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Cervical spine disorder Cervical vertebrate Cervical spine disorders are illnesses that affect the cervical spine, which is made up of the upper first seven vertebrae, encasing and shielding the spinal cord. This fragment of the spine starts from the region above the shoulder blades and ends by supporting and connecting the skull.[1] The cervical spine contains many different anatomic compositions, including muscles, bones, ligaments, and joints. All of these structures have nerve endings that can detect painful problems when they occur. Such nerves supply muscular control and sensations to the skull and arms while correspondingly providing our bodies with flexibility and motion.[1] However, if the cervical spine is injured it can cause many minor or traumatic problems, and although these injuries vary specifically they are more commonly known as "cervical spine disorders" as a whole.[1] ## Contents * 1 Symptoms * 1.1 Complications * 2 Cause * 2.1 Age factors * 3 Diagnosis * 4 Treatments * 5 See also * 6 References * 7 Further reading * 8 External links ## Symptoms[edit] It is through upper frontal chest discomfort (also known as cervical angina) and scapular pains which signs of cervical spine disorders are shown. In 1937 a man named Oille was the first to state that these chest pains originated from the cervical nerve root.[2] This new outlook helped shed light on exactly what signs indicated the beginning of these ailments for those suffering from cervical spine disorders. It is now recognized that these patients feel pain, numbness, discomfort, and weakness along with neurological symptoms.[2] * Numbness Numbness occurs when one develops a “pinched” nerve not allowing for the flow of electrical charges, which may result in the death of the nerve fiber.[3] * Weakness An individual becomes weak due to the compression of nerves encompassing cervical spine disorders, thus resulting in the inability to move or use arms.[3] Those who suffer from such symptoms should seek medical treatment as soon as possible.[3] ### Complications[edit] If not treated right away, there are many consequences and pains various cervical spine disorders can cause.[1] Brachial plexus * Neck pains Pains in the neck area tend to be tenacious and persistent and most muscles in the cervical spinal region tighten causing for discomfort.[1] * Headaches Headaches are further triggered through the stiffness of neck muscles, which pull at their attachment to the skull. These headaches are recurrent in nature and start from the base of the skull and emanate upwards; they can be painful or mild.[1] * Arm pains Muscular spasms within the arm are further common symptoms in which such spasms are seen right above the collarbones and pressure is placed on the Brachial plexus causing arms to feel heavy and ache.[1] * Difficulty walking Hardships arise with cervical spinal injuries when issues with walking, balancing, and posture are affected all due to the spinal cord being compressed resulting in Myelopathy.[3] * Those with extremely severe outcomes may result in:Impairment[4] ## Cause[edit] There are several conditions and syndromes that can affect the cervical spine and they all vary due to the difference in place and type of injury. * Rheumatoid arthritis Those affected with rheumatoid arthritis in their cervical spine are known to have neurological deficits. It results in occipital pain and myelopathy.[5] * Occipito-cervical junction This disorder may result from rheumatoid arthritis, causing the hypermobility of the connection between the neck and head, resulting in paralysis or pain.[6] * Cerebrovascular disease Cerebrovascular disease is a type of cervical spine disorder that can cause tetraplegia.[7] * Subaxial cervical spine[8] * Atlanto-axial joint ### Age factors[edit] * The elderly Because of such symptoms, people often mistake cervical spine disorder indicators for coronary artery disease, and although individuals of any age can develop spine threatening injuries, the people that are affected by it the most are the elderly. This is because as one ages spinal discs that absorb any type of shock wear out increasing elders' chances of developing degenerative alterations in their cervical spine.[3] * The young Patients younger than eight years old with cervical spinal cord casualties have an increased chance of dying while those older than eight years have similar effects as adults. They are usually immobilized from the shoulder up until consciousness is regained and symptoms are gone.[5] ## Diagnosis[edit] The diagnosis process might include a physician who tests that the movement, strength, and sensation of the arms and legs are normal. The spine is examined for its range of motion and any pain that may arise from movement. Blood work might be utilized in addition to radiographic imaging in order to identify spinal cord diseases. Basic imaging techniques, which includes x-ray imaging, can reveal degenerative changes of the spine, while more advanced imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), can allow visualization of more detailed anatomical structures, including that of the associated nerves and muscles. The most detailed and specific testing is electrodiagnostic, which helps to uncover whether the appropriate electrical signals are being sent to each muscle from the correlate nerves. This aids in localizing a problem's source.[1] There are risks to be considered with any diagnostic testing. For example, in the case of CT imaging, there is obvious benefit over x-ray in that a more thorough picture of the anatomy is exposed, but there is a trade-off in that CT has around a 10-fold increased radiation exposure; alternatively, while MRI provides highly detailed imaging of the anatomy with the benefit of no radiation exposure to the patient, the high cost of this test must be taken into account.[6] ## Treatments[edit] If one’s symptoms are mild, treatments like Massage, Exercise, and Stress management will suffice in reducing pain and pressure, but those with more severe symptoms are told to undergo unique therapies based on their exact situation. These patients most likely will have their postures and spine alignment fixed, and/or treatments like electrical stimulation may be used to help in reducing pain and aid in flexibility. Medicine, epidural injections and surgeries are also implemented to treat such a disorder.[1] ## See also[edit] * Clearing the cervical spine * Scoliosis ## References[edit] 1. ^ a b c d e f g h i "Neck Pain and Cervical Spine Disorders". Minneapolis Clinic of Neurology. 2. ^ a b Nakajima, H; Uchida, K; Kobayashi, S; Kokubo, Y; Yayama, T; Sato, R; Inukai, T; Godfrey, T; Baba, H (6 December 2005). "Cervical angina: a seemingly still neglected symptom of cervical spine disorder?". Spinal Cord. 44 (8): 509–513. doi:10.1038/sj.sc.3101888. PMID 16331305. ProQuest 229343382. 3. ^ a b c d e Cervical spine disorder. "Medtronic". Retrieved from http://wwwp.medtronic.com/Newsroom/LinkedItemDetails.do?itemId=1169645895363&itemType=backgrounder&lang=en_IN[dead link] 4. ^ Hermann, Karl M; Reese, C Shane (1 March 2001). "Relationships Among Selected Measures of Impairment, Functional Limitation, and Disability in Patients With Cervical Spine Disorders". Physical Therapy. 81 (3): 903–912. doi:10.1093/ptj/81.3.903. PMID 11268155. ProQuest 223115626. 5. ^ a b Neo, Masashi (15 April 2008). "Treatment of upper cervical spine involvement in rheumatoid arthritis patients". Modern Rheumatology. 18 (4): 327–335. doi:10.1007/s10165-008-0059-7. PMID 18414784. ProQuest 232743067. 6. ^ a b Dormans, John P. (January 2002). "Evaluation of Children with Suspected Cervical Spine Injury". The Journal of Bone and Joint Surgery. American Volume. 84 (1): 124–132. doi:10.2106/00004623-200201000-00018. PMID 11792790. ProQuest 205129467. 7. ^ McCormick, M T; Robinson, H K; Bone, I; McLean, A N; Allan, D B (28 November 2006). "Blunt cervical spine trauma as a cause of spinal cord injury and delayed cortical blindness". Spinal Cord. 45 (10): 687–689. doi:10.1038/sj.sc.3101995. PMID 17130891. ProQuest 229343756. 8. ^ Degenerative spine disorders. Retrieved from http://neurosurgery.ucsf.edu/index.php/spine_disorders_cervical.html[dead link] ## Further reading[edit] * Todd, Andrew G. (20 September 2011). "Cervical spine: degenerative conditions". Current Reviews in Musculoskeletal Medicine. 4 (4): 168–174. doi:10.1007/s12178-011-9099-2. PMC 3261239. PMID 22021015. ## External links[edit] Classification D * ICD-9-CM: 805 * v * t * e Human systems and organs Musculoskeletal Skeletal system * Bone * Carpus * Collar bone (clavicle) * Thigh bone (femur) * Fibula * Humerus * Mandible * Metacarpus * Metatarsus * Ossicles * Patella * Phalanges * Radius * Skull * Tarsus * Tibia * Ulna * Rib * Vertebra * Pelvis * Sternum * Cartilage Joints * Fibrous joint * Cartilaginous joint * Synovial joint Muscular system * Muscle * Tendon * Diaphragm Circulatory system Cardiovascular system * peripheral * Artery * Vein * Lymphatic vessel * Heart Lymphatic system * primary * Bone marrow * Thymus * secondary * Spleen * Lymph node * CNS equivalent * Glymphatic system Nervous system * * Brain * Spinal cord * Nerve * Sensory system * Ear * Eye Integumentary system * Skin * Subcutaneous tissue * Breast * Mammary gland Hematopoietic and immune systems * Myeloid * Myeloid immune system * Lymphoid * Lymphoid immune system Respiratory system * Upper * Nose * 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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	Cervical spine disorder	c1290145	8,300	wikipedia	https://en.wikipedia.org/wiki/Cervical_spine_disorder	2021-01-18T18:55:05	{"umls": ["C1290145"], "wikidata": ["Q5065358"]}
A cosmopolitan zoonotic disease caused in humans by the accidental ingestion of eggs or larvae of the ascarids Toxocara canis or Toxocara cati, the common round worm of dogs and cats respectively. The infestation can be asymptomatic or can present as visceral larva migrans caused by larval migration through major organs such as liver, lungs or central nervous system (manifesting with fever, cough, hepatomegaly, pneumonia or rarely encephalitis), or as ocular larva migrans caused by larval migration to the eye (manifesting as ocular inflammation and retinal scaring). [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	Toxocariasis	c0040553	8,301	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3343	2021-01-23T17:29:01	{"mesh": ["D014120"], "umls": ["C0040553"], "icd-10": ["B83.0"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Allergic reactions to anesthesia" – news · newspapers · books · scholar · JSTOR (January 2009) (Learn how and when to remove this template message) [1] An example of a hypersensitivity reaction on the hands from topical anesthesia. The incidence of life-threatening hypersensitivity reactions occurring during surgery and anesthesia is around one in 10,000 procedures.[2] Serious allergic reactions to anesthetic medications are rare and a usually attributable to factors other than the anesthetic. Neuromuscular blocking agents, natural rubber latex, and antibiotics are the most common causes of serious allergic reactions during surgery.[3] The mortality rate from these reactions ranges between 3-9%.[4] Successful immediate treatment requires prompt recognition by the attending anesthetist, or in the US, the attending anesthesiologist or nurse anesthetist. Anesthetists are trained to recognise if an allergic reaction is occurring. The identification of a complication is made by the recognition of issues such as low blood pressure, hives, wheezing, rash, swelling around the eyes or in the mouth and throat and other breathing difficulties.[5] Adrenaline (epinephrine) remains the mainstay of treatment, with corticosteroids and antihistamines providing limited benefit in the acute situation. Subsequent investigation aims to determine the responsible agent to allow its future avoidance. Skin testing is often useful to identify potentially cross-reactive compounds and appropriate therapeutic alternatives. This is done weeks after the initial reaction to allow the immune system to reset itself. However, skin testing can be misleading in giving false positive and false negative results. ## Anaphylaxis during anesthesia[edit] Although complications during anesthesia are rare, potentially life-threatening consequences may occur if an anaphylactic reaction develops. The severity of the reaction whilst under anesthesia is because the anesthetist is only made aware of the allergy when it is severe enough to compromise the cardiovascular system and the respiratory system. At this stage, there is little time to manage the situation and recognise the severity of the condition.[6] The immediate management of the issue consists of three processes: * The withdrawal of the substances * Interrupting the effects of the preformed substances released in response to toxin presentation * Prevention of further substance release Since the full withdrawal of the offending substance is near impossible, the administration of adrenalin is the main treatment to counteract the effects. Once the patient is stable they will need close observation for 24 hours.[6] ## References[edit] 1. ^ "International Academy of Cosmetic Dermatology". www.iacdworld.org. Archived from the original on 2016-05-17. Retrieved 2016-05-16. 2. ^ Mertes, P. M.; Tajima, K.; Regnier-Kimmoun, M. A.; Lambert, M.; Iohom, G.; Guéant-Rodriguez, R. M.; Malinovsky, J. M. (2010-07-01). "Perioperative anaphylaxis". The Medical Clinics of North America. 94 (4): 761–789, xi. doi:10.1016/j.mcna.2010.04.002. ISSN 1557-9859. PMID 20609862. 3. ^ Hepner DL, Castells MC (2003). "Anaphylaxis during the perioperative period". Anesthesia and Analgesia. 97 (5): 1381–95. doi:10.1213/01.ANE.0000082993.84883.7D. PMID 14570656. 4. ^ "World Allergy Organization". www.worldallergy.org. Retrieved 2016-05-17.[permanent dead link] 5. ^ "Possible complications \| All About Anaesthesia". allaboutanaesthesia.com.au. Retrieved 2016-05-17. 6. ^ a b Dippenaar, JM (March 2015). "Allergic Reactions and Anaphylaxis During Anaesthesia" (PDF). Current Allergy & Clinical Immunology. 28. Archived from the original (PDF) on 10 September 2016. Retrieved 16 May 2016. * v * t * e Anesthesia and anesthesiology Types * General * Sedation * Twilight anesthesia * Local * Topical * Intercostal nerve block * Neuraxial blockade * Spinal * Epidural * Dental * Inferior alveolar nerve Techniques * Airway management * Anesthesia provision in the US * Arterial catheter * Bronchoscopy * Capnography * Dogliotti's principle * Drug-induced amnesia * Intraoperative neurophysiological monitoring * Nerve block * Penthrox inhaler * Tracheal intubation Scientific principles * Blood–gas partition coefficient * Concentration effect * Fink effect * Minimum alveolar concentration * Second gas effect Measurements * ASA physical status classification system * Baricity * Bispectral index * Entropy monitoring * Fick principle * Goldman index * Guedel's classification * Mallampati score * Neuromuscular monitoring * Thyromental distance Instruments * Anaesthetic machine * Anesthesia cart * Boyle's machine * Gas cylinder * Laryngeal mask airway * Laryngeal tube * Medical monitor * Odom's indicator * Relative analgesia machine * Vaporiser * Double-lumen endotracheal tube * Endobronchial blocker Complications * Emergence delirium * Allergic reactions * Anesthesia awareness * Local anesthetic toxicity * Malignant hyperthermia * Perioperative mortality * Postanesthetic shivering * Postoperative nausea and vomiting * Postoperative residual curarization Subspecialties * Cardiothoracic * Critical emergency medicine * Geriatric * Intensive care medicine * Obstetric * Oral sedation dentistry * Pain medicine Professions * Anesthesiologist * Anesthesiologist assistant * Nurse anesthetist * Operating department practitioners * Certified Anesthesia Technician * Certified Anesthesia Technologist * Anaesthetic technician * Physicians' assistant (anaesthesia) History * ACE mixture * Helsinki Declaration for Patient Safety in Anaesthesiology * History of general anesthesia * History of neuraxial anesthesia * History of tracheal intubation Organizations * American Association of Nurse Anesthetists * American Society of Anesthesia Technologists & Technicians * American Society of Anesthesiologists * Anaesthesia Trauma and Critical Care * Association of Anaesthetists of Great Britain and Ireland * Royal College of Anaesthetists * Association of Veterinary Anaesthetists * Australian and New Zealand College of Anaesthetists * Australian Society of Anaesthetists * International Anesthesia Research Society * Category * Outline This surgery 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	Allergic reactions to anesthesia	None	8,302	wikipedia	https://en.wikipedia.org/wiki/Allergic_reactions_to_anesthesia	2021-01-18T18:45:00	{"wikidata": ["Q4732120"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-15 (SCAR15) is caused by homozygous mutation in the KIAA0226 gene (RUBCN; 613516) on chromosome 3q29. One such family has been reported. Clinical Features Assoum et al. (2010) reported a consanguineous Saudi Arabian family in which 3 sisters had onset of cerebellar ataxia in early childhood. All showed delayed motor development with delayed walking. Two sisters had a more severe form of the disorder, with an unsteady gait apparent since learning to walk, whereas the third developed unsteady gait around age 7 years. Other features included dysarthria, upper limb involvement, abnormal eye movements, and hyporeflexia. Two patients had increased reflexes in the lower limbs. At age 7 months the 2 sisters who were more severely affected developed epilepsy, which was responsive to treatment with no relapse in either girl since age 3 years; both subsequently showed moderate mental retardation. Brain MRI was normal in the 3 girls at ages 16, 9, and 8 years, respectively, but showed mild cerebellar atrophy and prominent folia in 1 patient at age 18 years, suggesting progression of the disorder. At ages 16 to 25 years, they had limited walking without aid, but were unable to run. Inheritance The transmission pattern of spinocerebellar ataxia in the family reported by Assoum et al. (2010) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 sisters, born of consanguineous Saudi Arabian parents, with autosomal recessive spinocerebellar ataxia, Assoum et al. (2010) identified a homozygous mutation in the KIAA0226 gene (613516.0001). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The mutation results in the loss of the highly conserved DAG binding-like motif. Heterozygous carriers were unaffected. No mutations in the KIAA0226 gene were found in 172 additional families with non-Friedreich (FRDA; 229300) ataxia. Assoum et al. (2013) found that transfection of mutant KIAA0226 in COS-1 and HeLa cells resulted in mislocalization of the mutant protein from the late endosome and lysosomes to diffuse cytosolic distribution. The findings suggested that the mutation results in a loss of proper protein function, and that the disorder may relate to defects in endolysosomal machinery. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Saccadic pursuit NEUROLOGIC Central Nervous System \- Delayed motor development \- Spinocerebellar ataxia (upper and lower limb involvement) \- Unsteady gait \- Dysarthria \- Mental retardation (in 2 of 3 patients) \- Epilepsy (in 2 of 3 patients) Peripheral Nervous System \- Hyporeflexia \- Hyperreflexia \- Cerebellar atrophy (1 patient) MISCELLANEOUS \- One family has been reported (last curated March 2014) \- Onset in early childhood \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the KIAA0226 gene (KIAA0226, 613516.0001 ) ▲ 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	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 15	c3810326	8,303	omim	https://www.omim.org/entry/615705	2019-09-22T15:51:14	{"doid": ["0080057"], "omim": ["615705"], "orphanet": ["404499"], "synonyms": ["Salih ataxia", "SCAR15", "Autosomal recessive spinocerebellar ataxia type 15", "Alternative titles", "SALIH ATAXIA"]}
Rosselli–Gulienetti syndrome Other namesZlotogora–Ogur syndrome This condition is inherited in an autosomal recessive manner[1] Rosselli–Gulienetti syndrome,[2] also known as Zlotogora–Ogur syndrome[3] and Bowen–Armstrong syndrome,[4] is a type of congenital ectodermal dysplasia syndrome. The syndrome is relatively rare[5] and has only been described in a few cases. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] There is a range of signs and symptoms including cleft lip or palate, mental retardation and various forms of ectodermal dysplasia. Additional symptoms may include fused eyelids, absent nails, delayed bone growth and dry skin. It is believed that this syndrome follows an autosomal dominant pattern of inheritance with incomplete penetrance,[5] and caused by a mutation affecting the TP63 gene.[6] It has been suggested that this syndrome, AEC syndrome and Rapp–Hodgkin syndrome may be variations of the same disease.[7] ## Cause[edit] This section is empty. You can help by adding to it. (August 2017) ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) ## Treatment[edit] There is no specific treatment or cure for individuals affected with this type of syndrome, though some of the abnormal physical features may be surgically correctable.[4] ## References[edit] 1. ^ "OMIM Entry - % 225000 - ROSSELLI-GULIENETTI SYNDROME". omim.org. Retrieved 7 August 2017. 2. ^ Rosselli, D.; Gulienetti, R. (1961). "Ectodermal dysplasia". British Journal of Plastic Surgery. 14: 190–204. doi:10.1016/S0007-1226(61)80036-2. PMID 14494246. 3. ^ ORPHANET - About rare diseases - About orphan drugs 4. ^ a b Bowen-Armstrong Syndrome 5. ^ a b Bowen, P; Armstrong HB (1976). "Ectodermal dysplasia, mental retardation, cleft lip/palate and other anomalies in three sibs". Clin. Genet. 9 (1): 35–42. doi:10.1111/j.1399-0004.1976.tb01547.x. PMID 174848. 6. ^ Dianzani I, Garelli E, Gustavsson P, et al. (2003). "Rapp-Hodgkin and AEC syndromes due to a new frameshift mutation in the TP63 gene". J. Med. Genet. 40 (12): 133e–133. doi:10.1136/jmg.40.12.e133. PMC 1735338. PMID 14684701. 7. ^ Zenteno JC, Venegas C, Kofman-Alfaro S (1999). "Evidence that AEC syndrome and Bowen--Armstrong syndrome are variable expressions of the same disease". Pediatr Dermatol. 16 (2): 103–107. doi:10.1046/j.1525-1470.1999.99009.x. PMID 10337671. ## External links[edit] Classification D * OMIM: 225000 * MeSH: C563117 * DiseasesDB: 32747 External resources * Orphanet: 90339 [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	Rosselli–Gulienetti syndrome	c0796139	8,304	wikipedia	https://en.wikipedia.org/wiki/Rosselli%E2%80%93Gulienetti_syndrome	2021-01-18T19:00:15	{"mesh": ["C563117"], "umls": ["C0796139"], "orphanet": ["90339"], "wikidata": ["Q7369769"]}
Food intolerances SpecialtyGastroenterology, immunology Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.[1] Food allergies are immune reactions, typically an IgE reaction caused by the release of histamine but also encompassing non-IgE immune responses.[1] This mechanism causes allergies to typically give immediate reaction (a few minutes to a few hours) to foods. Food intolerances can be classified according to their mechanism. Intolerance can result from the absence of specific chemicals or enzymes needed to digest a food substance, as in hereditary fructose intolerance. It may be a result of an abnormality in the body's ability to absorb nutrients, as occurs in fructose malabsorption. Food intolerance reactions can occur to naturally occurring chemicals in foods, as in salicylate sensitivity. Drugs sourced from plants, such as aspirin, can also cause these kinds of reactions. ## Contents * 1 Definitions * 2 Signs and symptoms * 3 Causes * 4 Pathogenesis * 5 Diagnosis * 6 Prevention * 7 Management * 8 Prognosis * 9 Epidemiology * 10 History * 11 Society and culture * 12 Research directions * 13 See also * 14 References * 15 External links ## Definitions[edit] Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.[1] There are a variety of earlier terms which are no longer in use such as "pseudo-allergy".[2] Food intolerance reactions can include pharmacologic, metabolic, and gastro-intestinal responses to foods or food compounds. Food intolerance does not include either psychological responses[3] or foodborne illness. A non-allergic food hypersensitivity is an abnormal physiological response. It can be difficult to determine the poorly tolerated substance as reactions can be delayed, dose-dependent, and a particular reaction-causing compound may be found in many foods.[4] * Metabolic food reactions are due to inborn or acquired errors of metabolism of nutrients, such as in lactase deficiency, phenylketonuria and favism. * Pharmacological reactions are generally due to low-molecular-weight chemicals which occur either as natural compounds, such as salicylates and amines, or to food additives, such as preservatives, colouring, emulsifiers and taste enhancers. These chemicals are capable of causing drug-like (biochemical) side effects in susceptible individuals.[5] * Gastro-intestinal reactions can be due to malabsorption or other GI Tract abnormalities. * Immunological responses are mediated by non-IgE immunoglobulins, where the immune system recognises a particular food as a foreign body. * Toxins may either be present naturally in food, be released by bacteria, or be due to contamination of food products.[5] Toxic food reactions are caused by the direct action of a food or substance without immune involvement.[5] * Psychological reactions involve manifestation of clinical symptoms caused not by food but by emotions associated with food. These symptoms do not occur when the food is given in an unrecognisable form.[5] Elimination diets are useful to assist in the diagnosis of food intolerance. There are specific diagnostic tests for certain food intolerances.[5][6][7] ## Signs and symptoms[edit] Food intolerance is more chronic, less acute, less obvious in its presentation, and often more difficult to diagnose than a food allergy.[8] Symptoms of food intolerance vary greatly, and can be mistaken for the symptoms of a food allergy. While true allergies are associated with fast-acting immunoglobulin IgE responses, it can be difficult to determine the offending food causing a food intolerance because the response generally takes place over a prolonged period of time. Thus, the causative agent and the response are separated in time, and may not be obviously related. Food intolerance symptoms usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may be delayed by up to 48 hours.[9] Food intolerance can present with symptoms affecting the skin, respiratory tract, gastrointestinal tract (GIT) either individually or in combination. On the skin may include skin rashes, urticaria (hives),[10] angioedema,[11] dermatitis,[12] and eczema.[13] Respiratory tract symptoms can include nasal congestion, sinusitis, pharyngeal irritations, asthma and an unproductive cough. GIT symptoms include mouth ulcers, abdominal cramp, nausea, gas, intermittent diarrhea, constipation, irritable bowel syndrome (IBS),[6][7][9] and may include anaphylaxis.[13] Food intolerance has been found associated with irritable bowel syndrome and inflammatory bowel disease,[14] chronic constipation,[15] chronic hepatitis C infection,[16] eczema,[17] NSAID intolerance,[18] respiratory complaints,[19] including asthma,[20] rhinitis and headache,[21][22] functional dyspepsia,[23] eosinophilic esophagitis[9] and ENT illnesses.[21][24] ## Causes[edit] Reactions to chemical components of the diet may be more common than true food allergies,[citation needed] although there is no evidence to support this. They are caused by various organic chemicals occurring naturally in a wide variety of foods, animal and vegetable, more often than to food additives, preservatives, colourings and flavourings, such as sulfites or dyes.[13] Both natural and artificial ingredients may cause adverse reactions in sensitive people if consumed in sufficient amounts, the degree of sensitivity varying between individuals. Pharmacological responses to naturally occurring compounds in food, or chemical intolerance, can occur in individuals from both allergic and non-allergic family backgrounds. Symptoms may begin at any age, and may develop quickly or slowly. Triggers may range from a viral infection or illness to environmental chemical exposure. Chemical intolerance occurs more commonly in women, which may be because of hormone differences, as many food chemicals mimic hormones.[citation needed] A deficiency in digestive enzymes can also cause some types of food intolerances. Lactose intolerance is a result of the body not producing sufficient lactase to digest the lactose in milk;[25][26] dairy foods which are lower in lactose, such as cheese, are less likely to trigger a reaction in this case. Another carbohydrate intolerance caused by enzyme deficiency is hereditary fructose intolerance. Celiac disease, an autoimmune disorder caused by an immune response to the protein gluten, results in gluten intolerance and can lead to temporary lactose intolerance.[27][28] The most widely distributed naturally occurring food chemical capable of provoking reactions is salicylate,[18] although tartrazine and benzoic acid are well recognised in susceptible individuals.[29][30][31] Benzoates and salicylates occur naturally in many foods, including fruits, juices, vegetables, spices, herbs, nuts, tea, wines, and coffee. Salicylate sensitivity causes reactions to not only aspirin and NSAIDs but also foods in which salicylates naturally occur, such as cherries. Other natural chemicals which commonly cause reactions and cross reactivity include amines, nitrates, sulphites and some antioxidants. Chemicals involved in aroma and flavour are often suspect.[20][32][33][34] The classification or avoidance of foods based on botanical families bears no relationship to their chemical content and is not relevant in the management of food intolerance.[citation needed] Salicylate-containing foods include apples, citrus fruits, strawberries, tomatoes, and wine, while reactions to chocolate, cheese, bananas, avocado, tomato or wine point to amines as the likely food chemical. Thus, exclusion of single foods does not necessarily identify the chemical responsible as several chemicals can be present in a food, the patient may be sensitive to multiple food chemicals and reaction more likely to occur when foods containing the triggering substance are eaten in a combined quantity that exceeds the patient's sensitivity thresholds. People with food sensitivities have different sensitivity thresholds, and so more sensitive people will react to much smaller amounts of the substance.[5][9][20][33][34] [35][36][37][38][39] ## Pathogenesis[edit] This section needs expansion. You can help by adding to it. (January 2009) Food intolerance are all other adverse reactions to food. Subgroups include enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (e.g. reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives).[40] Food intolerances can be caused by enzymatic defects in the digestive system, can also result from pharmacological effects of vasoactive amines present in foods (e.g. histamine),[6] among other metabolic, pharmacological and digestive abnormalities. Allergies and intolerances to a food group may coexist with separate pathologies; for example, cow's milk allergy (CMA) and lactose intolerance are two distinct pathologies. ## Diagnosis[edit] Diagnosis of food intolerance can include hydrogen breath testing for lactose intolerance and fructose malabsorption, professionally supervised elimination diets, and ELISA testing for IgG-mediated immune responses to specific foods. It is important to be able to distinguish between food allergy, food intolerance, and autoimmune disease in the management of these disorders.[41] Non-IgE-mediated intolerance is more chronic, less acute, less obvious in its clinical presentation, and often more difficult to diagnose than allergy, as skin tests and standard immunological studies are not helpful.[8] Elimination diets must remove all poorly tolerated foods, or all foods containing offending compounds. Clinical investigation is generally undertaken only for more serious cases, as for minor complaints which do not significantly limit the person's lifestyle the cure may be more inconvenient than the problem.[5] Immunoglobulin (IgG) tests measure the types of food-specific antibodies present. There are four types of IgG, IgG1 makes up 60-70% of the total IgG, followed by IgG2 (20-30%), IgG3 (5-8%), and IgG4 (1-4%). Most commercially available tests only test for IgG4 antibodies, however some companies such as YorkTest Laboratories test for all four types.[42] IgG4 only tests are debatably invalid; IgG4 presence indicates that the person has been repeatedly exposed to food proteins recognized as foreign by the immune system which is a normal physiological response of the immune system after exposure to food components.[43][1] Although elimination of foods based on IgG-4 testing in IBS patients resulted in an improvement in symptoms,[44] the positive effects of food elimination were more likely due to wheat and milk elimination than IgG-4 test-determined factors.[45] The IgG-4 test specificity is questionable as healthy individuals with no symptoms of food intolerance also test positive for IgG-4 to several foods.[46] Diagnosis is made using medical history and cutaneous and serological tests to exclude other causes, but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed.[6] Treatment can involve long-term avoidance,[47] or if possible re-establishing a level of tolerance. Today there are many methods available such as Cytotoxic testing, MRT testing, Elisa Testing, Microarray Elisa Testing, and ELISA/ACT. Allergy US reviewed these methods and Microarray technology appears to be the most reliable among them.[48][49][50][51] ## Prevention[edit] There is emerging evidence from studies of cord bloods that both sensitization and the acquisition of tolerance can begin in pregnancy, however the window of main danger for sensitization to foods extends prenatally, remaining most critical during early infancy when the immune system and intestinal tract are still maturing.[citation needed] There is no conclusive evidence to support the restriction of dairy intake in the maternal diet during pregnancy in order to prevent. This is generally not recommended since the drawbacks in terms of loss of nutrition can out-weigh the benefits. However, further randomised, controlled trials are required to examine if dietary exclusion by lactating mothers can truly minimize risk to a significant degree and if any reduction in risk is out-weighed by deleterious impacts on maternal nutrition.[52] A Cochrane review has concluded feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance.[53] In the case of allergy and celiac disease others recommend a dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4–6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.[54][55] ## Management[edit] Individuals can try minor changes of diet to exclude foods causing obvious reactions, and for many this may be adequate without the need for professional assistance. For reasons mentioned above foods causing problems may not be so obvious since food sensitivities may not be noticed for hours or even days after one has digested food. Persons unable to isolate foods and those more sensitive or with disabling symptoms should seek expert medical and dietitian help. The dietetic department of a teaching hospital is a good start. (see links below) Guidance can also be given to your general practitioner to assist in diagnosis and management. Food elimination diets have been designed to exclude food compounds likely to cause reactions and foods commonly causing true allergies and those foods where enzyme deficiency cause symptoms. These elimination diets are not everyday diets but intended to isolate problem foods and chemicals. It takes around five days of total abstinence to unmask a food or chemical, during the first week on an elimination diet withdrawal symptoms can occur but it takes at least two weeks to remove residual traces. If symptoms have not subsided after six weeks, food intolerance is unlikely to be involved and a normal diet should be restarted. Withdrawals are often associated with a lowering of the threshold for sensitivity which assists in challenge testing, but in this period individuals can be ultra-sensitive even to food smells so care must be taken to avoid all exposures.[citation needed] After two or more weeks if the symptoms have reduced considerably or gone for at least five days then challenge testing can begin. This can be carried out with selected foods containing only one food chemical, to isolate it if reactions occur. In Australia, purified food chemicals in capsule form are available to doctors for patient testing. These are often combined with placebo capsules for control purposes.[citation needed] This type of challenge is more definitive. New challenges should only be given after 48 hours if no reactions occur or after five days of no symptoms if reactions occur. Once all food chemical sensitivities are identified a dietitian can prescribe an appropriate diet for the individual to avoid foods with those chemicals. Lists of suitable foods are available from various hospitals and patient support groups can give local food brand advice. A dietitian will ensure adequate nutrition is achieved with safe foods and supplements if need be. Over a period of time it is possible for individuals avoiding food chemicals to build up a level of resistance by regular exposure to small amounts in a controlled way, but care must be taken, the aim being to build up a varied diet with adequate composition.[5][14][15][41][56][57][58] ## Prognosis[edit] The prognosis of children diagnosed with intolerance to milk is good: patients respond to diet which excludes cow's milk protein and the majority of patients succeed in forming tolerance.[59] Children with non-IgE-mediated cows milk intolerance have a good prognosis, whereas children with IgE-mediated cows milk allergy in early childhood have a significantly increased risk for persistent allergy, development of other food allergies, asthma and rhinoconjunctivitis.[60] A study has demonstrated that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical improvement and increased overall well being and quality of life.[58] ## Epidemiology[edit] Estimates of the prevalence of food intolerance vary widely from 2% to over 20% of the population.[61] So far only three prevalence studies in Dutch and English adults have been based on double-blind, placebo-controlled food challenges. The reported prevalences of food allergy/intolerance (by questionnaires) were 12% to 19%, whereas the confirmed prevalences varied from 0.8% to 2.4%. For intolerance to food additives the prevalence varied between 0.01 and 0.23%.[62] Food intolerance rates were found to be similar in the population in Norway. Out of 4,622 subjects with adequately filled-in questionnaires, 84 were included in the study (1.8%) Perceived food intolerance is a common problem with significant nutritional consequences in a population with IBS. Of these 59 (70%) had symptoms related to intake of food, 62% limited or excluded food items from the diet. Tests were performed for food allergy and malabsorption, but not for intolerance. There were no associations between the tests for food allergy and malabsorption and perceived food intolerance, among those with IBS. Perceived food intolerance was unrelated to musculoskeletal pain and mood disorders.[63] According to the RACP working group, "Though not considered a "cause" of CFS, some patients with chronic fatigue report food intolerances that can exacerbate symptoms."[64] ## History[edit] In 1978 Australian researchers published details of an 'exclusion diet' to exclude specific food chemicals from the diet of patients. This provided a basis for challenge with these additives and natural chemicals. Using this approach the role played by dietary chemical factors in the pathogenesis of chronic idiopathic urticaria (CIU) was first established and set the stage for future DBPCT trials of such substances in food intolerance studies.[65][66] In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. Reactions secondary to food ingestion are defined generally as 'adverse reactions to food'.[67] In 2003 the Nomenclature Review Committee of the World Allergy Organization issued a report of revised nomenclature for global use on food allergy and food intolerance, that has had general acceptance. Food intolerance is described as a 'non-allergic hypersensitivity' to food.[68] ## Society and culture[edit] In the UK, scepticism about food intolerance as a specific condition influenced doctors' perceptions of patients and of the patients' underlying problems. However, rather than risk damaging the doctor-patient relationship, general practitioners (GPs) chose - despite their scepticism and guided by an element of awareness of the limitations of modern medicine - to negotiate mutually acceptable ground with patients and with patients' beliefs. As a result, whether due to a placebo effect, a secondary benefit, or a biophysical result of excluding a food from the diet, the GPs acknowledge both personal and therapeutic benefits.[61] In the Netherlands, patients and their doctors (GPs) have different perceptions of the efficacy of diagnostic and dietary interventions in IBS. Patients consider food intolerance and GPs regard lack of fibre as the main etiologic dietary factor. It has been suggested that Dutch GPs explore the patients' expectations and potentially incorporate these in their approach to IBS patients.[69] New food labeling regulations were introduced into the US and Europe in 2006,[70] which are said to benefit people with intolerances.[71] In general, food-allergic consumers were not satisfied with the current labelling practices.[72] In the USA food companies propose distinguishing between food allergy and food intolerance and use a mechanism-based (i.e., immunoglobulin-E-mediated), acute life-threatening anaphylaxis that is standardized and measurable and reflects the severity of health risk, as the principal inclusion criterion for food allergen labeling.[73] Symptoms due to, or exacerbated by, food additives usually involve non-IgE-mediated mechanisms (food intolerance) and are usually less severe than those induced by food allergy, but can include anaphylaxis.[13] ## Research directions[edit] FODMAPs are fermentable oligo-, di-, monosaccharides and polyols, which are poorly absorbed in the small intestine and subsequently fermented by the bacteria in the distal small and proximal large intestine. This is a normal phenomenon, common to everyone. The resultant production of gas potentially results in bloating and flatulence.[74] Although FODMAPs can produce certain digestive discomfort in some people, not only do they not cause intestinal inflammation, but they avoid it, because they produce beneficial alterations in the intestinal flora that contribute to maintain the good health of the colon.[75][76][77] FODMAPs are not the cause of irritable bowel syndrome nor other functional gastrointestinal disorders, but rather a person develops symptoms when the underlying bowel response is exaggerated or abnormal.[74] A low-FODMAP diet might help to improve short-term digestive symptoms in adults with irritable bowel syndrome,[78][79][80][81] but its long-term follow-up can have negative effects because it causes a detrimental impact on the gut microbiota and metabolome.[82][79][81][83] It should only be used for short periods of time and under the advice of a specialist.[84] More studies are needed to assess the true impact of this diet on health.[79][81] Also, when a low FODMAP diet is used without a previous complete medical evaluation can cause serious health risks. It can ameliorate and mask the digestive symptoms of serious diseases, such as celiac disease, inflammatory bowel disease and colon cancer, avoiding their correct diagnosis and therapy.[85] [86] This is especially relevant in the case of celiac disease. Since the consumption of gluten is suppressed or reduced with a low-FODMAP diet, the improvement of the digestive symptoms with this diet may not be related to the withdrawal of the FODMAPs, but of gluten, indicating the presence of an unrecognized celiac disease, avoiding its diagnosis and correct treatment, with the consequent risk of several serious health complications, including various types of cancer.[86] A three monthts randomised, blinded, controlled trial on people with irritable bowel syndrome found that those who withdrew from the diet the foods to which they had shown an increased IgG antibody response experienced an improvement in their symptoms.[87] Increased intestinal permeability, so called leaky gut, has been linked to food allergies[88] and some food intolerances.[89][90] Research is currently focussing on specific conditions[91][92][93] and effects of certain food constituents.[94][95][96] At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of specific conditions.[90][94] ## See also[edit] * Drug intolerance * Egg intolerance * Elimination diet * Favism * Fructose malabsorption * Gluten sensitivity * Gluten-sensitive enteropathy * Fructose intolerance * Histamine intolerance, also related to biogenic amines intolerance / BAI * Lactose intolerance * Orthorexia * Salicylate sensitivity * Sodium phosphates * Sucrose intolerance ## References[edit] 1. ^ a b c d Lomer, M. C. E. (1 February 2015). "Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance". Alimentary Pharmacology & Therapeutics. 41 (3): 262–275. doi:10.1111/apt.13041. ISSN 1365-2036. PMID 25471897. 2. ^ Gerth van Wijk R, van Cauwenberge PB, Johansson SG (August 2003). "[Revised terminology for allergies and related conditions]". Ned Tijdschr Tandheelkd (in Dutch). 110 (8): 328–31. PMID 12953386. 3. ^ Johansson SG, Hourihane JO, Bousquet J, et al. (September 2001). "A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force". Allergy. 56 (9): 813–24. doi:10.1034/j.1398-9995.2001.t01-1-00001.x. PMID 11551246. Archived from the original on 5 January 2013. 4. ^ "Food allergy and intolerance \| Better Health Channel". betterhealth.vic.gov.au. Retrieved 27 June 2014. 5. ^ a b c d e f g h Clarke L, McQueen J, et al. (1996). "The dietary management of food allergy and food intolerance in children and adults". 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PMID 18931598. ## External links[edit] Classification D * ICD-10: K90.4-Z71.3 * ICD-9-CM: V69.1 * Food Intolerance Awareness from British Allergy Foundation [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	Food intolerance	c0149696	8,305	wikipedia	https://en.wikipedia.org/wiki/Food_intolerance	2021-01-18T18:45:10	{"mesh": ["D000073923"], "icd-9": ["V69.1"], "icd-10": ["K90.4", "Z71.3"], "wikidata": ["Q1727229"]}
A number sign (#) is used with this entry because of evidence that Seckel syndrome-8 (SCKL8) is caused by homozygous mutation in the DNA2 gene (601810) on chromosome 10q21. One such family has been reported. Description Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (summary by Shanske et al., 1997). For a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). Clinical Features Shaheen et al. (2014) studied an uncle and niece, both born of consanguineous marriages, with short stature and strikingly similar facial features consistent with Seckel syndrome. Both uncle and niece had decreased length at birth (-4.9 and -5.1 SD, respectively) and continued to have short stature at ages 18 years and 9 years (-9.5 and -6 SD) as well as severe microcephaly (-7.5 and -11.8 SD). Both had global developmental delay and intellectual disability. The uncle also had severe kyphoscoliosis resulting in spinal cord compression and paraplegia, whereas his niece had a normal spine but exhibited an ectopic kidney. Shaheen et al. (2014) noted that both parental pairs in the extended family had had numerous miscarriages. Molecular Genetics In an uncle and niece with short stature and strikingly similar facial features consistent with Seckel syndrome, Shaheen et al. (2014) performed autozygome analysis and found a single shared run of homozygosity on chr10:63,850,661-71,470,390 (GRCh37). Full sequencing of all genes within this interval revealed homozygosity for a 1-bp deletion in the DNA2 gene (601810.0004). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly, severe Face \- Micrognathia Nose \- Beaked nose GENITOURINARY Kidneys \- Ectopic kidney SKELETAL Skull \- Microcephaly Spine \- Kyphoscoliosis, severe \- Spinal cord compression NEUROLOGIC Central Nervous System \- Global developmental delay \- Intellectual disability \- Paraplegia secondary to spinal cord compression due to severe kyphosis MISCELLANEOUS \- Based on report of 2 individuals in 1 consanguineous family (last curated May 2014) MOLECULAR BASIS \- Caused by mutation in the homolog of yeast DNA replication helicase-2 gene (DNA2, 601810.0004 ) ▲ 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	SECKEL SYNDROME 8	c0265202	8,306	omim	https://www.omim.org/entry/615807	2019-09-22T15:51:03	{"doid": ["0070009"], "omim": ["615807"], "orphanet": ["808"]}
A number sign (#) is used with this entry because UV-sensitive syndrome-3 (UVSS3) can be caused by homozygous mutation in the UVSSA gene (614632) on chromosome 4p16. Description UV-sensitive syndrome-3 is an autosomal recessive disorder characterized by cutaneous photosensitivity and slight dyspigmentation, without an increased risk of skin tumors. Patient cells show impaired recovery of RNA synthesis (RRS) after UV irradiation due to defective preferential repair of DNA damage in actively transcribing genes, although unscheduled DNA repair is normal. The cellular findings are consistent with a defect in transcription-coupled nucleotide excision repair (TC-NER) of UV damage (summary by Itoh et al., 1994 and Nakazawa et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of UVSS, see UVSS1 (600630). Clinical Features Fujiwara et al. (1985) reported a 16-year-old Japanese girl (XP24KO) with mild photosensitivity reminiscent of xeroderma pigmentosum (see, e.g., 278700). She had an acute sun sensitivity reaction without blistering at age 1 year. Small pigmented freckles and telangiectases were noted on her face at age 11-12 years. She had no neoplasia and no other abnormalities. Patient fibroblasts were twice as sensitive to UV killing as normal cells, and were reported to show a reduced level (30-55%) of unscheduled DNA synthesis (UDS) after irradiation. The patient was initially assigned to XP complementation group E (278740). However, reinvestigation of the XP24KO cells by Itoh et al. (2000) showed normal UDS and nucleotide excision repair, but decreased recovery of RNA synthesis after UV irradiation; the phenotype was reclassified as UVSS. Kawada et al. (1986) reported a 5-year-old Japanese girl (XP70TO) with mild symptoms of xeroderma pigmentosum. She had neither skin malignancies nor neurologic abnormalities. Cellular studies showed UV sensitivity and reduced UV-induced unscheduled DNA synthesis, and the patient was initially assigned to XP complementation group E. However, cellular studies on XP70TO by Nakazawa et al. (2012) showed nearly normal UDS and markedly defective RRS, consistent with UVSS. Itoh et al. (1994, 1996) reported 2 teenaged Japanese sibs with mild clinical manifestations similar to those of xeroderma pigmentosum: acute sunburn, dryness with freckling and pigmentation anomalies of sun-exposed skin, and telangiectasia without neurologic abnormalities or tumors. Each showed photosensitivity at about 6 months of age, with erythema and edema on sun-exposed skin a few hours after exposure. Patient cells showed impaired RRS after UV irradiation, although unscheduled DNA synthesis was normal. The patients did not belong to any complementation group of the xeroderma pigmentosum (XP; e.g., 278730) or Cockayne (CSB; 133540) syndromes. Itoh et al. (1995) found that postreplication repair in cells derived from these patients was normal, indicating that they could not be classified as XP variant. Neither transfection nor microinjection of the cells with the human DNA repair gene ERCC1 (126380), which is known not to correct any complementation groups of XP or CS, failed to correct the defect of these cells, indicating that they do not belong to the rodent complementation group 1. However, the defect in recovery of RNA synthesis after UV irradiation was restored by microinjection of HeLa cell extract. The cellular characteristics such as UV sensitivity and defective RRS after UV irradiation with normal unscheduled DNA synthesis were reminiscent of Cockayne syndrome. On the basis of these results, Itoh et al. (1995) proposed that these patients be included under a general category designated 'UV-sensitive syndrome.' Inheritance The transmission pattern of UVSS3 in the families reported by Itoh et al. (1994), Nakazawa et al. (2012), and Zhang et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics By exome sequencing of 2 cell lines (Kps3 and XP24KO) derived from 2 unrelated patients with UV-sensitive syndrome-3, Nakazawa et al. (2012) identified a homozygous truncating mutation in the UVSSA gene (K123X; 614632.0001). The patients had previously been reported by Itoh et al. (1994), and Fujiwara et al. (1985) and Itoh et al. (2000), respectively. Direct sequencing of the UVSSA gene identified 2 additional homozygous mutations in 2 unrelated patients (614632.0002 and 614632.0003, respectively); the latter patient had been reported by Kawada et al. (1986). All of the cell lines showed defective RNA synthesis recovery after UV irradiation, which was restored after expression of wildtype UVSSA. Unscheduled DNA synthesis was nearly normal. Pathogenic UVSSA mutations were not found in 61 individuals with Cockayne syndrome (see, e.g., CSA, 216400). Zhang et al. (2012) used microcell-mediated chromosome transfers via mouse cells to identify the gene responsible for UVSS3 in the Kps3 cell line. The results indicated that the causative gene was on mouse chromosome 5. Sequencing of the UVSSA gene identified a homozygous K123X mutation in the Kps3 cell line and in the XP24KO cell line. Expression of wildtype UVSSA in Kps3 cells restored normal levels of recovery of RNA synthesis after UV irradiation and UV resistance. Zhang et al. (2012) noted that the Kps3 cell line is not hypersensitive to oxidative damage (Nardo et al., 2009), which may explain the mild phenotype. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Photosensitivity \- Freckling \- Telangiectasia \- Dry skin LABORATORY ABNORMALITIES \- Cells show defective transcription-coupled nucleotide excision repair (TC-NER) after UV irradiation \- Increased cellular sensitivity to UV light MISCELLANEOUS \- Onset in infancy \- No predisposition to skin tumor development MOLECULAR BASIS \- Caused by mutation in the UV-stimulated scaffold protein A gene (UVSSA, 614632.0001 ) ▲ 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	UV-SENSITIVE SYNDROME 3	c1833561	8,307	omim	https://www.omim.org/entry/614640	2019-09-22T15:54:38	{"doid": ["0060240"], "mesh": ["C563466"], "omim": ["614640"], "orphanet": ["178338"]}
Torlontano et al. (1979) suggested that hereditary elliptocytosis (HE) falls into four categories: (1) HE without clinical hemolysis; (2) HE with hemolysis and sometimes anemia; (3) hereditary hemolytic ovalocytosis (166900); and (4) defective erythropoiesis and incomplete response to splenectomy. They studied 4 families with the last disorder, all from central and southern Italy. The degree of red cell eccentricity is less marked in ovalocytosis than in typical elliptocytosis. Inheritance \- Autosomal dominant Misc \- Incomplete response to splenectomy Heme \- Ovalocytosis \- Hemolytic anemia \- Defective erythropoiesis ▲ 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	OVALOCYTOSIS, HEREDITARY HEMOLYTIC, WITH DEFECTIVE ERYTHROPOIESIS	c1833689	8,308	omim	https://www.omim.org/entry/166910	2019-09-22T16:36:49	{"mesh": ["C563479"], "omim": ["166910"]}
Poikiloderma with neutropenia (PN) is a disorder that mainly affects the skin and the immune system. This condition begins with a bumpy rash that usually appears between the ages of 6 and 12 months, gradually spreading from the arms and legs to the torso and face. At about age 2, the rash fades, and the affected child is left with darker and lighter patches of skin coloring (hyperpigmentation and hypopigmentation) and small clusters of blood vessels just under the skin (telangiectases); this combination is known as poikiloderma. Other skin problems include unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); calcium deposits that form small nodules (calcinosis cutis), especially on the knees, elbows, or ears; or sores (ulcers) that do not easily heal. Affected individuals also have fingernails and toenails that are thick and abnormally shaped (pachyonychia), fragile teeth, and low bone density. People with PN have chronic neutropenia, which is a persistent shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses. As a result, people with PN experience recurrent sinus infections and pneumonia, especially in the first few years of life. They often develop a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. The infections become less frequent after early childhood, but throughout life affected individuals usually have a chronic cough or a reactive airway disease. This term describes asthma and other conditions in which the airways abnormally constrict in response to stimuli such as smoke or a viral infection, leading to wheezing and shortness of breath. Researchers suggest that PN may increase the risk of cancer, although the level of risk is difficult to determine because only a small number of people have been diagnosed with PN. A type of skin cancer called squamous cell carcinoma, a precancerous blood disorder known as myelodysplastic syndrome (MDS), and a blood cancer called acute myelogenous leukemia that often follows MDS have occurred in a few people with PN. Some individuals with PN also develop unusual facial features as they grow. These features include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), a small nose with a depressed nasal bridge, and a chin that protrudes (prognathism). Short stature and hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) can also occur in this disorder. ## Frequency The prevalence of PN is unknown; only about 100 affected individuals have been described in the medical literature. Although it was first described in the Navajo population of the southwestern United States, it has since been identified in other individuals worldwide. ## Causes PN is caused by mutations in the USB1 gene. This gene provides instructions for making an enzyme that functions as an RNA exonuclease. RNA exonucleases cut off (cleave) building blocks called nucleotides one at a time from molecules of RNA (a chemical cousin of DNA). This process helps stabilize the RNA and protects it from damage. Specifically, the USB1 enzyme protects a small RNA molecule called U6, which helps in the assembly of the blueprints for protein production. Different versions (isoforms) of the USB1 enzyme are produced in different tissues, where they play various roles. In blood-forming tissues, the USB1 enzyme is thought to play a role in the maturation of neutrophils. In the skin, the enzyme is found in pigment-producing cells (melanocytes), cells in the outer layer of the skin called keratinocytes, and structural cells called fibroblasts. Its role in the function of these cells is unknown. Mutations in the USB1 gene are thought to lead to an enzyme whose function is impaired. As a result of the dysfunctional USB1 exonuclease, the U6 RNA is not protected from damage. The specific connection between USB1 gene mutations and the signs and symptoms of PN is unknown. However, the existence of tissue-specific isoforms of the enzyme could help explain why this disorder mainly affects the skin and immune system. ### Learn more about the gene associated with Poikiloderma with neutropenia * USB1 ## 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 [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	Poikiloderma with neutropenia	c1858723	8,309	medlineplus	https://medlineplus.gov/genetics/condition/poikiloderma-with-neutropenia/	2021-01-27T08:25:14	{"gard": ["4085"], "mesh": ["C565820"], "omim": ["604173"], "synonyms": []}
Cytomegalovirus colitis Other namesCMV colitis Micrograph of CMV colitis. H&E stain. SpecialtyInfectious disease Cytomegalovirus colitis, also known as CMV colitis, is an inflammation of the colon. ## Contents * 1 Causes * 1.1 Risk factors * 2 Diagnosis * 3 Treatment * 4 See also * 5 References ## Causes[edit] The infection is spread by saliva, urine, respiratory droplets, sexual contact, and blood transfusions. Most people are exposed to the virus in their lifetime, but it usually produces mild or no symptoms in healthy people.[citation needed] However, serious CMV infections can occur in people with weakened immune systems. This includes patients receiving chemotherapy for cancer and patients on immune-suppressing medicines following an organ transplant.[citation needed] In rare instances, more severe CMV infection involving the GI tract has been reported in people with a healthy immune system.[citation needed] ### Risk factors[edit] The systemic use of corticosteroids in the context of inflammatory bowel disease.[1] ## Diagnosis[edit] The diagnosis of CMV colitis is based on serology, CMV antigen testing and colonoscopy with biopsy. Clinical suspicion should be aroused in the setting of immunocompromised patient but it is much rarer in immunocompetent patient. Although it is known that CMV colitis is almost always caused by reactivation of latent CMV infection in immunocompromised patients, new infection of CMV or reinfection of different strain of CMV can cause colitis in immunocompetent hosts. Because asymptomatic CMV viremia and viruria is common and about 1/3 of symptomatic CMV infection is caused by reinfection of different strain of CMV, the diagnosis of CMV colitis needs more direct causality. It is practically achieved by colonoscopy or sigmoidoscopy tissue sampling and pathological evidence of CMV infection under microscope. Positive CMV IgG doesn't necessarily mean that it is reactivation of latent infection because of the possibility of reinfection of different strain.[citation needed] ## Treatment[edit] The usual treatment is antivirals, specifically ganciclovir or valganciclovir.[1] Severe CMV colitis may lead a colectomy.[2] ## See also[edit] * Crohn's disease ## References[edit] 1. ^ a b Kandiel A, Lashner B (December 2006). "Cytomegalovirus colitis complicating inflammatory bowel disease". Am. J. Gastroenterol. 101 (12): 2857–65. PMID 17026558. 2. ^ Lawlor G, Moss AC (September 2010). "Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander?". Inflamm. Bowel Dis. 16 (9): 1620–7. doi:10.1002/ibd.21275. PMID 20232408. S2CID 9785434. * 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 * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum * v * t * e Infectious diseases – viral systemic diseases Oncovirus DNA virus HBV Hepatocellular carcinoma HPV Cervical cancer Anal cancer Penile cancer Vulvar cancer Vaginal cancer Oropharyngeal cancer KSHV Kaposi's sarcoma EBV Nasopharyngeal carcinoma Burkitt's lymphoma Hodgkin lymphoma Follicular dendritic cell sarcoma Extranodal NK/T-cell lymphoma, nasal type MCPyV Merkel-cell carcinoma RNA virus HCV Hepatocellular carcinoma Splenic marginal zone lymphoma HTLV-I Adult T-cell leukemia/lymphoma Immune disorders * HIV * AIDS Central nervous system Encephalitis/ meningitis DNA virus Human polyomavirus 2 Progressive multifocal leukoencephalopathy RNA virus MeV Subacute sclerosing panencephalitis LCV Lymphocytic choriomeningitis Arbovirus encephalitis Orthomyxoviridae (probable) Encephalitis lethargica RV Rabies Chandipura vesiculovirus Herpesviral meningitis Ramsay Hunt syndrome type 2 Myelitis * Poliovirus * Poliomyelitis * Post-polio syndrome * HTLV-I * Tropical spastic paraparesis Eye * Cytomegalovirus * Cytomegalovirus retinitis * HSV * Herpes of the eye Cardiovascular * CBV * Pericarditis * Myocarditis Respiratory system/ acute viral nasopharyngitis/ viral pneumonia DNA virus * Epstein–Barr virus * EBV infection/Infectious mononucleosis * Cytomegalovirus RNA virus * IV: Human coronavirus 229E/NL63/HKU1/OC43 * Common cold * MERS coronavirus * Middle East respiratory syndrome * SARS coronavirus * Severe acute respiratory syndrome * SARS coronavirus 2 * Coronavirus disease 2019 * V, Orthomyxoviridae: Influenza virus A/B/C/D * Influenza/Avian influenza * V, Paramyxoviridae: Human parainfluenza viruses * Parainfluenza * Human orthopneumovirus * hMPV Human digestive system Pharynx/Esophagus * MuV * Mumps * Cytomegalovirus * Cytomegalovirus esophagitis Gastroenteritis/ diarrhea DNA virus Adenovirus Adenovirus infection RNA virus Rotavirus Norovirus Astrovirus Coronavirus Hepatitis DNA virus HBV (B) RNA virus CBV HAV (A) HCV (C) HDV (D) HEV (E) HGV (G) Pancreatitis * CBV Urogenital * BK virus * MuV * Mumps [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	Cytomegalovirus colitis	c0341335	8,310	wikipedia	https://en.wikipedia.org/wiki/Cytomegalovirus_colitis	2021-01-18T18:56:05	{"wikidata": ["Q5201361"]}
Thymus hyperplasia Other namesThymic hyperplasia SpecialtyImmunology Thymus hyperplasia refers to an enlargement ("hyperplasia") of the thymus.[1] It is not always a disease state. The size of the thymus usually peaks during adolescence and atrophies in the following decades. Before the immune function of the thymus was well understood, the enlargement was sometimes seen as a cause for alarm, and justification for surgical reduction. This approach is much less common today. It can be associated with myasthenia gravis.[2][3]MRI can be used to distinguish it from thymoma.[4] ## References[edit] 1. ^ "eMedicine - Surgery of the Thymus Gland : Article by Said Fadi Yassin". 2019-02-26. Cite journal requires `\|journal=` (help) 2. ^ "Thymus, hyperplasia". Medcyclopaedia. GE. 3. ^ Murakami M, Hosoi Y, Negishi T, et al. (November 1996). "Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus". J. Clin. Invest. 98 (10): 2228–34. doi:10.1172/JCI119032. PMC 507671. PMID 8941638. 4. ^ Inaoka T, Takahashi K, Mineta M, et al. (June 2007). "Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging". Radiology. 243 (3): 869–76. doi:10.1148/radiol.2433060797. PMID 17463136. ## External links[edit] Classification D * ICD-10: E32.0 * ICD-9-CM: 254.0 * MeSH: D013952 * v * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann disease This article related to pathology 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	Thymus hyperplasia	c0040115	8,311	wikipedia	https://en.wikipedia.org/wiki/Thymus_hyperplasia	2021-01-18T18:46:04	{"mesh": ["D013952"], "umls": ["C0040115"], "icd-9": ["254.0"], "icd-10": ["E32.0"], "wikidata": ["Q7799652"]}
