. (1994) found a heterozygous 100-kb deletion in the 3-prime end of the elastin gene with a breakpoint between elastin exons 27 and 28. The same region was disrupted in the familial reciprocal translocation reported by Morris et al. (1993). Ewart et al. (1993) found that deletion involving 7q11.23 and resulting in hemizygosity of the elastin gene is responsible for the Williams-Beuren syndrome (194050). Deletions limited to the elastin gene appear to result in SVAS, whereas deletions spanning at least 114 kb lead to Williams-Beuren syndrome.
Olson et al. (1995) used Southern blot analysis to screen for mutations in the ELN gene in 6 familial and 3 sporadic cases of SVAS. The familial cases included members of the large Middle Eastern pedigree in which linkage to the elastin gene region had been found by Olson et al. (1993). A 30-kb deletion extending from breakpoints in intron 1 and intron 27 (130160.0002) was identified in 2 members of the Middle Eastern family. The proband developed severe SVAS and peripheral pulmonary artery stenosis and underwent aortic operation in early childhood. He had no evidence of Williams syndrome or clinically apparent abnormalities of other elastin-containing tissue. The deletion was also demonstrated in his mother, an obligate carrier with subtle disease (a heart murmur and a nondiagnostic echocardiogram). Blood for DNA analysis was not available from a maternal uncle with SVAS and a sister with isolated peripheral pulmonary artery stenosis.
Li et al. (1997) identified a heterozygous nonsense mutation in the ELN gene (130160.0003) in a sporadic case of SVAS.
Metcalfe et al. (2000) described the mutation spectrum of the ELN gene in 35 unrelated patients with SVAS and normal karyotypes without major deletions of the ELN gene as determined by FISH. A marked phenotypic intrafamilial variability was illustrated by 2 large families with multiple affected members with disease severity ranging from asymptomatic carriers to mild or severe SVAS requiring surgery, or sudden infant death. No obvious genotype-phenotype correlation was detected; cases with missense or splicing mutations were as likely to have severe SVAS as cases with truncating mutations.
Pathogenesis
Tassabehji et al. (1997) found that isolated SVAS was associated with point mutations in the ELN gene that predicted premature chain termination. They stated that in their experience all patients with a classic Williams syndrome phenotype (194050) had been found to be hemizygous at the elastin locus; nevertheless, only 5% had severe clinical SVAS. In their 2 SVAS families with point mutations, each mutation manifested as severe SVAS in the proband, but as mild cardiac features or nonpenetrance in the mothers. Tassabehji et al. (1997) considered such variability typical of phenotypes produced by haploinsufficiency, where genetic background is expected to have a major modifying effect. An alternative hypothesis is that a dominant-negative elastin mutation results if truncated proteins have some but not all domains critical for intermolecular interactions and thus may disrupt posttranslational processing and development of elastic fibers.
Micale et al. (2010) analyzed the ELN gene in 31 familial and sporadic cases of SVAS and identified 7 novel mutations, including 5 frameshift mutations and 2 splice site mutations (see, e.g., 130160.0020). In vitro analysis of 3 of the frameshift mutations using minigene constructs and transfection assays confirmed that functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS. In addition, molecular analysis of patient fibroblasts showed that the 2044+5G-C (130160.0020) mutant allele encodes an aberrant shorter form of the elastin polypeptide that may hamper the normal assembly of elastin fibers in a dominant-negative manner.
Cardiac \- Supravalvar aortic stenosis \- Pulmonary valvular stenosis \- Pulmonary artery stenosis Inheritance \- Autosomal dominant Vascular \- Peripheral arterial stenosis ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| SUPRAVALVULAR AORTIC STENOSIS | c0003499 | 6,651 | omim | https://www.omim.org/entry/185500 | 2019-09-22T16:34:04 | {"doid": ["1929"], "mesh": ["D021921"], "omim": ["185500"], "icd-10": ["Q25.3"], "orphanet": ["3193"], "synonyms": ["Alternative titles", "SUPRAVALVAR AORTIC STENOSIS, EISENBERG TYPE"]} |
Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement, with symptoms that may range from mild to severe.
The mild form of this disorder is called TH-deficient dopa-responsive dystonia (DRD). Symptoms usually appear during childhood. Affected individuals may exhibit unusual limb positioning and a lack of coordination when walking or running. In some cases, people with TH-deficient DRD have additional movement problems such as shaking when holding a position (postural tremor) or involuntary upward-rolling movements of the eyes. The movement difficulties may slowly increase with age but almost always get better with medical treatment.
The severe forms of TH deficiency are called infantile parkinsonism and progressive infantile encephalopathy. These forms of the disorder appear soon after birth and are more difficult to treat effectively.
Babies with infantile parkinsonism have delayed development of motor skills such as sitting unsupported or reaching for a toy. They may have stiff muscles, especially in the arms and legs; unusual body positioning; droopy eyelids (ptosis); and involuntary upward-rolling eye movements. The autonomic nervous system, which controls involuntary body functions, may also be affected. Resulting signs and symptoms can include constipation, backflow of stomach acids into the esophagus (gastroesophageal reflux), and difficulty regulating blood sugar, body temperature, and blood pressure. People with the infantile parkinsonism form of the disorder may have intellectual disability, speech problems, attention deficit disorder, and psychiatric conditions such as depression, anxiety, or obsessive-compulsive behaviors.
Progressive infantile encephalopathy is an uncommon severe form of TH deficiency. It is characterized by brain dysfunction and structural abnormalities leading to profound physical and intellectual disability.
## Frequency
The prevalence of TH deficiency is unknown.
## Causes
Mutations in the TH gene cause TH deficiency. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system. Tyrosine hydroxylase takes part in the pathway that produces a group of chemical messengers (hormones) called catecholamines. Tyrosine hydroxylase helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine. Dopamine transmits signals to help the brain control physical movement and emotional behavior. Other catecholamines called norepinephrine and epinephrine are produced from dopamine. Norepinephrine and epinephrine are involved in the autonomic nervous system.
Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine and epinephrine. These catecholamines are necessary for normal nervous system function, and changes in their levels contribute to the abnormal movements, autonomic dysfunction, and other neurological problems seen in people with TH deficiency.
### Learn more about the gene associated with Tyrosine hydroxylase deficiency
* TH
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Tyrosine hydroxylase deficiency | c2673535 | 6,652 | medlineplus | https://medlineplus.gov/genetics/condition/tyrosine-hydroxylase-deficiency/ | 2021-01-27T08:24:38 | {"gard": ["1902"], "mesh": ["C537537"], "omim": ["605407"], "synonyms": []} |
Obesity in Argentina is a growing health concern with health officials stating that it is one of the leading causes of preventable deaths in the Argentina.[citation needed] According to FAO/UNO, the prevalence of obesity among adults in Argentina was of 29.4% in 2008.[1]
## Official Statistics[edit]
Information from the Argentina's Ministry of Health shows the following progression recorded since 2005 when was launched the National Survey for Risk Factors, in Spanish: "Encuesta Nacional de Factores de Riesgo" for Non-communicable diseases (ENFR)
Source [2]
* 2005 = 14.6%
* 2009 = 18%
* 2013 = 20.8%
* 2005-2013 period variation = 42,5%
6 out of 10 registered as overweight and 2 out of 10 as obese.[3]
The data of the survey was gathered by 1,000 surveyors who interviewed 32,365 adults older than 18 years in cities larger than 5,000 inhabitants around the nation.[4] The 70.7% (32.365) of the people that were asked to take survey did accept to be interviewed.[5]
## See also[edit]
* Epidemiology of obesity
## References[edit]
1. ^ FAO (2013). "The state of food and agriculture" (PDF). FAO. Retrieved 2014-01-26.
2. ^ 3º Encuesta Nacional de Factores de Riesgo msal.gov.ar
3. ^ Encuesta Nacional de Factores de Riesgo marca reducción en el consumo de sal y en exposición al humo de tabaco ajeno msal.gov.ar
4. ^ Los argentinos y su salud: más obesidad, menos tabaco y menos sal clarin.com
5. ^ Se expondrán los resultados de la Encuesta Nacional de Factores de Riesgo fcm.unl.edu.ar
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Obesity in Argentina | None | 6,653 | wikipedia | https://en.wikipedia.org/wiki/Obesity_in_Argentina | 2021-01-18T18:38:47 | {"wikidata": ["Q7074846"]} |
Deformity characterized by lateral deviation of the big toe
Bunion
Other namesHallux abducto valgus, hallux valgus, metatarsus primus varus[1]
SpecialtyOrthopedics, Podiatry
SymptomsProminent, red, and painful joint at the base of the big toe[2]
ComplicationsBursitis, arthritis[2]
Usual onsetGradual[2]
CausesUnclear[1]
Risk factorsWearing overly tight shoes, high-heeled shoes, family history, rheumatoid arthritis[2][3]
Diagnostic methodBased on symptoms, X-rays[2]
Differential diagnosisOsteoarthritis, Freiberg's disease, hallux rigidus, Morton's neuroma[4]
TreatmentProper shoes, orthotics, NSAIDs, surgery[2]
Frequency~23% of adults[1]
A bunion, also known as hallux valgus, is a deformity of the joint connecting the big toe to the foot.[2] The big toe often bends towards the other toes and the joint becomes red and painful.[2] The onset of bunions is typically gradual.[2] Complications may include bursitis or arthritis.[2]
The exact cause is unclear.[1] Proposed factors include wearing overly tight shoes, high-heeled shoes, family history, and rheumatoid arthritis.[2][3] Diagnosis is generally based on symptoms and supported by X-rays.[2] A similar condition of the little toe is referred to as a bunionette.[2]
Treatment may include proper shoes, orthotics, or NSAIDs.[2] If this is not effective for improving symptoms, surgery may be performed.[2] It affects about 23% of adults.[1] Females are affected more often than males.[2] Usual age of onset is between 20 and 50 years old.[1] The condition also becomes more common with age.[1] It was first clearly described in 1870.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Orthotics
* 5.2 Surgery
* 6 References
* 7 External links
## Signs and symptoms[edit]
Drawing of a bunion
The big toe often bends towards the other toes and the joint becomes red and painful.[2] The onset of bunions is typically gradual.[2] Complications may include bursitis or arthritis.[2]
Other symptoms may include irritation of the skin around the bunion, and blisters may form more easily at the site. Pain may be worse when walking
Bunions can lead to difficulties finding properly fitting footwear and may force a person to buy a larger size shoe to accommodate the width of the bunion. If the bunion deformity becomes severe enough, the foot can hurt in different places even without the constriction of shoes. It is then considered as being a mechanical function problem of the forefoot.
## Cause[edit]
High heels are associated with developing bunions.[3]
The exact cause is unclear.[1] It may be due to a combination of internal and external causes.[5] Proposed factors include wearing overly tight shoes, high-heeled shoes, family history, and rheumatoid arthritis.[2][3] The American College of Foot and Ankle Surgeons states that footwear only worsens a problem caused by genetics.[6]
Excessive pronation of the foot causes increased pressure on the inside of the big toe that can result in a deformation of the medial capsular structures of the joint, subsequently increasing the risk of developing bunions.[5][7]
## Pathophysiology[edit]
The bump itself is partly due to the swollen bursal sac or an osseous (bony) anomaly on the metatarsophalangeal joint. The larger part of the bump is a normal part of the head of the first metatarsal bone that has tilted sideways to stick out at its distal (far) end.
Bunions are commonly associated with a deviated position of the big toe toward the second toe, and the deviation in the angle between the first and second metatarsal bones of the foot. The small sesamoid bones found beneath the first metatarsal (which help the flexor tendon bend the big toe downwards) may also become deviated over time as the first metatarsal bone drifts away from its normal position. Osteoarthritis of the first metatarsophalangeal joint, diminished and/or altered range of motion, and discomfort with pressure applied to the bump or with motion of the joint, may all accompany bunion development. Atop of the first metatarsal head either medially or dorso-medially, there can also arise a bursa that when inflamed (bursitis), can be the most painful aspect of the process.
## Diagnosis[edit]
X-ray showing measurements of HV and IM angles of hallux valgus.
Bunion can be diagnosed and analyzed with a simple x-ray, which should be taken with the weight on the foot.[8] The hallux valgus angle (HVA) is the angle between the long axes of the proximal phalanx and the first metatarsal bone of the big toe. It is considered abnormal if greater than 15–18°.[9] The following HV angles can also be used to grade the severity of hallux valgus:[10][unreliable medical source?]
* Mild: 15–20°
* Moderate: 21–39°
* Severe: ≥ 40°
The intermetatarsal angle (IMA) is the angle between the longitudinal axes of the first and second metatarsal bones, and is normally less than 9°.[9] The IM angle can also grade the severity of hallux valgus as:[10]
* Mild: 9–11°
* Moderate: 12–17°
* Severe: ≥ 18°
## Treatment[edit]
Conservative treatment for bunions include changes in footwear, the use of orthotics (accommodative padding and shielding), rest, ice, and pain medications such as acetaminophen or nonsteroidal anti-inflammatory drugs. These treatments address symptoms but do not correct the actual deformity.[11] If the discomfort persists and is severe or when aesthetic correction of the deformity is desired, surgical correction by an orthopedic surgeon or a podiatric surgeon may be necessary.
### Orthotics[edit]
Gel toe spacers come in a variety of sizes and shapes.
Orthotics are splints or regulators while conservative measures include various footwear like toe spacers, valgus splints, and bunion shields. Toe spacers seem to be effective in reducing pain, but there is not evidence that any of these techniques reduces the physical deformity. There are a variety of available orthotics including off-the-shelf commercial products and custom-molded orthotics, which may be prescribed medical devices.[12]
### Surgery[edit]
Procedures are designed and chosen to correct a variety of pathologies that may be associated with the bunion. For instance, procedures may address some combination of:
* removing the abnormal bony enlargement of the first metatarsal,
* realigning the first metatarsal bone relative to the adjacent metatarsal bone,
* straightening the great toe relative to the first metatarsal and adjacent toes,
* realigning the cartilaginous surfaces of the great toe joint,
* addressing arthritic changes associated with the great toe joint,
* repositioning the sesamoid bones beneath the first metatarsal bone,
* shortening, lengthening, raising, or lowering the first metatarsal bone,
* correcting any abnormal bowing or misalignment within the great toe,
* connecting two parallel long bones side by side by syndesmosis procedure
At present there are many different bunion surgeries for different effects. The age, health, lifestyle and activity level of the patient may also play a role in the choice of procedure.
Traditional bunion surgery can be performed under local, spinal or general anesthetic. A person who has undergone bunion surgery can expect a 6- to 8-week recovery period during which crutches are usually required to aid mobility. An orthopedic cast is much less common today as newer, more stable procedures and better forms of fixation (stabilizing the bone with screws and other hardware) are used. Hardware may even include absorbable pins that perform their function and are then broken down by the body over the course of months. After recovery long term stiffness or limited range of motion may occur in some patients. Visible or limited scarring may also occur for patients.
Bunionectomy
## References[edit]
1. ^ a b c d e f g h i Dayton, Paul D. (2017). Evidence-Based Bunion Surgery: A Critical Examination of Current and Emerging Concepts and Techniques. Springer. pp. 1–2. ISBN 9783319603155.
2. ^ a b c d e f g h i j k l m n o p q r s t "Bunions". OrthoInfo - AAOS. February 2016. Retrieved 8 November 2017.
3. ^ a b c d Barnish, MS; Barnish, J (13 January 2016). "High-heeled shoes and musculoskeletal injuries: a narrative systematic review". BMJ Open. 6 (1): e010053. doi:10.1136/bmjopen-2015-010053. PMC 4735171. PMID 26769789.
4. ^ Ferri, Fred F. (2010). Ferri's Differential Diagnosis E-Book: A Practical Guide to the Differential Diagnosis of Symptoms, Signs, and Clinical Disorders. Elsevier Health Sciences. p. 323. ISBN 978-0323081634.
5. ^ a b Brukner, Peter (2010). Clinical sports medicine (3 ed.). McGraw-Hill. p. 667. ISBN 9780070278998.
6. ^ "Bunions (Hallux Abducto Valgus)". Footphysicians.com. 2009-12-18. Retrieved 2011-03-20.
7. ^ Chou, Loretta B. (19 June 2015). "Disorders of the First Metatarsophalangeal Joint". The Physician and Sportsmedicine. 28 (7): 32–45. doi:10.3810/psm.2000.07.1075. PMID 20086649. S2CID 21529142.
8. ^ Page 533 in: Sam W. Wiesel, John N. Delahay (2007). Essentials of Orthopedic Surgery (3 ed.). Springer Science & Business Media. ISBN 9780387383286.
9. ^ a b Rebecca Cerrato, Nicholas Cheney. "Hallux Valgus". American Orthopaedic Foot & Ankle Society. Archived from the original on 2016-12-30. Retrieved 2016-12-30. Last reviewed June 2015
10. ^ a b Piqué-Vidal, Carlos; Vila, Joan (2009). "A geometric analysis of hallux valgus: correlation with clinical assessment of severity". Journal of Foot and Ankle Research. 2 (1): 15. doi:10.1186/1757-1146-2-15. ISSN 1757-1146. PMC 2694774. PMID 19442286.
11. ^ Hecht, PJ; Lin, TJ (March 2014). "Hallux valgus". Medical Clinics of North America (Review). 98 (2): 227–32. doi:10.1016/j.mcna.2013.10.007. PMID 24559871.
12. ^ Park, CH; Chang, MC (May 2019). "Forefoot disorders and conservative treatment". Yeungnam University Journal of Medicine. 36 (2): 92–98. doi:10.12701/yujm.2019.00185. PMC 6784640. PMID 31620619. (see Figure Two for images of orthotics)
## External links[edit]
Wikimedia Commons has media related to Bunion.
Look up bunion in Wiktionary, the free dictionary.
* Textbook of Hallux Valgus and Forefoot Surgery, links to complete text in PDF files
Classification
D
* ICD-10: M20.1
* ICD-9-CM: 727.1
* MeSH: D006215
* DiseasesDB: 5604
External resources
* MedlinePlus: 001231
* eMedicine: orthoped/467
* Patient UK: Bunion
* v
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Acquired musculoskeletal deformities
Upper limb
shoulder
* Winged scapula
* Adhesive capsulitis
* Rotator cuff tear
* Subacromial bursitis
elbow
* Cubitus valgus
* Cubitus varus
hand deformity
* Wrist drop
* Boutonniere deformity
* Swan neck deformity
* Mallet finger
Lower limb
hip
* Protrusio acetabuli
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* Coxa vara
leg
* Unequal leg length
patella
* Luxating patella
* Chondromalacia patellae
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* Patella alta
foot deformity
* Bunion/hallux valgus
* Hallux varus
* Hallux rigidus
* Hammer toe
* Foot drop
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* Club foot
knee
* Genu recurvatum
Head
* Cauliflower ear
General terms
* Valgus deformity/Varus deformity
* Joint stiffness
* Ligamentous laxity
Authority control
* GND: 4131922-9
* NDL: 00576882
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
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## Summary
### Clinical characteristics.
Pycnodysostosis is characterized by short-limbed short stature, typical facial appearance (convex nasal ridge and small jaw with obtuse mandibular angle), osteosclerosis with increased bone fragility, acroosteolysis of the distal phalanges, delayed closure of the cranial sutures, and dysplasia of the clavicle. In affected individuals, the facial features become more prominent with age, likely due to progressive acroosteolysis of the facial bones, but can usually be appreciated from early childhood, particularly the small jaw and convex nasal ridge. Additional features include dental and nail anomalies. Intelligence is typically normal with mild psychomotor difficulties reported in some individuals.
### Diagnosis/testing.
The diagnosis of pycnodysostosis can be established in a proband with characteristic clinical and radiographic features and/or biallelic pathogenic variants in CTSK identified by molecular genetic testing.
### Management.
Treatment of manifestations: Growth hormone therapy; environmental or occupational modifications as needed; orthopedic management of fractures and scoliosis; craniofacial and neurosurgical management as required for cleft palate, craniosynostosis, maxillary and mandibular hypoplasia; pulmonology and sleep medicine specialist management of obstruction sleep apnea; consultation with expert anesthetist prior to any planned surgery; dental and orthodontic care for dental anomalies; standard management per ophthalmologist for vision concerns.
Surveillance: Annual physical examination including assessment for scoliosis, asymmetry, frequency of fractures, weight and nutrition, and psychological assessment; polysomnography every two years; annual evaluation with specialist dentist and ophthalmologist.
Agents/circumstances to avoid: If general anesthesia is needed, consider the possibility of difficult intubation prior to scheduling anesthesia.
Pregnancy management: In individuals with a small pelvis, delivery by cæsarean section should be considered. However, each individual should be assessed by an obstetrician and anesthetist familiar with skeletal dysplasia.
### Genetic counseling.
Pycnodysostosis is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CTSK pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CTSK pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
## Diagnosis
Formal diagnostic criteria for pycnodysostosis have not been established, however the radiographic features of acroosteolysis, osteosclerosis, and loss of the normal angle of the jaw are almost pathognomonic.
### Suggestive Findings
Pycnodysostosis should be suspected in individuals with the following clinical, radiographic, and laboratory findings.
Clinical findings
* Short-limbed short stature in all individuals (prenatal onset in ~30%)
* Brachydactyly
* Craniofacial findings
* Frontal bossing
* Persistently open anterior fontanelle
* Prominent nose with convex nasal ridge
* Midface retrusion and small jaw due to hypoplasia of the maxilla and mandible
* Stridor, laryngomalacia, and obstructive sleep apnea
* Prominent eyes with blueish sclera
* High arched palate / grooved palate
* Dental anomalies (e.g., delayed eruption of deciduous and permanent teeth, persistence of deciduous teeth resulting in a double row of teeth, hypodontia)
* Nail anomalies (e.g., dysplastic, grooved, flattened)
Radiographic findings (see Figure 1)
#### Figure 1.
Radiographic features of pycnodysostosis A. Hand and wrist radiograph in a female age 12 years, showing marked acroosteolysis of the terminal phalanges and generalized increase in bone density.
* Generalized progressive osteosclerosis, particularly of the long bones
* Acroosteolysis of the terminal phalanges
* Non-pneumatized mastoids
* Delayed fusion of the cranial sutures
* Obtuse mandibular angle due to loss of the normal mandibular (gonial) angle
* Increased incidence of fractures
* Clavicular dysplasia, congenital pseudarthrosis of the clavicle
Laboratory findings
* Normal serum calcium, phosphate, vitamin D, and alkaline phosphatase
* Growth hormone deficiency
* Low IGF-1
* No abnormalities of other pituitary hormones
Family history consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.
### Establishing the Diagnosis
The diagnosis of pycnodysostosis can be established in a proband with characteristic clinical and radiographic features and/or biallelic pathogenic variants in CTSK identified by molecular genetic testing (see Table 1).
Note: Identification of biallelic CTSK variants of uncertain significance (or identification of one known CTSK pathogenic variant and one CTSK variant of uncertain significance) does not establish or rule out the diagnosis of this disorder.
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with osteosclerosis and/or short stature are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and radiographic findings suggest the diagnosis of pycnodysostosis, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of CTSK is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
* A multigene panel that includes CTSK and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by osteosclerosis and short stature, comprehensive genomic testing (which does not require the clinician to determine which gene is likely involved) is an option. Exome sequencing is most commonly used; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Pycnodysostosis
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
CTSKSequence analysis 3~100% 4
Gene-targeted deletion/duplication analysis 5One reported 6
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Review of approximately 35 pathogenic variants in all available published case literature, ClinVar [Landrum et al 2014], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
A 301-bp Alu sequence insertion in intron 7 that creates a new potential splice acceptor site [Arman et al 2014]
## Clinical Characteristics
### Clinical Description
Pycnodysostosis is characterized by short stature, typical facial appearance (small jaw with obtuse mandibular angle and convex nasal ridge), osteosclerosis with increased bone fragility, acroosteolysis of the distal phalanges, delayed closure of the cranial sutures, and dysplasia of the clavicle. In affected individuals, the facial features become more prominent with age, likely due to progressive acroosteolysis of the facial bones, but can usually be appreciated from early childhood, particularly the small jaw and convex nasal ridge [Turan 2014].
A comprehensive review of previously published reports [Xue et al 2011] identified 159 individuals including 59 unrelated families with confirmed homozygous or compound heterozygous pathogenic variants in CTSK. A further 27 affected individuals from 17 unrelated families were recently described, with molecular data available for 14 families [Bizaoui et al 2019]. The following description of the phenotypic features associated with pycnodysostosis is based on these reports.
### Table 2.
Pycnodysostosis: Frequency of Select Features
View in own window
Feature% of Persons w/Feature
ClinicalShort limb, short stature~100%
Intrauterine growth restriction~30%
Brachydactyly>90%
Frontal bossing>80%
Persistently open anterior fontanelle80%
Convex nasal ridge~70%
Small jaw>70%
Midface retrusion60%
Proptosis60%
Blueish sclerae30%-40%
Obstructive sleep apnea>65%
Increased incidence of fractures~70%
Nail anomalies>50%
Dental anomalies30%-40%
RadiographicOsteosclerosis~100%
Acroosteolysis of the terminal phalanges>90%
Non-pneumatized mastoids80%
Delayed fusion of cranial sutures67%
Obtuse mandibular angle65%
Clavicular dysplasia25%
Growth deficiency / short stature. Short stature is reported in almost 100% of individuals with pycnodysostosis. Individuals typically develop short stature by early childhood with decreased growth velocity, although 30% are reported to have intrauterine growth deficiency. Limbs are often disproportionately short compared to the trunk, with rhizo-, meso-, and acromelia. Documented adult heights are typically <150 cm for males (average 2.9 SD below the mean) and 130-134 cm for females (average 4.1 SD below the mean) [Bizaoui et al 2019].
About 50% have growth hormone deficiency but almost all have low IGF-1 levels. Administration of growth hormone has been shown to result in a satisfactory elevation in IGF-1 levels and near-normalization of adult height and skeletal proportions [Rothenbühler et al 2010].
Individuals with a growth hormone deficiency often also have pituitary hypoplasia identified on head imaging; no other abnormalities in pituitary hormones or pubertal development have been detected [Turan 2014].
Three individuals (2 diagnosed clinically and 1 with a molecular diagnosis) have been reported with taller-than-expected stature including an adult Mexican male of 153 cm (-1.9 SD), an adult Mexican female of 150 cm (-0.6 SD), and a Chinese boy age eleven years with normal height (137cm; -0.9 SD) [Zheng et al 2013, Valdes-Flores et al 2014].
Craniofacial appearance. The characteristic facial features (midface retrusion due to hypoplastic maxilla and small jaw with an obtuse mandibular angle) can become more apparent with age but are often detectable in infants, along with large anterior and posterior fontanelles and open cranial sutures with frontal and parietal bossing [Appelman-Dijkstra & Papapoulos 2016]. Additional common facial features include a convex nasal ridge. Less common features include proptosis with blueish sclera, and cleft palate or high palate with a midline groove [Bizaoui et al 2019]. The apparent palatal midline groove is due to narrow palate with shallow vault and fallen palatal wings with prominent median palatal raphe in eight individuals studied by Otaify et al [2018].
Skeletal. The second most common feature (after short stature) is increased bone density (osteosclerosis), which occurs throughout the skeleton and is progressive. The medullary canals, while often narrowed, remain present with evidence of hematopoiesis.
More than 90% of reported individuals have short hands and feet with short digits and progressive acroosteolysis of the terminal phalanges of the fingers and toes. Short metatarsals and metacarpals have not been described.
Other common imaging features include non-pneumatized mastoids (80%) and delayed fusion of the skull sutures (67%). The clavicles may be dysplastic (25%) with acroosteolysis of the acromial end. Less common features include Wormian bones (18%), mild scoliosis (12%), leg length discrepancy (8%), spondylolysis, spondylolisthesis, and narrow ilia. Coronal craniosynostosis has been reported in four individuals [Bertola et al 2010, Caracas et al 2012, Bizaoui et al 2019]. Chronic pain is reported in up to 60% of adults with pycnodysostosis, with onset usually in the third decade [Bizaoui et al 2019].
Bone fragility. Individuals with pycnodysostosis have an increased fracture rate with an average 0.2 fractures per year and an average age of first fracture around age ten years [Bizaoui et al 2019]. The youngest reported individual with a fracture was age ten months; This individual had two sibs who died, reportedly from the same disorder, suggesting a more severe phenotype or genotype; however, molecular studies were not performed [Caracas et al 2012].
Fracture healing is often delayed with incomplete remodeling. Surgical fixation is often complicated by narrow medullary canals, and sclerotic bone poses an increased risk of intraoperative iatrogenic fracture [Grewal et al 2019]. To date, no effective pharmaceutical treatments have been established for the bone fragility. Bisphosphonate therapy is contraindicated due to underlying osteoclast dysfunction in pycnodysostosis.
ENT. Stridor and laryngomalacia (20%) are not uncommon manifestations, and can lead to an early suspicion of pycnodysostosis. Obstructive sleep apnea (OSA) is frequently reported (>60%), and can be particularly severe in children with pycnodysostosis. Of those with OSA, 48% required noninvasive ventilation between ages five and ten years [Testani et al 2014, Bizaoui et al 2019]. Mild conductive hearing loss occurs in up to 50% of individuals [Bizaoui et al 2019].
Dental abnormalities include delayed eruption of the deciduous and permanent teeth, persistence of deciduous teeth (resulting in a double row of teeth), hypodontia, malocclusion, enamel hypoplasia, and increased caries [Turan 2014, Khoja et al 2015, Otaify et al 2018].
Nails are often flat, grooved, and dysplastic. The skin may be wrinkled over the dorsa of the fingers, secondary to shortened digits and acroosteolysis.
Neurologic. Intelligence is typically normal in affected individuals unless a brain malformation is present. Mild psychomotor difficulties have been reported in up to 30% of individuals [Bizaoui et al 2019]. Rarely reported neurologic abnormalities include Chiari malformation (1 individual), cerebral demyelination (3 individuals), and pyramidal syndrome (1 individual) [Soliman et al 2001, Stark & Savarirayan 2009, Bizaoui et al 2019].
Ocular abnormalities have been reported, including refractive disorders and strabismus. One individual was reported to have severe vision loss as a result of intracranial hypertension and papilledema [Bizaoui et al 2019].