A number sign (#) is used with this entry because of evidence that craniofrontonasal syndrome (CFNS) is caused by mutation in the EFNB1 gene (300035) on chromosome Xq13. Description Craniofrontonasal syndrome is an X-linked developmental disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. Females have frontonasal dysplasia, craniofacial asymmetry, craniosynostosis, bifid nasal tip, grooved nails, wiry hair, and abnormalities of the thoracic skeleton, whereas males typically show only hypertelorism (Twigg et al., 2004; Wieland et al., 2004). Clinical Features Cohen (1979) identified CFNS as a subgroup of frontonasal dysplasia. CFNS is characterized in females by hypertelorism, coronal craniosynostosis, craniofacial asymmetry, frontal bossing, downslanting palpebral fissures, clefting of the nasal tip, longitudinally grooved fingernails, and other digital anomalies (Vasudevan et al., 2006). Pruzansky et al. (1982) described an extensively affected family in which 14 females and 1 male had CFNS. Kwee and Lindhout (1983) reported a 2-year-old boy, born of nonconsanguineous Dutch parents, who exhibited brachycephaly with a broad, prominent forehead, retracted supraorbital ridges, severe ocular hypertelorism, downslanting palpebral fissures, broad nasal bridge, and broad bifid tip of the nose. The mouth was tent-shaped, with a pseudocleft-like philtrum of the upper lip and high-arched palate. Ears were thick and low set, and the neck was short without webbing. The right thumb was broad and partially bifid at the tip, with a broad, concave, and longitudinally split fingernail; x-ray revealed duplication of the distal phalanx of the thumb. A rudimentary postaxial finger on this hand was surgically removed in infancy, and the nails of several other fingers and toes also showed a median longitudinal split. In addition, there was bilateral cryptorchidism. Skull x-rays showed synostosis of the coronal suture, and CT scan showed an enlarged ventricular system without apparent structural malformation. A second cousin of the proband also had unilateral duplication of the distal phalanx with concave fingernails and hypoplastic toenails, but no other anomalies. Other family members exhibited one or more minor anomalies, including longitudinally split nails, broad thumbs and first toes, hypertelorism, and/or downslanting palpebral fissures. Morris et al. (1987) described a 4-generation family in which 6 persons had frontonasal dysplasia with variable extracranial abnormalities. All affected persons had hypertelorism, bifid or broad nose, and highly arched palate. Cleft lip and palate were present in 1, Sprengel anomaly in 2, pseudarthrosis of the clavicle in 2, pectus excavatum in 3, diaphragmatic hernia in 2, broad first toe in 4, longitudinal grooves of the nails in 5, shawl scrotum in 2 of 3 males, 1 of whom had first-degree hypospadias, and mild retardation in 1. Morris et al. (1987) reviewed reported families, including those of Reynolds et al. (1982), Slover and Sujansky (1979), and Pruzansky et al. (1982). All daughters of affected males were affected, a finding consistent with X-linked dominant inheritance. Hurst and Baraitser (1988) confirmed the female preponderance in this condition and noted that all of their patients had thick, wiry hair. Smith et al. (1989) described a 3-generation family. In addition to the coronal craniosynostosis and facial changes, syndactyly of fingers and toes and longitudinally grooved nails were present. More mildly affected males did not have craniosynostosis but did show hypertelorism, broad great toes, and grooved nails. Smith et al. (1989) provided follow-up of the family reported by Slover and Sujansky (1979); 5 daughters were all affected, whereas 3 sons were all normal. Since there is no evidence of tissue dysplasia in CFNS, Michels et al. (1989) suggested that the disorder be designated craniofrontonasal dysostosis. They reported an affected mother and daughter who also had limited hip and shoulder abduction. In addition, the mother had axillary pterygia, congenital footplate fixation of the left ear, right sensorineural hearing loss, and limited forearm pronation. Kapusta et al. (1992) reported a patient who was only the second male in the literature with all the clinical features of classic CFNS. Devriendt et al. (1995) reported craniofrontal nasal dysplasia in mother and son, further illustrating 2 unexplained observations in this disorder: more severe clinical expression in females and an increased incidence of miscarriages. In a review of 41 patients with CFNS studied in Mexico City between 1979 and 1993, Saavedra et al. (1996) reported several unusual manifestations in females, including thick, wiry, and curly hair (49%), anterior cranium bifidum (6%), axillary pterygia (9%), unilateral breast hypoplasia, postpubertal (11%), and asymmetric lower limb shortness (14%). McGaughran et al. (2002) reported a mother and daughter with CFNS; the daughter also had diaphragmatic hernia. McGaughran et al. (2002) stated that this was the first reported female case of CFNS associated with diaphragmatic hernia and suggested that the brothers reported by Morris et al. (1987) with CFNS and diaphragmatic hernia instead had Teebi syndrome (145420). Wieland et al. (2002, 2004) reported a 5-generation German family in which 6 females had features of CFNS, including hypertelorism, orbital asymmetry, brachycephaly, brachydactyly, and Sprengel deformity (184400). One affected member, who had 4 miscarriages, had an arcuate uterus; she also had curly hair, grooved fingernails, and unilateral breast hypoplasia. One son of an affected female was considered to be affected because of hypertelorism with an inner canthal distance greater than the 97th centile at 9 years of age. One male with 2 affected daughters and no other children was judged to be unaffected or to have at the most 'microsymptoms.' Wieland et al. (2004) reported 2 more families with CFNS; additional variable features included agenesis of the corpus callosum, syndactyly, and scoliosis. Vasudevan et al. (2006) reported 2 unrelated families in which a mother and son had CFNS confirmed by molecular analysis. The mothers both had classic features of CFNS. Both sons had no major craniofacial features other than telecanthus, but both had congenital diaphragmatic hernia. Hogue et al. (2010) reported a father and daughter with CFNS and a truncating mutation in the EFNB1 gene (300035). The father displayed hypertelorism and a widow's peak, and had pectus carinatum that had been surgically corrected, whereas the daughter had hypertelorism, bifid nasal tip, widow's peak, frontal bossing, and a widened metopic suture. The paternal grandmother did not have hypertelorism, but had a dysplastic left fifth toe and a reported 'chest deformity' that was not examined. In addition, the mother had also previously undergone therapeutic abortion of a female fetus with congenital diaphragmatic hernia. Hogue et al. (2010) suggested that CFNS should be considered in patients presenting with congenital diaphragmatic hernia. Inheritance Rollnick et al. (1981) presented a pedigree most plausibly interpreted as indicating X-linked inheritance with 'metabolic interference,' a pattern proposed on theoretic grounds by Johnson (1980). Johnson (1980) suggested that some disorders may show up only in heterozygotes as a result of adverse interaction of 2 alleles, neither of which occasions abnormality when homozygous or hemizygous. Reynolds et al. (1982) reported a 3-generation family in which 4 females and 1 male were affected. The mode of inheritance was unclear. Young and Moore (1984) suggested that CFNS may be lethal in the male. From a study of 21 unrelated patients with CFNS and their families, Reich et al. (1985) suggested autosomal dominant inheritance based on 2 instances of apparent male-to-male transmission. An excess of females (19:2) remained unexplained, but the fact that 10 of 12 sibs of family-history-positive probands were male appeared to rule against semilethality in males. In the family reported by Kumar et al. (1986), the trait may have occurred in 6 females of 5 generations. Sax and Flannery (1986) reviewed 8 published pedigrees and added a ninth. They concluded that the segregation does not fit autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive inheritance. Kere et al. (1990) described variable expression of craniofrontonasal dysostosis in a 3-generation family. There were 3 severely affected females, 2 of them daughters of apparently healthy parents. Two male relatives, including the father of the 2 affected daughters, had orbital hypertelorism and other minor anomalies. Kere et al. (1990) concluded that the expression of the gene is modified by the sex of the subject. In connection with the description of 9 patients with CFNS, Kapusta et al. (1992) commented on the unusual pattern of familial occurrence: while affected females apparently transmit the disorder in equal proportions to sons and daughters, they stated that no male-to-male transmission had been documented (Grutzner and Gorlin, 1988). Two affected fathers in their series had an unaffected son. Added to published information, 8 affected males had reproduced, producing 21 females, all affected, and 8 males, all unaffected. Of 41 patients with CFNS studied in Mexico City between 1979 and 1993, Saavedra et al. (1996) found that 35 were female and 6 were male. Although most cases were sporadic, 7 familial instances were found. They pointed out that male-to-male transmission had not been observed. They stated the opinion that CFNS is an 'incompletely understood X-linked disorder.' Mapping Wieland et al. (2002) described a German family with CFNS in which the locus appeared to map to the pericentromeric region of the X chromosome, at Xq12, rather than to Xp22, as had previously been suggested by Feldman et al. (1997) and Muenke et al. (1997) (see below). Wieland et al. (2002) showed random X inactivation in affected females, and favored X-linked inheritance with metabolic interference as the explanation for the pedigree pattern. ### Possible Genetic Heterogeneity McPherson et al. (1991) reported a female with typical CFNS manifested by hypertelorism, slightly bifid nose, turribrachycephaly, sloping shoulders, minor digital anomalies, short stature, and moderate mental retardation who also had a terminal deletion of Xpter-p22.2. The phenotypically normal mother had normal chromosomes. Studying 2 independent cases of CFNS associated with breaks at Xp22, Muenke (1996) identified YACs that crossed the breakpoints. By linkage analysis of 12 CFNS families, Feldman et al. (1997) and Muenke et al. (1997) mapped the disorder to a 13-cM interval on Xp22 (maximum 2-point lod score of 3.9 at theta = 0.0 for DXS8022; and a multipoint lod score of 5.08 at DXS1224). Detailed phenotypic analysis in these families showed that females were more severely affected than males; affected males showed hypertelorism as the only sign, and none had coronal synostosis in contrast to the findings in their female relatives. In females, findings included severe hypertelorism with extremely broad nasal root and severe craniofacial asymmetry, including orbital asymmetry probably caused by unicoronal synostosis. Molecular Genetics In affected members of 3 unrelated families with CFNS, Wieland et al. (2004) identified mutations in the EFNB1 gene (300035.0001-300035.0003). In 24 affected females from 20 unrelated families with CFNS, Twigg et al. (2004) identified 17 different mutations in the EFNB1 gene (see, e.g., 300035.0004-300035.0007). Among 38 unrelated patients with CFNS, Wieland et al. (2005) identified 33 different mutations in the EFNB1 gene, including 26 novel mutations. Nine cases were familial, and 29 cases were sporadic. Wieland et al. (2007) identified mutations in the EFNB1 gene in 10 of 13 patients with CFNS. The 3 remaining patients had contiguous gene deletions involving EFNB1 and the neighboring genes OPHN1 (300127), PJA1 (300420), and EDA (300451). Wallis et al. (2008) analyzed the EFNB1 gene in 35 unrelated CFNS patients (16 sporadic cases and 19 familial), and identified mutations in 19 patients. The authors stated that 33 (20%) of 129 CFNS cases published to date have no identifiable mutation in the EFNB1 gene and suggested that those cases might involve misdiagnoses, undetected large deletions or rearrangements, or mutations outside the EFNB1 coding region, mosaicism, or additional CFNS loci. Wieland et al. (2008) showed that cultured fibroblasts derived from female patients with heterozygous EFNB1 mutations expressed both mutant and wildtype EFNB1 and that upon clonal expansion it was possible to separate wildtype and mutant EFNB1-expressing cells in vitro, indicating that they carry 2 distinct cell populations with respect to EFNB1 gene function. These results supported cellular interference as being the cause of the more severe phenotype in CFNS females. Such a situation does not occur in hemizygous carrier males, who are mildly affected. In 6 severely affected males with a diagnosis of CFNS, 2 of whom had previously been reported (Kwee and Lindhout, 1983; Kapusta et al., 1992), Twigg et al. (2013) analyzed multiple tissue samples and identified mosaic mutations in the EFNB1 gene in all 6 patients (see, e.g., 300035.0010-300035.0012), with levels of mutant cells between 15% and 69%. All 6 patients had documented coronal craniosynostosis and exhibited severe hypertelorism; other features included agenesis of the corpus callosum, bifid nasal tip, longitudinally split nails, cryptorchidism, and mild learning disability. Twigg et al. (2013) noted that these results demonstrated a more severe outcome in mosaic males than in constitutionally deficient males in an X-linked dominant disorder and provided further support for the cellular interference mechanism, which is normally related to X inactivation in females. INHERITANCE \- X-linked dominant GROWTH Height \- Short stature (males) HEAD & NECK Head \- Brachycephaly (females and mosaic males) Face \- Frontal bossing (females and mosaic males) \- Facial asymmetry \- Widow's peak Eyes \- Hypertelorism (males and females) \- Telecanthus (females) \- Exotropia (females) \- Nystagmus (females) \- Strabismus (females) \- Downslanting palpebral fissures Nose \- Broad nasal root \- Bifid nasal tip \- Hypoplastic nasal tip Mouth \- Cleft lip \- Cleft palate Teeth \- Dental anomalies (mosaic males) Neck \- Short neck CHEST External Features \- Narrow sloping shoulders Ribs Sternum Clavicles & Scapulae \- Sprengel deformity (females and mosaic males) \- Pectus excavatum (males) \- Clavicle pseudoarthrosis (males) Breasts \- Unilateral breast hypoplasia Diaphragm \- Diaphragmatic hernia ABDOMEN External Features \- Umbilical hernia GENITOURINARY External Genitalia (Male) \- Hypospadias \- Shawl scrotum Internal Genitalia (Male) \- Cryptorchidism SKELETAL Skull \- Coronal craniosynostosis (females and mosaic males) \- Increased interorbital distance (males) Limbs \- Asymmetric lower limb shortness \- Joint laxity Hands \- Syndactyly (females and mosaic males) \- Brachydactyly (males) \- Fifth finger clinodactyly (females and mosaic males) Feet \- Syndactyly \- Broad halluces SKIN, NAILS, & HAIR Skin \- Axillary pterygia Nails \- Brittle nails \- Longitudinal splitting \- Grooved nails Hair \- Thick, wiry hair (females and mosaic males) \- Widow's peak \- Low posterior hairline NEUROLOGIC Central Nervous System \- Normal intelligence \- Developmental delay \- Hypotonia \- Hypoplasia or agenesis of corpus callosum MISCELLANEOUS \- Primarily diagnosed in females \- Expression more severe in females than males, except for mosaic males \- Possible genetic heterogeneity (linkage to Xp22 in some families) MOLECULAR BASIS \- Caused by mutation in the ephrin B1 gene (EFNB1, 300035.0001 ) ▲ 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	CRANIOFRONTONASAL SYNDROME	c0220767	8,312	omim	https://www.omim.org/entry/304110	2019-09-22T16:18:28	{"doid": ["14737"], "mesh": ["C536456"], "omim": ["304110"], "orphanet": ["1520"], "synonyms": ["Alternative titles", "CRANIOFRONTONASAL DYSPLASIA", "CRANIOFRONTONASAL DYSOSTOSIS"]}
Birth at less than a specified gestational age Preterm birth Other namesPremature birth, preemies, premmies Intubated preterm baby in an incubator SpecialtyNeonatology, Pediatrics, Obstetrics SymptomsBirth of a baby at younger than 37 weeks' gestational age[1] ComplicationsCerebral palsy, delays in development, hearing problems, sight problems[1] CausesOften unknown[2] Risk factorsDiabetes, high blood pressure, being pregnant with more than one baby, obesity or underweight, a number of vaginal infections, celiac disease, tobacco smoking, psychological stress[2][3][4] PreventionProgesterone[5] TreatmentCorticosteroids, keeping the baby warm through skin-to-skin contact, supporting breastfeeding, treating infections, supporting breathing[2][6] Frequency~15 million a year (12% of deliveries)[2] Deaths805,800[7] Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks' gestational age, as opposed to the usual about 40 weeks.[1] These babies are known as preemies or premmies.[1] Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes or the leaking of fluid from the vagina.[8] Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and sight problems.[1] The earlier a baby is born, the greater these risks will be.[1] The cause of preterm birth is often not known.[2] Risk factors include diabetes, high blood pressure, being pregnant with more than one baby, being either obese or underweight, a number of vaginal infections, air pollution including tobacco smoking, and psychological stress.[2][3][9] It is recommended that labor not be medically induced before 39 weeks unless required for other medical reasons.[2] The same recommendation applies to cesarean section.[2] Medical reasons for early delivery include preeclampsia.[10] In those at risk, the hormone progesterone, if taken during pregnancy, may prevent preterm birth.[5] Evidence does not support the usefulness of bed rest.[5][11] It is estimated that at least 75% of preterm infants would survive with appropriate treatment, and the survival rate is highest among the infants born the latest.[2] In women who might deliver between 24 and 37 weeks, corticosteroids improve outcomes.[6][12] A number of medications, including nifedipine, may delay delivery so that a mother can be moved to where more medical care is available and the corticosteroids have a greater chance to work.[13] Once the baby is born, care includes keeping the baby warm through skin-to-skin contact, supporting breastfeeding, treating infections and supporting breathing.[2] Preterm birth is the most common cause of death among infants worldwide.[1] About 15 million babies are preterm each year (5% to 18% of all deliveries).[2] In the United Kingdom they are about 7.9% and in the United States they are about 12.3% of all births.[14][15] Approximately 0.5% of births are extremely early periviable births, and these account for most of the deaths.[16] In many countries, rates of premature births have increased between the 1990s and 2010s.[2] Complications from preterm births resulted in 0.81 million deaths in 2015, down from 1.57 million in 1990.[7][17] The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72%.[18] The chances of survival without any long-term difficulties are lower.[19] ## Contents * 1 Signs and symptoms * 1.1 Complications * 1.1.1 Mortality and morbidity * 1.1.2 Specific risks for the preterm neonate * 2 Risk factors * 2.1 Maternal factors * 2.2 Factors during pregnancy * 2.3 Infection * 2.4 Genetics * 3 Diagnosis * 3.1 Placental alpha microglobulin-1 * 3.2 Fetal fibronectin * 3.3 Ultrasound * 3.4 Classification * 4 Prevention * 4.1 Before pregnancy * 4.2 During pregnancy * 4.2.1 Screening of low risk women * 4.2.2 Self-care * 4.2.3 Cervical assessment by ultrasound * 4.3 Reducing existing risks * 4.3.1 Multiple pregnancies * 4.3.2 Reducing indicated preterm birth * 4.3.3 Reducing spontaneous preterm birth * 4.3.3.1 Antibiotics * 4.3.3.2 Progestogens * 4.3.3.3 Cervical cerclage * 5 Management * 5.1 Steroids * 5.2 Antibiotics * 5.3 Tocolysis * 5.4 Mode of delivery * 5.5 Neonatal care * 5.6 Nutrition * 5.7 Hearing assessment * 6 Prognosis * 7 Epidemiology * 8 Society and culture * 8.1 Economics * 8.2 Notable cases * 8.3 Effect of the coronavirus pandemic * 9 Neurological research * 10 See also * 11 References ## Signs and symptoms[edit] A new mother holds her premature baby at Kapiolani Medical Center NICU in Honolulu, Hawaii A preterm birth can be brought on by being induced, or can occur spontaneously. Preterm births can cause a range of problems.[20][21] The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labour, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process. A review into using uterine monitoring at home to detect contractions and possible preterm births in women at higher risk of having a preterm baby found that it did not reduce the number of preterm births.[22] The research included in the review was poor quality but it showed that home monitoring may increase the number of unplanned antenatal visits and may reduce the number of babies admitted to special care when compared with women receiving normal antenatal care.[22] ### Complications[edit] #### Mortality and morbidity[edit] In the U.S. where many neonatal infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%.[23] Prematurely born infants are also at greater risk for having subsequent serious chronic health problems as discussed below. The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, the limit of viability has reduced to approximately 24 weeks.[24][25] Most newborns who die, and 40% of older infants who die, were born between 20 and 25.9 weeks (gestational age), during the second trimester.[16] As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate.[26] #### Specific risks for the preterm neonate[edit] Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems. * Neurological problems include apnea of prematurity, hypoxic-ischemic encephalopathy (HIE), retinopathy of prematurity (ROP),[27] developmental disability, transient hyperammonemia of the newborn, cerebral palsy and intraventricular hemorrhage, the latter affecting 25% of babies born preterm, usually before 32 weeks of pregnancy.[28] Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death.[28] Neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet postnatal needs.[29] * Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA). * Respiratory problems are common, specifically the respiratory distress syndrome (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be chronic lung disease (previously called bronchopulmonary dysplasia or BPD). * Gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, rickets of prematurity, hypocalcemia, inguinal hernia, and necrotizing enterocolitis (NEC). * Hematologic complications include anemia of prematurity, thrombocytopenia, and hyperbilirubinemia (jaundice) that can lead to kernicterus. * Infection, including sepsis, pneumonia, and urinary tract infection [1] A study of 241 children born between 22 and 25 weeks who were currently of school age found that 46 percent had severe or moderate disabilities such as cerebral palsy, vision or hearing loss and learning problems. Thirty-four percent were mildly disabled and 20 percent had no disabilities, while 12 percent had disabling cerebral palsy.[30][31] Up to 15 out of 100 premature infants have significant hearing loss.[32] ## Risk factors[edit] The exact cause of preterm birth is difficult to determine and it may be multi-factorial.[33][citation needed] Labor is a complex process involving many factors. Four different pathways have been identified that can result in preterm birth and have considerable evidence: precocious fetal endocrine activation, uterine overdistension (placental abruption), decidual bleeding, and intrauterine inflammation/infection.[34] Identifying women at high risk of giving birth early would enable the health services to provide specialized care for these women to delay the birth or make sure they are in the best place to give birth (for example a hospital with a special care baby unit). Risk scoring systems have been suggested as a possible way of identifying these women. However, there is no research in this area so it is unclear whether the risk scoring systems would prolong pregnancy and reduce the numbers of preterm births or not.[35] ### Maternal factors[edit] Risk factor Relative risk[36] 95% confidence interval[36] Fetal fibronectin 4.0 2.9–5.5 Short cervical length 2.9 2.1–3.9 Chlamydia 2.2 1.0–4.8 Low socio-economic status 1.9 1.7–2.2 Large or small pregnancy weight gain 1.8 1.5–2.3 Short maternal height 1.8 1.3–2.5 Periodontitis 1.6 1.1–2.3 Celiac disease 1.4[37] 1.2–1.6[37] Asymptomatic bacteriuria 1.1 0.8–1.5 High or low BMI 0.96 0.66–1.4 odds ratio History of spontaneous preterm birth 3.6 3.2–4.0 Bacterial vaginosis 2.2 1.5–3.1 Black ethnicity/race 2.0 1.8–2.2 Filipino ancestry[38] 1.7 1.5–2.1 Unwanted pregnancy[39]:1 1.5 1.41-1.61 Unintended pregnancy[39]:1 1.31 1.09-1.58 Being single/unmarried[40] 1.2 1.03–1.28 Percentage premature births in England and Wales 2011, by age of mother and whether single or multiple birth. A number of factors have been identified that are linked to a higher risk of a preterm birth such as being less than 18 years of age.[41] Maternal height and weight can play a role.[42] Further, in the U.S. and the UK, black women have preterm birth rates of 15–18%, more than double than that of the white population. Many Black women have higher preterm birth rates due to multiple factors but the most common is high amounts of chronic stress, which can eventually lead to premature birth.[43] Adult chronic disease isn't always the case with premature birth in Black women, which makes the main factor of premature birth challenging to identify.[43] Filipinos are also at high risk of premature birth, and it is believed that nearly 11–15% of Filipinos born in the U.S. (compared to other Asians at 7.6% and whites at 7.8%) are premature.[44] Filipinos being a big risk factor is evidenced with the Philippines being the 8th highest ranking in the world for preterm births, the only non-African country in the top 10.[45] This discrepancy is not seen in comparison to other Asian groups or Hispanic immigrants and remains unexplained.[41] Pregnancy interval makes a difference as women with a six-month span or less between pregnancies have a two-fold increase in preterm birth.[46] Studies on type of work and physical activity have given conflicting results, but it is opined that stressful conditions, hard labor, and long hours are probably linked to preterm birth.[41] A history of spontaneous (i.e., miscarriage) or surgical abortion has been associated with a small increase in the risk of preterm birth, with an increased risk with increased number of abortions, although it is unclear whether the increase is caused by the abortion or by confounding risk factors (e.g., socioeconomic status).[47] Increased risk has not been shown in women who terminated their pregnancies medically.[48] Pregnancies that are unwanted or unintended are also a risk factor for preterm birth.[39] Adequate maternal nutrition is important. Women with a low BMI are at increased risk for preterm birth.[49] Further, women with poor nutrition status may also be deficient in vitamins and minerals. Adequate nutrition is critical for fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery.[50] Obesity does not directly lead to preterm birth;[51] however, it is associated with diabetes and hypertension which are risk factors by themselves.[41] To some degree those individuals may have underlying conditions (i.e., uterine malformation, hypertension, diabetes) that persist. Women with celiac disease have an increased risk of the development of preterm birth.[37] The risk of preterm birth is more elevated when celiac disease remains undiagnosed and untreated.[4] Marital status is associated with risk for preterm birth. A study of 25,373 pregnancies in Finland revealed that unmarried mothers had more preterm deliveries than married mothers (P=0.001).[40] Pregnancy outside of marriage was associated overall with a 20% increase in total adverse outcomes, even at a time when Finland provided free maternity care. A study in Quebec of 720,586 births from 1990 to 1997 revealed less risk of preterm birth for infants with legally married mothers compared with those with common-law wed or unwed parents.[52][needs update] Genetic make-up is a factor in the causality of preterm birth. Genetics has been a big factor into why Filipinos have a high risk of premature birth as the Filipinos have a large prevalence of mutations that help them be predisposed to premature births.[44] An intra- and transgenerational increase in the risk of preterm delivery has been demonstrated.[53] No single gene has been identified. Subfertility is associated with preterm birth. Couples who have tried more than 1 year versus those who have tried less than 1 year before achieving a spontaneous conception have an adjusted odds ratio of 1.35 (95% confidence interval 1.22-1.50) of preterm birth.[54] Pregnancies after IVF confers a greater risk of preterm birth than spontaneous conceptions after more than 1 year of trying, with an adjusted odds ratio of 1.55 (95% CI 1.30-1.85).[54] Exposure to heat also appear to increase the risk of preterm birth, with this occurring in about 25,000 pregnancies per year.[55] ### Factors during pregnancy[edit] Air pollution increases the risk of preterm birth.[9] One study attributed air pollution to 18% of premature births globally.[56] The countries with the highest air pollution associated preterm births were in South and East Asia, the Middle East, North Africa, and West sub-Saharan Africa. Living in an area with a high concentration of air pollution is a major risk factor, including living near major roadways or highways where vehicle emissions are high from traffic congestion or are a route for diesel trucks that tend to emit more pollution.[57][58] The use of fertility medication that stimulates the ovary to release multiple eggs and of IVF with embryo transfer of multiple embryos has been implicated as an important factor in preterm birth. Maternal medical conditions increase the risk of preterm birth. Often labor has to be induced for medical reasons; such conditions include high blood pressure,[59] pre-eclampsia,[60] maternal diabetes,[61] asthma, thyroid disease, and heart disease. In a number of women anatomical issues prevent the baby from being carried to term. Some women have a weak or short cervix[59] (the strongest predictor of premature birth)[62][63][64] Women with vaginal bleeding during pregnancy are at higher risk for preterm birth. While bleeding in the third trimester may be a sign of placenta previa or placental abruption – conditions that occur frequently preterm – even earlier bleeding that is not caused by these conditions is linked to a higher preterm birth rate.[65] Women with abnormal amounts of amniotic fluid, whether too much (polyhydramnios) or too little (oligohydramnios), are also at risk.[41] The mental status of the women is of significance. Anxiety[66] and depression have been linked to preterm birth.[41] The use of tobacco, cocaine, and excessive alcohol during pregnancy increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and contributes significantly to low birth weight delivery.[67] Babies with birth defects are at higher risk of being born preterm.[68] Passive smoking and/or smoking before the pregnancy influences the probability of a preterm birth. The World Health Organization published an international study in March 2014.[69] Presence of anti-thyroid antibodies is associated with an increased risk preterm birth with an odds ratio of 1.9 and 95% confidence interval of 1.1–3.5.[70] A 2004 systematic review of 30 studies on the association between intimate partner violence and birth outcomes concluded that preterm birth and other adverse outcomes, including death, are higher among abused pregnant women than among non-abused women.[71] The Nigerian cultural method of abdominal massage has been shown to result in 19% preterm birth among women in Nigeria, plus many other adverse outcomes for the mother and baby.[72] This ought not be confused with massage conducted by a fully trained and licensed massage therapist or by significant others trained to provide massage during pregnancy, which has been shown to have numerous positive results during pregnancy, including the reduction of preterm birth, less depression, lower cortisol, and reduced anxiety.[73] ### Infection[edit] The frequency of infection in preterm birth is inversely related to the gestational age. Mycoplasma genitalium infection is associated with increased risk of preterm birth, and spontaneous abortion.[74] Infectious microorganisms can be ascending, hematogeneous, iatrogenic by a procedure, or retrograde through the Fallopian tubes. From the deciduas they may reach the space between the amnion and chorion, the amniotic fluid, and the fetus. A chorioamnionitis also may lead to sepsis of the mother. Fetal infection is linked to preterm birth and to significant long-term handicap including cerebral palsy.[75] It has been reported that asymptomatic colonization of the decidua occurs in up to 70% of women at term using a DNA probe suggesting that the presence of micro-organism alone may be insufficient to initiate the infectious response. As the condition is more prevalent in black women in the US and the UK, it has been suggested to be an explanation for the higher rate of preterm birth in these populations. It is opined that bacterial vaginosis before or during pregnancy may affect the decidual inflammatory response that leads to preterm birth. The condition known as aerobic vaginitis can be a serious risk factor for preterm labor; several previous studies failed to acknowledge the difference between aerobic vaginitis and bacterial vaginosis, which may explain some of the contradiction in the results.[76] Untreated yeast infections are associated with preterm birth.[77] A review into prophylactic antibiotics (given to prevent infection) in the second and third trimester of pregnancy (13–42 weeks of pregnancy) found a reduction in the number of preterm births in women with bacterial vaginosis. These antibiotics also reduced the number of waters breaking before labor in full-term pregnancies, reduced the risk of infection of the lining of the womb after delivery (endometritis), and rates of gonococcal infection. However, the women without bacterial vaginosis did not have any reduction in preterm births or pre-labor preterm waters breaking. Much of the research included in this review lost participants during follow-up so did not report the long-term effects of the antibiotics on mothers or babies. More research in this area is needed to find the full effects of giving antibiotics throughout the second and third trimesters of pregnancy.[78] A number of maternal bacterial infections are associated with preterm birth including pyelonephritis, asymptomatic bacteriuria, pneumonia, and appendicitis. A review into giving antibiotics in pregnancy for asymptomatic bacteriuria (urine infection with no symptoms) found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight.[79] Another review found that one dose of antibiotics did not seem as effective as a course of antibiotics but fewer women reported side effects from one dose.[80] This review recommended that more research is needed to discover the best way of treating asymptomatic bacteriuria.[79] A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections.[81] The women being routinely tested also gave birth to fewer babies with a low birth weight. Even though these results look promising, the review was only based on one study so more research is needed into routine screening for low genital tract infections.[81] Also periodontal disease has been shown repeatedly to be linked to preterm birth.[82][83] In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth.[41] ### Genetics[edit] There is believed to be a maternal genetic component in preterm birth.[84] Estimated heritability of timing-of-birth in women was 34%. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature.[85] ## Diagnosis[edit] ### Placental alpha microglobulin-1[edit] Placental alpha microglobulin-1 (PAMG-1) has been the subject of several investigations evaluating its ability to predict imminent spontaneous preterm birth in women with signs, symptoms, or complaints suggestive of preterm labor.[86][87][88][89][90][91] In one investigation comparing this test to fetal fibronectin testing and cervical length measurement via transvaginal ultrasound, the test for PAMG-1 (commercially known as the PartoSure test) has been reported to be the single best predictor of imminent spontaneous delivery within 7 days of a patient presenting with signs, symptoms, or complaints of preterm labor. Specifically, the PPV, or positive predictive value, of the tests were 76%, 29%, and 30% for PAMG-1, fFN and CL, respectively (P < 0.01).[92] ### Fetal fibronectin[edit] Fetal fibronectin (fFN) has become an important biomarker—the presence of this glycoprotein in the cervical or vaginal secretions indicates that the border between the chorion and deciduas has been disrupted. A positive test indicates an increased risk of preterm birth, and a negative test has a high predictive value.[41] It has been shown that only 1% of women in questionable cases of preterm labor delivered within the next week when the test was negative.[93] ### Ultrasound[edit] Further information: Cervical incompetence Obstetric ultrasound has become useful in the assessment of the cervix in women at risk for premature delivery. A short cervix preterm is undesirable: A cervical length of less than 25 mm at or before 24 weeks of gestational age is the most common definition of cervical incompetence.[94] ### Classification[edit] Stages in prenatal development, with weeks and months numbered from last menstruation. In humans, the usual definition of preterm birth is birth before a gestational age of 37 complete weeks.[95] In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period. One of the main organs greatly affected by premature birth is the lungs. The lungs are one of the last organs to mature in the womb; because of this, many premature babies spend the first days and weeks of their lives on ventilators. Therefore, a significant overlap exists between preterm birth and prematurity. Generally, preterm babies are premature and term babies are mature. Preterm babies born near 37 weeks often have no problems relating to prematurity if their lungs have developed adequate surfactant, which allows the lungs to remain expanded between breaths. Sequelae of prematurity can be reduced to a small extent by using drugs to accelerate maturation of the fetus, and to a greater extent by preventing preterm birth. ## Prevention[edit] Historically efforts have been primarily aimed to improve survival and health of preterm infants (tertiary intervention). Such efforts, however, have not reduced the incidence of preterm birth. Increasingly primary interventions that are directed at all women, and secondary intervention that reduce existing risks are looked upon as measures that need to be developed and implemented to prevent the health problems of premature infants and children.[96] Smoking bans are effective in decreasing preterm births.[97] ### Before pregnancy[edit] Adoption of specific professional policies can immediately reduce risk of preterm birth as the experience in assisted reproduction has shown when the number of embryos during embryo transfer was limited.[96] Many countries have established specific programs to protect pregnant women from hazardous or night-shift work and to provide them with time for prenatal visits and paid pregnancy-leave. The EUROPOP study showed that preterm birth is not related to type of employment, but to prolonged work (over 42 hours per week) or prolonged standing (over 6 hours per day).[98] Also, night work has been linked to preterm birth.[99] Health policies that take these findings into account can be expected to reduce the rate of preterm birth.[96] Preconceptional intake of folic acid is recommended to reduce birth defects. There is significant evidence that long-term (> one year) use of folic acid supplement preconceptionally may reduce premature birth.[100][101][102] Reducing smoking is expected to benefit pregnant women and their offspring.[96] ### During pregnancy[edit] Healthy eating can be instituted at any stage of the pregnancy including nutritional adjustments, use of vitamin supplements, and smoking cessation.[96] Calcium supplementation in women who have low dietary calcium may reduce the number of negative outcomes including preterm birth, pre-eclampsia, and maternal death.[103] The World Health Organization (WHO) suggests 1.5–2 g of calcium supplements daily, for pregnant women who have low levels calcium in their diet.[104] Supplemental intake of C and E vitamins have not been found to reduce preterm birth rates.[105] Different strategies are used in the administration of prenatal care, and future studies need to determine if the focus can be on screening for high-risk women, or widened support for low-risk women, or to what degree these approaches can be merged.[96] While periodontal infection has been linked with preterm birth, randomized trials have not shown that periodontal care during pregnancy reduces preterm birth rates.[96] Additional support during pregnancy does not appear to prevent low birthweight or preterm birth.[106] #### Screening of low risk women[edit] Screening for asymptomatic bacteriuria followed by appropriate treatment reduces pyelonephritis and reduces the risk of preterm birth.[107] Extensive studies have been carried out to determine if other forms of screening in low-risk women followed by appropriate intervention are beneficial, including: Screening for and treatment of Ureaplasma urealyticum, group B streptococcus, Trichomonas vaginalis, and bacterial vaginosis did not reduce the rate of preterm birth.[96] Routine ultrasound examination of the length of the cervix identifies patients at risk, but cerclage is not proven useful, and the application of a progestogen is under study.[96] Screening for the presence of fibronectin in vaginal secretions is not recommended at this time in women at low risk. #### Self-care[edit] Self-care methods to reduce the risk of preterm birth include proper nutrition, avoiding stress, seeking appropriate medical care, avoiding infections, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Self-monitoring vaginal pH followed by yogurt treatment or clindamycin treatment if the pH was too high all seem to be effective at reducing the risk of preterm birth.[108][109] #### Cervical assessment by ultrasound[edit] There is tentative evidence that ultrasound measurement of the length of the cervix in those with preterm labor can help adjust management and results in the extension of pregnancy by about 4 days.[110] ### Reducing existing risks[edit] Women are identified to be at increased risk for preterm birth on the basis of their past obstetrical history or the presence of known risk factors. Preconception intervention can be helpful in selected patients in a number of ways. Patients with certain uterine anomalies may have a surgical correction (i.e. removal of a uterine septum), and those with certain medical problems can be helped by optimizing medical therapies prior to conception, be it for asthma, diabetes, hypertension and others. #### Multiple pregnancies[edit] In multiple pregnancies, which often result from use of assisted reproductive technology, there is a high risk of preterm birth. Selective reduction is used to reduce the number of fetuses to two or three.[111][112][113] #### Reducing indicated preterm birth[edit] A number of agents have been studied for the secondary prevention of indicated preterm birth. Trials using low-dose aspirin, fish oil, vitamin C and E, and calcium to reduce preeclampsia demonstrated some reduction in preterm birth only when low-dose aspirin was used.[96] Even if agents such as calcium or antioxidants were able to reduce preeclampsia, a resulting decrease in preterm birth was not observed.[96] #### Reducing spontaneous preterm birth[edit] Reduction in activity by the mother—pelvic rest, limited work, bed rest—may be recommended although there is no evidence it is useful with some concerns it is harmful.[114] Increasing medical care by more frequent visits and more education has not been shown to reduce preterm birth rates.[106] Use of nutritional supplements such as omega-3 polyunsaturated fatty acids is based on the observation that populations who have a high intake of such agents are at low risk for preterm birth, presumably as these agents inhibit production of proinflammatory cytokines. A randomized trial showed a significant decline in preterm birth rates,[115] and further studies are in the making. ##### Antibiotics[edit] While antibiotics can get rid of bacterial vaginosis in pregnancy, this does not appear to change the risk of preterm birth.[116] It has been suggested that chronic chorioamnionitis is not sufficiently treated by antibiotics alone (and therefore they cannot ameliorate the need for preterm delivery in this condition).[96] ##### Progestogens[edit] Progestogens, often given in the form of progesterone or hydroxyprogesterone caproate, relaxes the uterine musculature, maintains cervical length, and has anti-inflammatory properties, and thus exerts activities expected to be beneficial in reducing preterm birth. Two meta-analyses demonstrated a reduction in the risk of preterm birth in women with recurrent preterm birth by 40–55%.[117][118] Progestogen supplementation also reduces the frequency of preterm birth in pregnancies where there is a short cervix.[119] However, progestogens are not effective in all populations, as a study involving twin gestations failed to see any benefit.[120] Despite extensive research related to progestogen effectiveness, uncertainties remain concerning types of progesterone and routes of administration.[121] ##### Cervical cerclage[edit] In preparation for childbirth, the woman's cervix shortens. Preterm cervical shortening is linked to preterm birth and can be detected by ultrasonography. Cervical cerclage is a surgical intervention that places a suture around the cervix to prevent its shortening and widening. Numerous studies have been performed to assess the value of cervical cerclage and the procedure appears helpful primarily for women with a short cervix and a history of preterm birth.[119][122] Instead of a prophylactic cerclage, women at risk can be monitored during pregnancy by sonography, and when shortening of the cervix is observed, the cerclage can be performed.[96] ## Management[edit] Preterm birth at 32 weeks and 4 days with a weight of 2,000 g attached to medical equipment About 75% of nearly a million deaths due to preterm deliver would survive if provided warmth, breastfeeding, treatments for infection, and breathing support.[123] If a baby has cardiac arrest at birth and is before 23 weeks or less than 400 g attempts at resuscitation are not indicated.[124] Tertiary interventions are aimed at women who are about to go into preterm labor, or rupture the membranes or bleed preterm. The use of the fibronectin test and ultrasonography improves the diagnostic accuracy and reduces false-positive diagnosis. While treatments to arrest early labor where there is progressive cervical dilatation and effacement will not be effective to gain sufficient time to allow the fetus to grow and mature further, it may defer delivery sufficiently to allow the mother to be brought to a specialized center that is equipped and staffed to handle preterm deliveries.[125] In a hospital setting women are hydrated via intravenous infusion (as dehydration can lead to premature uterine contractions).[126] ### Steroids[edit] Severely premature infants may have underdeveloped lungs because they are not yet producing their own surfactant. This can lead directly to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, a steroid that crosses the placental barrier and stimulates the production of surfactant in the lungs of the baby.[12] Steroid use up to 37 weeks is also recommended by the American Congress of Obstetricians and Gynecologists.[12] Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the pregnancy has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There are still some concerns about the efficacy and side effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. A 2015 Cochrane review supports the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course.[127] Beside reducing respiratory distress, other neonatal complications are reduced by the use of glucocorticosteroids, namely intraventricular bleeding, necrotising enterocolitis, and patent ductus arteriosus.[128] A single course of antenatal corticosteroids could be considered routine for preterm delivery, but there are some concerns about applicability of this recommendation to low-resource settings with high rates of infections.[128] It remains unclear whether one corticosteroid (or one particular regimen) has advantages over another.[129] Concerns about adverse effects of prenatal corticosteroids include increased risk for maternal infection, difficulty with diabetic control, and possible long-term effects on neurodevelopmental outcomes for the infants. There is ongoing discussion about when steroids should be given (i.e. only antenatally or postnatally too) and for how long (i.e. single course or repeated administration). Despite these unknowns, there is a consensus that the benefits of a single course of prenatal glucocorticosteroids vastly outweigh the potential risks.[130][131][132] ### Antibiotics[edit] The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby to get infected with group B streptococcus and has been shown to reduce related mortality rates.[133] When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks.[134] Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav).[134] ### Tocolysis[edit] A number of medications may be useful to delay delivery including: nonsteroidal anti-inflammatory drugs, calcium channel blockers, beta mimetics, and atosiban.[135] Tocolysis rarely delays delivery beyond 24–48 hours.[136] This delay, however, may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects.[96][137] Magnesium sulfate does not appear to be useful to prevent preterm birth.[138] Its use before delivery, however, does appear to decrease the risk of cerebral palsy.[139] ### Mode of delivery[edit] The routine use of caesarean section for early delivery of infants expected to have very low birth weight is controversial,[140] and a decision concerning the route and time of delivery probably needs to be made on a case-by-case basis. ### Neonatal care[edit] Incubator for preterm baby After delivery, plastic wraps or warm mattresses are useful to keep the infant warm on their way to the neonatal intensive care unit (NICU).[141] In developed countries premature infants are usually cared for in an NICU. The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. Treatments may include fluids and nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support,[142] and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care (skin to skin warming), encouraging breastfeeding, and basic infection control measures can significantly reduce preterm morbidity and mortality. Bili lights may also be used to treat newborn jaundice (hyperbilirubinemia). Water can be carefully provided to prevent dehydration but no so much to increase risks of side effects.[143] In terms of respiratory support, there may be little or no difference in the risk of death or chronic lung disease between high flow nasal cannulae (HFNC) and continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NPPV).[144] For extremely preterm babies (born before 28 weeks' gestation), targeting a higher versus a lower oxygen saturation range makes little or no difference overall to the risk of death or major disability.[145] Babies born before 32 weeks' probably have a lower risk of death from bronchopulmonary dysplasia if they have CPAP immediately after being born, compared to receiving either supportive care or assisted ventilation.[146] One review found that when premature infants are given osteopathic manipulations, they are less likely to require as lengthy of a hospital stay than if they are not manipulated.[147] There is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding).[148] ### Nutrition[edit] In a 2012 policy statement, the American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including lower rates of necrotizing enterocolitis (NEC).[149] In the absence of evidence from randomised controlled trials about the effects of feeding preterm infants with formula compared with mother's own breast milk, data collected from other types of studies suggest that mother's own breast milk is likely to have advantages over formula in terms of the baby's growth and development.[150] It is unclear if fortification of breast milk improves outcomes in preterm babies, though it may speed growth.[151] Supplementing human milk with extra protein may increase short-term growth but the longer-term effects on body composition, growth and brain development are uncertain.[152] The evidence from clinical trials is uncertain regarding the effects on preterm babies' growth of supplementing human milk with carbohydrate[153] and fat.[154] When a mother's breastmilk is not available, formula is probably better than donor breast milk for preterm babies in terms of weight gain, linear growth and head growth but there may be little or no difference in terms of neurodevelopmental disability, death or necrotising enterocolitis.[155] There is some indication that preterm babies who cannot breastfeed may do better if they are fed only with diluted formula compared to full strength formula but the clinical trial evidence remains uncertain.[156] Higher protein formula (between 3 and 4 grams of protein per kilo of body weight) may be more effective than low protein formula (less than 3 grams per kilo per day) for weight gain in formula-fed low birth weight infants.[157] There is limited evidence to support prescribing a preterm formula for the preterm babies after hospital discharge.[158] ### Hearing assessment[edit] The Joint Committee on Infant Hearing (JCIH) state that for preterm infants who are in the neonatal intensive care unit (NICU) for a prolonged time should have a diagnostic audiologic evaluation before they are discharged from the hospital.[159] Well babies follow a 1-2-3 month benchmark timeline where they are screened, diagnosed, and receiving intervention for a hearing loss. However, very premature babies it might not be possible to complete a hearing screen at one month of age due to several factors. Once the baby is stable an audiologic evaluation should be performed. For premature babies in the NICU, auditory brainstem response (ABR) testing is recommended. If the infant doesn't pass the screen, they should be referred for an audiologic evaluation by an audiologist.[159] If the infant is on aminoglycosides such as gentamicin for less than five days they should be monitored and have a follow up 6–7 months of being discharged from the hospital to ensure there is no late onset hearing loss due to the medication.[159] ## Prognosis[edit] Preterm infants survival rates[160][161][162][163][164][165] The chance of survival at 22 weeks is about 6%, while at 23 weeks it is 26%, 24 weeks 55% and 25 weeks about 72% as of 2016.[18] With extensive treatment up to 30% of those who survive birth at 22 weeks survive longer term as of 2019.[166] The chances of survival without long-term difficulties is less.[19] Of those who survival following birth at 22 weeks 33% have severe disabilities.[166] In the developed world overall survival is about 90% while in low-income countries survival rates are about 10%.[123] Some children will adjust well during childhood and adolescence,[20] although disability is more likely nearer the limits of viability. A large study followed children born between 22 and 25 weeks until the age of 6 years old. Of these children, 46 percent had moderate to severe disabilities such as cerebral palsy, vision or hearing loss and learning disabilities, 34 percent had mild disabilities, and 20 percent had no disabilities. Twelve percent had disabling cerebral palsy.[31] As survival has improved, the focus of interventions directed at the newborn has shifted to reduce long-term disabilities, particularly those related to brain injury.[20] Some of the complications related to prematurity may not be apparent until years after the birth. A long-term study demonstrated that the risks of medical and social disabilities extend into adulthood and are higher with decreasing gestational age at birth and include cerebral palsy, intellectual disability, disorders of psychological development, behavior, and emotion, disabilities of vision and hearing, and epilepsy.[167] Standard intelligence tests showed that 41 percent of children born between 22 and 25 weeks had moderate or severe learning disabilities when compared to the test scores of a group of similar classmates who were born at full-term.[31] It is also shown that higher levels of education were less likely to be obtained with decreasing gestational age at birth.[167] People born prematurely may be more susceptible to developing depression as teenagers.[168] Some of these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes.[169] Studies of people born premature and investigated later with MRI brain imaging, demonstrate qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence.[170] Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.[20] Despite the neurosensory, mental and educational problems studied in school age and adolescent children born extremely preterm, the majority of preterm survivors born during the early years of neonatal intensive care are found to do well and to live fairly normal lives in young adulthood.[171] Young adults born preterm seem to acknowledge that they have more health problems than their peers, yet feel the same degree of satisfaction with their quality of life.[172] Beyond the neurodevelopmental consequences of prematurity, infants born preterm have a greater risk for many other health problems. For instance, children born prematurely have an increased risk for developing chronic kidney disease.[173] ## Epidemiology[edit] Disability-adjusted life year for prematurity and low birth weight per 100,000 inhabitants in 2004.[174] no data less than 120 120-240 240-360 360-480 480-600 600-720 720-840 840-960 960-1080 1080-1200 1200-1500 more than 1500 Preterm birth complicates the births of infants worldwide affecting 5% to 18% of births.[77] In Europe and many developed countries the preterm birth rate is generally 5–9%, and in the USA it has even risen to 12–13% in the last decades.[175] As weight is easier to determine than gestational age, the World Health Organization tracks rates of low birth weight (< 2,500 grams), which occurred in 16.5 percent of births in less developed regions in 2000.[176] It is estimated that one third of these low birth weight deliveries are due to preterm delivery. Weight generally correlates to gestational age, however, infants may be underweight for other reasons than a preterm delivery. Neonates of low birth weight (LBW) have a birth weight of less than 2500 g (5 lb 8 oz) and are mostly but not exclusively preterm babies as they also include small for gestational age (SGA) babies. Weight-based classification further recognizes Very Low Birth Weight (VLBW) which is less than 1,500 g, and Extremely Low Birth Weight (ELBW) which is less than 1,000 g.[177] Almost all neonates in these latter two groups are born preterm. Complications from preterm births resulted in 740,000 deaths in 2013, down from 1.57 million in 1990.[17] ## Society and culture[edit] ### Economics[edit] Preterm birth is a significant cost factor in healthcare, not even considering the expenses of long-term care for individuals with disabilities due to preterm birth. A 2003 study in the US determined neonatal costs to be $224,400 for a newborn at 500–700 g versus $1,000 at over 3,000 g. The costs increase exponentially with decreasing gestational age and weight.[178] The 2007 Institute of Medicine report Preterm Birth[179] found that the 550,000 premature babies born each year in the U.S. run up about $26 billion in annual costs, mostly related to care in neonatal intensive care units, but the real tab may top $50 billion.[180] ### Notable cases[edit] James Elgin Gill (born on 20 May 1987 in Ottawa, Ontario, Canada) was the earliest premature baby in the world, until that record was broken in 2004. He was 128 days premature (21 weeks and 5 days' gestation) and weighed 1 pound 6 ounces (624 g). He survived.[181][182] In 2014, Lyla Stensrud, born in San Antonio, Texas, U.S. became the youngest premature baby in the world. She was born at 21 weeks 4 days and weighed 410 grams (less than a pound). Kaashif Ahmad resuscitated the baby after she was born. As of November 2018, Lyla was attending preschool. She had a slight delay in speech, but no other known medical issues or disabilities.[183] Amillia Taylor is also often cited as the most premature baby.[184] She was born on 24 October 2006 in Miami, Florida, U.S. at 21 weeks and 6 days' gestation.[185] This report has created some confusion as her gestation was measured from the date of conception (through in vitro fertilization) rather than the date of her mother's last menstrual period, making her appear 2 weeks younger than if gestation was calculated by the more common method.[168] At birth, she was 9 inches (22.9 cm) long and weighed 10 ounces (280 g).[184] She suffered digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Children's Hospital on 20 February 2007.[184] The record for the smallest premature baby to survive was held for a considerable amount of time by Madeline Mann, who was born in 1989 at 26 weeks, weighing 9.9 ounces (280 g) and measuring 9.5 inches (241.3 mm) long.[186] This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital, Loyola University Medical Center in Maywood, Illinois.[187] at 25 weeks' gestation. At birth, she was 8 inches (200 mm) long and weighed 261 grams (9.2 oz).[188] Her twin sister was also a small baby, weighing 563 grams (1 lb 3.9 oz) at birth. During pregnancy their mother had pre-eclampsia, requiring birth by caesarean section. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February 2005 by which time her weight had increased to 1.18 kg (2.6 lb).[189] Generally healthy, the twins had to undergo laser eye surgery to correct vision problems, a common occurrence among premature babies. In May 2019, Sharp Mary Birch Hospital for Women & Newborns in San Diego announced that a baby nicknamed "Saybie" had been discharged almost five months after being born at 23 weeks gestation and weighing 244 grams (8.6 oz). Saybie was confirmed by Dr. Edward Bell of the University of Iowa, which keeps the Tiniest Babies Registry, to be the new smallest surviving premature baby in that registry.[190] The world's smallest premature boy to survive was born in February 2009 at Children's Hospitals and Clinics of Minnesota in Minneapolis, Minnesota, U.S. Jonathon Whitehill was born at 25 weeks' gestation with a weight of 310 grams (11 oz). He was hospitalized in a neonatal intensive care unit for five months, and then discharged.[191] Historical figures who were born prematurely include Johannes Kepler (born in 1571 at seven months' gestation), Isaac Newton (born in 1642, small enough to fit into a quart mug, according to his mother), Winston Churchill (born in 1874 at seven months' gestation), and Anna Pavlova (born in 1885 at seven months' gestation).[192] ### Effect of the coronavirus pandemic[edit] During the COVID-19 pandemic, a drastic drop in the rate of premature births has been reported in many countries, ranging from a 20% reduction to a 90% drop in the starkest cases. Studies in Ireland and Denmark first noticed the phenomenon, and it has been confirmed elsewhere. There is no universally accepted explanation for this drop as of August 2020. Hypotheses include additional rest and support for expectant mothers staying at home, less air pollution due to shutdowns and reduced car fumes, and reduced likelihood to catch other diseases and viruses in general due to the lockdowns.[193] ## Neurological research[edit] Brain injury is common among preterms, ranging from white matter injury to intraventricular and cerebellar haemorrhages.[194] The characteristic neuropathology of preterms has been described as the “encephalopathy of prematurity”.[195] The number of preterms that receive special education is doubled compared to the general population. School marks are lower and so are verbal learning, executive function, language skills, and memory performance scores,[196][197][198][199] as well as IQ scores .[200][201][202][203][197][199][204] Behaviourally, adolescents who were born very preterm and/or very low birth weight have similar self-reports of quality of life, health status and self-esteem as term controls.[205][206][207][208] Various structural magnetic resonance studies found consistent reductions in whole brain volume.[200][202][203][209][199] The extensive list of particular regions with smaller volumes compared to controls includes many cortical areas (temporal, frontal, parietal, occipital and cingulate), the hippocampal regions, thalamus, basal ganglia, amygdala, brain stem, internal capsule, corpus callosum and cerebellum. Brain volume reduction seems to be present throughout the whole brain. In contrast, larger volumes were found in some of the same areas including medial/anterior frontal, parietal and temporal cortex, cerebellum, middle temporal gyrus, parahippocampal gyrus, and fusiform gyrus, as well as larger lateral ventricles on average.[210] The cause of these inconsistencies are unknown. Additionally, reductions in cortical surface area/cortical thickness were found in the temporal lobes bilaterally and in left frontal and parietal areas.[201][211] Thicker cortex was found bilaterally in the medial inferior and anterior parts of the frontal lobes and in the occipital lobes. Gestational age was positively correlated with volumes of the temporal and fusiform gyri and sensorimotor cortex bilaterally, left inferior parietal lobule, brain stem, and various white matter tracts, as well as specific positive associations with the cerebellum and thalamus. Several structural brain alterations have been linked back to cognitive and behavioural outcome measures. For example, total brain tissue volume explained between 20 and 40% of the IQ and educational outcome differences between extremely preterm born adolescents and control adolescents.[202][203] In another study, a 25% quartile decrease in white matter values in middle temporal gyrus was associated with a 60% increase in the risk of cognitive impairment.[196] Nosarti and colleagues previously hypothesised that maturational patterns in preterm brains were consistent with the age-related stages typically observed in younger subjects. Their most recent study suggests however, that their trajectory may not only be delayed but also fundamentally distinctive. Since both smaller and larger regional volumes were found in very preterm individuals compared to controls.[197] ## See also[edit] * World Prematurity Day ## References[edit] 1. ^ a b c d e f g "Preterm Labor and Birth: Condition Information". National Institutes of Health. 3 November 2014. Archived from the original on 2 April 2015. 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S2CID 30594886. 206. ^ van Lunenburg, Afra; van der Pal, Sylvia M; van Dommelen, Paula; van der Pal – de Bruin, Karin M; Bennebroek Gravenhorst, Jack; Verrips, Gijsbert HW (2013). "Changes in quality of life into adulthood after very preterm birth and/or very low birth weight in the Netherlands". Health and Quality of Life Outcomes. 11 (1): 51. doi:10.1186/1477-7525-11-51. PMC 3618000. PMID 23531081. 207. ^ Walther, Frans J; den Ouden, A.Lya; Verloove-Vanhorick, S.Pauline (September 2000). "Looking back in time: outcome of a national cohort of very preterm infants born in The Netherlands in 1983". Early Human Development. 59 (3): 175–191. doi:10.1016/S0378-3782(00)00094-3. PMID 10996273. 208. ^ Zwicker, J. G.; Harris, S. R. (28 January 2008). "Quality of Life of Formerly Preterm and Very Low Birth Weight Infants From Preschool Age to Adulthood: A Systematic Review". Pediatrics. 121 (2): e366–e376. doi:10.1542/peds.2007-0169. PMID 18245409. S2CID 11674158. 209. ^ Martinussen, M; Flanders, DW; Fischl, B; Busa, E; Løhaugen, GC; Skranes, J; Vangberg, TR; Brubakk, AM; Haraldseth, O; Dale, AM (December 2009). "Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight". The Journal of Pediatrics. 155 (6): 848–853.e1. doi:10.1016/j.jpeds.2009.06.015. PMC 5875423. PMID 19683725. 210. ^ Allin, Matthew; Henderson, Max; Suckling, John; Nosarti, Chiara; Rushe, Teresa; Fearon, Paul; Stewart, Ann L; Bullmore, ET; Rifkin, Larry; Murray, Robin (13 February 2007). "Effects of very low birthweight on brain structure in adulthood". Developmental Medicine & Child Neurology. 46 (1): 46–53. doi:10.1111/j.1469-8749.2004.tb00433.x. S2CID 221649350. 211. ^ Skranes, J; Løhaugen, GC; Martinussen, M; Håberg, A; Brubakk, AM; Dale, AM (September 2013). "Cortical surface area and IQ in very-low-birth-weight (VLBW) young adults". Cortex. 49 (8): 2264–71. doi:10.1016/j.cortex.2013.06.001. PMID 23845237. S2CID 32770053. Classification D * ICD-10: O60.1, P07.3 * ICD-9-CM: 644, 765 * MeSH: D047928 * DiseasesDB: 10589 External resources * MedlinePlus: 001562 * eMedicine: ped/1889 * v * t * e Infants and their care Health (Pediatrics) * Baby food * Birth weight * Breast pump * Breastfeeding * Breastfeeding and medications * Bottle feeding * Colic * Immunizations * Cradle cap * Cross eyed * Failure to thrive * Immunization * Infant and toddler safety * Infant bathing * Infant food safety * Infant formula * Infant massage * Infant food safety * Infant nutrition * Infant respiratory distress syndrome * Infant sleep training * Neo-natal intensive care unit * Newborn care and safety * Oral rehydration therapy * Pedialyte * Preterm birth * Shaken baby syndrome * Soy formula * Sudden infant death syndrome * Breastfeeding and mental health Development * Attachment parenting * Baby-led weaning * Baby talk * Babbling * Childbirth * Congenital disorder * Crawling * Infant visual development * Diaper rash * Gestational age * Infant cognitive development * Kangaroo care * Mother * Nursery Rhyme * Object permanence * Parent * Parenting * Peekaboo * Play * Prenatal development * Prenatal development table * Teething * Types of crying * Walking * Weaning Socialization and Culture * Attachment * Babysitting * Child abuse * Child custody * Child's rights * UN Child rights * Circumcision * Daycare * Foster care * Grandparent visitation * Infant swimming * Milk bank * Nanny * Wet nurse Infant care and equipment * Baby bouncer * Baby gate * Baby monitor/Hidden camera * Baby powder * Baby shampoo * Baby toy * Baby walker * Bib * Baby swing * Baby transport * Bassinet * Car seat safety * Cloth diaper * Cradle board * Diaper * Diaper bag * Baby wipes * Haberman Feeder * High chair * Infant bed (American 'crib' and 'cradle', British 'cot') * Infant carrier * Infant clothing * Pacifier * Playpen * Stroller * Supplemental nursing system * Swaddling * Swim diaper * Teether * Travel cot Other topics * Baby shower * Babywearing * Child neglect * Closed adoption * Cry room * Infant ear piercing * Open adoption * Prenatal cocaine exposure * Neonatal withdrawal syndrome * Parental child abduction * Parental responsibility * Parenting plan * Paternity * Paternity fraud * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal Authority control * GND: 4155535-1 * NDL: 00571491 [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	Preterm birth	c0151526	8,313	wikipedia	https://en.wikipedia.org/wiki/Preterm_birth	2021-01-18T19:08:33	{"mesh": ["D047928"], "icd-9": ["765", "644"], "icd-10": ["O60.1"], "wikidata": ["Q625506"]}
Ogden syndrome Other namesPremature aging appearance-developmental delay-cardiac arrhythmia syndrome, N-terminal acetyltransferase deficiency Ogden Syndrome, also known as N-terminal acetyltransferase deficiency (NATD),[1] is an X-linked disorder of infancy comprising a distinct combination of distinctive craniofacial features producing an aged appearance, growth failure, hypotonia, global developmental delays, cryptorchidism, and spontaneous cardiac arrhythmias. The first family was identified in Ogden, Utah, with five affected boys in two generations of family members. A mutation was identified as a c.109T>C (p.Ser37Pro) variant in NAA10, a gene encoding the catalytic subunit of the major human N-terminal acetyltransferase enzyme system (NatA). This same mutation was identified in a second unrelated family, with three affected boys in two generations. This severe genetic disorder has provisionally been named Ogden Syndrome, as this is the city where the first affected family resides. Further information on this condition can be found at www.naa10gene.com ## Contents * 1 Signs and symptoms * 2 Biochemistry * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] This is an X-linked condition affecting males more than females and is characterized by postnatal growth failure with developmental delays and dysmorphic features characterized by wrinkled forehead, anterior and posterior fontanels, prominent eyes, large down-slanting palpebral fissures, thickened or hooded eyelids, large ears, flared nares, hypoplastic alae nasi, short columella, protruding upper lip, and microretrognathia. There is also delayed closing of fontanelle, and the boys also have broad great toes. Skin is characterized by redundancy or laxity with minimal subcutaneous fat, cutaneous capillary malformations, and very fine hair and eyebrows. Death resulted from cardiogenic shock following arrhythmia, which was noted in all affected individuals. The boys had heart rhythm abnormalities and craniofacial abnormalities, which accounted for their similar appearance. The boys were never able to sit up on their own, and none learned how to talk.[2] They all had a characteristically aged appearance, earning them the family nickname of “little old men.”[2] Several of the boys had structural anomalies of their hearts including ventricular septal defect, atrial septal defect, and pulmonary artery stenosis. Events recorded on electrocardiogram before death included torsades de pointes, premature ventricular contraction (PVC), premature atrial contraction (PAC), supraventricular tachycardia (SVtach), and ventricular tachycardia (Vtach). Most of the children had inguinal hernias, and the majority had, at least, unilateral cryptorchidism. All had neonatal hypotonia progressing to hypertonia, and cerebral atrophy on MRI; several, but not all, had neurogenic scoliosis. Death occurred prior to 2 years in all cases and prior to 1 year in the majority. There are extensive clinical details for each child reported in the original publication ## Biochemistry[edit] Ogden Syndrome is a lethal X-linked recessive condition. Because the affected gene is on the X-chromosome, it affects males far more severely due to the fact that males only carry one copy of the X chromosome so the mutation is in every cell but females carry two and therefore some cells may use the non mutated copy and others use the mutated copy. It was the first reported human genetic disorder linked with a mutation in an N-terminal acetyltransferase (NAT) gene.[3] The original Ogden family males have the Ser37Pro (S37P) mutation in the gene encoding NAA10, the catalytic subunit of NatA, the major human enzyme heterodimer involved in the post-translational acetylation of proteins. The S37P mutation swaps one amino acid for another, a serine for a proline, in just one part at the end of the resulting NatA protein subunit.[3] Other mutations have since been discovered in very small number of cases worldwide with the most prevalent being Arg83Cys mutation. Mutations to this gene changes the structure of the protein, which makes it less effective at N-terminal acetylation than the normal protein, causing a multitude of effects for the baby, as N-terminal acetylation is one of the most common protein modifications in humans, occurring on approximately 80% of all human proteins.[2][4] ## Diagnosis[edit] Whole exome sequencing is the definitive diagnostic method used to confirm OS. ## Treatment[edit] ## History[edit] Halena Black had her first son, Kenny Rae, in 1979. Being that he was her first born child, Black did not notice that something was wrong. Kenny Rae Black passed in 1980, right before his first birthday and was the first known infant to die from Ogden Syndrome.[5] However, it did not end there. Halena Black continued to have children and in 1987 she had her next boy, Hyrum. From the start, Black noticed that Hyrum had the same characteristics as Kenny Rae but thought it was due to the fact that they were brothers. It did not cross her mind that they could share the same underlying disease. Like Kenny Rae, Hyrum passed before his first birthday. It was only until Black's daughters began having children of their own that she realized something was not right. The sons born to Black's daughters looked identical to her own sons and that was when Halena sought medical help.[5] Answers came thirty years after Kenny Rae's death. Ogden Syndrome was discovered in 2011 by a team of researchers led by Gholson J. Lyon, consisting of: Alan F. Rope, Kai Wang, Rune Evjenth, Jinchuan Xing, Jennifer J. Johnston, Jeffrey J. Swensen, W. Evan Johnson, Barry Moore, Chad D. Huff, Lynne M. Bird, John C. Carey, John M. Opitz, Cathy A. Stevens, Tao Jiang, Christa Schank, Heidi Deborah Fain, Reid J. Robison, and 10 others. Just before Lyon was about to publish his findings, another team researching a family living mainly in California contacted him. The newly found family had also lost three infant boys all with similar characteristics. This new family shared the same rare mutation as the Black family. The existence of another family made this mutation a syndrome, and not something isolated.[2] ## References[edit] 1. ^ Rope, A.F. (2011). "Using VAAST to Identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency". American Journal of Human Genetics. 89 (1): 28–43. doi:10.1016/j.ajhg.2011.05.017. PMC 3135802. PMID 21700266. 2. ^ a b c d "More news on Ogden Syndrome from AAAS \| Utah Foundation For Biomedical Research". Retrieved 2015-09-25. 3. ^ a b Myklebust, Line; et al. (2015-01-08). "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects" (PDF). Human Molecular Genetics. 24 (7): 1956–76. doi:10.1093/hmg/ddu611. PMC 4355026. PMID 25489052. Retrieved 2015-10-02. 4. ^ Arnesen, T. (2009). "Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans". Proc Natl Acad Sci U S A. 106 (20): 8157–62. Bibcode:2009PNAS..106.8157A. doi:10.1073/pnas.0901931106. PMC 2688859. PMID 19420222. 5. ^ a b "Rare genetic mutation causes infant deaths in small town \| AAAS MemberCentral". membercentral.aaas.org. Archived from the original on 2015-12-19. Retrieved 2015-09-25. ## External links[edit] Classification D * OMIM: 300855 External resources * Orphanet: 276432 [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	Ogden syndrome	c3275447	8,314	wikipedia	https://en.wikipedia.org/wiki/Ogden_syndrome	2021-01-18T18:46:36	{"umls": ["C3275447"], "orphanet": ["276432"], "wikidata": ["Q17144188"]}
Poisoning caused by mercury chemicals For the song by Graham Parker, see Mercury Poisoning. Mercury poisoning Other namesMercury toxicity, mercury overdose, mercury intoxication, hydrargyria, mercurialism The bulb of a mercury-in-glass thermometer SpecialtyToxicology SymptomsMuscle weakness, poor coordination, numbness in the hands and feet[1] ComplicationsKidney problems, decreased intelligence[2] CausesExposure to mercury[1] Diagnostic methodDifficult[3] PreventionDecreasing use of mercury, low mercury diet[4] MedicationAcute poisoning: dimercaptosuccinic acid (DMSA), dimercaptopropane sulfonate (DMPS)[5] Mercury poisoning is a type of metal poisoning due to exposure to mercury.[3] Symptoms depend upon the type, dose, method, and duration of exposure.[3][4] They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes, anxiety, memory problems, trouble speaking, trouble hearing, or trouble seeing.[1] High-level exposure to methylmercury is known as Minamata disease.[2] Methylmercury exposure in children may result in acrodynia (pink disease) in which the skin becomes pink and peels.[2] Long-term complications may include kidney problems and decreased intelligence.[2] The effects of long-term low-dose exposure to methylmercury are unclear.[6] Forms of mercury exposure include metal, vapor, salt, and organic compound.[3] Most exposure is from eating fish, amalgam based dental fillings, or exposure at work.[3] In fish, those higher up in the food chain generally have higher levels of mercury.[3] Less commonly, poisoning may occur as a method of attempted suicide.[3] Human activities that release mercury into the environment include the burning of coal and mining of gold.[4] Tests of the blood, urine, and hair for mercury are available but do not relate well to the amount in the body.[3] Prevention includes eating a diet low in mercury, removing mercury from medical and other devices, proper disposal of mercury, and not mining further mercury.[4][2] In those with acute poisoning from inorganic mercury salts, chelation with either dimercaptosuccinic acid (DMSA) or dimercaptopropane sulfonate (DMPS) appears to improve outcomes if given within a few hours of exposure.[5] Chelation for those with long-term exposure is of unclear benefit.[5] In certain communities that survive on fishing, rates of mercury poisoning among children have been as high as 1.7 per 100.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Sources * 2.1.1 Methylmercury and related organomercury compounds * 2.1.2 Inorganic mercury compounds * 2.1.3 Elemental mercury * 3 Mechanism * 4 Diagnosis * 5 Prevention * 5.1 Cleaning spilled mercury * 6 Treatment * 6.1 Chelation therapy * 6.2 Other * 7 Prognosis * 7.1 Detection in biological fluids * 8 History * 8.1 Infantile acrodynia * 8.2 Medicine * 8.2.1 Thiomersal * 8.2.2 Dental amalgam toxicity * 8.3 Cosmetics * 8.4 Fluorescent lamps * 8.5 Assassination attempts * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (September 2015) (Learn how and when to remove this template message) Common symptoms of mercury poisoning include peripheral neuropathy, presenting as paresthesia or itching, burning, pain, or even a sensation that resembles small insects crawling on or under the skin (formication); skin discoloration (pink cheeks, fingertips and toes); swelling; and desquamation (shedding or peeling of skin). Mercury irreversibly inhibits selenium-dependent enzymes (see below) and may also inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-O-methyl transferase. Due to the body's inability to degrade catecholamines (e.g. adrenaline), a person suffering from mercury poisoning may experience profuse sweating, tachycardia (persistently faster-than-normal heart beat), increased salivation, and hypertension (high blood pressure). Affected children may show red cheeks, nose and lips, loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and increased sensitivity to light. Other symptoms may include kidney dysfunction (e.g. Fanconi syndrome) or neuropsychiatric symptoms such as emotional lability, memory impairment, or insomnia. Thus, the clinical presentation may resemble pheochromocytoma or Kawasaki disease. Desquamation (skin peeling) can occur with severe mercury poisoning acquired by handling elemental mercury.[7] ## Causes[edit] The consumption of fish is by far the most significant source of ingestion-related mercury exposure in humans, although plants and livestock also contain mercury due to bioconcentration of organic mercury from seawater, freshwater, marine and lacustrine sediments, soils, and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms.[8] Exposure to mercury can occur from breathing contaminated air,[9] from eating foods that have acquired mercury residues during processing,[10] from exposure to mercury vapor in mercury amalgam dental restorations,[11] and from improper use or disposal of mercury and mercury-containing objects, for example, after spills of elemental mercury or improper disposal of fluorescent lamps.[12] All of these, except elemental liquid mercury, produce toxicity or death with less than a gram. Mercury's zero oxidation state (Hg0) exists as vapor or as liquid metal, its mercurous state (Hg+) exists as inorganic salts, and its mercuric state (Hg2+) may form either inorganic salts or organomercury compounds.[citation needed] Consumption of whale and dolphin meat, as is the practice in Japan, is a source of high levels of mercury poisoning. Tetsuya Endo, a professor at the Health Sciences University of Hokkaido, has tested whale meat purchased in the whaling town of Taiji and found mercury levels more than 20 times the acceptable Japanese standard.[13] Human-generated sources, such as coal-burning power plants[14] emit about half of atmospheric mercury, with natural sources such as volcanoes responsible for the remainder. An estimated two-thirds of human-generated mercury comes from stationary combustion, mostly of coal. Other important human-generated sources include gold production, nonferrous metal production, cement production, waste disposal, human crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.[15] Small independent gold-mining operation workers are at higher risk of mercury poisoning because of crude processing methods. Such is the danger for the galamsey in Ghana and similar workers known as orpailleurs in neighboring francophone countries. While no official government estimates of the labor force have been made, observers believe 20,000–50,000 work as galamseys in Ghana, a figure including many women, who work as porters. Similar problems have been reported amongst the gold miners of Indonesia.[16] Some mercury compounds, especially organomercury compounds, can also be readily absorbed through direct skin contact. Mercury and its compounds are commonly used in chemical laboratories, hospitals, dental clinics, and facilities involved in the production of items such as fluorescent light bulbs, batteries, and explosives.[17] Many traditional medicines, including Ayurvedic medicine and Traditional Chinese medicine contain mercury and other heavy metals.[18][19] No scientific data support the claim that mercury compounds in vaccine preservatives cause autism[20] or its symptoms.[21] ### Sources[edit] Compounds of mercury tend to be much more toxic than either the elemental form or the salts. These compounds have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even on a latex glove, can cause death.[22][23] #### Methylmercury and related organomercury compounds[edit] Main article: Mercury in fish Methylmercury is the major source of organic mercury for all individuals.[24] Due to bioaccumulation it works its way up through the food web and thus biomagnifies, resulting in high concentrations among populations of some species. Top predatory fish, such as tuna or swordfish, are usually of greater concern than smaller species. The US FDA and the EPA advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackerel and tilefish from the Gulf of Mexico, and to limit consumption of albacore ("white") tuna to no more than 170 g (6 oz) per week, and of all other fish and shellfish to no more than 340 g (12 oz) per week.[25] A 2006 review of the risks and benefits of fish consumption found, for adults, the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.[26] Because the process of mercury-dependent sequestration of selenium is slow, the period between exposure to methylmercury and the appearance of symptoms in adult poisoning cases tends to be extended. The longest recorded latent period is five months after a single exposure, in the Dartmouth case (see History); other latent periods in the range of weeks to months have also been reported. When the first symptom appears, typically paresthesia (a tingling or numbness in the skin), it is followed rapidly by more severe effects, sometimes ending in coma and death. The toxic damage appears to be determined by the peak value of mercury, not the length of the exposure.[27] Methylmercury exposure during rodent gestation, a developmental period that approximately models human neural development during the first two trimesters of gestation,[28][29] has long-lasting behavioral consequences that appear in adulthood and, in some cases, may not appear until aging. Prefrontal cortex or dopamine neurotransmission could be especially sensitive to even subtle gestational methylmercury exposure[30] and suggests that public health assessments of methylmercury based on intellectual performance may underestimate the impact of methylmercury in public health. Ethylmercury is a breakdown product of the antibacteriological agent ethylmercurithiosalicylate, which has been used as a topical antiseptic and a vaccine preservative (further discussed under Thiomersal below). Its characteristics have not been studied as extensively as those of methylmercury. It is cleared from the blood much more rapidly, with a half-life of seven to ten days, and it is metabolized much more quickly than methylmercury. It is presumed not to have methylmercury's ability to cross the blood–brain barrier via a transporter, but instead relies on simple diffusion to enter the brain.[24] Other exposure sources of organic mercury include phenylmercuric acetate and phenylmercuric nitrate. These compounds were used in indoor latex paints for their antimildew properties, but were removed in 1990 because of cases of toxicity.[24] #### Inorganic mercury compounds[edit] Mercury occurs as salts such as mercuric chloride (HgCl2) and mercurous chloride (Hg2Cl2), the latter also known as calomel. Because they are more soluble in water, mercuric salts are usually more acutely toxic than mercurous salts. Their higher solubility lets them be more readily absorbed from the gastrointestinal tract. Mercury salts affect primarily the gastrointestinal tract and the kidneys, and can cause severe kidney damage; however, as they cannot cross the blood–brain barrier easily, these salts inflict little neurological damage without continuous or heavy exposure.[31] Mercuric cyanide (Hg(CN)2) is a particularly toxic mercury compound that has been used in murders, as it contains not only mercury but also cyanide, leading to simultaneous cyanide poisoning.[32] The drug n-acetyl penicillamine has been used to treat mercury poisoning with limited success.[33] #### Elemental mercury[edit] Quicksilver (liquid metallic mercury) is poorly absorbed by ingestion and skin contact. Its vapor is the most hazardous form. Animal data indicate less than 0.01% of ingested mercury is absorbed through the intact gastrointestinal tract, though it may not be true for individuals suffering from ileus. Cases of systemic toxicity from accidental swallowing are rare, and attempted suicide via intravenous injection does not appear to result in systemic toxicity,[27] though it still causes damage by physically blocking blood vessels both at the site of injection and the lungs. Though not studied quantitatively, the physical properties of liquid elemental mercury limit its absorption through intact skin and in light of its very low absorption rate from the gastrointestinal tract, skin absorption would not be high.[34] Some mercury vapor is absorbed dermally, but uptake by this route is only about 1% of that by inhalation.[35] In humans, approximately 80% of inhaled mercury vapor is absorbed via the respiratory tract, where it enters the circulatory system and is distributed throughout the body.[36] Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m3, has been shown in case–control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.[37][38] Acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. The most prominent symptoms include tremors (initially affecting the hands and sometimes spreading to other parts of the body), emotional lability (characterized by irritability, excessive shyness, confidence loss, and nervousness), insomnia, memory loss, neuromuscular changes (weakness, muscle atrophy, muscle twitching), headaches, polyneuropathy (paresthesia, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities), and performance deficits in tests of cognitive function.[34] ## Mechanism[edit] The toxicity of mercury sources can be expected to depend on its nature, i.e., salts vs. organomercury compounds vs. elemental mercury. The primary mechanism of mercury toxicity involves its irreversible inhibition of selenoenzymes, such as thioredoxin reductase (IC50 = 9 nM).[39] Although it has many functions, thioredoxin reductase restores vitamins C and E, as well as a number of other important antioxidant molecules, back into their reduced forms, enabling them to counteract oxidative damage.[40] Since the rate of oxygen consumption is particularly high in brain tissues, production of reactive oxygen species (ROS) is accentuated in these vital cells, making them particularly vulnerable to oxidative damage and especially dependent upon the antioxidant protection provided by selenoenzymes. High mercury exposures deplete the amount of cellular selenium available for the biosynthesis of thioredoxin reductase and other selenoenzymes that prevent and reverse oxidative damage,[41] which, if the depletion is severe and long lasting, results in brain cell dysfunctions that can ultimately cause death. Mercury in its various forms is particularly harmful to fetuses as an environmental toxin in pregnancy, as well as to infants. Women who have been exposed to mercury in substantial excess of dietary selenium intakes during pregnancy are at risk of giving birth to children with serious birth defects. Mercury exposures in excess of dietary selenium intakes in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Exposure to methylmercury causes increased levels of antibodies sent to myelin basic protein (MBP), which is involved in the myelination of neurons, and glial fibrillary acidic protein (GFAP), which is essential to many central nervous system (CNS). This causes an autoimmmune response against MBP and GFAP and results in the degradation of neural myelin and general decline in function of the CNS.[42] ## Diagnosis[edit] Diagnosis of elemental or inorganic mercury poisoning involves determining the history of exposure, physical findings, and an elevated body burden of mercury. Although whole-blood mercury concentrations are typically less than 6 μg/L, diets rich in fish can result in blood mercury concentrations higher than 200 μg/L; it is not that useful to measure these levels for suspected cases of elemental or inorganic poisoning because of mercury's short half-life in the blood. If the exposure is chronic, urine levels can be obtained; 24-hour collections are more reliable than spot collections. It is difficult or impossible to interpret urine samples of patients undergoing chelation therapy, as the therapy itself increases mercury levels in the samples.[43] Diagnosis of organic mercury poisoning differs in that whole-blood or hair analysis is more reliable than urinary mercury levels.[43] ## Prevention[edit] Mercury poisoning can be prevented or minimized by eliminating or reducing exposure to mercury and mercury compounds. To that end, many governments and private groups have made efforts to heavily regulate the use of mercury, or to issue advisories about the use of mercury. Most countries have signed the Minamata Convention on Mercury. The export from the European Union of mercury and some mercury compounds has been prohibited since 15 March 2010.[44] The European Union has banned most uses of mercury.[45] Mercury is allowed for fluorescent light bulbs because of pressure from countries such as Germany, the Netherlands and Hungary, which are connected to the main producers of fluorescent light bulbs: General Electric, Philips and Osram.[46] The examples and perspective in this article may not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (February 2019) (Learn how and when to remove this template message) US environmental limits[47] Country Regulating agency Regulated activity Medium Type of mercury compound Type of limit Limit US Occupational Safety and Health Administration occupational exposure air elemental mercury Ceiling (not to exceed) 0.1 mg/m3 US Occupational Safety and Health Administration occupational exposure air organic mercury Ceiling (not to exceed) 0.05 mg/m3 US Food and Drug Administration eating sea food methylmercury Maximum allowable concentration 1 ppm (1 mg/L) US Environmental Protection Agency drinking water inorganic mercury Maximum contaminant level 2 ppb (0.002 mg/L) The United States Environmental Protection Agency (EPA) issued recommendations in 2004 regarding exposure to mercury in fish and shellfish.[48] The EPA also developed the "Fish Kids" awareness campaign for children and young adults [49] on account of the greater impact of mercury exposure to that population. ### Cleaning spilled mercury[edit] EPA workers clean up residential mercury spill in 2004 Mercury thermometers and mercury light bulbs are not as common as they used to be, and the amount of mercury they contain is unlikely to be a health concern if handled carefully. However, broken items still require careful cleanup, as mercury can be hard to collect and it is easy to accidentally create a much larger exposure problem.[50] If available, powdered sulfur may be applied to the spill, in order to create a solid compound that is more easily removed from surfaces than liquid mercury.[51] ## Treatment[edit] Identifying and removing the source of the mercury is crucial. Decontamination requires removal of clothes, washing skin with soap and water, and flushing the eyes with saline solution as needed. ### Chelation therapy[edit] Chelation therapy for acute inorganic mercury poisoning, a formerly common method, was done with DMSA, 2,3-dimercapto-1-propanesulfonic acid (DMPS), D-penicillamine (DPCN), or dimercaprol (BAL).[24] Only DMSA is FDA-approved for use in children for treating mercury poisoning. However, several studies found no clear clinical benefit from DMSA treatment for poisoning due to mercury vapor.[52] No chelator for methylmercury or ethylmercury is approved by the FDA; DMSA is the most frequently used for severe methylmercury poisoning, as it is given orally, has fewer side-effects, and has been found to be superior to BAL, DPCN, and DMPS.[24] α-Lipoic acid (ALA) has been shown to be protective against acute mercury poisoning in several mammalian species when it is given soon after exposure; correct dosage is required, as inappropriate dosages increase toxicity. Although it has been hypothesized that frequent low dosages of ALA may have potential as a mercury chelator, studies in rats have been contradictory.[53] Glutathione and N-acetylcysteine (NAC) are recommended by some physicians, but have been shown to increase mercury concentrations in the kidneys and the brain.[53] Chelation therapy can be hazardous if administered incorrectly. In August 2005, an incorrect form of EDTA (edetate disodium) used for chelation therapy resulted in hypocalcemia, causing cardiac arrest that killed a five-year-old autistic boy.[54] ### Other[edit] Experimental animal and epidemiological study findings have confirmed the interaction between selenium and methylmercury. Instead of causing a decline in neurodevelopmental outcomes, epidemiological studies have found that improved nutrient (i.e., omega-3 fatty acids, selenium, iodine, vitamin D) intakes as a result of ocean fish consumption during pregnancy improves maternal and fetal outcomes.[55] For example, increased ocean fish consumption during pregnancy was associated with 4-6 point increases in child IQ's. ## Prognosis[edit] Some of the toxic effects of mercury are partially or wholly reversible provided specific therapy is able to restore selenium availability to normal before tissue damage from oxidation becomes too extensive.[56] Autopsy findings point to a half-life of inorganic mercury in human brains of 27.4 years.[57] Heavy or prolonged exposure can do irreversible damage, in particular in fetuses, infants, and young children. Young's syndrome is believed to be a long-term consequence of early childhood mercury poisoning.[58] Mercuric chloride may cause cancer as it has caused increases in several types of tumors in rats and mice, while methyl mercury has caused kidney tumors in male rats. The EPA has classified mercuric chloride and methyl mercury as possible human carcinogens (ATSDR, EPA) ### Detection in biological fluids[edit] Mercury may be measured in blood or urine to confirm a diagnosis of poisoning in hospitalized people or to assist in the forensic investigation in a case of fatal over dosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the metal. The concentrations in both fluids tend to reach high levels early after exposure to inorganic forms, while lower but very persistent levels are observed following exposure to elemental or organic mercury. Chelation therapy can cause a transient elevation of urine mercury levels.[59] ## History[edit] * Several Chinese emperors and other Chinese nobles are known or suspected to have died or been sickened by mercury poisoning after alchemists administered them "elixirs" to promote health, longevity, or immortality that contained either elemental mercury or (more commonly) cinnabar. Among the most prominent examples: * The first emperor of unified China, Qin Shi Huang, it is reported, died in 210 BC of ingesting mercury pills that were intended to give him eternal life.[60] * Emperor Xuānzong of Tang, one of the emperors of the late Tang dynasty of China, was prescribed "cinnabar that had been treated and subdued by fire" to achieve immortality.[61] Concerns that the prescription was having ill effects on the emperor's health and sanity were waved off by the imperial alchemists, who cited medical texts listing a number of the emperor's conditions (including itching, formication, swelling, and muscle weakness), today recognized as signs and symptoms of mercury poisoning, as evidence that the elixir was effectively treating the emperor's latent ailments.[61] Xuānzong became irritable and paranoid, and he seems to have ultimately died in 859 from the poisoning.[61] * During the Spanish conquest of the New World in the 16th and 17th centuries, slave mining of mercury deposits was common because the metal was used to purify the rich silver deposits in South America before being shipped back to Spain. To avoid the effects of mercury poisoning on their children, parents were known to purposefully maim or dismember their children to make them unable to work in the mines.[62] * The phrase mad as a hatter is likely a reference to mercury poisoning among milliners (so-called "mad hatter disease"), as mercury-based compounds were once used in the manufacture of felt hats in the 18th and 19th century. (The Mad Hatter character of Alice in Wonderland was, it is presumed, inspired by an eccentric furniture dealer named Theophilus Carter. Carter was not a victim of mad hatter disease although Lewis Carroll would have been familiar with the phenomenon of dementia that occurred among hatters.)[63][64] * In 1810, two British ships, HMS Triumph and HMS Phipps, salvaged a large load of elemental mercury from a wrecked Spanish vessel near Cadiz, Spain. The bladders containing the mercury soon ruptured. The element spread about the ships in liquid and vapor forms. The sailors presented with neurologic compromises: tremor, paralysis, and excessive salivation as well as tooth loss, skin problems, and pulmonary complaints. In 1823 William Burnet, MD published a report on the effects of Mercurial vapor.[65] The Triumph’s surgeon, Henry Plowman, had concluded that the ailments had arisen from inhaling the mercurialized atmosphere. His treatment was to order the lower deck gun ports to be opened, when it was safe to do so; sleeping on the orlop was forbidden; and no men slept in the lower deck if they were at all symptomatic. Windsails were set to channel fresh air into the lower decks day and night.[66] * Historically, gold amalgam was widely used in gilding, leading to numerous casualties among the workers. It is estimated that during the construction of Saint Isaac's Cathedral alone, 60 men died from the gilding of the main dome.[67][68] * For years, including the early part of his presidency, Abraham Lincoln took a common medicine of his time called "blue mass," which contained significant amounts of mercury. * On September 5, 1920, silent movie actress Olive Thomas ingested mercury capsules dissolved in an alcoholic solution at the Hotel Ritz in Paris.[69] There is still controversy over whether it was suicide, or whether she consumed the external preparation by mistake. Her husband, Jack Pickford (the brother of Mary Pickford), had syphilis, and the mercury was used as a treatment of the venereal disease at the time. She died a few days later at the American Hospital in Neuilly.[70] * An early scientific study of mercury poisoning was in 1923–6 by the German inorganic chemist, Alfred Stock, who himself became poisoned, together with his colleagues, by breathing mercury vapor that was being released by his laboratory equipment—diffusion pumps, float valves, and manometers—all of which contained mercury, and also from mercury that had been accidentally spilt and remained in cracks in the linoleum floor covering. He published a number of papers on mercury poisoning, founded a committee in Berlin to study cases of possible mercury poisoning, and introduced the term micromercurialism.[71] * The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed packing factory in Norwich, England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and preservative.[72] * Outbreaks of methylmercury poisoning occurred in several places in Japan during the 1950s due to industrial discharges of mercury into rivers and coastal waters. The best-known instances were in Minamata and Niigata. In Minamata alone, more than 600 people died due to what became known as Minamata disease. More than 21,000 people filed claims with the Japanese government, of which almost 3000 became certified as having the disease. In 22 documented cases, pregnant women who consumed contaminated fish showed mild or no symptoms but gave birth to infants with severe developmental disabilities.[73] * Mercury poisoning of two First Nation communities in Ontario, Canada occurred in the late 1960s due to industrial chemical waste released into the waterways and air. * Widespread mercury poisoning occurred in rural Iraq in 1971–1972, when grain treated with a methylmercury-based fungicide that was intended for planting only was used by the rural population to make bread, causing at least 6530 cases of mercury poisoning and at least 459 deaths (see Basra poison grain disaster).[74] * On August 14, 1996, Karen Wetterhahn, a chemistry professor working at Dartmouth College, spilled a small amount of dimethylmercury on her latex glove. She began experiencing the symptoms of mercury poisoning five months later and, despite aggressive chelation therapy, died a few months later from a mercury induced neurodegenerative disease[22][23] * In April 2000, Alan Chmurny attempted to kill a former employee, Marta Bradley, by pouring mercury into the ventilation system of her car.[75] * On March 19, 2008, Tony Winnett, 55, inhaled mercury vapors while trying to extract gold from computer parts (by using liquid mercury to separate gold from the rest of the alloy), and died ten days later. His Oklahoma residence became so contaminated that it had to be gutted.[76][77] * In December 2008, actor Jeremy Piven was diagnosed with mercury poisoning possibly resulting from eating sushi twice a day for twenty years or from taking herbal remedies.[78] * In India, a study by Centre for Science and Environment and Indian Institute of Toxicology Research has found that in the country's energy capital Singrauli, mercury is slowly entering people's homes, food, water and even blood.[79] ### Infantile acrodynia[edit] Further information: Acrodynia Infantile acrodynia (also known as "calomel disease", "erythredemic polyneuropathy", and "pink disease") is a type of mercury poisoning in children characterized by pain and pink discoloration of the hands and feet.[80] The word is derived from the Greek, where άκρο means end or extremity, and οδυνη means pain. Acrodynia resulted primarily from calomel in teething powders and decreased greatly after calomel was excluded from most teething powders in 1954.[81][82] Acrodynia is difficult to diagnose, "it is most often postulated that the etiology of this syndrome is an idiosyncratic hypersensitivity reaction to mercury because of the lack of correlation with mercury levels, many of the symptoms resemble recognized mercury poisoning."[83] ### Medicine[edit] Further information: Mercury (element) § Medicine Mercury was once prescribed as a purgative.[citation needed] Many mercury-containing compounds were once used in medicines. These include calomel (mercurous chloride), and mercuric chloride. #### Thiomersal[edit] Further information: Thiomersal controversy In 1999, the Centers for Disease Control (CDC) and the American Academy of Pediatrics (AAP) asked vaccine makers to remove the organomercury compound thiomersal (spelled "thimerosal" in the US) from vaccines as quickly as possible, and thiomersal has been phased out of US and European vaccines, except for some preparations of influenza vaccine.[84] The CDC and the AAP followed the precautionary principle, which assumes that there is no harm in exercising caution even if it later turns out to be unwarranted, but their 1999 action sparked confusion and controversy that Thiomersal was the cause of autism.[84] Since 2000, the thiomersal in child vaccines has been alleged to contribute to autism, and thousands of parents in the United States have pursued legal compensation from a federal fund.[85] A 2004 Institute of Medicine (IOM) committee favored rejecting any causal relationship between thiomersal-containing vaccines and autism.[86] Autism incidence rates increased steadily even after thiomersal was removed from childhood vaccines.[87] Currently there is no accepted scientific evidence that exposure to thiomersal is a factor in causing autism.[88] #### Dental amalgam toxicity[edit] Further information: Dental amalgam toxicity Dental amalgam is a possible cause of low-level mercury poisoning due to its use in dental fillings. Discussion on the topic includes debates on whether amalgam should be used, with critics arguing that its toxic effects make it unsafe. ### Cosmetics[edit] Some skin whitening products contain the toxic mercury(II) chloride as the active ingredient. When applied, the chemical readily absorbs through the skin into the bloodstream.[89] The use of mercury in cosmetics is illegal in the United States. However, cosmetics containing mercury are often illegally imported. Following a certified case of mercury poisoning resulting from the use of an imported skin whitening product, the United States Food and Drug Administration warned against the use of such products.[90][91] Symptoms of mercury poisoning have resulted from the use of various mercury-containing cosmetic products.[27][92][93] The use of skin whitening products is especially popular amongst Asian women.[94] In Hong Kong in 2002, two products were discovered to contain between 9,000 and 60,000 times the recommended dose.[95] ### Fluorescent lamps[edit] Fluorescent lamps contain mercury, which is released when bulbs break. Mercury in bulbs is typically present as either elemental mercury liquid, vapor, or both, since the liquid evaporates at ambient temperature.[96] When broken indoors, bulbs may emit sufficient mercury vapor to present health concerns, and the U.S. Environmental Protection Agency recommends evacuating and airing out a room for at least 15 minutes after breaking a fluorescent light bulb.[97] Breakage of multiple bulbs presents a greater concern. A 1987 report described a 23-month-old toddler who suffered anorexia, weight loss, irritability, profuse sweating, and peeling and redness of fingers and toes. This case of acrodynia was traced to exposure of mercury from a carton of 8-foot fluorescent light bulbs that had broken in a potting shed adjacent to the main nursery. The glass was cleaned up and discarded, but the child often used the area to play in.[98] ### Assassination attempts[edit] Mercury has, allegedly, been used at various times to assassinate people. In 2008, Russian lawyer Karinna Moskalenko claimed to have been poisoned by mercury left in her car,[99] while in 2010 journalists Viktor Kalashnikov and Marina Kalashnikova accused Russia's FSB of trying to poison them.[100] ## See also[edit] * Diagnosis Mercury: Money, Politics and Poison * Environmental impact of the coal industry * Erethism * Dental amalgam controversy * Got Mercury?, a public awareness campaign * Lead poisoning * Mercury vacuum * Mercury-containing and Rechargeable Battery Management Act * Methylmercury * Minamata disease * Niigata Minamata disease * Ontario Minamata disease * Mercury cycle ## References[edit] 1. ^ a b c "Mercury". NIEHS. Archived from the original on 19 November 2016. Retrieved 19 November 2016. 2. ^ a b c d e Bose-O'Reilly, S; McCarty, KM; Steckling, N; Lettmeier, B (September 2010). "Mercury exposure and children's health". Current Problems in Pediatric and Adolescent Health Care. 40 (8): 186–215. doi:10.1016/j.cppeds.2010.07.002. PMC 3096006. 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PMID 3575038. 99. ^ Russian lawyer suspects mercury poisoning Archived 2011-12-17 at the Wayback Machine, USA Today.com 100. ^ German inquiry into 'poisoning' of Russian dissidents Archived 2010-12-29 at the Wayback Machine, Telegraph ## External links[edit] * Hazardous Substances: Mercury at Curlie * Toxic Substances: Mercury at Curlie * Mercury poisoning at the Encyclopædia Britannica Classification D * ICD-10: T56.1 * ICD-9-CM: 985.0 * MeSH: D008630 * DiseasesDB: 8057 External resources * MedlinePlus: 002476 * eMedicine: emerg/813 * Orphanet: 330021 * Environment portal * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * 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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	Mercury poisoning	c0025427	8,315	wikipedia	https://en.wikipedia.org/wiki/Mercury_poisoning	2021-01-18T18:37:38	{"gard": ["7021"], "mesh": ["D008630"], "umls": ["C0025427"], "icd-9": ["985.0"], "icd-10": ["T56.1"], "orphanet": ["330021"], "wikidata": ["Q408089"]}
A rare, syndromic intellectual disability characterized by severe intellectual deficit, brachycephaly, plagiocephaly, and prominent forehead in male patients. Females may display moderate intellectual deficit without craniofacial dysmorphism. There have been no further descriptions in the literature since 1992. [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 intellectual disability-plagiocephaly syndrome	c2931516	8,316	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2898	2021-01-23T17:23:56	{"gard": ["2765"], "mesh": ["C537512"], "omim": ["300064"], "umls": ["C2931516"], "icd-10": ["Q87.0"], "synonyms": ["Hyde Forster-McCarthy-Berry syndrome"]}
Patent ductus arteriosus - bicuspid aortic valve - hand anomalies syndrome is a very rare heart-hand syndrome (see this term) that is characterized by a variety of cardiovascular anomalies including patent arterial duct, bicuspid aortic valve and pseudocoarctation of the aorta in conjunction with hand anomalies such as brachydactyly and ulnar ray derivative i.e. fifth metacarpal hypoplasia. Transmission is most likely autosomal dominant. [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	Patent ductus arteriosus-bicuspid aortic valve-hand anomalies syndrome	c1858420	8,317	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228190	2021-01-23T17:22:46	{"mesh": ["C565782"], "omim": ["604381"], "umls": ["C1858420"], "icd-10": ["Q87.2"], "synonyms": ["Patent arterial duct-bicuspid aortic valve-hand anomalies syndrome"]}
A number sign (#) is used with this entry because selective complement component C1s deficiency can be caused by homozygous mutation in the C1S gene (120580) on chromosome 12p13. Clinical Features Inoue et al. (1998) reported a patient with a systemic lupus erythematosus-like syndrome and chronic glomerulonephritis in whom no C1s protein was detectable by immunoblot. By Northern blot and RT-PCR analysis, C1s mRNA was of appropriate size, but only 10% of the level detected in HCS2/8, a human chondrosarcoma cell line. Levels of beta-actin and C1r (216950) mRNA were similar to levels detected in HCS2/8. In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey et al. (2001) determined that an absence of plasma C1S accounted for a lack of classic complement (CH50) pathway activity. At age 5, the child was alive and well while receiving immunosuppressive drugs daily and penicillin. Molecular Genetics Inoue et al. (1998) reported a patient with selective C1s deficiency resulting from a homozygous mutation in the C1S gene (120580.0001). In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey et al. (2001) detected selective C1S deficiency resulting from a nonsense mutation in exon 12 of the C1S gene (120580.0002). Restriction enzyme analysis showed that the propositus was homozygous for the mutation, while a paternal grandmother, maternal grandfather, and aunts on both sides of the family were heterozygous. The mutation was not detected in systemic lupus erythematosus (152700) patients or unrelated Caucasian controls, including some from the same geographic 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 [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 C1s DEFICIENCY	c3151078	8,318	omim	https://www.omim.org/entry/613783	2019-09-22T15:57:32	{"mesh": ["C565170"], "omim": ["613783"], "orphanet": ["169147"], "synonyms": ["Immunodeficiency due to C1, C4, or C2 component complement deficiency", "Alternative titles", "Immunodeficiency due to an early component of complement deficiency", "C1s DEFICIENCY"]}
A number sign (#) is used with this entry because of evidence that Shukla-Vernon syndrome (SHUVER) is caused by hemizygous mutation in the BCORL1 gene (300688) on chromosome Xq25. Description Shukla-Vernon syndrome (SHUVER) is an X-linked recessive neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development, and behavioral abnormalities, including autism spectrum disorder and ADHD. Dysmorphic features are common and may include tall forehead, downslanting palpebral fissures, and tapering fingers. Some patients may have seizures and/or cerebellar atrophy on brain imaging. Carrier mothers may have mild manifestations, including learning disabilities (summary by Shukla et al., 2019). Clinical Features Schuurs-Hoeijmakers et al. (2013) reported 2 Dutch brothers, born of unrelated parents, with hypotonia, coarse facial features, and severe intellectual disability. The patients did not have seizures. Shukla et al. (2019) reported 5 boys from 3 unrelated families with a similar neurodevelopmental disorder. The 2 unrelated boys, 15 and 7 years of age, were identified at a genetics clinic in the U.S. They had mild developmental delay and hypotonia apparent from infancy, although both learned to walk and speak, and both were diagnosed with autism spectrum disorder and ADHD. Only 1 was reported to have mild intellectual disability. Neither had seizures, and brain imaging was not performed. Three brothers from an Indian family had a more severe phenotype with poor overall growth, early-onset seizures associated with EEG abnormalities, and cerebellar atrophy on brain imaging. These sibs had severely impaired intellectual development with delayed walking and speech; 1 was nonverbal at age 15 years. All had been diagnosed with autism spectrum disorder. All patients had variable, but overlapping, dysmorphic features, including long face, tall forehead, hypertelorism, downslanting palpebral fissures, broad base of nose, thick vermilion, dysmorphic ears, strabismus or exotropia, and long fingers. Inheritance The transmission pattern of SHUVER in the families reported by Shukla et al. (2019) was consistent with X-linked recessive inheritance, although some carrier females demonstrated mild manifestations. Molecular Genetics In 2 Dutch brothers (family W07-1601), born of unrelated parents, with SHUVER, Schuurs-Hoeijmakers et al. (2013) identified a hemizygous missense mutation in the BCORL1 gene (N820S; 300688.0001). The variant, which was found by exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected mother. Schuurs-Hoeijmakers et al. (2013) noted that the BCORL1 gene is expressed in the brain or in neuronal tissue. No functional studies of the variant were performed. The family was 1 of 19 nonconsanguineous families with intellectual disability that underwent exome sequencing. In 5 boys from 3 families with SHUVER, Shukla et al. (2019) identified hemizygous missense mutations in the BCORL1 gene (300688.0002-300688.0004). The mutations, which were found by whole-exome sequencing, were inherited from mothers who were unaffected or had mild manifestations, such as learning disabilities. Functional studies of the variants and studies of patient cells were not performed. INHERITANCE \- X-linked recessive GROWTH Other \- Poor overall growth (1 family) HEAD & NECK Face \- Dysmorphic features, variable \- Coarse facial features \- Tall forehead \- Long face Ears \- Dysmorphic ears Eyes \- Hypertelorism \- Downslanting palpebral fissures \- Strabismus \- Exotropia Nose \- Broad nasal base Mouth \- Thick vermilion \- Drooling SKELETAL Hands \- Long fingers \- Tapering fingers SKIN, NAILS, & HAIR Hair \- Sparse hair MUSCLE, SOFT TISSUES \- Hypotonia (in some patients) NEUROLOGIC Central Nervous System \- Global developmental delay, variable severity \- Impaired intellectual development, mild to severe \- Speech delay \- Learning difficulties \- Wide-based gait (in some patients) \- Seizures (in some patients) \- Cerebellar atrophy (in some patients) Behavioral Psychiatric Manifestations \- Autism spectrum disorder \- Stereotypic behaviors \- Attention deficit-hyperactivity disorder MISCELLANEOUS \- Onset in infancy \- Variable severity \- Carrier females may have mild manifestations MOLECULAR BASIS \- Caused by mutation in the BCL6 corepressor-like 1 gene (BCORL1, 300688.0001 ) ▲ 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	SHUKLA-VERNON SYNDROME	None	8,319	omim	https://www.omim.org/entry/301029	2019-09-22T16:18:52	{"omim": ["301029"]}
Fear or disgust of objects with irregular patterns of holes or bumps The holes in lotus seedheads elicit feelings of discomfort or repulsion in some people.[1][2] Trypophobia is an aversion to the sight of irregular patterns or clusters of small holes or bumps.[3][4] It is not officially recognized as a mental disorder, but may be diagnosed as a specific phobia if excessive fear and distress occur.[1][3] People may express only disgust to trypophobic imagery.[3] The scientific understanding of trypophobia is limited.[3] Although few studies have been done on trypophobia, researchers hypothesize that it is the result of a biological revulsion that associates trypophobic shapes with danger or disease, and may therefore have an evolutionary basis.[1][3] Exposure therapy is a possible treatment.[1] The term trypophobia was coined by a participant in an online forum in 2005.[5] It has since become a popular topic on social media.[5] ## Contents * 1 Classification * 2 Signs and symptoms * 3 Causes * 4 Treatment * 5 Epidemiology * 6 Society and culture * 7 See also * 8 References ## Classification[edit] Trypophobia is not recognized by name as a mental disorder, and so is not a specific diagnosis in the American Psychiatric Association's Diagnostic and Statistical Manual, Fifth Edition (DSM-5). However, it may fall under the broad category of specific phobia if the fear is excessive, persistent, and associated with significant distress or impairment.[1] Whether trypophobia can be accurately described as a specific phobia might depend on whether the person mainly responds with fear or with disgust. Because phobias involve fear, a response to trypophobic imagery that is based mostly or solely on disgust renders its status as a specific phobia questionable.[3] In one study, most of the participants with trypophobia met the DSM-5 criteria for specific phobia, even though they experienced disgust instead of fear when shown imagery of clusters of holes; however, they did not meet the distress or impairment criterion.[3] ## Signs and symptoms[edit] Trypophobia often presents with an autonomic nervous system response.[3] Shapes that elicit a trypophobic reaction include clustered holes in innocuous contexts, such as fruit and bubbles, and in contexts associated with danger, such as holes made by insects and holes in wounds and diseased tissue such as those caused by mango flies in animals, especially dogs. Upon seeing these shapes, some people said they shuddered, felt their skin crawl, experienced panic attacks, sweated, palpitated, or felt nauseated or itchy.[1][6] Other reported symptoms include goose bumps, body shakes, feeling uncomfortable, and visual discomfort such as eyestrain, distortions, or illusions.[3][7] Trypophobia may manifest as a reaction of fear, disgust, or both.[3] Disgust is usually the stronger emotion in those with trypophobia.[3] ## Causes[edit] The understanding of trypophobia is limited.[3] Several possible causes have been proposed.[3] Geoff Cole and Arnold Wilkins believe the reaction is an "unconscious reflex reaction" based on a biological revulsion, rather than a learned cultural fear.[6] Imagery of various venomous animals (for example, certain types of snakes, insects, and spiders) have visual characteristics similar to trypophobic imagery. Because of this, it is hypothesized that trypophobia has an evolutionary basis meant to alert humans of dangerous organisms.[1][8][9] Can et al., however, believe the connection between trypophobia and evolution as a result of a threat from deadly creatures to be weak and that, if a connection does exist, it manifests later in life rather than in childhood.[3][10] Martínez-Aguayo et al. described trypophobia as usually involving "an intense and disproportionate fear towards holes, repetitive patterns, protrusions, etc., and, in general, images that present high-contrast energy at low and midrange spatial frequencies."[3] Cole and Wilkins also stated the imagery has high spatial frequency with a greater energy at midrange.[1][3] Whether together or separate, it appears that low and midrange spatial frequencies are necessary for inducing trypophobic reactions. Based on the imagery's visual cues, An Trong Dinh Le, Cole and Wilkins developed a symptom questionnaire that they believe can be used to identify trypophobia.[3] Researchers have also speculated that trypophobic reactions could be perceived as cues to infectious disease, which could be alerts that give one a survival advantage. In a study by Kupfer and Le, trypophobic and non-trypophobic participants showed significant aversion to disease-relevant cluster images, but only trypophobic participants displayed significant aversion to disease-irrelevant cluster images. Martínez-Aguayo et al. stated that, because the reactions could not be attributed to different sensitivity levels or neuroticism differences, Kupfer and Le believe it supports their hypothesis that trypophobia is "an overgeneralized aversion towards cluster stimuli that indicates a parasitic and infectious disease threat".[3] Yamada and Sasaki also propose that trypophobic reactions are due to the imagery's visual similarities to skin diseases.[3] Whether trypophobia is associated with obsessive–compulsive disorder (OCD) has also been studied. A significant minority of those with trypophobia meet the DSM-5 criteria for obsessive–compulsive disorder.[3] Martínez-Aguayo et al. stated that other findings refer to trypophobia having common comorbid psychiatric diagnosis, such as major depressive disorder or generalized anxiety disorder, although Le et al. felt that general anxiety does not cause trypophobia.[3] ## Treatment[edit] There are no known treatments for trypophobia, but exposure therapy, which has been used to treat phobias, is likely to be effective for treating trypophobia.[1] ## Epidemiology[edit] The extent to which trypophobia exists is unknown,[1] but the available data suggests that having an aversion to trypophobic imagery is relatively common.[1][2][3] 16% of a sample of 286 participants in a 2013 study reported discomfort or repulsion when presented with an image of a lotus seed pod and its authors found that non-trypophobic individuals also experienced more discomfort when viewing trypophobic imagery than when viewing neutral images.[1] Trypophobia appears to be more prevalent in women.[3] ## Society and culture[edit] The term trypophobia is believed to have been coined by a participant in an online forum in 2005.[5] The word is from the Greek: τρῦπα, trŷpa, meaning "hole" and φόβος, phóbos, meaning "fear".[5] Groups on social media sites such as Facebook and Instagram exist for self-identified trypophobics to share and discuss images that they say induce the reaction.[5][11] Because trypophobia is not well known to the general public, many people with the condition do not know the name for it and believe that they are alone in their trypophobic reactions and thoughts until they find an online community to share them with.[12] This has led to an increase in trypophobic images on social media; in some cases, people seek to intentionally induce trypophobia in those who have it by showing them trypophobic images, with the most trypophobic-inducing images being holes and clusters (especially the lotus seedhead) photoshopped onto human skin.[12] Cole and Wilkins also stated that the level of disgust with trypophobia increases if the holes are on human skin.[12] Writing in Popular Science, Jennifer Abbasi argues that emotional contagion within such social media groups may be responsible for some of the aversive reactions to such images.[5] In 2017, trypophobia received media attention when American Horror Story featured a trypophobic character[13] and trypophobia-inducing advertisements promoting the storyline; some people were disturbed by the imagery,[12][14] and criticized the show for "insensitivity towards sufferers of trypophobia".[14] Although there was sentiment that the increased media attention could lead to people trying to induce trypophobia, there were also opinions that it might help people understand trypophobia and encourage more research on the matter.[12] Some users responded to the September 2019 release of Apple's iPhone 11 Pro, which features three closely spaced camera lenses, with comments that it triggered their trypophobia.[15] Writer and editor Kathleen McAuliffe suggested that trypophobia is yet to be extensively studied because researchers have not given as much attention to topics of disgust as they have to other areas of research, and because of the revulsion viewing the images could incite in researchers.[16] ## See also[edit] * List of phobias ## References[edit] 1. ^ a b c d e f g h i j k l Milosevic, Irena; McCabe, Randi E. (2015). Phobias: The Psychology of Irrational Fear. ABC-CLIO. pp. 401–402. ISBN 978-1610695763. Retrieved October 25, 2017. 2. ^ a b Schacter, Daniel; Gilbert, Daniel; Wegner, Daniel; Hood, Bruce (2015). Psychology: Second European Edition. Palgrave Macmillan. p. 1391. ISBN 978-1137406750. Retrieved October 25, 2017. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w Martínez-Aguayo, Juan Carlos; Lanfranco, Renzo C.; Arancibia, Marcelo; Sepúlveda, Elisa; Madrid, Eva (2018). "Trypophobia: What Do We Know So Far? A Case Report and Comprehensive Review of the Literature". Frontiers in Psychiatry. 9: 15. doi:10.3389/fpsyt.2018.00015. ISSN 1664-0640. PMC 5811467. PMID 29479321. 4. ^ Le, An T. D.; Cole, Geoff G.; Wilkins, Arnold J. (January 30, 2015). "Assessment of trypophobia and an analysis of its visual precipitation". Quarterly Journal of Experimental Psychology. 68 (11): 2304–22. doi:10.1080/17470218.2015.1013970. PMID 25635930. 5. ^ a b c d e f Abbasi, Jennifer (July 25, 2011). "Is Trypophobia a Real Phobia?". Popular Science. Retrieved October 2, 2012. 6. ^ a b Cole, Geoff G.; Wilkins, Arnold J. (October 2013). "Fear of Holes" (PDF). Psychological Science. 24 (10): 1980–1985. doi:10.1177/0956797613484937. PMID 23982244. 7. ^ "Everything You Should Know About Trypophobia". Healthline. August 7, 2015. Retrieved October 26, 2017. 8. ^ Hockenbury, Don; Hockenbury, Sandra E. (2016). Discovering Psychology. Macmillan Higher Education. p. xxxii (sidebar). ISBN 978-1464176968. 9. ^ Kupfer, T. R.; Fessler, D. M. T. (19 July 2018). "Ectoparasite defence in humans: relationships to pathogen avoidance and clinical implications". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 373 (1751): 20170207. doi:10.1098/rstb.2017.0207. PMC 6000138. PMID 29866920. 10. ^ https://pubmed.ncbi.nlm.nih.gov/28558623/ 11. ^ Doucleff, Michaeleen. "Fear Of Cantaloupes And Crumpets? A 'Phobia' Rises From The Web". NPR. Retrieved 10 Apr 2016. 12. ^ a b c d e LaMottef, Sandee (September 14, 2017). "TV show triggers little-known phobia". CNN. Retrieved October 26, 2017. 13. ^ King, Eric (September 6, 2017). "American Horror Story: Cult: Why is Ally afraid of small holes?". Entertainment Weekly. Retrieved October 26, 2017. 14. ^ a b Pavey, Harriet (September 5, 2017). "What is trypophobia? Bizarre fear of small holes featured in new American Horror Story series". London Evening Standard. Retrieved October 26, 2017. 15. ^ "Apple's iPhone 11 Pro 'triggering' fear of holes". BBC News. 11 September 2019. Retrieved 11 September 2019. 16. ^ McAuliffe, Kathleen (2016). This Is Your Brain on Parasites: How Tiny Creatures Manipulate Our Behavior. Houghton Mifflin Harcourt. p. 154. ISBN 978-0544193222. Retrieved October 25, 2017. Look up trypophobia in Wiktionary, the free dictionary. [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	Trypophobia	None	8,320	wikipedia	https://en.wikipedia.org/wiki/Trypophobia	2021-01-18T18:51:16	{"wikidata": ["Q560107"]}
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-55 (RP55) is caused by homozygous mutation in the ARL6 gene (608845) on chromosome 3q11. One such family has been reported. Mutation in the ARL6 gene can also cause a form of Bardet-Biedl syndrome (BBS3; see 209900), in which retinitis pigmentosa is one of the primary features. Mapping Aldahmesh et al. (2009) used homozygosity mapping to suggest causative genes in 52 Saudi Arabian patients with nonsyndromic retinitis pigmentosa (RP), and found linkage to the BBS3 locus on chromosome 3p12-q13. Molecular Genetics In 4 Saudi Arabian sibs with nonsyndromic retinitis pigmentosa (RP) mapping to chromosome 3p12-q13, Aldahmesh et al. (2009) identified homozygosity for a missense mutation in the ARL6 gene (608845.0006). Thorough examination of the affected sibs by Safieh et al. (2010) revealed no recognizable primary or secondary features of BBS other than retinitis pigmentosa. Analysis of more than 50 additional RP patients yielded no similar cases, suggesting that the contribution of ARL6 to nonsyndromic RP is infrequent. [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	RETINITIS PIGMENTOSA 55	c0035334	8,321	omim	https://www.omim.org/entry/613575	2019-09-22T15:58:16	{"doid": ["0110370"], "mesh": ["D012174"], "omim": ["613575"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