Obesity has not been reported as a typical feature of pycnodysostosis; however, in a cohort of 27 individuals, 26% were found to be overweight [Bizaoui et al 2019].
Prognosis. Individuals with pycnodysostosis usually have normal life expectancy.
Other. Less commonly reported features include joint laxity, deformities of the chest shape (narrow chest, kyphosis, and lordosis), and hepatosplenomegaly. An ectopic pelvic kidney and unexplained pancytopenia have each been reported in one individual.
### Genotype-Phenotype Correlations
No genotype-phenotype correlations for CTSK have been identified.
### Nomenclature
The clinical features of pycnodysostosis (Greek: pycnos = dense; dys = defective; osteon= bone) were first described by Maroteaux and Lamy in 1962; hence, it is variably known as Maroteaux-Lamy syndrome [Xue et al 2011, Bizaoui et al 2019] (a term primarily used to refer to the unrelated condition, mucopolysaccharidosis type VI, caused by pathogenic variants in ARSB).
Pycnodysostosis is also sometimes referred to as "Toulouse-Lautrec syndrome," after the French artist Henri de Toulouse-Lautrec (1864-1901), who was retrospectively thought to have this condition based on several phenotypic features of the disorder including short stature, parental consanguinity, facial dysmorphism, frequent fractures, and large fontanels [Turan 2014] (see Figure 2).
#### Figure 2.
Portrait of the painter Henri de Toulouse-Lautrec, considered to have had pycnodysostosis 1898, by Edouard Vuillard (1868-1940)
### Prevalence
Approximately 200 affected individuals have been reported in the medical literature. Pycnodysostosis is estimated to affect about 1-1.7 individuals per million.
## Differential Diagnosis
It is critical to distinguish pycnodysostosis from other primary sclerosing conditions of bone (see Table 3) characterized by osteopetrosis, since early hematopoietic stem cell transplantation may be a therapeutic option in some forms of osteopetrosis, whereas it would be of no benefit in individuals with pycnodysostosis, which rarely presents with bone marrow insufficiency [Bizaoui et al 2019].
### Table 3.
Disorders Characterized by Osteopetrosis in the Differential Diagnosis of Pycnodysostosis
View in own window
Features of DiffDx Disorder Overlapping w/
PycnodysostosisGene(s)DiffDx DisorderMOIFeatures of DIffDx Disorder Not Observed in Pycnodysostosis
Osteosclerosis, diffuse & focal sclerosis of varying severity, modeling defects at metaphysis, osteomyelitis, pathologic fractures, tooth eruption defectsCA2Osteopetrosis w/renal tubular acidosis (OMIM 259730)ARBone marrow impairment is rare; cranial nerve compression, DD, intracranial calcification, renal tubular acidosis
CLCN7
SNX10
TCIRG1Osteopetrosis, severe neonatal or infantile forms (OMIM 611490, 615085, 259700)ARCranial nerve compression (II, VII, VIII), extramedullary hematopoiesis, hydrocephalus, hypocalcemia, pancytopenia
CLCN7
PLEKHM1
TNFSF11Osteopetrosis, intermediate form 1 (OMIM 611497, 259710)ARAnemia, extramedullary hematopoiesis, occasional optic nerve compression
CLCN7Osteopetrosis, late onset form type 2 (OMIM 166600)ADModerate hematologic failure, cranial nerve compression
FERMT3Osteopetrosis, moderate form w/defective leukocyte adhesion (OMIM 612840)ARDefective neutrophil adhesion to endothelial cells, hepatosplenomegaly, leukocytosis, mucosal bleeding
IKBKGOsteopetrosis w/ectodermal dysplasia & immune defect (OMIM 300291)XLAnhidrotic ectodermal dysplasia, immunodeficiency (→ overwhelming infection), lymphedema
OSTM1Osteopetrosis, infantile form, w/nervous system involvement (OMIM 259720)ARCranial nerve compression (II, VII, VIII), extramedullary hematopoiesis, hydrocephalus, hypocalcemia, pancytopenia, primary neurodegeneration incl retinal atrophy
TNFRSF11AOsteopetrosis, infantile form, osteoclast-poor w/immunoglobulin deficiency (OMIM 612301)ARAnemia, hepatosplenomegaly, hypogammaglobulinemia, thrombocytopenia
Osteosclerosis, short stature, pathologic fracturesCSF1R
TNFRSF11A
SLC29A3Dysosteosclerosis (OMIM 618476) 2ARBrain abnormalities, progressive neurologic deterioration (specific to CSF1R), patches of hyperpigmented skin, platyspondyly, radiolucency of widened submetaphyseal portions of tubular bones
Osteosclerosis localized mainly to metaphyses & epiphyseal margins of appendicular bones & metaphyseal equivalents of axial bonesLRRK1Osteosclerotic metaphyseal dysplasia 3ARDD; ↑ urinary pyridinoline & deoxypyridinoline excretion; ↑ serum alkaline phosphatase, aspartate aminotransferase & creatine kinase; seizures
Acroosteolysis, joint laxity, short stature, skull deformitiesNOTCH2Hajdu-Cheney syndrome (OMIM 102500)ADMild ID (in a small proportion), osteoporosis
Clavicular dysplasia, delayed anterior fontanelle closure, delayed eruption of teeth, high arched palate, short statureRUNX2Cleidocranial dysplasia spectrum disorderADAbnormally shaped pelvic & pubic bones, absent clavicles, thoracic deformations
AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked
1\.
Li et al [2019]
2\.
Campeau et al [2012], Xue et al [2019]
3\.
Iida et al [2016]
Secondary causes of bone sclerosis. Pycnodysostosis and other primary sclerosing conditions of bone caused by osteoclast dysfunction should be distinguished from the large number of secondary causes of bone sclerosis. Some alternative diagnoses to consider include fluorosis; beryllium, lead, and bismuth poisoning; myelofibrosis; Paget disease, sclerosing form (OMIM PS167250); and malignancies (lymphoma, osteoblastic cancer metastases) [Stark & Savarirayan 2009].
## Management
There are no published treatment or surveillance guidelines for pycnodysostosis or standard guidelines on the best method or surgical intervention for fracture treatment in this condition. Management should emphasize multidisciplinary care and a considered approach to surgical intervention when appropriate.
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with pycnodysostosis, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with Pycnodysostosis
View in own window
System/ConcernEvaluationComment
Constitutional
* Growth assessment
* Eval for growth hormone & IGF-1 deficiency as early as practicable
Consider referral to nutritionist if needed for weight management.
MusculoskeletalComplete radiographic skeletal survey incl lateral spine radiographs
Consider skull CT.If clinical concern re craniosynostosis
Orthopedic consultationEval by specialist experienced in skeletal dysplasia if possible
ENT
* Eval for cleft palate or narrow nasal passages
* Baseline audiology eval
RespiratoryPolysomnographyFor all patients as early as practicable
DentalBaseline dental eval
NeurologicConsider MRI.If neurologic symptoms or concern re Chiari malformation
EyesBaseline ophthalmologic exam
Genetic
counselingBy genetics professionals 1To inform patients & families re nature, MOI, & implications of pycnodysostosis in order to facilitate medical & personal decision making
Family support/
resourcesAssess:
* Use of community or online resources such as Parent to Parent;
* Need for social work involvement for parental support;
* Need for home nursing referral.
MOI = mode of inheritance
1\.
Medical geneticist, certified genetic counselor, certified advanced genetic nurse
### Treatment of Manifestations
### Table 5.
Treatment of Manifestations in Individuals with Pycnodysostosis
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
Growth hormone
deficiency /
Short stature
* Referral to endocrinologist
* Consideration of growth hormone therapy
* Environmental or occupational modifications may be needed (e.g., step stools, lower desks).
* Consultation w/OT may be beneficial.
Fractures
* Specialist orthopedic mgmt
* Intervention may incl osteosynthesis or immobilization.
* At least 35% of persons require orthopedic intervention.
* Complications incl non-union have been described following orthopedic surgery.
ScoliosisMgmt per orthopedist
CraniofacialCraniofacial/neurosurgical mgmt as required for cleft palate, craniosynostosis, maxillary & mandibular hypoplasiaMay incl distraction osteogenesis of mandible &/or maxilla
Obstructive
sleep apnea
* Referral to pulmonologist & sleep physician
* Noninvasive ventilation
Be aware of nasal obstruction due to small/narrowed airways.
Requirement for
anesthesiaConsultation w/expert anesthetist prior to any planned surgeryMay be at risk for difficult intubation
Dental
* Maintenance of oral hygiene
* Regular dental care to prevent oral complications
* May benefit from orthodontic input
At ↑ risk for post-extraction osteomyelitis due to ↑ bone density
Vision concernsStandard mgmt per ophthalmologist
OT = occupational therapist
### Surveillance
### Table 6.
Recommended Surveillance for Individuals with Pycnodysostosis
View in own window
System/ConcernEvaluationFrequency
General healthPhysical examAnnually or as indicated
Musculoskeletal
* Exam for scoliosis & asymmetry
* Assess frequency of fractures.
Annually
RespiratoryPolysomnographyEvery 2 yrs
DentalEval w/specialist dentistAnnually
VisionOphthalmology exam
ObesityWeight assessment ± dietitian reviewAnnually or as indicated
PsychologicalSpecific attention to any issues when taking history & during physical exam
Bizaoui et al [2019]
### Agents/Circumstances to Avoid
In the case of general anesthesia, consideration should be given to the possibility of difficult intubation prior to scheduling anesthesia.
Bisphosphonate therapy is contraindicated due to underlying osteoclast dysfunction in pycnodysostosis.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
In individuals with a small pelvis, delivery by cæsarean section should be considered. However, each individual should be assessed by an obstetrician and anesthetist familiar with skeletal dysplasia [Savarirayan et al 2018].
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Pycnodysostosis | c0238402 | 6,655 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK563694/ | 2021-01-18T21:01:16 | {"mesh": ["D058631"], "synonyms": ["Pyknodysostosis", "Toulouse-Lautrec Syndrome"]} |
Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs. This syndrome can also cause severe malformations of other parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. The condition has been associated with a mutation in the WNT3 gene in one family, and it appears to be inherited in an autosomal recessive manner. Treatment for those that survive depends upon the presence and severity of the associated symptoms and may require the coordinated efforts of a team of specialists.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Tetra-amelia syndrome | c4012268 | 6,656 | gard | https://rarediseases.info.nih.gov/diseases/5148/tetra-amelia-syndrome | 2021-01-18T17:57:23 | {"omim": ["273395"], "orphanet": ["294971"], "synonyms": ["Total amelia", "Tetra-amelia", "Total Amelia", "Tetraamelia, autosomal recessive", "Tetra-amelia, autosomal recessive"]} |
X-linked calvarial hyperostosis is a rare, genetic, primary bone dysplasia with increased bone density disorder characterized by benign, isolated, calvarial thickening, presenting with prominent frontoparietal bones, a high forehead with ridging of the metopic and sagittal sutures, lateral frontal prominences, and facial dysmorphism comprising a flat nasal root and short, upturned nose. Increased intracranial pressure and cranial nerve entrapment are not associated. There have been no further descriptions in the literature since 1986.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| X-linked calvarial hyperostosis | c1863351 | 6,657 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391327 | 2021-01-23T19:11:53 | {"gard": ["1058"], "mesh": ["C537963"], "omim": ["302030"], "icd-10": ["M85.2"]} |
Transient neonatal multiple acyl-CoA dehydrogenase deficiency describes a very rare condition where a maternal riboflavin deficiency causes an infant to present with manifestations similar to those seen in multiple acyl-CoA dehydrogenase (MAD) deficiency (see this term) such as poor suck, metabolic acidosis and hypoglycemia, but that resolves completely with oral riboflavin. In the one patient described haploinsufficiency of the human riboflavin transporter (hRFT1) was described in the mother.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Transient neonatal multiple acyl-CoA dehydrogenase deficiency | c4509950 | 6,658 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329942 | 2021-01-23T17:25:06 | {"icd-10": ["E71.3"], "synonyms": ["Transient neonatal MAD deficiency", "Transient neonatal MADD", "Transient neonatal glutaric acidemia type 2", "Transient neonatal glutaric aciduria type 2"]} |
Green et al. (2003) reported an Australian family in which 22 members over 4 generations had progressive patterned scalp hypotrichosis and wiry hair similar to that seen in Marie Unna hereditary hypotrichosis (MUHH; 146550). Features differing from those of MUHH included absence of signs of abnormality at birth, relative sparing of body hair, distal onycholysis, and intermittent cosegregation with autosomal dominant cleft lip and palate. Five individuals had associated cleft lip and palate. Green et al. (2003) excluded linkage of the disorder in the Australian family to the MUHH locus on chromosome 8p21.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| HYPOTRICHOSIS, PROGRESSIVE PATTERNED SCALP, WITH WIRY HAIR, ONYCHOLYSIS, AND CLEFT LIP/PALATE | c1836521 | 6,659 | omim | https://www.omim.org/entry/609250 | 2019-09-22T16:06:30 | {"mesh": ["C563765"], "omim": ["609250"], "synonyms": ["Alternative titles", "MARIE UNNA-LIKE SCALP HYPOTRICHOSIS"]} |
A very rare genetic gastroenterological disease characterized by severe malabsorptive diarrhea (requiring parenteral nutrition and disappearing at fasting) due to a lack of intestinal enteroendocrine cells. It is associated with early-onset (within the first weeks of life) dehydration, metabolic acidosis and diabetes mellitus (that can develop until late childhood). Patient may display various degrees of pancreatic insufficiency that does not explain diarrhea, as it is not reduced with pancreatic enzyme supplementation. Central hypogonadism (developing in the second decade), as well as an association with celiac disease have been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Enteric anendocrinosis | c1835888 | 6,660 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83620 | 2021-01-23T18:47:11 | {"mesh": ["C563673"], "omim": ["610370"], "icd-10": ["P78.3"], "synonyms": ["Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells"]} |
Injury to one or both recurrent laryngeal nerves
Vocal fold paresis
Other namesRecurrent laryngeal nerve paralysis, vocal fold paralysis
SpecialtyOtorhinolaryngology
Vocal cord paresis, also known as recurrent laryngeal nerve paralysis or vocal fold paralysis, is an injury to one or both recurrent laryngeal nerves (RLNs), which control all muscles of the larynx except for the cricothyroid muscle. The RLN is important for speaking, breathing and swallowing.[1][2]
The primary larynx-related functions of the mainly efferent nerve fiber RLN, include the transmission of nerve signals to the muscles responsible for regulation of the vocal folds' position and tension to enable vocalization, as well as the transmission of sensory nerve signals from the mucous membrane of the larynx to the brain.
A unilateral injury of the nerve typically results in hoarseness caused by a reduced mobility of one of the vocal folds. It may also cause minor shortages of breath as well as aspiration problems especially concerning liquids. A bilateral injury causes the vocal folds to impair the air flow resulting in breathing problems, stridor and snoring sounds, and fast physical exhaustion. This strongly depends on the median or paramedian position of the paralyzed vocal folds. Hoarseness rarely occurs in bilaterally paralyzed vocal folds.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Congenital
* 2.2 Infection
* 2.3 Tumors
* 2.4 Trauma
* 2.5 Thyroid disease
* 2.6 Systemic neurologic diseases
* 2.7 Cardiovascular
* 3 Diagnosis
* 3.1 Classification
* 4 Treatment
* 4.1 Voice therapy
* 4.1.1 Hard glottal attacks
* 4.1.2 Half-swallow boom
* 4.1.3 Abdominal breathing
* 4.1.4 Lip and tongue trills
* 4.2 Surgery
* 4.2.1 Post-surgical outcomes
* 4.2.2 Voice therapy after surgery
* 5 Epidemiology
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Symptoms from RLN damage Symptoms from SLN damage
* Rough voice quality[3]
* Breathy voice quality[4]
* Vocal fold bowing[4]
* Decreased vocal fold mobility[5]
* Glottal insufficiency[6]
* Hyperfunction[3]
* Vocal fatigue
* Reduced vocal stamina[6]
* Changes in voice pitch or pitch range[6]
* Difficulty varying pitch at a quick rate[3]
* Difficulty projecting voice or speaking loudly or in noisy environments [3][5]
* Throat pain[5]
* Bouts of choking[5]
* Diplophonia[3]
* Swallowing difficulties[4]
* Chronic coughing[3]
* Globus sensation[3]
* Hypersensitivity or abnormal sensation[6]
* Vocal fold spasms[3]
* Pain from vocal use[6]
* Loss of voice in high pitch ranges[3]
Typically, patients with vocal fold paresis or paralysis are able to identify the onset of their symptoms.[4] The most commonly reported symptom patients with either vocal fold paresis or paralysis make is having a rough voice quality.[3][6][5] It is important to note that the symptoms of vocal fold paresis are not specific to the condition and tend to be common symptoms of other voice disorders as well.[3] Vocal fold bowing, decreased vocal fold mobility, especially decreased mobility of the arytenoid cartilage, are often observed in vocal fold paresis.[4][3][5] Glottal insufficiency is another common symptom observed in vocal fold paresis.[3][6] In this case, the vocal folds do not come together properly.[3][6] Glottal insufficiency may be hard to identify, especially when the area above the vocal folds is hyperfunctional.[3] Hyperfunction may also make it difficult to detect the presence of vocal fold paresis.[3] Hyperfunction of the area above the vocal folds may be considered a sign of glottal insufficiency and potentially, vocal fold paresis.[3]
In some cases, glottal closure may appear to be normal, however, asymmetries in the vocal folds may still be present.[4][5] Though voice qualities may appear normal in some cases of vocal fold paresis or paralysis,[3] mild differences in tension between the two vocal folds of the larynx can result in changes of voice pitch, intensity and reduced vocal stamina.[6][5]
Patients with either vocal fold paresis or paralysis may exhibit a breathy voice quality.[4][3] This voice quality results from the increased activity of the vocal folds to compensate for the immobility of the PCA muscle(s).[3][5] Patients may need to use more effort than normal when speaking and may find that their voice quiets or grows tired after speaking for a long time.[3][6] This is known as vocal fatigue.[3][6] Patients may also complain about having a limited pitch range[4][6][7] and trouble varying their pitch at quick rate.[3] It is often difficult for the speaker to project their voice and speak loud enough to be heard in noisy environments, over background noise, or when speaking to someone from a distance.[4][3] It is possible for symptoms to surface only in situations where the environmental acoustics are poor, such as outdoors.[6] Patients may report feeling pain in the throat or experiencing bouts of choking.[5] A patient presenting with diplophonia is of major concern as this typically means that the mass and tension of their vocal folds are asymmetrical which may also indicate vocal fold paresis.[3]
Swallowing difficulties (dysphagia) are not commonly seen in vocal fold paresis that results from RLN damage.[4][6] Dysphagia may however, suggest SLN damage.[4][6] Symptoms of sensory nerve damage include: chronic coughing, the feeling of having a lump in the throat (globus sensation), hypersensitivity or abnormal sensation, spasms of the vocal folds (laryngospasms), dysphagia, pain from vocal use, and voice loss in high pitch ranges.[3][6] It is possible for both the RLN and the SLN to be damaged simultaneously, so the symptoms of RLN and SLN damage may be seen independently or alongside one another.[3]
If maladaptive compensatory strategies are used more and more to try to offset the voice difficulties, the vocal mechanisms will fatigue and the above symptoms will worsen.[6]
## Causes[edit]
There are a wide variety of possible causes of vocal fold (VF) paresis, including congenital (i.e. present at birth) causes, infectious causes, tumors, traumatic causes, endocrinologic diseases (i.e. thyroid disease), and systemic neurologic diseases.[4][3][6]
### Congenital[edit]
Congenital conditions that are implicated in VFP include neurological disorders like hydrocephalus and Arnold-Chiari malformation, dysmorphic neurological disorders such as Moebius syndrome or Goldenhar Syndrome, anatomical abnormalities such as a tracheoesophageal fistula, vascular anomalies (e.g. vascular ring) affecting the vocal mechanism, syndromes affecting brainstem function or atrophic diseases such as Charcot-Marie-Tooth.[3]
In the absence of imaging, either invasive (e.g. laryngoscopy) or non-invasive (e.g. computed tomography scan), congenital VFP can be detected in infants through the presence of stridor (i.e. a high-pitched wheezing resulting from a blockage in the larynx or trachea), difficulties feeding, an abnormal sounding cry or excessive hoarseness.[8]
Recovery from congenital VFP varies and is reliant on the severity of the condition. Some cases of VFP recover spontaneously, often within the first year. If the paresis is persistent, surgical options such as vocal fold injections or tracheotomy can be taken into consideration.[8]
### Infection[edit]
Many viral infections have been reported as a cause for VF paresis, including herpes simplex virus, Epstein-Barr virus, Varicella-Zoster, cytomegalovirus, HIV, West Nile virus, and upper respiratory infection.[3] Bacterial infections have also been reported to cause VF paresis, such as syphilis and Lyme disease.[4][3][6]
### Tumors[edit]
When abnormal cells group together in the body, they are said to form a tumor. Tumors can be either malignant (cancerous) or benign (non-cancerous). Tumors may lead to paralysis of the vocal folds when they affect the recurrent laryngeal nerves (RLNs) either directly or indirectly:
* RLN paralysis can be caused by tumors of the thyroid, lung, esophagus, and mediastinum.[9]
* Radiation as a treatment for malignant head and neck tumors can reduce the number of blood vessels in the treatment area and lead to scarring. In some cases, this can paralyze the vagus nerve, of which the RLNs are branches.[9]
* Tumors of the vagus nerve, called vagal neurilemmomas, can also paralyze the vocal folds.[9]
### Trauma[edit]
VF paresis can result from trauma to one of more laryngeal nerves during intubation, surgery (e.g. thyroidectomy, spine surgery, carotid endartectomy, vagal nerve stimulator implantation[4][6]), injection of botulinum neurotoxin, or penetrating neck trauma.[3]
### Thyroid disease[edit]
Causes of VF paresis also include diseases of the thyroid gland, such as hypothyroidism, goiter, and thyroiditis.[4][3][6]
### Systemic neurologic diseases[edit]
Several neurological diseases can cause VF paresis including:
* Myasthenia Gravis (MG), a rare neuromuscular autoimmune disease. MG's dominant characteristic is muscles weakness including facial, jaw, pharyngeal and laryngeal muscles.[10][11]
* Charcot-Marie-Tooth (CMT), a neurological heredity disease that affects both motor and sensory functions. CMT affects the nerve cells and interrupts the transmission of nerve impulses as it concerns the axons and the myelination of the nerve cells.[12]
* Multiple Sclerosis (MS), which is an autoimmune disease that damages the myelin sheet surrounding the axons of the cranial nerves and the spinal nerves. There are several types of MS depending on the course of the disease.[11]
* Spinocerebellar Degeneration, a term that refers to a rare yet diverse chronic disease that affects the brain and the spinal cord. Spinocerebellar Degeneration is usually an inherited progressive disease; however, toxicity and vitamin deficiency can result in the acquired type of cerebellar degeneration disease.[4][3][13][6]
Additionally, there are pieces of evidence that some Systemic Rheumatological Diseases such as sarcoidosis, rheumatoid, scleroderma can result in having VF paresis.[3]
### Cardiovascular[edit]
A rare cause of vocal cord paresis that often presents itself as unexplained hoarseness is cardiovocal syndrome or Ortner's syndrome. Although it was originally identified in patients with left atrial enlargement,[14] the definition has expanded to include aneurysms of the aortic arch,[15] pulmonary hypertension due to mixed connective tissue disease,[16] or aberrant subclavian artery[17] syndrome among other causes of left recurrent laryngeal nerve palsy with cardiovascular origin.
## Diagnosis[edit]
There are a variety of ways to diagnose vocal fold paralysis. Important indications of possible causes can be revealed in the patient's medical history, which may inform which diagnostic approach is taken. Voice diagnostics are used to assess voice quality and vocal performance. Voice assessment is necessary to plan and estimate the success of a possible speech therapy.[12]
An auditory-perceptual evaluation is conducted by a Speech-Language Pathologist (S-LP), and allows changes in voice quality to be monitored over time.[18] There are two scales which can be used to subjectively measure voice quality: the GRBAS (grade, roughness, breathiness, asthenia, strain) and the CAPE-V (Consensus Auditory Perceptual Evaluation of Voice). The GRBAS is used to rate the patient's voice quality on 5 dimensions: grade (overall severity), roughness, breathiness, asthenia (weakness) and strain. Each dimension will receive a severity rating from 0 (not present) to 3 (severe). This allows the S-LP to make a judgment about the overall severity of the voice quality. The CAPE-V is used in a similar manner, rating of the dimensions of voice quality on a subjective scale from 0–100, and using this to determine an overall severity score.[citation needed]
In the presence of neural lesions with unknown cause, a thorough ENT endoscopy[19] with additional imaging techniques (computed tomography (CT) of the chest, particularly in the case of left-sided paralyses, and magnetic resonance imaging (MRI) of the neck including the base of the skull and the brain, ultrasound examination of the neck) are performed to exclude tumors along the laryngeal nerves. When tumor formation is suspected, parts of the hypopharynx and the upper esophagus and passive mobility of the arytenoid cartilage are endoscopically examined under anesthesia.[citation needed]
Voice diagnostics are used to assess voice quality and vocal performance. Voice assessment is necessary to plan and estimate the success of a possible speech therapy.[20] In incompletely or only partially healed paralyses, stroboscopic larynx examinations yield a type of slow motion picture to assess tension and fine mobility of the vocal folds during vocalization. Stroboscopy[19][5] and voice assessment are important to establish an individual treatment plan to improve the voice.
Breathing tests (spirometry, body plethysmography) are used to measure impairment of respiratory flow through the larynx, particularly in patients with bilateral paralysis.
Electromyography of the larynx muscles (larynx EMG),[1][21] which measures the electrical activity of the larynx muscles via thin needle electrodes, allows better differentiation between a neural lesion and other causes of impaired mobility of the vocal fold and localization of the lesion along the nerve. The larynx EMG can, within limits, provide a prognosis of the development of a recurrent laryngeal nerve paralysis. Patients with a poor chance of healing can be identified at an early stage. Unfortunately, this advanced examination technique is not available in all treatment centers.
The treating physician must view all examination results combined[5] and establish an individual diagnosis and treatment plan for each patient.
### Classification[edit]
Vocal fold paresis refers to a partial loss of input to the nerve of the vocal folds.[4][3] This loss of neural input leads to reduced vocal fold mobility.[4][3] It is a condition with a variable profile, as the severity of the paresis can range on a wide continuum from minor to major loss of vocal fold mobility.[4][6] Vocal fold paralysis, distinguished from vocal paresis, is the total loss of vocal fold mobility due to a lack of neural input to the vocal folds.[4] These conditions result from continuous damage to the laryngeal nerves[4][3] and often lead to vocal disability.[6] Recurrent laryngeal nerve damage is the most common cause of vocal fold paresis.[4] The RLN is responsible for motor input to the vocal folds.[4] Physicians may also use the term recurrent laryngeal nerve paralysis.[19] Additionally, superior laryngeal nerve damage (SLN) can also lead to vocal fold paresis.[4] The SLN is responsible for sensory input to the vocal folds.[4] Due to its variable nature, the progression of vocal fold paresis may fluctuate, so it may be characterized differently from one evaluation to the next.[3] Fluctuating vocal fold paresis has been observed in neurodegenerative disorders like Guillain–Barré syndrome or myasthenia gravis.[3][5]
The posterior cricoarytenoid (PCA) is a muscle of the larynx that is responsible for pulling the vocal folds apart from one another.[5] Vocal fold paresis describes the weakness of the PCA and an impairment to its functioning.[22] Unilateral vocal fold paresis is the term used when there is damage to the RLN on one side of the body.[7] In unilateral vocal fold paresis, there is a lack of nerve supply to one side of the vocal fold's PCA muscle.[5][7] This lack of nerve supply renders the arytenoid cartilage immobile.[5][7] The RLN may be damaged during surgical procedures.[5] The right RLN in particular, has a greater chance of being damaged during surgery due to its position in the neck.[5] When both of the vocal folds' PCA muscles lack a nerve supply, the term bilateral vocal fold paresis is used.[5] With bilateral vocal fold paresis, a person's airway may become blocked as the muscles are unable to pull the vocal folds apart fully.[5]
## Treatment[edit]
The treatment of vocal fold paralysis varies depending on its cause and main symptoms. For example, if laryngeal nerve paralysis is caused by a tumor, suitable therapy should be initiated. In the absence of any additional pathology, the first step of clinical management should be observation to determine whether spontaneous nerve recovery will occur.[23] Voice therapy with a speech-language pathologist is suitable at this time, to help manage compensatory vocal behaviours which may manifest in response to the paralysis.[23]
### Voice therapy[edit]
The overall goal of voice therapy is to narrow the glottis without causing hyperfunction of the surrounding muscles. In the past, forced adduction exercises were used to push the vocal folds together, but often resulted in additional stress on the vocal folds. Current methods focus more generally on improving abdominal support, muscle strength and agility.[24]
#### Hard glottal attacks[edit]
Hard glottal attacks involve building up subglottal pressure (air pressure below the vocal folds) before letting out a vowel sound. Often, this method is beneficial for clients who compensate by use of a falsetto register.[24]
#### Half-swallow boom[edit]
The half-swallow boom allows for a repositioning of the vocal folds by taking advantage of laryngeal positioning when swallowing. The client is asked to take a breath and then initiate the movement of swallowing, followed by forcefully saying “boom”. When performed properly, the "boom" sounds loud and clear. Eventually, this sound can be generalized to other words and phrases.[24]
#### Abdominal breathing[edit]
Training in breath support is essential for those clients who identify as professional voice users. Shifting the awareness of the breath to the belly (diaphragmatic breathing) aids in efficient vocal function, reducing the risk of hyperfunction and muscular tension.[24]
#### Lip and tongue trills[edit]
Lip and tongue trills aid in the balance of resonance, as well as coordinate the muscles of respiration, phonation and articulation. In addition, subglottal pressure may increase during lip trills, and result in the generation greater vocal fold vibration.[24]
### Surgery[edit]
After 9 months of observation, should the paralysis not resolve and the patient be dissatisfied with the outcomes of voice therapy, the next option is temporary injection medialization.[25] In this procedure, a variety of materials can be injected into the body of the vocal fold in order to bring it closer to the midline of the glottis.[25] Materials such as Teflon, autologous fat, collagens acellular dermis, fascia, hydroxyapatite and hyaluronates are available to be used in the procedure.[26] The choice of substance is dependent on several factors, taking into consideration the specific condition and preference of the patient as well as the clinical practice of the surgeon.[27] The materials serve the purpose of filling up the vocal folds and increasing their volume.[26] This allows the paralyzed vocal fold to make contact with the alternate fold, in order to more efficiently produce phonation.[25] While injection augmentation has been long considered best practice, neither technique nor materials used have been standardized across clinicians.[25] With this, results prove to be both safe and effective, but variable in their duration, lasting anywhere from 2 to 12 months.[23]
For patients with significant paralysis at 12 months post-onset, medialization thyroplasty may be suggested.[25] This surgical procedure introduces a shim between the inner wall of the larynx and the soft tissue supporting the vocal fold.[28] As a result, the paralyzed vocal fold is supported in a position closer to the midline of the glottis, and retains its ability to vibrate and phonate efficiently.[28]
In addition to medialization thyroplasty, arytenoid adduction can be performed to improve phonation results.[26] This medical procedure consists of pulling the vocal processes of the arytenoid medially while monitoring the voicing quality being produced by the patient.[26] When the best phonation appears to be achieved, the vocal processes are then maintained in place by a thread.[26]
A further surgical intervention used to mitigate vocal fold paresis is laryngeal reinnervation.[29] This procedure restores nerve supply to the larynx and can be accomplished according to different techniques.[29][30][31] Depending on the specific condition (i.e. bilateral versus unilateral vocal fold paralysis), these techniques include reconnecting parts of the RLN, supplying the laryngeal muscles with a donor nerve like the ansa cervicalis, or connecting the RLN to a donor nerve.[29][30][31]
#### Post-surgical outcomes[edit]
In many cases, the surgical treatment options described above (temporary injection medialization, medialization thyroplasty, arytenoid adduction, and laryngeal reinnervation) have led to favourable outcomes as measured perceptually, acoustically, by laryngoscope, or via quality of life measures.[32] However, none of these surgical interventions has been shown to be significantly better than the others.[32]
#### Voice therapy after surgery[edit]
It is generally recommended that voice therapy start 1 to 2 months after surgery, when swelling has subsided. Post-surgical intervention is warranted to restore laryngeal muscle strength, agility and coordination.[24]
## Epidemiology[edit]
Due to the complex and controversial nature of this condition,[3] epidemiological (incidence) reports vary significantly and more research in this area is needed. Instead of reporting the incidence of this condition within the general population, most studies are conducted within specialized voice disorder clinics. In such a setting, one study found that approximately 26% of patients are diagnosed with paralysis or paresis of the vocal folds.[7] Yet, incidence rates as high as 80% for vocal fold paresis have been reported elsewhere.[6] Yet another source reported only 71 cases of vocal fold paresis over 7 years.[6] Incidence rates of vocal fold paresis after undergoing thyroid surgery have been reported between 0.3% and 13.2%, whereas these incidence rates are between 2% and 21.6% after undergoing spinal surgery.[5]
## See also[edit]
* Puberphonia
## References[edit]
1. ^ a b Pototschnig C, Thumfart WF (1997). "Electromyographic evaluation of vocal cord disorders". Acta Oto-rhino-laryngologica Belgica. 51 (2): 99–104. PMID 9241376.