In medicine, a stinger,[1][2] also called a burner or nerve pinch injury, is a neurological injury suffered by athletes, mostly in high-contact sports such as ice hockey, rugby, American football, and wrestling. The spine injury is characterized by a shooting or stinging pain that travels down one arm, followed by numbness and weakness in the parts of the arms, including the biceps, deltoid, and spinati muscles. Many athletes in contact sports have suffered stingers, but they are often unreported to medical professionals. Anyone who experiences significant trauma to his or her head or neck needs immediate medical evaluation for the possibility of a spinal injury. In fact, it's safest to assume that trauma victims have a spinal injury until proven otherwise because: * The time between injury and treatment can be critical in determining the extent of complications and the amount of recovery * A serious spinal injury is not always immediately obvious. If it is not recognized, more severe injury may occur * Numbness or paralysis may develop immediately or come on gradually as bleeding or swelling occurs in or around the spinal cord[3] ## Contents * 1 Mechanism * 2 Diagnosis and treatment * 3 Returning to play * 4 Prevention * 5 Epidemiology * 6 History * 7 References * 8 External links ## Mechanism[edit] The three main mechanisms of a stinger include receiving direct blows, extension, and compression of the brachial plexus, with most of the brachial plexus injuries being an extension-compression mechanism. A stinger is an injury that is caused by restriction of the nerve supply to the upper extremity via the brachial plexus. The brachial plexus is formed by the anterior rami of the nerves at the 5th cervical level of the spinal cord all the way to the nerves at the 1st thoracic level of the spinal cord. The brachial plexus innervates the upper extremity as well as some muscles in the neck and shoulder.[4] Damage to the brachial plexus can occur when the nerves are stretched too far from the head and neck; specifically the upper trunk of the plexus –nerve roots at the 5th and 6th cervical level –are primarily affected. The upper trunk provides part of the nerve to supply to the upper extremity via the Musculocutaneous, Axillary, Radial and Median nerves.[5] It is for this reason that stingers do not affect both arms simultaneously, however it is possible for both arms to accrue injuries. Repeated nerve trauma can cause recurring stingers, chronic pain, and muscle weakness, while recovery can take weeks to months in severe cases.[6] Since stingers are a nerve injury, a stinger can fall into two different categories of peripheral nerve injury with physiological differences. Grade I is neurapraxia, which involves focal damage of the myelin fibers around the axon, with the axon and the connective tissue sheath remaining intact. The disruption of nerve function involves demyelination. Axonal integrity is preserved, and remyelination occurs within days or weeks.[7][8] Grade II is categorized by axonotmesis which is the most severe case of nerve injury in the context of stingers and involves the injury of the axon.[7] Grade III is classified as neurotmesis where there is a complete disruption of the axon, where it is unlikely of recovery. If this is to happen it is not considered a stinger, and usually is a high-energy injury to the shoulder-girdle.[8] ## Diagnosis and treatment[edit] Stingers are best diagnosed by a medical professional. This person will assess the athlete's pain, range of head and neck motion, arm numbness, and muscle strength. Often, the affected athlete is allowed to return to play within a short time, but persistent symptoms will result in removal. Athletes are also advised to receive regular evaluations until symptoms have ceased, specifically, the restoration of pain-free mobility.[2] If they have not after two weeks, or increase, additional tests such as magnetic resonance imaging (MRI) can be performed to detect a more serious injury, such as a herniated disc. The order of treatments applied depends on whether the athlete's main complaint is pain or weakness. Both can be treated with an analgesic, anti-inflammatory medication, ice and heat, restriction of movement, and if necessary, cervical collar or traction. Surgery is only necessary in the most severe cases. ## Returning to play[edit] Returning from this injury depends on the number of burners that occurs. If a stinger occurs, the athletes usually return to play after they restore full strength, are asymptomatic where no pain persists, and painless range of motion in the cervical spine. At low frequencies of stingers, like 1 or 2, there is a much lower risk of the symptoms reoccurring. If three or more stingers occur in one season, one has a higher increased risk at the symptoms persisting.[9] If one is returning from play to contact sports it is important to adopt a strict exercise regimen of the neck muscles so the player has the ability to handle the trauma associated with tackles.[10] ## Prevention[edit] Stingers can be prevented by several of the following factors, but first, it is crucial to identify the severity of the stinger because treatment usually depends on that factor. If strengthening treatment starts too early with a severe case, it can prevent one from healing. The dysfunctions that caused the peripheral nerve injury must be identified to treat and prevent future injury.[11] Flexibility and strength of the neck, shoulder, and upper extremity are essential because stiffness and weakness are predisposing factors for a burner as well as consequences of this injury. Factors that could help in the prevention of stingers could include strengthening the muscles, increasing the range of motion, and improving technique when playing.[12] Simple measures can be taken to help in the recovery from stingers. A chest-out posture should be adapted to prevent the neck from extending too far because it brings the head over the shoulders. The chest-out posture is emphasized due to it not being commonly adopted by athletes due to developed shoulders and is perpetuated by brachial plexus irritation. The chest-out posture also reduces pressure on the brachial plexus by opening the thoracic outlet.[13] Finally, stingers can be prevented by wearing protective gear, such as butterfly restrictors, designed to protect the head and neck from being forced into unnatural positions. This equipment is more feasible in positions where unrestricted head and neck movement is not required, such as American football lineman, than in positions like quarterback, where such movement is integral. Regardless of equipment, it is important to report even minor symptoms to an athletic trainer or team physician, and to allow appropriate recovery time.[citation needed] ## Epidemiology[edit] Stingers commonly occur in contact sports like wrestling, hockey, basketball, boxing, rugby, weightlifting, and, most notably, football. One study found that up to 65% of college football players have suffered at least one stinger. However, it is difficult to ping an exact number of athletes that suffer from stingers as stingers are historically under-reported. This could be due to the players fear of being removed from play or the injury being viewed as unimportant.[14] The following study found different frequencies in the number of stingers that occur. Incidence of stingers over a six-year study period with only 1.5 stingers per team each season. Most of the stingers reported were either during competitions or preseason. Exactly 93% of stingers were due to player contact, specifically 36.7% occurring while tackling and 25.8% occurring while blocking.[15] ## History[edit] In 1976 most major American football leagues banned the technique of spearing in the sport due to the risk of injury. When a player makes head-down contact, that player has much more of a chance of a significant spinal cord injury. After the initial rule change, many of the cervical spine injuries stopped.[16] Therefore, this prompted a new tackling technique to be adopted, such as the head-up tackling technique. This technique does prevent catastrophic spine injuries, but it can result in brachial plexus injuries. After the rule change, it has been estimated that stingers have gone up in prevalence.[17] ## References[edit] 1. ^ "Burners and Stingers - OrthoInfo - AAOS". aaos.org. 2. ^ a b McKeag, Douglas B.; Kuhlman, Geoffrey S. (1999-11-01). "The "Burner": A Common Nerve Injury in Contact Sports". American Family Physician. 60 (7): 2035. ISSN 1532-0650. PMID 10569506. 3. ^ "Spinal cord injury - Symptoms and causes". mayoclinic.org. 4. ^ Saladin, Kenneth S. Anatomy & Physiology: The Unity of Form and Function. 6th ed. New York, NY: McGraw-Hill, 2012. Print. 5. ^ PM&R Knowledge. "AAPM&R - American Academy of Physical Medicine and Rehabilitation." PM&R Knowledge NOW. American Academy of Physical Medicine and Rehabilitation, 2012. 6. ^ Kuhlman, Geoffrey S.; McKeag, Douglas B. (1 November 1999). "The "Burner": A Common Nerve Injury in Contact Sports". American Family Physician. 60 (7): 2035–2040. PMID 10569506. 7. ^ a b Neal, S. L., & Fields, K. B. (2010). Peripheral Nerve Entrapment and Injury in the Upper Extremity. American Family Physician , 81(2), 147–155. Retrieved from https://www.aafp.org/afp/2010/0115/p147.html 8. ^ a b Kuhlman , G. S., & Mckeag , D. B. (1999). The “Burner”: A Common Nerve Injury in Contact Sports. American Family Physician , 2035–2040. Retrieved from https://www.aafp.org/afp/1999/1101/p2035.html 9. ^ Qureshi, Sheeraz A.; Hecht, Andrew C. (2010-12-01). "Burner Syndrome and Cervical Cord Neuropraxia". Seminars in Spine Surgery. Athletic Spine Injuries: State of the Art. 22 (4): 193–197. doi:10.1053/j.semss.2010.06.005. ISSN 1040-7383. 10. ^ Chao, Simon; Pacella, Marisa J.; Torg, Joseph S. (2010-01-01). "The Pathomechanics, Pathophysiology and Prevention of Cervical Spinal Cord and Brachial Plexus Injuries in Athletics". Sports Medicine. 40 (1): 59–75. doi:10.2165/11319650-000000000-00000. ISSN 1179-2035. PMID 20020787. 11. ^ Weinstein, Stuart M. (1998-01-01). "ASSESSMENT AND REHABILITATION OF THE ATHLETE WITH A "STINGER": A Model for the Management of Noncatastrophic Athletic Cervical Spine Injury". Clinics in Sports Medicine. 17 (1): 127–135. doi:10.1016/S0278-5919(05)70067-3. ISSN 0278-5919. PMID 9475977. 12. ^ KUHLMAN, GEOFFREY S, and DOUGLAS B MCKEAG. “The ‘Burner’: A Common Nerve Injury in Contact Sports.” American Family Physician, 1 Nov. 1999, https://www.aafp.org/afp/1999/1101/p2035.html. 13. ^ Qureshi, Sheeraz A.; Hecht, Andrew C. (2010-12-01). "Burner Syndrome and Cervical Cord Neuropraxia". Seminars in Spine Surgery. Athletic Spine Injuries: State of the Art. 22 (4): 193–197. doi:10.1053/j.semss.2010.06.005. ISSN 1040-7383. 14. ^ Weinberg , J., Rokito , S., & Silber , J. S. (2003). Etiology, treatment, and prevention of athletic ‘‘stingers.’’ CLINICS IN SPORTS MEDICINE , 493–500. Retrieved from http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.624.6013&rep=rep1&type=pdf 15. ^ Green, James; Zuckerman, Scott L.; Dalton, Sara L.; Djoko, Aristarque; Folger, Dustin; Kerr, Zachary Y. (2017-01-02). "A 6-year surveillance study of "Stingers" in NCAA American Football". Research in Sports Medicine. 25 (1): 26–36. doi:10.1080/15438627.2016.1258642. ISSN 1543-8627. PMID 27873542. 16. ^ Heck, Jonathan F.; Clarke, Kenneth S.; Peterson, Thomas R.; Torg, Joseph S.; Weis, Michael P. (2004). "National Athletic Trainers' Association Position Statement: Head-Down Contact and Spearing in Tackle Football". Journal of Athletic Training. 39 (1): 101–111. ISSN 1062-6050. PMC 385269. PMID 15085218. 17. ^ Chao, Simon; Pacella, Marisa J.; Torg, Joseph S. (2010-01-01). "The Pathomechanics, Pathophysiology and Prevention of Cervical Spinal Cord and Brachial Plexus Injuries in Athletics". Sports Medicine. 40 (1): 59–75. doi:10.2165/11319650-000000000-00000. ISSN 1179-2035. PMID 20020787. ## External links[edit] * Stinger article at spine.org * Burner article at WebMD [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	Stinger (medicine)	None	8,322	wikipedia	https://en.wikipedia.org/wiki/Stinger_(medicine)	2021-01-18T18:55:05	{"icd-10": ["S14.3"], "wikidata": ["Q7617424"]}
A number sign (#) is used with this entry because of evidence that microvillus inclusion disease is caused by homozygous or compound heterozygous mutation in the MYO5B (606540) gene on chromosome 18q21. Description Microvillus inclusion disease (MVID) is characterized by onset of intractable life-threatening watery diarrhea during infancy. Two forms are recognized: early-onset MVID with diarrhea beginning in the neonatal period, and late-onset, with first symptoms appearing after 3 or 4 months of life. Definite diagnosis is made by transmission electron microscopy demonstrating shortening or absence of apical microvilli with pathognomonic microvillus inclusions in mature enterocytes and peripheral accumulation of periodic acid-Schiff (PAS)-positive granules or vesicles in immature enterocytes (Muller et al., 2008). The natural course of MVID is often fatal, but partial or total weaning from parenteral nutrition has been described. For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700). Clinical Features Davidson et al. (1978) described a group of infants who presented with an apparently familial enteropathy characterized by protracted diarrhea from birth and hypoplastic villus atrophy. Electron microscopic examination of surface enterocytes in a jejunal biopsy specimen from 1 of the patients showed peculiar intracytoplasmic inclusions composed of neatly arranged brush-border microvilli. Similar intracytoplasmic inclusions were described in other infants who had protracted diarrhea starting at or soon after birth (Phillips et al., 1985). Cutz et al. (1989) described the clinical and pathologic features of 9 cases. Three of the patients were from their original group of 5 patients reported by Davidson et al. (1978). Five were girls and four boys. Polyhydramnios was not observed in any of the patients, in contrast to congenital chloride diarrhea and diarrhea due to deficient sodium-hydrogen exchange, both of which are invariably associated with polyhydramnios. Three sets of sibs were represented among the 9 patients. In 2 families the parents were first cousins. One of the patients was still alive at 20 months; the other 8 had died at ages varying from 9 to 18 months. Cutz et al. (1989) concluded that this disorder may represent the most common cause of severe refractory diarrhea in the neonatal period. They suggested that microvillus inclusion disease may result from defective brush-border assembly and differentiation; it may represent an inborn error of intracellular transport, leading to aberrant assembly of the components of the enterocyte surface membrane. Rectal biopsy was proposed as a dependable and relatively easy method for early diagnosis. From a review of 23 cases of microvillus atrophy collected from medical centers around the world, Phillips and Schmitz (1992) concluded that congenital and late-onset forms could be identified and that cases of late onset appeared to have a better prognosis. They concluded that the first morphologic abnormality to be detected in the intestinal epithelium was accumulation of 'secretory granules'; microvillus inclusions were seen in older cells in the upper villus region. Phillips and Schmitz (1992) suggested that a fundamental defect affects the intracellular traffic of certain cell components. Their patients included 8 boys and 15 girls from 22 families, one family having 2 affected sisters. One Caucasian parental couple out of 15 was consanguineous and 5 Arab couples out of 6 were consanguineous. In 20 families in which information was available, more than 1 child was affected in 5. In 4 additional families, sibs had died from intractable diarrhea in the first months of life. In all but 3 cases, diarrhea was the only symptom during the first days of life. Fifteen infants (75%) died between 3 and 9 months, mostly of dehydration, malnutrition, and sepsis. The oldest patient at the time of survey was 5 years old and growing normally. Aspirin in low dosage decreased stool output in this patient. All patients were receiving total parenteral nutrition (TPN). Three of the patients still alive at the time of survey had 'late-onset' diarrhea. Fish and Molitoris (1994) discussed microvillus inclusion disease in connection with the role of changes in epithelial polarity in the pathogenesis of disease states. Likely possibilities for the mechanism of formation of these abnormal cytoplasmic vesicular bodies and apical surface membranes are centered around the abnormal delivery of Golgi-derived vesicles to the apical membrane. Processes mediated by both microtubules and actin microfilaments are involved in the delivery of vesicles to the apical region. Treatment of cultured fetal intestinal epithelium with microfilament-disrupting drugs resulted in the collapse of the apical membrane, with the formation of intracellular microvillus inclusion bodies (Carruthers et al., 1986). Intractable diarrhea of infancy (IDIF) was first defined by Avery et al. (1968) as a noninfectious diarrhea lasting for more than 2 weeks, with onset before a few months of age, with consequent malabsorption and failure to thrive. It comprises a heterogeneous group of conditions; while the great majority of cases have no known etiology, several reports distinguished ED2 subgroups. Straussberg et al. (1997) noted that in one subgroup, there is evidence of autoimmune involvement of the gastrointestinal tract as part of a systemic immune response. A second subgroup is characterized by a genetic basis, as indicated by parental consanguinity and a pattern of autosomal recessive inheritance. In this form, onset is usually before 2 months of age, extra intestinal involvement is infrequent, and there is no improvement of the diarrhea with diet and/or immunosuppression. Straussberg et al. (1997) reported a cluster of cases with Jewish Iraqi ancestry who showed no evidence of antienterocyte antibodies, did not respond to an elemental diet, steroid or immunosuppression therapy, and were dependent on total parenteral nutrition for years. Their 5 Iraqi Jewish patients with intractable diarrhea beginning during the first days of life belonged to 4 families. The parents were consanguineous in 3 families and the disorder recurred in a second sib in 1 family. The patients were all born after uneventful pregnancy and labor, with birth weight in the normal range. There were no dysmorphic features. Three patients were breastfed. Diarrhea was of the secretory type. Jejunal biopsies performed on all patients ranged from normal to severe partial villus atrophy. No similar cases were known in other ethnic groups in Israel, suggesting a possibly high gene frequency among Jews of Iraqi origin. Straussberg et al. (1997) concluded that the suggestion of a hereditary inborn defect of enterocyte differentiation as the pathogenetic mechanism is not certain and pointed out that the reports are probably based on a heterogeneous population of patients. In 4 patients from the Navajo reservation in northern Arizona, Pohl et al. (1999) observed microvillus inclusion disease with early onset. A fifth, unrelated affected Navajo child had been reported by Schofield et al. (1992). Van der Velde et al. (2013) described their curated online international patient registry, which includes detailed information on patients with microvillus inclusion disease as well as identified MYO5B mutations. Biochemical Features Straussberg et al. (1997) found that the activity of prostaglandin synthetase (176805), which catalyzes the conversion of arachidonic acid to PGE2, was 2 to 3 times the control values in their Iraqi Jewish patients with this disorder. Assmann et al. (1997) described a boy born of consanguineous parents who suffered from intractable diarrhea due to congenital microvillus atrophy. He developed severe cholestasis starting at 2 weeks of age that led to liver cirrhosis. His psychomotor development appeared only slightly delayed. At the age of 7 months he died of septicemia. In addition to disturbances of electrolyte balance and renal tubular function, which could be attributed to microvillus atrophy, the investigators also found marked elevations of dihydrouracil and dihydrothymine, as well as moderately elevated excretion of uracil and thymine in urine, suggesting a disorder of pyrimidine degradation. An enzymatic defect of dihydropyrimidinase (613326) was demonstrated in liver biopsy. Dihydropyrimidinuria (222748), due to dihydropyrimidinase deficiency, is an exceedingly rare autosomal recessive disorder. Assmann et al. (1997) questioned whether this was 1 disorder or 2 independent recessive disorders or whether it represented a contiguous gene syndrome. The patient of Assmann et al. (1997) was of Turkish extraction; 1 of the 2 cases of dihydropyrimidinuria that had previously been described was also Turkish. Kagitani et al. (1998) described an 11-year-old boy with hypophosphatemic rickets associated with congenital microvillus atrophy. He had suffered from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition since he was 67 days old. The diagnosis of congenital villus atrophy was made by intestinal biopsy when he was 4 years old. Rickets was discovered at the age of 11 years, at which time laboratory data revealed hypophosphatemia, elevated vitamin D levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. The parents were said to be unrelated. Using immunohistochemistry, Sato et al. (2007) observed a marked decrease in the level of RAB8 (165040) protein in small intestine in 1 patient. Mapping Muller et al. (2008) applied a positional candidate approach to identify the genetic basis of microvillus inclusion disease in an extended Turkish kindred. Homozygosity mapping identified a 16.99-Mb region of extended homozygosity in both affected individuals, who were first cousins, with haplotypes consistent with inheritance of the mutation from a common ancestor. Muller et al. (2008) obtained multipoint lod scores of Z = 3.40 with theta = 0.0 at several SNPs within this critical interval on chromosome 18q21, with boundaries set between rs1521791 and rs1369766 by 2 recombinants. Molecular Genetics Among 79 genes contained in the critical interval for MVID identified by Muller et al. (2008) using homozygosity mapping, MYO5B (606540) was considered a plausible candidate. The authors performed mutation analysis of the 40 MYO5B exons and all splice sites in the proband of the linked family and identified a homozygous in-frame insertion (606540.0001). They then identified 6 distinct, homozygous germline MYO5B mutations in 6 of 9 additional probands. Each of the mutations segregated with disease status, and none was present among 188 controls. Two additional affected individuals had a heterozygous nonsense mutation, with no second mutation identified on the other allele; however, Muller et al. (2008) noted that direct sequencing might have missed larger deletions or intronic gene mutations. In 7 Navajo patients with severe, early-onset MVID, Erickson et al. (2008) identified a homozygous missense mutation (P660L; 606540.0006) in exon 16 of the MYO5B gene. Five obligate carriers were heterozygous for the mutation, which was not found in and 8 unrelated Navajos. Heterogeneity Muller et al. (2008) identified 1 patient with MVID from a consanguineous family in whom no mutation in MYO5B was found at either the genomic or the cDNA level, suggesting genetic heterogeneity for this disorder. Animal Model Sato et al. (2007) found that Rab8 (165040) knockout mice show a phenotype almost identical to human MVID, including diarrhea, malnutrition, shortening of the microvilli, and microvillus inclusion, to patients with microvillus inclusion disease. However, sequencing of 2 early-onset cases and 1 late-onset case showed no mutations in the exons of the RAB8 gene. Growth \- Growth delay \- Infantile death often Lab \- Hypoplastic villus atrophy \- Surface enterocytes have intracytoplasmic inclusions composed of neatly arranged brush-border microvilli on EM GI \- Enteropathy \- Protracted diarrhea \- Dehydration \- Malnutrition 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	DIARRHEA 2, WITH MICROVILLUS ATROPHY	c0341306	8,323	omim	https://www.omim.org/entry/251850	2019-09-22T16:25:12	{"doid": ["0060775"], "mesh": ["C537470"], "omim": ["251850"], "orphanet": ["2290"], "synonyms": ["Alternative titles", "MICROVILLUS INCLUSION DISEASE", "MICROVILLUS ATROPHY, CONGENITAL", "DAVIDSON DISEASE", "CONGENITAL FAMILIAL PROTRACTED DIARRHEA WITH ENTEROCYTE BRUSH-BORDER ABNORMALITIES", "INTRACTABLE DIARRHEA OF INFANCY"]}
Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities. ## Epidemiology Prevalence is estimated to be 1-2 in 100,000 with significant geographical and ethnic variations. ## Clinical description The disease typically presents in the 4th decade (age range = 4-74 years). Ataxia gradually progresses and additional features may emerge including proprioceptive loss, hypoactive reflexes, ophthalmoparesis, and mild optic neuropathy. Initial presentation with blepharospasm, oromandibular dystonia, and retrocollis preceding ataxia has been reported. Cognition is relatively spared early on; however, executive dysfunction and impaired verbal memory may develop in later stages. ## Etiology SCA1 is caused by CAG repeat expansions in the ATXN1 gene region on chromosome 6p23. ## Prognosis Prognosis is poor. In the late stages of the disease, usually 10 to 15 years following onset, bulbar dysfunction secondary to affection of lower medullary nuclei results in aspiration which is life-threatening. [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	Spinocerebellar ataxia type 1	c0752120	8,324	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98755	2021-01-23T17:31:54	{"gard": ["4071"], "mesh": ["D020754"], "omim": ["164400"], "umls": ["C0752120"], "icd-10": ["G11.8"], "synonyms": ["SCA1"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant spastic paraplegia-73 (SPG73) is caused by heterozygous mutation in the CPT1C gene (608846) on chromosome 19q13. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). Clinical Features Rinaldi et al. (2015) reported a large 3-generation family from southern Italy with pure spastic paraplegia. The mean age at onset was 36 years (range 19-48 years), and the disorder was slowly progressive, resulting in gait impairment or loss of ambulation 10 to 15 years later. Features included spasticity of the lower limbs, proximal muscle weakness, mild muscle atrophy, hyperreflexia with extensor plantar responses, decreased vibratory sense at the ankles, and mild urinary dysfunction. Two patients had foot deformities. Neurophysiologic examination showed prolonged central motor conduction time and delayed sensory-evoked potentials, indicating abnormalities of the corticospinal tract and dorsal column. Peripheral nerve conduction studies, cognitive function, and brain imaging were normal. Inheritance The transmission pattern of SPG73 in the family reported by Rinaldi et al. (2015) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a large 3-generation Italian family with SPG73, Rinaldi et al. (2015) identified a heterozygous missense mutation in the CPT1C gene (R37C; 608846.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. No CPT1C mutations were found in 163 additional individuals with pure SPG. Structural modeling suggested that the mutation would destabilize the protein and disturb a likely interaction between the regulatory and catalytic domains. Transfection of the mutation into COS-7 cells decreased the number and size of lipid droplets via a dominant-negative effect. The findings suggested a role for altered lipid-mediated signal transduction in the pathogenesis of the disorder. Animal Model Carrasco et al. (2013) found that Cpt1c-deficient mice developed early onset of progressive motor disturbances, including impaired gait and coordination, severe muscle weakness, and reduced locomotor activity. Cerebellar, striatum, and motor cortex extracts from Cpt1c-knockout mice showed reduced levels of ceramide and its derivative, sphingosine, mainly during the fasting state, compared to wildtype animals. The results indicated that altered ceramide metabolism in motor brain areas induced by Cpt1c deficiency can cause progressive motor dysfunction. INHERITANCE \- Autosomal dominant GENITOURINARY Bladder \- Urinary dysfunction, mild SKELETAL Feet \- Foot deformities (in some patients) MUSCLE : Muscle weakness, proximal, mild \- Muscle atrophy, mild NEUROLOGIC Central Nervous System \- Spastic paraplegia \- Difficulty walking \- Loss of ambulation (in some patients) \- Hyperreflexia \- Extensor plantar responses \- Decreased vibration sense at ankles due to abnormalities of the dorsal column \- Delayed central sensory evoked potentials \- Prolonged central motor conduction time MISCELLANEOUS \- Adult onset (range 19 to 48 years) \- Slowly progressive \- One family has been reported (last curated March 2015) MOLECULAR BASIS \- Caused by mutation in the carnitine palmitoyltransferase IC gene (CPT1C, 608846.0001 ) ▲ 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	SPASTIC PARAPLEGIA 73, AUTOSOMAL DOMINANT	c4225387	8,325	omim	https://www.omim.org/entry/616282	2019-09-22T15:49:25	{"doid": ["0110818"], "omim": ["616282"], "orphanet": ["444099"], "synonyms": ["SPG73"]}
This article needs to be updated. Please update this article to reflect recent events or newly available information. (March 2019) Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 430 recognized PIDs as of 2019, most are very rare.[1] About 1 in 500 people in the United States are born with a primary immunodeficiency.[2] Immune deficiencies can result in persistent or recurring infections, auto-inflammatory disorders, tumors, and disorders of various organs. There are currently limited treatments available for these conditions; most are specific to a particular type of PID. Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classifications * 4 Treatment * 5 Epidemiology * 6 Research * 7 History * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.[2] ## Causes[edit] By definition, primary immune deficiencies are due to genetic causes. They may result from a single genetic defect, but most are multifactorial. They may be caused by recessive or dominant inheritance. Some are latent, and require a certain environmental trigger to become manifest, like the presence in the environment of a reactive allergen. Other problems become apparent due to aging of bodily and cellular maintenance processes. ## Diagnosis[edit] The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).[2] Other tests are performed depending on the suspected disorder:[2] * Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers: HLA-DR, CD25, CD80 (B cells). * Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells * Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses * Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity. Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.[2] Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease which are present, but not all.[3] ### Classifications[edit] Main article: List of primary immunodeficiencies There are many forms of PID. The International Union of Immunological Societies recognizes nine classes of primary immunodeficiencies, totaling over 120 conditions. A 2014 update of the classification guide added a 9th category and added 30 new gene defects from the prior 2009 version.[4][5] As of 2019[update], there are approximately 430 forms of PID that have been identified.[1] Different forms of PID have different mechanisms. Rough categorizations of conditions divide them into humoral immunity disorders, T-cell and B-cell disorders, phagocytic disorders, and complement disorders.[6] Most forms of PID are very rare. IgA deficiency is an exception, and is present in 1 in 500 people. Some of the more frequently seen forms of PID include common variable immunodeficiency, severe combined immunodeficiency, X-linked agammaglobulinemia, Wiskott–Aldrich syndrome, DiGeorge syndrome, ataxia–telangiectasia,[7] ## Treatment[edit] The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system. Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised. In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available. In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed. For primary immunodeficiencies that are caused by genetic mutation does not exist a causal therapy that would "repair" the mutation. Although there is a therapeutic option, gene therapy which has been in a trial for few immune deficiencies affecting the hematopoietic system. Over the past two decades there were some successful treatments of patients with specific primary immunodeficiencies (PID), including X-linked severe combined immunodeficiency (SCID), Wiskott–Aldrich syndrome and metabolic conditions such as leukodystrophy.[8] Gene therapy evolved in the 90s from using of gammaretroviral vectors to more specific self-inactivating vector platforms around 2006.[9] The viral vectors randomly insert their sequences into the genomes. However, it is rarely used because of a risk of developing post-treatment T-cell leukemia as a result of interfering tumor-suppressor genes [9] and because of ethical issues.[10] But the progress in gene therapy is promising for the future of treating primary immunodeficiencies.[11] ## Epidemiology[edit] A survey of 10,000 American households revealed that the prevalence of diagnosed primary immunodeficiency approaches 1 in 1200. This figure does not take into account people with mild immune system defects who have not received a formal diagnosis.[12] Milder forms of primary immunodeficiency, such as selective immunoglobulin A deficiency, are fairly common, with random groups of people (such as otherwise healthy blood donors) having a rate of 1:600. Other disorders are distinctly more uncommon, with incidences between 1:100,000 and 1:2,000,000 being reported.[2] ## Research[edit] Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.[13] Virus-specific T-lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency.[14] T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away. Induced pluripotent stem cells obtained repogramming patients' cells, for example leukocytes, are a promising tool to study these pathologies and develop personalized therapies.[15] ## History[edit] X-linked agammaglobulinemia was one of the first described primary immunodeficiencies, discovered by Ogden Bruton in 1952.[1][16] Primary immunodeficiencies were initially classified in 1970 by a committee of the World Health Organization. At the time, they identified 16 immunodeficiencies. By 1998, the number had reached 50.[17] Discovery of novel genetic causes of innate immunodeficiencies accelerated greatly in the 2010s due to high-throughput DNA sequencing technologies.[18] As of 2019, more than 430 have been categorized.[1] ## See also[edit] * Immunodeficiency * Inborn errors of immunity ## References[edit] 1. ^ a b c d Tangye, Stuart G.; Al-Herz, Waleed; Bousfiha, Aziz; Chatila, Talal; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Holland, Steven M.; Klein, Christoph; Morio, Tomohiro; Ochs, Hans D. (January 2020). "Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee". Journal of Clinical Immunology. 40 (1): 24–64. doi:10.1007/s10875-019-00737-x. ISSN 1573-2592. PMC 7082301. PMID 31953710. 2. ^ a b c d e f Lim MS, Elenitoba-Johnson KS (2004). "The Molecular Pathology of Primary Immunodeficiencies". The Journal of Molecular Diagnostics. 6 (2): 59–83. doi:10.1016/S1525-1578(10)60493-X. PMC 1867474. PMID 15096561. 3. ^ Conley ME, Notarangelo LD, Etzioni A (1999). "Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)". Clin. Immunol. 93 (3): 190–7. doi:10.1006/clim.1999.4799. PMID 10600329. 4. ^ Waleed Al-Herz; Aziz Bousfiha; Jean-Laurent Casanova; et al. (2014). "Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency" (PDF). Frontiers in Immunology. 5 (162): 1–33. doi:10.3389/fimmu.2014.00162. PMC 4001072. PMID 24795713. 5. ^ Notarangelo L, Casanova JL, Conley ME, et al. (2006). "Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005". J. Allergy Clin. Immunol. 117 (4): 883–96. doi:10.1016/j.jaci.2005.12.1347. PMID 16680902. 6. ^ Cooper, Megan A.; Pommering, Thomas; Koranyi, Katalin (15 November 2003). "Primary Immunodeficiencies". American Family Physician. 68 (10): 2001–2008. PMID 14655810. 7. ^ McCusker, Christine; Warrington, Richard (10 November 2011). "Primary immunodeficiency". Allergy, Asthma, and Clinical Immunology. 7 (Suppl 1): S11. doi:10.1186/1710-1492-7-S1-S11. PMC 3245434. PMID 22165913. 8. ^ Booth, Claire; Romano, Rosa; Roncarolo, Maria Grazia; Thrasher, Adrian J. (2019-07-11). "Gene therapy for primary immunodeficiency". Human Molecular Genetics. 28 (R1): R15–R23. doi:10.1093/hmg/ddz170. ISSN 1460-2083. PMID 31297531. 9. ^ a b Cavazzana, Marina; Six, Emmanuelle; Lagresle-Peyrou, Chantal; André-Schmutz, Isabelle; Hacein-Bey-Abina, Salima (2016-02-01). "Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?". Human Gene Therapy. 27 (2): 108–116. doi:10.1089/hum.2015.137. ISSN 1043-0342. PMC 4779287. PMID 26790362. 10. ^ Rabino, Isaac (2003). "Gene therapy: ethical issues". Theoretical Medicine and Bioethics. 24 (1): 31–58. doi:10.1023/A:1022967623162. ISSN 1386-7415. PMID 12735489. S2CID 34605125. 11. ^ McCusker, Christine; Warrington, Richard (2011-11-10). "Primary immunodeficiency". Allergy, Asthma, and Clinical Immunology. 7 (Suppl 1): S11. doi:10.1186/1710-1492-7-S1-S11. ISSN 1710-1484. PMC 3245434. PMID 22165913. 12. ^ Boyle JM, Buckley RH (2007). "Population prevalence of diagnosed primary immunodeficiency diseases in the United States". J. Clin. Immunol. 27 (5): 497–502. doi:10.1007/s10875-007-9103-1. PMID 17577648. 13. ^ Porta F, Forino C, De Martiis D, et al. (June 2008). "Stem cell transplantation for primary immunodeficiencies". Bone Marrow Transplant. 41 Suppl 2: S83–6. doi:10.1038/bmt.2008.61. PMID 18545252. 14. ^ Naik, S; Nicholas, S; Martinez, C; Leen, A; Hanley, P; Gottschalk, S; Rooney, C; Hanson, I; Krance, R; Shpall, E; Cruz, C; Amrolia, P; Lucchini, G; Bunin, N; Heimall, J; Klein, O; Gennery, A; Slatter, M; Vickers, M; Orange, J; Heslop, H; Bollard, C; Keller, M (24 February 2016). "Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes". Journal of Allergy and Clinical Immunology. 137 (5): 1498–1505.e1. doi:10.1016/j.jaci.2015.12.1311. PMC 4860050. PMID 26920464. 15. ^ Genova, Elena; Cavion, Federica; Lucafò, Marianna; Pelin, Marco; Lanzi, Gaetana; Masneri, Stefania; Ferraro, Rosalba Monica; Fazzi, Elisa Maria; Orcesi, Simona; Decorti, Giuliana; Tommasini, Alberto; Giliani, Silvia; Stocco, Gabriele (2020). "Biomarkers and Precision Therapy for Primary Immunodeficiencies: An In Vitro Study Based on Induced Pluripotent Stem Cells From Patients". Clinical Pharmacology & Therapeutics. 108 (2): 358–367. doi:10.1002/cpt.1837. PMID 32243572. 16. ^ Bruton, O. C. (June 1952). "Agammaglobulinemia". Pediatrics. 9 (6): 722–728. ISSN 0031-4005. PMID 14929630. 17. ^ Picard, Capucine; Bobby Gaspar, H.; Al-Herz, Waleed; Bousfiha, Aziz (2018). "International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity". Journal of Clinical Immunology. 38 (1): 96–128. doi:10.1007/s10875-017-0464-9. ISSN 0271-9142. PMC 5742601. PMID 29226302. 18. ^ Bucciol, Giorgia; Moens, Leen; Bosch, Barbara; Bossuyt, Xavier; Casanova, Jean-Laurent; Puel, Anne; Meyts, Isabelle (February 2019). "Lessons learned from the study of human inborn errors of innate immunity". The Journal of Allergy and Clinical Immunology. 143 (2): 507–527. doi:10.1016/j.jaci.2018.07.013. ISSN 1097-6825. PMC 6358521. PMID 30075154. ## External links[edit] * International Union of Immunological societies (IUIS) * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency [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 immunodeficiency	c0021051	8,326	wikipedia	https://en.wikipedia.org/wiki/Primary_immunodeficiency	2021-01-18T18:28:15	{"mesh": ["D007153", "D000081207"], "umls": ["C0021051"], "orphanet": ["101997"], "wikidata": ["Q3043160"]}
Familial adenomatous polyposis (FAP) is characterized by the development of hundreds to thousands of adenomas in the rectum and colon during the second decade of life. ## Epidemiology FAP has a birth incidence of about 1/8,300, manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the EU, prevalence is estimated at 1/11,300-1/37,600. ## Clinical description Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present some extraintestinal manifestations such as osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP; see this term), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner syndrome, whereas the association of FAP and medulloblastoma is referred to as the Turcot syndrome (see these terms). ## Etiology Classic FAP results from a germline mutation in the APC gene (5q21-q22). Most patients (about 70%) have a family history of colorectal polyps and cancer. In one patient subset, a MUTYH mutation (1p34.1) causes a recessively inherited polyposis condition, MUTYH-related familial adenomatous polyposis (see this term), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. ## Diagnostic methods Diagnosis is based on family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. ## Differential diagnosis Differential diagnoses include other disorders causing multiple polyps (Peutz-Jeghers syndrome, familial juvenile polyposis or hyperplastic polyposis, hereditary mixed polyposis syndrome, and Lynch syndrome; see these terms). ## Antenatal diagnosis Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing, is possible. Referral to a geneticist or genetic counselor is mandatory. ## Genetic counseling Classic FAP is inherited in an autosomal dominant manner. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. ## Management and treatment Cancer prevention and maintaining a good quality of life are the main goals of management, and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy, and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy. They need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery. Celecoxib has received marketing authorization by the US Food and Drug Administration (FDA) and the European Medicines Agency to be used as an adjunctive therapy in patients with FAP. ## Prognosis Patients with FAP carry a 100% risk of CRC. However, this risk is reduced significantly when patients enter a screening-treatment program. [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	Familial adenomatous polyposis	c0032580	8,327	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=733	2021-01-23T19:05:07	{"gard": ["6408"], "mesh": ["D011125"], "omim": ["175100"], "umls": ["C0032580"], "icd-10": ["D12.6"], "synonyms": ["Colorectal adenomatous polyposis", "FAP", "Familial polyposis coli"]}
Mitochondrial DNA depletion syndrome, hepatocerebrorenal form is a rare, genetic, mitochondrial DNA depletion syndrome characterized by neonatal or early-infantile onset hepatopathy (manifesting with hepatomegaly, cholestasis, increased transaminases, coagulopathy, hypoalbuminemia, ascites, and/or liver failure), associated with renal tubulopathy and progressive neurodegenerative manifestations, which include muscular atrophy, hyporeﬂexia, ataxia, sensory neuropathy, epilepsy, sensorineural hearing impairment, psychomotor regression, athetosis, nystagmus, and/or ophthalmoplegia. Patients typically present with recurrent vomiting, severe failure to thrive, feeding difficulties, and fasting hypoglycemia. [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	Mitochondrial DNA depletion syndrome, hepatocerebrorenal form	c1849096	8,328	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363534	2021-01-23T17:19:13	{"mesh": ["C535523"], "omim": ["271245"], "icd-10": ["E88.8"], "synonyms": ["mtDNA depletion syndrome, hepatocerebrorenal form"]}
Foster Kennedy syndrome Other namesGowers–Paton–Kennedy syndrome, Kennedy's phenomenon, Kennedy's syndrome Frontal lobe (on the right) SpecialtyNeurology Foster Kennedy syndrome is a constellation of findings associated with tumors of the frontal lobe.[1] Although Foster Kennedy syndrome is sometimes called "Kennedy syndrome",[2] it should not be confused with Kennedy disease, or spinal and bulbar muscular atrophy, which is named after William R. Kennedy. Pseudo-Foster Kennedy syndrome is defined as one-sided optic atrophy with papilledema in the other eye but with the absence of a mass.[3] ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 History * 5 References * 6 External links ## Presentation[edit] The syndrome is defined as the following changes: * optic atrophy in the ipsilateral eye * disc edema in the contralateral eye * central scotoma (loss of vision in the middle of the visual fields) in the ipsilateral eye * anosmia (loss of smell) ipsilaterally This syndrome is due to optic nerve compression, olfactory nerve compression, and increased intracranial pressure (ICP) secondary to a mass (such as meningioma or plasmacytoma, usually an olfactory groove meningioma).[4][5] There are other symptoms present in some cases such as nausea and vomiting, memory loss and emotional lability (i.e., frontal lobe signs).[5] ## Diagnosis[edit] Brain tumor can be visualized very well on CT scan, but MRI gives better detail and is the preferred study. Clinical localization of brain tumors may be possible by virtue of specific neurologic deficits or symptom patterns. Tumor at the base of the frontal lobe produces inappropriate behavior, optic nerve atrophy on the side of the tumor, papilledema on the other side, and anosmia. [6] ## Treatment[edit] The treatment, and therefore prognosis, varies depending upon the underlying tumour.[5] While awaiting surgical removal, treat any increased intracranial pressure with high-dose steroids (i.e., dexamethasone). ## History[edit] The syndrome was first extensively noted by Robert Foster Kennedy in 1911, an Irish neurologist, who spent most of his career working in the United States of America.[7] However, the first mention of the syndrome came from a William Gowers in 1893. Schultz–Zehden described the symptoms again in 1905. A later description was written by Wilhelm Uhthoff in 1915.[8] ## References[edit] 1. ^ "Kennedy syndrome" at Dorland's Medical Dictionary 2. ^ "Foster Kennedy syndrome" at Dorland's Medical Dictionary 3. ^ Bansal S, Dabbs T, Long V (2008). "Pseudo-Foster–Kennedy Syndrome due to unilateral optic nerve hypoplasia: a case report". J Med Case Rep. 2: 86. doi:10.1186/1752-1947-2-86. PMC 2278154. PMID 18348732. 4. ^ Longmore, Murray; Ian Wilkinson; Tom Turmezei; Chee Kay Cheung (2007). Oxford Handbook of Clinical Medicine (7th ed.). Oxford University Press. p. 690. ISBN 978-0-19-856837-7. 5. ^ a b c Willacy, Hayley. "Foster Kennedy syndrome". Retrieved 2008-08-13. 6. ^ Kaplan USMLE step 2 CK Lecture Notes 2018, Surgery 7. ^ Thorofare, NJ (1911). Kennedy F; Retrobulbar neuritis as an exact diagnostic sign of certain tumors and abscesses in the frontal lobe. American Journal of the Medical Sciences. 8. ^ "Kennedy's syndrome". Retrieved 2008-08-13. ## External links[edit] Classification D * ICD-9-CM: 377.04 * DiseasesDB: 31967 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [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	Foster Kennedy syndrome	c0152112	8,329	wikipedia	https://en.wikipedia.org/wiki/Foster_Kennedy_syndrome	2021-01-18T18:54:43	{"mesh": ["D009901"], "umls": ["C0152112"], "wikidata": ["Q751261"]}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 6q. Description The cardinal features of chromosome 6q11-q14 interstitial deletions include hypotonia, short stature, skeletal/limb anomalies, umbilical hernia, and urinary tract anomalies, as well as characteristic facial features including upslanting palpebral fissures, low-set and/or dysplastic ears, and high-arched palate (summary by Wang et al., 2009). Clinical Features Young et al. (1985) described a 2.75-year-old Caucasian girl with feeding problems in infancy, hiatal and inguinal hernias, left exotropia, lacrimal duct atresia, and short achilles tendons. She had generalized hypotonia and was unable to sit, with obvious developmental delay. Her head circumference was in the 70th centile, and she had a dolichocephalic cranium, low temporal hairline, lateral widening of eyebrows, large ears with prehelical and lobar pits, mild enophthalmos, upslanting palpebral fissures, epicanthic folds, broad nose, long philtrum, narrow palate, and missing upper lateral incisors. She also had short hands, single palmar creases, ulnar deviation of the second fingers, and small, concave nails; her great toes were long with valgus deviation, and she had right partial 2/3 syndactyly. Slater et al. (1988) described a 9-month-old male infant who was born with head circumference in the 3rd centile, micrognathia, high-arched palate, shallow philtrum, narrow upper vermilion border, short neck, undescended testicles, long slender fingers, long flat feet with prominent heels, and a pigmented nevus on the thigh. At 9 months of age, his height, weight, and head circumference were all below the 3rd centile, there was obvious psychomotor retardation; additional findings included horizontal palpebral fissures, hypotelorism, and a strange, laugh-like cry. Gershoni-Baruch et al. (1996) reported a 2-year-old Arab Moslem boy who was initially seen at 8 months of age for developmental delay, postnatal growth failure, and facial anomalies that included deep-set eyes, small palpebral fissures, hypotelorism, nystagmus, blue sclerae, mongolian slant, mild synophrys, posteriorly rotated low-set ears with large pinnae, low frontal hairline, slender nose with small anteverted nostrils, flat maxillae, high-arched palate, micrognathia, short frenulum, and broad short neck. He had a single palmar crease, hyperextensible fingers and wrists, 2/3 and 4/5 skin syndactyly of fingers and 2/3 syndactyly of toes, clubfeet, hyperelastic and redundant skin, umbilical hernia, right inguinal hernia, micropenis, and left undescended testis. In addition to global developmental delay, there was generalized hypotonia. Kumar et al. (1997) reported an 8-year-old boy with a known interstitial deletion of chromosome 6q, who at birth was noted to have mild facial asymmetry, large low-set ears with auricular pits, bifrontal narrowing of the forehead, prominent occiput with dolichocephalic skull shape, wide bulbous tip of nose, elongated philtrum, high-arched palate, bilateral single palmar creases, long tapered digits, bilateral cryptorchidism, subluxation of the hips, and hypermobility of all large joints. At 8 years of age, he exhibited significant hypotonia and psychomotor delay. Wang et al. (2009) described 7 patients with chromosome 6q11-q14 interstitial deletions, 3 of whom were from the same large pedigree. Features consistent with previous reports included hypotonia, upslanting palpebral fissures, low-set and/or dysplastic ears, high-arched palate, single palmar creases, and umbilical hernia; however, less than 30% of these patients displayed other typical features such as epicanthic folds, hypertelorism, short nose, broad nasal tip, long philtrum, thin upper lip, strabismus, short neck, and scoliosis, which were shared by over 50% of previously reported patients. Cytogenetics Young et al. (1985) performed karyotype analysis in a 2.75-year-old girl with hypotonia, developmental delay, hiatal and inguinal hernias, and facial dysmorphism, and found an interstitial deletion of chromosome 6q13-q15. In a 9-month-old male infant with failure to thrive, psychomotor delay, facial dysmorphism, and umbilical hernia, chromosome analysis by Slater et al. (1988) revealed an interstitial deletion of chromosome 6q11-q15. In a 2-year-old Arab Moslem boy with growth retardation, developmental delay, umbilical and inguinal hernias, and facial and urogenital anomalies, Gershoni-Baruch et al. (1996) performed karyotype analysis and detected a deletion of chromosome 6q13-q15. In an 8-year-old boy with a characteristic facial appearance and psychomotor delay, Kumar et al. (1997) demonstrated a deletion of chromosome 6q13-q14.2. In 7 patients with chromosome 6q11-q14 interstitial deletions of various sizes, Wang et al. (2009) analyzed the breakpoints by dual-color BAC-FISH analysis and found the average deletion size to be 13.9 Mb. The minimum deleted region was between base positions 73.9 and 79.5 Mb at chromosome 6q13-q14.1 and contained the COL12A1 gene (120320). In addition, the COL9A1 (120210) and COL19A1 (120165) genes were deleted in 3 patients with deletion breakpoints that were more centromeric than the other 4 patients. SNP array analysis confirmed the deletion breakpoints in 1 of 2 half sibs inheriting a recombinant chromosome 6 containing a 6q13-q14.2 deletion from their carrier mother who had a chromosome 6 between-arm intrachromosomal insertion. The mother's male second cousin was also a carrier of the intrachromosomal insertion, and his son inherited a recombinant chromosome 6 containing a 6q13-q14.2 deletion as well. Van Esch et al. (2010) reported 4 patients with a de novo interstitial deletion of chromosome 6q13-q14, resulting in a common 3.7-Mb minimum deleted region between base positions 72.65 and 76.31 Mb. All presented with developmental delay, mild dysmorphism similar to that seen in previously reported patients, including long philtrum, thin upper vermilion border, pointed chin, and large ear lobes, and signs of lax connective tissue. Van Esch et al. (2010) noted that the common deleted region harbored 16 genes, of which COL12A1 was a good candidate for the connective tissue pathology. INHERITANCE \- Isolated cases GROWTH Height \- Short stature HEAD & NECK Ears \- Low-set ears \- Dysplastic ears Eyes \- Upslanting palpebral fissures \- Epicanthic folds \- Hypertelorism \- Hypotelorism (in some patients) Nose \- Short nose \- Broad nasal tip \- Long philtrum Mouth \- High-arched palate \- Thin upper lip Neck \- Short neck ABDOMEN External Features \- Umbilical hernia \- Inguinal hernia (in some patients) SKELETAL Hands \- Single palmar crease NEUROLOGIC Central Nervous System \- Hypotonia \- Psychomotor delay MISCELLANEOUS \- Contiguous gene deletion syndrome MOLECULAR BASIS \- Caused by deletion of 3.7Mb on chromosome 6q13-q14 ▲ 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	CHROMOSOME 6q11-q14 DELETION SYNDROME	c3150790	8,330	omim	https://www.omim.org/entry/613544	2019-09-22T15:58:20	{"omim": ["613544"]}
A number sign (#) is used with this entry because of evidence that fast-channel congenital myasthenic syndrome-3B (CMS3B) is caused by homozygous or compound heterozygous mutation in the CHRND gene (100720) on chromosome 2q37. Mutation in the CHRND gene can also cause slow-channel congenital myasthenic syndrome (CMS3A; 616321) and congenital myasthenic syndrome associated with acetylcholine receptor (AChR) deficiency (CMS3C; 616323). Description Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Brownlow et al. (2001) reported a 6-year-old girl who showed decreased fetal movements and was born with CMS and congenital contractures of both hands. She showed breathing and eating difficulties soon after birth and had mildly delayed walking. At age 6, while on pyridostigmine, she had ptosis, limitation of eye movements, intermittent swallowing difficulty, and fatigable muscle weakness of the upper and lower limbs. Single-fiber EMG showed increased jitter with blocking. A brother had reduced fetal movements and hand contractures, and died at age 5 months. Shen et al. (2002) reported 3 Saudi Arabian patients with FCCMS. All 3 patients came from consanguineous unions, and 2 of the patients were first cousins. Three similarly affected sibs died in infancy from muscle weakness and respiratory complications. The disease course of all 3 patients was similar, with neonatal hypotonia, weak cry, respiratory difficulties, and poor feeding. Later, easy fatigability was noticed, as well as ptosis, ophthalmoplegia, facial weakness, and weakness of the neck flexor muscles. One patient had a high-arched palate, micrognathia, and large ears. EMG showed decremental muscle action potential responses to stimulation and small miniature endplate potential (MEPP) and current (MEPC). Muscle biopsy revealed type 2 fiber atrophy, a reduced number of AChRs, increased numbers of endplate regions, and preserved junctional structure. Functional studies showed abnormally brief AChR-induced ion channel-opening events. Shen et al. (2008) reported a 20-year-old woman with moderately severe to severe myasthenic symptoms since birth, no anti-AChR antibodies, and a decremental compound muscle action potential (CMAP) response on repetitive stimulation. She responded poorly to pyridostigmine alone, but improved markedly after the addition of 3,4-diaminopyridine. A similarly affected sibling died at age 11 months. There was decreased expression of the AChR at the endplate, with numerous and small endplate regions. Electrophysiologic studies showed decreased MEPP and MEPC amplitudes. Shen et al. (2008) concluded that the safety margin of neuromuscular transmission was compromised by the combined effects of endplate AChR deficiency, altered endplate geometry, reduced opening probability of the available AChRs, and abnormally fast decay of the synaptic current. Inheritance The transmission pattern of CMS3B in the families reported by Shen et al. (2002) was consistent with autosomal recessive inheritance. Molecular Genetics In a patient with FCCMS, Brownlow et al. (2001) identified compound heterozygosity for 2 mutations in the CHRND gene: a glu59-to-lys substitution (E59K; 100720.0003) and a null mutation (100720.0004). In 3 Saudi Arabian patients with FCCMS, Shen et al. (2002) identified a homozygous missense mutation in the CHRND gene (P250Q; 100720.0002). In vitro functional expression studies showed that the opening burst duration of the AChR was decreased and that disassociation of ACh was increased, resulting in brief channel-opening episodes. In a 20-year-old woman with CMS3B, Shen et al. (2008) identified compound heterozygosity for 2 missense mutations in the CHRND gene (L42P, 100720.0008 and I58K, 100720.0009). In vitro functional expression studies showed that the I58K substitution prevented expression of the delta subunit and was a null mutation. The L42P substitution resulted in reduced gating efficiency, slower opening of the channel, and decreased probability that the channel would open in response to ACh. Further studies showed that the L42P-mutant protein altered the intersubunit linkage of the adjacent delta subunit asn41 with the juxtaposed alpha subunit (CHRNA1; 100690) residue tyr127. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial muscle weakness Eyes \- Ptosis \- Ophthalmoplegia Mouth \- High-arched palate Neck \- Neck muscle weakness RESPIRATORY \- Respiratory insufficiency ABDOMEN Gastrointestinal \- Poor feeding SKELETAL Hands \- Hand contractures (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Muscle weakness \- Easy fatigability \- Decremental response to repetitive nerve stimulation \- Decreased amplitudes of the miniature endplate potential (MEPP) and current (MEPC) \- Shortened open channel duration \- Accelerated decay of the synaptic current \- Increased number of small endplates \- Reduced postsynaptic cleft area \- Decreased postsynaptic AChR NEUROLOGIC Central Nervous System \- Delayed motor development due to muscle weakness PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements (in some patients) MISCELLANEOUS \- Onset in infancy \- May respond to cholinesterase inhibitors of amifampridine MOLECULAR BASIS \- Caused by mutation in the cholinergic receptor, nicotinic, delta polypeptide gene (CHRND, 100720.0002 ) ▲ 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	MYASTHENIC SYNDROME, CONGENITAL, 3B, FAST-CHANNEL	c0751882	8,331	omim	https://www.omim.org/entry/616322	2019-09-22T15:49:13	{"doid": ["0110665"], "mesh": ["D020294"], "omim": ["616322"], "orphanet": ["98913", "590"], "synonyms": [], "genereviews": ["NBK1168"]}
Mastocytosis Other namesClonal bone marrow disorder Micrograph of mastocytosis. Skin biopsy. H&E stain. SpecialtyOncology, allergology, hematology Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called mastocytes) and CD34\+ mast cell precursors.[1] People affected by mastocytosis are susceptible to a variety of symptoms, including itching, hives, and anaphylactic shock, caused by the release of histamine and other pro-inflammatory substances from mast cells.[2] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Major criterion * 3.2 Minor criteria * 3.3 Other mast cell diseases * 3.4 Classification * 3.4.1 Cutaneous mastocytosis (CM) * 3.4.2 Systemic mastocytosis (SM) * 4 Treatment * 4.1 Anti-mediator therapy * 4.2 Cytoreductive therapy * 4.3 Other * 5 Prognosis * 6 Epidemiology * 7 Research * 8 History * 9 See also * 10 References * 11 Further reading ## Signs and symptoms[edit] Mastocytosis When mast cells undergo degranulation, the substances that are released can cause a number of symptoms that can vary over time and can range in intensity from mild to severe. Because mast cells play a role in allergic reactions, the symptoms of mastocytosis often are similar to the symptoms of an allergic reaction. They may include, but are not limited to[3] * Fatigue * Skin lesions (urticaria pigmentosa), itching, and dermatographic urticaria (skin writing) * "Darier's Sign", a reaction to stroking or scratching of urticaria lesions. * Abdominal discomfort * Nausea and vomiting * Diarrhea * Olfactive intolerance * Ear/nose/throat inflammation * Anaphylaxis (shock from allergic or immune causes) * Episodes of very low blood pressure (including shock) and faintness * Bone or muscle pain * Decreased bone density or increased bone density (osteoporosis or osteosclerosis) * Headache * Depression[4] * Ocular discomfort * Increased stomach acid production causing peptic ulcers (increased stimulation of enterochromaffin cell and direct histamine stimulation on parietal cell) * Malabsorption (due to inactivation of pancreatic enzymes by increased acid)[5] * Hepatosplenomegaly There are few qualitative studies about mastocytosis effects on daily life. But a Danish study from 2018 describes the disease multidimensional impact on the everyday life.[6] ## Pathophysiology[edit] Mast cells are located in connective tissue, including the skin, the linings of the stomach and intestine, and other sites. They play an important role in the immune defence against bacteria and parasites. By releasing chemical "alarms" such as histamine, mast cells attract other key players of the immune defense system to areas of the body where they are needed.[citation needed] Mast cells seem to have other roles as well. Because they gather together around wounds, mast cells may play a part in wound healing. For example, the typical itching felt around a healing scab may be caused by histamine released by mast cells. Researchers also think mast cells may have a role in the growth of blood vessels (angiogenesis). No one with too few or no mast cells has been found, which indicates to some scientists we may not be able to survive with too few mast cells.[citation needed] Mast cells express a cell surface receptor, c-kit[7] (CD117), which is the receptor for stem cell factor (scf). In laboratory studies, scf appears to be important for the proliferation of mast cells. Mutations of the gene coding for the c-kit receptor (mutation KIT(D816V)), leading to constitutive signalling through the receptor is found in >90% of patients with systemic mastocytosis.[8] ## Diagnosis[edit] Diagnosis of urticaria pigmentosa (cutaneous mastocytosis, see above) can often be done by seeing the characteristic lesions that are dark brown and fixed. A small skin sample (biopsy) may help confirm the diagnosis.[citation needed] In case of suspicion of systemic disease the level of serum tryptase in the blood can be of help. If the base level of s-tryptase is elevated, this implies that the mastocytosis can be systemic. In cases of suspicion of SM help can also be drawn from analysis of mutation in KIT(D816V) in peripheral blood using sensitive PCR-technology[citation needed] To set the diagnosis of systemic mastocytosis, certain criteria must be met. Either one major + one minor criterium or 3 minor criteria has to be fulfilled:[9] ### Major criterion[edit] * Dense infiltrates of >15 mast cells in the bone marrow or an extracutaneous organ ### Minor criteria[edit] * Aberrant phenotype on the mast cells (pos. for CD2 and/or CD25) * Aberrant mast cell morphology (spindle-shaped) * Finding of mutation in KIT(D816V) * S-tryptase >20 ng/ml ### Other mast cell diseases[edit] Other types of mast cell disease include: * Monoclonal mast cell activation, defined by the World Health Organization definitions 2010, also has increased mast cells but insufficient to be systemic mastocytosis (in World Health Organization Definitions) * Mast cell activation syndrome – has normal number of mast cells, but all the symptoms and in some cases the genetic markers of systemic mastocytosis[10] * Another known but rare mast cell proliferation disease is mast cell sarcoma.[11] ### Classification[edit] Mastocytosis can occur in a variety of forms: #### Cutaneous mastocytosis (CM)[edit] * The most common cutaneous mastocytosis is maculopapular cutaneous mastocytosis, previously named papular urticaria pigmentosa (UP), more common in children, although also seen in adults. Telangiectasia macularis eruptiva perstans (TMEP) is a much rarer form of cutaneous mastocytosis that affects adults.[2] MPCM and TMEP can be a part of indolent systemic mastocytosis. This should be considered if patients develop any systemic symptoms[12] * Generalized eruption of cutaneous mastocytosis (adult type) is the most common pattern of mastocytosis presenting to the dermatologist, with the most common lesions being macules, papules, or nodules that are disseminated over most of the body but especially on the upper arms, legs, and trunk[13] * Diffuse cutaneous mastocytosis' has diffuse involvement in which the entire integument may be thickened and infiltrated with mast cells to produce a peculiar orange color, giving rise to the term "homme orange."[14] Cutaneous mastocytosis in children usually presents in the first year after birth and in most cases vanishes during adolescence. #### Systemic mastocytosis (SM)[edit] Systemic mastocytosis involves the bone marrow in the majority of cases and in some cases other internal organs, usually in addition to involving the skin. Mast cells collect in various tissues and can affect organs where mast cells do not normally inhabit such as the liver, spleen and lymph nodes, and organs which have normal populations but where numbers are increased. In the bowel, it may manifest as mastocytic enterocolitis.[15] There are five types of systemic mastocytosis:[9] * Indolent systemic mastocytosis (ISM). The most common SM (>90%) * Smouldering systemic mastocytosis (SSM) * Systemic mastocytosis with associated haematological neoplasm (SM-AHN) * Aggressive systemic mastocytosis (ASM) * Mast cell leukemia (MCL) ## Treatment[edit] There is no cure for mastocytosis, but there are a number of medicines to help treat the symptoms:[16] ### Anti-mediator therapy[edit] * Antihistamines block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful, often in combination.[17] * Leukotriene antagonists block receptors targeted by leukotrienes released from mast cells. * Mast cell stabilizers help prevent mast cells from releasing their chemical contents. Cromoglicic acid is the only medicine specifically approved by the FDA for the treatment of mastocytosis. Ketotifen is available in Canada and Europe and more recently in the U.S. It is also available as eyedrops (Zaditor). * Proton-pump inhibitors help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus, and small intestine. * Epinephrine constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused anaphylaxis. * Salbutamol and other beta-2 agonists open airways that can constrict in the presence of histamine. * Corticosteroids can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis. * Drugs to prevent/treat osteoporosis include Calcium-Vitamine D, bisphosphonates and in rare cases inhibitors of RANK-L Antidepressants are an important and often overlooked tool in the treatment of mastocytosis. Depression and other neurological symptoms have been noted in mastocytosis.[4][18] Some antidepressants, such as doxepin, are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms. ### Cytoreductive therapy[edit] In cases of advanced systemic mastocytosis or rare cases with indolent systemic mastocytosis with very troublesome symptoms, cytoreductive therapy can be indicated.[19] * ɑ-interferon. Given as subcutaneous injections. Side effects include fatigue and influenza-like symptoms * Cladribine (CdA). Chemotherapy which is given as subcutaneous injections. Side effects include immunodeficiency and infections. * Tyrosine kinase inhibitors (TKI) * Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA for advanced mastocytosis * Imatinib. Can have effect in rare cases without mutation in KIT(D816V) * Masitinib. Is being tested in trials. Not approved. * Midostaurin \- 60% respond.[20] * Avapritinib in trials; currently being tested but showing promise in reduction of tryptase levels.[20] Allogeneic stem cell transplantation has been used in rare cases with aggressive systemic mastocytosis in patients deemed to be fit for the procedure. ### Other[edit] Treatment with ultraviolet light can relieve skin symptoms, but may increase the risk of skin cancer.[21] ## Prognosis[edit] Patients with indolent systemic mastocytosis have a normal life expectancy. The prognosis for patients with advanced systemic mastocytosis differs depending on type of disease with MCL being the most serious form with short survival.[19] ## Epidemiology[edit] The true incidence and prevalence of mastocytosis is unknown, but mastocytosis generally has been considered to be an "orphan disease"; orphan diseases affect 200,000 or fewer people in the United States. Mastocytosis, however, often may be misdiagnosed, as it typically occurs secondary to another condition, and thus may occur more frequently than assumed.[[citation needed] ## Research[edit] National Institute of Allergy and Infectious Diseases scientists have been studying and treating patients with mastocytosis for several years at the National Institutes of Health (NIH) Clinical Center.[citation needed] Some of the most important research advances for this rare disorder include improved diagnosis of mast cell disease and identification of growth factors and genetic mechanisms responsible for increased mast cell production.[22] Researchers are currently evaluating approaches to improve ways to treat mastocytosis.[citation needed] Scientists also are focusing on identifying disease-associated mutations (changes in genes). NIH scientists have identified some mutations, which may help researchers understand the causes of mastocytosis, improve diagnosis, and develop better treatments.[citation needed] In Europe the European Competence Network on Mastocytosis (ECNM) coordinates studies, registries and education on mastocytosis.[citation needed] ## History[edit] Urticaria pigmentosa was first described in 1869.[23] The first report of a primary mast cell disorder is attributed to Unna, who in 1887 reported that skin lesions of urticaria pigmentosa contained numerous mast cells.[24] Systemic mastocytosis was first reported by French scientists in 1936.[25] ## See also[edit] * Mastocytoma ## References[edit] 1. ^ Horny HP, Sotlar K, Valent P (2007). "Mastocytosis: state of the art". Pathobiology. 74 (2): 121–32. doi:10.1159/000101711. PMID 17587883. 2. ^ "Mastocytosis & mast cell disorders". Mastocytosis Society Canada. Archived from the original on 2013-12-28. Retrieved 2017-11-02. 3. ^ Hermine, Olivier; Lortholary, Olivier; Leventhal, Phillip S.; Catteau, Adeline; Soppelsa, Frédérique; Baude, Cedric; Cohen-Akenine, Annick; Palmérini, Fabienne; Hanssens, Katia; Yang, Ying; Sobol, Hagay; Fraytag, Sylvie; Ghez, David; Suarez, Felipe; Barete, Stéphane; Casassus, Philippe; Sans, Beatrice; Arock, Michel; Kinet, Jean Pierre; Dubreuil, Patrice; Moussy, Alain; Soyer, H. Peter (28 May 2008). "Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis". PLOS ONE. 3 (5): e2266. Bibcode:2008PLoSO...3.2266H. doi:10.1371/journal.pone.0002266. PMC 2386235. PMID 18509466. 4. ^ a b Moura, Daniela Silva; Sultan, Serge; Georgin-Lavialle, Sophie; Pillet, Nathalie; Montestruc, François; Gineste, Paul; Barete, Stéphane; Damaj, Gandhi; Moussy, Alain; Lortholary, Olivier; Hermine, Olivier; Hashimoto, Kenji (21 October 2011). "Depression in Patients with Mastocytosis: Prevalence, Features and Effects of Masitinib Therapy". PLOS ONE. 6 (10): e26375. Bibcode:2011PLoSO...626375M. doi:10.1371/journal.pone.0026375. PMC 3198767. PMID 22031830. 5. ^ Lee, JK; Whittaker, SJ; Enns, RA; Zetler, P (Dec 7, 2008). "Gastrointestinal manifestations of systemic mastocytosis". World Journal of Gastroenterology. 14 (45): 7005–8. doi:10.3748/wjg.14.7005. PMC 2773867. PMID 19058339. 6. ^ Jensen, Britt; Broesby-Olsen, Sigurd; Bindslev-Jensen, Carsten; Nielsen, Dorthe S. (April 2019). "Everyday life and mastocytosis from a patient perspective-a qualitative study". Journal of Clinical Nursing. 28 (7–8): 1114–1124. doi:10.1111/jocn.14676. PMID 30230078. 7. ^ Orfao A, Garcia-Montero AC, Sanchez L, Escribano L (2007). "Recent advances in the understanding of mastocytosis: the role of KIT mutations". Br. J. Haematol. 138 (1): 12–30. doi:10.1111/j.1365-2141.2007.06619.x. hdl:10261/62846. PMID 17555444. S2CID 12120327. 8. ^ Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, et al. (March 2017). "Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future". Cancer Research. 77 (6): 1261–1270. doi:10.1158/0008-5472.CAN-16-2234. PMC 5354959. PMID 28254862. 9. ^ a b Arber, Daniel A.; Orazi, Attilio; Hasserjian, Robert; Thiele, Jürgen; Borowitz, Michael J.; Le Beau, Michelle M.; Bloomfield, Clara D.; Cazzola, Mario; Vardiman, James W. (19 May 2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. PMID 27069254. 10. ^ Akin C, Valent P, Metcalfe DD (2010). "Mast cell activation: proposed diagnostic criteria". The Journal of Allergy and Clinical Immunology. 126 (6): 1099–104. doi:10.1016/j.jaci.2010.08.035. PMC 3753019. PMID 21035176. 11. ^ National Organization for Rare Disorders (NORD) "Mastocytosis", 2017 12. ^ Ellis DL (1996). "Treatment of telangiectasia macularis eruptiva perstans with the 585-nm flashlamp-pumped dye laser". Dermatol Surg. 22 (1): 33–7. doi:10.1016/1076-0512(95)00388-6. PMID 8556255. 13. ^ Noack, F.; Escribano, L.; Sotlar, K.; Nunez, R.; Schuetze, K.; Valent, P.; Horny, H.-P. (July 2009). "Evolution of Urticaria Pigmentosa into Indolent Systemic Mastocytosis: Abnormal Immunophenotype of Mast Cells without Evidence of c-kit Mutation ASP-816-VAL". Leukemia & Lymphoma. 44 (2): 313–319. doi:10.1080/1042819021000037967. PMID 12688351. S2CID 30459720. 14. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.[page needed] 15. ^ Ramsay, David B.; Stephen, Sindu; Borum, Marie; Voltaggio, Lysandra; Doman, David B. (December 2010). "Mast Cells in Gastrointestinal Disease". Gastroenterology & Hepatology. 6 (12): 772–777. PMC 3033552. PMID 21301631. 16. ^ "Mastocytosis - Treatment Options". Cancer.Net. 25 June 2012. 17. ^ Cardet, Juan Carlos; Akin, Cem; Lee, Min Jung (October 2013). "Mastocytosis: update on pharmacotherapy and future directions". Expert Opinion on Pharmacotherapy. 14 (15): 2033–2045. doi:10.1517/14656566.2013.824424. PMC 4362676. PMID 24044484. 18. ^ Rogers, M P; Bloomingdale, K; Murawski, B J; Soter, N A; Reich, P; Austen, K F (July 1986). "Mixed organic brain syndrome as a manifestation of systemic mastocytosis". Psychosomatic Medicine. 48 (6): 437–447. doi:10.1097/00006842-198607000-00006. PMID 3749421. S2CID 37335288. 19. ^ a b Pardanani, Animesh (November 2016). "Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management". American Journal of Hematology. 91 (11): 1146–1159. doi:10.1002/ajh.24553. PMID 27762455. 20. ^ a b Gilreath, JA; Tchertanov, L; Deininger, MW (July 2019). "Novel approaches to treating advanced systemic mastocytosis". Clinical Pharmacology: Advances and Applications. 11: 77–92. doi:10.2147/CPAA.S206615. PMC 6630092. PMID 31372066. 21. ^ Broesby-Olsen, Sigurd; Farkas, Dóra Körmendiné; Vestergaard, Hanne; Hermann, Anne Pernille; Møller, Michael Boe; Mortz, Charlotte Gotthard; Kristensen, Thomas Kielsgaard; Bindslev-Jensen, Carsten; Sørensen, Henrik Toft; Frederiksen, Henrik (November 2016). "Risk of solid cancer, cardiovascular disease, anaphylaxis, osteoporosis and fractures in patients with systemic mastocytosis: A nationwide population-based study". American Journal of Hematology. 91 (11): 1069–1075. doi:10.1002/ajh.24490. PMID 27428296. S2CID 24088671. 22. ^ Garde, Damian, To quell unpredictable allergic reactions, an experimental drug takes aim at a genetic cause, not symptoms, Stat, March 16, 2020 23. ^ Nettleship E, Tay W (1869). "Reports of Medical and Surgical Practice in the Hospitals of Great Britain". Br Med J. 2 (455): 323–4. doi:10.1136/bmj.2.455.323. PMC 2260962. PMID 20745623. 24. ^ Unna, Paul Gerson; Unna (1887). Beiträge zur Anatomie und Pathogenese der Urticaria simplex und Pigmentosa [Contributions to the anatomy and pathogenesis of urticaria simplex and pigmentosa] (in German). Verlag von Leopold Voss. OCLC 840287852. 25. ^ Sézary A, Levy-Coblentz G, Chauvillon P (1936). "Dermographisme et mastocytose". Bulletin de la Société Française de Dermatologie et de Syphiligraphie. 43: 359–61. ## Further reading[edit] * Gruchalla, Rebecca S. (June 1995). "Mastocytosis: Developments During the Past Decade". The American Journal of the Medical Sciences. 309 (6): 328–338. doi:10.1097/00000441-199506000-00007. PMID 7771504. Classification D * ICD-10: Q82.2, C96.2 * ICD-9-CM: 757.33, 202.6 * ICD-O: 9741/3 * OMIM: 154800 * MeSH: D008415 * DiseasesDB: 7864 External resources * eMedicine: derm/258 med/1401 * Orphanet: 98292 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark [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	Mastocytosis	c0024899	8,332	wikipedia	https://en.wikipedia.org/wiki/Mastocytosis	2021-01-18T18:55:03	{"gard": ["6987"], "mesh": ["D008415"], "umls": ["C0024899"], "icd-9": ["202.6", "757.33"], "orphanet": ["98292"], "wikidata": ["Q112670"]}