2. ^ Zealear DL, Billante CR (February 2004). "Neurophysiology of vocal fold paralysis". Otolaryngologic Clinics of North America. 37 (1): 1–23, v. doi:10.1016/S0030-6665(03)00165-8. PMID 15062684.
3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao Syamal MN, Benninger MS (June 2016). "Vocal fold paresis: a review of clinical presentation, differential diagnosis, and prognostic indicators". Current Opinion in Otolaryngology & Head and Neck Surgery. 24 (3): 197–202. doi:10.1097/moo.0000000000000259. PMID 27092906. S2CID 46882995.
4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Sulica L, Blitzer A (June 2007). "Vocal fold paresis: evidence and controversies". Current Opinion in Otolaryngology & Head and Neck Surgery. 15 (3): 159–62. doi:10.1097/moo.0b013e32814b0875. PMID 17483683. S2CID 10972665.
5. ^ a b c d e f g h i j k l m n o p q r s t u Rubin AD, Sataloff RT (October 2007). "Vocal fold paresis and paralysis". Otolaryngologic Clinics of North America. 40 (5): 1109–31, viii–ix. doi:10.1016/j.otc.2007.05.012. PMID 17765698.
6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Sulica L (2013-05-08). "Vocal Fold Paresis: An Evolving Clinical Concept". Current Otorhinolaryngology Reports. 1 (3): 158–162. doi:10.1007/s40136-013-0019-4.
7. ^ a b c d e Stager SV (December 2014). "Vocal fold paresis: etiology, clinical diagnosis and clinical management". Current Opinion in Otolaryngology & Head and Neck Surgery. 22 (6): 444–9. doi:10.1097/moo.0000000000000112. PMID 25254404. S2CID 23164908.
8. ^ a b Daya H, Hosni A, Bejar-Solar I, Evans JN, Bailey CM (January 2000). "Pediatric vocal fold paralysis: a long-term retrospective study". Archives of Otolaryngology–Head & Neck Surgery. 126 (1): 21–5. doi:10.1001/archotol.126.1.21. PMID 10628706.
9. ^ a b c Myssiorek, David (2004-02-01). "Recurrent laryngeal nerve paralysis: anatomy and etiology". Otolaryngologic Clinics of North America. 37 (1): 25–44. doi:10.1016/S0030-6665(03)00172-5. ISSN 0030-6665. PMID 15062685.
10. ^ Mao ZF, Mo XA, Qin C, Lai YR, Olde Hartman TC (July 2010). "Course and prognosis of myasthenia gravis: a systematic review". European Journal of Neurology. 17 (7): 913–21. doi:10.1111/j.1468-1331.2010.03017.x. PMID 20402761. S2CID 37012410.
11. ^ a b Shaker R (2013). Principles of deglutition : a multidisciplinary text for swallowing and its disorders. New York, NY: Springer. ISBN 978-1-4614-3794-9. OCLC 812017272.
12. ^ Corrado B, Ciardi G, Bargigli C (April 2016). "Rehabilitation Management of the Charcot-Marie-Tooth Syndrome: A Systematic Review of the Literature". Medicine. 95 (17): e3278. doi:10.1097/md.0000000000003278. PMC 4998680. PMID 27124017.
13. ^ Brice A, Pulst S (2007). Spinocerebellar degenerations : the ataxias and spastic paraplegias (1st ed.). Philadelphia, PA: Butterworth-Heinemann/Elsevier. ISBN 978-0-7506-7503-1. OCLC 785831061.
14. ^ Ortner N. Recurrent nerve palsy in patient with mitral stenosis. Wien Klin Wochenschr. 1897;10:753–755. [in German]).
15. ^ Al Kindi, Adil H.; Al Kindi, Faiza A.; et al. (October 2016). "Ortner's syndrome: Cardiovocal syndrome caused by aortic arch pseudoaneurysm". Journal of the Saudi Heart Association. 28 (4): 266–269. doi:10.1016/j.jsha.2016.02.006. PMC 5034482. PMID 27688676.
16. ^ M. Hirata et al, (2018) Cardiovocal syndrome (Ortner syndrome) associated with secondary pulmonary arterial hypertension in a patient with mixed connective tissue disease, Modern Rheumatology Case Reports, 2:1, 54-58
17. ^ Escribano, Josè F. Guijarro; Carnès, Jerûnimo; et al. (January 2006). "Ortner's Syndrome and Endoluminal Treatment of a Thoracic Aortic Aneurysm: A Case Report". Vascular and Endovascular Surgery. 40 (1): 75–78. doi:10.1177/153857440604000111. PMID 16456610. S2CID 46119392.
18. ^ Misono S, Merati AL (October 2012). "Evidence-based practice: evaluation and management of unilateral vocal fold paralysis". Otolaryngologic Clinics of North America. 45 (5): 1083–108. doi:10.1016/j.otc.2012.06.011. PMID 22980687.
19. ^ a b c Benjamin B (October 2003). "Vocal cord paralysis, synkinesis and vocal fold motion impairment". ANZ Journal of Surgery. 73 (10): 784–6. doi:10.1046/j.1445-2197.2003.02799.x. PMID 14525565. S2CID 45597024.
20. ^ Benninger MS, Crumley RL, Ford CN, Gould WJ, Hanson DG, Ossoff RH, Sataloff RT (October 1994). "Evaluation and treatment of the unilateral paralyzed vocal fold". Otolaryngology–Head and Neck Surgery. 111 (4): 497–508. doi:10.1177/019459989411100419. PMID 7936686. S2CID 21781450.
21. ^ Volk GF, Hagen R, Pototschnig C, Friedrich G, Nawka T, Arens C, Mueller A, Foerster G, Finkensieper M, Lang-Roth R, Sittel C, Storck C, Grosheva M, Kotby MN, Klingner CM, Guntinas-Lichius O (October 2012). "Laryngeal electromyography: a proposal for guidelines of the European Laryngological Society". European Archives of Oto-rhino-laryngology. 269 (10): 2227–45. doi:10.1007/s00405-012-2036-1. PMID 22576246. S2CID 14637397.
22. ^ Rosen CA, Mau T, Remacle M, Hess M, Eckel HE, Young VN, Hantzakos A, Yung KC, Dikkers FG (August 2016). "Nomenclature proposal to describe vocal fold motion impairment". European Archives of Oto-rhino-laryngology. 273 (8): 1995–9. doi:10.1007/s00405-015-3663-0. PMC 4930794. PMID 26036851.
23. ^ a b c Costello D (June 2015). "Change to earlier surgical interventions: contemporary management of unilateral vocal fold paralysis". Current Opinion in Otolaryngology & Head and Neck Surgery. 23 (3): 181–4. doi:10.1097/moo.0000000000000156. PMID 25943963. S2CID 1241559.
24. ^ a b c d e f Miller S (February 2004). "Voice therapy for vocal fold paralysis". Otolaryngologic Clinics of North America. 37 (1): 105–19. doi:10.1016/s0030-6665(03)00163-4. PMID 15062689.
25. ^ a b c d e Sulica L, Rosen CA, Postma GN, Simpson B, Amin M, Courey M, Merati A (February 2010). "Current practice in injection augmentation of the vocal folds: indications, treatment principles, techniques, and complications". The Laryngoscope. 120 (2): 319–25. doi:10.1002/lary.20737. PMID 19998419. S2CID 1824379.
26. ^ a b c d e Colton RH, Casper JK, Leonard R (2011). Understanding voice problems : a physiological perspective for diagnosis and treatment (Fourth ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-1-60913-874-5. OCLC 660546194.
27. ^ Shen T, Damrose EJ, Morzaria S (February 2013). "A meta-analysis of voice outcome comparing calcium hydroxylapatite injection laryngoplasty to silicone thyroplasty". Otolaryngology–Head and Neck Surgery. 148 (2): 197–208. doi:10.1177/0194599812464193. PMID 23077153. S2CID 22078103.
28. ^ a b Isshiki N (March 2000). "Progress in laryngeal framework surgery". Acta Oto-Laryngologica. 120 (2): 120–7. doi:10.1080/000164800750000748. PMID 11603755. S2CID 25214750.
29. ^ a b c Paniello RC (February 2004). "Laryngeal reinnervation". Otolaryngologic Clinics of North America. 37 (1): 161–81, vii–viii. doi:10.1016/S0030-6665(03)00164-6. PMID 15062692.
30. ^ a b Fancello V, Nouraei SA, Heathcote KJ (December 2017). "Role of reinnervation in the management of recurrent laryngeal nerve injury: current state and advances". Current Opinion in Otolaryngology & Head and Neck Surgery. 25 (6): 480–485. doi:10.1097/MOO.0000000000000416. PMID 29095795. S2CID 30566805.
31. ^ a b Li Y, Garrett G, Zealear D (September 2017). "Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review". Clinical and Experimental Otorhinolaryngology. 10 (3): 203–212. doi:10.21053/ceo.2017.00199. PMC 5545703. PMID 28669149.
32. ^ a b Siu J, Tam S, Fung K (July 2016). "A comparison of outcomes in interventions for unilateral vocal fold paralysis: A systematic review". The Laryngoscope. 126 (7): 1616–24. doi:10.1002/lary.25739. PMID 26485674. S2CID 40706249.
## External links[edit]
Classification
D
* ICD-10: J38.0
* ICD-9-CM: 478.30
* MeSH: D014826
External resources
* eMedicine: ent/347
* v
* t
* e
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Vocal fold nodule
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
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*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
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*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Vocal cord paresis | c0751576 | 6,661 | wikipedia | https://en.wikipedia.org/wiki/Vocal_cord_paresis | 2021-01-18T18:31:24 | {"mesh": ["D014826"], "umls": ["C1843187", "C1853729", "C1832690", "C0751576"], "icd-9": ["478.30"], "icd-10": ["J38.0"], "wikidata": ["Q684045"]} |
Eng and Strom (1987) reported a mother and daughter who had low-birth-weight dwarfism and intermittent locking of the fingers such that a fist was formed which required traction to be reduced. The mother, who had an adult height of 129.5 cm, also had a ventricular septal defect. The daughter was born by cesarean section because of cephalopelvic disproportion. Birth weight was 2528 g and length was 39.1 cm with a normal head size. The mother was thought to represent a new dominant mutation; her mother was 41 and her father 49 at the time of her birth. The daughter began to have recurrent locking of index and third fingers at age 3. At first these could be reduced by gentle traction. By age 8 or 9 years, the locking was no longer reducible by traction, occurred more often in the winter, and continued for about 2 weeks before spontaneously reducing during sleep.
Limbs \- Intermittent finger locking Growth \- Low-birth-weight dwarfism Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| FINGER LOCKING, RECURRENT, WITH INTRAUTERINE GROWTH RETARDATION AND PROPORTIONATE SHORT STATURE | c2931545 | 6,662 | omim | https://www.omim.org/entry/135950 | 2019-09-22T16:41:09 | {"mesh": ["C537603"], "omim": ["135950"], "orphanet": ["1937"]} |
Neitlich (1966) described a kindred with increased plasma cholinesterase activity and decreased responsiveness to succinylcholine.
Inheritance \- Autosomal dominant Lab \- Increased plasma cholinesterase activity Metabolic \- Decreased responsiveness to succinylcholine ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| PSEUDOCHOLINESTERASE, INCREASE IN PLASMA LEVEL OF | c1867466 | 6,663 | omim | https://www.omim.org/entry/177600 | 2019-09-22T16:35:36 | {"omim": ["177600"]} |
XYLT1-CDG is a rare congenital disorder of glycosylation characterized by moderate intellectual disability, short stature, mild skeletal changes and distinctive facial features with coarse face, synophyrs and deep nasolabial ridges. Skeletal features include broad ribs, stocky long bones, short femoral necks with coxa valga, clinodactyly and broad thumbs.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| XYLT1-CDG | None | 6,664 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=370930 | 2021-01-23T19:10:59 | {"icd-10": ["E77.8"]} |
Bothriocephalosis is a mammalian cosmopolitan intestinal parasitosis. In addition to non-specific digestive problems (nausea, abdominal pain, lack of appetite), bothriocephalosis provokes an anaemia caused by vitamin B12 deficiency that resembles Biermer anaemia (anaemia characterised by abnormally large red blood cells).
## Epidemiology
The prevalence is Europe is unknown but more than 10 cases are reported each year, principally from the Italian, Swiss and French Alps.
## Etiology
It is an adult cestodosis caused by the large (more than 10 metres) fish tapeworm Diphyllobothrium latum. The life cycle of the parasite is complex and involves two intermediate hosts: a microscopic crustacean, followed by a freshwater fish. Mammals are contaminated through eating fleshy parts of lightly cooked, smoked or undersalted fish.
## Diagnostic methods
Diagnosis is made by examination of the stools.
## Management and treatment
Standard tapeworm treatments (niclosamide or praziquantel) are effective at treating this parasitosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Diphyllobothriasis | c0277032 | 6,665 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=128 | 2021-01-23T18:40:23 | {"gard": ["942"], "umls": ["C0012561", "C0277032"], "icd-10": ["B70.0"], "synonyms": ["Bothriocephalosis"]} |
Johnson–McMillin syndrome
Other namesJohnson neuroectodermal syndrome,[1] alopecia–anosmia–deafness–hypogonadism syndrome[1]
Johnson–McMillin syndrome is inherited in an autosomal dominant manner.
Johnson–McMillin syndrome, also known as Johnson neuroectodermal syndrome, is a neuroectodermal syndrome that consists of conductive hearing loss and microtia.[2]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ a b "OMIM Entry - % 147770 - JOHNSON NEUROECTODERMAL SYNDROME". www.omim.org. Retrieved 2019-12-24.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 831. ISBN 978-1-4160-2999-1.
## External links[edit]
Classification
D
* ICD-10: Q87.8
* OMIM: 147770
* MeSH: C535882
External resources
* Orphanet: 2316
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Johnson–McMillin syndrome | c0796002 | 6,666 | wikipedia | https://en.wikipedia.org/wiki/Johnson%E2%80%93McMillin_syndrome | 2021-01-18T18:35:52 | {"gard": ["378"], "mesh": ["C535882"], "umls": ["C0796002"], "orphanet": ["2316"], "wikidata": ["Q16940647"]} |
## Clinical Features
Reichel (1900) described a disorder in which foci of cartilage form in the synovial membrane of joints, tendon sheaths, and bursae by metaplasia of the connective tissue. These foci may become detached from the synovial membrane and enter the joint cavity as floating cartilage. If calcification occurs, these bodies can be detected by x-ray. Bone erosions may occur, particularly in the joints with a tight capsule (Murphy et al., 1962). Clinical symptoms include pain, swelling, crepitus, and palpable loose bodies. Steinberg et al. (1989) reported a family in which 3 members had this disorder; their habitus was tall and thin.
Felbel et al. (1992) described a family in which at least 3 members and presumably 2 others had the articular disorder combined with dwarfism. All affected members were below the 3rd percentile in height. Two children of an affected male were dwarfed but were perhaps too young to show the joint abnormalities.
Inheritance
In the family reported by Steinberg et al. (1989), X-linked inheritance with incomplete penetrance was suggested.
Radiology \- Calcified joint bodies \- Bone erosions in joints Joints \- Foci of cartilage in synovial membranes \- Floating cartilage in joint cavity \- Joint pain, swelling, crepitus, and palpable loose bodies Growth \- Dwarfism Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| SYNOVIAL CHONDROMATOSIS, FAMILIAL, WITH DWARFISM | c1861304 | 6,667 | omim | https://www.omim.org/entry/186575 | 2019-09-22T16:32:57 | {"mesh": ["C566087"], "omim": ["186575"]} |
For a general discussion of susceptibility to Mycobacterium tuberculosis (TB), see 607948.
An epidemic of TB occurred in a community of aboriginal Canadians during the period of 1987 to 1989. Greenwood et al. (2000) collected genetic and epidemiologic data on an extended family from this community, and assessed evidence for linkage to the NRAMP1 gene (600266). Individuals were grouped into risk (liability) classes based on vaccination, age, previous disease, and tuberculin skin-test results. Using YAC analysis, and under the assumption of a dominant mode of inheritance and a relative risk of 10, which is associated with the high-risk genotypes, Greenwood et al. (2000) observed a maximum lod score of 3.81 for linkage between a TB susceptibility locus and D2S424, which is located just distal to NRAMP1, in 2q35. Significant linkage was also observed between a TB susceptibility locus and a haplotype of 10 NRAMP1 intragenic variants. No linkage to the major histocompatibility complex region on 6p was observed, despite distortion of transmission from one member of the oldest couple to their affected offspring.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| MYCOBACTERIUM TUBERCULOSIS, SUSCEPTIBILITY TO, 1 | c1842762 | 6,668 | omim | https://www.omim.org/entry/607949 | 2019-09-22T16:08:29 | {"omim": ["607949"], "synonyms": ["Alternative titles", "MTBS1"]} |
Primary tethered cord syndrome is a genetic, non-syndromic congenital malformation of the neurenteric canal, spinal cord and column characterized by progressive neurologic deterioration (pain, sensorimotor deficits, abnormal gait, decreased tone or abnormal reflexes), musculoskeletal changes (foot deformities and asymmetry, muscle atrophy, limb weakness and numbness, gait disturbances, scoliosis) and/or genitourinary manifestations (bladder and bowel dysfunction). Midline cutaneous stigmata in the lumbosacral region, such as turfs of hair, skin appendages, dimples, subcutaneous lipomas, skin discoloration or hemangiomas, are frequently associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Primary tethered cord syndrome | c4708602 | 6,669 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268861 | 2021-01-23T16:56:21 | {"gard": ["4018"], "synonyms": ["Primary tethered spinal cord syndrome"]} |
Glanzmann thrombasthenia (GT) is a rare inherited blood clotting disorder that is present at birth. It is characterized by the impaired function of specialized blood cells, called platelets, that are essential for proper blood clotting. Signs and symptoms vary greatly from person to person. Symptoms usually include abnormal bleeding, which can be severe. Other symptoms may include easy bruising, nose bleeds, bleeding from the gums, and/or heavy menstrual bleeding. Rarely, internal bleeding and blood in the urine (hematuria) can occur. Prolonged untreated or unsuccessfully treated bleeding may be life threatening. This condition is inherited in an autosomal recessive fashion and is caused by mutations in either the ITGA2B or ITGB3 genes.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Glanzmann thrombasthenia | c0040015 | 6,670 | gard | https://rarediseases.info.nih.gov/diseases/2478/glanzmann-thrombasthenia | 2021-01-18T18:00:19 | {"mesh": ["D013915"], "omim": ["273800"], "umls": ["C0040015"], "orphanet": ["849"], "synonyms": ["Thrombasthenia of Glanzmann and Naegeli", "GT", "Platelet fibrinogen receptor, deficiency of", "Platelet glycoprotein 2B 3A deficiency", "Deficiency of GP 2B 3A complex", "Glanzmann thrombasthenia type A", "Diacyclothrombopathia 2B 3A"]} |
A number sign (#) is used with this entry because of evidence that aortic valve disease-2 (AOVD2) is caused by heterozygous mutation in the SMAD6 gene (602931) on chromosome 15q22.
Description
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Clinical Features
Tan et al. (2012) studied 2 patients with aortic valve disease. One was a man who at 30 years of age was undergoing evaluation for hypertension and was found to have a bicuspid aortic valve with mild aortic stenosis and aortic coarctation. He underwent repair of the coarctation, and subsequently developed significant aortic stenosis and underwent aortic valve replacement and re-repair of the aortic arch. At that time it was noted that the transverse aortic arch, proximal to and distant from the previous conduit, was heavily calcified. There was no evidence of inappropriate calcification in noncardiovascular tissues. The other patient studied by Tan et al. (2012) presented with a heart murmur at 18 months of age and was found to have bicuspid aortic valve with moderate aortic stenosis, without evidence of coarctation.
Park et al. (2019) reported a 42-year-old Korean man with ascending aorta dilation in whom echocardiography revealed a severely calcified bicuspid aortic valve. CT angiography showed significant dilation of the ascending aorta, with a diameter of 5.5 cm, and confirmed dense calcification in the aortic valve. By echocardiography of the aortic root, the aortic valve annulus was measured at 2.5 cm, the sinus of Valsalva at 3.1 cm, and the sinotubular junction at 3.3 cm. The BAV was of the lateral subtype. There was no family history of cardiovascular disease.
Molecular Genetics
In a discovery cohort of 90 patients with cardiovascular malformations, Tan et al. (2012) analyzed the candidate genes BMPR2 (600799), BMPR1A (601299), and SMAD6 (602931), and identified a missense mutation in the MH2 domain of the SMAD6 protein (C484F; 602931.0001) in a man with bicuspid aortic valve, aortic valve stenosis, and coarctation and calcification of the aorta. No mutations were identified in BMPR2 or BMPR1A in the cohort. Resequencing of the MH2 domain of SMAD6 in a replication cohort consisting of 346 additional probands with a broad range of cardiovascular malformation phenotypes revealed another missense mutation (P415L; 602931.0002) in an infant with bicuspid aortic valve and moderate aortic stenosis. A third missense mutation, A325T, was identified in a patient with mitral valve prolapse, but in contrast to the other 2 mutated residues, A325 does not have a high degree of evolutionary conservation, and functional analysis showed similar activity to that of wildtype SMAD6. None of the mutations were found in 1,000 Caucasian controls of British ancestry, in 629 individuals in the 1000 Genomes project, or in 200 individuals in the Danish Exome Project.
Luyckx et al. (2019) studied 473 unrelated patients with nonsyndromic thoracic aortic aneurysm (AAT), who were all negative for mutation in known AAT genes, and 65 of whom also had bicuspid aortic valve. SMAD6-targeted resequencing identified 6 probands with likely pathogenic variants (see, e.g., 602931.0006 and 602931.0007), all of whom were individuals with BAV/AAT. Familial segregation studies demonstrated reduced penetrance (82%) and variable clinical expressivity, with coarctation of the aorta being a common comorbidity.
In a 42-year-old Korean man with a severely calcified BAV and aneurysm of the ascending aorta, Park et al. (2019) screened 20 BAV-associated genes and identified heterozygosity for a 6-bp in-frame duplication in the SMAD6 gene (602931.0008). The mutation was not found in his unaffected mother or brother, or in public variant databases; no DNA was available from his father, who died of bladder cancer at age 69 years and had no history of cardiovascular disease.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Bicuspid aortic valve \- Stenosis of aortic valve Vascular \- Coarctation of the aorta \- Calcification of the aorta \- Aortic aneurysm MOLECULAR BASIS \- Caused by mutation in the mothers against decapentaplegic, Drosophila, homolog of, 6 gene (SMAD6, 602931.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| AORTIC VALVE DISEASE 2 | c3542024 | 6,671 | omim | https://www.omim.org/entry/614823 | 2019-09-22T15:54:07 | {"doid": ["0080334"], "omim": ["614823", "109730"], "orphanet": ["402075"], "synonyms": ["AORTIC VALVE STENOSIS", "Alternative titles", "Familial BAV", "BICUSPID AORTIC VALVE"]} |
Esophageal intramural pseudodiverticulosis
Other namesEIPD
Endoscopic image of esophageal intramural pseudodiverticulosis demonstrating the flask-like outpouchings of the esophageal wall.
SpecialtyGastroenterology
SymptomsDifficulty swallowing
ComplicationsPeridiverticulitis, esophageal cancer
Diagnostic methodUpper endoscopy, barium esophagram
TreatmentEsophageal dilation
MedicationProton-pump inhibitors
Esophageal intramucosal pseudodiverticulosis (EIPD) is a rare condition wherein the wall of the esophagus develops numerous small outpouchings (pseudodiverticulae). Individuals with the condition typically develop difficulty swallowing. The outpouchings represent the ducts of submucosal glands of the esophagus. It typically affects individuals in their sixth and seventh decades of life. While it is associated with certain chronic conditions, particularly alcoholism, diabetes and gastroesophageal reflux disease, the cause of the condition is unknown. Treatment involves medications to treat concomitant conditions such as reflux (such as proton pump inhibitors) and esophageal spasm, and dilation of strictures in the esophagus.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Management
* 5 Prognosis
* 6 Epidemiology
* 7 References
## Signs and symptoms[edit]
As the condition involves alterations in the wall of the esophagus and reduction in the calibre of the esophagus, the symptoms of esophageal intramucosal pseudodiverticulosis are primarily related to swallowing. Difficulty swallowing solids is a typical symptom.[1] In extreme cases, food may become impacted in the esophagus.[2] Some individuals may have bleeding in the esophagus, manifesting as vomiting of blood or as melena stools.[1] With the reduction of oral intake due to difficulty swallowing, affected individuals usually lose weight.[3]
## Cause[edit]
The cause of esophageal intramucosal pseudodiverticulosis is uncertain. It has been hypothesized that the pseudodiverticulae are not a primary phenomenon, but rather are secondary to a chronic irritant to the esophagus, or to accentuation in the movement of the esophagus (hypermotility). Both of these factors lead to obstruction or compression of the subucosal ducts of the esophagus, leading to the formation of the pseudodiverticulae.[1] Autopsy specimens of individuals with esophageal intramucosal pseudodiverticulosis have confirmed that the flask-like openings are indeed dilated submucosal glands.[2] The condition is associated with alcohol abuse, diabetes mellitus, and gastroesophageal reflux disease.[1]
## Diagnosis[edit]
Esophageal intramucosal pseudodiverticulosis is typically diagnosed at the time of endoscopy of the esophagus. Endoscopy shows evidence of the pseudodiverticulae, which are typically numerous, appear like pits in the wall, and may be preferentially located in the upper esophagus.[2][4] The mucosal lining of the esophagus may be inflamed, and this can be seen on endoscopy or on biopsy; the mucosa, however, may also be normal if esophagitis is not the cause of the pseudodiverticulosis. The condition must also be excluded from esophageal cancer, which may be done at the time of endoscopy, or which may require esophageal biopsy.[2]
Pseudodiverticulae may also be seen on barium swallow imaging of the esophagus. The appearance is of flask-shaped pseudodiverticulae, which may be present in the entire esophagus diffusely, or may be segmental. The pseudodiverticulae may be seen preferentially in the lower esophagus on barium swallow also. Strictures or narrowings in the esophagus may also be seen, typically in the upper esophagus.[4][5]
As esophageal intramucosal pseudodiverticulosis is also associated with motility disturbances of the esophagus, manometry testing of esophageal pressures may provide information to assist in the diagnosis. Irregularity in the contractions of the esophagus, prominent tertiary contractions of the esophagus, or lack of esophageal contraction (aperistalsis) have all been reported on manometric testing of the esophagus.[6]
## Management[edit]
Several treatment regimens have been described for esophageal intramucosal pseudodiverticulosis. Because the condition is associated with gastroesophageal reflux disease, proton pump inhibitors as anti-acid medications are used to treat the condition.[2] If the condition is associated with spasm of the esophagus, antispasmodic medications such as butylscopolamine can be used.[5] Dilation of areas of stricturing using esophageal bougies may provide relief of swallowing symptoms.[2] The pseudodiverticulae themselves rarely cause symptoms, and treatment is not directed toward them.
## Prognosis[edit]
Periodic surveillance of the esophagus with endoscopy has been recommended due to a reported association of the condition with esophageal cancer. Rarely a condition called peridiverticulitis, associated with inflammation around the pseudodiverticulae has been reported over time leading to chest pain or pain while swallowing.[2][7]
## Epidemiology[edit]
Approximately 200 cases of esophageal intramucosal pseudodiverticulosis have been reported.[citation needed] One study of over 14000 barium swallow x-rays identified the condition in 0.15% of individuals who had the procedure.[4] While the disease has been reported as occurring at any time during life, it most frequently affects individuals in their 50s and 60s.[2]
## References[edit]
1. ^ a b c d Hahne, M.; Schilling, D.; Arnold, J. C.; Riemann, J. F. (2001). "Esophageal intramural pseudodiverticulosis: Review of symptoms including upper gastrointestinal bleeding". Journal of Clinical Gastroenterology. 33 (5): 378–382. doi:10.1097/00004836-200111000-00007. PMID 11606853.
2. ^ a b c d e f g h Attila, T.; Marcon, N.E. (2006). "Esophageal intramural pseudodiverticulosis with food impaction". Canadian Journal of Gastroenterology. 20 (1): 37–38. doi:10.1155/2006/373264. PMC 2538963. PMID 16432558.
3. ^ Ritz, J. P.; Germer, C. T.; Zimmer, T.; Isbert, C.; Buhr, H. J. (2000). "Esophageal hypermotility associated with intramural pseudodiverticulosis. Primary esophageal disease or epiphenomena?". Surgical Endoscopy. 14 (7): 681. doi:10.1007/s004640000139. PMID 11265072.
4. ^ a b c Levine, M. S.; Moolten, D. N.; Herlinger, H.; Laufer, I. (1986). "Esophageal intramural pseudodiverticulosis: A reevaluation". AJR. American Journal of Roentgenology. 147 (6): 1165–1170. doi:10.2214/ajr.147.6.1165. PMID 3096096.
5. ^ a b Pache, G.; Nadir, G.; Henning, S.; Mathias, L. (2005). "Intramural pseudodiverticulosis of the esophagus". Journal of Postgraduate Medicine. 51 (4): 328–329. PMID 16388181.
6. ^ Sabanathan, S.; Salama, F. D.; Morgan, W. E. (1985). "Oesophageal intramural pseudodiverticulosis". Thorax. 40 (11): 849–857. doi:10.1136/thx.40.11.849. PMC 1020564. PMID 3934782.
7. ^ Plavsic, B. M.; Chen, M. Y.; Gelfand, D. W.; Drnovsek, V. H.; Williams Jp, 3.; Kogutt, M. S.; Terry, J. A.; Plenkovich, D. (1995). "Intramural pseudodiverticulosis of the esophagus detected on barium esophagograms: Increased prevalence in patients with esophageal carcinoma". AJR. American Journal of Roentgenology. 165 (6): 1381–1385. doi:10.2214/ajr.165.6.7484570. PMID 7484570.CS1 maint: numeric names: authors list (link)
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
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* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
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Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
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(Appendix/Colon)
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Pancreatic
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Peritoneal
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* Pneumoperitoneum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Esophageal intramural pseudodiverticulosis | None | 6,672 | wikipedia | https://en.wikipedia.org/wiki/Esophageal_intramural_pseudodiverticulosis | 2021-01-18T18:38:08 | {"umls": ["CL380989"], "wikidata": ["Q5398633"]} |
"Egomaniac" redirects here. For other uses, see Egomania (disambiguation).
Egomania is psychiatric term used to describe excessive preoccupation with one's ego, identity or self[1] and applies the same preoccupation to anyone who follows one’s own ungoverned impulses, is possessed by delusions of personal greatness & grandeur and feels a lack of appreciation.[2] Someone suffering from this extreme egocentric focus is an egomaniac. Egomania as a condition, while not a classified personality disorder, is considered psychologically abnormal.[1]
The term egomania is often used by laypersons in a pejorative fashion to describe an individual who is perceived as intolerably self-centered. The clinical condition that most resembles egomania, and most often associated with is narcissistic personality disorder, though they differ vastly according to the individual's responses to others.[3]
## Contents
* 1 History
* 2 Substance abuse
* 3 See also
* 4 References
## History[edit]
Egomania was brought into polemical prominence at the end of the 19th century by Max Nordau, one of the first critics who perceived the centrality of the concept of egoism for an understanding of Modernism, with criticism on the ideology of egomania'.[4] Nordau distinguished egoism from the egomania. He described egoism as a lack of amiability while maintaining the ability to look after oneself, and egomania as a condition where one does not see things as they are, does not understand the world, and cannot take up a right attitude towards it.[5] Nordau's attack was aimed at the avant-garde of the fin de siècle. His describes the self-proclaimed geniuses as criminals & madmen obsessed with culte de moi (the cult of self).[6]
Over a century later, the term egomania re-appeared with a positive gloss to mark the post-modern quest for success and celebrity. "Self-confidence is the key to all success..." By contrast, reticent personalities may be labelled: it may well be a form of egomania, if you aren't willing to take a chance".[7]
## Substance abuse[edit]
Egomania has also been linked with alcoholism.[8]
A recovering alcoholic may well look back at the past as "the land of self-loathing, egomania, and decay".[9]
The danger with the egomaniac is always that 'underneath the apparent over-confidence and bravado lies a fragile personality', driven by "grandiose fantasies of boundless success or power or perfect love"[10] which cannot be fulfilled.
## See also[edit]
* Egotism
* Mania
* -mania (suffix)
* Narcissism
* Omnipotence
## References[edit]
1. ^ a b dictionary.com
2. ^ H.C.R. Norriss Indulgent parents; Alienist Says they Make their Children Egomaniacs, July 24, 1913, The New York Times
3. ^ Gretchen Reevy et al eds., Encyclopedia of Emotions: Volume I (2010) p. 217
4. ^ Jean-Michel Rabaté, James Joyce and the Politics of Egoism (2001) p. 27
5. ^ Max Simon Nordau, Degeneration (1895) p. 243
6. ^ Rabaté, p. 29
7. ^ Michael Flocker, The Fame Game (2005) p. 62
8. ^ James Graham, Vessels of Rage, Engines of Power (1994) p. 10
9. ^ Anne Lamott, "Thirst", in Autumn Stephens ed., Roar Softly and Carry a Great Lipstick (2004) p. 6
10. ^ Reevy, p. 217
* v
* t
* e
Narcissism
Types
* Collective
* Egomania
* Flying monkeys
* Healthy
* Malignant
* Narcissistic personality disorder
* Spiritual
* Workplace
Characteristics
* Betrayal
* Boasting
* Egocentrism
* Egotism
* Empathy (lack of)
* Envy
* Entitlement (exaggerated sense of)
* Fantasy
* Grandiosity
* Hubris
* Magical thinking
* Manipulative
* Narcissistic abuse
* Narcissistic elation
* Narcissistic rage and narcissistic injury
* Narcissistic mortification
* Narcissistic supply
* Narcissistic withdrawal
* Perfectionism
* Self-esteem
* Self-righteousness
* Shamelessness
* Superficial charm
* Superiority complex
* True self and false self
* Vanity
Defences
* Denial
* Idealization and devaluation
* Distortion
* Projection
* Splitting
Cultural phenomena
* Control freak
* Don Juanism
* Dorian Gray syndrome
* My way or the highway
* Selfie
Related articles
* Codependency
* Counterdependency
* Dark triad
* Ego ideal
* "Egomania" (film)
* Egotheism
* Empire-building
* God complex
* History of narcissism
* Messiah complex
* Micromanagement
* Narcissism of small differences
* Narcissistic leadership
* Narcissistic parent
* Narcissistic Personality Inventory
* Narcissus (mythology)
* On Narcissism
* Sam Vaknin
* Self-love
* Self-serving bias
* Spoiled child
* The Culture of Narcissism
* Workplace bullying
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Egomania | c0233695 | 6,673 | wikipedia | https://en.wikipedia.org/wiki/Egomania | 2021-01-18T18:54:51 | {"umls": ["C0233695"], "wikidata": ["Q1298422"]} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2012)
Anorectal disorders are painful but common conditions like hemorrhoids, tears, fistulas, or abscesses that affect the anal region.[1][2] Most people experience some form of anorectal disorder during their lifetime.[3] Primary care physicians can treat most of these disorders,[1] however, high-risk individuals include those with HIV, roughly half of whom need surgery to remedy the disorders.[3]Because these disorders affect the rectum, people are often embarrassed or afraid to confer with a medical professional.[1]
## Contents
* 1 Symptoms and signs
* 2 Diagnosis
* 3 Treatment
* 4 Notes
## Symptoms and signs[edit]
Itchiness, a burning sensation, pus discharge, blood, and swelling in around the rectum and anus,[3] diarrhea.[4]
## Diagnosis[edit]
Doctors uses a variety of tools and techniques to evaluate the type of anorectal disorder, including digital and anoscopic investigations, palpations, and palpitations. The initial examination can be painful because a gastroenterologist will need to spread the buttocks and probe the painful area, which may require a local anesthetic.[1]
## Treatment[edit]
Treatments range from recommendations for over-the-counter products to more invasive surgical procedures.
Among the most common outpatient advice given to patients with less severe disorders include a high-fiber diet, application of ointment, and increased water intake. More serious procedures include the removal of affected tissue, injection of botulinum toxin, or surgically opening the fistula tract in the sphincter muscle.[1]
## Notes[edit]
1. ^ a b c d e Schubert, Moonkyung Cho; Sridhar, Subbaramiah; Schade, Robert R; Wexner, Steven D (14 July 2009). "What every gastroenterologist needs to know about common anorectal disorders". World J Gastroenterol. 15 (26): 3201–3209. doi:10.3748/wjg.15.3201. PMC 2710774. PMID 19598294.
2. ^ "Anorectal disorders". The Free Dictionary by Farlex. Retrieved 14 October 2012.
3. ^ a b c Ehrenpreis, Eli (2003). Anal and Rectal Diseases Explained. Remedica. ISBN 978-1-901346-67-1.
4. ^ Givel, Jean-Claude (2009). Anorectal and Colonic Diseases: A Practical Guide to their Management. Springer. ISBN 978-3-54069418-2.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Anorectal disorder | c0687707 | 6,674 | wikipedia | https://en.wikipedia.org/wiki/Anorectal_disorder | 2021-01-18T18:41:58 | {"mesh": ["D012002"], "icd-10": ["K62"], "wikidata": ["Q4770164"]} |
GMS syndrome
Other namesGoniodysgenesis-intellectual disability-short stature syndrome
GMS syndrome is a syndrome characterised by goniodysgenesis, intellectual disability, and short stature.[1]
## References[edit]
1. ^ Kupchik GS, Ludman MD, Raab EL, Gilbert F (January 1992). "GMS syndrome: a new dominant condition with goniodysgenesis, mental retardation, and short stature". Am. J. Med. Genet. 42 (1): 1–4. doi:10.1002/ajmg.1320420102. PMID 1308345.
## External links[edit]
Classification
D
* ICD-10: Q87.8
* OMIM: 138770
* MeSH: C564214
External resources
* Orphanet: 2090
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| GMS syndrome | c1841854 | 6,675 | wikipedia | https://en.wikipedia.org/wiki/GMS_syndrome | 2021-01-18T18:48:07 | {"gard": ["2545", "2523"], "mesh": ["C564214"], "umls": ["C1841854"], "orphanet": ["2090"], "wikidata": ["Q5513797"]} |
Abdominal aortic aneurysms (AAAs) are aneurysms that occur in the part of the aorta that passes through the abdomen. They may occur at any age, but are most common in men between 50 and 80 years of age. Many people with an AAA have no symptoms, but some people have a pulsing sensation in the abdomen and/or pain in the back. If the aneurysm ruptures, it may cause deep, severe pain; nausea; vomiting; fast heart rate; clammy skin; and/or shock. About 20% of AAAs eventually rupture and are often fatal. The condition has multiple genetic and environmental risk factors, and may sometimes occur as part of an inherited syndrome. When more than one family member is affected, it may be considered "familial abdominal aortic aneurysm." Treatment depends on the size of the aneurysm and may include blood pressure medications, or surgery to repair the aneurysm.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Abdominal aortic aneurysm | c0162871 | 6,676 | gard | https://rarediseases.info.nih.gov/diseases/9181/abdominal-aortic-aneurysm | 2021-01-18T18:02:24 | {"mesh": ["D017544"], "omim": ["100070"], "umls": ["C0162871"], "orphanet": ["86"], "synonyms": ["Aneurysm, abdominal aortic"]} |
A malignancy that develops from epithelial cells
Not to be confused with carcinoid, which is sometimes a type of carcinoma but is more often benign.
Carcinoma
Micrograph of a lung primary small cell carcinoma, a type of carcinoma. The clustered cancerous cells consist primarily of nucleus (purple); they have only a scant rim of cytoplasm. The surrounding pale staining, discoid cells are red blood cells. Cytopathology specimen. Field stain.
SpecialtyOncology
Carcinoma is a malignancy that develops from epithelial cells.[1] Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal[2] or ectodermal germ layer during embryogenesis.[3]
Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the Greek: καρκίνωμα, romanized: karkinoma, lit. 'sore, ulcer, cancer' (itself derived from karkinos meaning crab).[4]
## Contents
* 1 Classification
* 1.1 Histological types
* 1.2 Carcinoma of unknown primary site
* 1.3 ICD-10 code
* 1.4 Carcinoma In situ
* 2 Pathogenesis
* 2.1 Invasion and metastasis
* 2.2 Mutation
* 2.2.1 Cause of mutations
* 2.2.1.1 High frequency
* 2.2.2 DNA repair
* 3 Diagnosis
* 3.1 Types
* 3.2 Staging
* 3.3 Grading
* 4 Epidemiology
* 5 References
* 6 External links
## Classification[edit]
As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community.[5] Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including:[6]
The cell type from which they start; specifically:
* Epithelial cells ⇨ carcinoma
* Non-hematopoietic mesenchymal cells ⇨ sarcoma
* Hematopoietic cells
* Bone marrow-derived cells that normally mature in the bloodstream ⇨ leukemia
* Bone marrow-derived cells that normally mature in the lymphatic system ⇨ lymphoma
* Germ cells ⇨ germinoma
Other criteria that play a role include:
* The degree to which the malignant cells resemble their normal, untransformed counterparts
* The appearance of the local tissue and stromal architecture
* The anatomical location from which tumors arise
* Genetic, epigenetic, and molecular features
### Histological types[edit]
Adenocarcinoma
(adeno = gland) Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin.
Squamous cell carcinoma
Refers to a carcinoma with observable features and characteristics indicative of squamous differentiation (intercellular bridges, keratinization, squamous pearls).
Adenosquamous carcinoma
Refers to a mixed tumor containing both adenocarcinoma and squamous cell carcinoma, wherein each of these cell types comprise at least 10% of the tumor volume.
Anaplastic carcinoma
Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as anaplastic or undifferentiated carcinomas.
Large cell carcinoma
Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm.
Small cell carcinoma
Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte and with little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells.[7]
There are a large number of rare subtypes of anaplastic, undifferentiated carcinoma. Some of the more well known include the lesions containing pseudo-sarcomatous components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma (mixtures of spindle and giant cell carcinoma). Pleomorphic carcinoma contains spindle cell and/or giant cell components, plus at least a 10% component of cells characteristic of more highly differentiated types (i.e. adenocarcinoma and/or squamous cell carcinoma). Very rarely, tumors may contain individual components resembling both carcinoma and true sarcoma, including carcinosarcoma and pulmonary blastoma.[7] A history of cigarette smoking is the most common cause of large cell carcinoma.
### Carcinoma of unknown primary site[edit]
The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see cancer of unknown primary origin; CUP), but that possess certain specific molecular, cellular, and histological characteristics typical of epithelial cells. This may include the production of one or more forms of cytokeratin or other intermediate filaments, intercellular bridge structures, keratin pearls, and/or tissue architectural motifs such as stratification or pseudo-stratification.[5][6]
### ICD-10 code[edit]
* (8010-8045) Epithelial neoplasms, NOS
* (8050-8080) Squamous cell neoplasms
* (M8070/3) Squamous cell carcinoma, NOS
* (8090-8110) Basal cell neoplasms
* (M8090/3) Basal cell carcinoma, NOS
* (8120-8130) Transitional cell carcinomas
* (8140-8380) Adenocarcinomas
* (M8140/3) Adenocarcinoma, NOS
* (M8142/3) Linitis plastica
* (M8155/3) Vipoma
* (M8160/3) Cholangiocarcinoma
* (M8170/3) Hepatocellular carcinoma, NOS
* (M8200/3) Adenoid cystic carcinoma
* (M8312/3) Renal cell carcinoma
* (M8312/3) Grawitz tumor
* (8390-8420) Adnexal and Skin appendage Neoplasms
* (8430-8439) Mucoepidermoid Neoplasms
* (8440-8490) Cystic, Mucinous and Serous Neoplasms
* (8500-8540) Ductal, Lobular and Medullary Neoplasms
* (8550-8559) Acinar cell neoplasms
* (8560-8580) Complex epithelial neoplasms
### Carcinoma In situ[edit]
The term carcinoma in situ (or CIS) is a term for cells that are significantly abnormal but not cancer.[8] They are thus not typically carcinomas.[9]
## Pathogenesis[edit]
Cancer occurs when a single progenitor cell accumulates mutations and other changes in the DNA, histones, and other biochemical compounds that make up the cell's genome. The cell genome controls the structure of the cell's biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also called a cancer stem cell) displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of cancer, including:
* the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant cancerous "daughter cells" (uncontrolled mitosis);
* the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness);
* the ability to spread to other sites within the body (metastasize) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis).[10]
If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the end result is that the host suffers a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions carried out by the host's organs, and death ultimately ensues.
Carcinoma is but one form of cancer—one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells.[5][6] A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell,[11] a multipotent cell,[11] or a mature differentiated cell.[12]
### Invasion and metastasis[edit]
The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood.
### Mutation[edit]
Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.[13]
Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase (Mb) in some carcinomas,[14] as shown in the table (along with the indicated frequencies of mutations per genome).
Mutation frequencies Cell type Mutation frequency
Per megabase Per dipload genome
Germline 0.023 70
Prostate cancer 0.9 5,400
Colorectal carcinoma ~5 ~30,000
Microsatellite stable (MSS) colon cancer 2.8 16,800
Microsatellite instable (MSI) colon cancer (mismatch repair deficient) 47 282,000
Hepatocellular carcinoma 4.2 25,200
Breast cancer 1.18–1.66 7,080–9,960
Lung cancer 17.7 106,200
Small cell lung cancer 7.4 44,400
Non-small cell lung cancer (smokers) 10.5 63,000
Non-small cell lung cancer (never-smokers) 0.6 3,600
Lung adenocarcinoma (smokers) 9.8 58,500
Lung adenocarcinoma (never-smokers) 1.7 10,200
#### Cause of mutations[edit]
Further information: DNA damage (naturally occurring
The likely major underlying cause of mutations in carcinomas is DNA damage.[citation needed] For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene).[15] Endogenous (metabolically-caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells.[citation needed] Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. by non-homologous end joining).
##### High frequency[edit]
The high frequency of mutations in the total genome within carcinomas suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repair[16]
A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects (causing a very high mutation rate), likely give rise to the high frequency of total genome mutations seen in carcinomas.
#### DNA repair[edit]
In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT protein expression due to methylation of the MGMT promoter region.[17]
## Diagnosis[edit]
Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,.[18] Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.
### Types[edit]
* Oral: Most of oral cancers are squamous-cell carcinoma
* Lung: Carcinoma comprises >98% of all lung cancers.
* Breast: Nearly all breast cancers are ductal carcinoma.
* Prostate: The most common form of carcinoma of the prostate is adenocarcinoma.
* Colon and rectum: Nearly all malignancies of the colon and rectum are either adenocarcinoma or squamous cell carcinoma.
* Pancreas: Pancreatic carcinoma is almost always of the adenocarcinoma type and is highly lethal.
* Ovaries: One of the most deadly forms due to late detection.[19]
Some carcinomas are named for their or the putative cell of origin, (e.g.hepatocellular carcinoma, renal cell carcinoma).
### Staging[edit]
Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.
Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.
In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma in situ, and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).
In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.
Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.
The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon[20] and bladder cancer[21] staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.[22]
The UICC/AJCC TNM systems are most often used.[clarification needed][23] For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.
### Grading[edit]
Grading of carcinomas refers to the employment of criteria intended to semi-quantify the degree of cellular and tissue maturity seen in the transformed cells relative to the appearance of the normal parent epithelial tissue from which the carcinoma derives.
Grading of carcinoma is most often done after a treating physician and/or surgeon obtains a sample of suspected tumor tissue using surgical resection, needle or surgical biopsy, direct washing or brushing of tumor tissue, sputum cytopathology, etc. A pathologist then examines the tumor and its stroma, perhaps utilizing staining, immunohistochemistry, flow cytometry, or other methods. Finally, the pathologist classifies the tumor semi-quantitatively into one of three or four grades, including:
* Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity;
* Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed;
* Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive;
* Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.
Although there is definite and convincing statistical correlation between carcinoma grade and tumor prognosis for some tumor types and sites of origin, the strength of this association can be highly variable. It may be stated generally, however, that the higher the grade of the lesion, the worse is its prognosis.[24][25]
## Epidemiology[edit]
While cancer is generally considered a disease of old age, children can also develop cancer.[26] In contrast to adults, carcinomas are exceptionally rare in children. Less than 1% of carcinoma diagnoses are in children.[27]
The two biggest risk factors for ovarian carcinoma are age and family history.[28]
## References[edit]
1. ^ Lemoine, Nigel Kirkham, Nicholas R. (2001). Progress in pathology. London: Greenwich Medical Media. p. 52. ISBN 9781841100500.
2. ^ 1942-, Weinberg, Robert A. (Robert Allan) (24 May 2013). The biology of cancer (Second ed.). New York. ISBN 9780815345282. OCLC 841051175.CS1 maint: numeric names: authors list (link)
3. ^ "Definition of Carcinoma". Retrieved 27 January 2014.
4. ^ Oxford English Dictionary, 3rd edition, s.v.
5. ^ a b c Berman JJ (March 2004). "Tumor classification: molecular analysis meets Aristotle". BMC Cancer. 4 (1): 10. doi:10.1186/1471-2407-4-10. PMC 415552. PMID 15113444.
6. ^ a b c Berman JJ (November 2004). "Tumor taxonomy for the developmental lineage classification of neoplasms". BMC Cancer. 4 (1): 88. doi:10.1186/1471-2407-4-88. PMC 535937. PMID 15571625.
7. ^ a b Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; Harris, Curtis C, eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 978-92-832-2418-1. Archived from the original (PDF) on 23 August 2009. Retrieved 27 January 2014.
8. ^ Chang, Alfred (2007). Oncology: An Evidence-Based Approach. Springer. p. 162. ISBN 9780387310565.
9. ^ Looijenga, LH; Hersmus, R; de Leeuw, BH; Stoop, H; Cools, M; Oosterhuis, JW; Drop, SL; Wolffenbuttel, KP (April 2010). "Gonadal tumours and DSD". Best Practice & Research. Clinical Endocrinology & Metabolism. 24 (2): 291–310. doi:10.1016/j.beem.2009.10.002. PMID 20541153.
10. ^ "Carcinoma". Academic Press Dictionary of Science and Technology. Cite journal requires `|journal=` (help)
11. ^ a b Vassilev, Alex; DePamphilis, Melvin L. (25 January 2017). "Links between DNA Replication, Stem Cells and Cancer". Genes. 8 (2): 45. doi:10.3390/genes8020045. ISSN 2073-4425. PMC 5333035. PMID 28125050.
12. ^ Anandakrishnan, Ramu; Varghese, Robin T.; Kinney, Nicholas A.; Garner, Harold R. (7 March 2019). "Estimating the number of genetic mutations (hits) required for carcinogenesis based on the distribution of somatic mutations". PLOS Computational Biology. 15 (3): e1006881. doi:10.1371/journal.pcbi.1006881. ISSN 1553-734X. PMC 6424461. PMID 30845172.
13. ^ Roach JC, Glusman G, Smit AF, et al. (April 2010). "Analysis of genetic inheritance in a family quartet by whole-genome sequencing". Science. 328 (5978): 636–9. doi:10.1126/science.1186802. PMC 3037280. PMID 20220176.
14. ^ Tuna M, Amos CI (November 2013). "Genomic sequencing in cancer". Cancer Lett. 340 (2): 161–70. doi:10.1016/j.canlet.2012.11.004. PMC 3622788. PMID 23178448.
15. ^ Cunningham FH, Fiebelkorn S, Johnson M, Meredith C (2011). "A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants". Food Chem Toxicol. 49 (11): 2921–2933. doi:10.1016/j.fct.2011.07.019. PMID 21802474.
16. ^ Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM (December 2006). "Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6". Carcinogenesis. 27 (12): 2402–8. doi:10.1093/carcin/bgl079. PMC 2612936. PMID 16728433.
17. ^ Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I (June 2005). "O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions". Gut. 54 (6): 797–802. doi:10.1136/gut.2004.059535. PMC 1774551. PMID 15888787.
18. ^ Wagman LD (2008). "Principles of Surgical Oncology". In Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (eds.). Cancer Management: A Multidisciplinary Approach (11th ed.).
19. ^ Boyraz; Selcuk; Yazicioglu; Selcuk-Tuncer (September 2013). "Ovarian Carcinoma Associated with endometriosis". European Journal of Obstetrics and Gynecology and Reproductive Biology. 170 (1): 211–213. doi:10.1016/j.ejogrb.2013.06.001. PMID 23849309.
20. ^ Puppa G, Sonzogni A, Colombari R, Pelosi G (2010). "TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues". Arch Pathol Lab Med. 134 (6): 837–52. doi:10.1043/1543-2165-134.6.837 (inactive 16 January 2021). PMID 20524862.CS1 maint: DOI inactive as of January 2021 (link)
21. ^ Sharir S (2006). "Update on clinical and radiological staging and surveillance of bladder cancer". Can J Urol. 13 (Suppl 1): 71–6. PMID 16526987.
22. ^ Pepek JM, Chino JP, Marks LB, D'amico TA, Yoo DS, Onaitis MW, Ready NE, Hubbs JL, Boyd J, Kelsey CR (2011). "How well does the new lung cancer staging system predict for local/regional recurrence after surgery?: A comparison of the TNM 6 and 7 systems". J Thorac Oncol. 6 (4): 757–61. doi:10.1097/JTO.0b013e31821038c0. PMID 21325975. S2CID 24598745.
23. ^ "What is Cancer Staging?". Archived from the original on 25 October 2007. Retrieved 27 January 2014.
24. ^ Sun Z, Aubry MC, Deschamps C, Marks RS, Okuno SH, Williams BA, Sugimura H, Pankratz VS, Yang P (2006). "Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases". J Thorac Cardiovasc Surg. 131 (5): 1014–20. doi:10.1016/j.jtcvs.2005.12.057. PMID 16678584.
25. ^ "Poorly differentiated carcinoma of unknown primary site". Retrieved 27 January 2014.[permanent dead link]
26. ^ Kuriakose MA, Hicks WL, Loree TR, Yee H (August 2001). "Risk group-based management of differentiated thyroid carcinoma". J R Coll Surg Edinb. 46 (4): 216–23. PMID 11523714. Archived from the original on 5 May 2010.
27. ^ "Key Statistics for Childhood Cancers". www.cancer.org. Retrieved 6 May 2019.
28. ^ "Ovarian Cancer: An Overview". American Family Physician. Cite journal requires `|journal=` (help)
## External links[edit]
Classification
D
* ICD-O: 8010-8580
* MeSH: D002277
* SNOMED CT: 68453008
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
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| Carcinoma | c0007097 | 6,677 | wikipedia | https://en.wikipedia.org/wiki/Carcinoma | 2021-01-18T18:51:56 | {"mesh": ["D002277"], "umls": ["C1368683", "C0553707", "C0007097"], "wikidata": ["Q33525"]} |
A number sign (#) is used with this entry because pulmonary venoocclusive disease-2 (PVOD2) is caused by homozygous or compound heterozygous mutation in the EIF2AK4 gene (609280) on chromosome 15q15.
Description
Pulmonary venoocclusive disease-2 is an autosomal recessive subtype of primary pulmonary hypertension (PPH; see 178600). It is characterized histologically by widespread fibrous intimal proliferation of septal veins and preseptal venules, and is frequently associated with pulmonary capillary dilatation and proliferation. The disorder can cause occult alveolar hemorrhage. High-resolution CT imaging of the chest shows patchy centrilobular ground-glass opacities, septal lines, and lymph node enlargement (summary by Eyries et al., 2014).
For a discussion of genetic heterogeneity of pulmonary venoocclusive disease, see PVOD1 (265450).
Clinical Features
Langleben et al. (1988) reported cases of familial pulmonary capillary hemangiomatosis. They described 3 sibs, 2 brothers and a sister in a French Canadian family, who died from primary pulmonary hypertension. Lung specimens obtained in 2 of the sibs showed extensive pulmonary capillary hemangiomatosis, with normal capillaries proliferating in the veins and the alveoli. Of their 3 cases and 6 nonfamilial cases in the literature, 4 had the presenting clinical picture of primary pulmonary hypertension.
Eyries et al. (2014) identified 13 families with pulmonary hypertension due to PVOD2 in a French referral center. Many of the families originated from North Africa. All families contained at least 2 affected sibs and unaffected parents, consistent with autosomal recessive inheritance. PVOD was confirmed histologically after lung transplantation or by lung biopsy in members from 8 of these families. Findings included intimal fibrosis of septal veins, intimal remodeling of pulmonary arteries, and patch-like foci of pulmonary capillary hemangiomatosis. Five additional patients with sporadic disease were subsequently identified. Among all patients, the age at diagnosis ranged between 11 and 50 years, although most patients were diagnosed in their twenties. Virtually all patients underwent lung transplantation or died.