High myopia-sensorineural deafness syndrome is a rare genetic disease characterized by high myopia, typically ranging from -6.0 to -11.0 diopters, and moderate to profound, bilateral, progressive sensorineural hearing loss with prelingual-onset. Affected individuals do not present other systemic, ocular or connective tissue manifestations. [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	High myopia-sensorineural deafness syndrome	c3806275	8,333	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363396	2021-01-23T17:40:27	{"gard": ["12844"], "omim": ["221200"], "icd-10": ["H90.5"], "synonyms": ["High myopia-sensorineural hearing loss syndrome"]}
Congenital autosomal recessive sideroblastic anemia (ARSA) is a non-syndromic, microcytic/hypochromic sideroblastic anemia, present from early infancy and characterized by severe microcytic anemia, which is not pyridoxine responsive, and increased serum ferritin. ## Epidemiology To date, fewer than 30 unrelated genetically characterized individuals with congenital ARSA have been reported in the northern hemisphere. ## Clinical description Congenital ARSA presents in early infancy, within the first weeks or months after birth, and is associated with severe microcytic anemia, increased transferrin saturation and increased serum ferritin. Clinical features are those of anemia and iron overload and include pallor, fatigue, weakness, breathlessness, splenomegaly, hyperglycemia, glucose intolerance and skin hyperpigmentation. Complications of iron overload include heart arrhythmias, heart attacks and liver disease (cirrhosis, cancer). Patients need blood transfusions to survive and do not respond to treatment with pyridoxine (vitamin B6). ## Etiology ARSA is caused by a homozygous or compound heterozygous mutation in the SLC25A38 gene located on chromosome 3p22.1. ## Diagnostic methods Diagnosis is based on clinical findings together with full blood examination including blood smear and reticulocyte count, measurement of iron stores and bone marrow aspirate showing ringed sideroblasts. Unresponsiveness to pyridoxine treatment often leads to confirming SLC25A38 gene mutation analysis. ## Differential diagnosis Differential diagnosis includes other types of sideroblastic anemia and particularly bears resemblance with X-linked sideroblastic anemia (XLSA, see this term). ## Antenatal diagnosis In case of family history, prenatal diagnosis by amniocentesis or chorionic villus sampling and cytogenetic analysis is possible, as early diagnosis in a child may be of great benefit for treatment of anemia and avoidance of iron overload, historically the main cause of early death. ## Genetic counseling The SLC25A38 gene mutation is transmitted as an autosomal recessive trait. Genetic counseling should be offered to affected individuals and their families informing them of the possibilities of carrier testing for at-risk family members and the genetic risk for transmitting it on to their children. ## Management and treatment ARSA differs from X-linked sideroblastic anemias because it is usually more severe and is not responsive to treatment with pyridoxine. Treatment is supportive and involves hematological monitoring, the surveillance of iron levels and nearly always comprises chronic blood transfusions. If iron overload has already developed, iron chelation can be used to normalize iron levels. In some cases, bone marrow transplantation is considered as a successful treatment option. ## Prognosis Prognosis is variable and depends on the severity of microcytic anemia. Quality of life is affected in the case chronic blood transfusions are needed. In well treated patients life expectancy is thought to be normal. [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	Autosomal recessive sideroblastic anemia	c4225428	8,334	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=260305	2021-01-23T17:18:15	{"omim": ["182170", "205950"], "icd-10": ["D64.0"], "synonyms": ["ARSA", "Congenital sideroblastic anemia"]}
Dobrow syndrome is a rare multiple congenital defects/dysmorphic syndrome characterized by variable degrees of bony syngnathia associated with variable additional abnormalities, including growth retardation, intellectual disability, microcephaly, iris coloboma, nystagmus, deafness, and vertebral segmentation defects, as well as genital, limb and additional facial malformations, among others. [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	Dobrow syndrome	None	8,335	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3262	2021-01-23T17:58:17	{"gard": ["5092"], "synonyms": ["Syngnathia-multiple anomalies syndrome"]}
A number sign (#) is used with this entry because myoclonic epilepsy of Unverricht and Lundborg (ULD), also known as progressive myoclonic epilepsy-1A (EPM1A), is caused by mutation in the cystatin B gene (CSTB; 601145) on chromosome 21q22. Description Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. Although it is considered a progressive myoclonic epilepsy, it differs from other forms in that is appears to be progressive only in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilizes in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline (summary by Ramachandran et al., 2009). ### Genetic Heterogeneity of Progressive Myoclonic Epilepsy Progressive myoclonic epilepsy refers to a clinically and genetically heterogeneous group of neurodegenerative disorders, usually with debilitating symptoms, although severity varies. See also EPM1B (612437), caused by mutation in the PRICKLE1 gene (608500); Lafora disease (EPM2A/B; 254780), caused by mutation in either the EPM2A (607566) or the NHLRC1 (608072) gene; EPM3 (611726), caused by mutation in the KCTD7 gene (611725); EPM4 (254900), caused by mutation in the SCARB2 gene (602257); EPM6 (614018), caused by mutation in the GOSR2 gene (604027); EPM7 (616187), caused by mutation in the KCNC1 gene (176258); EPM8 (616230), caused by mutation in the CERS1 gene (606919); EPM9 (616540), caused by mutation in the LMNB2 gene (150341); and EPM10 (616640), caused by mutation in the PRDM8 gene (616639). A form of progressive myoclonic epilepsy, formerly designated EPM5, is included in 607459 with the primary designation of spinocerebellar ataxia with epilepsy (SCAE). Other disorders characterized by progressive myoclonic epilepsy include the neuronal ceroid lipofuscinoses (see, e.g., CLN1 (256730); sialidosis (256550); MERFF (545000); and DRPLA (125370), among others (reviews by Ramachandran et al., 2009 and de Siqueira, 2010).) Clinical Features Unverricht (1891, 1895) and Lundborg (1903) first reported a type of progressive myoclonic epilepsy common in Finland. Onset of the disorder occurred around age 10 years, and was characterized by progressive myoclonus resulting in incapacitation, but only mild mental deterioration. Histological studies of the brain showed 'degenerative' changes without inclusion bodies. Severity and survival were variable (Norio and Koskiniemi, 1979). Eldridge et al. (1981, 1983) referred to this disorder as the 'Baltic type' of myoclonic epilepsy because the descriptions first by Unverricht and then by Lundborg were in families from Estonia and Eastern Sweden and subsequent patients were found in Finland. Eldridge et al. (1983) found 15 families in the United States. The 27 affected members had the following features starting at about age 10 years: stimulus- and photo-sensitive and occasionally violent myoclonus, usually worse upon waking; generalized tonic-clonic seizures, sometimes associated with absence attacks; and light-sensitive, generally synchronous, spike-and-wave discharges on EEG that preceded clinical manifestations. Necropsy showed marked loss of Purkinje cells of the cerebellum, but no inclusion bodies. Phenytoin was associated with progressive motor and intellectual deterioration, marked ataxia, and even death. Treatment with valproic acid was associated with marked improvement. Contrary to myoclonic epilepsy with Lafora bodies, intelligence in this form was only slightly affected and psychotic symptoms were not found. In addition, Lafora body disease is invariably fatal. Kyllerman et al. (1991) described 4 sibs who demonstrated a subclinical stage of this disorder at the age of 9 to 11 years, with visual blackouts and polyspike electroencephalographic (EEG) activity on photic stimulation; an early myoclonic stage at the age of 12 to 15 years, with increasing segmental, stimulus-sensitive myoclonus, occasional nocturnal buildup myoclonic 'cascade' seizures, slowing of EEG alpha-activity, episodic 4-6 Hz bilateral sharp waves and polyspikes with myoclonus on photic stimulation; and a disabling myoclonic stage at the age of 16 to 18 years, with periodic generalized myoclonus, nocturnal myoclonic 'cascade' seizures, ataxia, dysarthria, mental changes, intermittent wheelchair dependency, and continuous EEG slow waves with polyspikes and intense myoclonus on photic stimulation. One of the sibs died at the age of 18 years with no apparent cause of death. As pointed out by the Marseille Consensus Group (1990), patients with Ramsay Hunt syndrome (159700) cannot be distinguished clinically from patients with Unverricht-Lundborg disease. Linkage studies may help determine whether that disorder is caused by mutation at the same locus. Cochius et al. (1994) reported for the first time a pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease. They found membrane-bound vacuoles with clear contents in eccrine clear cells and dark cells in 5 of 7 patients, as well as in 1 clinically unaffected sib. Sweat gland vacuoles were not seen in the biopsies of 8 patients with Lafora disease. Photosensitivity, i.e., precipitation of myoclonic jerks by intermittent photic stimulation, is a characteristic feature of progressive myoclonic epilepsies. Mazarib et al. (2001) described an affected Arab family in which photosensitivity was absent. Mascalchi et al. (2002) performed MRI and proton MRS on 10 patients with genetically confirmed EPM1 and found significant loss of bulk of the basis pontis, medulla, and cerebellar hemispheres as well as mild cerebral atrophy, compared to 20 healthy controls. The findings differed in some critical features from those in olivopontocerebellar atrophy. Mascalchi et al. (2002) concluded that their findings support the hypothesis that the disease results from a decreased inhibitory control of the cerebral cortex by the brainstem and cerebellum via the thalamocortical loop. Canafoglia et al. (2004) found different electrophysiologic profiles representing sensorimotor cortex hyperexcitability in 8 patients with Lafora disease (age range, 14 to 27 years) and 10 patients with Unverricht-Lundborg disease (age range, 25 to 62 years). In general, the ULD patients had a quasistationary disease course, rare seizures, and little or no mental impairment, whereas the Lafora disease patients had recurrent seizures and worsening mental status. Patients with ULD had prominent action myoclonus clearly triggered by voluntary movements. Lafora disease patients experienced spontaneous myoclonic jerks associated with clear EEG paroxysms with only minor action myoclonus. Although both groups had enlarged or giant somatosensory evoked potentials, the pattern in the Lafora group was consistent with a distortion of cortical circuitry. Patients with ULD had enhanced long-loop reflexes with extremely brief cortical relay times. The findings were consistent with an aberrant subcortical or cortical loop, possibly short-cutting the somatosensory cortex, that may be involved in generating the prominent action myoclonus that characterizes ULD. Patients with Lafora disease had varied cortical relay times and delayed and prolonged facilitation as evidenced by sustained hyperexcitability of the sensorimotor cortex in response to afferent stimuli. The findings were consistent with an impairment of inhibitory mechanisms in Lafora disease. Inheritance Noad and Lance (1960) described myoclonic epilepsy with cerebellar ataxia in several offspring of a mating of first cousins once removed, indicating autosomal recessive inheritance. Clinical Management Pennacchio et al. (1996) stated that, even in chronic and severe cases, patients with EPM1 show marked improvement when treated with the antiepileptic drug sodium valproate; however, phenytoin, another drug that is effective against some other forms of epilepsy, does not improve the condition of EPM1 patients, often shows toxic effects, and, in some cases, is fatal. They stated that the identification of mutant genes encoding cystatin B in patients with EPM1 may help understanding of the differential response to these 2 drugs. Furthermore, this knowledge provides a biochemical pathway and molecular target for the treatment of EPM1 and perhaps other forms of epilepsy. Selwa (1999) reported significant improvement in seizures, tremors, speech and ambulation in a 40-year-old patient with Unverricht-Lundborg disease who was given N-acetylcysteine as well as other vitamin preparations containing antioxidants. The patient relapsed when medication was discontinued, but improvement was sustained during a 10-month follow-up after resumption of treatment. Improvement had previously been reported in 4 similarly treated sibs (Hurd et al., 1996). Edwards et al. (2002) found low glutathione levels in a patient with Unverricht-Lundborg disease proven by DNA studies. Glutathione levels increased during treatment with N-acetylcysteine (NAC). This increase was mirrored by an improvement in seizures, but not in myoclonus or ataxia. Three other patients with clinically determined Unverricht-Lundborg disease showed a variable response and some notable side effects during treatment with NAC, including sensorineural deafness. Kinrions et al. (2003) reported that levetiracetam, a piracetam analog, markedly improved myoclonus and quality of life in a 38-year-old woman with genetically confirmed Unverricht-Lundborg disease. Her illness began at age 13 and had progressed to leave her wheelchair-bound, dysarthric, and with multifocal myoclonus. Treatment with multiple medications had been unsuccessful. The authors cited previous reports of the effectiveness of levetiracetam in symptomatic myoclonus of various etiologies. Mapping Lehesjoki et al. (1991) demonstrated close linkage between the EPM1 locus and 3 markers on distal chromosome 21. The loci BCEI (113710) and D21S154 gave the highest positive lod scores of 5.49 and 4.25, respectively, at zero recombination. The third locus, D21S112, gave a lod score of 6.91 at a recombination fraction of 0.034. No evidence of heterogeneity was found in the 12 families studied. Multipoint lod scores calculated against a fixed map of the 3 marker loci gave a maximum 4-point lod score of 10.08 at a location of the disease gene at 6.0 cM distal to locus BCEI and 0.8 cM proximal to D21S154. Both of these markers had previously been localized to 21q22.3. Lehesjoki et al. (1992) refined the localization of EPM1 by linkage analysis between the disease phenotype and 9 DNA markers in 13 Finnish families. A maximum multipoint lod score of 11.04 was reached at loci D21S154/PFKL (171860), which had previously been mapped to 21q22.3. Lehesjoki et al. (1993) narrowed the assignment of EPM1 to an interval of approximately 7 cM, between loci D21S212 and CD18, by analyzing crossover events in multiplex families. They refined the localization further by applying linkage disequilibrium mapping in 38 Finnish families, consisting of 12 with multiple affected children and 26 with a single affected child. In this way, they were able to conclude that EPM1 resides within 0.3 cM of PFKL, D21S25, and D21S154. This represents a likely physical distance of 300 kb or less. In a family reported by Eldridge et al. (1983), of mixed Italian and Irish ancestry, living in the United States, Lehesjoki et al. (1993) again found linkage to markers in the distal part of chromosome 21. Crossover events in the family helped refine the gene localization by placing EPM1 between CBS (613381) and D21S112. Uncertainty has existed about the relationship between Unverricht-Lundborg disease, also referred to as Baltic myoclonus, and Mediterranean myoclonus, formerly considered to be a subgroup of the Ramsay Hunt syndrome. Lehesjoki et al. (1994) studied 7 phenotypically homogeneous Mediterranean myoclonus families, using DNA markers from the genetically defined EPM1 region on chromosome 21. No recombination between the disease phenotype and the markers studied was detected. Within the EPM1 region, the highest lod score was 5.07 (at theta = 0.00) for PFKL. Significant allelic association between the disease mutation and PFKL was detected, suggesting a founder effect in Mediterranean myoclonus. However, haplotype data from 4 marker loci residing within 300 kb of each other and of EPM1 suggested the occurrence of more than 1 mutation. Using linkage disequilibrium and recombination breakpoint mapping with Finnish EPM1 patients, Pennacchio et al. (1996) refined the location of the EPM1 gene to a region between markers D21S2040 and D21S1259. This region was entirely encompassed in a 750-kb bacterial clone contig generated by sequence tagged site content mapping and walking. A detailed restriction map of the contig determined that the distance between the DNA markers defining the boundaries of EPM1 was about 175 kb. Heterogeneity Carr et al. (2007) reported 2 large families from the Western Cape province of South Africa with generalized tonic-clonic seizures and myoclonus. The mean age at onset was 20 years (range 13 to 31). Myoclonus predominantly affected the trunk and upper limbs but was also observed in the lower limbs. Hand tremor became apparent on posture holding. Additional features included nystagmus, abnormal pursuit, dysarthria, hyperreflexia, cerebellar ataxia, and cerebellar atrophy. A number of patients also had progressive cognitive impairment, resulting in dementia in some. EEG studies were abnormal in the majority of patients, with polyspike and wave activity and/or clear epileptogenic activity. Postmortem examination of 1 patient showed cerebellar atrophy and cerebellar neuronal loss. Several patients died in their thirties and forties. The families were of mixed ancestry, predominantly resulting from intermarriage between the original inhabitants of the area, the Khoi-San, and early settlers of European origin. Carr et al. (2007) noted that the phenotype was more severe and showed earlier onset than typical familial adult myoclonic epilepsy (FAME1; 601068). The phenotype was also progressive, falling within the spectrum of progressive myoclonic epilepsies. Linkage analysis excluded FAME1 and FAME2 (607876). Striano et al. (2008) commented that the phenotype described by Carr et al. (2007) was more severe than typically seen for FAME, and suggested that the disorder described by Carr et al. (2007) as 'FAME3,' should be placed within the group of progressive myoclonic epilepsies. Striano et al. (2008) suggested that the designation FAME be reserved for familial nonprogressive cortical tremor and epilepsy. In a large French family with FAME, a locus designated FAME3 (613608) was mapped to chromosome 5p15 by Depienne et al. (2010). Molecular Genetics Pennacchio et al. (1996) used a combination of genetic and physical mapping information to search systematically for the causative gene for EPM1. Several cDNAs identified with a bacterial artificial chromosome (BAC) clone encoded a previously described protein, cystatin B (601145), a cysteine protease inhibitor. Because of the wide expression of the cystatin B gene in normal individuals and the finding of reduced expression in lymphoblastoid cells from affected individuals, Pennacchio et al. (1996) sequenced the cystatin B gene (also known as stefin B) from affected individuals and identified 2 different mutations in the gene. Cystatin C (CST3; 604312) is the site of heterozygous mutations causing hereditary cerebral amyloid angiopathy. This dominantly inherited disorder is characterized by the deposition of cystatin C-rich amyloid fibrils in affected brain arteries. EPM1 is inherited as a recessive and appears to be the result of decreased amounts of cystatin B, suggesting different mechanisms for the 2 diseases. The genes responsible for Lafora disease (254780) (EPM2A; 607566) and juvenile myoclonic epilepsy (254770) mapped to 6q and 6p, respectively. The identification of cystatin B defects in EPM1 suggested that other members of the cystatin superfamily or their substrates may be defective in these related epilepsies. See 601145 for point mutations identified in the stefin B gene in patients with EPM1. Lafreniere et al. (1997) and Virtaneva et al. (1997) reported a novel type of disease-causing mutation, an unstable minisatellite repeat expansion in the putative promoter region of the gene (601145.0003). The mutation accounted for most EPM1 patients worldwide. Virtaneva et al. (1997) noted that haplotype data from their study were compatible with a single ancestral founder mutation. The length of the repeat array differed between chromosomes and families, but changes in repeat number seemed to be comparatively rare events. Lalioti et al. (1997) identified 6 nucleotide changes in the CSTB gene in non-Finnish EPM1 families from northern Africa and Europe. One of these, a homozygous G-to-C transversion at nucleotide 426 in exon 1, resulted in a gly4-to-arg substitution (G4R; 601145.0004) and was the first missense mutation described in association with EPM1. Molecular modeling predicted that this substitution would severely affect the contact of cystatin B with papain. The 6 mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. They also found a tandem repeat of a dodecamer (CCCCGCCCCGCG) in the 5-prime untranslated region as a polymorphism (601145.0003). They identified 2 allelic variants with 2 or 3 tandem copies. The frequency of the 3-copy allele was 66% in the normal Caucasian population. In an elaboration on their previous work, Lalioti et al. (1997) stated that the common mutation mechanism in EPM1 is the expansion of the dodecamer repeat (601145.0003), and considered this mutation to be the most likely source of the disorder. An examination of 58 EPM1 alleles revealed that 50 of these contained the dodecamer repeat expansion. In addition to the expanded repeat mutation and the 2 or 3 repeats found in alleles considered to be normal, Lalioti et al. (1997) identified alleles with 12 to 17 repeats, which they termed 'premutational,' that were transmitted unstably to offspring. These 'premutational' alleles were not connected with a clinical phenotype of EPM1. Lalioti et al. (1997) stated that no correlation between number of repeat expansions and age of onset or severity had been found. Antonarakis (1997) confirmed that the only EPM1-related point mutation in the cystatin B gene found in homozygous state was the G4R amino acid substitution. All other point mutations identified in EPM1 patients were found as compound heterozygotes with the 12-bp repeat expansion allele. The repeat expansion allele was also homozygous in some patients. Antonarakis (1997) found no patients with null point mutations (e.g., nonsense, frameshift, or splice site) in homozygous state; all EPM1 patients had residual gene activity. He proposed that homozygosity for null alleles was either nonviable or presented a different phenotype. ### Associations Pending Confirmation For discussion of a possible association between progressive myoclonic epilepsy and variation in the GPR37L1 gene, see 617630.0001. Population Genetics Koskiniemi et al. (1980) estimated that over 100 cases in 70 sibships had been identified in Finland. Fewer cases had been found in all the rest of the world. The incidence in Finland is about 1 in 20,000. Moulard et al. (2002) stated that Unverricht-Lundborg disease is also common North Africa but less common in western Europe. They performed a haplotype study of Unverricht-Lundborg disease chromosomes with a dodecamer repeat expansion in the CSTB gene (601145.0003), the most frequent cause of the disorder. They found that 29 (61.7%) of 47 patients from North Africa shared the same haplotype, thus establishing a founder effect in this population. The haplotypes from 48 Caucasian patients from western Europe were heterogeneous. History Stevenson pointed out, in a discussion of genetic aspects of the study by Harriman and Millar (1955), that Lundborg's study is 'of considerable historic interest in human genetics.' Lundborg's data were used to test statistically the recessive hypothesis, the first such analysis in man. The statistical analysis was done first by Weinberg (1912) and later by Bernstein (1929). Lundborg's report was one of the earliest of recessive inheritance. He published the names of those affected. When Book (1978) later attempted a follow-up, he found that marriage of relatives had been carefully avoided in the group and no more cases had occurred. Book (1978) suggested that this was one of the earliest and largest instances of group genetic counseling. Animal Model A possibly homologous disorder in Poll Hereford cattle was shown by Gundlach et al. (1988) to have a defect in glycine/strychnine receptors. The symptoms of the disorder suggested a failure of spinal interneuron inhibition and are similar to those in subconvulsive strychnine poisoning. Strychnine blocks the synaptic action of the inhibitory amino acid transmitter glycine by interacting with the postsynaptic glycine receptor. The mouse mutant 'spastic' may have a similar defect. The gene for the 'spastic' mutant maps to mouse chromosome 3 (Eicher and Lane, 1980). Grenningloh et al. (1990) indicated that it is the alpha-1 form of the glycine receptor (138491) that is coded by an autosome, whereas the alpha-2 receptor (305990) is X-linked. The features of EPM1 were reproduced by targeted disruption of the cystatin B gene in mice (Pennacchio et al., 1998). Lieuallen et al. (2001) identified 7 genes with consistently increased transcript levels in neurologic tissues from Cstb-deficient knockout mice: cathepsin S (116845), C1q B-chain of complement (120570), beta-2-microglobulin (109700), glial fibrillary acidic protein (137780), apolipoprotein D (107740), fibronectin-1 (135600), and metallothionein II (156360). These proteins are expected to be involved in increased proteolysis, apoptosis, and glial activation. The molecular changes in Cstb-deficient mice were consistent with the pathology found in the mouse model. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Visual blackouts (stage 1) \- EEG - polyspike on photic stimulation (stage 1) \- Stimulation sensitive segmental myoclonus (stage 2) \- Stimulation sensitive generalized myoclonus (stage 3) \- Generalized tonic-clonic seizures (stage 2 and 3) \- Absence seizures (stage 2 and 3) \- Minor motor impairment (stage 2) \- Intermittent wheelchair dependence (stage 3) \- EEG - alpha slowing, 4-6 Hz spike waves, myoclonus on photic stimulation (stage 2) \- EEG - alpha abolished, continuous spike waves, intense myoclonus on photic stimulation (stage 3) \- Action myoclonus (triggered by voluntary movements) \- Ataxia \- Mild mental deterioration \- Dysarthria MISCELLANEOUS \- Onset 6-13 years \- Three stages of disease progression - Stage 1 (subclinical), Stage 2 (early myoclonic), Stage 3 (disabling myoclonic) \- Incidence of 1 in 20,000 live births \- High frequency in Finnish population MOLECULAR BASIS \- Caused by mutation in the cystatin B gene (CSTB, 601145.0001 ) ▲ 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	MYOCLONIC EPILEPSY OF UNVERRICHT AND LUNDBORG	c0751785	8,336	omim	https://www.omim.org/entry/254800	2019-09-22T16:24:39	{"doid": ["3535"], "mesh": ["D020194"], "omim": ["254800"], "orphanet": ["308"], "synonyms": ["Alternative titles", "ULD", "EPILEPSY, PROGRESSIVE MYOCLONIC, 1A", "EPILEPSY, PROGRESSIVE MYOCLONIC, 1", "PROGRESSIVE MYOCLONIC EPILEPSY", "BALTIC MYOCLONIC EPILEPSY"], "genereviews": ["NBK1142"]}
natural fear typical of most mammals For other uses, see Fear of falling (disambiguation). 530 feet above the streets of Calgary The fear of falling (FOF), also referred to as basophobia (or basiphobia), is a natural fear and is typical of most humans and mammals, in varying degrees of extremity. It differs from acrophobia (the fear of heights), although the two fears are closely related. The fear of falling encompasses the anxieties accompanying the sensation and the possibly dangerous effects of falling, as opposed to the heights themselves. Those who have little fear of falling may be said to have a head for heights. Basophobia is sometimes associated with astasia-abasia, the fear of walking/standing erect. ## Contents * 1 In humans * 1.1 Infants * 1.2 Elderly persons * 2 In animals * 3 Factors that influence the fear of falling * 3.1 Postural control * 3.2 Height vertigo * 3.3 Space and motion discomfort * 4 Falling in dreams * 5 Media treatment * 6 See also * 7 References ## In humans[edit] ### Infants[edit] Studies done by psychologists Eleanor J. Gibson and Richard D. Walk have further explained the nature of this fear. One of their more famous studies is the "visual cliff". Below is their description of the cliff: > …a board laid across a large sheet of heavy glass which is supported a foot or more above the floor. On one side of the board a sheet of patterned material is placed flush against the undersurface of the glass, giving the glass the appearance as well as the substance of solidity. On the other side a sheet of the same material is laid upon the floor; this side of the board thus becomes the visual cliff.[1] Thirty-six infants were tested in their experiments, ranging from six to fourteen months. Gibson and Walk found that when placed on the board, 27 of the infants would crawl on the shallow side when called by their mothers; only three ventured off the "edge" of the cliff. Many infants would crawl away from their mothers who were calling from the deep end, and some would cry because they couldn’t reach their mothers without crossing an apparent chasm. Some would pat the glass on the deep end, but even with this assurance would not crawl on the glass. These results, although unable to prove that this fear is innate, indicate that most human infants have well developed depth perception and are able to make the connection between depth and the danger that accompanies falling. In May 1998, Behaviour Research and Therapy published a longitudinal survey by psychologists Richie Poulton, Simon Davies, Ross G. Menzies, John D. Langley, and Phil A. Silva of subjects sampled from the Dunedin Multidisciplinary Health and Development Study who had been injured in a fall between the ages of 5 and 9, compared them to children who had no similar injury, and found that at age 18, acrophobia was present in only 2 percent of the subjects who had an injurious fall but was present among 7 percent of subjects who had no injurious fall (with the same sample finding that typical basophobia was 7 times less common in subjects at age 18 who had injurious falls as children than subjects that did not).[2] Psychiatrists Isaac Marks and Randolph M. Nesse and evolutionary biologist George C. Williams have noted that people with systematically deficient responses to various adaptive phobias (e.g. basophobia, ophidiophobia, arachnophobia) are more temperamentally careless and more likely to end up in potentially fatal accidents and have proposed that such deficient phobia should be classified as "hypophobia" due to its selfish genetic consequences.[3][4][5] ### Elderly persons[edit] See also: Falls in older adults For a long time, the fear of falling was merely believed to be a result of the psychological trauma of a fall, also called "post-fall syndrome".[6] This syndrome was first mentioned in 1982 by Murphy and Isaacs,[7] who noticed that after a fall, ambulatory persons developed intense fear and walking disorders. Fear of falling has been identified as one of the key symptoms of this syndrome. Since that time, FOF has gained recognition as a specific health problem among older adults. However, FOF was also commonly found among elderly persons who had not yet experienced a fall.[8] Prevalence of FOF appears to increase with age and to be higher in women. Age remains significant in multiple logistic regression analyses.[9] The results of different studies have reported gender as a somewhat significant risk factor for fear of falling.[10][11] Other risk factors of fear of falling in the elderly include dizziness, self-rated health status, depression, and problems with gait and balance.[12][13] ## In animals[edit] Studies of nonhuman subjects support the theory that falling is an inborn fear. Gibson and Walk performed identical experiments with chicks, turtles, rats, kids, lambs, kittens, and puppies.[1] The results were similar to those of the human infants, although each animal behaved a little differently according to the characteristics of its species. The chicks were tested less than 24 hours after birth. It suggested that depth perception develops quickly in chickens, as the chicks never made the "mistake" of walking off the "deep" side of the cliff. The kids and lambs were also tested as soon as they could stand on their own. During the experiment, no goat or lamb ever stepped onto the glass of the deep side. When placed there, the animals displayed typical behavior by going into a posture of defense, with their front legs rigid and their back legs limp. In this state of immobility, the animals were pushed forward across the glass until their head and field of vision crossed the solid edge on the opposite side of the cliff; the goats and lambs would then relax and proceed to spring forward upon its surface. Based on the results of the animals tested, the danger and fear of falling is instilled in animals at a very young age. ## Factors that influence the fear of falling[edit] ### Postural control[edit] The postural control system has two functions: to ensure that balance is maintained by bracing the body against gravity, and to fix the orientation and position of the features that serve as a frame of reference for perception and action with respect to the external world.[14] Postural control relies on multisensory processing and motor responses that seem to be automatic and occur without awareness. Studies have shown that people afraid of heights or falling have poor postural control, especially in the absence of strong visual cues. These individuals rely heavily on vision to regulate their posture and balance.[15] When faced with high or unstable ground, the vestibular system in these individuals senses the instability and attempts to correct it by increasing postural sway to reactivate visual balance feedback (postural sway refers to the phenomenon of constant displacement and correction of the position of the center of gravity within the base of support).[16] This often fails, however, resulting in a feeling of increased instability and anxiety, which is often interpreted as fear. ### Height vertigo[edit] Closely related to postural control is the sensation of vertigo: a warning signal created by a loss of postural control when the distance between the observer and visible stationary objects becomes too large, and caused by a dysfunction of the vestibular system in the inner ear. In short, it is the feeling of motion when one is actually stationary. Symptoms of vertigo include dizziness, nausea, vomiting, shortness of breath, and the inability to walk or stand. Some individuals are more reliant on visual cues to control posture than others. Vestibular sensations can arise when unsound information is detected along the sensory channels (this happens even to those with normal vestibular function), and feelings of vertigo can result in people with postural control issues. ### Space and motion discomfort[edit] Studies have shown that people with acrophobia and/or an extreme fear of falling have higher scores of SMD, or space and motion discomfort. These are physical symptoms elicited by visual or kinesthetic information that is inadequate for normal spatial orientation. Space and motion discomfort arises when conflicting information is detected among visual, kinesthetic, and vestibular sensory channels. Evidence has supported the claim that patients with anxiety and SMD rely more heavily on visual cues for postural changes. ## Falling in dreams[edit] Sleeping child – falling is a common occurrence in dreams According to Sigmund Freud's The Interpretation of Dreams, falling dreams fall under the category of "typical dreams", meaning the "dreams which almost everyone has dreamt alike and which we are accustomed to assume must have the same meaning for everyone".[17] In the fairly recent study, "The Typical Dreams of Canadian University Students", common dreams were investigated by administering a Typical Dreams Questionnaire (TDQ).[18] The results confirmed that typical dreams are consistent over time, region, and gender, and a few themes can be considered almost universal: falling (73.8% prevalence), flying or soaring in the air (48.3%) and swimming (34.3%). In 1967, Saul and Curtis published a paper entitled "Dream Form and Strength of Impulse in Dreams of Falling and Other Dreams of Descent".[19] According to Saul and Curtis, dreams of falling can have various meanings, such as the sensation of falling asleep, the symbolization of a real risk of falling from bed, the repetition of traumatic experiences of falling or sensations of falling from parents’ arms in childhood, birth and delivery, ambition or the renouncement of responsibility, or life experiences such as flying in an airplane. They quote another author, Gutheil (1951), who suggests a range of possible meanings subsumed under the general idea of loss of (mental) equilibrium. These include loss of temper, loss of self-control, yielding, decline of the accepted moral standard or loss of consciousness.[1] Studies performed in recent years on the dream patterns of a group of 685 students attending secondary schools in Milan have concluded that, in dreams, fear is more frequently associated with falling, while happiness is connected with flying, and surprise with suspension and vertical movement (climbing, descent, ladder) content.[20] ## Media treatment[edit] In the Alfred Hitchcock film Vertigo, the hero, played by James Stewart, has to resign from the police force after an incident which causes him to develop both acrophobia and vertigo. Early on in the film he faints while climbing a stepladder. There are numerous references throughout the film to fear of heights and falling, ## See also[edit] * Acrophobia – Extreme or irrational fear of heights * Head for heights * List of phobias – Wikipedia list article * Vertigo – Type of dizziness where a person has the sensation of moving or surrounding objects moving ## References[edit] 1. ^ a b c Gibson, E.J.; Walk, R. D. (1960). "The "visual cliff"". Scientific American. 202 (4): 67–71. doi:10.1038/scientificamerican0460-64. PMID 13827949. 2. ^ Poulton, Richie; Davies, Simon; Menzies, Ross G.; Langley, John D.; Silva, Phil A. (1998). "Evidence for a non-associative model of the acquisition of a fear of heights". Behaviour Research and Therapy. Elsevier. 36 (5): 537–544. doi:10.1016/S0005-7967(97)10037-7. PMID 9648329. 3. ^ Nesse, Randolph; Williams, George C. (1994). Why We Get Sick: The New Science of Darwinian Medicine. New York: Vintage Books. pp. 212–214. ISBN 978-0679746744. 4. ^ Nesse, Randolph M. (2005). "32. Evolutionary Psychology and Mental Health". In Buss, David M. (ed.). The Handbook of Evolutionary Psychology (1st ed.). Hoboken, NJ: Wiley. pp. 911–913. ISBN 978-0471264033. 5. ^ Nesse, Randolph (2019). Good Reasons for Bad Feelings: Insights from the Frontier of Evolutionary Psychiatry. Dutton. pp. 64–76. ISBN 978-1101985663. 6. ^ Legsters, K. (2002). "Fear of falling". Phys Ther. 82 (3): 264–272. doi:10.1093/ptj/82.3.264. PMID 11869155. 7. ^ Murphy, J.; B. Isaacs (1982). "The post-fall syndrome: a study of 36 elderly patients". Gerontology. 28 (4): 265–270. doi:10.1159/000212543. PMID 7117852. 8. ^ Suzuki, M.; Ohyama N.; Yamada K.; et al. (2002). "The relationship between fear of falling, activities of daily living and quality of life among elderly individuals". Nurs Health Sci. 4 (4): 155–161. doi:10.1046/j.1442-2018.2002.00123.x. PMID 12406202. 9. ^ Friedman, SM; Munoz B; West SK; et al. (2002). "Falls and fear of falling: which comes first? A longitudinal prediction model suggest strategies for primary and secondary prevention". Am Geriatr Soc. 50 (8): 329–335. doi:10.1046/j.1532-5415.2002.50352.x. PMID 12164987. 10. ^ Lachman, ME; Howland J.; Tennstedt S.; et al. (1998). "Fear of falling and activity restriction: the survey of activities and fear of falling in the elderly (SAFE)". J Gerontol B Psychol Sci Soc Sci. 53 (1): 43–50. doi:10.1093/geronb/53b.1.p43. PMID 9469171. 11. ^ Howland, J.; Peterson EW; Levin WC (1993). "Fear of falling among the community-dwelling elderly". J Aging Health. 5 (2): 229–243. doi:10.1177/089826439300500205. PMID 10125446. S2CID 42164488. 12. ^ Arfken, Cl; Lach HW; Birge SJ; et al. (1994). "The prevalence and correlates of fear of falling in elderly persons living in the community". Am J Public Health. 84 (4): 565–570. doi:10.2105/AJPH.84.4.565. PMC 1614787. PMID 8154557. 13. ^ Tinetti, ME; Richman D; Powell L (1990). "Falls efficacy as a measure of fear of falling". J Gerontol. 45 (6): 239–243. doi:10.1093/geronj/45.6.P239. PMID 2229948. 14. ^ Massion, J. (1994). "Postural control system". Current Opinion in Neurobiology. 4 (6): 877–887. doi:10.1016/0959-4388(94)90137-6. PMID 7888772. S2CID 29283651. 15. ^ Strang, Adam J.; Joshua Haworth; Hieronymus Mathias; et al. (Jul 2011). "Structural changes in postural sway lend insight into effects of balance training, vision, and support surface on postural control in a healthy population". European Journal of Applied Physiology. 111 (7): 1485–1495. doi:10.1007/s00421-010-1770-6. PMID 21165641. S2CID 8229315. 16. ^ "Physical Therapy Dictionary". Retrieved 29 Sep 2011. 17. ^ Freud, Sigmund (1999). The Interpretation of Dreams. Oxford: Oxford UP. 18. ^ Nielsen, A. T.; Zadra A. L.; Simard V.; Saucier S.; Stenstro P.; Smith C.; et al. (2003). "The typical dreams of Canadian University students". Dreaming. 13 (4): 211–235. doi:10.1023/b:drem.0000003144.40929.0b. S2CID 146248464. 19. ^ Saul, Leon J.; George C. Curtis (1967). "Dream Form and Strength of Impulse in Dreams of Falling and Other Dreams of Descent". The International Journal of Psychoanalysis. 48 (2): 281–287. PMID 4166095. 20. ^ Maggiolini, A.; Persico, A.; Crippa, F. – Univ. of Milan, Italy (2007). "Gravity Content in Dreams". Dreaming. 17 (2): 87–97. doi:10.1037/1053-0797.17.2.87. [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	Fear of falling	c0877040	8,337	wikipedia	https://en.wikipedia.org/wiki/Fear_of_falling	2021-01-18T18:36:08	{"umls": ["C0877040"], "wikidata": ["Q5439393"]}
Florida keratopathy, also known as Florida spots, is an eye condition characterized by the presence of multiple spots within both corneas.[1] It is most commonly seen in dogs and cats, but is also rarely seen in horses and birds.[2] The disease is found in the southeastern parts of the United States.[2] In other parts of the world it is confined to tropics and subtropics, and it is known as tropical keratopathy.[1] Florida keratopathy appears as multiple cloudy opacities in the stromal layer of the cornea.[1] The spots appear concentrated at the center and become more diffuse at the periphery. They can range in size from one to eight millimeters.[3] There are no other symptoms, and there is no response to treatment with either anti-inflammatory or antimicrobial drugs. Histological analysis of affected corneas has found acid-fast staining organisms, suggesting Florida keratopathy may be caused by a type of mycobacterium.[3] The disease may be induced by repeated stings to the eyes by the little fire ant, Wasmannia auropunctata.[4][non-primary source needed] ## References[edit] 1. ^ a b c Roze, Maurice (2005). "Corneal Diseases in Cats". Proceedings of the 30th World Congress of the World Small Animal Veterinary Association. Retrieved 2007-03-23. 2. ^ a b Gelatt, Kirk N.; Gilger, Brian C.; Kern, Thomas J. (2013). "Section IV: Special ophthalmology". Veterinary ophthalmology (5 ed.). Ames, Iowa: Wiley-Blackwell. pp. 1499–1500. ISBN 9780470960400. 3. ^ a b Gelatt, Kirk N. (ed.) (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8.CS1 maint: extra text: authors list (link) 4. ^ Theron, Leonard (2005). Wasmannia auropunctata linked keratopathy Hypothesis - The Polynesian Case. Doctorate in Veterinary Medicine Master (Thesis). hdl:2268/652. [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	Florida keratopathy	c4523781	8,338	wikipedia	https://en.wikipedia.org/wiki/Florida_keratopathy	2021-01-18T18:36:04	{"wikidata": ["Q3201122"]}
Heart-hand syndrome refers to a group of congenital disorders characterized by malformations of the upper limbs and heart. To date, heart-hand syndrome comprises the following rare syndromes; Holt-Oram syndrome; heart-hand syndrome type 2; heart-hand syndrome type 3; heart hand syndrome, Slovenian type, brachydactyly-long thumb; and patent ductus arteriosus-bicuspid aortic valve - hand anomalies (see these terms). [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	Heart-hand syndrome	c0265264	8,339	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228184	2021-01-23T18:24:29	{"mesh": ["C535326"], "umls": ["C0265264"], "icd-10": ["Q87.2"], "synonyms": ["Atriodigital dysplasia"]}
A number sign (#) is used with this entry because of evidence that leukoencephalopathy with ataxia (LKPAT) is caused by homozygous or compound heterozygous mutation in the CLCN2 gene (600570) on chromosome 3q27. Description Leukoencephalopathy with ataxia is an autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient (ADC) values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles. The findings suggest myelin microvacuolation restricted to certain brain regions. Clinical features include ataxia and unstable gait; more variable abnormalities may include visual field defects, headaches, and learning disabilities (summary by Depienne et al., 2013). Clinical Features Depienne et al. (2013) reported 6 unrelated patients with a characteristic pattern of leukoencephalopathy on brain MRI, including 3 with adult onset and 3 with childhood onset of the disorder. Clinical features overlapped, but were variable. The adult patients had mild cerebellar ataxia with a variable combination of chorioretinopathy, visual field defects, optic neuropathy, and headaches. One patient had a schizophrenia-like disorder. The children had mild cerebellar ataxia and a variable combination of mild spasticity, visual field defects, learning disabilities, and headaches. None of the patients had seizures. ### Neuroradiologic Features Brain MRI of all 6 patients with leukoencephalopathy and ataxia reported by Depienne et al. (2013) showed prominent signal abnormalities in the middle cerebellar peduncles, midbrain cerebral peduncles, pyramidal tracts in the pons, and posterior limbs of the internal capsule. There were additional abnormalities in specific brainstem tracts and the cerebellar white matter. ADC values were decreased in all patients, indicating small water spaces within tissue microstructure. The pediatric patients also had diffuse mild signal abnormalities of the white matter, which were hyperintense compared to gray matter on T2- and T1-weighted images. These changes suggested myelin microvacuolation rather than hypomyelination. Depienne et al. (2013) noted that the clinical features of these patients were nonspecific and did not allow a diagnosis, whereas the MRI findings were specific enough to allow a diagnosis. Inheritance The transmission pattern of leukoencephalopathy with ataxia in the families reported by Depienne et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 unrelated patients with LKPAT, Depienne et al. (2013) identified homozygous or compound heterozygous mutations in the CLCN2 gene (see, e.g., 600570.0006-600570.0009). The first mutations were found by whole-exome sequencing. CLCN2, which is involved in brain ion and water homeostasis, was detected in astrocytes and all components of the panglial syncytium. CLCN2 was also enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. All mutations were shown to cause a loss of protein function. The clinical findings were similar to those observed in Clcn2-deficient mice (see ANIMAL MODEL). Animal Model Bosl et al. (2001) found that Clcn2-null mice developed severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina, and germ cells failed to complete meiosis. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, Clcn2 disruption resulted in the death of 2 cell types that depend on supporting cells that form the blood-testes and blood-retina barriers. Blanz et al. (2007) found that Clcn2-null mice were blind and developed progressive widespread spongiform vacuolation of white matter in the brain and spinal cord. Fluid-filled spaces appeared between myelin sheaths of the central but not the peripheral nervous system. However, neuronal morphology appeared normal, and neurologic deficits were mild, mainly including decreased conduction velocity in neurons of the central auditory pathway. The phenotype resembled a leukodystrophy; however, no CLCN2 mutations were found in 150 human leukodystrophy patients. Heterozygous loss of Clcn2 had no detectable functional or morphologic consequences. Neither heterozygous nor homozygous Clcn2 knockout mice had lowered seizure thresholds. Blanz et al. (2007) postulated a role for CLCN2 in glial function and ionic homeostasis in the central nervous system. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Visual field defects (in some patients) \- Chorioretinopathy (in some patients) \- Optic neuropathy (in some patients) NEUROLOGIC Central Nervous System \- Gait ataxia \- Limb ataxia \- Headache \- Learning disabilities (in some patients) \- Leukoencephalopathy \- Signal abnormalities in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles seen on MRI \- Low apparent diffusion coefficient (ADC) values \- Diffuse hyperintense signal abnormalities in the white matter (in children) \- Myelin microvacuolation MISCELLANEOUS \- Two peaks of onset, childhood and adult \- Variable clinical features MOLECULAR BASIS \- Caused by mutation in the chloride channel 2 gene (CLCN2, 600570.0006 ) ▲ 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	LEUKOENCEPHALOPATHY WITH ATAXIA	c3810242	8,340	omim	https://www.omim.org/entry/615651	2019-09-22T15:51:21	{"omim": ["615651"], "orphanet": ["363540"], "synonyms": [], "genereviews": ["NBK326661"]}
A number sign (#) is used with this entry because of evidence that premature ovarian failure-10 (POF10) is caused by homozygous mutation in the MCM8 gene (608187) on chromosome 20p. Description Premature ovarian failure-10 (POF10) represents a syndrome characterized by primary amenorrhea, hypergonadotropic ovarian insufficiency, and genomic instability in somatic cells. For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360). For a discussion of genetic heterogeneity of age at natural menopause, see MENOQ1 (300488). Clinical Features AlAsiri et al. (2015) studied 3 sisters from a consanguineous Saudi Arabian family who had premature ovarian failure. All 3 sisters had a normal 46,XX karyotype, elevated follicle-stimulating hormone (FSH; see 136530) levels, and infantile uteri and small atrophic ovaries on pelvic ultrasound. Secondary sexual characteristics were delayed. All 3 patients were also diagnosed with hypothyroidism, which responded to thyroxine. Tenenbaum-Rakover et al. (2015) reported 2 unrelated consanguineous Arab families with gonadal failure. In the first family, the proband was a 46,XX woman who at age 15 years was completely prepubertal with elevated gonatotropins and primary amenorrhea. At age 22, she had normal pubic hair but only breast bud formation while on hormone replacement therapy. Ultrasound revealed a 6-mm uterus but did not detect ovaries; these findings were confirmed by MRI, which also showed a rudimentary vagina. Her 21-year-old 46,XY brother, who had been diagnosed with a 22q11 microdeletion (DiGeorge syndrome; 188400), exhibited normal pubic hair and penile development, but testicular volume was only 3 mL and he was azoospermic with high basal and GnRH-stimulated gonadotropins, consistent with primary testicular failure. Their father reported delayed puberty and at age 49, had elevated FSH with normal luteinizing hormone (LH; see 152780) and testosterone concentrations. Their mother had delayed menarche at age 15 years, but had regular menses since then and a normal hormonal profile at age 40 years. Other features present in the proband included mild unilateral conductive hearing loss, agenesis of the left kidney, and temporal seizures; both sibs exhibited mild mental retardation. Tenenbaum-Rakover et al. (2015) suggested that these additional features might be related to the familial consanguinity. In the second family, 3 sisters presented consecutively at 14.5 to 15 years of age with delayed puberty, primary amenorrhea, and hypergonadotropic hypogonadism; absence of ovaries and a small uterus were demonstrated by ultrasound and MRI. Their karyotype was 46,XX, and SRY (480000) testing was negative. The sisters responded well to estrogen and progesterone replacement therapy, achieving normal height and pubertal development and experiencing regular menses. Their parents and a healthy older sister had normal pubertal development and normal hormonal profile. Following the sisters' diagnosis, 2 paternal female cousins, aged 30 and 28 years, were also diagnosed with primary hypergonadotropic hypogonadism. There was no history of malignancies in either family. Mapping ### Premature Ovarian Failure 10 By SNP analysis in a consanguineous Saudi Arabian family in which 3 sisters had hypergonadotropic primary amenorrhea, AlAsiri et al. (2015) identified a 3.3-Mb region of homozygosity on chromosome 20p13-p12.3, flanked by SNPs rs1547618 and rs1012891, which was present only in the affected sibs. ### Age At Natural Menopause Quantitative Trait Locus 3 Stolk et al. (2009) conducted a 2-stage genomewide association study for age at natural menopause in 2,979 European women and identified a SNP on chromosome 20p12.3 that was significant: rs236114 (p = 9.71 x 10(-11)). The authors subsequently conducted fine mapping using metaanalysis of imputed data from the stage 1 study and found an additional SNP with higher significance compared to that of the initially reported SNP, located in the same LD block on chromosome 20 as the genomewide-significant SNP (rs16991615; p = 3.00 x 10(-7)). Stolk et al. (2009) noted that rs236114 is located in an intron of the MCM8 gene (608187) and that rs16991615 is a nonsynonymous SNP (E341K) located in exon 9 of MCM8. In a genomewide association study of 17,438 women, He et al. (2009) found significant association with age at natural menopause for rs16991615 (p = 1.2 x 10(-21)). Molecular Genetics By whole-exome sequencing in a consanguineous Saudi Arabian family in which 3 sisters had hypergonadotropic primary amenorrhea mapping to chromosome 20p13-p12.3, AlAsiri et al. (2015) identified homozygosity for a missense mutation in the MCM8 gene (P149R; 608187.0001) that segregated with the disorder. The mutation was not found in 200 fertile women or in the Exome Variant Server or 1000 Genomes Project databases. By whole-exome sequencing in 2 unrelated consanguineous Arab families with primary gonadal failure, Tenenbaum-Rakover et al. (2015) identified homozygosity for mutations in the MCM8 gene: a splice site mutation in the first family (608187.0002) and a 2-bp insertion in the MCM8 gene (608187.0003) in the second. Each mutation segregated with disease in the respective family and neither was found in 100 ethnically matched controls. INHERITANCE \- Autosomal recessive CHEST Breasts \- Delayed or absent thelarche GENITOURINARY External Genitalia (Male) \- Small testes \- Azoospermia Internal Genitalia (Female) \- Primary amenorrhea \- Atrophic or absent ovaries on ultrasound \- Infantile uterus on ultrasound ENDOCRINE FEATURES \- Primary amenorrhea \- Azoospermia \- Hypergonadotropic premature ovarian failure \- Hypergonadotropic testicular failure \- Delay of secondary sexual characteristics \- Elevated follicle-stimulating hormone (FSH) \- Elevated luteinizing hormone (LH) \- Hypothyroidism (in some patients) MISCELLANEOUS \- One male patient has been reported (last curated September 2015) MOLECULAR BASIS \- Caused by mutation in the minichromosome maintenance complex component-8 gene (MCM8, 608187.0001 ) ▲ 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	PREMATURE OVARIAN FAILURE 10	c2752067	8,341	omim	https://www.omim.org/entry/612885	2019-09-22T16:00:24	{"omim": ["612885"]}
A number sign (#) is used with this entry because Farber lipogranulomatosis (FRBRL) is caused by homozygous or compound heterozygous mutation in the gene encoding acid ceramidase (ASAH1; 613468) on chromosome 8p. Description Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age (summary by Alves et al., 2013). Clinical Features In the few reported cases of Farber disease, manifestations appeared in the first few weeks of life and consisted of irritability, hoarse cry, and nodular, erythematous swellings of the wrists and other sites, particularly those subject to trauma. Severe motor and mental retardation was evident. Death occurred by 2 years of age. The histologic appearance was granulomatous. In the nervous system, both neurons and glial cells were swollen with stored material characteristic of nonsulfonated acid mucopolysaccharide (Abul-Haj et al., 1962). Parental consanguinity had not been identified. However, in 1 case parents had the same family name in ancestors, and 2 of 3 families seen at Children's Hospital, Boston, were of Portuguese extraction. The family with 2 affected sibs had father from the Azores Islands and mother from the Madeira Islands. The parents of the other family were both born in the Azores (Crocker et al., 1967). Clausen and Rampini (1970) proposed that an enzymatic defect in glycolipid degradation is the basic fault. Sugita et al. (1972) suggested that the basic defect is a deficiency of acid ceramidase (AC), also called N-acylsphingosine amidohydrolase (ASAH), which normally catalyzes the synthesis and degradation of ceramide. No activity of this enzyme could be demonstrated in kidney and cerebellum. Antonarakis et al. (1984) described 2 sibs, a 12-week-old girl with classic severe features (subcutaneous periarticular nodules, hoarse cry, failure to thrive, and respiratory insufficiency) and a 10-week-old boy, who presented earlier, with clinical features suggestive of malignant histiocytosis. They died at 6 months and at 12 weeks, respectively. The girl also had hepatosplenomegaly, a relatively unusual feature of Farber disease; of 27 reported cases, 7 had hepatomegaly and 1 had splenomegaly. Thus, Farber disease should be considered in infants with seeming malignant histiocytosis. Because of the 25% recurrence risk and ability to make prenatal diagnosis, assay of ceramidase is important in such cases. Pellissier et al. (1986) studied 2 severely affected sibs born of consanguineous Tunisian parents. Involvement of both the central and peripheral nervous system was documented. Macular cherry red spots were observed in 1. Moser et al. (1989) identified 5 types of Farber lipogranulomatosis. In the classic type 1, the diagnosis can be made almost at a glance by the triad of subcutaneous nodules, arthritis, and laryngeal involvement. When 1 aspect is missing, the possibility of juvenile rheumatoid arthritis, multicentric reticulohistiocytosis, or juvenile hyaline fibromatosis (228600) may be entertained, but ceramidase levels are normal in all of these conditions. Patients with types 2 and 3 survive longer. Liver and lung appear not to be involved. Normal intelligence in many of these patients and the postmortem findings suggest that brain involvement is limited or missing entirely. Moser et al. (1989) stated that several patients with type 3 were 'in relatively stable condition near the end of the second decade.' Type 4 patients present with hepatosplenomegaly and severe debility in the neonatal period and all die before 6 months of age. Massive histiocytic infiltration of liver, spleen, lungs, thymus, and lymphocytes is found at autopsy. Antonarakis et al. (1984) reported patients with severe type 4 lipogranulomatosis. Their case 1 had not been recognized even after postmortem study, and the diagnosis of Farber disease was considered only in retrospect when subcutaneous nodules were noted in a subsequently born sib. Type 5 lipogranulomatosis, described by Zarbin et al. (1985) and Eviatar et al. (1986), is characterized particularly by psychomotor deterioration beginning at age 1 to 2.5 years. The family of Zarbin et al. (1985) included 2 affected sisters from a marriage of a Korean national and a Caucasian female; the affected girls may represent a genetic compound. As in the case of Pellissier et al. (1986), macular cherry red spots were noted. The patient of Eviatar et al. (1986) was a black child. Qualman et al. (1987) described a family in which 1 child, a 3-month-old boy, presented with only hepatosplenomegaly and had a fulminant clinical course suggestive of malignant histiocytosis. The second child, a 5.5-month-old girl, had the typical clinical presentation of Farber disease, with hoarseness and painful swollen joints. Visceral involvement was prominent in both, and included a newly described nephropathy with elevated urine ceramide levels. Liver and spleen contained massive histiocytic infiltrates in association with elevated ceramide levels. Lymph nodes also contained histiocytic infiltrates but without the sinusoidal involvement typical of proliferative histiocytic disorders. Nowaczyk et al. (1996) described a 16-week-old female infant with the rare type IV Farber lipogranulomatosis featuring hepatosplenomegaly, macular cherry red spot, and subcutaneous nodules. The patient developed liver dysfunction with jaundice and ascites and myelophthisic anemia because of infiltration of the bone marrow with storage cells. Direct assay of skin fibroblasts confirmed the diagnosis of ceramidase deficiency. Kattner et al. (1997) reported a severe case of Farber lipogranulomatosis presenting as nonimmune hydrops fetalis. Prenatal ultrasound at 26 weeks' gestation showed hydrops fetalis with hepatosplenomegaly. The infant died 3 days after birth. Postmortem examination showed edema and multiple white nodules disseminated throughout the body that consisted of storage macrophages and fibrosis. Splenic tissue showed an accumulation of ceramide, and ceramidase activity was profoundly reduced in patient tissues. The parents were unrelated and a prior pregnancy had resulted in early spontaneous abortion. Diagnosis Ben-Yoseph et al. (1989) used N-laurylsphingosine deacylase as a substrate for studying the usefulness of plasma specimens for diagnosis and carrier detection of Farber disease. This made a highly sensitive assay because the substrate is cleaved by acid ceramidase at a much faster rate than are other substrates. Inheritance Farber lipogranulomatosis shows autosomal recessive inheritance (summary by Alves et al., 2013). Mapping Farber disease is caused by mutations in the ASAH1 gene, which Li et al. (1999) mapped to chromosome 8p22-p21.3. Molecular Genetics In a patient with Farber disease, Koch et al. (1996) identified a homoallelic thr222-to-lys (T222K; 613468.0001) in the ASAH1 gene. Bar et al. (2001) identified 6 novel mutations in the ASAH gene causing Farber disease: 3 point mutations resulting in single amino acid substitutions, 1 intronic splice site mutation resulting in exon skipping, and 2 point mutations leading to occasional or complete exon skipping. The latter 2 mutations occurred in adjacent nucleotides and led to abnormal splicing of the same exon. Metabolic labeling studies in fibroblasts of 4 patients showed that even though acid ceramidase precursor protein was synthesized in these individuals, rapid proteolysis of the mutated, mature acid ceramidase occurred within the lysosome. In a patient with severe Farber disease resulting in hydrops fetalis and death at age 3 days (Kattner et al., 1997), Alves et al. (2013) identified compound heterozygosity for 2 null mutations in the ASAH1 gene (613468.0008 and 613468.0009). The severe phenotype correlated with a complete loss of the full-length protein. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Eyes \- Macular cherry-red spots (in some patients) RESPIRATORY Larynx \- Laryngeal nodules ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Painful swollen joints \- Arthritis SKIN, NAILS, & HAIR Skin \- Lipogranulomatosis \- Periarticular subcutaneous nodules \- Nodule show lipid-laden macrophages NEUROLOGIC Central Nervous System \- Irritability \- Motor retardation \- Mental retardation (in some patients) VOICE \- Hoarse cry due to laryngeal involvement LABORATORY ABNORMALITIES \- Elevated urine ceramide levels \- Histiocytic infiltration of liver, spleen, and lungs \- Ceramidase deficiency MISCELLANEOUS \- Onset in infancy or first years of life \- Progressive disorder \- Early death (in some patients) \- Variable severity MOLECULAR BASIS \- Caused by mutation in the N-acylsphingosine amidohydrolase 1 gene (ASAH1, 613468.0001 ) ▲ 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	FARBER LIPOGRANULOMATOSIS	c0268255	8,342	omim	https://www.omim.org/entry/228000	2019-09-22T16:27:57	{"doid": ["0050464"], "mesh": ["D055577"], "omim": ["228000"], "orphanet": ["333"], "synonyms": ["Alternative titles", "FARBER DISEASE", "CERAMIDASE DEFICIENCY", "ACID CERAMIDASE DEFICIENCY", "AC DEFICIENCY", "N-LAURYLSPHINGOSINE DEACYLASE DEFICIENCY"], "genereviews": ["NBK488189"]}
Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein. People with lysinuric protein intolerance have features associated with protein intolerance, including an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and progressively brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD) in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability. The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods. ## Frequency Lysinuric protein intolerance is estimated to occur in 1 in 60,000 newborns in Finland and 1 in 57,000 newborns in Japan. Outside these populations this condition occurs less frequently, but the exact incidence is unknown. ## Causes Mutations in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestine and kidneys to the rest of the body is necessary for the body to be able to use proteins. Mutations in the y+LAT-1 protein disrupt the transportation of amino acids, leading to a shortage of lysine, arginine, and ornithine in the body and an abnormally large amount of these amino acids in urine. A shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood. Lysine is particularly abundant in collagen molecules that give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine contributes to the short stature and osteoporosis seen in people with lysinuric protein intolerance. Other features of lysinuric protein intolerance are thought to result from abnormal protein transport (such as protein deposits in the lungs) or a lack of protein that can be used by the body (protein malnutrition). ### Learn more about the gene associated with Lysinuric protein intolerance * SLC7A7 ## 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 [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	Lysinuric protein intolerance	c0268647	8,343	medlineplus	https://medlineplus.gov/genetics/condition/lysinuric-protein-intolerance/	2021-01-27T08:24:45	{"gard": ["3335"], "mesh": ["C562687"], "omim": ["222700"], "synonyms": []}
Not to be confused with Allergies to cats. See also: Cat health § Food allergy A cat showing extreme signs of pruritus. Cats exposed to allergens may develop allergies or allergic reactions. Allergies tend to become evident and intensify over extended periods of time and can take years to develop.[1] Some allergic diseases and allergies in cats include feline atopic dermatitis, flea allergy dermatitis, feline-mosquito hypersensitivity, and food-induced allergy. In the case of feline atopy, hypersensitivity to allergens is due to genetic predisposition. However, various allergies may arise due to environmental factors. Allergens, ingested, inhaled, or airborne, can be seasonal or non-seasonal, similar to allergies in humans.[2] Suspected seasonal allergens include but are not limited to pollen, fleas, and mosquito bites; suspected non-seasonal allergens include but are not limited to plastic materials, food, dust, trees, and grass. After exposure to suspected allergens, symptoms may be immediate or delayed, arising within a few minutes to two hours. Symptoms can include both dermatological and gastrointestinal signs[3] such as itchy skin, hair loss and excessive scratching. In cases of feline atopic dermatitis or atopy in cats, pruritic skin diseases may result; however, signs can also include miliary dermatitis, symmetrical alopecia, and lesions of the eosinophilic granuloma complex.[4] Food allergies account for approximately 10% of allergies in both dogs and cats.[5] Food allergies are often mistaken for food intolerances, which can result in vomiting and diarrhea instead of dermal issues. In most cases where food allergies occur, they do so with foods that cats eat most often. Common food allergens in cats include beef, dairy, fish, eggs, and chicken. Preservatives and other additives are also occasionally involved in triggering an allergic reaction.[6] There is no specific breed or age range that food allergies target; however, there are certain breeds that are more susceptible to food allergies than others.[7] For example, Siamese and Siamese crosses may have a higher risk of food allergies than other breeds.[7] ## Contents * 1 Allergy identification and treatment * 2 Hypoallergenic elimination diets for cats * 2.1 Limited ingredient diets * 2.2 Homemade diets * 2.3 Hydrolyzed proteins * 2.4 Novel proteins * 3 See also * 4 References ## Allergy identification and treatment[edit] While it is possible to identify what type of symptoms the cat is suffering from, it is best to seek attention from a veterinarian to identify the best treatment possible. In order to identify to which allergens the cat is allergic, veterinarians will commonly use a serum allergy test. Veterinarians will often recommend over the counter allergy relief products to alleviate mild problems. If the allergy is more severe, allergy immunotherapy may be recommended.[citation needed] ## Hypoallergenic elimination diets for cats[edit] Further information: Elimination diet ### Limited ingredient diets[edit] Main article: Limited ingredient cat diet (LID) A limited-ingredient diet, also known as limited-antigen food,[8] is an elimination diet that restricts the problematic foods that cause a reaction. Usually these diets focus on removing specific proteins (protein-elimination diets) due to dietary allergies usually being caused by water-soluble glycoproteins,[9][10] but they can also be targeted towards the removal of gluten/wheat, vegetables, or a combination of both.[9] In commercially available versions of these diets, producers usually include one protein and one carbohydrate source, in an effort to minimize reactions to any foods.[9] ### Homemade diets[edit] See also: Cat food § Homemade food Homemade diets are a type of elimination diet, which are made specifically for the cat with allergies, either by the owner or a third-party person like a chef.[11] Studies suggest that commercial elimination diets may still react negatively with a cat, even if they are devoid of the target protein/other problematic foods.[11] Many pet owners, for this reason, choose the homemade option, as it allows them to personally identify the pet's history, tailor the diet with various ingredients, and consider the process a bonding experience.[9][11] Some drawbacks to a homemade diet are the time needed to shop for the ingredients and the potential financial setback.[9] Also, homemade diets are generally nutritionally deficient. For example, a study found that 90% of homemade elimination diets are not adequate in terms of nutrition.[9] However, homemade diets are a great way to determine which ingredient is causing the negative symptoms in the cat.[9] ### Hydrolyzed proteins[edit] Main article: Hydrolyzed protein Hydrolyzed proteins are often used as the primary source of protein in a diet, particularly in elimination diets, since these proteins do not cause allergenic responses.[12] This is because the digestive tract breaks down the protein into individual amino acids that the body is unable to recognize as the offending protein, allowing the protein source to bypass the allergenic immune response associated with IgE.[13] This avoidance of the immune reaction allows the animal to eat a sufficient protein source without the immune system interfering.[13] ### Novel proteins[edit] A novel protein is a protein source used in hypoallergenic diets to which the cat has not previously been exposed.[14] Common examples of novel proteins are lamb, rabbit, venison, duck, elk, kangaroo, ostrich, emu, goose and goat.[8] However, there is a chance of cross-reactivity when there is a higher taxonomic relationship between the two species. For example, cross-reactivity could be caused by other ruminant meats if the cat reacted negatively to beef, or avian meats if the cat reacted negatively to chicken.[8] Rabbit meat Novel proteins can be used in elimination diets as well for long-term management. Many commercialized novel protein diets are nutritionally adequate and balanced. They have only one protein source and one carbohydrate source that the cats are unlikely to have ingested before.[15] Owners are more likely to be compliant when feeding a commercial novel protein diet than when feeding a home cooked diet.[8] This is due to the fact that it can be difficult to obtain novel proteins for food preparation,[15] and it takes less time to provide a commercial diet than to prepare a home cooked one.[8] In the early '90s, an experiment was performed showing that novel protein diets had a 70 to 80% success rate.[14] However, commercialized novel protein diets are not always effective, since they are not always tested on animals that have food sensitivities, and the manufacturing process of the diets can cause adverse reactions due to the inclusion of additives which may be allergens to some cats.[14] It is recommended that human-grade meat be used in the diet instead of pet food meats since pet food meats can include preservatives, which can be detrimental to the success of the diet.[15] Also, a study showed that if the processing machinery was not cleaned properly, ground meat that came from one animal could be contaminated with the ground meat from another animal. This study found that four commercial diets using venison included products that were not on the label. Soy, beef and poultry were found in three of the diets, which are common antigens in cats. However, if the commercial novel protein diet does not cause an adverse reaction in the cat, it can be used long term.[8] ## See also[edit] * Cat health * Allergies * Cat food * Allergies in dogs ## References[edit] 1. ^ "Feline Food Allergies". www.vet.cornell.edu. Retrieved 2017-11-29. 2. ^ "Feline Atopic Dermatitis - Integumentary System - Merck Veterinary Manual". Merck Veterinary Manual. Retrieved 2018-01-02. 3. ^ Guaguère, E (1995). "Food intolerance in cats with cutaneous manifestations: a review of 17 cases". European Journal of Companion Animal Practice. 5: 27–35. 4. ^ DACVD, Hilary A. Jackson BVM&S DVD. "Dermatologic manifestations and nutritional management of adverse food reactions". dvm360.com. Retrieved 2017-11-29. 5. ^ Scott, D. (2001). "Skin Immune System and Allergic Skin Diseases". Muller & Kirk's Small Animal Dermatology. pp. 543–666. doi:10.1016/B978-0-7216-7618-0.50012-2. ISBN 978-0-7216-7618-0. 6. ^ Carlotti, Didier N. (2013). "Cutaneous Manifestations of Food Hypersensitivity". Veterinary Allergy. pp. 108–114. doi:10.1002/9781118738818.ch16. ISBN 978-1-118-73881-8. 7. ^ a b Carlotti, Didier N.; Remy, Isabelle; Prost, Christine (1990-06-01). "Food Allergy In Dogs And Cats. A Review and Report of 43 Cases". Veterinary Dermatology. 1 (2): 55–62. doi:10.1111/j.1365-3164.1990.tb00080.x. ISSN 1365-3164. 8. ^ a b c d e f Gaschen, Frédéric P.; Merchant, Sandra R. (March 2011). "Adverse Food Reactions in Dogs and Cats". Veterinary Clinics of North America: Small Animal Practice. 41 (2): 361–379. doi:10.1016/j.cvsm.2011.02.005. PMID 21486641. 9. ^ a b c d e f g Case, Linda (2010). Canine and Feline Nutrition-E-Book. Maryland Heights, Missouri: Mosby, Inc. p. 400. 10. ^ Leistra, M.; Willemse, T. (December 2002). "Double-blind evaluation of two commercial hypoallergenic diets in cats with adverse food reactions". Journal of Feline Medicine and Surgery. 4 (4): 185–188. doi:10.1053/jfms.2001.0193. ISSN 1098-612X. PMID 12468310. 11. ^ a b c Case, Linda (2010). Canine and Feline Nutrition-E-Book. 3251 Riverpool Lane, Maryland Heights, Missouri: Mosby, Inc. p. 399.CS1 maint: location (link) 12. ^ Zoran, Deb (November 2003). "Nutritional management of gastrointestinal disease". Clinical Techniques in Small Animal Practice. 18 (4): 211–217. doi:10.1016/S1096-2867(03)00074-4. PMC 7129079. PMID 14738201. 13. ^ a b Cave, Nicholas J. (November 2006). "Hydrolyzed Protein Diets for Dogs and Cats". Veterinary Clinics of North America: Small Animal Practice. 36 (6): 1251–1268. doi:10.1016/j.cvsm.2006.08.008. PMID 17085233. 14. ^ a b c Verlinden, A.; Hesta, M.; Millet, S.; Janssens, G. P.J. (18 January 2007). "Food Allergy in Dogs and Cats: A Review". Critical Reviews in Food Science and Nutrition. 46 (3): 259–273. doi:10.1080/10408390591001117. PMID 16527756. 15. ^ a b c Vogelnest, LJ; Cheng, KY (November 2013). "Cutaneous adverse food reactions in cats: retrospective evaluation of 17 cases in a dermatology referral population (2001-2011)". Australian Veterinary Journal. 91 (11): 443–451. doi:10.1111/avj.12112. PMID 24571298. [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	Allergies in cats	None	8,344	wikipedia	https://en.wikipedia.org/wiki/Allergies_in_cats	2021-01-18T18:57:44	{"wikidata": ["Q48801082"]}
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time. MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability). Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression. MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA). ## Frequency MPAN is a rare condition that is estimated to affect less than 1 in 1 million people. ## Causes Mutations in the C19orf12 gene cause MPAN. The protein produced from this gene is found in the membrane of cellular structures called mitochondria, which are the energy-producing centers of the cell. Although its function is unknown, researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis. The gene mutations that cause this condition lead to an altered C19orf12 protein that likely has little or no function. It is unclear how these genetic changes lead to the neurological problems associated with MPAN. Researchers are working to determine whether there is a link between problems with lipid homeostasis and brain iron accumulation and how these abnormalities might contribute to the features of this disorder. ### Learn more about the gene associated with Mitochondrial membrane protein-associated neurodegeneration * C19orf12 ## 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 [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	Mitochondrial membrane protein-associated neurodegeneration	c3280371	8,345	medlineplus	https://medlineplus.gov/genetics/condition/mitochondrial-membrane-protein-associated-neurodegeneration/	2021-01-27T08:25:08	{"gard": ["12569"], "omim": ["614298"], "synonyms": []}
Amobarbital normally undergoes two hydroxylations, leading to 3-prime-hydroxyamobarbital (C-OH) and N-hydroxyamobarbital (N-OH). Kalow et al. (1977) described a kindred in which 2 mothers who were identical twins showed a gross deficiency of N-OH in the urine. Family data suggested that the twins were homozygous for a gene regulating N-OH formation. There was no evidence of compensatory or concordant regulation of the two hydroxylation reactions. This example illustrates that a defect in biotransformation is likely to be overlooked if one measures only the disappearance of a multimetabolized drug. Lab \- Deficient N-hydroxyamobarbital after amobarbital 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	AMOBARBITAL, DEFICIENT N-HYDROXYLATION OF	c1859816	8,346	omim	https://www.omim.org/entry/204800	2019-09-22T16:31:08	{"mesh": ["C565959"], "omim": ["204800"]}
This condition must be distinguished from myotonia congenita and from the Debre-Semelaigne syndrome of congenital hypothyroidism. Poch et al. (1971) described a well-documented family with male-to-male transmission. Striking hypertrophy of the calf muscles and less constantly of the masseter muscles was found. Muscle \- Muscular hypertrophy, esp. calf muscles 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	HYPERTROPHIA MUSCULORUM VERA	c1840361	8,347	omim	https://www.omim.org/entry/145800	2019-09-22T16:39:46	{"mesh": ["C564152"], "omim": ["145800"]}
Degloving A Morel-Lavallée lesion is a closed traumatic soft-tissue degloving injury, caused by separation of the hypodermis from the underlying fascia.[1] It most frequently occurs in the peritrochanteric region along the proximal lateral thigh,[1] such as in this CT scan. A degloving injury is a type of avulsion in which an extensive section of skin is completely torn off the underlying tissue, severing its blood supply. It is named by analogy to the process of removing a glove. ## Contents * 1 Effects * 2 Other animals * 3 References * 4 External links ## Effects[edit] Typically, degloving injuries affect the extremities and limbs; in these cases, they are frequently associated with underlying fractures. [2] Any injury which would induce degloving of the head or torso is likely to be lethal. However, controlled facial degloving is often featured in plastic surgery. Degloving injuries invariably require major surgical interventions. Treatment options include replantation or revascularization of the degloved skins, or when these are not possible, skin grafts or skin flaps. While the preservation of the extremities and limbs is normally preferred, in some cases amputations may be advised or required. Post-operative physiotherapy is of particular importance for degloving injuries involving the hand.[3] ## Other animals[edit] Many small mammals are able to induce degloving of their tails to escape capture;[4] this is comparable to tail autotomy in reptiles. ## References[edit] 1. ^ a b Scolaro, John A.; Chao, Tom; Zamorano, David P. (2016). "The Morel-Lavallée Lesion". Journal of the American Academy of Orthopaedic Surgeons. 24 (10): 667–672. doi:10.5435/JAAOS-D-15-00181. ISSN 1067-151X. PMID 27579812. 2. ^ Lekuya, HM; Galukande, M (January 2018). "Degloving injuries with versus without underlying fracture in a sub-Saharan African tertiary hospital: a prospective observational study". Journal of Orthopaedic Surgery and Research. 13 (2): 2. doi:10.1186/s13018-017-0706-9. PMC 5756448. PMID 29304820. 3. ^ Krishnamoorthy, R; Karthikeyan, G (May–August 2011). "Degloving injuries of the hand". Indian Journal of Plastic Surgery. 44 (2): 227–236. doi:10.4103/0970-0358.85344. PMC 3193635. PMID 22022033. 4. ^ "Guide to treatment of degloving injuries in pet rats". Ratguide.com. Retrieved 2018-03-02. ## External links[edit] * Report on degloving injuries in children * v * t * e Trauma Principles * Polytrauma * Major trauma * Traumatology * Triage * Resuscitation * Trauma triad of death Assessment Clinical prediction rules * Revised Trauma Score * Injury Severity Score * Abbreviated Injury Scale * NACA score Investigations * Diagnostic peritoneal lavage * Focused assessment with sonography for trauma Management Principles * Advanced trauma life support * Trauma surgery * Trauma center * Trauma team * Damage control surgery * Early appropriate care Procedures * Resuscitative thoracotomy Pathophysiology Injury * MSK * Bone fracture * Joint dislocation * Degloving * Soft tissue injury * Resp * Flail chest * Pneumothorax * Hemothorax * Diaphragmatic rupture * Pulmonary contusion * Cardio * Internal bleeding * Thoracic aorta injury * Cardiac tamponade * GI * Blunt kidney trauma * Ruptured spleen * Neuro * Penetrating head injury * Traumatic brain injury * Intracranial hemorrhage Mechanism * Blast injury * Blunt trauma * Burn * Penetrating trauma * Crush injury * Stab wound * Ballistic trauma * Electrocution Region * Abdominal trauma * Chest trauma * Facial trauma * Head injury * Spinal cord injury Demographic * Geriatric trauma * Pediatric trauma Complications * Posttraumatic stress disorder * Wound healing * Acute lung injury * Crush syndrome * Rhabdomyolysis * Compartment syndrome * Contracture * Volkmann's contracture * Embolism * air * fat * Chronic traumatic encephalopathy * Subcutaneous emphysema This article related to pathology 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	Degloving	c0433122	8,348	wikipedia	https://en.wikipedia.org/wiki/Degloving	2021-01-18T19:03:11	{"mesh": ["D000069836"], "umls": ["C0433122"], "wikidata": ["Q786854"]}
Variant Creutzfeldt-Jakob disease (vCJD) is a type of Creutzfeldt-Jakob disease (CJD) characterized by early psychiatric symptoms and cognitive decline. All forms of CJD belong to a rare family of progressive neurodegenerative disorders that affect both humans and animals, called prion diseases. The term "prion" refers to abnormal proteins within the brain, called prion proteins. vCJD, described primarily in the United Kingdom and France, accounts for less than 1% of cases of CJD, and tends to affect younger people. It can result when someone is exposed to contaminated products. The infection responsible for the disease in cows (bovine spongiform encephalitis) is believed to be the same one responsible for vCJD in humans. Another variant, called the panencephalopathic form, occurs primarily in Japan and has a relatively long course, with symptoms often progressing for several years. Scientists are trying to gain a better understanding about what causes these variations in the symptoms and course of the disease.There is no specific treatment for CJD or vCJD, so the goal is to make a person as comfortable as possible. [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	Variant Creutzfeldt-Jakob disease	c0376329	8,349	gard	https://rarediseases.info.nih.gov/diseases/9550/variant-creutzfeldt-jakob-disease	2021-01-18T17:57:11	{"mesh": ["D007562"], "umls": ["C0376329"], "synonyms": ["Variant Creutzfeldt-Jacob disease", "VCJD", "Variant CJD", "New variant of CJD", "Nv-CJD"]}
A rare disorder of plasmalogen biosynthesis characterized by syndromic severe intellectual disability with congenital cataracts, early-onset epilepsy, microcephaly, global developmental delay, growth retardation and short stature, and spastic quadriparesis. Dysmorphic facial features may be present, including high-arched eyebrows, flattened nasal root, hypertelorism, and long and smooth philtrum. Rhizomelia is not part of the syndrome. Cerebellar atrophy, white matter abnormalities, and Dandy-Walker malformation have been described on brain imaging. [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	Fatty acyl-CoA reductase 1 deficiency	c4015344	8,350	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=438178	2021-01-23T18:39:16	{"omim": ["616154"], "icd-10": ["E71.3"], "synonyms": ["FAR1 deficiency", "PFCRD", "Peroxisomal fatty acyl-CoA reductase 1 disorder"]}
Pacman dysplasia Other namesEpiphyseal stippling with osteoclastic hyperplasia Pacman dysplasia is inherited in an autosomal recessive manner Pacman dysplasia is a lethal autosomal recessive skeletal dysplasia. The dysplasia is present during fetal development.[1] ## References[edit] 1. ^ http://www.omim.org/entry/167220 * Wilcox WR, Wenger DA, Lachman RS, Rimoin DL (2005). "Distinguishing Pacman dysplasia from mucolipidosis II: comment on Saul et al. [2005]". Am J Med Genet A. 135 (3): 333. doi:10.1002/ajmg.a.30717. PMID 15887286. * Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J (2005). "Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia". Am J Med Genet A. 135 (3): 328–32. doi:10.1002/ajmg.a.30716. PMID 15887289. * Wilcox WR, Lucas BC, Loebel B, Bachman RP, Lachman RS, Rimoin DL (1998). "Pacman dysplasia: report of two affected sibs". Am J Med Genet. 77 (4): 272–6. doi:10.1002/(SICI)1096-8628(19980526)77:4<272::AID-AJMG4>3.0.CO;2-P. PMID 9600734. * Shohat M, Rimoin DL, Gruber HE, Lachman R (1993). "New epiphyseal stippling syndrome with osteoclastic hyperplasia". Am J Med Genet. 45 (5): 558–61. doi:10.1002/ajmg.1320450506. PMID 8456823. * Miller SF, Proud VK, Werner AL, Field FM, Wilcox WF, Lachman RS, Rimoin DL (2003). "Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features". Pediatr Radiol. 33 (4): 256–60. doi:10.1007/s00247-002-0859-4. PMID 12709756. ## External links[edit] Classification D * ICD-10: Q77.8 * OMIM: 167220 * MeSH: C538095 * SNOMED CT: 722127006 External resources * Orphanet: 1952 * Online Mendelian Inheritance in Man (OMIM): 167220 This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a disease of musculoskeletal and connective tissue 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	Pacman dysplasia	c1833676	8,351	wikipedia	https://en.wikipedia.org/wiki/Pacman_dysplasia	2021-01-18T19:04:12	{"gard": ["4189"], "mesh": ["C538095"], "umls": ["C1833676"], "orphanet": ["1952"], "wikidata": ["Q7123066"]}
Manganese poisoning Manganism SpecialtyOccupational medicine Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese.[1] It was first identified in 1837 by James Couper.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] Chronic exposure to excessive manganese levels can lead to a variety of psychiatric and motor disturbances, termed manganism. Generally, exposure to ambient manganese air concentrations in excess of 5 micrograms Mn/m3 can lead to Mn-induced symptoms.[3] In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.[4] Upon protracted exposure symptoms are more prominent and resemble those of idiopathic Parkinson's disease, as which it is often misdiagnosed, although there are particular differences in both the symptoms; for example, the nature of the tremors, response to drugs such as levodopa, and affected portion of the basal ganglia. Symptoms are also similar to Lou Gehrig's disease and multiple sclerosis. ## Causes[edit] Manganism has become an active issue in workplace safety as it has been the subject of numerous product liability lawsuits against manufacturers of arc welding supplies. In these lawsuits, welders have accused the manufacturers of failing to provide adequate warning that their products could cause welding fumes to contain dangerously high manganese concentrations that could lead welders to develop manganism. Companies employing welders are also being sued, for what colloquially is known as "welders' disease." However, studies fail to show any link between employment as a welder and manganism (or other neurological problems).[5][6][7] Manganism is also documented in reports of illicit methcathinone manufacturing.[8] This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser.[9] Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.[10] Reports also mention such sources as contaminated drinking water,[11] and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT),[12] which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust,[13][14][15] and manganese ethylene-bis-dithiocarbamate (Maneb), a pesticide.[16] ## Pathophysiology[edit] Manganese may affect liver function, but the threshold of acute toxicity is very high. On the other hand, more than 95 percent of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma.[17] The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron,[18][19][20][21] zinc,[22] aluminum,[18][22] and copper.[22] Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.[23] It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders.[24] A study of the exposed workers showed that they have significantly fewer children.[25] This may indicate that long-term accumulation of manganese affects fertility. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls.[26] It is found in large quantities in paint and steelmaking. ## Diagnosis[edit] This section is empty. You can help by adding to it. (October 2017) ## Treatment[edit] The current mainstay of manganism treatment is levodopa and chelation with EDTA. Both have limited and at best transient efficacy. Replenishing the deficit of dopamine with levodopa has been shown to initially improve extrapyramidal symptoms,[27][28][29] but the response to treatment goes down after 2 or 3 years,[30] with worsening condition of the same patients noted even after 10 years since last exposure to manganese.[31] Enhanced excretion of manganese prompted by chelation therapy brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.[32][33] Increased ferroportin protein expression in human embryonic kidney (HEK293) cells is associated with decreased intracellular manganese concentration and attenuated cytotoxicity, characterized by the reversal of Mn-reduced glutamate uptake and diminished lactate dehydrogenase (LDH) leakage.[3] ## Epidemiology[edit] The Red River Delta near Hanoi has high levels of manganese or arsenic in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium, and barium.[34] ## References[edit] 1. ^ Silva Avila, Daiana; Luiz Puntel, Robson; Aschner, Michael (2013). "Chapter 7. Manganese in Health and Disease". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (ed.). Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. 13. Springer. pp. 199–227. doi:10.1007/978-94-007-7500-8_7. PMC 6589086. PMID 24470093. 2. ^ Couper, J. (1837). "Sur les effets du peroxide de manganèse". Journal de chimie médicale, de pharmacie et de toxicologie. 3: 223–5. 3. ^ a b Yin, Zhaobao; Jiang, Haiyan; Lee, Eun-Sook Y.; Ni, Mingwei; Erikson, Keith M.; Milatovic, Dejan; Bowman, Aaron B.; Aschner, Michael (2010). "Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation" (PDF). Journal of Neurochemistry. 112 (5): 1190–8. doi:10.1111/j.1471-4159.2009.06534.x. PMC 2819584. PMID 20002294. 4. ^ Roth JA (2006). "Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination". Biol. Res. 39 (1): 45–57. doi:10.4067/S0716-97602006000100006. PMID 16629164. 5. ^ Fryzek JP, Hansen J, Cohen S, Bonde JP, Llambias MT, Kolstad HA, Skytthe A, Lipworth L, Blot WJ, Olsen JH (May 2005). "A cohort study of Parkinson's disease and other neurodegenerative disorders in Danish welders" (PDF). Journal of Occupational and Environmental Medicine. 47 (5): 466–72. doi:10.1097/01.jom.0000161730.25913.bf. PMID 15891525. 6. ^ Fored, C M; Fryzek, JP; Brandt, L; Nise, G; Sjögren, B; McLaughlin, JK; Blot, WJ; Ekbom, A (2006). "Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders". Occupational and Environmental Medicine. 63 (2): 135–40. doi:10.1136/oem.2005.022921. PMC 2078076. PMID 16421393. 7. ^ Marsh GM, Gula MJ (October 2006). "Employment as a welder and Parkinson disease among heavy equipment manufacturing workers". Journal of Occupational and Environmental Medicine. 48 (10): 1031–46. doi:10.1097/01.jom.0000232547.74802.d8. 8. ^ de Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE (June 2007). "Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse". Arch. Neurol. 64 (6): 886–9. doi:10.1001/archneur.64.6.886. PMID 17562938. Archived from the original on 2010-08-07. 9. ^ Sanotsky, Y., Lesyk, R., Fedoryshyn, L., Komnatska, I., Matviyenko, Y. and Fahn, S. (June 2007). "Manganic encephalopathy due to "ephedrone" abuse". Movement Disorders. 22 (9): 1337–1343. doi:10.1002/mds.21378. PMID 17566121.CS1 maint: multiple names: authors list (link) 10. ^ Ensing, J. G. (1985). "Bazooka: Cocaine-Base and Manganese Carbonate". Journal of Analytical Toxicology. 9 (1): 45–46. doi:10.1093/jat/9.1.45. PMID 3981975. 11. ^ Kondakis, Xenophon G.; Makris, Nicolas; Leotsinidis, Michael; Prinou, Mary; Papapetropoulos, Theodore (1989). "Possible Health Effects of High Manganese Concentration in Drinking Water". Archives of Environmental Health. 44 (3): 175–178. doi:10.1080/00039896.1989.9935883. PMID 2751354. 12. ^ Hudnell, HK (1999). "Effects from environmental manganese exposures: A review of the evidence from non-occupational exposure studies". Neurotoxicology. 20 (2–3): 379–397. PMID 10385898. 13. ^ Lynam, DR; Roos, JW; Pfeifer, GD; Fort, BF; Pullin, TG (1999). "Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline". Neurotoxicology. 20 (2–3): 145–150. PMID 10385878. 14. ^ Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AR, 1997. 15. ^ Lynam, D.R.; Pfeifer, G.D.; Fort, B.F.; Gelbcke, A.A. (1990). "Environmental assessment of MMT™ fuel additive". Science of the Total Environment. 93: 107–114. Bibcode:1990ScTEn..93..107L. doi:10.1016/0048-9697(90)90098-F. PMID 2113712. 16. ^ Ferraz, H. B.; f. Bertolucci, P. H.; Pereira, J. S.; Lima, J.G.C.; f. Andrade, L. A. (1988). "Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication". Neurology. 38 (4): 550–553. doi:10.1212/WNL.38.4.550. PMID 3352909. 17. ^ Ballatori, N. (2000). "12. Molecular mechanisms of hepatic metal transport". In Zalups, R.K.; Koropatnick, J. (eds.). Molecular Biology and Toxicology of Metals. Taylor & Francis. pp. 346–381. ISBN 0748407987. 18. ^ a b Verity, MA (1999). "Manganese neurotoxicity: A mechanistic hypothesis". Neurotoxicology. 20 (2–3): 489–497. PMID 10385907. 19. ^ Zheng, Wei; Zhao, Qiuqu (2001). "Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells". Brain Research. 897 (1–2): 175–9. doi:10.1016/S0006-8993(01)02049-2. PMC 3980869. PMID 11282372. 20. ^ Zheng, Wei; Zhao, Qiuqu; Slavkovich, Vesna; Aschner, Michael; Graziano, Joseph H (1999). "Alteration of iron homeostasis following chronic exposure to manganese in rats". Brain Research. 833 (1): 125–132. doi:10.1016/S0006-8993(99)01558-9. PMC 4126166. PMID 10375687. 21. ^ Zheng, Wei (2001). "Neurotoxicology of the Brain Barrier System: New Implications" (PDF). Clinical Toxicology. 39 (7): 711–719. doi:10.1081/CLT-100108512. PMC 4111935. PMID 11778669. 22. ^ a b c Lai, JC; Minski, MJ; Chan, AW; Leung, TK; Lim, L (1999). "Manganese mineral interactions in brain". Neurotoxicology. 20 (2–3): 433–444. PMID 10385902. 23. ^ Zheng, Wei; Ren, Sean; Graziano, Joseph H. (1998). "Manganese inhibits mitochondrial aconitase: A mechanism of manganese neurotoxicity". Brain Research. 799 (2): 334–342. doi:10.1016/S0006-8993(98)00481-8. PMC 4126159. PMID 9675333. 24. ^ Li G, Zhang L, Lu L, Wu P, Zheng W (2004). "Occupational exposure to welding fume among welders: alterations of manganese, iron, zinc, copper, and lead in body fluids and the oxidative stress status". J. Occup. Environ. Med. 46 (3): 241–8. PMC 4126160. PMID 15091287. 25. ^ Lauwerys, Robert (1985). "Fertility of male workers exposed to mercury vapor or to manganese dust: A questionnaire study". American Journal of Industrial Medicine. 7 (2): 171–176. doi:10.1002/ajim.4700070208. PMID 3976664. 26. ^ Treinen, Kimberley A.; Gray, Tim J. B.; Blazak, William F. (1995). "Developmental toxicity of mangafodipir trisodium and manganese chloride in Sprague-Dawley rats". Teratology. 52 (2): 109–115. doi:10.1002/tera.1420520207. PMID 8588182. 27. ^ Lee, J.-W. (2000). "Manganese Intoxication". Archives of Neurology. 57 (4): 597–599. doi:10.1001/archneur.57.4.597. PMID 10768639. 28. ^ Mena I, Court J, Fuenzalida S, Papavasiliou PS, Cotzias GC (1970). "Modification of chronic manganese poisoning. Treatment with L-dopa or 5-OH tryptophane". N Engl J Med. 282 (1): 5–10. doi:10.1056/NEJM197001012820102. PMID 5307796. 29. ^ Rosenstock HA, Simons DG, Meyer JS (1971). "Chronic manganism. Neurologic and laboratory studies during treatment with levodopa". JAMA. 217 (10): 1354–8. doi:10.1001/jama.217.10.1354. PMID 4998860. 30. ^ Huang, C.-C.; Lu, C.-S.; Chu, N.-S.; Hochberg, F.; Lilienfeld, D.; Olanow, W.; Calne, D. B. (1993). "Progression after chronic manganese exposure". Neurology. 43 (8): 1479–83. doi:10.1212/WNL.43.8.1479. PMID 8351000. 31. ^ Huang, C.-C.; Chu, N.-S.; Lu, C.-S.; Chen, R.-S.; Calne, D. B. (1998). "Long-term progression in chronic manganism: Ten years of follow-up". Neurology. 50 (3): 698–700. doi:10.1212/WNL.50.3.698. PMID 9521259. 32. ^ Ono, Kenjiro; Komai, Kiyonobu; Yamada, Masahito (2002). "Myoclonic involuntary movement associated with chronic manganese poisoning". Journal of the Neurological Sciences. 199 (1–2): 93–96. doi:10.1016/S0022-510X(02)00111-9. PMID 12084450. 33. ^ Calne, DB; Chu, NS; Huang, CC; Lu, CS; Olanow, W (1994). "Manganism and idiopathic parkinsonism: Similarities and differences". Neurology. 44 (9): 1583–1586. doi:10.1212/WNL.44.9.1583. PMID 7936278. 34. ^ "Groundwater Pollution Red River Delta/Vietnam". Eawag — Swiss Federal Institute of Aquatic Science and Technology. 2011. Winkel LH, Pham TK, Vi ML, Stengel C, Amini M, Nguyen TH, Pham HV, Berg M (2011). "Arsenic pollution of groundwater in Vietnam exacerbated by deep aquifer exploitation for more than a century". Proc Natl Acad Sci U S A. 108 (4): 1246–51. doi:10.1073/pnas.1011915108. PMC 3029707. PMID 21245347. ## Further reading[edit] * Lucchini et al., "Metals and Neurodegeneration" — Research paper on heavy metals poisoning * Antonini, James M. (2003). "Health Effects of Welding". Critical Reviews in Toxicology. 33 (1): 61–103. doi:10.1080/713611032. PMID 12585507. — Critical review including manganese discussion from National Institute for Occupational Safety and Health (NIOSH) * "Welding and Manganese Poisoning". Safety Corner. IBEW Journal. July–August 2003. p. 8. * AWS Study on Welding and Exposure to Manganese — Report of an independent study commissioned by the American Welding Society * Welding Fume Product Liability — Viewpoint of plaintiffs on welding rod litigation * Welding Rod Litigation Information Network — Viewpoint of defense on welding rod litigation ## External links[edit] Classification D * ICD-10: T57.2 * ICD-9-CM: 985.2 * MeSH: D020149 * SNOMED CT: 88687001 * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [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	Manganism	c0677050	8,352	wikipedia	https://en.wikipedia.org/wiki/Manganism	2021-01-18T18:39:50	{"mesh": ["D020149"], "umls": ["C0677050"], "icd-9": ["985.2"], "icd-10": ["T57.2"], "orphanet": ["306682"], "wikidata": ["Q2480013"]}
A number sign (#) is used with this entry because of evidence that central precocious puberty-2 (CPPB2) is caused by heterozygous mutation on the paternal allele of the MKRN3 gene (603856) on chromosome 15q11. Description Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The timing of puberty is associated with risks of subsequent disease: earlier age of menarche in girls is associated with increased risk of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Central precocious puberty has also been associated with an increased incidence of conduct and behavior disorders during adolescence (summary by Abreu et al., 2013). For discussion of genetic heterogeneity of central precocious puberty, see CPPB1 (176400). Clinical Features Abreu et al. (2013) studied 15 patients, 8 female and 7 male, from 5 families with central precocious puberty associated with mutation in the MKRN3 gene (see MOLECULAR GENETICS). Each of the patients had clinical and hormonal features typical of premature activation of the reproductive axis, including early pubertal signs such as breast development or testicular enlargement, pubic hair, advanced linear growth and bone age, and elevated basal luteinizing hormone (LH; see 152780) levels, elevated GnRH (152760)-stimulated LH levels, or both. The median age at onset of puberty in the girls was 5.75 years, ranging from 5.0 to 6.5 years, whereas in the boys it was 8.1 years, ranging from 5.9 to 8.5 years. All patients had normal MRI of the central nervous system. Molecular Genetics Abreu et al. (2013) performed whole-exome sequencing in 40 members of 15 families with central precocious puberty and identified heterozygosity for 3 frameshift mutations and 1 missense mutation in the MKRN3 gene (603856.0001-603856.0004) in affected individuals from 5 of the families. Sanger sequencing confirmed the mutations, and there was complete cosegregation with the phenotype in each of the families. All affected family members inherited their mutations from their fathers, consistent with a paternally expressed imprinted gene; the 1 heterozygous carrier known to have inherited his mutation from his mother was unaffected. INHERITANCE \- Autosomal dominant CHEST Breasts \- Premature thelarche GENITOURINARY External Genitalia (Male) \- Premature increase in testicular volume \- Premature increase in penile length Internal Genitalia (Female) \- Premature increase in uterine length SKELETAL \- Advanced bone age SKIN, NAILS, & HAIR Hair \- Premature pubic hair maturation ENDOCRINE FEATURES \- Premature pubertal basal levels of luteinizing hormone (LH) \- Premature pubertal stimulated levels of LH \- Elevated prepubertal levels of testosterone \- Elevated prepubertal levels of estradiol MISCELLANEOUS \- Median age at onset of puberty is 5.75 years in affected girls and 8.1 years in affected boys MOLECULAR BASIS \- Caused by mutation in the makorin-3 gene (MKRN3, 603856.0001 ) ▲ 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	PRECOCIOUS PUBERTY, CENTRAL, 2	c0342543	8,353	omim	https://www.omim.org/entry/615346	2019-09-22T15:52:29	{"mesh": ["D011629"], "omim": ["615346"], "orphanet": ["759"]}
Benign hyperplasia of fibrous connective tissue Epulis fissuratum Other namesInflammatory fibrous hyperplasia,[1] Denture-induced fibrous inflammatory hyperplasia,[2] Denture injury tumor,[1] Denture epulis,[1] Denture induced granuloma,[3] and Granuloma fissuratum[4]:808) Epulis fissuratum is a benign hyperplasia of fibrous connective tissue which develops as a reactive lesion to chronic mechanical irritation produced by the flange of a poorly fitting denture.[1] More simply, epulis fissuratum is where excess folds of firm tissue form inside the mouth, as a result of rubbing on the edge of dentures that do not fit well. It is a harmless condition and does not represent oral cancer. Treatment is by simple surgical removal of the lesion, and also by adjustment of the denture or provision of a new denture. It is a closely related condition to inflammatory papillary hyperplasia, but the appearance and location differs.[5] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] The lesion is usually painless.[6] The usual appearance is of two excess tissue folds in alveolar vestibule/buccal sulcus, with the flange of the denture fitting in between the two folds.[1] It may occur in either the maxillary or mandibular sulci,[1] although the latter is more usual.[6] Anterior locations are more common than posterior.[6] Less commonly there may be a single fold, and the lesion may appear on the lingual surface of the mandibular alveolar ridge.[1] The swelling is firm and fibrous, with a smooth, pink surface.[1][6] The surface may also show ulceration or erythema.[1] The size of the lesion varies from less than 1 cm to involving the entire length of the sulcus.[1] ## Causes[edit] Fibrous hyperplasia around a dental implant, caused by a broken denture clasp.[7] The cause is usually pressure from the flange of a denture which causes chronic irritation and a hyperplastic response in the soft tissues.[6] Women during pregnancy can also present with an epulis, which will resolve after birth. Fibroepithelial polyps, pedunculated lesions of the palate beneath an upper denture, are associated with this condition. A cobble-stone appearance similar to an epulis fissuratum in a patient without dentures can be diagnostic of Crohn's disease.[8] Epulis fissuratum can also appear around dental implants. ## Diagnosis[edit] The diagnosis is made clinically, and usually this is clear cut if the lesion is associated with the flange of a complete denture.[6] Tissue biopsy is not usually indicated before removal of the lesion, since the excises surgical specimen is usually sent for histopathologic examination and the diagnosis is confirmed retrospectively. Rarely, incisional biopsy may be indicated to rule out neoplasia, e.g. in the presence of suspicious ulceration. The appearance may also be confused with pyogenic granuloma.[1] The excessive tissue is composed of cellular, inflamed fibrous connective tissue. The appearance of an epulis fissuratum microscopically is an overgrowth of cells from the fibrous connective tissue. The epithelial cells are usually hyperkeratotic and irregular, hyperplastic rete ridges are often seen. ### Classification[edit] Epulis (literally, 'on the gingiva') is a general term for any gingival or alveolar tumor (i.e. lump on the gum).[1] This term describes only the location of a lump and has no implication on the histologic appearance of a lesion.[3] Epulis is also sometimes used synonymously with epulis fissuratum,[1] however other conditions are classified as epulides, e.g. giant cell epulis (peripheral giant cell granuloma), ossifying fibroid epulis (peripheral ossifying fibroma), and congenital epulis.[1] ## Treatment[edit] Treatment is by surgical excision (complete removal) of the fibrous tissue overgrowth and addressing the causative factor to prevent recurrence of the lesion.[1][9] Other sources suggest that surgical excision may not be required in all cases.[2] Common techniques for removal of the excess tissue include traditional removal with a surgical scalpel, electrical scalpel, or laser excision with a laser scalpel, e.g. a carbon dioxide laser, erbium:YAG laser, Neodymium-YAG laser, or diode laser.[9] The poorly fitting denture can be adapted to fit better (a "reline") or a new denture constructed.[1][9] Alternatively, the section of flange that is sharp/over-extended can be smoothed and reduced with a drill.[6] ## Prognosis[edit] If the causative factor persists, tissue will become more fibrous over time.[9] ## Epidemiology[edit] This condition occurs in association with denture wearing, and so those affected tend to be middle aged or older adults. 66-75% are estimated to occur in women.[1] Epulis fissuratum is the third most common reactive lesion that occurs in the mouth, after peripheral giant cell granuloma and pyogenic granuloma.[10] ## References[edit] * Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. 1. ^ a b c d e f g h i j k l m n o p q Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2. ed.). Philadelphia: W.B. Saunders. pp. 440–442. ISBN 978-0721690032. 2. ^ a b Thomas, GA (1993). "Denture-induced fibrous inflammatory hyperplasia (epulis fissuratum): research aspects". Australian Prosthodontic Journal. 7: 49–53. PMID 8695194. 3. ^ a b Cawson RA, Odell EW (2002). Cawson's essentials of oral pathology and oral medicine (7. ed.). Edinburgh: Churchill Livingstone. pp. 275–276. ISBN 978-0443071065. 4. ^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 5. ^ Barnes L (2009). Surgical pathology of the head and neck, vol. 1 (3rd ed.). New York: Informa Healthcare. pp. 220–221. ISBN 978-0849390234. 6. ^ a b c d e f g Scully C (2008). Oral and maxillofacial medicine : the basis of diagnosis and treatment (2nd ed.). Edinburgh: Churchill Livingstone. p. 352. ISBN 9780443068188. 7. ^ Dorfman J, The Center for Special Dentistry. http://www.nycdentist.com/dental-photo-detail/2446/215/Oral-Pathology-Dental-Medicine-diagnosis-treatment-cyst 8. ^ Laskaris, George (2003). Colour Atlas of Oral Diseases. Thieme. p. 216. ISBN 9781588901385. 9. ^ a b c d de Arruda Paes-Junior, Tarcisio José; Cavalcanti, Sâmia Carolina Mota; Nascimento, D. F.; Saavedra Gde, S.; Kimpara, E. T.; Borges, A. L.; Niccoli-Filho, W.; Komori, P. C. (1 January 2011). "CO2 Laser Surgery and Prosthetic Management for the Treatment of Epulis Fissuratum". ISRN Dentistry. 2011: 282361. doi:10.5402/2011/282361. PMC 3170081. PMID 21991461. 10. ^ Naderi, NJ; Eshghyar, N; Esfehanian, H (May 2012). "Reactive lesions of the oral cavity: A retrospective study on 2068 cases". Dental Research Journal. 9 (3): 251–5. PMC 3469888. PMID 23087727. ## External links[edit] Classification D * DiseasesDB: 32595 External resources * eMedicine: article/1077440 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [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	Epulis fissuratum	c0399495	8,354	wikipedia	https://en.wikipedia.org/wiki/Epulis_fissuratum	2021-01-18T18:43:14	{"umls": ["C0399495"], "wikidata": ["Q5384044"]}
Prevalence of HIV/AIDS in Africa, total (% of population ages 15–49), in 2011 (World Bank) over 15% 5-15% 2-5% 1-2% 0.5-1% 0.1-0.5% not available HIV/AIDS originated in Africa in the early 20th century and is a major public health concern and cause of death in many African countries. AIDS rates vary dramatically although the majority of cases are concentrated in Southern Africa. Although the continent is home to about 15.2 percent of the world's population,[1] more than two-thirds of the total infected worldwide – some 35 million people – were Africans, of whom 15 million have already died.[2] Sub-Saharan Africa alone accounted for an estimated 69 percent of all people living with HIV[3] and 70 percent of all AIDS deaths in 2011.[4] In the countries of sub-Saharan Africa most affected, AIDS has raised death rates and lowered life expectancy among adults between the ages of 20 and 49 by about twenty years.[2] Furthermore, the life expectancy in many parts of Africa is declining, largely as a result of the HIV/AIDS epidemic with life-expectancy in some countries reaching as low as thirty-four years.[5] Countries in North Africa and the Horn of Africa have significantly lower prevalence rates, as their populations typically engage in fewer high-risk cultural patterns that promote the virus' spread in Sub-Saharan Africa.[6][7] Southern Africa is the worst affected region on the continent. As of 2011, HIV has infected at least 10 percent of the population in Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Eswatini, Zambia, and Zimbabwe.[8] In response, a number of initiatives have been launched in various parts of the continent to educate the public on HIV/AIDS. Among these are combination prevention programmes, considered to be the most effective initiative, such as the abstinence, be faithful, use a condom campaign and the Desmond Tutu HIV Foundation's outreach programs.[9] The number of HIV positive people in Africa receiving anti-retroviral treatment in 2012 was over seven times the number receiving treatment in 2005, with nearly 1 million added in the previous year.[10][11]:15 The number of AIDS-related deaths in Sub-Saharan Africa in 2011 was 33 percent less than the number in 2005.[12] The number of new HIV infections in Sub-Saharan Africa in 2011 was 25 percent less than the number in 2001.[12] ## Contents * 1 Overview * 2 Origins of HIV/AIDS in Africa * 3 History * 4 Prevention of HIV infections * 4.1 Public education initiatives * 4.2 The role of stigma * 4.2.1 Combination prevention programmes * 4.2.2 Abstinence, be faithful, use a condom * 4.2.3 Prevention efforts * 4.3 African Union's efforts * 4.3.1 AIDS Watch Africa * 4.3.2 Roadmap on Shared Responsibility and Global Solidarity for AIDS, TB and Malaria Response in Africa * 4.4 Preventing HIV transmission from pregnant women to children * 5 Causes and spread * 5.1 Behavioral factors * 5.2 Health industry * 5.3 Medical factors * 5.3.1 Circumcision * 5.3.2 Medical suspicion * 5.4 Pharmaceutical industry * 5.5 Political factors * 5.6 Subtype factor * 5.7 Religious factors * 6 Health Care delivery * 7 Measurement * 8 Regional prevalence * 8.1 North Africa * 8.2 Horn of Africa * 8.3 Central Africa * 8.4 Eastern Africa * 8.4.1 Kenya * 8.4.2 Tanzania * 8.4.3 Uganda * 8.5 Western Africa * 8.6 Southern Africa * 8.6.1 Eswatini * 9 Tuberculosis coinfections * 10 See also * 11 Notes * 12 References * 13 Further reading * 14 External links ## Overview[edit] In a 2019 research article titled "The Impact of HIV & AIDS in Africa", the charitable organization AVERT wrote: > HIV ... has caused immense human suffering in the continent. The most obvious effect ... has been illness and death, but the impact ... has ... not been confined to the health sector; households, schools, workplaces and economies have also been badly affected. ... > > > > In sub-Saharan Africa, people with HIV-related diseases occupy more than half of all hospital beds. ... [L]arge numbers of healthcare professionals are being directly affected.... Botswana, for example, lost 17% of its healthcare workforce due to AIDS between 1999 and 2005. > > ... > > The toll of HIV and AIDS on households can be very severe. ... [I]t is often the poorest sectors of society that are most vulnerable.... In many cases, ... AIDS causes the household to dissolve, as parents die and children are sent to relatives for care and upbringing. ... Much happens before this dissolution takes place: AIDS strips families of their assets and income earners, further impoverishing the poor. ... > > The ... epidemic adds to food insecurity in many areas, as agricultural work is neglected or abandoned due to household illness. ... > > Almost invariably, the burden of coping rests with women. Upon a family member becoming ill, the role of women as carers, income-earners and housekeepers is stepped up. They are often forced to step into roles outside their homes as well. ... > > Older people are also heavily affected by the epidemic; many have to care for their sick children and are often left to look after orphaned grandchildren. ... > > It is hard to overemphasise the trauma and hardship that children ... are forced to bear. ... As parents and family members become ill, children take on more responsibility to earn an income, produce food, and care for family members. ... [M]ore children have been orphaned by AIDS in Africa than anywhere else. Many children are now raised by their extended families and some are even left on their own in child-headed households. ... > > HIV and AIDS are having a devastating effect on the already inadequate supply of teachers in African countries.... The illness or death of teachers is especially devastating in rural areas where schools depend heavily on one or two teachers. ... [I]n Tanzania[,] for example[,] ... in 2006 it was estimated that around 45,000 additional teachers were needed to make up for those who had died or left work because of HIV.... > > AIDS damages businesses by squeezing productivity, adding costs, diverting productive resources, and depleting skills. ... Also, as the impact of the epidemic on households grows more severe, market demand for products and services can fall. ... > > In many countries of sub-Saharan Africa, AIDS is erasing decades of progress in extending life expectancy. ... The biggest increase in deaths ... has been among adults aged between 20 and 49 years. This group now accounts for 60% of all deaths in sub-Saharan Africa.... AIDS is hitting adults in their most economically productive years and removing the very people who could be responding to the crisis. ... > > As access to treatment is slowly expanded throughout the continent, millions of lives are being extended and hope is being given to people who previously had none. Unfortunately though, the majority of people in need of treatment are still not receiving it, and campaigns to prevent new infections ... are lacking in many areas.[13] Regional comparisons of HIV in 2011 World region Adult HIV prevalence (ages 15–49)[12] Persons living with HIV[12] AIDS deaths, annual[12] New HIV infections, annual[3] Worldwide 0.8% 34,000,000 1,700,000 2,500,000 Sub-Saharan Africa 4.9% 23,500,000 1,200,000 1,800,000 South and Southeast Asia 0.3% 4,000,000 250,000 280,000 Eastern Europe and Central Asia 1.0% 1,400,000 92,000 140,000 East Asia 0.1% 830,000 59,000 89,000 Latin America 0.4% 1,400,000 54,000 83,000 Middle East and North Africa 0.2% 300,000 23,000 37,000 North America 0.6% 1,400,000 21,000 51,000 Caribbean 1.0% 230,000 10,000 13,000 Western and Central Europe 0.2% 900,000 7,000 30,000 Oceania 0.3% 53,000 1,300 2,900 ## Origins of HIV/AIDS in Africa[edit] Main article: Origin of AIDS Historical prevalence of HIV-1 subtypes (2002). The earliest known cases of human HIV infection were in western equatorial Africa, probably in southeast Cameroon where groups of the central common chimpanzee live. "Phylogenetic analyses ... revealed that all HIV-1 strains known to infect humans, including HIV-1 groups M, N, and O, were closely related to just one of these SIVcpz lineages: that found in P. t. troglodytes [Pan troglodytes troglodytes i.e. the central chimpanzee]." It is suspected that the disease jumped to humans from butchering of chimpanzees for human consumption.[14][15] Current hypotheses also include that, once the virus jumped from chimpanzees or other apes to humans, medical practices of the 20th century helped HIV become established in human populations by 1930.[16] The virus likely moved from primates to humans when hunters came into contact with the blood of infected primates. The hunters then became infected with HIV and passed on the disease to other humans through bodily fluid contamination. This theory is known as the "Bushmeat theory".[17] HIV made the leap from rural isolation to rapid urban transmission as a result of urbanization that occurred during the 20th century. There are many reasons for which there is such prevalence of AIDS in Africa. One of the most formative explanations is the poverty that dramatically impacts the daily lives of Africans. The book, Ethics and AIDS in Africa: A Challenge to Our Thinking, describes how "Poverty has accompanying side-effects, such as prostitution (i.e. the need to sell sex for survival), poor living conditions, education, health and health care, that are major contributing factors to the current spread of HIV/AIDS."[18] Researchers believe HIV was gradually spread by river travel. All the rivers in Cameroon run into the Sangha River, which joins the Congo River running past Kinshasa in the Democratic Republic of the Congo. Trade along the rivers could have spread the virus, which built up slowly in the human population. By the 1960s, about 2,000 people in Africa may have had HIV,[15] including people in Kinshasa whose tissue samples from 1959 and 1960 have been preserved and studied retrospectively.[19] The first epidemic of HIV/AIDS is believed to have occurred in Kinshasa in the 1970s, signalled by a surge in opportunistic infections such as cryptococcal meningitis, Kaposi's sarcoma, tuberculosis, and pneumonia.[20][21] ## History[edit] Acquired immunodeficiency syndrome (AIDS) is a fatal disease caused by the slow-acting human immunodeficiency virus (HIV). The virus multiplies in the body until it causes immune system damage, leading to diseases of the AIDS syndrome. HIV emerged in Africa in the 1960s and traveled to the United States and Europe the following decade. In the 1980s it spread across the globe until it became a pandemic. Some areas of the world were already significantly impacted by AIDS, while in others the epidemic was just beginning. The virus is transmitted by bodily fluid contact including the exchange of sexual fluids, by blood, from mother to child in the womb, and during delivery or breastfeeding. AIDS first was identified in the United States and France in 1981, principally among homosexual men. Then in 1982 and 1983, heterosexual Africans also were diagnosed.[2] In the late 1980s, international development agencies regarded AIDS control as a technical medical problem rather than one involving all areas of economic and social life. Because public health authorities perceived AIDS to be an urban phenomenon associated with prostitution, they believed that the majority of Africans who lived in "traditional" rural areas would be spared. They believed that the heterosexual epidemic could be contained by focusing prevention efforts on persuading the so-called core transmitters—people such as sex workers and truck drivers, known to have multiple sex partners—to use condoms. These factors retarded prevention campaigns in many countries for more than a decade.[2] Although many governments in Sub-saharan Africa denied that there was a problem for years, they have now begun to work toward solutions. AIDS was at first considered a disease of gay men and drug addicts, but in Africa it took off among the general population. As a result, those involved in the fight against HIV began to emphasize aspects such as preventing transmission from mother to child, or the relationship between HIV and poverty, inequality of the sexes, and so on, rather than emphasizing the need to prevent transmission by unsafe sexual practices or drug injection. This change in emphasis resulted in more funding, but was not effective in preventing a drastic rise in HIV prevalence.[22] The global response to HIV and AIDS has improved considerably in recent years. Funding comes from many sources, the largest of which are the Global Fund to Fight AIDS, Tuberculosis and Malaria and the President's Emergency Plan for AIDS Relief.[23] According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), the number of HIV positive people in Africa receiving anti-retroviral treatment rose from 1 million to 7.1 million between 2005 and 2012, an 805% increase. Almost 1 million of those patients were treated in 2012.[11] The number of HIV positive people in South Africa who received such treatment in 2011 was 75.2 percent higher than the number in 2009.[12] Additionally, the number of AIDS-related deaths in 2011 in both Africa as a whole and Sub-Saharan Africa alone was 32 percent less than the number in 2005.[11][12] The number of new HIV infections in Africa in 2011 was also 33 percent less than the number in 2001, with a "24% reduction in new infections among children from 2009 to 2011".[11] In Sub-Saharan Africa, new HIV positive cases over the same period declined by 25%.[12] According to UNAIDS, these successes have resulted from "strong leadership and shared responsibility in Africa and among the global community".[10] ## Prevention of HIV infections[edit] AIDS awareness sign in central Dar es Salaam, Tanzania. ### Public education initiatives[edit] Numerous public education initiatives have been launched to curb the spread of HIV in Africa. ### The role of stigma[edit] This section's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (April 2015) (Learn how and when to remove this template message) Many activists have drawn attention to stigmatization of those testing as HIV positive. This is due to many factors such as a lack of understanding of the disease, lack of access to treatment, the media, knowing that AIDS is incurable, and prejudices brought on by a cultures beliefs.[24] "When HIV/AIDS became a global disease, African leaders played ostrich and said that it was a gay disease found only in the West and Africans did not have to worry because there were no gays and lesbians in Africa".[25] Africans were blind to the already huge epidemic that was infesting their communities. The belief that only homosexuals could contract the diseases was later debunked as the number of heterosexual couples living with HIV increased. Unfortunately there were other rumors being spread by elders in Cameroon. These "elders speculated that HIV/AIDS was a sexually transmitted disease passed on from Fulani women only to non-Fulani men who had sexual contact with them. They also claimed if a man was infected as a result of having sexual contact with a Fulani woman, only a Fulani healer could treat him".[26] This communal belief is shared by many other African cultures who believe that HIV and AIDS originated from women. Because of this belief that men can only get HIV from women many "women are not free to speak of their HIV status to their partners for fear of violence".[24] In general HIV carries a negative stigma in Sub-Saharan Africa. Unfortunately This stigma makes it very challenging for Sub-Saharan Africans to share that they have HIV because they are afraid of being an outcast from their friends and family. In every Sub-Saharan community HIV is seen as the bringer of death. The common belief is that once you have HIV you are destined to die. People seclude themselves based on these beliefs. They don't tell their family and live with guilt and fear because of HIV. However, there is a way to treat HIV and AIDS the problem is that many are just not aware of how HIV is spread or what effects it has on the body. "80.8% of participants would not sleep in the same room as someone who was HIV positive, while 94.5% would not talk to someone who was HIV positive".[24] Social stigma plays a significant role in the state of HIV and AIDS infection in Africa. "In a normatively HIV/AIDS-stigmatizing Sub Saharan African communities, this suspicion of one's status by others is also applicable to individuals who are not HIV positive, but who may wish to utilize healthcare services for preventive purposes. This group of individuals under fear of suspicion may avoid being mistakingly identified as stigmatized by simply avoiding HARHS utilization." (151)[18] "At the individual level, persons living with HIV/AIDS in Sub-Saharan Africa likely want to conceal their stigmatized identities whenever possible in order to gain these rewards associated with having a 'normal' identity. The rewards of being considered normal' in the context of high-HIV-prevalence Sub-Saharan Africa are varied and great... such rewards for which there is empirical support in this context include perceived sexual freedom, avoidance of discrimination, avoidance of community or family rejection, avoidance of losing one's job or residence, and avoidance of losing one's sexual partners. Other potential rewards of being considered normal include avoidance of being associated with promiscuity or prostitution, avoidance of emotional, social and physical isolation and avoidance of being blamed for others' illness" (150).[18] #### Combination prevention programmes[edit] The Joint United Nations Programme on HIV/AIDS defines combination prevention programmes as: > rights-based, evidence-informed, and community-owned programmes that use a mix of biomedical, behavioural, and structural interventions, prioritised to meet the current HIV prevention needs of particular individuals and communities, so as to have the greatest sustained impact on reducing new infections. Well-designed ... programmes are carefully tailored to national and local needs and conditions; focus resources on the mix of programmatic and policy actions required to address both immediate risks and underlying vulnerability; and ... are thoughtfully planned and managed to operate synergistically and consistently on multiple levels (e.g. individual, relationship, community, society) and over an adequate period of time. ... Using different prevention strategies in combination is not a new idea. ... [C]ombination approaches have been used effectively to generate sharp, sustained reductions in new HIV infections in diverse settings. Combination prevention reflects common sense, yet it is striking how seldom the approach has been put into practice. ... Prevention efforts to date have overwhelmingly focused on reducing individual risk, with fewer efforts made to address societal factors that increase vulnerability to HIV. ... UNAIDS' combination prevention framework puts structural interventions—including programmes to promote human rights, to remove punitive laws that block the AIDS response, and to combat gender inequality and HIV related stigma and discrimination—at the centre of the HIV prevention agenda.[27] "It is the consensus in the HIV scientific community that abstinence, be faithful, use a condom [(ABC)] principles are vital guides for public health intervention, but are better bundled with biomedical prevention approaches; lone behavioral change approaches are not likely to stop the global pandemic."[28] Uganda has replaced its ABC strategy with a combination prevention programme because of an increase in the annual HIV infection rate. Most new infections were coming from people in long-term relationships who had multiple sexual partners.[29] #### Abstinence, be faithful, use a condom[edit] The abstinence, be faithful, use a condom (ABC) strategy to prevent HIV infection promotes safer sexual behavior and emphasizes the need for fidelity, fewer sexual partners, and a later age of sexual debut. The implementation of ABC differs among those who use it. For example, the President's Emergency Plan for AIDS Relief has focused more on abstinence and fidelity than condoms[30] while Uganda has had a more balanced approach to the three elements.[31] The effectiveness of ABC is controversial. At the 16th International AIDS Conference in 2006, African countries gave the strategy mixed reviews. In Botswana, > [M]uch of the ABC message was getting through, but ... it was not making much of a difference. ... A program called Total Community Mobilization sent 450 AIDS counselors door-to-door, giving prevention advice, urging HIV testing and referring infected people to treatment. ... People who had talked to the counselors were twice as likely to mention abstinence and three times as likely to mention condom use when asked to describe ways to avoid infection. However, they were no more likely than the uncounseled to mention being faithful as a good strategy. The people who had been counseled were also twice as likely to have been tested for HIV in the previous year, and to have discussed that possibility with a sex partner. However, they were just as likely to have a partner outside marriage as the people who had not gotten a visit from a counselor, and they were no more likely to be using a condom in those liaisons.