Best et al. (2014) reported 2 brothers with pulmonary capillary hemangiomatosis. They presented in young adulthood with marked dyspnea, cough, and fatigue. Pulmonary function studies showed severe reduction of carbon monoxide diffusion capacity, and lung CT scans showed bilateral diffuse nodular opacities. Cardiac catheterization showed pulmonary hypertension. Analysis of explanted diseased lungs showed extensive proliferation of pulmonary capillaries and alveolar thickening, consistent with the diagnosis. Two additional unrelated patients with apparently sporadic disease and similar clinical features were also reported.
Inheritance
The transmission pattern of PVOD2 in the families reported by Eyries et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In affected members of 13 unrelated families with autosomal recessive pulmonary venoocclusive disease-2, Eyries et al. (2014) identified homozygous or compound heterozygous mutations in the EIF2AK4 gene (see, e.g., 609280.0001-609280.0006). The initial mutations were found using linkage analysis and whole-exome sequencing; subsequent mutations were found by direct Sanger sequencing of the EIF2AK4 gene. Biallelic mutations were also found in 5 (25%) of 20 additional patients with apparently sporadic disease. In all, 22 different mutations were identified. Most were truncating or insertion/deletion mutations that disrupted the function of the gene. Detectable EIF2AK4 was found in lung tissue from a patient with a homozygous truncating mutation, consistent with a loss of function. There were no apparent genotype/phenotype correlations to explain the range in age at onset.
In 2 brothers with PVOD2, Best et al. (2014) identified compound heterozygous mutations in the EIF2AK4 gene (609280.0007 and 609280.0008). The mutations, which were found by exome sequencing, segregated with the disorder in the family. Screening of this gene in 11 additional probands with the disorder identified biallelic mutations in 2 patients (609280.0001 and 609280.0009-609280.0010). All mutations were predicted to result in a truncated protein, but functional studies were not performed. Best et al. (2014) noted that the EIF2AK4 gene belongs to a family of kinases that regulate angiogenesis.
INHERITANCE \- Autosomal recessive CARDIOVASCULAR Vascular \- Pulmonary arterial hypertension RESPIRATORY \- Dyspnea \- Cough \- Decreased carbon monoxide diffusion capacity Lung \- Occult alveolar hemorrhage \- Ground-glass opacities seen on CT \- Septal lines seen on CT \- Lymph node enlargement seen on CT \- Pulmonary venoocclusive disease seen on biopsy \- Fibrous intimal proliferation of septal veins and preseptal venules \- Pulmonary capillary hemangiomatosis \- Pulmonary capillary proliferation and dilation \- Intimal remodeling of the pulmonary artery MISCELLANEOUS \- Onset usually in the third decade (range 11 to 50 years) \- Fatal without lung transplant MOLECULAR BASIS \- Caused by mutation in the eukaryotic translation initiation factor 2-alpha kinase 4 gene (EIF2AK4, 609280.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| PULMONARY VENOOCCLUSIVE DISEASE 2, AUTOSOMAL RECESSIVE | c0340548 | 6,678 | omim | https://www.omim.org/entry/234810 | 2019-09-22T16:27:11 | {"omim": ["234810"], "orphanet": ["199241"], "synonyms": ["Alternative titles", "HEMANGIOMATOSIS, FAMILIAL PULMONARY CAPILLARY"]} |
Acute myeloid leukemia (AML) is a cancer that affects the blood and bone marrow. Conditions are generally called "acute" when they develop quickly and have an aggressive course. The signs and symptoms of AML vary but may include easy bruising; bone pain or tenderness; fatigue; fever; frequent nosebleeds; bleeding from the gums; shortness of breath; and/or weightloss. AML is one of the most common types of leukemia among adults and is rarely diagnosed in people under age 40. There are many potential causes of AML such as certain blood disorders, inherited syndromes, environmental exposures, and drug exposures; however, most people who develop AML have no identifiable risk factor. Treatment may include a combination of chemotherapy, radiation therapy, bone marrow transplant and/or other drug therapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Acute myeloid leukemia | c0023467 | 6,679 | gard | https://rarediseases.info.nih.gov/diseases/12757/acute-myeloid-leukemia | 2021-01-18T18:02:18 | {"mesh": ["D015470"], "omim": ["601626"], "orphanet": ["519"], "synonyms": ["Acute myelogenous leukemia"]} |
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Dermatographic urticarial
Other namesDermographism, dermatographism, dermatographia, skin writing
Dermatographic urticaria is sometimes called "skin writing".
SpecialtyDermatology, allergy and immunology
Dermatographic urticaria is a skin disorder and one of the most common types of urticaria, affecting 2-5% of the population.[1][2]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
The condition manifests as an allergic-like reaction, causing a warm red wheal to appear on the skin. As it is often the result of scratches, involving contact with other materials, it can be confused with an allergic reaction, when in fact it is the act of being scratched that causes a wheal to appear. These wheals are a subset of urticaria (hives), and appear within minutes, in some cases accompanied by itching. The first outbreak of urticaria can lead to other reactions on body parts not directly stimulated, scraped, or scratched. In a normal case, the swelling will decrease without treatment within 15–30 minutes, but, in extreme cases, itchy red welts may last anywhere from a few hours to days.
## Causes[edit]
Symptoms are thought to be the result of histamine being released by mast cells on the surface of the skin. Due to the lack of antigens, histamine causes the skin to swell in affected areas.[3] If the membrane that surrounds the mast cells is too weak it will easily and rapidly break down under physical pressure, which then causes an allergic-like reaction.[3]
Symptoms can be caused or induced by:[3]
* stress
* tight or abrasive clothing
* watches
* glasses
* heat
* cold
* pressure on exposed skin
* infection
* diet [4]
* air currents : air flow moving hairs on skin surface[citation needed]
The underlying cause of dermographism is not known, and it can last for many years without relief. The condition may subside and be effectively cured; however, it is often a lifelong ailment.[dubious – discuss] It is not a life-threatening disease, and it is not contagious.[citation needed]
Dermographism may occur in mastocytosis (systemic mast cell proliferation).
## Diagnosis[edit]
This condition is diagnosed by a health care provider writing or drawing on the patient's skin with a tongue depressor or other implement, to see whether a red wheal appears soon afterwards.[5]
## Treatment[edit]
Dermographism can be treated by substances which prevent histamine from causing the reaction (i.e. an antihistamine). These may need to be given as a combination of H1 antagonists, or possibly with an H2-receptor antagonist such as cimetidine.[6][7]
Over-the-counter vitamin C, 1000 mg daily, increases histamine degradation and removal.[8][further explanation needed]
Refraining from taking hot baths or showers may help if the condition is generalized (i.e. all over), as well as possibly for localized cases (i.e. in a specific area). If taking hot showers helps, it may be a condition called shower eczema. If it affects mainly the head, it may be psoriasis. In rare cases, allergy tests may uncover substances the patient is allergic to.[7]
While cromoglycate, which prevents histamine from being released from mast cells, is used topically in rhinitis and asthma, it is not effective orally for treating chronic urticaria.[citation needed]
## See also[edit]
* Triple response of Lewis
## References[edit]
1. ^ Jedele, Kerry B.; Michels, Virginia V. (1991). "Familial dermographism". Am. J. Med. Genet. 39 (2): 201–203. doi:10.1002/ajmg.1320390216. PMID 2063925.
2. ^ Kontou-Fili, K.; Borici-Mazi, R.; Kapp, A.; Matjevic, L.J.; Mitchel, F.B. (1997). "Physical urticaria: classification and diagnostic guidelines. An EAACI position paper". Allergy. 52 (5): 504–513. doi:10.1111/j.1398-9995.1997.tb02593.x. PMID 9201361.
3. ^ a b c Fadden, Helen (2016-09-27). "Dermographia (Dermographism- Causes, Symptoms, Treatment)". thehealthyapron.com online. Helen Fadden. Retrieved 2018-01-09.
4. ^ Brown, Keith (2019-03-05). "Dermographia Diet". dermatographia.com online. Keith Brown. Retrieved 2019-03-07.
5. ^ "Dermatographia - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2019-05-06.
6. ^ Wozel G, Sahre EM, Barth J (1990). "[Effectiveness of combination treatment with H1-(Tavegyl) and H2-antagonists (Altramet) in chronic/chronically-recurrent urticaria]". Dermatologische Monatsschrift (in German). 176 (11): 653–659. ISSN 0011-9083. OCLC 1566270. PMID 2083605.
7. ^ a b Negro-Álvarez, J.M.; Miralles-López, J.C. (2001). "Chronic idiopathic urticaria treatment". Allergologia et Immunopathologia. 29 (4): 129–132. doi:10.1016/S0301-0546(01)79045-3. ISSN 0301-0546. PMID 11674926.
8. ^ Johnston, C. S.; Martin, L. J.; Cai, X. (1992-04-01). "Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis". Journal of the American College of Nutrition. 11 (2): 172–176. ISSN 0731-5724. PMID 1578094.
## External links[edit]
Classification
D
* ICD-10: L50.3
* ICD-9-CM: 708.3
* OMIM: 125635
* MeSH: C536612
* DiseasesDB: 12736
External resources
* eMedicine: derm/446
* v
* t
* e
Urticaria and erythema
Urticaria
(acute/chronic)
Allergic urticaria
* Urticarial allergic eruption
Physical urticaria
* Cold urticaria
* Familial
* Primary cold contact urticaria
* Secondary cold contact urticaria
* Reflex cold urticaria
* Heat urticaria
* Localized heat contact urticaria
* Solar urticaria
* Dermatographic urticaria
* Vibratory angioedema
* Pressure urticaria
* Cholinergic urticaria
* Aquagenic urticaria
Other urticaria
* Acquired C1 esterase inhibitor deficiency
* Adrenergic urticaria
* Exercise urticaria
* Galvanic urticaria
* Schnitzler syndrome
* Urticaria-like follicular mucinosis
Angioedema
* Episodic angioedema with eosinophilia
* Hereditary angioedema
Erythema
Erythema multiforme/
drug eruption
* Erythema multiforme minor
* Erythema multiforme major
* Stevens–Johnson syndrome, Toxic epidermal necrolysis
* panniculitis (Erythema nodosum)
* Acute generalized exanthematous pustulosis
Figurate erythema
* Erythema annulare centrifugum
* Erythema marginatum
* Erythema migrans
* Erythema gyratum repens
Other erythema
* Necrolytic migratory erythema
* Erythema toxicum
* Erythroderma
* Palmar erythema
* Generalized erythema
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Dermatographic urticaria | c1852145 | 6,680 | wikipedia | https://en.wikipedia.org/wiki/Dermatographic_urticaria | 2021-01-18T18:43:16 | {"gard": ["9480"], "mesh": ["C536612"], "umls": ["C1852145"], "wikidata": ["Q1200268"]} |
Myhre syndrome is a rare condition that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Myhre syndrome has a variety of signs and symptoms that affect many parts of the body, though not everyone has all the possible features. The features of the condition can range in severity, and some features become more apparent with age.
Common signs and symptoms of Myhre syndrome include short stature, skeletal abnormalities, limited joint mobility, characteristic facial features, intellectual and behavioral problems, hearing loss, a tendency for the buildup of scar tissue (fibrosis) in the skin and internal organs, and heart and lung abnormalities.
Growth is reduced in most people with Myhre syndrome, beginning before birth and continuing through adolescence. Affected individuals usually have a low birth weight and are generally shorter than about 97 percent of their peers throughout life. They have shortened long bones of the arms and legs, unusually short fingers and toes (brachydactyly), and curved pinky fingers (fifth finger clinodactyly). Other skeletal abnormalities associated with this disorder include thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, and underdevelopment of the wing-shaped structures of the pelvis (hypoplastic iliac wings). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility.
Typical facial features in people with Myhre syndrome include narrow openings of the eyelids (short palpebral fissures), deeply set eyes, a shortened distance between the nose and upper lip (a short philtrum), a narrow mouth with a thin upper lip, an underdeveloped upper jaw, and a protruding lower jaw (prognathism). Some affected individuals are born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Vision problems are common in this disorder and can include eyes that do not point in the same direction (strabismus), nearsightedness (myopia), farsightedness (hyperopia), an irregular curvature of the front of the eye (astigmatism), clouding of the lenses (cataracts), or rarely, an abnormality of the back of the eye called pseudopapilledema.
Children with Myhre syndrome have delayed development, which is noticeable by age 5. Speech and language delay are the most significant. Motor skills such as crawling and walking may be delayed, although children with Myhre syndrome eventually learn to walk. Most affected individuals have intellectual disability that ranges from mild to moderate, yet some are able to have jobs or pursue higher education.
People with Myhre syndrome typically have behavioral problems like those in autism spectrum disorder, which affects communication and social interaction. These problems vary in severity, and they usually improve over time.
Hearing loss occurs in most people with Myhre syndrome, usually beginning in childhood and gradually worsening. If not detected promptly, hearing problems can contribute to learning and behavioral problems.
Fibrosis in Myhre syndrome can occur in the absence of injury (spontaneously) or develop following surgery or trauma. Affected individuals typically have stiff, thickened skin, usually beginning in childhood. Typically, the skin changes first appear on the palms of the hands, the soles of the feet, the back of the elbows, and the front of the knees. Eventually the skin thickens on other parts of the body. As a result of the thicker skin, affected individuals typically have fewer facial creases (wrinkles) than others of their age. Scars may be more noticeable or become unusually thickened after healing (keloids or hypertrophic scars).
Individuals with Myhre syndrome often have problems with the structure of the heart that are present at birth (congenital heart defects). Fibrosis in the heart and blood vessels (cardiovascular system) can lead to the development of additional problems such as high blood pressure (hypertension) and narrowing (stenosis) of the heart valves or blood vessels. Other cardiovascular problems can include swelling and tightening of the pericardium, which is the membrane that surrounds the heart (pericarditis), and rarely, restrictive cardiomyopathy, in which the heart muscle is stiff and cannot fully relax after each contraction. These cardiovascular problems can be life-threatening.
Abnormalities of the lungs and airways (respiratory tract) in people with Myhre syndrome include narrowing of the windpipe (laryngotracheal stenosis) and the passages leading from the windpipe to the lungs (bronchi); difficulty filling the lungs with air when inhaling (restrictive pulmonary disease); or widespread lung damage (interstitial lung disease). These respiratory tract problems can be life-threatening.
Additional features of Myhre syndrome include problems in the gastrointestinal tract, such as narrowing of the lower part of the stomach (pyloric stenosis) or of the upper part of the small intestine (duodenal strictures) and severe constipation. People with Myhre syndrome also may have an increased risk of developing cancerous or noncancerous tumors, including cancer of the lining of the uterus (endometrial cancer).
## Frequency
Myhre syndrome is a rare disorder; its prevalence is unknown. Almost 100 cases have been documented in the medical literature.
## Causes
Mutations in the SMAD4 gene cause Myhre syndrome. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-β) pathway, allows the environment outside the cell to affect gene activity and protein production within the cell. As part of this pathway, the SMAD4 protein interacts with other proteins to control the activity of particular genes. These genes influence the development of many body systems.
Studies suggest that the SMAD4 gene mutations that cause Myhre syndrome result in an abnormally stable SMAD4 protein that remains active in the cell longer than it is needed. Increased SMAD4 availability allows the protein more time to interact with other proteins and may result in abnormal TGF-β signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.
### Learn more about the gene associated with Myhre syndrome
* SMAD4
## Inheritance Pattern
Myhre syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered SMAD4 gene in each cell is sufficient to cause the disorder.
In almost all cases, the condition results from new mutations in the gene and occurs in people with no history of the disorder in their family. Rarely, an affected person inherits the mutation from one affected parent.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Myhre syndrome | c0796081 | 6,681 | medlineplus | https://medlineplus.gov/genetics/condition/myhre-syndrome/ | 2021-01-27T08:25:08 | {"gard": ["2572"], "mesh": ["C537620"], "omim": ["139210"], "synonyms": []} |
Nonverbal autism is a subset of autism where the person does not learn how to speak. It is estimated that 25% to 50% of children diagnosed with autism spectrum disorder (ASD) never develop spoken language beyond a few words or utterances.[1]
## Contents
* 1 Background
* 2 Early predictors
* 3 Potential causes
* 3.1 The amygdala theory
* 4 Language outcomes
* 5 See also
* 6 References
## Background[edit]
Despite the growing field of research on ASD, there is not much information available pertaining to people with autism who never develop oral language; that, in fact, nonverbal autistic individuals are considered to be underrepresented in all of autism research.[2] Because of the limited research on nonverbal autism, there are not many validated measurements appropriate for this population. For example, while they may be appropriate for younger children, they lack the validity for school children and have continued to be a roadblock for nonverbal autism research.[3] Often in autism research, nonverbal autistic individuals are subgrouped with LFA, categorized by learning to speak one word or having minimal verbal language.[2]
Most of the existing body of research in nonverbal autism focuses on early interventions that predict successful language outcomes. Research suggests that acquiring language before age five is a good indicator of positive child development,[4] and the likelihood of acquiring functional language in the future past this age is minimal,[5] that early language development is crucial to educational achievement, employment, independence during adulthood, and social relationships.[1]
Most children with ASD can be diagnosed between age two and three because of their behaviors and lack of social skills. They can also have gastrointestinal problems, seizures, and sleep disorders.[6]
## Early predictors[edit]
The causes of nonverbal autism are unknown. However, there appears to be a relationship between joint attention and verbal communication. Joint attention occurs between two individuals when one draws the other’s attention to an object through gesturing (i.e. eye gazing, pointing).[7] The ability to achieve joint attention at an early age plays a significant role in language development, and studies indicate severe lapses in joint attention in children with autism.[7] In one study, researchers suggest that a displayed pattern of delays, absences, or a general impaired response to stimuli (hyporesponsiveness) and a fascination with intense or repetitive stimulation (sensory seeking) is more likely in nonverbal children with autism, suggesting that both hyporesponsiveness and sensory seeking is related to poor communication outcomes in children with ASD.[1]
## Potential causes[edit]
### The amygdala theory[edit]
There is a growing body of tentative evidence indicating the amygdala's involvement in the development of autism. The amygdala theory of autism focuses on the importance of the amygdala in relation to social functioning and observes that autism is largely a severe impairment of social functioning. The amygdala is thought to be associated with the fight or flight response in animals and its activity is heavily correlated with fear in humans. Additionally, it has been heavily implicated in relation to social functioning in various animal studies. Evidence suggests an amygdala hyperactivity model may be more accurate than one comparing it to a lesion.[8]
Lesion studies have shown that amygdala damage results in severe social impairment among animal models. Vervet monkey mothers with amygdala lesions were shown to be much less caring with their young neglecting and even abusing them.[9] Rats with amygdala ablations become much more docile.[9] Monkeys with lesions to the anterior temporal lobe develop a disorder known as Klüver–Bucy syndrome, characterized by loss of fear, hypersexuality, hyperorality, and an inability to recognize visual objects (often, but not always).[9]
Evidence shows the amygdala accounts for the emotional, oral, and sexual abnormalities listed above.[9] These abnormalities coincide with several characteristics of the diagnostic guidelines for autism, at least passably for an animal model.
Post-mortem analysis of humans shows an increased neuronal density in the amygdala in autism compared to controls, indicating a potential linkage and supporting the hyperactivity model.[9]
Several studies presented subjects with ASD photographs of human eyes and had them report the emotional state of the person in the picture. A smaller amygdala was associated with increased response time but not decreased accuracy.[9] There was also significantly less amygdaloid activation in the brains of those with ASD, than controls. Subjects compensated for this lack of amygdaloid activity with increased activation in the temporal lobe, and are associated with verbally labeling images.[8] This activity is thought to imply less usage of emotional/social cues to identify objects and rather more objective, factually based processing. One may extrapolate from this model that patients with autism may learn that a specific facial configuration represents an emotional state and what that emotional state implies socially, but they may not come to truly understand how that person feels. This supports a theory of mind deficit, or inability to empathize with others – a characteristic symptom of ASD.[citation needed]
Studies conducted specifically on nonverbal autistics[which?] provide similar evidence. Brain studies have shown several amygdaloid impairments among those with ASD. The amygdala in those with nonverbal autism have less volume compared to controls, contain a higher density of neurons suggesting hyperconnection, and show a negative correlation between amygdala size and impairment severity among subjects.[8]
Infantile autism is actually associated with an oversized amygdala, there are developmental theories as to how this may occur. Research on major depressive disorder has shown that excessive activation such as stress or fear leads to allostasis, or degeneration of the neurons involved in creating the phenomenon. Initial hypertrophy results in atrophy and reduction of brain size in the given region.[8] Over time, this occurs in patients with severe depression, and they develop a decreased amygdala size. Some scientists[who?] theorize that this is happening early during infancy the autistic brain, accounting for the initial overgrowth and later observed size reduction.[8]
When eye tracking software is employed to record where subjects focus their visual attention on images of human faces, small amygdala volume is associated with decreased eye fixation.[8] Eyes are considered to be especially important for establishing human connection and conveying emotion, thus fixation on them is considered to be a crucial part of identifying people and emotions in a social setting.
In addition to a negative correlation to eye fixation studies showed a smaller amygdala was associated with impairment in nonverbal communication skills as well.[8] This suggests that the amygdala is critical in developing all types of communicative abilities, not just verbal. This suggests the amygdala may play a crucial role in relating to other humans in a way that allows for behavioral mimicry.
Among patients with nonverbal ASD researchers could predict symptom severity based on amygdala activity. Those with the least amygdala activity had the most impaired nonverbal communication abilities, those with the most activity had the strongest communication abilities.[8]
The development of language, similar to the development of most physical skills, relies heavily on mimicry of other humans.[8] ASDs are known to impair one's ability to focus on and relate with people possibly as a result of a damaged amygdala. Nonverbal autistics will often be able to learn more basic communicative skills such as pointing to objects or selecting a picture from a list. These skills are far more simple and do not require the degree of personal connection needed for language development.
It is important to note that these studies must be considered with great caution. Cross-sectional studies can only suggest so much about the pathology of a disorder. Further study, particular longitudinal studies, are needed to gain a more complete understanding.[8] It is also important to recognize that most disorders arise from a complex interworking of the entire brain and restricting a theory to one subsystem would be a mistake, this theory merely suggests how the amygdala may be involved with develop of ASD and provides evidence to support an association.
## Language outcomes[edit]
For nonverbal grade school children and adolescents with autism, communication systems and interventions have been implemented to enhance language and communication outcomes. Speech-generating devices such as tablet computers use visual displays for children who lack verbal language, giving them the task of selecting icons indicating a request or need.[10] For adolescents with nonverbal autism, interventions can condition them to learn more advanced operations on speech-generating devices that require more steps (i.e. turning on device, scrolling through pages), which would allow them to enhance their communicative abilities independently.[10]
The picture exchange system (PECS) is a form of spontaneous communication for children with autism in which an individual selects a picture indicating a request.[11] PECS can be utilized in educational settings and at the child’s home. Longitudinal studies suggest PECS can have long-term positive outcomes for school-aged children with nonverbal autism, specifically their social-communicative skills, such as higher frequencies of joint attention and initiation, and duration of cooperative play,[11] which are all important roles in improving language outcomes.
It has also been suggested that a significant stage in acquiring verbal language is learning how to identify and reproduce syllables of words. One study found that nonverbal and minimally verbal children with autism are capable of enhancing their oral production and vocalizing written words by isolating each syllable of a word one at a time.[5] The process of breaking down a syllable at a time and having it visually displayed and audibly available to the child can prompt him or her to imitate and create nonrandom and meaningful utterances.[5]
Most of these studies contain small sample sizes and were pilot studies, making additional research significant to assess whether these findings can be generalized to all age groups of the same population. Furthermore, most studies on nonverbal autism and speech-generating device communication were based on more basic skills, such as naming pictures and making requests for stimuli, while studies in advanced communication are limited.[12]
## See also[edit]
* Facilitated communication: a scientifically discredited technique which purports to help non-verbal people communicate
* Low-functioning autism: verbal abilities may be lacking
* Language delay and speech delay
* Late talkers: sometimes mistaken as nonverbal autistics
* Nonverbal communication
## References[edit]
1. ^ a b c Patten, Elena; Ausderau, Karla K; Watson, Linda R; Baranek, Grace T (2013). "Sensory Response Patterns in Nonverbal Children with ASD". Autism Research and Treatment. 2013: 436286. doi:10.1155/2013/436286. PMC 3727194. PMID 23956859.
2. ^ a b Bardikoff, Nicole; McGonigle-Chalmers, Margaret (2014). "Testing nonverbal IQ in children with Autism Spectrum Disorders". Research in Autism Spectrum Disorders. 8 (9): 1200–7. doi:10.1016/j.rasd.2014.06.007.
3. ^ Kasari, Connie; Brady, Nancy; Lord, Catherine; Tager-Flusberg, Helen (2013). "Assessing the Minimally Verbal School-Aged Child with Autism Spectrum Disorder". Autism Research. 6 (6): 479–93. doi:10.1002/aur.1334. PMC 4139180. PMID 24353165.
4. ^ Mayo, Jessica; Chlebowski, Colby; Fein, Deborah A.; Eigsti, Inge-Marie (February 2013). "Age of First Words Predicts Cognitive Ability and Adaptive Skills in Children with ASD". Journal of Autism and Developmental Disorders. 43 (2): 253–264. doi:10.1007/s10803-012-1558-0. ISSN 0162-3257. PMC 4386060. PMID 22673858.
5. ^ a b c Vernay, Frédérique; Kahina, Harma; Thierry, Marrone; Jean-Yves, Roussey (2017). "Self-paced segmentation of written words on a touchscreen tablet promotes the oral production of nonverbal and minimally verbal autistic children". Journal of Research in Special Educational Needs. 17 (4): 265–73. doi:10.1111/1471-3802.12384.
6. ^ "What Is Autism? | Autism Speaks". Autism Speaks. Retrieved 2018-10-25.
7. ^ a b Paparella, Tanya; Goods, Kelly Stickles; Freeman, Stephanny; Kasari, Connie (2011). "The emergence of nonverbal joint attention and requesting skills in young children with autism". Journal of Communication Disorders. 44 (6): 569–83. doi:10.1016/j.jcomdis.2011.08.002. PMID 21907346.
8. ^ a b c d e f g h i j Nacewicz, Brendon M; Dalton, Kim M; Johnstone, Tom; Long, Micah T; McAuliff, Emelia M; Oakes, Terrence R; Alexander, Andrew L; Davidson, Richard J (2006). "Amygdala Volume and Nonverbal Social Impairment in Adolescent and Adult Males with Autism". Archives of General Psychiatry. 63 (12): 1417–1428. doi:10.1001/archpsyc.63.12.1417. PMC 4767012. PMID 17146016.
9. ^ a b c d e f Baron-Cohen, S; Ring, H.A; Bullmore, E.T; Wheelwright, S; Ashwin, C; Williams, S.C.R (2000). "The amygdala theory of autism". Neuroscience & Biobehavioral Reviews. 24 (3): 355–64. doi:10.1016/S0149-7634(00)00011-7. PMID 10781695.
10. ^ a b Achmadi, Donna; Kagohara, Debora M; Van Der Meer, Larah; o'Reilly, Mark F; Lancioni, Giulio E; Sutherland, Dean; Lang, Russell; Marschik, Peter B; Green, Vanessa A; Sigafoos, Jeff (2012). "Teaching advanced operation of an iPod-based speech-generating device to two students with autism spectrum disorders". Research in Autism Spectrum Disorders. 6 (4): 1258–64. doi:10.1016/j.rasd.2012.05.005.
11. ^ a b Lerna, Anna; Esposito, Dalila; Conson, Massimiliano; Massagli, Angelo (2014). "Long-term effects of PECS on social-communicative skills of children with autism spectrum disorders: A follow-up study". International Journal of Language & Communication Disorders. 49 (4): 478–85. doi:10.1111/1460-6984.12079. PMID 24655345.
12. ^ Kagohara, Debora M; Van Der Meer, Larah; Ramdoss, Sathiyaprakash; O'Reilly, Mark F; Lancioni, Giulio E; Davis, Tonya N; Rispoli, Mandy; Lang, Russell; Marschik, Peter B; Sutherland, Dean; Green, Vanessa A; Sigafoos, Jeff (2013). "Using iPods® and iPads® in teaching programs for individuals with developmental disabilities: A systematic review". Research in Developmental Disabilities. 34 (1): 147–56. doi:10.1016/j.ridd.2012.07.027. PMID 22940168.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
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*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Nonverbal autism | None | 6,682 | wikipedia | https://en.wikipedia.org/wiki/Nonverbal_autism | 2021-01-18T18:59:54 | {"wikidata": ["Q42417308"]} |
Infectious arthritis is joint pain, soreness, stiffness and swelling caused by a bacterial, viral, or fungal infection that spreads from another part of the body. Depending on the type of infection, one or more joints may be affected. Certain bacteria can cause a form of infectious arthritis called reactive arthritis, which appears to be caused by the immune system reacting to bacteria, rather than by the infection itself. In reactive arthritis, joint inflammation develops weeks, months or even years after the infection. Reactive arthritis happens most commonly after infections of the genital and gastrointestinal tracts. To diagnose infectious arthritis, your health care provider may do tests of your blood, urine, and joint fluid. Treatment includes medicines and sometimes surgery.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Infectious arthritis | c0003869 | 6,683 | gard | https://rarediseases.info.nih.gov/diseases/6781/infectious-arthritis | 2021-01-18T17:59:46 | {"mesh": ["D001170"], "umls": ["C0003869"], "synonyms": ["Septic arthritis"]} |
A number sign (#) is used with this entry because polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is caused by homozygous or compound heterozygous mutation in the ABHD12 gene (613599) on chromosome 20p11.
Clinical Features
Fiskerstrand et al. (2009) reported a consanguineous Norwegian family in which 3 individuals had a slowly progressive neurologic disorder resembling the clinical features of Refsum disease (266500). The authors suggested naming the disorder PHARC, an acronym that describes the major features of the disorder. Features in childhood included pes cavus and Achilles tendon contractures; 1 had poor hearing in childhood. Hearing loss and visual problems related to cataracts developed in the third decade. Two patients had evidence of retinitis pigmentosa, whereas the third had borderline normal electroretinogram results. All patients developed ataxic and/or spastic gait disturbances with a progressive sensorimotor peripheral neuropathy. Other features included hyporeflexia, hyperreflexia, extensor plantar responses, and neurogenic changes on EMG. Nerve conduction velocities were decreased, indicating a demyelinating neuropathy. MRI showed minor cerebellar atrophy in 1 patient. Cognition was not affected. Biochemical studies showed normal serum phytanic and pristanic acid levels, as well as normal alpha-oxidation enzymatic activity, thus excluding Refsum disease. The family originated from a small island community, and genealogic studies showed that both sets of parents were descendants of a man born in 1585.
Fiskerstrand et al. (2010) reported 19 persons from 9 families from Norway, United Arab Emirates, United States, and Algeria, with PHARC. The phenotype in general was slowly progressive, with symptom recognition in the teens, and full expression apparent only in adulthood. The Norwegian patients tended to have onset of peripheral neuropathy in adulthood, although many had pes cavus, decreased sensation, and sensorineural hearing loss from childhood. Hearing loss occurred in childhood or teenage years in 4 and in the third or fourth decade in 4. Retinitis pigmentosa and cataracts developed in adulthood. Frank ataxia was variable and also showed a later onset. In the Emirati family, 2 patients were in their twenties, and 1 was age 6 years. Common features included absent tendon reflexes, hearing loss, ataxia, cataracts; and hearing loss occurred in childhood in all 3. Only the older 2 patients had retinitis pigmentosa. There were 7 affected individuals from 4 Algerian families. The patients ranged in age from 10 to 44 years. The older individuals were more severely affected. All patients had some evidence of a polyneuropathy, with hyporeflexia, pes cavus, and/or sensory loss, and most had gait ataxia with onset in the childhood. Four of the older patients had hearing loss, but only 1 had retinitis pigmentosa and cataract. Other common features included extensor plantar responses and cerebellar atrophy. A 50-year-old woman from the U.S., who was of French Canadian origin, developed sensorineural hearing loss at age 17 years, ataxia and dysarthria at 18, and retinitis pigmentosa and cataracts in her twenties. She had pes cavus and hammertoes, and a mild peripheral neuropathy at when examined at age 34 years. She had myoclonic seizures, but cognition was not affected, and the disease showed a slowly progressive course. None of the patients had deficits of cerebral cortical function, although 1 Algerian patient was mentally retarded.
### Clinical Variability
Nishiguchi et al. (2014) studied 3 families with mutations in the ABHD12 gene (see MOLECULAR GENETICS) in which the initial diagnosis was nonsyndromic autosomal recessive retinitis pigmentosa (RP; see 268000). All affected individuals were symptom-free in the first 2 decades of life and presented with night blindness followed by central visual field loss and reduction of visual acuity; posterior subcapsular cataract was also observed in all of the patients. One proband was a 34-year-old Dutch man who did not report any neurologic symptoms but in whom a detailed examination revealed a wide-based gait, peripheral sensitivity loss in the lower extremities, and decreased tendon reflexes. Signs of ataxia included stuttering speech, an ataxic heel-knee sign, and intentional tremor with the finger-to-nose test. Audiography revealed significantly decreased sensitivity to frequencies higher than 1500 Hz to levels of 40 dB or lower in both ears. Another proband, a 38-year-old Spanish woman, was found to have bilateral hearing loss; in addition, electroneurographic study was consistent with a moderate demyelinating sensorimotor polyneuropathy in the upper and lower limbs, and MRI revealed cerebral and cerebellar atrophy. In the third family, 4 Spanish sibs ranging in age from 66 to 78 years had RP, posterior subcapsular cataract, and sensorineural hearing loss. However, examination revealed no polyneuropathy or ataxia, and their sensorineural hearing loss and cataract were attributed to either age or the normal course of RP. Nishiguchi et al. (2014) suggested that this family expanded the spectrum of phenotypes associated with ABHD12 mutations to include a nonsyndromic form of retinal degeneration.
Mapping
By homozygosity mapping of a consanguineous Norwegian family with PHARC, followed by linkage analysis and fine mapping, Fiskerstrand et al. (2009) identified a 15.96-Mb (9.88-cM) region on chromosome 20p11.21-q12 between D20S477 and D20S107, containing approximately 200 genes (maximum lod score of 6.33). Sequencing of 23 candidate genes failed to demonstrate detrimental sequence variants.
Inheritance
The transmission pattern of PHARC in the Norwegian family reported by Fiskerstrand et al. (2009) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 19 persons from 9 families from Norway, United Arab Emirates, United States, and Algeria, with PHARC, Fiskerstrand et al. (2010) identified 4 different homozygous loss-of-function mutations in the ABHD12 gene (613599.0001-613599.0004). Common mutations were found in families from Norway (613599.0001) and Algeria (613599.0003). All the mutations were predicted to result in complete loss of enzyme function. None of the patients had behavioral disturbances or appetite abnormalities potentially related to increased levels of the endocannabinoid, arachidonoyl glycerol (2-AG). The findings indicated that ABHD12 performs essential functions in the central and peripheral nervous systems and the eye. Fiskerstrand et al. (2010) noted that future drug-mediated interference with this enzyme to treat neurodegenerative diseases must consider the potential risk of long-term effects.
In a 38-year-old Spanish woman and a 34-year-old Dutch man who were initially believed to have nonsyndromic retinitis pigmentosa, Nishiguchi et al. (2014) identified homozygosity and compound heterozygosity, respectively, for mutations in the ABHD12 gene (613599.0005-613599.0007). Detailed examination of the 2 patients revealed that both had hearing loss and neurologic abnormalities, including sensorimotor polyneuropathy. In a Spanish family in which 4 sibs had retinitis pigmentosa, posterior subcapsular cataract, and sensorineural hearing loss, and were negative for known mutations associated with autosomal recessive RP, Nishiguchi et al. (2014) identified compound heterozygosity for a 1-bp deletion and a missense mutation in the ABHD12 gene. No signs of polyneuropathy or ataxia were detected in the 4 affected sibs, and their sensorineural hearing loss and cataract were attributed to either age or the normal course of RP. Nishiguchi et al. (2014) therefore suggested that this family expanded the spectrum of phenotypes associated with ABHD12 mutations to include a nonsyndromic form of retinal degeneration.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural Eyes \- Subcapsular cataracts \- Retinitis pigmentosa \- Optic atrophy \- Nystagmus SKELETAL Feet \- Pes cavus \- Achilles tendon contracture MUSCLE, SOFT TISSUES \- Distal muscle atrophy due to neurologic disease NEUROLOGIC Central Nervous System \- Ataxia \- Spasticity \- Extensor plantar responses \- Hyperreflexia \- Intention tremor \- Dysarthria \- Dysmetria \- Cerebellar atrophy Peripheral Nervous System \- Sensorimotor peripheral neuropathy \- Distal sensory loss \- Demyelinating neuropathy \- Hyporeflexia \- Decreased nerve conduction velocities LABORATORY ABNORMALITIES \- Normal serum phytanic and pristanic acid MISCELLANEOUS \- Onset in childhood or second decade \- Variable phenotype \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the abhydrolase domain-containing protein 12 gene (ABHD12, 613599.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| POLYNEUROPATHY, HEARING LOSS, ATAXIA, RETINITIS PIGMENTOSA, AND CATARACT | c2675204 | 6,684 | omim | https://www.omim.org/entry/612674 | 2019-09-22T16:00:47 | {"doid": ["0080181"], "mesh": ["C567203"], "omim": ["612674"], "orphanet": ["171848"]} |
## Clinical Features
Dianzani et al. (1997) identified 6 unrelated patients with a clinical picture resembling that of autoimmune lymphoproliferative syndrome (ALPS; 601859), but the patients showed no expansion of CD4 (186940)/CD8 (see 186910) double-negative T cells. T cells displayed reduced FAS (134637) capacity to induce programmed cell death, but no mutations of the FAS gene were identified. However, the FAS defect seemed to involve the FAS signaling pathway because ceramide, a second messenger for FAS signaling, did not overcome the programmed cell death defect.
Ramenghi et al. (2000) assessed the inherited component of the Dianzani form of autoimmune lymphoproliferative disease by evaluating FAS- and ceramide-induced T-cell death in both parents and 4 close relatives of 10 unrelated patients with the disorder. Most of them (22 of 24) displayed defective FAS- or ceramide-induced (or both) cell death. Moreover, analysis of the family histories showed that frequencies of autoimmunity and cancer were significantly increased in the paternal and maternal line, respectively. Defective FAS- or ceramide-induced T-cell death was also detected in 9 of 17 autoimmune patients from 7 families displaying more than a single case of autoimmunity within first- or second-degree relatives, examples of the multiple autoimmune syndrome (MAS). Autoimmune disease as displayed by the Dianzani syndrome patients and the MAS families included several organ-specific and systemic forms. Ramenghi et al. (2000) interpreted their findings as indicating that the Dianzani form of autoimmune lymphoproliferative disease is due to accumulation of several defects in the same subject and that these defects predispose to development of cancer or autoimmune diseases other than ALPS or the Dianzani syndrome.
Molecular Genetics
Clementi et al. (2006) identified the ala91-to-val (A91V; 170280.0011) substitution in the PRF1 gene in 6 of 28 DALD patients. Presence of A91V conferred an odds ratio of 3 for DALD, and the odds ratio increased to 17 if variations in the osteopontin (SPP1; 166490) gene associated with increased osteopontin production were also present. However, A91V was relatively frequent (4.6%) in controls. Clementi et al. (2006) suggested that A91V may be a susceptibility factor for DALD in patients with defective FAS function.
Nomenclature
Although Dianzani et al. (1997) referred to this condition as autoimmune lymphoproliferative disease with the symbol ALD, these seem to be unsatisfactory designations because the name is too similar to the autoimmune lymphoproliferative syndrome (ALPS) and the symbol has already been used for adrenoleukodystrophy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| DIANZANI AUTOIMMUNE LYMPHOPROLIFERATIVE DISEASE | c2931071 | 6,685 | omim | https://www.omim.org/entry/605233 | 2019-09-22T16:11:27 | {"mesh": ["C535950"], "omim": ["605233"], "orphanet": ["275523"], "synonyms": ["Alternative titles", "DALD"]} |
Mutagen sensitivity has been found to be increased in patients with environmentally related cancers, including cancers of the head and neck, lung, and colon. In combination with carcinogenic exposure, this susceptibility can greatly influence cancer risk. Hsu et al. (1989) reported that susceptibility to bleomycin-induced (see 602403) chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. Cloos et al. (1999) determined the number of bleomycin-induced breaks per cell for 135 healthy volunteers without cancer. These individuals were from 53 different pedigrees and included 25 monozygotic (MZ) twin pairs, 14 dizygotic (DZ) twin pairs, and 14 families selected on the basis of a first-degree relative who was successfully treated for head and neck cancer and who had no sign of recurrence for at least 1 year. Results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks. On the other hand, genetic influences were statistically significant and accounted for 75% of the total variance.
Wu et al. (2006) used a classic twin study to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals (148 pairs of monozygotic twins, 57 pairs of dizygotic twins, and 50 sibs). Intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sib pairs combined) for sensitivity to 4 different mutagen challenges. Applying biometric genetic modeling, Wu et al. (2006) calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo(a)pyrene diol epoxide, gamma-radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provided strong and direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| MUTAGEN SENSITIVITY | c1864867 | 6,686 | omim | https://www.omim.org/entry/610452 | 2019-09-22T16:04:28 | {"omim": ["610452"]} |
Gestational trophoblastic tumors (GTT) are malignant forms of gestational trophoblastic disease. The tumor always follows pregnancy, most often molar pregnancy (hydatidiform mole; see this term). Four histological subtypes have been described: invasive mole, gestational choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor (see these terms).
## Epidemiology
Exact annual incidence is not known but it is estimated to be about 1/1,000,000 women.
## Clinical description
GTTs occur following hydatidiform moles (see this term) (15% of complete moles and about 3% of partial moles), following spontaneous miscarriage (1/150) or childbirth (1/40,000). Indicative signs are an absence of normalization or a secondary elevation of total serum chorionic gonadotropin (hCG) levels after evacuation of a hydatidiform mole (more than 60% of cases), persistent unexplained metrorrhagia following spontaneous miscarriage or voluntary termination of pregnancy (VTP) (about 30% of cases) and very occasionally, unexplained metrorrhagia in the weeks or months following normal childbirth or ectopic pregnancy (about 10% of cases). Exceptionally, metastasis may be a sign of the disease in women of childbearing age.
## Etiology
The etiology of gestational trophoblastic tumors is not known. Identification of a GTT is based on a total serum hCG assay, which is recommended following hydatidiform moles in patients with metrorrhagia persisting for more than six weeks after pregnancy, and in any patient of childbearing age who has metastasis (lung, liver, brain, kidney, vagina) with no known primary tumor.
## Diagnostic methods
Diagnosis of a post-molar GTT relies on one of the following four criteria: stable hCG levels (variation of less than 10%) with at least four weekly assays over a period of at least three weeks (days 1, 7, 14, 21), increase of at least 10% in hCG with at least three weekly assays over at least two weeks (days 1, 7, 14), persistence of detectable hCG values for more than six months following mole evacuation or based on histological diagnosis of a choriocarcinoma.
## Differential diagnosis
GTTs must not be confused with hydatidiform moles (see this term) and, for choriocarcinomas, with non-gestational choriocarcinomas, which are most often ovarian.
## Management and treatment
As soon as the diagnosis is made, staging must be performed to identify frequent metastases. Staging involves endovaginal pelvic color doppler ultrasound, pelvic and cerebral MRI, and abdominal/chest CT. A lung X-ray must be performed to calculate the FIGO 2000 score (International Federation of Obstetrics and Gynecology) in case of lung metastasis on CT. This score makes it possible to distinguish between low-risk GTTs (score of 6 or lower) and high-risk GTTs (score of 7 or higher). Management should be multidisciplinary and must be discussed by a panel of physicians in a specialized center. Low-risk tumors are treated by systemic single-agent chemotherapy, e.g. methotrexate (marketing authorization). High-risk tumors are treated first line with systemic multi-agent chemotherapy. Hysterectomy can of course not be considered for first-line treatment in women who wish to become pregnant, unless there is no option. Placental site trophoblastic tumors and epithelioid trophoblastic tumors are special cases: the FIGO score is not appropriate and total hysterectomy is the standard treatment as these tumors are usually chemo-resistant.
## Prognosis
The overall recovery rate is around 99%. The prognosis is very closely related to the rapidity of diagnosis, the risk level of the tumor (low or high) and the suitability of treatment.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Gestational trophoblastic neoplasm | c1135868 | 6,687 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=59305 | 2021-01-23T18:41:52 | {"gard": ["6498"], "mesh": ["D031901"], "umls": ["C1135868"], "synonyms": ["GTN"]} |
A number sign (#) is used with this entry because complement component 8 deficiency type II (C8B deficiency) is caused by homozygous or compound heterozygous mutation in the C8B gene (120960) on chromosome 1p32.
Description
Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. Most such patients are discovered among those having their first episode of meningitis at ages older than 10 years (Ross and Densen, 1984).
Two types of inherited C8 deficiency have been reported in man: type I (613790), in which only C8 alpha (C8A, 120950) and C8 gamma (C8G; 120930) are deficient, and type II, in which only C8 beta is deficient (Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically indistinguishable (Ross and Densen, 1984).
Clinical Features
Wulffraat et al. (1994) described a family in which a 13-year-old boy was found to be homozygous for C8B deficiency and to have juvenile chronic arthritis of 6 months' duration. Antinuclear antibodies, anti-double-stranded DNA antibodies, and rheumatoid factor were not detected. The same deficiency was present in the patient's sister, and both parents were heterozygous. There was no history of meningococcal disease in the family.
Pathogenesis
Activation of the terminal complement components (C5-C9) results in the assembly of the membrane attack complex. Effective insertion of this complex into cell membranes is responsible for C-dependent bactericidal activity, as well as the lysis or death of other cell types. A deficiency of any of the terminal C components is associated with the absence of this functional activity, and accounts for the substantially increased risk of developing meningococcal disease observed in individuals with such a deficiency (summary by Saucedo et al., 1995).
Population Genetics
Ross and Densen (1984) stated that C8B deficiency had been reported exclusively in Caucasians (12 kindreds), and that C8AG deficiency had been found in 4 Black families, 1 Hispanic family, and no Caucasian families.
Saucedo et al. (1995) stated that C8B deficiency has been reported primarily in Caucasians, whereas C8AG deficiency has been reported predominantly in Blacks and Hispanics.
Mapping
In a family with deficiency of C8 beta, Pericak-Vance et al. (1982) found a suggestion of linkage of the disorder to 1p markers: lod score of 1.44 for UMPK at male theta of 0.14 and female theta of 0.17; lod score of 1.65 for PGM1 at male theta of 0.0 and female theta of 0.22.
Tanaka et al. (1991) studied deficient activity of the beta subunit of C8 in mice and demonstrated by linkage studies that this form of C8 deficiency is controlled by a single recessive gene, designated C8b, located on mouse chromosome 4.
Molecular Genetics
Raum et al. (1979) used serum from patients with type I deficiency (which lacks alpha-gamma chains but has normal beta chains) to raise antisera against beta C8 and to demonstrate polymorphism thereof.
By direct sequence analysis of all exon-specific PCR products from normal and C8B-deficient persons, Kaufmann et al. (1993) found a single C-T change in exon 9 leading to a stop codon (120960.0001). An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the TaqI polymorphism located in intron 11, 5 families with 7 C8B-deficient members were investigated. The mutant allele was observed in all 7 affected members of the families investigated and could therefore be regarded as a major cause of C8B deficiency in Caucasians. Five patients were homozygous for the mutation. In the 2 others, only 1 chromosome carried the mutation; the molecular nature of the other allele had not been determined.
In a study of 34 unrelated families with C8B deficiency from the U.S. and the former U.S.S.R., Saucedo et al. (1995) found that 59 (86%) of 69 null alleles were due to the C-to-T transition in exon 9. An additional 6 null alleles were caused by C-to-T transitions in exons 3 (120960.0003 and 120960.0004) and 6 (120960.0002). Two null alleles were caused by cytosine deletions in exons 3 (120960.0005) and 5 (120960.0006). Of the null alleles, 97% were C-to-T transitions in which an arg (64 alleles) or gln (1 allele) was replaced by a stop codon.
History
Tedesco et al. (1983) studied restoration of hemolytic activity in sera from 7 unrelated persons with C8 deficiency. The sera fell into 2 groups, depending on whether hemolytic activity was restored by addition of the beta subunit (group 1) or the alpha-gamma subunit (group 2) purified from normal human C8. A dysfunctional C8 was demonstrated by antigenic analysis in all 4 sera of group 1. A different dysfunctional C8 was found in one of the group 2 cases. Chromatographic analysis demonstrated that the generation of hemolytic activity in the mixture of 2 sera resulted from reconstitution of the C8 molecule rather than the sequential action of the two C8 subunits. By the technique used by Rogde et al. (1984), 2 different protein patterns, each with polymorphism, were demonstrated: A for acidic; B for basic. The B pattern, which was absent from a serum with known beta-chain deficiency, reflected the presence of 4 or 5 frequently occurring alleles in the Norwegian population.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Meningitis IMMUNOLOGY \- C8 deficiency \- Recurrent neisserial infections \- Antigenically defective C8 detected MOLECULAR BASIS \- Caused by mutation in the complement component-8, beta polypeptide gene (C8B, 120960.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| COMPLEMENT COMPONENT 8 DEFICIENCY, TYPE II | c3151080 | 6,688 | omim | https://www.omim.org/entry/613789 | 2019-09-22T15:57:32 | {"doid": ["0060302"], "omim": ["613789"], "orphanet": ["169150"], "synonyms": ["Immunodeficiency due to C5 to C9 component complement deficiency", "Alternative titles", "COMPLEMENT COMPONENT 8B DEFICIENCY", "C8B DEFICIENCY", "C8 DEFICIENCY, TYPE II", "Terminal complement pathway deficiency", "C8 BETA DEFICIENCY"]} |
Raphaelson et al. (1983) described 2 brothers who had onset of precocious puberty (due to Leydig cell hyperplasia) and spastic paraplegia at the age of 2 years. Both later had moderate mental retardation. Relatives (2 sisters, father, paternal grandfather, paternal half brother) had brisk leg reflexes and dysarthria in a pattern suggesting autosomal dominant inheritance with variable expression.
Endocrine \- Precocious puberty Neuro \- Spastic paraplegia \- Mental retardation \- Brisk leg reflexes \- Dysarthria Lab \- Leydig cell hyperplasia Inheritance \- Autosomal dominant with variable expression ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| SPASTIC PARAPLEGIA WITH PRECOCIOUS PUBERTY | c1866850 | 6,689 | omim | https://www.omim.org/entry/182820 | 2019-09-22T16:34:39 | {"mesh": ["C536874"], "omim": ["182820"], "orphanet": ["2826"], "synonyms": ["Alternative titles", "PRECOCIOUS PUBERTY WITH SPASTIC PARAPLEGIA"]} |
In 10 persons in 4 generations, Furukawa et al. (1968) found muscular atrophy, ataxia, retinitis pigmentosa, and diabetes mellitus. The diabetes was of relatively late onset. The disorder resembled Refsum syndrome (266500) except in its mode of inheritance. Several instances of male-to-male transmission were observed.
Endocrine \- Diabetes mellitus Eyes \- Retinitis pigmentosa Muscle \- Muscular atrophy Neuro \- Ataxia Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| MUSCULAR ATROPHY, ATAXIA, RETINITIS PIGMENTOSA, AND DIABETES MELLITUS | c0342281 | 6,690 | omim | https://www.omim.org/entry/158500 | 2019-09-22T16:37:57 | {"mesh": ["C562774"], "omim": ["158500"], "orphanet": ["2579"]} |
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (December 2012) (Learn how and when to remove this template message)
Stickler syndrome (hereditary progressive arthro-ophthalmopathy)
Stickler syndrome is inherited in an autosomal dominant pattern.
SpecialtyMedical genetics
Stickler syndrome (hereditary progressive arthro-ophthalmodystrophy) is a group of very rare genetic disorders affecting connective tissue, specifically collagen.[1] Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint and skeletal problems. It was first studied and characterized by Gunnar B. Stickler in 1965.[1]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Genetics
* 4 Diagnosis
* 4.1 Types
* 5 Treatment
* 6 Epidemiology
* 7 History
* 8 See also
* 9 References
* 10 External links
## Signs and symptoms[edit]
Individuals with Stickler syndrome experience a range of signs and symptoms. Some people have no signs and symptoms; others have some or all of the features described below. In addition, each feature of this syndrome may vary from subtle to severe.[2]
A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called the Pierre Robin sequence, is common in children with Stickler syndrome. Robin sequence includes a U-shaped or sometimes V-shaped cleft palate (an opening in the roof of the mouth) with a tongue that is too large for the space formed by the small lower jaw. Children with a cleft palate are also prone to ear infections and occasionally swallowing difficulties.
Many people with Stickler syndrome are very nearsighted (described as having high myopia) because of the shape of the eye. People with eye involvement are prone to increased pressure within the eye (ocular hypertension) which could lead to glaucoma and tearing or detachment of the light-sensitive retina of the eye (retinal detachment). Cataract may also present as an ocular complication associated with Stickler's Syndrome. The jelly-like substance within the eye (the vitreous humour) has a distinctive appearance in the types of Stickler syndrome associated with the COL2A1 and COL11A1 genes. As a result, regular appointments to a specialist ophthalmologist are advised. The type of Stickler syndrome associated with the COL11A2 gene does not affect the eye.[3]
People with this syndrome have problems that affect things other than the eyes and ears.[2] Arthritis, abnormality to ends of long bones, vertebrae abnormality, curvature of the spine, scoliosis, joint pain, and double jointedness are all problems that can occur in the bones and joints. Physical characteristics of people with Stickler can include flat cheeks, flat nasal bridge, small upper jaw, pronounced upper lip groove, small lower jaw, and palate abnormalities, these tend to lessen with age and normal growth and palate abnormalities can be treated with routine surgery. Another characteristic of this syndrome is a mild spondyloepiphyseal dysplasia which can cause reduced height.
Another sign of Stickler syndrome is mild to severe hearing loss that, for some people, may be progressive (see hearing loss with craniofacial syndromes). The joints of affected children and young adults may be very flexible (hypermobile). Arthritis often appears at an early age and worsens as a person gets older. Learning difficulties not due to a deficit in intelligence can also occur because of hearing and sight impairments if the school is not informed and the student is not assisted within the learning environment.[4][5]
Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.
## Causes[edit]
The syndrome is thought to arise from a mutation of several collagen genes during fetal development. It is a sex independent autosomal dominant trait meaning a person with the syndrome has a 50% chance of passing it on to each child. There are three variants of Stickler syndrome identified, each associated with a collagen biosynthesis gene. A metabolic defect concerning the hyaluronic acid and the collagen of the 2-d type is assumed to be the cause of this syndrome.
## Genetics[edit]
Mutations in the COL11A1, COL11A2 and COL2A1 genes cause Stickler syndrome. These genes are involved in the production of type II and type XI collagen. Collagens are complex molecules that provide structure and strength to connective tissue (the tissue that supports the body's joints and organs). Mutations in any of these genes disrupt the production, processing, or assembly of type II or type XI collagen. Defective collagen molecules or reduced amounts of collagen affect the development of bones and other connective tissues, leading to the characteristic features of Stickler syndrome.[3][6][2][5][7]
Other, as yet unknown, genes may also cause Stickler syndrome because not all individuals with the condition have mutations in one of the three identified genes.[8]
## Diagnosis[edit]
### Types[edit]
Genetic changes are related to the following types of Stickler syndrome:[3][6]
* Stickler syndrome, COL2A1 (75% of Stickler cases)
* Stickler syndrome, COL11A1
* Stickler syndrome, COL11A2(non-ocular)
* Stickler syndrome, COL9A1 (recessive variant)
* Stickler syndrome, COL9A2 (recessive variant)
* Stickler syndrome, COL9A3 (recessive variant)
* Stickler Syndrome, LOX3 (Recessive, 7 cases reported)
Whether there are two or three types of Stickler syndrome is controversial. Each type is presented here according to the gene involved. The classification of these conditions is changing as researchers learn more about the genetic causes.
## Treatment[edit]
Many professionals that are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists, occupational therapists, physical therapists and rheumatologists.
## Epidemiology[edit]
In the US, the estimated prevalence of Stickler syndrome is about 1 in 10,000 people, but it can affect as few as 1 in 1,000,000 in other areas of the world.[citation needed]
## History[edit]
Scientists associated with the discovery of this syndrome include:
* B. David (medicine)
* Gunnar B. Stickler
* G. Weissenbacher
* Ernst Zweymüller
## See also[edit]
* Mandy Haberman, invented the Haberman Feeder when her daughter, born with Stickler syndrome, required special feeding due to cleft palate.
* Marshall syndrome
* Pierre Robin syndrome
## References[edit]
1. ^ a b Stickler G. B.; Belau P. G.; Farrell F. J.; Jones J. F.; Pugh D. G.; Steinberg A. G.; Ward L. E. (1965). "Hereditary Progressive Arthro-Ophthalmopathy". Mayo Clin Proc. 40: 433–55. PMID 14299791.
2. ^ a b c Richards AJ, Baguley DM, Yates JR, Lane C, Nicol M, Harper PS, Scott JD, Snead MP (2000). "Variation in the vitreous phenotype of Stickler syndrome can be caused by different amino acid substitutions in the X position of the type II collagen Gly-X-Y triple helix". Am J Hum Genet. 67 (5): 1083–94. doi:10.1016/S0002-9297(07)62938-3. PMC 1288550. PMID 11007540.
3. ^ a b c Annunen S, Korkko J, Czarny M, Warman ML, Brunner HG, Kaariainen H, Mulliken JB, Tranebjaerg L, Brooks DG, Cox GF, Cruysberg JR, Curtis MA, Davenport SL, Friedrich CA, Kaitila I, Krawczynski MR, Latos-Bielenska A, Mukai S, Olsen BR, Shinno N, Somer M, Vikkula M, Zlotogora J, Prockop DJ, Ala-Kokko L (1999). "Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes". Am J Hum Genet. 65 (4): 974–83. doi:10.1086/302585. PMC 1288268. PMID 10486316.
4. ^ Admiraal RJ, Szymko YM, Griffith AJ, Brunner HG, Huygen PL (2002). "Hearing impairment in Stickler syndrome". Adv Otorhinolaryngol. Advances in Oto-Rhino-Laryngology. 61: 216–23. doi:10.1159/000066812. ISBN 3-8055-7449-5. PMID 12408087.
5. ^ a b Nowak CB (1998). "Genetics and hearing loss: a review of Stickler syndrome". J Commun Disord. 31 (5): 437–53, 453–4. doi:10.1016/S0021-9924(98)00015-X. PMID 9777489.
6. ^ a b Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI (2003). "The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1". Genet Med. 5 (1): 21–7. doi:10.1097/00125817-200301000-00004. PMID 12544472.
7. ^ Snead MP, Yates JR (1999). "Clinical and Molecular genetics of Stickler syndrome". J Med Genet. 36 (5): 353–9. doi:10.1136/jmg.36.5.353 (inactive 2021-01-11). PMC 1734362. PMID 10353778.CS1 maint: DOI inactive as of January 2021 (link)
8. ^ Parke DW (2002). "Stickler syndrome: clinical care and molecular genetics". Am J Ophthalmol. 134 (5): 746–8. doi:10.1016/S0002-9394(02)01822-6. PMID 12429253.