[32] In Nigeria, > There was a somewhat different result in a study of young Nigerians, ages 15 to 24, most unmarried, living in the city and working in semiskilled jobs. People in specific neighborhoods were counseled with an ABC message as part of a seven-year project funded by the U.S. Agency for International Development and its British counterpart. ... The uncounseled group showed no increase in condom use—it stayed about 55 percent. In the counseled group, however, condom use by women in their last nonmarital sexual encounter rose from 54 percent to 69 percent. For men, it rose from 64 percent to 75 percent. Stigmatizing attitudes appeared to be less common among the counseled group. ... But ... "We did not see a reduction in the number of partners," said Godpower Omoregie, the researcher from Abuja who presented the findings.[32] In Kenya, > A survey of 1,400 Kenyan teenagers found a fair amount of confusion about ABC's messages. ... Half of the teenagers could correctly define abstinence and explain why it was important. Only 23 percent could explain what being faithful meant and why it was important. Some thought it meant being honest, and some thought it meant having faith in the fidelity of one's partner. Only 13 percent could correctly explain the importance of a condom in preventing HIV infection. About half spontaneously offered negative opinions about condoms, saying they were unreliable, immoral and, in some cases, were designed to let HIV be transmitted.[32] Eswatini in 2010 announced that it was abandoning the ABC strategy because it was a dismal failure in preventing the spread of HIV. "If you look at the increase of HIV in the country while we've been applying the ABC concept all these years, then it is evident that ABC is not the answer," said Dr. Derek von Wissell, Director of the National Emergency Response Council on HIV/AIDS.[33] #### Prevention efforts[edit] In 1999, the Henry J. Kaiser Family Foundation and the Bill and Melinda Gates Foundation provided major funding for the loveLife website, an online sexual health and relationship resource for teenagers.[34] In 2011, the Botswana Ministry of Education introduced new HIV/AIDS educational technology in local schools. The TeachAIDS prevention software, developed at Stanford University, was distributed to every primary, secondary, and tertiary educational institution in the country, reaching all learners from 6 to 24 years of age nationwide.[35] ### African Union's efforts[edit] #### AIDS Watch Africa[edit] During the Abuja African Union Summit on HIV/AIDS in April 2001, the heads of state and heads of government of Botswana, Ethiopia, Kenya, Mali, Nigeria, Rwanda, South Africa, and Uganda established the AIDS Watch Africa (AWA) advocacy platform. The initiative was formed to "accelerate efforts by Heads of State and Government to implement their commitments for the fight against HIV/AIDS, and to mobilize the required national and international resources."[36] In January 2012, AWA was revitalized to include all of Africa and its objectives were broadened to include malaria and tuberculosis.[37] #### Roadmap on Shared Responsibility and Global Solidarity for AIDS, TB and Malaria Response in Africa[edit] In 2012, the African Union adopted a Roadmap on Shared Responsibility and Global Solidarity for AIDS, TB and Malaria Response in Africa.[10] This Roadmap presents a set of practical African-sourced solutions for enhancing shared responsibility and global solidarity for AIDS ... responses in Africa on a sustainable basis by 2015. The solutions are organized around three strategic pillars: diversified financing; access to medicines; and enhanced health governance. The Roadmap defines goals, results and roles and responsibilities to hold stakeholders accountable for the realization of these solutions between 2012 and 2015.[38] ### Preventing HIV transmission from pregnant women to children[edit] The Joint United Nations Programme on HIV/AIDS reported that the following sixteen African nations in 2012 "ensure[d] that more than three-quarters of pregnant women living with HIV receive antiretroviral medicine to prevent transmission to their child": Botswana, Gabon, Gambia, Ghana, Mauritius, Mozambique, Namibia, Rwanda, São Tomé and Principe, Seychelles, Sierra Leone, South Africa, Eswatini, Tanzania, Zambia and Zimbabwe.[10][12] ## Causes and spread[edit] ### Behavioral factors[edit] High-risk behavioral patterns are largely responsible for the significantly greater spread of HIV/AIDS in Sub-Saharan Africa than in other parts of the world. Chief among these are the traditionally liberal attitudes espoused by many communities inhabiting the subcontinent toward multiple sexual partners and pre-marital and outside marriage sexual activity.[6][7] HIV transmission is most likely in the first few weeks after infection, and is therefore increased when people have more than one sexual partner in the same time period. In most of the developed world outside Africa, this means HIV transmission is high among prostitutes and other people who may have more than one sexual partner concurrently. Within the cultures of sub-Saharan Africa, it is relatively common for both men and women to be carrying on sexual relations with more than one person, which promotes HIV transmission.[22] This practice is known as concurrency, which Helen Epstein describes in her book, The Invisible Cure: Africa, the West, and the Fight against AIDS, in which her research into the sexual mores of Uganda revealed the high frequency with which men and women engage in concurrent sexual relationships.[39] In addition, in sub-Saharan Africa AIDS is the leading killer and a large reason for the high transmission rates is because of the lack of education provided to youth. When infected, most children die within one year because of the lack of treatment.[40] The entire population in Sub-Saharan Africa is being infected with HIV, from men to women, and from pregnant woman to children. Rather than having more of a specific group infected, male or female, the ratio of men and women infected with HIV are quite similar. With the HIV infection, 77% of men, women, and children, develop AIDS, and die in Sub-Saharan Africa. Of those deaths, "more than 90% of AIDS orphans and children [were] infected with HIV".[41] Lack of money is an obvious challenge, although a great deal of aid is distributed throughout developing countries with high HIV/AIDS rates. For African countries with advanced medical facilities, patents on many drugs have hindered the ability to make low cost alternatives.[42] Natural disasters and conflict are also major challenges, as the resulting economic problems people face can drive many young women and girls into patterns of sex work in order to ensure their livelihood or that of their family, or else to obtain safe passage, food, shelter or other resources.[43] Emergencies can also lead to greater exposure to HIV infection through new patterns of sex work. In Mozambique, an influx of humanitarian workers and transporters, such as truck drivers, attracted sex workers from outside the area.[43] Similarly, in the Turkana District of northern Kenya, drought led to a decrease in clients for local sex workers, prompting the sex workers to relax their condom use demands and search for new truck driver clients on main highways and in peri-urban settlements.[43] ### Health industry[edit] Sub-Saharan "Africans have always appreciated the importance of health care because good health is seen as necessary for the continuation and growth of their lineage".[44] Without proper health the culture will not be able to thrive and grow. Unfortunately, "health services in many countries are swamped by the need to care for increasing numbers of infected and sick people. Ameliorative drugs are too expensive for most victims, except for a very small number who are affluent".[44] The greatest number of sick people with the fewest doctors, Sub-Saharan Africa "has 11 percent of the world's population but carries 24 percent of the global disease burden. With less than 1 percent of global health expenditure and only 3 percent of the world's health workers".[45] Measuring an HIV patient's CD4 count at the Kyabugimbi Health Center in Uganda. When family members get sick with HIV or other sicknesses, family members often end up selling most of their belongings in order to provide health care for the individual. Medical facilities in many African countries are lacking. Many health care workers are also not available, in part due to lack of training by governments and in part due to the wooing of these workers by foreign medical organisations where there is a need for medical professionals.[46] Unfortunately, many individuals who get a medical degree end up leaving Sub-Saharan Africa to work abroad "either to escape instability or to practice where they have better working conditions and a higher salary".[47] Many low income communities are very far away from a hospital and they cannot afford to bus there or pay for medical attention once they arrive. "Healthcare in Africa differs widely, depending on the country and also the region – those living in urban areas are more likely to receive better healthcare services than those in rural or remote regions".[47] It is very common to just wait out a sickness or seek help from a neighbor or relative. Currently antiretroviral therapy is the closest to a cure. However, many hospitals lack enough antiretroviral drugs to treat everyone. This may be because most Sub-Saharan African countries invest "as little as 1-4 dollars per capita, [so] overseas aid is a major source of funding for healthcare".[47] Many overseas organizations are very hesitant to give antiretroviral drugs to Sub-Saharan Africa because they are expensive, which means that there is only so much they can give. Relying on other countries for help in general requires more paperwork and faith in another country very far away. Also, delivery of drugs and other aid takes many month and years to arrive in the hands of those that need help. ### Medical factors[edit] #### Circumcision[edit] According to a 2007 report, male and female circumcision were statistically associated with an increased incidence of HIV infection among the females in Kenya and the males in Kenya, Lesotho, and Tanzania who self-reported that they both underwent the procedure and were virgins.[Note 1] "Among adolescents, regardless of sexual experience, circumcision was just as strongly associated with prevalent HIV infection." Circumcised adults, however, were statistically less likely to be HIV positive than their uncircumcised counterparts, especially among older age groups.[Note 2][48] Similarly, a randomized, controlled intervention trial in South Africa from 2005 found that male circumcision "provides a degree of protection against acquiring HIV infection [by males], equivalent to what a vaccine of high efficacy would have achieved".[49] #### Medical suspicion[edit] An HIV/AIDS educational outreach session in Angola. There are high levels of medical suspicion throughout Africa, and there is evidence that such distrust may have a significant impact on the use of medical services.[50][51] The distrust of modern medicine is sometimes linked to theories of a "Western Plot"[52] of mass sterilization or population reduction, perhaps a consequence of several high-profile incidents involving western medical practitioners.[53] ### Pharmaceutical industry[edit] African countries are also still fighting against what they perceive as unfair practices in the international pharmaceutical industry.[54] Medical experimentation occurs in Africa on many medications, but once approved, access to the drug is difficult.[54] South African scientists in a combined effort with American scientists from Gilead Sciences recently tested and found effective a tenofivir-based anti-retroviral vaginal gel that could be used as pre-exposure prophylaxis. Testing of this gel was conducted at the University of KwaZulu-Natal in Durban, South Africa.[55] The FDA in the US is in the process of reviewing the drug for approval for US use.[56][57] The AIDS/HIV epidemic has led to the rise in unethical medical experimentation in Africa.[54] Since the epidemic is widespread, African governments sometimes relax their laws in order to get research conducted in their countries which they would otherwise not afford.[54] However, global organizations such as the Clinton Foundation, are working to reduce the cost of HIV/AIDS medications in Africa and elsewhere. For example, the philanthropist Inder Singh oversaw a program which reduced the cost of pediatric HIV/AIDS drugs by between 80 and 92 percent by working with manufacturers to reduce production and distribution costs.[58] Manufacturers often cite distribution and production difficulties in developing markets, which create a substantial barrier to entry. ### Political factors[edit] Major African political leaders have denied the link between HIV and AIDS, favoring alternate theories.[59] The scientific community considers the evidence that HIV causes AIDS to be conclusive and rejects AIDS-denialist claims as pseudoscience based on conspiracy theories, faulty reasoning, cherry picking, and misrepresentation of mainly outdated scientific data. Proponents of apartheid promoted the spread of HIV in South Africa and its sphere of influence throughout the 1980s. As a result HIV and AIDS prevalance reached the highest levels worldwide in the Southern African region.[60] ### Subtype factor[edit] In Africa, subtype C of HIV-1 is very common, whereas it is rare in America or Europe. People with subtype C progress to AIDS faster than those with subtype A, the predominant subtype in America and Europe (see HIV disease progression rates#HIV subtype variation and effect on progression rates). ### Religious factors[edit] Pressure from both Christian and Muslim religious leaders has resulted in the banning of a number of safe-sex campaigns, including condom promoting advertisements being banned in Kenya.[61] ## Health Care delivery[edit] While there currently isn’t a cure or vaccine for HIV/AIDS there are emerging treatments. It has been extensively discussed that antiretroviral drugs (ART) are crucial for preventing the acquiring of AIDS. AIDS is acquired at the final stage of the HIV virus, which can be completely averted. It is overwhelmingly possible to live with the virus and never acquire AIDS. The proper obedience to ART drugs can provide an infected person with a limitless future. ART drugs are key in preventing the diseases from progressing as well as ensuring the disease is well controlled, thus forbidding the disease from becoming resistant to the treatments.[62] In countries like Nigeria and the Central African Republic, a mere less than 25% of the population has access to the ART drugs.[63] Funds devoted to ART drug access were measured at $19.1 billion in 2013 in low and middle-income countries among the region, however the funds were short of the UNAIDS′ previous resource needs estimates of $22–24 billion by 2015.[64] ## Measurement[edit] Archbishop Desmond Tutu gets an HIV test on the Desmond Tutu HIV Foundation's Tutu Tester, a mobile test unit. Prevalence measures include everyone living with HIV and AIDS, and present a delayed representation of the epidemic by aggregating the HIV infections of many years. Incidence, in contrast, measures the number of new infections, usually over the previous year. There is no practical, reliable way to assess incidence in Sub-Saharan Africa. Prevalence in 15- to 24-year-old pregnant women attending antenatal clinics is sometimes used as an approximation. The test done to measure prevalence is a serosurvey in which blood is tested for the presence of HIV. Health units that conduct serosurveys rarely operate in remote rural communities, and the data collected also does not measure people who seek alternate healthcare. Extrapolating national data from antenatal surveys relies on assumptions which may not hold across all regions and at different stages in an epidemic. Thus, there may be significant disparities between official figures and actual HIV prevalence in some countries. A minority of scientists claim that as many as 40 percent of HIV infections in African adults may be caused by unsafe medical practices rather than by sexual activity.[65] The World Health Organization states that about 2.5 percent of HIV infections in Sub-Saharan Africa are caused by unsafe medical injection practices and the "overwhelming majority" by unprotected sex.[66] ## Regional prevalence[edit] In contrast to areas in North Africa and the Horn of Africa, traditional cultures and religions in Sub-Saharan Africa have generally exhibited a more liberal attitude to female out-of-marriage sexual activity. The latter includes practices such as multiple sexual partners and unprotected sex, high-risk cultural patterns that have been implicated in the much greater spread of HIV in the subcontinent.[7] ### North Africa[edit] Uniquely among countries in this region, Morocco's HIV prevalence rate has increased from less than 0.1 percent in 2001 to 0.2 percent in 2011.[12] Country Adult prevalence ages 15–49, 2014 Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2014[8] Number of people living with HIV, 2001[12] AIDS deaths, 2014[8] AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Algeria <0.1%[8] <0.1% 2,500-25,000 not available <1,000-1,500 <100-<500 not available not available Egypt <0.1%[8] <0.1% 5,800-14,000 9,100 <500 <500 not available not available Libya not available not available not available not available not available not available not available not available Morocco 0.1%[8] <0.1% 30,000 12,000 1,200 <1,000 not available not available Sudan 0.2%[12] 0.5% 53,000 not available 2,900 6,000 not available not available Tunisia <0.1%[8] <0.1% 2,700 <1,000 <100 <100 not available not available ### Horn of Africa[edit] As with North Africa, the HIV infection rates in the Horn of Africa are quite low. This has been attributed to the Muslim nature of many of the local communities and adherence to Islamic morals.[7] Ethiopia's HIV prevalence rate has decreased from 3.6 percent in 2001 to 1.4 percent in 2011.[12] The number of new infections per year also has decreased from 130,000 in 2001 to 24,000 in 2011.[12] Country Adult prevalence ages 15–49, 2011[8] Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2011[8] Number of people living with HIV, 2001[12] AIDS deaths, 2011[8] AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Djibouti 1.4% 2.7% 9,200 12,000 <1,000 1,000 <1,000 1,300 Eritrea 0.6% 1.1% 23,000 23,000 1,400 1,500 not available not available Ethiopia 1.4% 3.6% 790,000 1,300,000 54,000 100,000 24,000 130,000 Somalia 0.7% 0.8% 35,000 34,000 3,100 2,800 not available not available ### Central Africa[edit] HIV infection rates in central Africa are moderate to high.[6] Country Adult prevalence ages 15–49, 2011 Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2011 Number of people living with HIV, 2001[12] AIDS deaths, 2011 AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Angola 2.1%[8] 1.7% 230,000[8] 130,000 12,000[8] 8,200 23,000 20,000 Cameroon 4.6%[8] 5.1% 550,000[8] 450,000 34,000[8] 28,000 43,000 57,000 Central African Republic 4.6%[8] 8.1% 130,000[8] 170,000 10,000[8] 16,000 8,200 15,000 Chad 3.1%[8] 3.7% 210,000[8] 170,000 12,000[8] 13,000 not available not available Congo 3.3%[8] 3.8% 83,000[8] 74,000 4,600[8] 6,900 7,900 7,200 Democratic Republic of the Congo 1.2%-1.6%[6] not available 430,000-560,000[6] not available 26,000-40,000 (2009)[6] not available not available not available Equatorial Guinea 4.7%[8] 2.5% 20,000[8] 7,900 <1,000[8] <500 not available not available Gabon 5.0%[8] 5.2% 46,000[8] 35,000 2,500[8] 2,100 3,000 4,900 São Tomé and Principe 1.0%[8] 0.9% <1,000[8] <1,000 <100[8] <100 not available not available ### Eastern Africa[edit] World AIDS Day 2006 event in Kenya. HIV infection rates in eastern Africa are moderate to high. #### Kenya[edit] Main article: HIV/AIDS in Kenya Kenya, according to a 2008 report from the Joint United Nations Programme on HIV/AIDS, had the third largest number of individuals in Sub-Saharan Africa living with HIV.[67] It also had the highest prevalence rate of any country outside of Southern Africa.[67] Kenya's HIV infection rate dropped from around 14 percent in the mid-1990s to 5 percent in 2006,[6] but rose again to 6.2 percent by 2011.[67] The number of newly infected people per year, however, decreased by almost 30 percent, from 140,000 in 2001 to 100,000 in 2011.[12] As of 2012, Nyanza Province had the highest HIV prevalence rate at 13.9 percent, with the North Eastern Province having the lowest rate at 0.9 percent.[67] Christian men and women also had a higher infection rate than their Muslim counterparts.[67] This discrepancy was especially marked among women, with Muslim women showing a rate of 2.8 percent versus 8.4 percent among Protestant women and 8 percent among Catholic women.[67] HIV was also more common among the wealthiest than among the poorest (7.2 percent versus 4.6 percent).[67] Historically, HIV had been more prevalent in urban than rural areas, although the gap is closing rapidly.[67] Men in rural areas are now more likely to be HIV-infected (at 4.5 percent) than those in urban areas (at 3.7 percent).[67] #### Tanzania[edit] Main article: HIV/AIDS in Tanzania Between 2004 and 2008, the HIV incidence rate in Tanzania for ages 15–44 slowed to 3.37 per 1,000 person-years (4.42 for women and 2.36 for men).[68] The number of newly infected people per year increased slightly, from 140,000 in 2001 to 150,000 in 2011.[12] There were also significantly fewer HIV infections in Zanzibar, which in 2011 had a prevalence rate of 1.0 percent compared to 5.3 percent in mainland Tanzania.[69] #### Uganda[edit] Main article: HIV/AIDS in Uganda Uganda has registered a gradual decrease in its HIV rates from 10.6 percent in 1997, to a stabilized 6.5-7.2 percent since 2001.[6][7] This has been attributed to changing local behavioral patterns, with more respondents reporting greater use of contraceptives[citation needed] and a two-year delay in first sexual activity as well as fewer people reporting casual sexual encounters and multiple partners.[7] The number of newly infected people per year, however, has increased by over 50 percent, from 99,000 in 2001 to 150,000 in 2011.[12] More than 40 percent of new infections are among married couples, indicating widespread and increasing infidelity.[70] This increase has caused alarm. The director of the Centre for Disease Control – Uganda, Wuhib Tadesse, said in 2011 that, > for every person started on antiretroviral therapy, there are three new HIV infections[,] and this is unsustainable. We are ... very concerned. ... [C]omplacence could be part of the problem. Young people nowadays no longer see people dying; they see people on ARVs but getting children. We need to re-examine our strategies.... Leaders at all levels are spending ... [more] time in workshops than in the communities to sensitive the people[,] and this must stop."[71] Country Adult prevalence ages 15–49, 2011 Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2011[8] Number of people living with HIV, 2001[12] AIDS deaths, 2011[8] AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Burundi 1.3%[8] 3.5% 80,000 130,000 5,800 13,000 3,000 6,900 Comoros 0.1%[8] <0.1% <500 <100 <100 <100 not available not available Kenya 6.2%[8] 8.5% 1,600,000 1,600,000 62,000 130,000 100,000 140,000 Madagascar 0.3%[8] 0.3% 34,000 22,000 2,600 1,500 not available not available Mauritius 1.0%[8] 0.9% 7,400 6,600 <1,000 <500 not available not available Mayotte not available not available not available not available not available not available not available not available Réunion not available not available not available not available not available not available not available not available Rwanda 2.9%[8] 4.1% 210,000 220,000 6,400 21,000 10,000 19,000 Seychelles not available[8] not available not available not available not available not available not available not available South Sudan 3.1%[8] not available 150,000 not available 11,000 not available not available not available Tanzania 5.1%[69] 7.2% 1,600,000 1,400,000 84,000 130,000 150,000 140,000 Uganda 7.2%[8] 6.9% 1,400,000 990,000 62,000 100,000 150,000 99,000 ### Western Africa[edit] Western Africa has moderate levels of infection of both HIV-1 and HIV-2. The onset of the HIV epidemic in the region began in 1985 with reported cases in Senegal,[72] Benin,[73] and Nigeria.[74] These were followed in 1986 by Côte d'Ivoire.[75] The first identification of HIV-2 occurred in Senegal by microbiologist Souleymane Mboup and his collaborators.[72] HIV prevalence in western Africa is lowest in Senegal and highest in Nigeria, which has the second largest number of people living with HIV in Africa after South Africa. Nigeria's infection rate (number of patients relative to the entire population), however, is much lower (3.7 percent) compared to South Africa's (17.3 percent). In Niger in 2011, the national HIV prevalence rate for ages 15–49 was 0.8 percent while for sex workers it was 36 percent.[12] Country Adult prevalence ages 15–49, 2011[8] Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2011[8] Number of people living with HIV, 2001[12] AIDS deaths, 2011[8] AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Benin 1.2% 1.7% 64,000 66,000 2,800 6,400 4,900 5,300 Burkina Faso 1.1% 2.1% 120,000 150,000 6,800 15,000 7,100 13,000 Cape Verde 1.0% 1.0% 3,300 2,700 <200 <500 not available not available Côte d'Ivoire 3.0% 6.2% 360,000 560,000 23,000 50,000 not available not available Gambia 1.5% 0.8% 14,000 5,700 <1,000 <500 1,300 1,200 Ghana 1.5% 2.2% 230,000 250,000 15,000[Note 3] 18,000 13,000 28,000 Guinea 1.4% 1.5% 85,000 72,000 4,000[Note 4] 5,100 not available not available Guinea-Bissau 2.5% 1.4% 24,000 9,800 <1,000 <1,000 2,900 1,800 Liberia 1.0% 2.5% 25,000 39,000 2,300[Note 5] 2,500 not available not available Mali 1.1% 1.6% 110,000 110,000 6,600 9,700 8,600 12,000 Mauritania 1.1% 0.6% 24,000 10,000 1,500 <1,000 not available not available Niger 0.8% 0.8% 65,000 45,000 4,000 3,200 6,400 6,200 Nigeria 3.7% 3.7% 3,400,000 2,500,000 210,000[Note 6] 150,000 340,000 310,000 Senegal 0.7% 0.5% 53,000 24,000 1,600 1,400 not available not available Sierra Leone 1.6% 0.9% 49,000 21,000 2,600 <1,000 3,900 4,500 Togo 3.4% 4.1% 150,000 120,000 8,900[Note 7] 8,100 9,500 17,000 ### Southern Africa[edit] Graphs of life expectancy at birth for some Sub-Saharan countries showing the fall in the 1990s primarily due to the AIDS pandemic.[76] In the mid-1980s, HIV and AIDS were virtually unheard of in southern Africa. However, it is now the worst-affected region in the world. Currently, Eswatini and Lesotho have the highest and second highest HIV prevalence rates in the world, respectively.[8] Of the nine southern African countries (Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Eswatini, Zambia, and Zimbabwe), four are estimated to have an infection rate of over 15 percent. In Botswana, the number of newly infected people per year has declined by 67 percent, from 27,000 in 2001 to 9,000 in 2011. In Malawi, the decrease has been 54 percent, from 100,000 in 2001 to 46,000 in 2011. All but two of the other countries in this region have also recorded major decreases (Namibia, 62 percent; Zambia, 54 percent; Zimbabwe, 47 percent; South Africa, 38 percent; Eswatini, 32 percent). The number has remained virtually the same in Lesotho and Mozambique.[12] Zimbabwe's first reported case of HIV was in 1985.[77] There are widespread practices of sexual networking that involve multiple overlapping or concurrent sexual partners.[78] Men's sexual networks, in particular, tend to be quite extensive,[79][80] a fact that is tacitly accepted or even encouraged by many communities.[81] Along with having multiple sexual partners, unemployment and population displacements resulting from drought and conflict have contributed to the spread of HIV/AIDS.[81] According to Susser and Stein (2000), men refuse to use condoms during intercourse with girls or women performing sex work (p. 1043-1044). Unfortunately, the girls and women are in desperate need of money and do not have a choice. This leads to multiple sex partners, which increases the likelihood of their infection with HIV/AIDS.[82] A 2008 study in Botswana, Namibia, and Eswatini found that intimate partner violence, extreme poverty, education, and partner income disparity explained almost all of the differences in HIV status among adults aged 15–29 years. Among young women with any one of these factors, the HIV rate increased from 7.7 percent with no factors to 17.1 percent. Approximately 26 percent of young women with any two factors were HIV positive, with 36 percent of those with any three factors and 39.3 percent of those with all four factors being HIV-positive.[83] Country Adult prevalence ages 15–49, 2011[8] Adult prevalence ages 15–49, 2001[12] Number of people living with HIV, 2011[8] Number of people living with HIV, 2001[12] AIDS deaths, 2011[8] AIDS deaths, 2001[12] New HIV infections, 2011[12] New HIV infections, 2001[12] Botswana 23.4% 27.0% 300,000 270,000 4,200 18,000 9,000 27,000 Lesotho 23.3% 23.4% 320,000 250,000 14,000[Note 8] 15,000 26,000 26,000 Malawi 10.0% 13.8% 910,000 860,000 44,000[Note 9] 63,000 46,000 100,000 Mozambique 11.3% 9.7% 1,400,000 850,000 74,000 46,000 130,000 140,000 Namibia 13.4% 15.5% 190,000 160,000 5,200[Note 10] 8,600 8,800 23,000 South Africa 17.3% 15.9% 5,600,000 4,400,000 270,000[Note 11] 210,000 380,000 610,000 Eswatini 26.0% 22.2% 190,000 120,000 6,800[Note 12] 6,700 13,000 19,000 Zambia 12.5% 14.4% 970,000 860,000 31,000 72,000 51,000 110,000 Zimbabwe 14.9% 25.0% 1,200,000 1,800,000 58,000 150,000 74,000 140,000 #### Eswatini[edit] Main article: HIV/AIDS in Eswatini As of 2011, the HIV prevalence rate in Eswatini was the highest in the world at 26.0 percent of persons aged 15–49.[8] The United Nations Development Programme wrote in 2005, > The immense scale of AIDS-related illness and deaths is weakening governance capacities for service delivery, with serious consequences on food security, economic growth[,] and human development. AIDS undermines the capacities of individuals, families, communities[,] and the state to fulfill their roles and responsibilities in society. If current trends are not reversed, the longer-term survival of Swaziland as a country will be seriously threatened.[84] The HIV epidemic in Eswatini has reduced its life expectancy at birth to 49 for men and 51 for women (based on 2009 data).[85] Life expectancy at birth in 1990 was 59 for men and 62 for women.[86] Based on 2011 data, Eswatini's crude death rate of 19.51 per 1,000 people per year was the third highest in the world, behind only Lesotho and Sierra Leone.[87] HIV/AIDS in 2002 caused 64 percent of all deaths in the country.[88] ## Tuberculosis coinfections[edit] Workshop on HIV/AIDS and Tuberculosis in South Africa. Much of the deadliness of the epidemic in Sub-Saharan Africa is caused by a deadly synergy between HIV and tuberculosis, termed a "co-epidemic".[89] The two diseases have been "inextricably bound together" since the beginning of the HIV epidemic.[90] "Tuberculosis and HIV co-infections are associated with special diagnostic and therapeutic challenges and constitute an immense burden on healthcare systems of heavily infected countries like Ethiopia."[91] In many countries without adequate resources, the tuberculosis case rate has increased five to ten-fold since the identification of HIV.[90] Without proper treatment, an estimated 90 percent of persons living with HIV die within months after contracting tuberculosis.[89] The initiation of highly active antiretroviral therapy in persons coinfected with tuberculosis can cause an immune reconstitution inflammatory syndrome with a worsening, in some cases severe worsening, of tuberculosis infection and symptoms.[92] An estimated 874,000 people in Sub-Saharan Africa were living with both HIV and tuberculosis in 2011,[12] with 330,000 in South Africa, 83,000 in Mozambique, 50,000 in Nigeria, 47,000 in Kenya, and 46,000 in Zimbabwe.[93] In terms of cases per 100,000 population, Eswatini's rate of 1,010 was by far the highest in 2011.[93] In the following 20 African countries, the cases-per-100,000 coinfection rate has increased at least 20 percent between 2000 and 2011: Algeria, Angola, Chad, Comoros, Republic of the Congo, Democratic Republic of the Congo, Equatorial Guinea, The Gambia, Lesotho, Liberia, Mauritania, Mauritius, Morocco, Mozambique, Senegal, Sierra Leone, South Africa, Eswatini, Togo, and Tunisia. Since 2004, however, tuberculosis-related deaths among people living with HIV have fallen by 28 percent in Sub-Saharan Africa, which is home to nearly 80 percent of the people worldwide who are living with both diseases.[12] Country Concurrent HIV/Tuberculosis infections, 2011 (cases per 100,000 population)[93] Concurrent HIV/Tuberculosis infections, 2011 (cases)[93] Concurrent HIV/Tuberculosis infections, 2000 (cases per 100,000 population)[93] Concurrent HIV/Tuberculosis infections, 2000 (cases)[93] NORTH AFRICA Algeria 1 360 0.3 100 Egypt <0.1 43 <0.1 56 Libya 3.4 220 not available not available Morocco 0.9 300 0.4 110 Sudan 8.2 2,800 9.3 3,200 Tunisia 0.6 66 0.6 53 HORN OF AFRICA Djibouti 63 570 86 730 Eritrea 8.2 440 20 750 Ethiopia 45 38,000 141 93,000 Somalia 22 2,100 27 2,000 CENTRAL AFRICA Angola 43 8,500 44 6,100 Cameroon 93 19,000 130 20,000 Central African Republic 159 7,100 591 22,000 Chad 45 5,200 51 4,200 Congo 119 4,900 126 3,900 Democratic Republic of the Congo 49 34,000 57 28,000 Equatorial Guinea 52 370 47 250 Gabon 185 2,800 203 2,500 Sao Tome and Principe 9 15 9.7 14 EASTERN AFRICA Burundi 30 2,600 121 7,700 Comoros 1.4 11 0 <10 Kenya 113 47,000 149 47,000 Madagascar 0.6 130 0.8 120 Mauritius 1.6 21 1.1 13 Mayotte not available not available not available not available Réunion not available not available not available not available Rwanda 27 2,900 141 11,000 Seychelles 5.8 <10 not available not available South Sudan not available not available not available not available Tanzania 65 30,000 106 36,000 Uganda 102 35,000 244 59,000 WESTERN AFRICA Benin 12 1,100 20 1,300 Burkina Faso 9.5 1,600 22 2,700 Cape Verde 19 97 19 84 Côte d'Ivoire 50 10,000 155 26,000 Gambia 45 800 18 230 Ghana 18 4,600 47 9,000 Guinea 47 4,800 58 4,900 Guinea-Bissau 99 1,500 25 310 Liberia 31 1,300 33 940 Mali 9.4 1,500 16 1,800 Mauritania 43 1,500 21 550 Niger 11 1,700 18 2,000 Nigeria 30 50,000 42 52,000 Senegal 14 1,700 7.9 750 Sierra Leone 64 3,800 20 810 Togo 16 1,000 18 840 SOUTHERN AFRICA Botswana 292 5,900 611 11,000 Lesotho 481 11,000 425 8,300 Malawi 114 18,000 324 36,000 Mozambique 347 83,000 279 51,000 Namibia 359 8,400 787 15,000 South Africa 650 330,000 317 140,000 Eswatini 1,010 12,000 607 6,500 Zambia 285 38,000 493 50,000 Zimbabwe 360 46,000 666 83,000 ## See also[edit] * Africa portal * 28: Stories of AIDS in Africa * Demographics of Africa * The Global Fund to Fight AIDS, Tuberculosis and Malaria * HIV/AIDS in Eswatini * HIV/AIDS in Malawi * HIV/AIDS in Asia * HIV/AIDS in Australia * HIV/AIDS in Europe * HIV/AIDS in North America * HIV/AIDS in South America * Origin of AIDS * President's Emergency Plan for AIDS Relief * South African model of the pandemic * United Nations Special Envoy for HIV/AIDS in Africa ## Notes[edit] 1. ^ Kenyan females: 3.2 percent versus 1.4 percent. Kenyan males: 1.8 percent versus 0.0 percent. Lesothoan males: 6.1 percent versus 1.9 percent. Tanzanian males: 2.9 percent versus 1.0 percent. 2. ^ Kenyan females: 4.8 percent versus 12.2 percent. Kenyan males: 4.0 percent versus 25.4 percent. Lesothoan males: 26.3 percent versus 28.8 percent. Tanzanian males: 8.5 percent versus 10.8 percent. 3. ^ The number of AIDS deaths in Ghana in 2006 was 22,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 4. ^ The number of AIDS deaths in Guinea in 2006 was 6,100. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 5. ^ The number of AIDS deaths in Liberia in 2006 was 3,400. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 6. ^ The number of AIDS deaths in Nigeria in 2006 was 220,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 7. ^ The number of AIDS deaths in Togo in 2006 was 11,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 8. ^ The number of AIDS deaths in Lesotho in 2006 was 22,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 9. ^ The number of AIDS deaths in Malawi in 2006 was 75,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 10. ^ The number of AIDS deaths in Namibia in 2006 was 12,000. Data on the size of the HIV/AIDS epidemic: Number of deaths due to AIDS by country, World Health Organization, 2006 11. ^ The number of AIDS deaths in South Africa in 2006 was 390,000. 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Washington, 31 July 2007 54. ^ a b c d Meier, Benjamin Mason: International Protection of Persons Undergoing Medical Experimentation: Protecting the Right of Informed Consent, Berkeley journal of international law [1085-5718] Meier yr:2002 vol:20 iss:3 pg:513 -554 55. ^ Rahman SM, Vaidya NK, Zou X (April 2014). "Impact of Tenofovir gel as a PrEP on HIV infection: a mathematical model". Journal of Theoretical Biology. 347: 151–9. doi:10.1016/j.jtbi.2013.12.021. PMID 24380779. 56. ^ "New AIDS gel could protect women from HIV". South Africa — The Good News — Sagoodnews.co.za. 2010-07-20. Archived from the original on 2011-02-21. Retrieved 2011-03-29. 57. ^ Fox M (2010-10-27). "Groups moving forward to develop AIDS gel". Reuters. Retrieved 2011-03-29. 58. ^ "Inder Singh, Executive Vice President for the Clinton Foundation, on Expanding Access to Health Care". Wharton Magazine. 2011-03-29. Retrieved 2011-08-10. 59. ^ Mark Schoofs (2000-07-04). "Debating the Obvious — Page 1 - News — New York". Village Voice. Retrieved 2012-02-21. 60. ^ https://www.independent.co.uk/news/world/africa/south-africa-apartheid-aids-saimr-plot-infect-hiv-virus-black-cold-case-hammarskj-ld-documentary-a8749176.html 61. ^ Mark Schoofs (20 March 2013). "Kenya condom advert pulled after religious complaints". BBC. Retrieved 2013-03-21. 62. ^ Kunutsor S, Walley J, Muchuro S, Katabira E, Balidawa H, Namagala E, Ikoona E (2012-05-24). "Improving adherence to antiretroviral therapy in sub-Saharan African HIV-positive populations: an enhanced adherence package". AIDS Care. 24 (10): 1308–15. doi:10.1080/09540121.2012.661833. PMID 22621288. 63. ^ Kharsany AB, Karim QA (2016-04-08). "HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities". The Open AIDS Journal. 10: 34–48. doi:10.2174/1874613601610010034. PMC 4893541. PMID 27347270. 64. ^ Remme M, Siapka M, Sterck O, Ncube M, Watts C, Vassall A (November 2016). 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PMID 19915447. 69. ^ a b Tanzania HIV/AIDS and Malaria Indicator Survey 2011-12, authorized by the Tanzania Commission for AIDS (TACAIDS) and the Zanzibar Commission for AIDS; implemented by the Tanzania National Bureau of Statistics in collaboration with the Office of the Chief Government Statistician (Zanzibar); funded by the United States Agency for International Development, TACAIDS, and the Ministry of Health and Social Welfare, with support provided by ICF International; data collected 16 December 2011 to 24 May 2012; report published in Dar es Salaam in March 2013 Archived 20 October 2014 at the Wayback Machine 70. ^ "Uganda's Soaring HIV Infection Rate Linked to Infidelity". VOA. Archived from the original on 24 September 2013. Retrieved 18 March 2015. 71. ^ "Uganda: 25,000 Babies Born With HIV/Aids Annually", The Monitor, reported by Yasiin Mugerwa, reprinted on the website of allAfrica.com, 17 July 2011 72. ^ a b Boston, 677 Huntington Avenue; Ma 02115 +1495-1000 (2018-06-29). "The Senegal Sex Workers Study". Harvard AIDS Initiative. Retrieved 2020-06-18. 73. ^ "HEALTH-BENIN: Growing Number of AIDS Orphans". Retrieved 18 March 2015. 74. ^ "Chapter 2: The Epidemiology of HIV/AIDS in Nigeria", contributed by Abdulsalami Nasidi and Tekena O. Harry, in the book "AIDS in Nigeria: A Nation on the Threshold", edited by Olusoji Adeyi, Phyllis J. Kanki, and Oluwole Odutolu, Harvard Center for Population and Development Studies, Harvard University Press, 2006 75. ^ "Epidemological Fact Sheet on HIV/AIDS and sexually transmitted infections", UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance, 2000 76. ^ "Life expectancy at birth, total (years)". Retrieved 18 March 2015. 77. ^ ""AIDS in Africa During the Nineties Zimbabwe. A review and analysis of survey and research results", National AIDS Council, Ministry of Health and Child Welfare, The MEASURE Project, Centers for Disease Control and Prevention (CDC/Zimbabwe), Carolina Population Center, University of North Carolina at Chapel Hill, 2002, page 1". Retrieved 18 March 2015. 78. ^ The Political Economy of AIDS in Africa, edited by Nana K. Poku and Alan W. Whiteside, Ashgate Publishing, Ltd., 2004, page 235 79. ^ Ragnarsson A, Townsend L, Thorson A, Chopra M, Ekstrom AM (October 2009). "Social networks and concurrent sexual relationships--a qualitative study among men in an urban South African community". AIDS Care. 21 (10): 1253–8. doi:10.1080/09540120902814361. PMID 20024701. 80. ^ Ragnarsson A, Townsend L, Ekström AM, Chopra M, Thorson A (July 2010). "The construction of an idealised urban masculinity among men with concurrent sexual partners in a South African township". Global Health Action. 3: 5092. doi:10.3402/gha.v3i0.5092. PMC 2905206. PMID 20644656. 81. ^ a b Stenger MR, Baral S, Stahlman S, Wohlfeiler D, Barton JE, Peterman T (February 2017). "As through a glass, darkly: the future of sexually transmissible infections among gay, bisexual and other men who have sex with men". Sexual Health. 14 (1): 18–27. doi:10.1071/SH16104. PMC 5334461. PMID 27585033. 82. ^ Susser I, Stein Z (July 2000). "Culture, sexuality, and women's agency in the prevention of HIV/AIDS in southern Africa". American Journal of Public Health. 90 (7): 1042–8. doi:10.2105/ajph.90.7.1042. PMC 1446308. PMID 10897180. 83. ^ Andersson N, Cockcroft A (January 2012). "Choice-disability and HIV infection: a cross sectional study of HIV status in Botswana, Namibia and Swaziland". AIDS and Behavior. 16 (1): 189–98. doi:10.1007/s10461-011-9912-3. PMC 3254870. PMID 21390539. 84. ^ ""Draft country programme document for Swaziland (2006-2010)", United Nations Development Programme" (PDF). Archived from the original (PDF) on 2011-11-18. Retrieved 2013-05-29. 85. ^ "WHO - Swaziland". Retrieved 18 March 2015. 86. ^ "Global Health Observatory Data Repository". Retrieved 18 March 2015. 87. ^ "Global Health Observatory Data Repository". Retrieved 18 March 2015. 88. ^ "Country Health System Fact Sheet: Swaziland", World Health Organization, 2006 89. ^ a b "'Dual epidemic' threatens Africa". BBC News. 2 November 2007. Retrieved 2011-03-29. 90. ^ a b Gerald Friedland. "Tuberculosis and HIV Coinfection: Current State of Knowledge and Research Priorities". Retrieved 18 March 2015. 91. ^ Wondimeneh Y, Muluye D, Belyhun Y (June 2012). "Prevalence of pulmonary tuberculosis and immunological profile of HIV co-infected patients in Northwest Ethiopia". BMC Research Notes. 5: 331. doi:10.1186/1756-0500-5-331. PMC 3434071. PMID 22738361. 92. ^ Leone S, Nicastri E, Giglio S, Narciso P, Ippolito G, Acone N (April 2010). "Immune reconstitution inflammatory syndrome associated with Mycobacterium tuberculosis infection: a systematic review". International Journal of Infectious Diseases. 14 (4): e283-91. doi:10.1016/j.ijid.2009.05.016. PMID 19656712. 93. ^ a b c d e f Table A4.2, Annex 4: Global, regional and country-specific data for key indicators, Global Tuberculosis Report 2012, World Health Organization ## Further reading[edit] * Smith RA, ed. (January 2001). Encyclopedia of AIDS: A Social, Political, Cultural, and Scientific Record of the HIV Epidemic. Penguin Books. ISBN 0-14-051486-4. * Iliffe J (2006). The African AIDS Epidemic: A History. Jamedn s Currey. ISBN 0-85255-890-2. * Fourie P (2006). The Political Management of HIV and AIDS in South Africa: One burden too many?. Palgrave Macmillan. ISBN 0-230-00667-1. * Dionne KY (2018). Doomed Interventions: The Failure of Global Responses to AIDS in Africa. Cambridge University Press. ## External links[edit] Wikimedia Commons has media related to AIDS in Africa. * AIDS Turns Africa's Demographics Upside Down, Allianz Knowledge, October 18, 2007 * AIDS: Voices From Africa \- slideshow by Life magazine * Aids Clock (UNFPA) * Visualization tool for HIV/AIDS prevalence in sub-Saharan Africa from 2000-2017 * Information about STD's in Africa * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance 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Urbanization * cities * urban areas * Youth in Africa By year * 2005 * 2006 * 2007 * 2008 * 2009 * 2010 * 2011 * 2012 * 2013 * 2014 * 2015 * 2016 * 2017 * 2018 * 2019 * 2020 * Outline * Index * Category * Portal [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	HIV/AIDS in Africa	None	8,355	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Africa	2021-01-18T19:02:58	{"wikidata": ["Q1358589"]}
A very rare form of botulism, a rare acquired neuromuscular junction disease with descending flaccid paralysis caused by botulinum neurotoxins (BoNTs), and is due to intestinal colonization by Clostridium botulinum leading to toxin-mediated infection with toxemia. ## Epidemiology Exact prevalence is unknown. To date, about 20 cases have been reported. ## Clinical description The disease affects adults and older children. Clinical manifestations are similar to other forms of botulism (flaccid and symmetrical cranial nerve palsy, followed by symmetrical flaccid descending motor paralysis). Compared to foodborne botulism (see this term), the onset is generally gradual and less dramatic. In some cases, diarrhea due to C. difficile co-infection has been reported. ## Etiology The disease results from prolonged intestinal absorption of small quantities of BoNTs produced in situ by C. botulinum type A and B, or rarely by C.botulinum type C (one case) or by neurotoxigenic strains of C. baratiitype F or C. butyricum type E, that can temporarily colonize the intestinal tract. Colonization is generally associated with anatomical abnormalities of the gastrointestinal tract or alteration of protective endogenous microflora by broad-spectrum antibiotics following inflammatory intestinal disease or surgery. Some patients who underwent laparotomy for suspected appendicitis have shown worsening paralysis probably due to the post-surgical antibiotic therapy. Presence of Meckel's diverticulum may be a predisposing factor for intestinal colonization by C. butyricum. ## Diagnostic methods Diagnosis is based on clinical presentation. Confirmation of adult intestinal botulism is based on the detection of BoNTs in serum and stools. In addition, stools can be screened for BoNT-producing Clostridia. Diagnosis is also performed by demonstration of prolonged excretion of microorganisms and toxin in the stool in patients with sporadic botulism and no known contaminated food or wound. ## Differential diagnosis Differential diagnosis includes myasthenia gravis, Guillain-Barré syndrome (Miller Fisher syndrome), Lambert-Eaton syndrome and foodborne and wound botulism (see these terms). ## Management and treatment The antitoxin therapy must be associated with supportive care in an intensive care unit (ICU). Equine antitoxin treatment for adults has a half-life of 5-8 days. In Europe, the formulation currently available for adults is trivalent (anti A, B, E). A heptavalent (anti A to G) product is also available. In the USA, a bivalent (anti A, B) and a monovalent (anti E) antitoxin are available. Antibiotic therapy is ineffective on the toxin action and can exacerbate the neuromuscular blockade, but it is useful when secondary infections are present. In the severe forms, respiratory failure and paralysis may require ventilation for weeks as well as intensive care. ## Prognosis When treatment is administered early and with appropriate intensive care, the prognosis is generally good, no long-term side effects have been observed, and death resulting from respiratory failure is extremely rare. Complications can occur during hospitalization including nosocomial adverse events. [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	Adult intestinal botulism	c4289991	8,356	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178487	2021-01-23T18:16:50	{"icd-10": ["A05.1"], "synonyms": ["Adult intestinal colonization botulism", "Adult intestinal toxemia botulism", "Adult intestinal toxin-mediated botulism", "Infant-like botulism"]}
A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-8 (HLD8) is caused by compound heterozygous mutation in the POLR3B gene (614366) on chromosome 12q23. Description Hypomyelinating leukodystrophy-8 is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism (summary by Tetreault et al., 2011). See also HLD7 (607694), which has similar features and is caused by mutation in the POLR3A gene (614258) on chromosome 10q22. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III. For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. Clinical Features Saitsu et al. (2011) reported 3 patients from 2 unrelated nonconsanguineous Japanese families with childhood-onset hypomyelinating leukodystrophy. Two sibs had a very similar phenotype, with normal early infantile development and walking at ages 14 and 15 months, respectively. At age 3 years, 1 showed unstable walking and frequent falls and the other became poor at exercise. They had mild intellectual disability but were able to finish high school. As adults, both had cerebellar signs, including ataxic speech, wide-based ataxic gait, dysdiadochokinesis, and dysmetria, hypotonia, and mild hyperreflexia without extensor plantar responses. However, the motor deterioration was not considered to be progressive. Both also showed signs of hypogonadotropic hypogonadism. Other features included myopia, mild horizontal nystagmus, slowing of smooth-pursuit eye movements, and vertical gaze limitation. Brain MRI showed high-intensity areas in the white matter on T2-weighted images, consistent with diffuse cerebral hypomyelination, as well as cerebellar atrophy, and hypoplastic corpus callosum. A third unrelated patient, previously reported as patient 1 by Sasaki et al. (2009), could still walk in her teens, showed cerebellar signs, mild spasticity, slowing of smooth-pursuit eye movements, vertical gaze limitations, and intellectual disability. She did not have hypogonadism. None of the 3 had hypodontia. Tetreault et al. (2011) studied 3 unrelated patients of European descent who had a phenotype consistent with 4H syndrome (HLD7; 607694) but who did not have mutations in the POLR3A gene (614258). All presented in early childhood with mild developmental delays and developed dysarthria as well as progressive motor difficulties, including cerebellar ataxia. Two showed progressive spasticity. Two individuals developed hypogonadotropic hypogonadism, whereas the third was too young to evaluate for endocrine dysfunction. All 3 individuals had teeth abnormalities, such as neonatal upper incisors, delayed eruption of deciduous teeth and permanent teeth, abnormal sequence of eruption, and malposition. Brain MRI showed thin corpus callosum, cerebellar atrophy, and hypomyelination. Molecular Genetics Using whole-exome sequencing, Saitsu et al. (2011) identified compound heterozygous mutations in the POLR3B gene (614366.0001-614366.0004) in 3 patients from 2 unrelated Japanese families with hypomyelinating leukodystrophy-8. Two of the patients had hypogonadotropic hypogonadism, but none had hypodontia. One of the patients had previously been reported as patient 1 by Sasaki et al. (2009). In 3 unrelated patients of European descent with HLD8, Tetreault et al. (2011) identified compound heterozygous mutations in the POLR3B gene (614366.0005-614366.0008). All had hypodontia and 2 developed hypogonadotropic hypogonadism. In a cohort of 565 patients with isolated hypogonadotropic hypogonadism, with or without anosmia, Richards et al. (2017) performed whole-exome sequencing and identified 4 patients from 3 unrelated families who were compound heterozygous for rare variants in the POLR3B gene and did not have variants in 7 other ataxia-associated genes. An M415T polymorphism (rs199504211) of unclear pathologic significance was carried by 2 of the patients in addition to another variant in POLR3B; no segregation information was reported in those families. In 2 affected sibs, the V523E variant (614366.0005; rs138249161) and an F400S missense variant in POLR3B were identified, each inherited from an unaffected heterozygous parent. None of the 4 patients were reported to have frank neurologic symptoms at their most recent evaluations in their early 30s, and 1 had a brain MRI at age 23 years that was reported as normal. The authors suggested that a possible reason for the lack of neurodegenerative symptoms might be that the variants identified are less harmful to protein function than those identified in patients with HLD8, and noted that computational programs yielded mixed predictions regarding pathogenicity of the variants. No in vivo or in vitro functional analysis of the variants was reported. Genotype/Phenotype Correlations Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Except for the French Canadian patients, who carried a common POLR3A mutation (G672E; 614258.0001), most patients of European descent carried POLR3B mutations. Among all patients, about half had delayed development, including 19 (17%) who were never able to walk independently (4 with POLR3A mutations and 15 and POLR3B mutations). Ten (10%) of patients presented after age 10 years. All patients except one, who was older at the time of diagnosis, had cerebellar signs, such as severe intention tremor, dysmetria, ataxia, abnormal smooth pursuit, and nystagmus. Deterioration of speech and swallowing occurred later. Only a few patients had extrapyramidal signs, mainly dystonia. Cognition varied widely from normal in a few patients to moderate intellectual disability in most. About 20% of patients had seizures. Neurologic deterioration with infection occurred in about half of patients. Dental abnormalities, such as delayed dentition and hypodontia, were common (in 87%). Delayed puberty, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations. Most (87%) patients had severe and often progressive myopia, and about half had short stature. Growth hormone deficiency was found in 5 of 10 patients tested. Brain imaging showed hypomyelination in all patients and cerebellar atrophy in most. Supratentorial atrophy and thin corpus callosum were seen in older patients, reflecting white matter loss. A T2-weighted hypodense dot in the posterior limb of the internal capsule was seen in 70% of patients with POLR3B mutations, but only 13% of those with POLR3A mutations. In general, patients with POLR3A mutations had a more severe disease than those with POLR3B mutations. Two sibs with a homozygous POLR3B V523E mutation (614366.0005) had an exceptionally mild clinical course. Wolf et al. (2014) concluded that 4H syndrome is an insidiously progressive neurologic disorder with declining motor function of variable severity, but dental abnormalities and hypogonadism are not obligatory for the diagnosis. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Eyes \- Myopia \- Nystagmus \- Abnormal smooth pursuit \- Vertical gaze limitation Teeth \- Hypodontia (variable) \- Oligodontia (variable) \- Delayed eruption \- Malpositioning ABDOMEN Gastrointestinal \- Dysphagia (1 patient) NEUROLOGIC Central Nervous System \- Mildly delayed or normal early development \- Cerebellar ataxia \- Unsteady, wide-based gait \- Tremor \- Dysarthria \- Dysdiadochokinesis \- Dysmetria \- Mental retardation, mild to moderate \- Intellectual disability, mild \- Spasticity (variable) \- Leukodystrophy \- Brain MRI shows diffuse hypomyelination \- Cerebellar atrophy \- Thin corpus callosum ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism (variable) MISCELLANEOUS \- Onset in early childhood (2 to 4 years) \- Variable phenotype \- Slowly progressive or nonprogressive MOLECULAR BASIS \- Caused by mutation in the RNA polymerase III, subunit B gene (POLR3B, 614366.0001 ) ▲ 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	LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM	c2676243	8,357	omim	https://www.omim.org/entry/614381	2019-09-22T15:55:27	{"doid": ["0060797"], "mesh": ["C567313"], "omim": ["614381"], "orphanet": ["88637"], "genereviews": ["NBK99167", "NBK1334"]}
PIK3CA-related overgrowth spectrum (PROS) is a group of rare disorders that cause overgrowth of parts of the body, due to mutations in the PIK3CA gene. Specific disorders in this spectrum include: * Fibroadipose hyperplasia (also called fibroadipose overgrowth) * CLOVES syndrome * Megalencephaly-capillary malformation syndrome (MCAP syndrome) * Hemihyperplasia‐multiple lipomatosis syndrome (HHML syndrome) * Hemimegalencephaly * Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face) Signs and symptoms of PROS depend on the specific disorder present. Depending on the disorder, they can include having a larger-than-normal brain (megalencephaly), low muscle tone (hypotonia), seizures, intellectual disability, changes in the blood vessels (vascular system), and overgrowth of one area of the body (focal overgrowth) or of multiple areas of the body (segmental overgrowth), with normal growth elsewhere. PROS is usually caused by somatic mutations in the PIK3CA gene. These changes typically are only present in some cells or some areas of the body (called mosaicism), and are not known to be inherited. Rarely, PROS is caused by a de novo germline mutation, which is present in all cells of the body. The diagnosis of a PROS disorder can be confirmed with genetic testing of the PIK3CA gene. Treatment for a PROS disorder may involve surgical interventions, special education, and speech and physical therapies. [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	PIK3CA-related overgrowth spectrum	None	8,358	gard	https://rarediseases.info.nih.gov/diseases/12182/pik3ca-related-overgrowth-spectrum	2021-01-18T17:58:19	{"synonyms": ["PIK3CA-associated segmental overgrowth"]}
Good syndrome is a rare, adult-onset primary immunodeficiency suspected in patients who exhibit hypogammaglobulinemia and low levels of B cells along with a benign thymic tumor (thymoma) on chest X-ray. Symptoms include frequent opportunistic infections involving the sinuses and lungs, including severe CMV disease, P. carinii pneumonia, and mucocutaneous candidiasis. While the cause of Good syndrome remains unknown, there is some evidence that a defect of the bone marrow is involved. Treatment includes removal of the thymic tumor and immunoglobulin replacement. [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	Immunodeficiency with thymoma	c0221027	8,359	gard	https://rarediseases.info.nih.gov/diseases/8622/immunodeficiency-with-thymoma	2021-01-18T17:59:49	{"umls": ["C0221027"], "orphanet": ["169105"], "synonyms": ["Thymoma-immunodeficiency syndrome", "Good syndrome"]}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-39 (EIEE39) is caused by homozygous mutation in the SLC25A12 gene (603667) on chromosome 2q31. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features Wibom et al. (2009) reported a 3-year-old girl, born of distantly related Swedish parents, with severe psychomotor retardation, hypotonia, and hypomyelination of the central nervous system. Delayed development was first noted at age 5 months. Seizures and episodic apnea began at age 7 months. She had poor head control, could not roll over or grasp objects, and had poor eye contact. Plasma lactate was increased. She had no psychomotor development by age 3 years 8 months, and developed severe spasticity with hyperreflexia. Brain MRI showed global lack of myelination in the cerebral hemispheres and decreased supratentorial volume. The cerebellum, brainstem, and thalami were essentially normal. Focal lesions were not observed in gray matter. MR spectroscopy showed decreased N-acetylaspartate (NAA). Wolf and van der Knapp (2009) commented that the patient described by Wibom et al. (2009) had a primary defect in the cortical gray matter, rather than a leukoencephalopathy. The reduced peak of NAA found on spectroscopy indicates neuronal degeneration, and impaired formation of myelin can result from neuronal dysfunction. In response, Kucinski et al. (2009) agreed that the primary defect in this condition is in the gray matter, and suggested that abnormal neuronal metabolism could result in disrupted crosstalk between neurons and oligodendrocytes, and defective myelination. However, neuronal dysfunction was not as apparent as the lack of normal myelin development in the imaging data. Falk et al. (2014) reported 2 sibs, born of consanguineous Indian parents, with EIEE39. The proband was a 6.7-year-old girl who had onset of focal and generalized seizures at 10 months of age, followed by delayed psychomotor development and profound mental retardation with absent speech, inability to sit or walk, profound hypotonia, and inability to follow commands. Brain imaging showed delayed myelination and cerebral volume loss. MR spectroscopy showed decreased NAA and increased choline and lactate. Extensive metabolic work-up and muscle biopsy did not show any etiology. Her brother presented with seizures at age 10 months and a similar neurologic disorder as his sister. Inheritance The transmission pattern of EIEE39 in the family reported by Falk et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In a Swedish girl with global cerebral hypomyelination and severe psychomotor retardation, Wibom et al. (2009) identified a homozygous mutation in the SLC25A12 gene (603667.0001). In vitro functional expression studies showed impaired protein activity. Wibom et al. (2009) postulated that the disease pathogenesis did not result from impaired neuronal energy production, but rather from reduced mitochondrial aspartate efflux, which is necessary for NAA and myelin formation. In 2 sibs, born of consanguineous Indian parents, with EIEE39, Falk et al. (2014) identified a homozygous missense mutation in the SLC25A12 gene (R353Q; 603667.0002). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies in E. coli showed that the mutant protein had about 15% residual activity. Falk et al. (2014) suggested that the brain myelination defect in these patients stems primarily from neuronal loss attributable to the energy deficit caused by a lack of cellular reducing equivalents generated by the glutamate-aspartate shuttle, and that the brain insult may be compounded by a lack of neuronal-generated NAA that is required for myelin synthesis. Animal Model Jalil et al. (2005) found that Slc25a12-null mice had no detectable malate-aspartate shuttle activity in skeletal muscle and brain mitochondria. Mutant mice showed retarded growth, generalized tremor, pronounced motor coordination defects, and decreased survival. Analysis of the central nervous system showed impaired myelination without a change in neuron number. Analysis of lipid components showed a marked decrease in the myelin lipid galactosyl cerebroside. Brain content of the myelin lipid precursor, N-acetylaspartate, and that of aspartate were drastically decreased. The findings showed that aralar plays an important role in myelin formation by providing aspartate for the synthesis of N-acetylaspartate in neuronal cells. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Poor eye contact RESPIRATORY \- Apneic spells MUSCLE, SOFT TISSUES \- Hypotonia, severe NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Delayed psychomotor development, profound \- Crawling and standing not achieved \- Lack of speech \- Seizures \- Hypotonia, severe \- Spasticity \- Hyperreflexia \- Global lack of myelination in the cerebral hemispheres seen on MRI \- Decreased supratentorial volume \- Decreased N-acetyl aspartate seen on MR spectroscopy \- Gray matter appears relatively unaffected LABORATORY ABNORMALITIES \- Increased plasma lactate MISCELLANEOUS \- Onset in infancy \- Two unrelated families have been reported (last curated July 2016) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 25 (mitochondrial carrier, aralar), member 12 gene (SLC25A12, 603667.0001 ) ▲ 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	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 39	c2751855	8,360	omim	https://www.omim.org/entry/612949	2019-09-22T16:00:12	{"doid": ["0080349"], "mesh": ["C567847"], "omim": ["612949"], "orphanet": ["353217"], "synonyms": ["AGC1 deficiency", "HYPOMYELINATION, GLOBAL CEREBRAL", "ASPARTATE-GLUTAMATE CARRIER 1 DEFICIENCY", "Alternative titles", "Mitochondrial aspartate-glutamate carrier 1 deficiency", "AGC1 DEFICIENCY"]}
Goblet cell carcinoid (GCC) is a rare tumor normally occurring in the appendix which displays features of both a neuroendocrine tumor and a more aggressive form of cancer known as an adenocarcinoma. It is usually diagnosed in people over the age of 50. People with this tumor may develop acute appendicitis, abdominal pain, and diarrhea. Prognosis largely depends on the size of the tumor and whether it has spread to other parts of the body. Treatment involves surgery to remove the tumor. Depending on how much the tumor has spread, surgeons may remove the appendix, part of the colon, or the ovaries (in women). Some people will have chemotherapy after 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	Goblet cell carcinoid	c0205695	8,361	gard	https://rarediseases.info.nih.gov/diseases/10414/goblet-cell-carcinoid	2021-01-18T18:00:14	{"mesh": ["D002276"], "orphanet": ["329984"], "synonyms": ["Goblet cell carcinoma", "Mucinous carcinoid", "GCC", "Goblet cell adenocarcinoid", "Goblet cell tumor"]}
A rare urogenital disease characterized by otherwise unexplained chronic urinary retention of more than 1 liter of sterile urine on catheterization, an asensitive bladder with loss of urge to void, and no help of straining. Poor tolerance of self-catheterization is typically reported. The condition occurs in women between menarche and menopause. [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	Fowler urethral sphincter dysfunction syndrome	c2931462	8,362	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2795	2021-01-23T18:04:49	{"gard": ["2365"], "mesh": ["C537271"], "umls": ["C2931462"], "synonyms": ["Fowler syndrome", "Fowler-Christmas-Chapple syndrome"]}
An extremely rare developmental defect during embryogenesis malformation syndrome characterized by bands of extensile tissue connecting the margins of the upper and lower eyelids, in association with anal atresia. Patients may additionally present cleft palate, hydrocephalus and meningomyelocele. There have been no further descriptions in the literature since 1993. [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	Ankyloblepharon filiforme adnatum-imperforate anus syndrome	None	8,363	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1074	2021-01-23T17:33:07	{"gard": ["697"], "icd-10": ["Q87.8"], "synonyms": ["Aughton-Hufnagle syndrome"]}