## External links[edit]
Classification
D
* ICD-10: Q87.8
* ICD-9-CM: 759.89
* OMIM: 108300 277610 184840
* MeSH: C537492
* DiseasesDB: 29327
* GeneReviews/NCBI/NIH/UW entry on Stickler Syndrome
* v
* t
* e
Diseases of collagen, laminin and other scleroproteins
Collagen disease
COL1:
* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7
COL2:
* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)
COL3:
* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome
COL4:
* Alport syndrome
COL5:
* Ehlers–Danlos syndrome, types 1 & 2
COL6:
* Bethlem myopathy
* Ullrich congenital muscular dystrophy
COL7:
* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn
COL8:
* Fuchs' dystrophy 1
COL9:
* Multiple epiphyseal dysplasia 2, 3, 6
COL10:
* Schmid metaphyseal chondrodysplasia
COL11:
* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17:
* Bullous pemphigoid
COL18:
* Knobloch syndrome
Laminin
* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome
Other
* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21
see also fibrous proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Stickler syndrome | c0265253 | 6,691 | wikipedia | https://en.wikipedia.org/wiki/Stickler_syndrome | 2021-01-18T18:45:55 | {"gard": ["10782"], "mesh": ["C537492"], "umls": ["C0265253"], "icd-9": ["759.89"], "icd-10": ["Q89.8"], "orphanet": ["828"], "wikidata": ["Q2288646"]} |
Multiple congenital anomalies, prominently including malformations of the head and face (small, malformed, or missing ears, micrognathia, and cleft palate), heart (particularly conotruncal defects and aortic arch anomalies), and central nervous system (especially hydrocephalus and posterior fossa abnormalities), result from maternal use of isotretinoin, a vitamin A analog for treatment of acne (Benke, 1984; Braun et al., 1984; Lott et al., 1984; Lammer et al., 1985). The associated anomalies are also consistent with those described for excessive maternal vitamin A use. Kawashima et al. (1987) described 3 male sibs with findings consistent with isotretinoin embryopathy; each had malformations of the ears and an interrupted aortic arch. The mother of the patients, however, had no prenatal history of exposure to isotretinoin, and her diet was not unusual. The patients had normal lymphocytes and serum calcium values, making the diagnosis of DiGeorge syndrome (188400) untenable.
Guion-Almeida et al. (2000) described a Brazilian boy with the same abnormalities as those described by Kawashima et al. (1987), although middle and inner ear defects were also present. Guion-Almeida and Kokitsu-Nakata (2003) described a single case. Their patient had a complex heart defect, and computed tomography of the temporal bone showed agenesis of the external auditory canal on the left and ossicular chain abnormalities bilaterally. All 5 reported cases have been in males, and parental consanguinity was not described in any. All 5 patients died before the second year of life.
Derbent et al. (2005) reported a male patient with right microtia, atresia of the external auditory canal, growth retardation, a complex heart defect, and extra-lobar pulmonary sequestration. The cardiac anomalies were persistent left superior vena cava, aortic stenosis, bicuspid aortic valves and subaortic membrane. Spinal films revealed complete fusion of the C2-C3 and C5-C6 vertebrae, and scoliosis of the lumbar spine. The patient's mental development was normal, and there were no abnormalities on ophthalmologic examination. Derbent et al. (2005) suggested that their patient and 5 previously reported patients (Kawashima et al., 1987; Guion-Almeida et al., 2000; Guion-Almeida and Kokitsu-Nakata, 2003) had a variant of the oculoauriculovertebral spectrum, with the cardinal features of microtia, atresia of the external auditory canal, complex cardiac defects, growth retardation, normal mental and motor development in most cases, and vertebral anomalies. Because all 6 patients were male, Derbent et al. (2005) raised the possibility of X-linked inheritance.
Cardiac \- Conotruncal defect \- Aortic arch anomaly HEENT \- Small ears \- Malformed ears \- Absent ears \- Micrognathia \- Cleft palate Neuro \- Hydrocephalus \- Posterior fossa anomaly Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| ISOTRETINOIN EMBRYOPATHY-LIKE SYNDROME | c0432364 | 6,692 | omim | https://www.omim.org/entry/243440 | 2019-09-22T16:26:16 | {"mesh": ["C535542"], "omim": ["243440"], "orphanet": ["2306"], "synonyms": ["Alternative titles", "MICROTIA-AORTIC ARCH SYNDROME"]} |
A number sign (#) is used with this entry because combined oxidative phosphorylation deficiency-5 (COXPD5) can be caused by homozygous mutation in the MRPS22 gene (605810) on chromosome 3q23.
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Clinical Features
Saada et al. (2007) reported 3 sibs, born of consanguineous parents, with antenatal onset of a severe mitochondrial disorder. Late in gestation, ultrasound showed generalized edema, especially of the neck, labia, and palms, with prominent subcutaneous edema and ascites at birth. Laboratory investigations showed severe lactic acidemia and increased serum ammonia. Hypertrophic cardiomyopathy and tubulopathy developed within the first week, and the infants died within the first month of life. Skeletal muscle biopsy of 1 affected infant showed that enzymatic activities of mitochondrial complexes I, II, IV, and V were reduced to between 8 and 30% of normal controls, but complex II activity was normal. Southern blot analysis showed decreased mtDNA content.
Smits et al. (2011) reported a boy, born of consanguineous Pakistani parents, with combined oxidative phosphorylation deficiency-5. At birth, the patient had microcephaly, dilated cardiomyopathy, dysmorphic features, and hypotonia. He developed severe chronic metabolic acidosis and had transient seizures at age 2. At age 5.5 years, he had very poor growth, lack of development, truncal hypotonia, and spastic tetraplegia. He did not develop tubulopathy. Brain MRI showed hypoplasia of the corpus callosum, leukoencephalopathy, and delayed myelination. Studies in patient fibroblasts showed that activities of mitochondrial respiratory chain complexes I, III, and IV were reduced to between 36 and 59% of controls. Pulse labeling of mitochondrial protein synthesis products showed a marked and generalized defect in mitochondrial translation, which was about 26% that of controls.
Molecular Genetics
By homozygosity mapping, followed by sequence analysis, Saada et al. (2007) identified a homozygous mutation in the MRPS22 gene (605810.0001) in 3 sibs with combined mitochondrial oxidative phosphorylation deficiency. In vitro studies showed that recombinant MRPS22 restored COX enzyme activities in patient cells.
In a Pakistani boy with COXPD5, Smits et al. (2011) identified a homozygous mutation in the MRPS22 gene (L215P; 605810.0002).
INHERITANCE \- Autosomal recessive GROWTH Other \- Very poor growth HEAD & NECK Head \- Microcephaly Face \- Retrognathia Ears \- Low-set ears \- Posteriorly rotated ears Neck \- Redundant neck skin CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy ABDOMEN \- Ascites GENITOURINARY Kidneys \- Tubulopathy (1 family) MUSCLE, SOFT TISSUES \- Edema \- Hypotonia NEUROLOGIC Central Nervous System \- Psychomotor retardation, profound, in those who survive \- Corpus callosum hypoplasia \- Leukoencephalopathy \- Seizures \- Delayed myelination \- Truncal hypotonia \- Spastic quadriplegia METABOLIC FEATURES \- Metabolic acidosis, severe LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased serum ammonia \- Skeletal muscle shows decreased activities of mitochondrial respiratory complexes I, III, IV, and V MISCELLANEOUS \- Antenatal onset \- Death often in first months of life \- Two families have been reported (as of June 2011) MOLECULAR BASIS \- Caused by mutation in the mitochondrial ribosomal protein S22 gene (MRPS22, 605810.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 5 | c2673642 | 6,693 | omim | https://www.omim.org/entry/611719 | 2019-09-22T16:03:03 | {"doid": ["0060286"], "mesh": ["C567126"], "omim": ["611719"], "orphanet": ["137908"]} |
Mixed connective tissue disease
Other namesSharp's syndrome[1]
SpecialtyImmunology, rheumatology
Differential diagnosisCPT2.
Mixed connective tissue disease commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms of systemic lupus erythematosus (SLE), scleroderma, and polymyositis.[2] The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. MCTD was characterized as an individual disease in 1972 by Sharp et al.,[3][4] and the term was introduced by Leroy[5] in 1980.[6]
It is sometimes said to be the same as undifferentiated connective tissue disease,[1] but other experts specifically reject this idea[7] because undifferentiated connective tissue disease is not necessarily associated with serum antibodies directed against the U1-RNP, and MCTD is associated with a more clearly defined set of signs/symptoms.[7]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Standard
* 5.2 Investigational
* 6 Prognosis
* 6.1 Disease progression
* 7 Epidemiology
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
Differential diagnosis CPT2 MCTD combines features of scleroderma, myositis, systemic lupus erythematosus, and rheumatoid arthritis[8] (with some sources adding polymyositis, dermatomyositis, and inclusion body myositis)[9] and is thus considered an overlap syndrome.
The initial clinical manifestations of MCTD usually are unspecific, they can consist of general malaise, arthralgias, myalgias, and fever. The specific signs to suspect this disease is the presence of positive antinuclear antibodies (ANA), specifically anti-RNP, associated with Raynaud's phenomenon.[4] Almost every organ can be affected by MCTD.[2] Raynaud's phenomenon is the most common presenting symptom seen in patients, with arthralgia and swollen hands being the second and third most common respectively.[3] With patients that meet full criteria for MCTD, arthritis is the most common symptom with Raynaud's, swollen hands, leukopenia/lymphopenia, and heartburn following in descending order. A 2016 epidemiological population based study found 3.6 years to be the average amount of time from the first manifestations of the disease until all the criteria for diagnosis were met.[3]
Manifestations include:
* Skin: Raynaud's phenomenon is universal and almost always is present at the beginning of the disease course. The absence puts the diagnosis in question. The capillary alterations are similar to that of scleroderma. Other cutaneous alterations can be observed similar to the types observed in LES and scleroderma.[citation needed]
* Arthritis: Swollen fingers and occasionally diffuse edema are distinctive signs. Arthritis usually is more frequent and severe than that observed in SLE. Approximately 60% present with an obvious arthritis, with deformities similar to those observed in rheumatoid arthritis.[citation needed]
* Myositis: Myalgias – muscular aches and pains – are common, but in the majority of patients muscular debilitation, electromyographic alterations, and elevations in muscular enzymes, like in pure polymyositis are not observed.[citation needed]
* Cardiac disease: Pericarditis is the most common cardiac manifestation, observed in 10–30% of patients. Myocardial involvement can also be observed, usually secondary to pulmonary hypertension, as well as conduction anomalies.
* Pulmonary involvement: Is observed in 75% of patients. It can present as pleural effusion, pulmonary hypertension, interstitial lung disease, thromboembolic disease, and others.[citation needed]
* Renal disease: The absence of severe renal disease is a marker of MCTD. Membranous nephropathy can be observed in some cases.[citation needed]
* Gastrointestinal disease: The most common change is the alteration of esophageal motility like that observed in scleroderma.
* Central nervous system involvement (CNS): The original description of this disease stressed the absence of changes to the CNS, however, there have been trigeminal neuropathies (cranial nerve V), sensorineural hearing loss, and headaches observed in patients with MCTD. [citation needed]
* Hematologic anomalies: The presence of mild anemia and hypergammaglobulinemia are common, other hematologic anomalies such as those observed in SLE can also be observed.[citation needed]
* Laboratory value changes: Rheumatoid factor is positive in 50–70% of patients, and anti–citrullinated protein antibody is detected in 50% of patients. The universal serological findings in patients with MCTD is the presence of anti-nuclear antibody, with anti-nRNP specificity, especially antibodies against protein 68 kD.[citation needed]
## Genetics[edit]
The contribution of genetics toward developing MCTD is unknown.[10] Family members have been known to develop MCTD suggesting that genetics may play a role in MCTD, however most cases present individually.[11] As MCTD can present with comorbid connective tissue diseases there must be a genetic link, however it has not yet been discovered. DNA methylation may affect the as yet unknown genetic risks of this disease as patients with MCTD have decreased DNA methylation levels in opposition to their healthy counterparts.[citation needed]
## Pathophysiology[edit]
MCTD is an autoimmune disorder. Anti-RNP antibodies develop against RNP when RNP is found outside of the nucleus. RNP is immunologically protected due to its location, however if a cell dies and RNP is no longer contained in the nucleus and thus unprotected, the immune system can respond by forming antibodies due to cellular mimicry. Risk to develop MCTD can increase if the body has exposed to molecules or viruses with a similar structure to RNP in the past.[12]
There are currently no known environmental factors or triggers contributing to MCTD.[citation needed]It has been associated with HLA-DR4.[13]
## Diagnosis[edit]
Distinguishing laboratory characteristics are a positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody.[14][15]
After the original 1972 description of MCTD by Sharp, there was some controversy over whether MCTD was a distinct connective tissue disease, however after four decades and more than 2000 publications, it seems that there is a consensus that MCTD should be considered a distinctive clinical entity, and is thus considered as such by the majority of rheumatologists,[16] however there is a subgroup of patients that could evolve in their disease course towards another connective tissue disease.
Although almost any organ can be affected by MCTD, there are various clinical manifestations that make it more likely to suspect the disease is MCTD over other connective tissue diseases:[2]
1. Raynaud’s phenomenon.
2. Edematous hands and swollen fingers.
3. Arthritis more severe than that of SLE.
4. Pulmonary hypertension (does not need to be pulmonary fibrosis) differentiates MCTD from SLE and scleroderma.
5. Anti-RNP antibodies in elevated levels, especially antibodies against protein 68 kD.
6. Absence of severe renal or CNS disease.
Several criteria have been described to standardize the diagnosis of the disease, some of the most used being those of Alarcón-Segovia, although there are no universally accepted criteria.[17][18][19] In general the criteria require the presence of high titres of anti-RNP antibodies, the presence of some characteristic signs of the disease –Raynaud or swollen hands/fingers– and the presence of some clinical manifestations of at least two other connective tissue diseases –SLE, scleroderma, polymyositis.[citation needed]
A. Serologic criteria:
Positive Anti-RNP at a titre> 1:1600 by hemagglutination
B. Clinical Criteria
1\. Edema of the hands
2\. Synovitis
3\. Myositis
4\. Raynaud’s phenomenon
5\. Acrosclerosis
MCTD is present with:
Criteria A together with 3 or more clinical criteria
–one of which must be synovitis or myositis–
It is often several years before sufficient signs and symptoms appear to make the diagnosis of MCTD, relative to the more sequential clinical manifestations of SLE, scleroderma, and polymyositis, so often, in the initial phases, the diagnosis most appropriate for patients is “undifferentiated connective tissue disease”.[19]
If the patient has edematous hands and/or swollen fingers in conjunction with elevated titers of antinuclear antibodies, an elevated titre of anti-U1 RNP antibody is a good predictor of progressing to MCTD.[20] The presence of this specific antibody is sine qua non for the diagnosis of MCTD,[19] although its isolated presence does not guarantee that a patient has MCTD or will develop it. If the dominant autoantibodies are antiDNAn, Sm, Scl70 or Ro, it is likely the patient will develop another connective disease distinct from MCTD. The clinical manifestations of MCTD appear correlated more intensely to the antibodies against protein A’ and 68 kD of the U1 RNP complex. The typical phenotype of MCTD also appears to be in part genetically determined, as patients with MCTD are associated with HLA-DR4 or HLA-DR2, meanwhile those with SLE are associated with HLA-DR3 and those with scleroderma are associated with HLA-DR5.[21]
SLE, scleroderma, and in MCTD have antibodies against anti-U1-snRNP at differing percentages. These antibodies are in most MCTD patients but are seen in only 30-35% of SLE and 2-14% of scleroderma patients, therefore they can help differentiate MCTD from other connective tissue disorders. There are different haplotypes of SNRNP70 which due to their differences in patients with MCTD versus those with SLE or scleroderma help substantiate the claim that MCTD is a separate disease. The T-G-CT-G haplotype is more common in patients with MCTD, whereas the T-G-C-G haplotype is more commonly seen in scleroderma and SLE.[22]
## Treatment[edit]
Although MCTD was originally described as a disease with a good treatment response to corticosteroids, the treatment of the disease is based on the specific manifestations and clinical complications, similar to how other signs and symptoms are treated in other connective tissue disease. [23][24]
### Standard[edit]
For arthritis, non-steroidal anti-inflammatories or low dose prednisone are usually used, which can be used in association with methotrexate or hydroxychloroquine. Temporomandibular joint arthritis has been shown to be successfully treated with condylar reconstruction using chondral grafts.[25] Higher doses of corticosteroids (0.25 to 1 mg/kg/day) are used in complications such as myositis, meningitis, pleuritis, pericarditis, myocarditis, interstitial lung disease, or hematologic abnormalities. On the contrary, Raynaud’s phenomenon, acrosclerosis or peripheral neuropathies are usually resistant to corticosteroids. Cyclophosphamide are useful in interstitial lung disease and in the eventual serious renal involvement. In cases of myositis or thrombocytopenias resistant to corticosteroids, intravenous immunoglobulins may be useful. For Raynaud, general measures (such as tobacco cessation, protection against the cold), calcium antagonists, endovenous prostaglandins or endothelin-2 antagonists may be useful. In patients with gastroesophageal reflux, proton pump inhibitors and H2 receptor antagonists can be used, following protocol for the usual treatment of these scleroderma problems.[23][24]
Since pulmonary hypertension is the leading cause of death, its early diagnosis by routine echocardiography and the rapid initiation of treatment with endothelin-1 antagonists (bosentan), phosphodiesterase 5 inhibitors (sildenafil) or endovenous prostacyclins (epoprostenol) manage to considerably improve morbidity and mortality.[23][24]
### Investigational[edit]
Further investigation into appropriate treatment options for MCTD are in progress. Treatment for various rheumatoid diseases are currently undergoing research and have the potential to be used for patients presenting with similar signs and symptoms. Better understanding the pathophysiology of the disease and its progression will enable better targeted treatment options.[12]
## Prognosis[edit]
The original description of the disease is characterized by a generally good prognosis and an excellent response to treatment with corticosteroids; however, in actuality it is clear that there is a group of patients with elevated morbidity and mortality. In a recent study the survival rates at 5, 10, and 15 years were 98%, 96%, and 88% respectively, with the main causes of death being pulmonary hypertension, cardiovascular problems, and infections.[26] The presence of anticardiolipin antibodies is a more serious risk factor for the disease, as well as the presence of more scleroderma and polymyositis signs and symptoms.[24]
Morbidity is quite high in patients with MCTD. In addition to fatigue and recurrent musculoskeletal complaints, patients can develop a fibromyalgia symptom as a result of occasional outbreaks requiring medium-high doses of corticosteroid. The steroids, in combination with their adverse effects, frequently cause fibromyalgia symptoms and thus complicate treatment.[24]
The prognosis of mixed connective tissue disease is in one third of cases worse than that of systemic lupus erythematosus (SLE). In spite of prednisone treatment, this disease is progressive and may in many cases evolve into a progressive systemic sclerosis (PSS), also referred to as diffuse cutaneous systemic scleroderma (dcSSc) which has a poor outcome. In some cases though the disease is mild and may only need aspirin as a treatment and may go into remission where no Anti-U1-RNP antibodies are detected, but that is rare or within 30% of cases.[citation needed] Most deaths from MCTD are due to heart failure caused by pulmonary arterial hypertension (PAH).
### Disease progression[edit]
Patients diagnosed with MCTD may progress to a clinical picture more consistent with other connective tissue diseases like SLE, scleroderma, or rheumatoid arthritis. In some studies these patients become reclassified over time with other diseases, such as rheumatoid arthritis in 9%, SLE in 15%, and scleroderma in 21% of cases.[27] Such progression is, in part, determined genetically, thus SLE is more likely in patients with HLA-DR3 and scleroderma in patients with HLA-DR5.[24]
## Epidemiology[edit]
The prevalence of MCTD is higher than that of dermatomyositis and lower than that of SLE.[28] In a 2011 Norwegian study, the prevalence of MCTD was 3.8 per 100,000 adults, with an incidence of 2.1 per million per year.[29]
MCTD is much more frequent in women than in men at between a 3:1 to 16:1 ratio, and in women younger than 50.[10] The general age at onset is around 15–25 years old.[citation needed]
## See also[edit]
* Autoimmunity
* Overlap syndrome
* Rheumatoid arthritis
* Autoimmune disease
* Scleroderma
* Systemic lupus erythematosus
* Polymyositis
* Rheumatology
## References[edit]
1. ^ a b Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ a b c Bennett, Robert (2014). "Clinical manifestations of mixed connective tissue disease". www.uptodate.com. Retrieved 2019-10-12.
3. ^ a b c Ungprasert, Patompong; Crowson, Cynthia S.; Chowdhary, Vaidehi R.; Ernste, Floranne C.; Moder, Kevin G.; Matteson, Eric L. (December 2016). "Epidemiology of Mixed Connective Tissue Disease 1985-2014: A Population Based Study". Arthritis Care & Research. 68 (12): 1843–1848. doi:10.1002/acr.22872. ISSN 2151-464X. PMC 5426802. PMID 26946215.
4. ^ a b Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (February 1972). "Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)". The American Journal of Medicine. 52 (2): 148–59. doi:10.1016/0002-9343(72)90064-2. PMID 4621694.
5. ^ Tsokos GC, Gordon C, Smolen JS (2007). Systemic lupus erythematosus: a companion to Rheumatology. Elsevier Health Sciences. pp. 429–. ISBN 978-0-323-04434-9.
6. ^ LeRoy EC, Maricq HR, Kahaleh MB (March 1980). "Undifferentiated connective tissue syndromes". Arthritis and Rheumatism. 23 (3): 341–3. doi:10.1002/art.1780230312. PMID 7362686.
7. ^ a b Hoffman RW (1 June 2009). "Mixed Connective Disease". In Stone J (ed.). Pearls & Myths in Rheumatology. Springer. pp. 169–172. ISBN 978-1-84800-933-2. Retrieved 26 June 2010.
8. ^ "Mixed Connective Tissue Disease, MCTD". The Free Dictionary by Farlex.
9. ^ Nevares AM, Larner R. "Mixed Connective Tissue Disease (MCTD): Autoimmune Disorders of Connective Tissue". Merck Manual Home Health Handbook.
10. ^ a b "Mixed connective tissue disease - Symptoms and causes". Mayo Clinic. Retrieved 2019-10-12.
11. ^ Yang, Chia-Fu; Chiu, Jih-Yu; Su, Chang-Wei; Chen, Chun-Ming (2019). "Chondral grafts for condylar reconstruction in treatment of temporomandibular joint arthritis in a mixed connective tissue disease patient". The Kaohsiung Journal of Medical Sciences. 0 (12): 787–788. doi:10.1002/kjm2.12128. ISSN 2410-8650. PMID 31512336.
12. ^ a b "Mixed Connective Tissue Disease (MCTD)". NORD (National Organization for Rare Disorders). Retrieved 2019-10-12.
13. ^ Aringer M, Steiner G, Smolen JS (August 2005). "Does mixed connective tissue disease exist? Yes". Rheumatic Diseases Clinics of North America. 31 (3): 411–20, v. doi:10.1016/j.rdc.2005.04.007. PMID 16084315.
14. ^ Venables PJ (2006). "Mixed connective tissue disease". Lupus. 15 (3): 132–7. doi:10.1191/0961203306lu2283rr. PMID 16634365. S2CID 25736411.
15. ^ Sato T, Fujii T, Yokoyama T, Fujita Y, Imura Y, Yukawa N, Kawabata D, Nojima T, Ohmura K, Usui T, Mimori T (December 2010). "Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease". Arthritis and Rheumatism. 62 (12): 3730–40. doi:10.1002/art.27700. hdl:2433/142082. PMID 20722023.
16. ^ Cappelli, Susanna; Bellando Randone, Silvia; Martinović, Dušanka; Tamas, Maria-Magdalena; Pasalić, Katarina; Allanore, Yannick; Mosca, Marta; Talarico, Rosaria; Opris, Daniela; Kiss, Csaba G.; Tausche, Anne-Kathrin (February 2012). ""To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity". Seminars in Arthritis and Rheumatism. 41 (4): 589–598. doi:10.1016/j.semarthrit.2011.07.010. ISSN 1532-866X. PMID 21959290.
17. ^ Alarcón-Segovia, D.; Cardiel, M. H. (March 1989). "Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients". The Journal of Rheumatology. 16 (3): 328–334. ISSN 0315-162X. PMID 2724251.
18. ^ "Sociedad Española de Reumatología :: Criterios diagnósticos". 2014-08-10. Archived from the original on 2014-08-10. Retrieved 2019-10-12.
19. ^ a b c Bennett, Robert. "Definition and diagnosis of mixed connective tissue disease".
20. ^ Greidinger, Eric L.; Hoffman, Robert W. (August 2005). "Autoantibodies in the pathogenesis of mixed connective tissue disease". Rheumatic Diseases Clinics of North America. 31 (3): 437–450, vi. doi:10.1016/j.rdc.2005.04.004. ISSN 0889-857X. PMID 16084317.
21. ^ Gendi, N. S.; Welsh, K. I.; Van Venrooij, W. J.; Vancheeswaran, R.; Gilroy, J.; Black, C. M. (February 1995). "HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients". Arthritis and Rheumatism. 38 (2): 259–266. doi:10.1002/art.1780380216. ISSN 0004-3591. PMID 7848317.
22. ^ "Table 1: The Single Nucleotide Polymorphisms in cathepsin B protein mined from literature (PMID: 16492714)". doi:10.7717/peerj.7425/table-1. Cite journal requires `|journal=` (help)
23. ^ a b c Mobasat, A.; Turrión Nieves, A.; Bohorquez Heras, C. (January 2013). "Enfermedad mixta del tejido conectivo. Síndromes de solapamiento". Medicine - Programa de Formación Médica Continuada Acreditado. 11 (32): 1991–1996. doi:10.1016/s0304-5412(13)70567-5. ISSN 0304-5412.
24. ^ a b c d e f Bennett, Robert. "Prognosis and treatment of mixed connective tissue disease".
25. ^ Yang, Chia‐Fu; Chiu, Jih‐Yu; Su, Chang‐Wei; Chen, Chun‐Ming (2019-09-11). "Chondral grafts for condylar reconstruction in treatment of temporomandibular joint arthritis in a mixed connective tissue disease patient". The Kaohsiung Journal of Medical Sciences. 35 (12): 787–788. doi:10.1002/kjm2.12128. ISSN 1607-551X. PMID 31512336.
26. ^ Hajas, Agota; Szodoray, Peter; Nakken, Britt; Gaal, Janos; Zöld, Eva; Laczik, Renata; Demeter, Nora; Nagy, Gabor; Szekanecz, Zoltan; Zeher, Margit; Szegedi, Gyula (July 2013). "Clinical course, prognosis, and causes of death in mixed connective tissue disease". The Journal of Rheumatology. 40 (7): 1134–1142. doi:10.3899/jrheum.121272. ISSN 0315-162X. PMID 23637328. S2CID 19625256.
27. ^ Ruiz Pombo, Mónica; Labrador Horrillo, Moisés; Selva O'Callaghan, Albert (2004-11-20). "[Undifferentiated, overlapping and mixed connective tissue diseases]". Medicina Clinica. 123 (18): 712–717. doi:10.1016/s0025-7753(04)75337-3. ISSN 0025-7753. PMID 15563821.
28. ^ "Mixed Connective-Tissue Disease: Practice Essentials, Pathophysiology, Etiology". 2019-07-17. Cite journal requires `|journal=` (help)
29. ^ Gunnarsson, Ragnar; Molberg, Oyvind; Gilboe, Inge-Margrethe; Gran, Jan Tore; PAHNOR1 Study Group (June 2011). "The prevalence and incidence of mixed connective tissue disease: a national multicentre survey of Norwegian patients". Annals of the Rheumatic Diseases. 70 (6): 1047–1051. doi:10.1136/ard.2010.143792. hdl:10852/36041. ISSN 1468-2060. PMID 21398332. S2CID 206864939.
## Further reading[edit]
* Alana M. Nevares, Mixed Connective Tissue Disease (MCTD), MSD Manual: Consumer edition (April 2018), Professional edition (February 2018)
* Shiel WC (May 2016). Driver CB (ed.). "Mixed Connective Tissue Disease (MCTD)". MedicineNet.com.
* Nevares AM, Larner R. "Mixed Connective Tissue Disease (MCTD): Autoimmune Rheumatic Disorders". Merck Manual Professional.
* Racaza G, Gonzales Penserga E (January–March 2014). "Mixed Connective Tissue Disease in Filipinos – A 13-Year Retrospective Review of 14 Cases in the Philippine General Hospital". Philippine Journal of Internal Medicine. 52 (1): 1–7.
## External links[edit]
Classification
D
* ICD-10: M35.1
* ICD-9-CM: 710.8
* MeSH: D008947
* DiseasesDB: 8312
External resources
* eMedicine: med/3417
* Patient UK: Mixed connective tissue disease
* Orphanet: 809
* v
* t
* e
Systemic connective tissue disorders
General
Systemic lupus erythematosus
* Drug-induced SLE
* Libman–Sacks endocarditis
Inflammatory myopathy
* Myositis
* Dermatopolymyositis
* Dermatomyositis/Juvenile dermatomyositis
* Polymyositis* Inclusion body myositis
Scleroderma
* Systemic scleroderma
* Progressive systemic sclerosis
* CREST syndrome
* Overlap syndrome / Mixed connective tissue disease
Other hypersensitivity/autoimmune
* Sjögren syndrome
Other
* Behçet's disease
* Polymyalgia rheumatica
* Eosinophilic fasciitis
* Eosinophilia–myalgia syndrome
* fibrillin
* Marfan syndrome
* Congenital contractural arachnodactyly
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Mixed connective tissue disease | c0026272 | 6,694 | wikipedia | https://en.wikipedia.org/wiki/Mixed_connective_tissue_disease | 2021-01-18T19:07:15 | {"gard": ["7051"], "mesh": ["D008947"], "umls": ["C0026272"], "icd-9": ["710.8"], "orphanet": ["809"], "wikidata": ["Q1622407"]} |
Lymphoid leukemia
Other namesLymphocytic, lymphogenous, lymphoblastic leukemias
SpecialtyOncology, hematology
Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cells. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.
## Contents
* 1 Classification
* 1.1 B-cell leukemias
* 1.2 T-cell leukemias
* 1.3 NK cell leukemia
* 1.3.1 Diagnosis
* 1.3.2 Treatment
* 2 Diagnosis
* 3 Treatment
* 3.1 NK cell therapy
* 4 References
* 5 External links
## Classification[edit]
Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:
* Acute lymphoblastic leukemia
* Chronic lymphocytic leukemia
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:
* B-cell leukemia
* T-cell leukemia
* NK-cell leukemia
The most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.
### B-cell leukemias[edit]
B-cell leukemia describes several different types of lymphoid leukemia which affect B cells.
Comparison of most common B-cell leukemias Incidence Histopathology Cell markers Comments
B-cell chronic lymphocytic leukemia
(ICD-O: 9823/3) 30% of all leukemias. Also 3 to 4% of lymphomas in adults[1] Small resting lymphocytes mixed with variable number of large activated cells. Lymph nodes are diffusely effaced[1] CD5, surface immunoglobulin[1] Occurs in older adults. Usually involves lymph nodes, bone marrow and spleen. Most patients have peripheral blood involvement. Indolent.[1]
Precursor B-cell lymphoblastic leukemia
(ICD-O: 9835/3-9836/3) 85% of acute leukemias in childhood,[1] Less common in adults[1] Lymphoblasts with irregular nuclear contours, condensed chromatin, small nucleoli and scant cytoplasm without granules.[1] TdT, CD19[1] Usually presents as acute leukemia[1]
Other types include (with ICD-O code):
* 9826/3 – Acute lymphoblastic leukemia, mature B-cell type
* 9833/3 – B-cell prolymphocytic leukemia
* 9940/3 – Hairy cell leukemia
### T-cell leukemias[edit]
T-cell leukemia describes several different types of lymphoid leukemias which affect T cells.
The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia.[1] It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood.[1] It is most common in adolescent males.[1] Its morphology is identical to that of precursor B-cell lymphoblastic leukemia.[1] Cell markers include TdT, CD2, CD7.[1] It often presents as a mediastinal mass because of involvement of the thymus.[1] It is highly associated with NOTCH1 mutations.[1]
Other types include:
* Large granular lymphocytic leukemia
* Adult T-cell leukemia/lymphoma
* T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
### NK cell leukemia[edit]
Aggressive NK-cell leukemia (ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. Most patients will die within 2 years.[2]
#### Diagnosis[edit]
The requirements for diagnosing ANKL are as follows:[3]
1. Immature-looking NK cells
2. Certain immunophenotypes[4]
3. Germline configuration genes: TCR-β and IgH
4. Restricted cytotoxicity
The T-cell receptor (TCR) is an important factor when ANKL is being diagnosed along with T-cell leukemia. The TCR gene transcripts are normally positive for ANKL. [5] Current Research is attempting to find the causation of ANKL. So far, the researchers have concluded that lineage of the T-cell receptor gene does not predict the behavior of the disease.
#### Treatment[edit]
ANKL is treated similarly to most B-cell lymphomas. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. [6][7]
Most patients will die 2 years after diagnosis.[2]
## Diagnosis[edit]
Flow cytometry is a diagnostic tool in order to count/visualize the amount of lymphatic cells in the body. T cells, B cells and NK cells are nearly impossible to distinguish under a microscope, therefore one must use a flow cytometer to distinguish them.
## Treatment[edit]
### NK cell therapy[edit]
Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice.[8]
NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them.[9] One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective.[9] One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety.[10] Unfortunately, there is always the possibility of Graft vs host disease while transplanting bone marrow.
NK cell therapy is a possible treatment for many different cancers such as Malignant glioma.[11]
## References[edit]
1. ^ a b c d e f g h i j k l m n o p Table 12-8 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
2. ^ a b Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, Abe M, Kinoshita T, Yoshino T, Iwatsuki K, Kagami Y, Tsuzuki T, Kurokawa M, Ito K, Kawa K, Oshimi K (May 2010). "Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type". Ann. Oncol. 21 (5): 1032–40. doi:10.1093/annonc/mdp418. PMID 19850638.
3. ^ Oshimi K (July 2003). "Leukemia and lymphoma of natural killer lineage cells". Int. J. Hematol. 78 (1): 18–23. doi:10.1007/bf02983235. PMID 12894846.
4. ^ Landay AL, Muirhead KA (July 1989). "Procedural guidelines for performing immunophenotyping by flow cytometry". Clin. Immunol. Immunopathol. 52 (1): 48–60. doi:10.1016/0090-1229(89)90192-x. PMID 2656019.
5. ^ Hong M, Lee T, Young Kang S, Kim SJ, Kim W, Ko YH (May 2016). "Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior". Mod. Pathol. 29 (5): 430–43. doi:10.1038/modpathol.2016.47. PMID 27015135.
6. ^ Mercadal S, Briones J, Xicoy B, Pedro C, Escoda L, Estany C, Camós M, Colomo L, Espinosa I, Martínez S, Ribera JM, Martino R, Gutiérrez-García G, Montserrat E, López-Guillermo A (May 2008). "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma". Ann. Oncol. 19 (5): 958–63. doi:10.1093/annonc/mdn022. PMID 18303032.
7. ^ Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M (2004). "Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study". Hematol. J. 5 (4): 304–11. doi:10.1038/sj.thj.6200359. PMID 15297846.
8. ^ Rubnitz JE, Inaba H, Kang G, Gan K, Hartford C, Triplett BM, Dallas M, Shook D, Gruber T, Pui CH, Leung W (August 2015). "Natural killer cell therapy in children with relapsed leukemia". Pediatr Blood Cancer. 62 (8): 1468–72. doi:10.1002/pbc.25555. PMC 4634362. PMID 25925135.
9. ^ a b Sakamoto, N; Ishikawa, T; Kokura, S; Okayama, T; Oka, K; Ideno, M; Sakai, F; Kato, A; Tanabe, M; Enoki, T; Mineno, J; Naito, Y; Itoh, Y; Yoshikawa, T (2015). "Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer". Journal of Translational Medicine. 13: 277. doi:10.1186/s12967-015-0632-8. PMC 4548900. PMID 26303618.
10. ^ Bachanova, Veronika; Miller, Jeffrey S. (2014). "NK Cells in Therapy of Cancer". Critical Reviews in Oncogenesis. 19 (1–2): 133–41. doi:10.1615/CritRevOncog.2014011091. PMC 4066212. PMID 24941379.
11. ^ Ogbomo, Henry; Cinatl, Jindrich; Mody, Christopher H.; Forsyth, Peter A. (2011). "Immunotherapy in gliomas: Limitations and potential of natural killer (NK) cell therapy". Trends in Molecular Medicine. 17 (8): 433–41. doi:10.1016/j.molmed.2011.03.004. PMID 21507717.
## External links[edit]
Classification
D
* ICD-10: C91
* ICD-9-CM: 204
* MeSH: D007945
* SNOMED CT: 32280000
* v
* t
* e
Leukaemias, lymphomas and related disease
B cell
(lymphoma,
leukemia)
(most CD19
* CD20)
By
development/
marker
TdT+
* ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
CD5+
* naive B cell (CLL/SLL)
* mantle zone (Mantle cell)
CD22+
* Prolymphocytic
* CD11c+ (Hairy cell leukemia)
CD79a+
* germinal center/follicular B cell (Follicular
* Burkitt's
* GCB DLBCL
* Primary cutaneous follicle center lymphoma)
* marginal zone/marginal zone B-cell (Splenic marginal zone
* MALT
* Nodal marginal zone
* Primary cutaneous marginal zone lymphoma)
RS (CD15+, CD30+)
* Classic Hodgkin lymphoma (Nodular sclerosis)
* CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma)
PCDs/PP
(CD38+/CD138+)
* see immunoproliferative immunoglobulin disorders
By infection
* KSHV (Primary effusion)
* EBV
* Lymphomatoid granulomatosis
* Post-transplant lymphoproliferative disorder
* Classic Hodgkin lymphoma
* Burkitt's lymphoma
* HCV
* Splenic marginal zone lymphoma
* HIV (AIDS-related lymphoma)
* Helicobacter pylori (MALT lymphoma)
Cutaneous
* Diffuse large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Primary cutaneous marginal zone lymphoma
* Primary cutaneous immunocytoma
* Plasmacytoma
* Plasmacytosis
* Primary cutaneous follicle center lymphoma
T/NK
T cell
(lymphoma,
leukemia)
(most CD3
* CD4
* CD8)
By
development/
marker
* TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
* prolymphocyte (Prolymphocytic)
* CD30+ (Anaplastic large-cell lymphoma
* Lymphomatoid papulosis type A)
Cutaneous
MF+variants
* indolent: Mycosis fungoides
* Pagetoid reticulosis
* Granulomatous slack skin
aggressive: Sézary disease
* Adult T-cell leukemia/lymphoma
Non-MF
* CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
* Pleomorphic T-cell lymphoma
* Lymphomatoid papulosis type B
* CD30+: CD30+ cutaneous T-cell lymphoma
* Secondary cutaneous CD30+ large-cell lymphoma
* Lymphomatoid papulosis type A
Other
peripheral
* Hepatosplenic
* Angioimmunoblastic
* Enteropathy-associated T-cell lymphoma
* Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma)
* Subcutaneous T-cell lymphoma
By infection
* HTLV-1 (Adult T-cell leukemia/lymphoma)
NK cell/
(most CD56)
* Aggressive NK-cell leukemia
* Blastic NK cell lymphoma
T or NK
* EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
* Large granular lymphocytic leukemia
Lymphoid+
myeloid
* Acute biphenotypic leukaemia
Lymphocytosis
* Lymphoproliferative disorders (X-linked lymphoproliferative disease
* Autoimmune lymphoproliferative syndrome)
* Leukemoid reaction
* Diffuse infiltrative lymphocytosis syndrome
Cutaneous lymphoid hyperplasia
* Cutaneous lymphoid hyperplasia
* with bandlike and perivascular patterns
* with nodular pattern
* Jessner lymphocytic infiltrate of the skin
General
* Hematological malignancy
* leukemia
* Lymphoproliferative disorders
* Lymphoid leukemias
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Lymphoid leukemia | c0152271 | 6,695 | wikipedia | https://en.wikipedia.org/wiki/Lymphoid_leukemia | 2021-01-18T18:33:20 | {"mesh": ["D007945"], "umls": ["C0152271"], "icd-10": ["C91"], "wikidata": ["Q6708277"]} |
## Clinical Features
Chan and Bird (2004) reported a family with abdominal wall muscular hypoplasia as an isolated defect and not associated with the urethral obstruction sequence known as prune belly syndrome (100100). The proband was a 3-year-old boy who presented with abdominal wall laxity and severe constipation. His mother, maternal grandmother, and younger brother had varying degrees of abdominal wall muscular deficiency and constipation. His mother's condition was aggravated by her 2 pregnancies. None of the individuals had evidence of urinary tract or renal pathology, and the muscle deficiency was limited to the abdominal wall. The transmission pattern was consistent with autosomal dominant inheritance. Chan and Bird (2004) postulated that expression in the sons would remain incomplete because abdominal distention due to pregnancy would not occur.
Digilio et al. (2008) reported autosomal dominant transmission of hypoplasia of the abdominal wall muscles with weakness of the linea alba and diastasis recti. A mother, son, and maternal grandmother were affected. All affected patients showed anterior abdominal deficiency without associated dysmorphic features or internal malformations. Echocardiography and abdominal ultrasonography were normal, and urethral obstruction sequence was excluded by urethral cystography, distinguishing the disorder from prune belly syndrome. Digilio et al. (2008) noted the similarities to the family reported by Chan and Bird (2004).
Inheritance
The pattern of transmission of the disorder in the families reported by Chan and Bird (2004) and Digilio et al. (2008) suggests autosomal dominant inheritance.
INHERITANCE \- Autosomal dominant ABDOMEN External Features \- Diastasis recti \- Abdominal wall laxity \- Abdominal wall muscular deficiency \- Weakness of the linea alba Gastrointestinal \- Constipation MISCELLANEOUS \- Congenital defect \- Nonsyndromic ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| DIASTASIS RECTI AND WEAKNESS OF THE LINEA ALBA | c2677303 | 6,696 | omim | https://www.omim.org/entry/612198 | 2019-09-22T16:02:16 | {"mesh": ["C567402"], "omim": ["612198"]} |
Leber `plus' disease describes patients with the clinical features of Leber's hereditary optic neuropathy (LHON; see term) in combination with other serious systemic or neurological abnormalities. These abnormalities include: postural tremor, motor disorder, multiple sclerosis-like syndrome, spinal cord disease, skeletal changes, Parkinsonism with dystonia, anarthria, dystonia, motor and sensory peripheral neuropathy, spasticity and mild encephalopathy. It is caused by maternally-inherited mitochondrial DNA (mtDNA) mutations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Leber plus disease | c1833830 | 6,697 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99718 | 2021-01-23T18:09:24 | {"gard": ["8476"], "mesh": ["C563496"], "omim": ["165200", "500001"], "icd-10": ["H47.2"], "synonyms": ["LHON plus disease"]} |
Radioulnar synostosis-microcephaly-scoliosis syndrome, also known as Guiffré-Tsukahara syndrome, is an extremely rare syndrome characterized by the association of radioulnar synostosis with microcephaly, scoliosis, short stature and intellectual deficit.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| Radioulnar synostosis-microcephaly-scoliosis syndrome | c1863881 | 6,698 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3268 | 2021-01-23T18:39:00 | {"gard": ["394"], "omim": ["603438"], "umls": ["C1863881"], "synonyms": ["Giuffré-Tsukahara syndrome", "Tsukahara syndrome"]} |
## Summary
### Clinical characteristics.
ASXL3-related disorder is characterized by developmental delay or intellectual disability, typically in the moderate to severe range, with speech and language delay and/or absent speech. Affected individuals may also display autistic features. There may be issues with feeding. While dysmorphic facial features have been described, they are typically nonspecific. Affected individuals may also have hypotonia that can transition to spasticity resulting in unusual posture with flexion contractions of the elbows, wrists, and fingers. Other findings may include poor postnatal growth, strabismus, seizures, sleep disturbance, and dental anomalies.
### Diagnosis/testing.
The diagnosis of ASXL3-related disorder is established in a proband by identification of a heterozygous pathogenic variant in ASXL3 by molecular genetic testing.
### Management.
Treatment of manifestations: Feeding therapy; gastrostomy tube placement for those with persistent feeding issues; anti-reflux medication and/or fundoplication for those with gastroesophageal disease; standard treatment for epilepsy, joint contractures, sleep apnea, dental anomalies, strabismus and/or refractive error, and developmental delay / intellectual disability.
Surveillance: At each visit: Measurement of growth parameters and nutritional status; assessment of developmental progress, behavioral issues, new neurologic manifestations (change in tone, seizure onset and/or frequency), mobility and self-help skills, as well as signs and symptoms of sleep disturbance. Dental evaluation every six months after age three years or as clinically indicated. At least annual ophthalmology evaluation.
### Genetic counseling.
ASXL3-related disorder is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Rarely, individuals diagnosed with ASXL3-related disorder have the disorder as the result of a pathogenic variant inherited from a parent. If the ASXL3 pathogenic variant identified in the proband is not identified in either parent, the risk to sibs is presumed to be low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the ASXL3 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
## Diagnosis
Formal clinical diagnostic criteria for ASXL3-related disorder have not been established.
### Suggestive Findings
ASXL-related disorder should be considered in individuals with the following clinical findings:
* Developmental delay (DD) or intellectual disability, typically in the moderate to severe range; AND
* Any of the following features presenting in infancy or childhood:
* Speech and language delay and/or absent speech
* Autism spectrum disorder or autistic traits
* Dysmorphic facial features including prominent forehead; highly arched eyebrows; synophrys, widely spaced eyes; downslanted palpebral fissures; long, tubular nose with prominent nasal bridge; wide mouth with full, everted vermilion of the lower lip; and crowded teeth
* Feeding difficulties
* Hypotonia
* Poor postnatal growth
* Epilepsy including generalized tonic-clonic seizures and absence seizures
* Vision impairment including strabismus
* Skeletal findings such as Marfanoid habitus, pectus excavatum, scoliosis, arachnodactyly, and joint flexion with contractures
### Establishing the Diagnosis
The diagnosis of ASXL3-related disorder is established in a proband by identification of a heterozygous pathogenic variant in ASXL3 by molecular genetic testing (see Table 1). Note: Identification of a heterozygous ASXL3 variant of uncertain significance does not establish or rule out a diagnosis of ASXL3-related disorder.
Molecular genetic testing in a child with developmental delay or an older individual with intellectual disability typically begins with chromosomal microarray analysis (CMA). If CMA is not diagnostic, the next step is typically either a multigene panel or exome sequencing. Note: Single-gene testing (sequence analysis of ASXL3, followed by gene-targeted deletion/duplication analysis) is rarely useful due to the nonspecific nature of clinical presentation and typically NOT recommended.
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including ASXL3) that cannot be detected by sequence analysis.
An intellectual disability multigene panel that includes ASXL3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition in a person with a nondiagnostic CMA at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used, but genome sequencing may be performed, and yields results similar to an ID multigene panel with the additional advantage that exome and genome sequencing includes genes recently identified as causing ID, whereas some multigene panels may not.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in ASXL3-Related Disorder
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
ASXL3Sequence analysis 398%-99% 4, 5
Gene-targeted deletion/duplication analysis 61%-2% 7
CMA 8Rare 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
From Balasubramanian et al [2017], Kuechler et al [2017], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
5\.
Most individuals so far reported with ASXL3-related disorder have truncating or splice site variants in ASXL3.
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
7\.
At least two individuals in a cohort with typical ASXL3-related disorder have ASXL3 deletions identified on chromosomal microarray (CMA) [Authors, personal observation]. Both individuals had deletions that included only ASXL3 without deletion of adjacent genes.
8\.
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including ASXL3) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 18q12.1 region. CMA designs in current clinical use target the 18q12.1 region.
## Clinical Characteristics
### Clinical Description
To date, 44 individuals from 40 families have been identified with a pathogenic variant in ASXL3 [Bainbridge et al 2013, Dinwiddie et al 2013, Hori et al 2016, Retterer et al 2016, Srivastava et al 2016, Balasubramanian et al 2017, Chinen et al 2017, Dad et al 2017, Kuechler et al 2017, Bacrot et al 2018, Contreras-Capetillo et al 2018, Koboldt et al 2018, Myers et al 2018a, Myers et al 2018b, Verhoeven et al 2018, Zhang et al 2018, Qiao et al 2019, Wayhelova et al 2019, Schirwani et al 2020]. The authors have collected clinical and molecular data on another 45 affected individuals in an additional cohort study that will be submitted for publication. The following description of the phenotypic features associated with this condition is based on these published reports and the additional cohort study (n=89 affected individuals).
### Table 2.
Select Features of ASXL3-Related Disorder
View in own window
Feature% of Persons
w/FeatureComment
Speech delay100%Most are nonverbal or have very limited speech.
Intellectual disability99%Typically moderate to severe
Facial dysmorphism98%See Suggestive Findings.
Hypotonia86%Central hypotonia can be assoc w/↑ tone in upper & lower limbs.
Behavioral concerns78%Incl autistic traits or an ASD diagnosis
Feeding difficulties78%Most patients in the early stages are referred w/feeding difficulties & failure to thrive.
Skeletal findings74%
Eyes~50%Strabismus is the most common finding.
Seizures38%GTCS & absence seizures; most have normal brain MRI imaging.
ASD = autism spectrum disorder; GTCS = generalized tonic-clonic seizures
Speech delay. All individuals with ASXL3-related disorder have delayed speech and language development. First word was achieved in 32% of affected individuals, at an average age of 28.8 months [Authors, personal observation].
* A majority of known individuals with ASXL3-related disorder are nonverbal.
Use of communication devices with expert speech and language therapy input can often be helpful in these individuals to develop alternate modes of communication, as it appears that receptive language skills may be better than expressive language skills in persons with this disorder.
* Less commonly, communication through gesture, sounds, words, and sentences has been described.
Intellectual disability (ID). A majority of the individuals with ASXL3-related disorder have developmental delay and intellectual disability that is generally moderate to severe. However, a spectrum of intellectual capabilities has been described.
* Initial reports were of affected individuals with profound ID partly attributed to ascertainment bias; however, as more affected individuals have been identified, milder degrees of ID are being observed.
* The authors are aware of a father and son with a paternally inherited truncating ASXL3 pathogenic variant, suggesting that a few individuals with ASXL3-related disorder may have normal cognition [Authors, personal observation].
Children with ASXL3-related disorder may be able to attend a mainstream school with dedicated support. However, so far, most individuals have required special educational provisions. The vast majority of adults described to date have required assisted living with some degree of independence.
Dysmorphic features. Individuals with ASXL3-related disorder have similar but typically nonspecific facial features (see Suggestive Findings) which are often recognized only after a diagnosis has been established.
Behavioral concerns. More than three-quarters of individuals with ASXL3-related disorder have significant behavioral, social, and communication difficulties with substantial impact on the affected individuals and their families.
* About half of affected individuals meet the formal clinical diagnostic criteria of an autism spectrum disorder (ASD), whereas others have autistic-like features. However, others are described as having a very friendly, placid personality.
* Other (more rarely) associated behaviors can include:
* Hand flapping
* Agitation
* Motor and/or vocal tics (Tourette syndrome)
* Hyperventilation episodes
* Teeth grinding (bruxism)
* Attention-deficit disorder (ADD)
* Pica
* Self-harm behaviors including self-biting, face scratching, and head banging
Onset of self-injurious behavior can be as early as age two years; some individuals display this behavior later in life.
Growth. Most affected individuals display normal birth weight for gestational age but often experience poor postnatal growth due to feeding issues during infancy. During this time, growth may decline to 2 SD below the mean or more for age. Short stature is not a primary feature of ASXL3-related disorder and growth (both weight and length/height) typically stabilize or normalize after appropriate treatment of feeding issues (see following).
Feeding issues. Most individuals with ASXL3-related disorder, especially in the younger age groups, come to medical attention due to poor postnatal growth (see above) and ongoing feeding difficulties. They may display poor suck and swallow, recurrent vomiting, and gastroesophageal reflux disease.
* Swallow studies have shown impairment of oral stage of swallowing and oral sensorimotor feeding delay characterized by oral motor weakness, reduced mastication skills for age, and suspected oral hypersensitivity. This may result in delay in weaning and food refusal behavior. Affected individuals may also have a high arched palate.
* The severity of feeding difficulties varies considerably, with some affected children requiring long-term gastrostomy tube insertion while in others, feeding may be improved with the use of slow-flow nipples (see Treatment of Manifestations).
* Although initial feeding issues may resolve with age, there may be ongoing difficulties with feeding due to food aversion, sensitivity to different food textures, and behavioral issues that may affect eating.
Neurologic
* Hypotonia is a common feature in individuals with ASXL3-related disorder, especially during the neonatal period and in early infancy. Later in life, some children develop an unusual posture and contractures with elbow, wrist, and fingers held in the flexion position. This is likely due to spasticity that becomes apparent with age.
* Seizures occur in about one third of affected individuals and can range from generalized tonic-clonic seizures to absence seizures. Seizures typically respond to standard antiepileptic medications.
* Imaging. Most individuals with ASXL3-related disorder have normal brain imaging and do not have any characteristic brain findings.
Skeletal features. More than two thirds of individuals with ASXL3-related disorder have a skeletal abnormality. Findings may include:
* Marfanoid habitus
* Pectus excavatum
* Joint hypermobility
* Pes planus
* Digital abnormalities including arachnodactyly, syndactyly, clinodactyly, contractures, and tapering fingers
* Postural scoliosis (possibly due to hypotonia)
* Delayed bone age
Sleep. Sleep disturbance is a common finding, with some affected individuals reported to have sleep apnea, for which a sleep study and further evaluation to establish a cause is warranted. Some affected individuals have abnormal breathing patterns including apnea, breath-holding episodes, and irregular breathing patterns (particularly at night) that coincide with sleep disturbances.
Eyes. Strabismus has been described in more than half of affected individuals. It can be persistent or intermittent. Some affected individuals have myopia, hyperopia, and ptosis. Visual difficulties (including astigmatism) needing correction may also be seen.
Dental. Dental abnormalities, ranging from dental overcrowding, malocclusion, and large teeth to severe hypodontia, are present in nearly 50% of individuals.
Other
* Some affected individuals have problems with temperature regulation and are insensitive to cold/heat.
* Altered pain perception has been described in association with this condition but is not a consistent finding.
### Genotype-Phenotype Correlations
No genotype-phenotype correlations for ASXL3 have been identified.
### Nomenclature
ASXL3-related disorder was first described by Bainbridge et al [2013] in four unrelated individuals with truncating variants in ASXL3; it is sometimes referred to as Bainbridge-Ropers syndrome.
### Prevalence
The prevalence of ASXL3-related disorder is not known. However, to date ASXL3 is one of the top ten genes in which pathogenic variants have been found in large-scale exome sequencing studies of individuals with ID [Fitzgerald et al 2015, Wright et al 2015].
Affected individuals have been reported from all ethnicities and most have been identified in countries that undertake genomic testing in individuals with ID.
## Differential Diagnosis
Because the clinical presentation of ASXL3-related disorder is typically nonspecific global developmental delay, all disorders associated with intellectual disability (ID) without other distinctive findings should be considered in the differential diagnosis. To date more than 180 such disorders with ID have been identified. See OMIM Phenotypic Series: Autosomal dominant ID; Autosomal recessive ID; Nonsyndromic X-linked ID; and Syndromic X-linked ID.
Note: Heterozygous pathogenic variants ASXL1 and ASXL2, the other two genes in the ASXL gene family (see Molecular Pathogenesis), are associated with Bohring-Opitz syndrome (BOS) and Shashi-Pena syndrome, respectively. Both disorders are characterized by developmental delay but can be distinguished from ASXL3-related disorder by the characteristic facial dysmorphism associated with BOS, and by macrocephaly and abnormal brain imaging in Shashi-Pena syndrome.
## Management
Consensus clinical management guidelines for ASXL3-related disorder have not been published.
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with ASXL3-related disorder, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with ASXL3-Related Disorder
View in own window
System/ConcernEvaluationComment
DevelopmentDevelopmental assessmentTo incl motor, adaptive, cognitive, & speech/language eval
Eval for early intervention / special education
Psychiatric/
BehavioralNeuropsychiatric evalFor persons age >12 mos: screen for behavior concerns incl sleep disturbances, ADD, &/or traits suggestive of ASD.
ConstitutionalMeasurement of growth parametersTo evaluate for growth deficiency
Gastrointestinal/
FeedingGastroenterology / nutrition / feeding team evalTo incl eval of aspiration risk, GERD, & nutritional status
Consider eval for gastric tube placement in those w/dysphagia &/or aspiration risk.
NeurologicNeurologic eval
* To incl brain MRI
* Consider EEG if seizures are a concern.
MusculoskeletalOrthopedics / physical medicine & rehab / PT / OT evalTo incl assessment of:
* Gross motor & fine motor skills
* Contractures, pes planus, scoliosis & joint hypermobility
* Mobility, activities of daily living, & need for adaptive devices
* Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)
RespiratoryAssessment for sleep disturbance &/or evidence of sleep apnea
DentalAge-appropriate dental evalTo assess for malocclusion & hypodontia
EyesOphthalmologic evalTo assess for strabismus & ↓ vision
Miscellaneous/
OtherConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling
Family support/resourcesAssess:
* Use of community or online resources such as Parent to Parent;
* Need for social work involvement for parental support;
* Need for home nursing referral.
ADD = attention-deficit disorder; ASD = autism spectrum disorder; GERD = gastroesophageal reflux disease; OT = occupational therapy; PT = physical therapy
### Treatment of Manifestations
### Table 4.
Treatment of Manifestations in Individuals with ASXL3-Related Disorder
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
DD/IDSee Developmental Delay / Intellectual Disability Management Issues.
Poor weight gain /
Failure to thriveFeeding therapy; gastrostomy tube placement may be required for persistent feeding issues.Low threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia
GERDAnti-reflux medication; fundoplication or percutaneous endoscopic gastrostomy in severe situationsConsider consultation w/gastroenterology specialist in those w/severe disease.
EpilepsyStandardized treatment w/AEDs by experienced neurologist
* Many AEDs may be effective; none is demonstrated effective specifically for this disorder.
* Education of parents/caregivers 1
Pes planus, joint
contractures,
scoliosisStandard treatment per orthopedist
Sleep apneaStandard treatment per ENT / sleep specialist
Malocclusion
&/or hypodontiaStandard treatment per dentist/orthodontist
Strabismus &/or
refractive errorStandard treatment per ophthalmologist
Family/
Community
* Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
* Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
* Ongoing assessment of need for palliative care involvement &/or home nursing
* Consider involvement in adaptive sports or Special Olympics.
AED = antiepileptic drug; DD = developmental delay; GERD = gastroesophageal reflux disease; ID = intellectual disability; OT = occupational therapy; PT = physical therapy
1\.
Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit.
#### Developmental Disability / Intellectual Disability Management Issues
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:
* Individualized education plan (IEP) services:
* An IEP provides specially designed instruction and related services to children who qualify.
* IEP services will be reviewed annually to determine whether any changes are needed.
* As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.
* Vision consultants should be a part of the child's IEP team to support access to academic material.
* PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
* As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
* A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
* Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
#### Motor Dysfunction
Gross motor dysfunction
* Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g, contractures, scoliosis, and hip dislocation).
* Consider use of durable medical equipment and positioning devices as needed (e.g, wheelchairs, walkers, bath chairs, orthotics, and adaptive strollers).
* For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.
Communication issues. Consider evaluation for alternative means of communication (e.g, Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, and in many cases can improve it.
#### Social/Behavioral Concerns
Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.
Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder (ADHD), when necessary.
Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.
### Surveillance
### Table 5.
Recommended Surveillance for Individuals with ASXL3-Related Disorder
View in own window
System/ConcernEvaluationFrequency
DevelopmentMonitor developmental progress & educational needs.At each visit
Psychiatric/
BehavioralBehavioral assessment for attention & aggressive or self-injurious behavior
Feeding
* Measurement of growth parameters
* Eval of nutritional status & signs/symptoms of GERD or feeding aversion
Neurologic
* Monitor those w/seizures as clinically indicated.
* Assess for new manifestations incl seizures & changes in tone.
MusculoskeletalPhysical medicine, OT/PT assessment of mobility, self-help skills
RespiratoryAssess for signs/symptoms of sleep disturbance & sleep apnea.
Miscellaneous/
OtherAssess family need for social work support (e.g, palliative/respite care, home nursing, & other local resources) & care coordination.
DentalEval by dentistEvery 6 mos after age 3 yrs or as clinically indicated
EyesOphthalmology evalAnnually or as clinically indicated
GERD = gastroesophageal disease; OT = occupational therapy; PT = physical therapy
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
| ASXL3-Related Disorder | None | 6,699 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK563693/ | 2021-01-18T21:44:20 | {"synonyms": ["Bainbridge-Ropers Syndrome (BRPS)"]} |
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