Not to be confused with Ectropion. Cervical Ectropion Other namesCervical eversion Cervical ectropion SpecialtyGynecology Cervical ectropion is a condition in which the cells from the 'inside' of the cervical canal, known as glandular cells (or columnar epithelium), are present on the 'outside' of the vaginal portion of the cervix. The cells on the 'outside' of the cervix are typically squamous epithelial cells. Where the two cells meet is called the transformation zone, also known as the stratified squamous epithelium. Cervical ectropion can be grossly indistinguishable from early cervical cancer and must be evaluated by a physician to determine risks and prognosis. It may be found incidentally when a vaginal examination (or pap smear test) is done. The area may look red because the glandular cells are red. While many women are born with cervical ectropion, it can be caused by a number of reasons, such as: * Hormonal changes, meaning it can be common in young women * Using oral contraceptives * Pregnancy. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] Cervical ectropion can be associated with excessive, non-purulent vaginal discharge due to the increased surface area of columnar epithelium containing mucus-secreting glands as well as intermenstrual bleeding (bleeding outside of regular menses).[1] It may also give rise to post-coital bleeding, as fine blood vessels present within the columnar epithelium are easily traumatized. ## Causes[edit] Cervical ectropion is a normal phenomenon, especially in the ovulatory phase in younger women, during pregnancy, and in women taking oral contraceptive, which increases the total estrogen level in the body.[2] It also may be a congenital problem by the persistence of the squamocolumnar junction which is normally present prior to birth. Mucopurulent cervicitis may increase the size of the cervical ectropion.[3] ## Mechanism[edit] The squamocolumnar junction, where the columnar secretory epithelium of the endocervical canal meets the stratified squamous covering of the ectocervix, is located at the external os before puberty. As estrogen levels rise during puberty, the cervical os opens, exposing the endocervical columnar epithelium onto the ectocervix. This area of columnar cells on the ectocervix forms an area that is red and raw in appearance called an ectropion (cervical erosion). It is then exposed to the acidic environment of the vagina and, through a process of squamous metaplasia, transforms into stratified squamous epithelium.[4] ## Treatment[edit] Usually no treatment is indicated for clinically asymptomatic cervical ectropions. Hormonal therapy may be indicated for symptomatic erosion. If it becomes troublesome to the patient, it can be treated by discontinuing oral contraceptives, cryotherapy treatment, or by using ablation treatment under local anesthetic. Ablation involves using a preheated probe (100 °C) to destroy 3–4 mm of the epithelium. In post-partum erosion, observation and re-examination are necessary for 3 months after labour. ## References[edit] 1. ^ https://www.uptodate.com/contents/approach-to-abnormal-uterine-bleeding-in-nonpregnant-reproductive-age-women 2. ^ Standring: Gray's Anatomy, 40th ed. 3. ^ Bope: Conn's Current Therapy 2011, 1st Edition. 4. ^ Standring: Gray's Anatomy, 40th ed. ## External links[edit] Classification D * ICD-10: N86 * MeSH: D002579 * DiseasesDB: 2288 * v * t * e Female reproductive system Internal Adnexa Ovaries Follicles * corpus * hemorrhagicum * luteum * albicans * Theca of follicle * externa * interna * Follicular antrum * Follicular fluid * Corona radiata * Zona pellucida * Membrana granulosa * Perivitelline space Other * Germinal epithelium * Tunica albuginea * cortex * Cumulus oophorus * Stroma * Medulla Fallopian tubes * Isthmus * Ampulla * Infundibulum * Fimbria * Ostium Ligaments * Ovarian ligament * Suspensory ligament Wolffian vestiges * Gartner's duct * Epoophoron * Vesicular appendages of epoophoron * Paroophoron Uterus Regions * Body * Uterine cavity * Fundus * Cervix * External orifice * Cervical canal * Internal orifice * Supravaginal portion * Vaginal portion * Uterine horns Layers * Endometrium * epithelium * Myometrium * Perimetrium * Parametrium Ligaments * Round ligament * Broad ligament * Cardinal ligament * Uterosacral ligament * Pubocervical ligament General * Uterine glands Vagina * Fossa of vestibule of vagina * Vaginal fornix * Hymen * Vaginal rugae * Support structures * Vaginal epithelium External Vulva Labia * Mons pubis * Labia majora * Anterior commissure * Posterior commissure * Pudendal cleft * Labia minora * Frenulum of labia minora * Frenulum of clitoris * Vulval vestibule * Interlabial sulci * Bulb of vestibule * Vaginal orifice * vestibular glands/ducts * Bartholin's glands/Bartholin's ducts * Skene's glands/Skene's ducts Clitoris * Crus of clitoris * Body of clitoris (Corpus cavernosum) * Clitoral glans * Hood Urethra * Urethral crest Other * G-spot * Urethral sponge * Perineal sponge [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	Cervical ectropion	c0269189	8,364	wikipedia	https://en.wikipedia.org/wiki/Cervical_ectropion	2021-01-18T18:40:02	{"mesh": ["D002579"], "umls": ["C0269189", "C0007869"], "icd-10": ["N86"], "wikidata": ["Q720523"]}
Stratton-Parker Syndrome Other namesMullerian aplasia with hypoplastic thumbs SpecialtyOrthopedic Michels Caskey syndrome is a rare disorder that combines spinal and skeletal abnormalities, especially of the thumbs, with abnormal or absent female reproductive organs. Examples include the absence of a cervix and upper vagina or abnormalities of the uterus or vagina. Symptoms may also include scoliosis and primary amenorrhea. Synonyms include hypoplastic thumb Mullerian aplasia, and Mullerian aplasia with unilateral hypoplasia of the thumbs and skeletal spine deformities.[1] ## See also[edit] * Mullerian aplasia ## References[edit] 1. ^ "Michels Caskey syndrome". Genetic and Rare Disease Information Center. Retrieved 2012-08-19. ## External links[edit] Classification D * ICD-10: none * ICD-9-CM: none * OMIM: 601076 * MeSH: C537576 This article about a disease of musculoskeletal and connective tissue 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	Michels Caskey syndrome	c2931537	8,365	wikipedia	https://en.wikipedia.org/wiki/Michels_Caskey_syndrome	2021-01-18T18:33:25	{"gard": ["3590"], "mesh": ["C537576"], "umls": ["C2931537"], "icd-9": [], "icd-10": [], "wikidata": ["Q6837318"]}
L-Arginine:glycine amidinotransferase (AGAT) deficiency is a very rare type of creatine deficiency sydrome characterized by global developmental delay, intellectual disability, and myopathy. ## Epidemiology Less than 20 patients have been described with AGAT deficiency to date. ## Clinical description AGAT deficiency is characterized by global developmental delay, appearing in infancy, which can be associated with language impairment and autistic behavior in some, as well as a mild to moderate intellectual disability. Progressive muscle weakness and fatigability have been reported in older patients. Seizures and failure to thrive have also been described. If creatine supplementation is administered early enough, psychomotor delay may be avoided. ## Etiology AGAT deficiency is caused by mutations in the L-arginine:glycine amidinotransferase gene (GATM) located to chromosome 15q15.1. This gene encodes AGAT, which converts arginine and glycine to ornithine and guanidinoacetate in the creatine cycle pathway. ## Genetic counseling AGAT deficiency is transmitted in an autosomal recessive manner and genetic counseling is possible. [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	L-Arginine:glycine amidinotransferase deficiency	c2675179	8,366	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35704	2021-01-23T18:20:02	{"gard": ["10323"], "mesh": ["C567192"], "omim": ["612718"], "umls": ["C2675179"], "icd-10": ["E72.8"], "synonyms": ["AGAT deficiency"]}
Macrozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility). In affected males, almost all sperm cells have abnormally large and misshapen heads. The head of the sperm cell contains the male's genetic information that is to be passed on to the next generation. Normally, the head of a sperm cell contains one copy of each chromosome. In men with macrozoospermia, the sperm cell head contains extra chromosomes, usually four copies of each instead of the usual one. This additional genetic material accounts for the larger head size of the sperm cell. Additionally, instead of having one tail (flagellum) per sperm cell, affected sperm have multiple flagella, most often four. Because of the additional genetic material, if one of these abnormal sperm cells combines with an egg cell, the embryo will not develop or the pregnancy will result in miscarriage. ## Frequency Macrozoospermia is estimated to affect 1 in 10,000 males in North Africa. The prevalence of the condition outside this region is unknown. ## Causes Mutations in the AURKC gene cause macrozoospermia. The AURKC gene provides instructions for making a protein called aurora kinase C. This protein is abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. In the testes, this protein regulates the division of sperm cells. Aurora kinase C ensures that the mechanisms for cell division are in place and helps chromosomes properly align with each other so that every new sperm cell contains one copy of each chromosome after cell division. AURKC gene mutations that cause macrozoospermia lead to the production of a nonfunctional protein or a protein that is quickly broken down. This lack of aurora kinase C blocks cell division in sperm cells. Without cell division, the chromosomes are not split among multiple new sperm cells. As a result, affected sperm cells contain extra chromosomes, usually four copies of each instead of the usual one. ### Learn more about the gene associated with Macrozoospermia * AURKC ## 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 [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	Macrozoospermia	c0403812	8,367	medlineplus	https://medlineplus.gov/genetics/condition/macrozoospermia/	2021-01-27T08:25:09	{"gard": ["12385"], "mesh": ["C562903"], "omim": ["243060"], "synonyms": []}
A number sign (#) is used with this entry because Bloom syndrome (BLM), also referred to here as microcephaly, growth restriction, and increased sister chromatid exchange-1 (MGRISCE1), is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein-like-3 (RECQL3; 604610) on chromosome 15q26. Description Bloom syndrome is an autosomal recessive disorder characterized by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability. ### Genetic Heterogeneity of Microcephaly, Growth Restriction, and Increased Sister Chromatid Exchange See also MGRISCE2 (618097), caused by mutation in the TOP3A gene (601243) on chromosome 17p12. Clinical Features Landau et al. (1966) described a patient whose parents were second cousins and who showed low gamma-A and gamma-M serum proteins. German et al. (1984) collected information on 103 patients. German and Takebe (1989) suggested that differences in skin pigmentation in various ethnic groups may confer a degree of protection against actinic radiation and thus obscure one of the characteristic facial signs of Bloom syndrome, i.e., telangiectasia. As a result, Bloom syndrome may be underdiagnosed in some populations. Legum et al. (1991) described an affected Iranian Jewish male, possibly the first definite non-Ashkenazi Jewish patient. The patient had another unique complication, cardiomyopathy. Ferrara et al. (1967) described the disease in a 'Chinese-American'; however, the diagnosis was later (Ferrara, 1972) revised to focal dermal hypoplasia (305600). The 14 Japanese cases reported by German and Takebe (1989) differed somewhat from most cases recognized elsewhere in that dolichocephaly was a less constant feature, the facial skin lesions were less prominent, and life-threatening infections were less frequent. The characteristic predisposition to neoplasia, as well as the probable tendency to diabetes mellitus, was found, however. German (1990) stated that diabetes mellitus of maturity-onset type, developing, however, in the second or third decade, is proving to be a frequent feature. Mori et al. (1990) reported diabetes mellitus in Bloom syndrome. Kelly (1977) observed a case of Bloom syndrome in a black female. German (Szalay, 1978) confirmed the diagnosis of Bloom syndrome in the black female reported by Szalay (1972). German (1988) stated that the longest survival known to him is that of a man who died of esophageal cancer at the age of 48 years, having survived sigmoid cancer which had occurred 10 years earlier. Almost 150 cases worldwide have been cataloged by German (1990); he has personally examined 96 of these patients. Jewish patients represent 32% of the group, all but 1 of them being Ashkenazi. Complementation studies using sister chromatid exchange (SCE) as the measure of cross-correction indicate that this is one disease. Parental consanguinity was identified in 2 of 36 Jewish cases and in 25 of 75 non-Jewish cases. Heterozygotes do not show increased sister chromatid exchanges. German (1990) has not found an increased frequency of cancer in obligatory heterozygotes. Passarge (1991) observed 10 patients in Germany during a 20-year period. One patient died at the age of 5 years of acute leukemia, a second at the age of 18 years of pulmonary fibrosis and bronchiectasis, and a third at the age of 21 years of Hodgkin lymphoma and subsequently leukemia. German (1992) reported that there were 132 cases in the Bloom's Syndrome Registry as of January 1, 1990. One hundred and twenty seven had survived infancy. In all, 93 were still alive. Of the 39 deceased patients, 31 had died of cancer at a mean age of 27.8; cancer had been diagnosed at ages ranging from 4 years to 46 years. Of the 46 cancer patients, 14 had more than 1 primary, 2 had more than 2 primaries, and 1 had more than 3 primaries. Chisholm et al. (2001) reported a 19-year-old woman with typical clinical features of Bloom syndrome with a successful pregnancy. Because of her small pelvis on clinical examination, the patient underwent computed tomography pelvimetry, which showed adequate pelvic capacity. Preterm labor occurred at 32 weeks' gestation, and the infant was ultimately delivered at 35 weeks' gestation. The infant was less than the tenth percentile for length and weight for gestational age, but was otherwise healthy. Since preterm labor had occurred in this and a previously reported pregnancy in Bloom syndrome (Mulcahy and French, 1981), Chisholm et al. (2001) suggested increased surveillance for preterm labor in pregnancies of women with Bloom syndrome. Biochemical Features Vijayalaxmi et al. (1983) found that lymphocytes from patients with Bloom syndrome showed an incidence of cell resistance to the purine analog 6-thioguanine about 8 times the normal. Cells with specific locus mutations have been reported to be present in abnormally great numbers in BS fibroblast cultures, e.g., 6-thioguanine-resistant and diphtheria toxin-resistant cells. Seal et al. (1991) compared the uracil DNA glycosylase from 2 nontransformed cell strains derived from persons of different ethnic backgrounds, with 2 different, similarly highly purified, normal human uracil DNA glycosylases. For each of the 4, a molecular mass of 37 kD was observed. The Bloom syndrome enzymes differed substantially in their isoelectric point and were thermolabile as compared to the normal human enzymes. They displayed a different K(m) and V(max) and were strikingly insensitive to 5-fluorouracil and 5-bromouracil, pyrimidine analogs that drastically decreased the activity of the normal human enzymes. In particular, each Bloom syndrome enzyme required 10- to 100-fold higher concentrations of each analog to achieve comparable inhibition of enzyme activity. Other Features Langlois et al. (1989) used a glycophorin A assay to measure the frequency in persons of blood type MN of variant erythrocytes that lack the expression of 1 allelic form of the protein, presumably due to mutational or recombinational events in erythroid precursor cells. Blood from persons with Bloom syndrome showed 50- to 100-fold increases in the frequency of variants of 3 types, those with a hemizygous phenotype, those with a homozygous phenotype, and those with what appeared to be partial loss of the expression of 1 locus. The high frequency of homozygous variants, indicating altered allelic segregation, could be taken as evidence for increased somatic crossing-over in vivo. An increased generation of functional hemizygosity and homozygosity in somatic cells may play a role in the high cancer risk of persons with Bloom syndrome. Accumulation of p53 (191170) protein is seen in the nuclei of mammalian cells following DNA damage caused by ultraviolet radiation, x-ray, or a restriction enzyme. Promoters containing p53-binding sites show a dramatic transcriptional response to DNA damage. The p53 response to x-ray is rapid, reaching a peak at 2 hours after radiation, but is very transitory and reduced in magnitude compared with that seen in response to UV. Lu and Lane (1993) found no substantive defect in the p53 response of cells from ataxia-telangiectasia (208900) or xeroderma pigmentosum complementation group A (278700) patients. In contrast, 2 out of 11 primary cultures from Bloom syndrome patients showed complete absence of p53 accumulation following UV irradiation or SV40 infection and a grossly delayed and aberrant response following x-ray. Van Kerckhove et al. (1988) found a specific defect in the pokeweed mitogen-induced alternative pathway of lymphocyte activation in BS patients. Krejci et al. (2003) clarified the role of Srs2 in recombination modulation by purifying its encoded product and examining its interactions with the RAD51 recombinase (179617). Srs2 has a robust ATPase activity that is dependent on single-stranded DNA and binds RAD51, but the addition of a catalytic quantity of Srs2 to RAD51-mediated recombination reactions causes severe inhibition of these reactions. Krejci et al. (2003) showed that Srs2 acts by dislodging RAD51 from single-stranded DNA. Thus, the attenuation of recombination efficiency by Srs2 stems primarily from its ability to dismantle the RAD51 presynaptic filament efficiently. Krejci et al. (2003) suggested that their findings have implications for the basis of Bloom and Werner (277700) syndromes, which are caused by mutations in DNA helicases and are characterized by increased frequencies of recombination and a predisposition to cancers and accelerated aging. Inheritance Szalay (1963) provided the first evidence of a genetic basis. He described an isolated case in the child of first-cousin parents and 2 affected sibs. Autosomal recessive inheritance was established by German (1969), who maintains a worldwide registry which he periodically reports on (e.g., German et al., 1979). Of the then-known 21 families with Bloom syndrome, 12 were Ashkenazi and in these only 1 parental couple was consanguineous. On the other hand, 6 of the 9 non-Jewish unions were consanguineous. The Jewish gene appeared to have originated in a local area of eastern Europe. German and Takebe (1989) reported that 14 cases in 12 families had been identified in Japan. Widely separated birthplaces and a frequency of parental consanguinity greater than in the general population suggested that the mutation, although rare, is widely distributed in that country. Complementation studies indicated that the same genetic locus is involved in the Japanese cases as in the Ashkenazi Jewish cases and non-Ashkenazi Jewish cases. Cytogenetics Multiple seemingly nonspecific chromosomal breaks have been observed in Bloom syndrome, as in Fanconi anemia (227650), and may be related causally to the high frequency of leukemia (German et al., 1965; German, 1992). (The Bloom and Fanconi syndromes are chromosome breakage or clastogenic syndromes.) Schroeder and German (1974) showed that chromosomal aberrations were more numerous in Fanconi cells than in Bloom cells. In Bloom syndrome most interchanges were between homologous chromosomes, i.e., sister chromatid exchanges, whereas in Fanconi syndrome they were usually between nonhomologous chromosomes. Sister chromatid exchanges represent a cytologic marker useful for diagnosis including prenatal diagnosis. No test for the carrier state is known; the frequency of sister chromatid exchanges is not abnormal in heterozygotes (German et al., 1977). Although the nature of the basic defect was not known, the absence of a substance that is supplied by cocultivated normal cells and reduced the rate of sister chromatid exchanges in Bloom syndrome fibroblasts was suggested by the work of Rudiger et al. (1980). Spontaneous SCE, but not mutagen-induced SCE, is inhibited by the Bloom corrective factor present in normal cell-conditioned culture medium. Control cells and cells of Fanconi anemia and xeroderma pigmentosum reduced the rate of sister chromatid exchanges in Bloom cells by about 45 to 50% (Bartram et al., 1981). In contrast, Bloom heterozygous cells reduced the rate of SCE by only 16 to 18%. Bartram et al. (1981) interpreted the findings as indicative of dosage effect. They concluded that the data suggest the existence of a 'corrective factor' which is either inactive or absent in homozygous Bloom cells and reduced in heterozygotes. It may be identical with or closely related to the normal gene product of the Bloom locus. Thompson et al. (1982) found greatly increased sister chromatid exchanges in a mutant Chinese hamster ovary (CHO) cell line (EM9) with a DNA repair deficiency (see 126340). The deficiency was complemented in human-CHO somatic cell hybrids by human chromosome 19. Is this the Bloom syndrome defect? The mapping of Bloom syndrome to chromosome 15 excludes that possibility. (See Mapping Information.) Weksberg et al. (1988) addressed the issue of dominance or recessivity of the low-SCE Bloom syndrome phenotype. Although most cells from BS patients exhibit high SCE, lymphoid cells from some patients exhibit dimorphism for high and low SCE. A high-SCE lymphoblast line was mutagenized, and a clone carrying the markers ouabain resistance and thioguanine resistance was isolated to serve as a fusion parent. When fused with low-SCE BS lines, the hybrid was found to have low SCE levels, establishing dominance of the low-SCE phenotype. By the same methodology, Weksberg et al. (1988) did a complementation analysis using high-SCE lymphoblast cell lines derived from patients of diverse ethnic origin: Ashkenazi Jewish, French-Canadian, Mennonite, and Japanese. No correction of the high SCE characteristic of BS cells was seen in any hybrids. Thus, a single gene is responsible for the high-SCE phenotype in BS patients. Poppe et al. (2001) presented the cytogenetic findings in a Bloom syndrome patient diagnosed with acute myeloid leukemia (AML) of the FAB subtype M1, as well as a review of the literature, which showed the preferential occurrence of total or partial loss of chromosome 7 in BS patients with AML or myelodysplastic syndromes. Mapping Lander and Botstein (1987) pointed out that recessive disorders can be efficiently mapped using RFLPs in the study of the DNA of affected children from consanguineous marriages. The method, which the authors called 'homozygosity mapping,' involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. They showed that a single affected child of a first-cousin marriage contains the same total information about linkage as a nuclear family with 3 affected children. They presented calculations to show that it should be practical to map a recessive disease gene by studying DNA from fewer than a dozen unrelated, affected inbred children, given a complete RFLP linkage map. Bloom syndrome was pointed to by Lander and Botstein (1987) as a good candidate for this type of mapping. About 100 living affected persons are known, but there are only 8 known families with 2 living affected members and 1 with 3 affected members. This is insufficient for traditional linkage analysis. By contrast, at least 24 affected persons are children of marriages between cousins. In some more common recessive disorders such as Werdnig-Hoffmann syndrome (253300), multiplex families may be difficult to collect because affected children die at a young age. Because of the high parental consanguinity rate in non-Ashkenazi families with Bloom syndrome, Ellis et al. (1992) were able to do homozygosity mapping. Tight linkage was found with loci on distal 15q, specifically 15q26.1 (German et al., 1994). A polymorphic tetranucleotide repeat in an intron of the FES gene (190030) was homozygous in 25 of 26 individuals with Bloom syndrome whose parents were consanguineous (German et al., 1994). The location of the BLM gene on chromosome 15 was further supported by the finding of maternal uniparental disomy for that chromosome in a patient reported by Woodage et al. (1994). The patient had features of both Bloom syndrome and Prader-Willi syndrome (176270). Meiotic recombination between the 2 chromosomes 15 derived from the mother had resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual, Bloom syndrome was probably due to homozygosity for a gene located telomeric to D15S95, which is at 15q25, rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represented the first application of disomy analysis to the regional localization of a disease gene. Ellis et al. (1994) found a striking association of a specific allele at the FES locus and at the D15S127 locus, both of which are tightly linked to BLM. This linkage disequilibrium constituted strong support for a founder-effect hypothesis to account for the fact that approximately 1 in 110 Ashkenazi Jews carries the Bloom syndrome mutation. The rarity of Bloom syndrome and the recessive nature of its inheritance limits mapping of the gene by linkage approaches. McDaniel and Schultz (1992) used Bloom syndrome cells as recipients for microcell-mediated chromosome transfer to map a locus that results in complementation of the elevated sister chromatid exchange phenotype. Studying the Bloom cell line GM08505 (Coriell Institute) with a stable frequency of SCEs 10-fold higher than control values, they demonstrated that transfer of human chromosome 15 corrected the defect. Straughen et al. (1996) described a 2-Mb contiguous map of the 15q26.1 region constructed from P1 clones and yeast artificial chromosomes (YACs) that contains the BLM gene. They also reported a long-range restriction map of this region. Molecular Genetics ### Phenotype/Genotype Willis and Lindahl (1987) and Chan et al. (1987) independently demonstrated an abnormality of DNA ligase I (126391) in Bloom syndrome. DNA ligase I and DNA polymerase alpha (312040) are enzymes that function during DNA replication; DNA ligase II and DNA polymerase beta (174760) function during DNA repair. That the primary defect resides in the structural gene for DNA ligase I was suggested by the changes in the physical properties of the enzyme, specifically, heat sensitivity (Willis and Lindahl, 1987) and altered aggregation properties (Chan et al., 1987). Experiments with a fibroblast line derived from a Japanese case of Bloom syndrome showed that DNA ligase I from that source was not obviously heat sensitive or present in reduced amounts. Chan and Becker (1988) also came to the conclusion that mutation of the DNA ligase I gene may account for the primary metabolic defect in Bloom syndrome. Their data suggested that the defect in DNA ligase I is not due to a reduction in the number of protein molecules or to inhibitory substances but rather, at least in part, to the ATP binding and/or hydrolytic activity of the enzyme. Willis et al. (1987) found that all cell lines derived from 7 patients with Bloom syndrome contained a DNA ligase I with unusual properties. In 6 lines the enzyme activity was reduced and the residual enzyme was anomalously heat-labile. In the seventh line, they found a dimeric rather than a monomeric form of ligase I. Several cell lines representative of other inherited disorders had apparently normal DNA ligases. The data were interpreted as indicating that BLM is due to a defect in the structure of DNA ligase I caused by a 'leaky' point mutation occurring at one of at least 2 alternative sites. If the primary defect lies in the structural gene for DNA ligase I, then Barnes et al. (1990) reasoned that the mutation for Bloom syndrome is on chromosome 19, which encodes DNA ligase I. Since alteration of the DNA ligase I activity is a consistent biochemical feature of Bloom syndrome cells, Petrini et al. (1991) cloned DNA ligase I cDNA from normal human cells. Human DNA ligase I cDNAs from normal and BS cells complemented an S. cerevisiae DNA ligase mutation, and protein extracts prepared from S. cerevisiae transformants expressing normal and BS cDNA contained comparable levels of DNA ligase I activity. DNA sequencing and Northern blot analysis of DNA ligase I expression in 2 BS fibroblast lines representing each of 2 aberrant DNA ligase I molecular phenotypes demonstrated that the gene was unchanged in BS cells. Thus, a factor other than mutation in the ligase I gene must be involved as the basic defect. Nicotera et al. (1989) suggested that the major biochemical defect in Bloom syndrome is chronic overproduction of the superoxide radical anion. They thought that inefficient removal of peroxide might be responsible for high rates of sister chromatid exchange and chromosomal damage in Bloom syndrome cells. Seal et al. (1988) described a monoclonal antibody, defined by enzyme-linked immunosorbent assay (ELISA), that reacted with normal uracil DNA glycosylase (191525) of human placenta as well as with the glycosylases from normal human cell types and 13 abnormal human cell strains. On the other hand, the antibody neither recognized nor inhibited native uracil DNA glycosylase from any of 5 separate Bloom syndrome cell strains. Lack of immunoreactivity with this antibody, which the authors designated 40.10.09, was suggested as a test for the early diagnosis of Bloom syndrome. Cairney et al. (1987) described Wilms tumor in 3 patients with Bloom syndrome. Wilms tumor was bilateral in 1 of the 3 patients. Cairney et al. (1987) postulated that the elevated somatic recombination may mediate a high rate of conversion to homozygosity. Somatic recombination leading to homozygosity in Bloom syndrome has been suggested by several findings, including 'twin spots' or areas of hyper- and hypopigmentation on the skin of affected black children (Festa et al., 1979), increased frequency of exchange between the satellite stalks of acrocentric chromosomes (Therman et al., 1981), and increased variant blood group phenotypes in red cells from a patient with Bloom syndrome who was heterozygous for the AB blood group (Ben-Sasson et al., 1985). Petrella et al. (1991) observed autosomal triple trisomy involving chromosomes 2, 8, and 11 in a pregnancy conceived by a couple at risk for an offspring with Bloom syndrome. The SCE rate suggested that the conceptus was either heterozygous for the Bloom syndrome mutation or homozygous normal. They also found the Bloom syndrome gene in a non-Ashkenazi Jew and reported medulloblastoma in a patient with Bloom syndrome. The hypermutability of Bloom syndrome cells includes hyperrecombinability. Ellis et al. (1995) noted that although cells from all persons with Bloom syndrome exhibit the diagnostic high SCE rate, in some persons a minor population of low SCE lymphocytes exist in the blood. Lymphoblastoid cell lines (LCLs) with low SCE rates can be developed from these low SCE lymphocytes. In multiple low SCE LCLs examined from 11 patients with BS, polymorphic loci distal to BLM on 15q had become homozygous in LCLs from 5 persons, whereas polymorphic loci proximal to BLM remained heterozygous in all low SCE LCLs. These observations supported the hypothesis that low SCE lymphocytes arose through recombination within BLM in persons with BS who had inherited paternally and maternally derived BLM alleles mutated at different sites. Such a recombination event in a precursor stem cell in these compound heterozygotes thus gave rise to a cell whose progeny had a functionally wildtype gene and phenotypically a low SCE rate (Ellis et al., 1995). Ellis et al. (1995) used the low SCE LCLs in which reduction to homozygosity had occurred for localizing BLM by an approach referred to as somatic crossover point (SCP) mapping. The precise map position of BLM was determined by comparing the genotypes of the recombinant low SCE LCLs from the 5 persons mentioned above with their constitutional genotypes at loci in the region around BLM. The strategy was to identify the most proximal polymorphic locus possible that was constitutionally heterozygous and that had been reduced to homozygosity in the low SCE LCLs, and to identify the most distal polymorphic locus possible that had remained constitutionally heterozygous in them. BLM would have to be in the short interval defined by the reduced (distal) and the unreduced (proximal) heterozygous markers. The power of this approach was limited only by the density of polymorphic loci available in the immediate vicinity of BLM. A candidate for BLM was identified by direct selection of a cDNA derived from a 250-kb segment of the genome to which BLM had been assigned by SCP mapping. cDNA analysis of the candidate gene identified a 4437-bp cDNA that encoded a 1417-amino acid peptide with homology to the RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases (RECQL3; 604610). The presence of chain-terminating mutations in the candidate gene in persons with Bloom syndrome proved that it was BLM. Mutational analysis in the first 13 unrelated persons with BS examined permitted the identification of 7 unique mutations in 10 of them. The fact that 4 of the 7 mutations resulted in premature termination of translation indicated that the cause of most Bloom syndrome is the loss of enzymatic activity of the BLM gene product. Identification of loss-of-function mutations in BLM is consistent with the autosomal recessive transmission, and the homology of BLM and RecQ suggested that BLM has enzymatic activity. In 4 persons with Jewish ancestry, a 6-bp deletion and a 7-bp insertion at nucleotide 2281 were identified, and each of the 4 persons were homozygous for the mutation (604610.0001). Homozygosity was predictable because linkage disequilibrium had been detected in Ashkenazi Jews with Bloom syndrome between BLM, D15S127, and FES (Ellis et al., 1994). Thus a person who carried this deletion/insertion mutation was a founder of Ashkenazi Jewish population and nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. The RecQ gene family, of which BLM is a member, is named after the E. coli gene. RecQ is an E. coli gene that is a member of the RecF recombination pathway, a pathway of genes in which mutations abolish the conjugational recombination proficiency and ultraviolet resistance of a mutant strain. RecQL (600537) is a human gene isolated from HeLa cells, the product of which possesses DNA-dependent ATPase, DNA helicase, and 3-prime-to-5-prime single-stranded DNA translocation activities. Ellis et al. (1995) suggested that the absence of the BLM gene product probably destabilizes other enzymes that participate in DNA replication and repair, perhaps through direct interaction and through more general responses to DNA damage. Ellis and German (1996) reported that the BLM protein has similarity to 2 other proteins that are members of the RecQ family of helicases, namely the gene product encoded by the Werner syndrome gene (WRN; 277700) and the product of the yeast gene SGS1. SGS1 was identified by a mutation that suppressed the slow-growth phenotype of mutations in the topoisomerase gene. These proteins have 42 to 44% amino acid identity across the conserved helicase motifs. In addition, the proteins are of similar length and contain highly negatively charged N-terminal regions and highly positively charged C-terminal regions. Ellis and German (1996) noted that these similarities in overall structure have raised the possibility that the proteins play similar roles in metabolism. Since the SGS1 gene product is known to interact with the products of the yeast topoisomerase genes, they predicted that the BLM and WRN genes interact with human topoisomerases. Sinclair et al. (1997) showed that mutation of the yeast SGS1 gene causes premature aging in yeast mother cells as demonstrated by shortened life span and the aging-induced phenotypes of sterility and redistribution of the Sir3 silencing protein from telomeres to the nucleolus. Further, in old SGS1 cells the nucleolus was enlarged and fragmented, changes that also occur in old wildtype cells. Their findings suggested a conserved mechanism of cellular aging that may be related to nucleolar structure. The similar effect of the related SGS1 and WRN genes on yeast and human aging, along with age-associated changes in rDNA content reported for several mammalian species, suggested that a common mechanism may underlie aging in eukaryotes. Men with Bloom syndrome are sterile; women have reduced fertility and a shortened reproductive span. In an immunocytologic study of mouse spermatocytes, Walpita et al. (1999) showed that the BLM protein is first evident as discrete foci along the synaptonemal complexes of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociated from the synapsed autosomal axes during early pachynema and were no longer seen in mid-pachynema. BLM colocalized with the single-stranded DNA-binding replication protein A (see 179835), which had been shown to be involved in meiotic synapsis. However, there was a temporary delay in the appearance of BLM protein along the synaptonemal complexes relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomolog interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the synaptonemal complexes, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I. Ellis et al. (1999) described the effects on the abnormal cellular phenotype of BS, namely an excessive rate of SCE, when normal BLM cDNA was stably transfected into 2 types of BS cells, SV40-transformed fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cells. The experiments proved that BLM cDNA encodes a functional protein capable of restoring to or toward normal the uniquely characteristic high-SCE phenotype of BS cells. In a patient with Bloom syndrome and both high- and low-SCE cell lines, Foucault et al. (1997) identified compound heterozygosity for a cys1036-to-phe (C1036F; 604610.0004) substitution in the C-terminal region of the peptide and an unidentified mutation affecting expression of the RECQL3 gene. Foucault et al. (1997) concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low-SCE phenotype. Topoisomerase II-alpha (126430) mRNA and protein levels were decreased in the high-SCE cells, whereas they were normal in the corresponding low-SCE cells. Foucault et al. (1997) proposed that in addition to its putative helicase activity, RECQL3 might be involved in transcription regulation. ### Associations Pending Confirmation For discussion of a possible association between a Bloom syndrome-like phenotype and variation in the RMI1 gene, see 610404.0001. For discussion of a possible association between a Bloom syndrome-like phenotype and deletion of the RMI2 gene, see 612426.0001. Clinical Management German (1992) commented that BS neoplasms themselves, e.g., leukemic marrow cells, demonstrate a high sister chromatid exchange rate similar to nonneoplastic cells of BS patients. A clinical difference is that leukemia in BS usually presents itself with leukopenia rather than leukocytosis. He also commented on the fact that there is pitifully little that one can do in relation to the proneness to cancer. In contrast to the situation with carcinoma, early diagnosis of leukemia is at present not known to improve the chances of curative therapy. German (1992) advised against frequent hematologic examinations in children for fear of untoward psychologic effects. Allogeneic marrow grafting has not been carried out in BS. An argument can be made for identifying as soon as possible a potential donor of bone marrow for any person with BS, and the cryopreservation of cord-blood stem cells of HLA-matched sibs who might be born after the BS child is identified can be considered, for possible later transplantation. Animal Model Chester et al. (1998) found that mouse embryos homozygous for a targeted mutation in the murine Bloom syndrome gene are developmentally delayed and die by embryonic day 13.5. They determined that the interrupted gene is the homolog of the human BLM gene by its homologous sequence, its chromosomal location, and the demonstration of high numbers of sister chromatid exchanges in cultured murine Blm -/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12 to 24 hours) seen during midgestation in murine Blm -/- embryos. The growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early postimplantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm -/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes. Using embryonic stem cell technology, Luo et al. (2000) generated viable Bloom syndrome mice that were prone to a wide variety of cancers. Cell lines from these mice showed elevations in the rates of mitotic recombination. They demonstrated that the increased rate of loss of heterozygosity resulting from mitotic recombination in vivo constituted the underlying mechanism causing tumor susceptibility in these mice. INHERITANCE \- Autosomal recessive GROWTH Height \- Average adult male height 151cm \- Average adult female height 144cm Other \- Prenatal onset growth retardation \- Growth failure HEAD & NECK Head \- Dolichocephaly \- Microcephaly Face \- Narrow \- Malar hypoplasia Ears \- Prominent ears Nose \- Prominent nose Teeth \- Absent upper lateral incisors RESPIRATORY Airways \- Bronchiectasis Lung \- Chronic lung disease GENITOURINARY Internal Genitalia (Male) \- Azoospermia \- Cryptorchidism Internal Genitalia (Female) \- Reduced fertility in females SKELETAL Hands \- Syndactyly \- Polydactyly \- Fifth finger clinodactyly SKIN, NAILS, & HAIR Skin \- Facial telangiectasia in butterfly midface distribution (exacerbated by sun) \- Spotty hypopigmentation \- Spotty hyperpigmentation \- Cafe-au-lait spots \- Hypertrichosis \- Photosensitivity NEUROLOGIC Central Nervous System \- Mild mental retardation in some \- Learning disability VOICE \- High-pitched ENDOCRINE FEATURES \- Noninsulin-dependent diabetes mellitus IMMUNOLOGY \- Immunoglobulin deficiency (IgA, IgG, IgM) \- Impaired lymphocyte proliferation response to malignancy NEOPLASIA \- Leukemia \- Lymphoma \- Adenocarcinoma \- Squamous cell carcinoma \- Hypersensitivity to chemotherapy LABORATORY ABNORMALITIES \- High sister chromatid exchange (SCE) rate \- SCE normal in heterozygotes \- Increased chromosomal breakage \- Decreased IgA, IgG, IgM MISCELLANEOUS \- Life-threatening infections \- Predisposition to neoplasia MOLECULAR BASIS \- Caused by mutation in the RecQ protein-like 3 gene (RECQL3, 604610.0001 ) ▲ 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	BLOOM SYNDROME	c0005859	8,368	omim	https://www.omim.org/entry/210900	2019-09-22T16:30:22	{"doid": ["2717"], "mesh": ["D001816"], "omim": ["210900"], "orphanet": ["125"], "synonyms": ["Alternative titles", "BS", "MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 1"], "genereviews": ["NBK1294", "NBK1398"]}
A number sign (#) is used with this entry because of evidence that Heimler syndrome-1 (HMLR1) is caused by homozygous or compound heterozygous mutations in the PEX1 gene (602136) on chromosome 7q21. Description Heimler syndrome-1 (HMLR1), which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). ### Genetic Heterogeneity of Heimler Syndrome Another form of Heimler syndrome (HMLR2; 616617) is caused by mutation in the PEX6 gene (601498) on chromosome 6p21. Clinical Features Heimler et al. (1991) described an 11-year-old boy and his 9-year-old sister, born of healthy, unrelated parents. Both children had severe bilateral sensorineural hearing loss which developed in the first or second year of life. Both had normal primary dentition, but the permanent teeth showed generalized enamel hypoplasia. Both children had Beau lines (transverse ridges) of the toenails and the brother had white patches in the fingernails (leukonychia). The sibs had been reported earlier by Fox et al. (1989). Tischkowitz et al. (1999) reported a 12-year-old girl who presented at age 7 years with unilateral sensorineural hearing loss. In addition, she had hypomineralized amelogenesis imperfecta of the permanent dentition only, and Beau lines, but no leukonychia. Tischkowitz et al. (1999) pointed out that although the amelogenesis imperfecta in the original report by Heimler et al. (1991) was said to be hypoplastic in nature, this diagnosis had been made on the basis of clinical and radiographic appearances rather than on histopathologic examination of teeth, which was available in the later case. Pollak et al. (2003) reported a pair of sibs with Heimler syndrome who had sensorineural hearing loss diagnosed after the first year of life and enamel hypoplasia with normal primary dentition. Nail findings of Beau lines and leukonychia, which were described in previously reported cases, were absent to questionable. The parents were unaffected and nonconsanguineous. Inheritance Heimler et al. (1991) and Pollak et al. (2003) suggested autosomal recessive inheritance of this disorder. Molecular Genetics Ratbi et al. (2015) performed whole-exome sequencing in 8 families with Heimler syndrome and identified biallelic mutations in the PEX1 gene in 4 of the families, including the family reported by Heimler et al. (1991) (602136.0004 and 602136.0006-602136.0009). In 2 families (see HMLR2, 616617), they identified mutations in the PEX6 gene (601498.0010-601498.0013). No mutations in any of the known PEX genes were identified in the 2 remaining families, 1 of which was the family previously studied by Tischkowitz et al. (1999). Ratbi et al. (2015) noted phenotypic differences between the affected individuals from these 2 families and those in whom PEX mutations were identified, including less severe hearing loss and minimal to no nail defects. Additionally, no fundus abnormalities were observed in the latter 2 families, whereas 3 patients with PEX1 mutations, including the 2 sibs previously reported by Heimler et al. (1991), exhibited retinal pigmentation abnormalities; the sibs reported by Heimler et al. (1991) also showed macular dystrophy. All 4 patients with PEX1 mutations had retinal pigmentation abnormalities. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss Eyes \- Retinal pigmentation abnormalities (in some patients) \- Macular dystrophy (rare) Teeth \- Normal primary teeth \- Amelogenesis imperfecta (secondary teeth) SKIN, NAILS, & HAIR Nails \- Beau's lines (fingernails and toenails) \- Punctate leukonychia MOLECULAR BASIS \- Caused by mutation in the peroxisome biogenesis factor 1 gene (PEX1, 602136.0006 ) ▲ 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	HEIMLER SYNDROME 1	c1856186	8,369	omim	https://www.omim.org/entry/234580	2019-09-22T16:27:22	{"mesh": ["C535994"], "omim": ["234580"], "orphanet": ["3220"], "synonyms": ["Alternative titles", "HEARING LOSS, SENSORINEURAL, WITH ENAMEL HYPOPLASIA AND NAIL DEFECTS", "PEROXISOME BIOGENESIS DISORDER 1C"]}
A number sign (#) is used with this entry because of evidence that familial adenomatous polyposis-4 (FAP4) is caused by compound heterozygous mutation in the MSH3 gene (600887) on chromosome 5q11. Description Familial adenomatous polyposis-4 is an autosomal recessive tumor predisposition syndrome characterized by the development of multiple colonic adenomas in adulthood, often with progression to colorectal cancer. Proliferative lesions in other tissues may also occur (summary by Adam et al., 2016). For a discussion of genetic heterogeneity of familial adenomatous polyposis, see FAP1 (175100). Clinical Features Adam et al. (2016) reported 2 pairs of sibs from 2 unrelated families of central European origin with colorectal adenomatous polyposis. Three patients were diagnosed with polyps in their thirties; the fourth patient was diagnosed with colorectal adenocarcinoma at age 56. The 3 older patients, including both probands, had additional significant proliferative disorders affecting other organs, including thyroid adenoma, duodenal polyps, intraductal papillomas of the breast, uterine myoma, cutaneous fibrolipoma, astrocytoma, and gastric carcinoma. Inheritance The transmission pattern of FAP4 in the families reported by Adam et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of 2 unrelated families with FAP4, Adam et al. (2016) identified 4 different mutations in the MSH3 gene in compound heterozygosity (600887.0001-600887.0004). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Each patient carried a truncating mutation on 1 allele and a splice site mutation on the other allele, all with a loss-of-function effect. Normal and adenomatous colonic samples from 1 patient showed complete loss of nuclear MSH3 immunostaining. Tumor tissue from both probands showed high microsatellite instability of di- and tetranucleotides (EMAST). Adenomatous tissue from 1 patient also showed several different somatic mutations in the APC gene (611731). INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Colorectal adenomas, multiple \- Duodenal adenomas, multiple NEOPLASIA \- Increased susceptibility to multiple proliferative tumors or cancers \- Colorectal cancer \- Gastric cancer \- Thyroid adenoma \- Breast papilloma \- Uterine leiomyomas \- Skin fibromas \- Astrocytoma MISCELLANEOUS \- Increased susceptibility to multiple carcinomas \- Colorectal adenomas develop in mid adulthood (30s) \- Two unrelated families have been reported (last curated August 2016) MOLECULAR BASIS \- Caused by mutation in the mutS homolog 3 gene (MSH3, 600887.0001 ) ▲ 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	FAMILIAL ADENOMATOUS POLYPOSIS 4	c4310719	8,370	omim	https://www.omim.org/entry/617100	2019-09-22T15:46:55	{"doid": ["0080412"], "omim": ["617100"], "orphanet": ["480536"], "synonyms": ["MSH3-related AFAP", "MSH3-related attenuated FAP", "MSH3-related attenuated familial polyposis coli"]}
Hyper IgM syndrome is a type of primary immunodeficiency syndrome. Primary immunodeficiency occurs when part of a person’s immune system is missing or does not work correctly. The bodies of people with primary immunodeficiency can’t get rid of germs or protect themselves from new germs as well as they should. Primary immunodeficiencies are inherited, meaning they are passed down from parents to children. Hyper IgM syndromes are characterized by normal or elevated serum immunoglobulin M levels with absence of immunoglobulin G, A, and E. Immunoglobulins are proteins found in the blood. Hyper IgM results in a susceptibility to bacterial infections and sometimes opportunistic infections. There are five different types of hyper IgM syndromes (types 1-5). The types are distinguished by the location of the gene mutation involved. [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	Immunodeficiency with hyper IgM type 1	c0398689	8,371	gard	https://rarediseases.info.nih.gov/diseases/73/immunodeficiency-with-hyper-igm-type-1	2021-01-18T17:59:49	{"mesh": ["D053307"], "omim": ["308230", "605258", "606843", "608106", "608184"], "orphanet": ["101088"], "synonyms": ["X-linked hyper IgM syndrome", "Hyper IgM immunodeficiency, x-linked", "Hyper IgM syndrome", "Hyper IgM syndrome 1", "XHIM", "HIGM", "IHIS", "HIGM1"]}
For the medical journal, see Childhood Obesity (journal). Childhood obesity Children with varying degrees of body fat SpecialtyEndocrinology, pediatrics, bariatrics Part of a series on Human body weight General concepts * Obesity (Epidemiology) * Overweight * Underweight * Body shape * Weight gain * Weight loss * Gestational weight gain * Diet (nutrition) * Weight management * Overnutrition * Childhood obesity (Epidemiology) Medical concepts * Adipose tissue * Classification of obesity * Genetics of obesity * Metabolic syndrome (Epidemiology of metabolic syndrome) * Metabolically healthy obesity * Obesity paradox Measurements * Body adiposity index * Body mass index * Body fat percentage * Body Shape Index * Corpulence index * Lean body mass * Relative Fat Mass * Waist–hip ratio * Waist-to-height ratio Related conditions * Diabetes (Type 1) * Eating disorder (Anorexia • Bulimia • Binge eating disorder) * Food addiction * Hyperthyroidism * Malnutrition * RED-S * Starvation (Starvation response) * PCOS Obesity-associated morbidity * Arteriosclerosis * Atherosclerosis * Fatty liver disease * GERD * Heart disease * Hypertension * Obesity and cancer * Osteoarthritis * Prediabetes * Sleep apnea * Type 2 diabetes Management of obesity * Anti-obesity medication * Bariatrics * Bariatric surgery * Dieting (List of diets) * Caloric deficit * Exercise (outline) * Liposuction * Obesity medicine * Weight loss camp * Weight loss coaching * Yo-yo effect Social aspects * Comfort food * Fast food (Criticism) * Fat acceptance movement * Fat fetishism * Health at Every Size * Hunger * Obesity and the environment * Sedentary lifestyle * Social determinants of obesity * Social stigma of obesity * Weight cutting * Weight class * v * t * e Childhood obesity is a condition where excess body fat negatively affects a child's health or well-being. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of obesity in children and its many adverse health effects it is being recognized as a serious public health concern.[1] The term overweight rather than obese is often used when discussing childhood obesity, especially in open discussion, as it is less stigmatizing.[2] The prevalence of childhood obesity is known to differ by sex and gender.[3] ## Contents * 1 Classification * 2 Effects on health * 2.1 Psychological * 2.2 Physical * 2.3 Long-term effects * 3 Causes * 3.1 Genetics * 3.2 Family practices * 3.3 Social policies * 3.3.1 Advertising * 3.4 Socioeconomic status * 4 Prevention * 4.1 Maternal Body Mass Index * 4.2 Dietary * 4.3 Legal * 4.4 Physical activity * 4.5 Home environment * 4.6 Developmental factors * 4.7 Medical illness * 4.8 Psychological factors * 5 Management * 5.1 Lifestyle * 5.2 Medications * 5.3 Surgery * 6 Epidemiology * 6.1 Canada * 6.2 Brazil * 6.3 United States * 6.4 Australia * 7 Research * 8 See also * 9 Footnotes * 10 Further reading * 11 External links ## Classification Main article: Classification of childhood obesity BMI for age percentiles for boys 2 to 20 years of age. BMI for age percentiles for girls 2 to 20 years of age. Body mass index (BMI) is acceptable for determining obesity for children two years of age and older.[4] It is determined by the ratio of weight to height.[5] The normal range for BMI in children vary with age and sex. While a BMI above the 85th percentile is defined as overweight, a BMI greater than or equal to the 95th percentile is defined as obesity by Centers for Disease Control and Prevention. It has published tables for determining this in children.[6] The US Preventive Service Task Force reported that not all children with a high BMI need to lose weight though. High BMI can identify a possible weight problem, but does not differentiate between fat or lean tissue.[7] Additionally, BMI may mistakenly rule out some children who do have excess adipose tissue. It is therefore beneficial to supplement the reliability of a BMI diagnosis with additional screening tools such as adipose tissue or skin fold measurements.[8] ## Effects on health ### Psychological The first problems to occur in obese children are usually emotional or psychological.[9] Obese children often experience bullying by their peers.[10][11] Some are harassed or discriminated against by their own family.[11] Stereotypes abound and may lead to low self-esteem and depression.[12] ### Physical Childhood obesity however can also lead to life-threatening conditions including diabetes, high blood pressure, heart disease, sleep problems, cancer, and other disorders.[13][14] Some of the other disorders would include liver disease, early puberty or menarche, eating disorders such as anorexia and bulimia, skin infections, and asthma and other respiratory problems.[15] The early physical effects of obesity in adolescence include, almost all of the child's organs being affected, gallstones, hepatitis, sleep apnoea and increased intracranial pressure.[16] Overweight children are also more likely to grow up to be overweight adults.[14] Obesity during adolescence has been found to increase mortality rates during adulthood.[17] A 2008 study has found that children who are obese have carotid arteries which have prematurely aged by as much as thirty years as well as abnormal levels of cholesterol.[18] System Condition System Condition Endocrine * Impaired glucose tolerance * Diabetes mellitus * Metabolic syndrome * Hyperandrogenism * Effects on growth and puberty * Nulliparity and nulligravidity[19] Cardiovascular * Hypertension * Hyperlipidemia * Increased risk of coronary heart disease as an adult Gastroentestinal * Nonalcoholic fatty liver disease * Cholelithiasis Respiratory * Obstructive sleep apnea * Obesity hypoventilation syndrome Musculoskeletal * Slipped capital femoral epiphysis (SCFE) * Tibia vara (Blount disease) Neurological * Idiopathic intracranial hypertension Psychosocial * Distorted peer relationships * Poor self-esteem [20] * Anxiety * Depression Skin * Furunculosis * Intertrigo [21] ### Long-term effects Children who are obese are likely to be obese as adults. Thus, they are more at risk for adult health problems such as heart disease, type 2 diabetes, stroke, several types of cancer, and osteoarthritis. One study showed that children who became obese as early as age 2 were more likely to be obese as adults.[22] According to an article in The New York Times all of these health effects are contributing to a shorter lifespan of five years for these obese children. It is the first time in two centuries that the current generation of children in America may have a shorter lifespan than their parents.[23] ## Causes Childhood obesity can be brought on by a range of factors which often act in combination.[24][25][26][27][28] “Obesogenic environment” is the medical term set aside for this mixture of elements.[29] The greatest risk factor for child obesity is the obesity of both parents. This may be reflected by the family's environment and genetics.[30] Other reasons may also be due to psychological factors and the child's body type. A 2010 review stated that childhood obesity likely is the result of the interaction of natural selection favouring those with more parsimonious energy metabolism and today's consumerist society with easy access to energy dense cheap foods and less energy requirements in daily life.[31] Factors include the increase in use of technology, increase in snacks and portion size of meals, and the decrease in the physical activity of children. A study found kids that use electronic devices 3 or more hours a day had between a 17- 44% increased risk of being overweight, or a 10- 61% increased risk of obese (Cespedes 2011).[full citation needed] Childhood obesity is common among children from, low-income, African American and Hispanic communities. This is mainly because minority children spend less time playing outside the house and staying active. Some contributors to childhood obesity is that parents would rather have their children stay inside the home because they fear that gang, drug violence, and other dangers might harm them.[32] ### Genetics Childhood obesity is often the result of an interplay between many genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose individuals to obesity when sufficient calories are present. Over 200 genes affect weight by determining activity level, food preferences, body type, and metabolism.[33] Having two copies of the allele called FTO increases the likelihood of both obesity and diabetes.[34] As such, obesity is a major feature of a number of rare genetic conditions that often present in childhood: * Prader–Willi syndrome with an incidence between 1 in 12,000 and 1 in 15,000 live births is characterized by hyperphagia and food preoccupations which leads to rapid weight gain in those affected. * Bardet–Biedl syndrome * MOMO syndrome * Leptin receptor mutations * Congenital leptin deficiency * Melanocortin receptor mutations In children with early-onset severe obesity (defined by an onset before ten years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.[35][36] One study found that 80% of the offspring of two obese parents were obese in contrast to less than 10% of the offspring of two parents who were of normal weight.[1][37] The percentage of obesity that can be attributed to genetics varies from 6% to 85% depending on the population examined.[38] ### Family practices In the recent decades, family practices have significantly changed, and several of these practices greatly contribute to childhood obesity:[5] * With a decreasing number of mothers who breast-feed, more infants become obese children as they grow up and are reared on infant formula instead.[39] * Less children go outside and engage in active play as technology, such as television and video games, keep children indoors. * Rather than walking or biking to a bus-stop or directly to school, more school-age children are driven to school by their parents, reducing physical activity. * As family sizes decrease, the children's pester power, their ability to force adults to do what they want, increases. This ability enables them to have easier access to calorie-packed foods, such as candy and soda drinks. * The social context around family meal-time plays a role in rates of childhood obesity ### Social policies Former First Lady Michelle Obama with students in Virginia sampling healthy meals being introduced by the United States Department of Agriculture Different communities and nations have adopted varying social practices and policies that are either beneficial or detrimental to children's physical health. These social factors include:[5] * the quality of school lunches * the emphasis of schools on physical activity * access to vending machines and fast-food restaurants * prevalence of and access to parks, bike paths, and sidewalks * government subsidies for corn oil and sugar * advertising of fast-food restaurants and candy * prices of healthy and unhealthy foods * access to fresh, healthy, and affordable food[40] #### Advertising Advertising of unhealthy foods correlates with childhood obesity rates.[5] In some nations, advertising of candy, cereal, and fast-food restaurants is illegal or limited on children's television channels.[41] The media defends itself by blaming the parents for yielding to their children's demands for unhealthy foods.[5] ### Socioeconomic status It is much more common for young people who come from a racial or ethnic minority, or for those who have a lower socioeconomic status, to be overweight and to engage in less healthy behaviors and sedentary activities.[42] ## Prevention Schools play a large role in preventing childhood obesity by providing a safe and supporting environment with policies and practices that support healthy behaviors.[43] At home, parents can help prevent their children from becoming overweight by changing the way the family eats and exercises together. The best way children learn is by example, so parents should lead by example by living a healthy lifestyle.[44] Screening for obesity is recommended in those over the age of six.[45] Both physical activity and diet can help to reduce the risk of obesity in children from 0 to 5 years old; meanwhile, exclusive physical activity can reduce the risk of obesity for children aged from 6 to 12 years old, and adolescents aged from 13 to 18 years old.[46] The implementation of strategies to improve childcare services such as preschools, nurseries, daycare, and kindergarten on healthy eating, physical activity, and obesity prevention shows little effect on a child's diet, physical activity, and weight status.[47] ### Maternal Body Mass Index Maternal body mass index (BMI) is an important predictor of childhood obesity. Mothers with pre-pregnancy obesity, as defined by BMI ≥30kg/m², are known to have children that have higher growth rates and more likely to have obesity.[48] ### Dietary The effects of eating habits on childhood obesity are difficult to determine. A three-year randomized controlled study of 1,704 3rd grade children which provided two healthy meals a day in combination with an exercise program and dietary counsellings failed to show a significant reduction in percentage body fat when compared to a control group. This was partly due to the fact that even though the children believed they were eating less their actual calorie consumption did not decrease with the intervention. At the same time observed energy expenditure remained similar between the groups. This occurred even though dietary fat intake decreased from 34% to 27%.[49] A second study of 5,106 children showed similar results. Even though the children ate an improved diet there was no effect found on BMI.[50] Why these studies did not bring about the desired effect of curbing childhood obesity has been attributed to the interventions not being sufficient enough. Changes were made primarily in the school environment while it is felt that they must occur in the home, the community, and the school simultaneously to have a significant effect.[37] A Cochrane review of a lower fat diet in children (30% or less of total energy) to prevent obesity found the existing evidence of very low to moderate quality, and firm conclusions could not be made.[51] Calorie-rich drinks and foods are readily available to children. Consumption of sugar-laden soft drinks may contribute to childhood obesity. In a study of 548 children over a 19-month period the likelihood of obesity increased 1.6 times for every additional soft drink consumed per day.[52][53] Calorie-dense, prepared snacks are available in many locations frequented by children. As childhood obesity has become more prevalent, snack vending machines in school settings have been reduced by law in a small number of localities. Some research suggests that the increase in availability of junk foods in schools can account for about one-fifth of the increase in average BMI among adolescents over the last decade.[54] Eating at fast food restaurants is very common among young people with 75% of 7th to 12th grade students consuming fast food in a given week.[55] The fast food industry is also at fault for the rise in childhood obesity. This industry spends about $4.2 billion on advertisements aimed at young children. McDonald's alone has thirteen websites that are viewed by 365,000 children and 294,000 teenagers each month. In addition, fast food restaurants give out toys in children's meals, which helps to entice children to buy the fast food. Forty percent of children ask their parents to take them to fast food restaurants on a daily basis. To make matters worse, out of 3000 combinations created from popular items on children's menus at fast food restaurants, only 13 meet the recommended nutritional guidelines for young children.[56] Some literature has found a relationship between fast food consumption and obesity.[57] Including a study which found that fast food restaurants near schools increases the risk of obesity among the student population.[58] Whole milk consumption verses 2% milk consumption in children of one to two years of age had no effect on weight, height, or body fat percentage. Therefore, whole milk continues to be recommended for this age group. However the trend of substituting sweetened drinks for milk has been found to lead to excess weight gain.[59] ### Legal Some jurisdictions use laws and regulations in an effort to steer children and parents towards making healthier food choices. Two examples are calorie count laws and banning soft drinks from sale at vending machines in schools.[60] In the United Kingdom the Obesity Health Alliance has called on whichever party wins the general election to take measures to reduce childhood obesity, for example by banning advertisements for unhealthy foods before 9:00 pm and banning sports sponsorship by manufacturers of unhealthy foods. The failure of the present UK government to cut sugar, fat and salt content in foods has been criticised.[61] Health experts, the health select committee and campaigners described Conservative plans over childhood obesity as, "weak" and "watered down".[62] ### Physical activity Secondary students in Havana, Cuba during a physical education class Physical inactivity of children has also shown to be a serious cause, and children who fail to engage in regular physical activity are at greater risk of obesity. Researchers studied the physical activity of 133 children over a three-week period using an accelerometer to measure each child's level of physical activity. They discovered the obese children were 35% less active on school days and 65% less active on weekends compared to non-obese children. Physical inactivity as a child could result in physical inactivity as an adult. In a fitness survey of 6,000 adults, researchers discovered that 25% of those who were considered active at ages 14 to 19 were also active adults, compared to 2% of those who were inactive at ages 14 to 19, who were now said to be active adults.[63] Staying physically inactive leaves unused energy in the body, most of which is stored as fat. Researchers studied 16 men over a 14-day period and fed them 50% more of their energy required every day through fats and carbohydrates. They discovered that carbohydrate overfeeding produced 75–85% excess energy being stored as body fat and fat overfeeding produced 90–95% storage of excess energy as body fat.[64] Many children fail to exercise because they spend long periods of time engaging in sedentary activities such as computer usage, playing video games or watching television. Technology has a large factor on the children's activeness. Researchers provided a technology questionnaire to 4,561 children, ages 14, 16, and 18. They discovered children were 21.5% more likely to be overweight when watching 4+ hours of TV per day, 4.5% more likely to be overweight when using a computer one or more hours per day, and unaffected by potential weight gain from playing video games.[64] A randomized trial showed that reducing TV viewing and computer use can decrease age-adjusted BMI; reduced calorie intake was thought to be the greatest contributor to the BMI decrease.[65] Technological activities are not the only household influences of childhood obesity. Low-income households can affect a child's tendency to gain weight. Over a three-week period researchers studied the relationship of socioeconomic status (SES) to body composition in 194 children, ages 11–12. They measured weight, waist girth, stretch stature, skinfolds, physical activity, TV viewing, and SES; researchers discovered clear SES inclines to upper class children compared to the lower class children.[66] Childhood inactivity is linked to obesity in the United States with more children being overweight at younger ages. In a 2009 preschool study 89% of a preschoolers' day was found to be sedentary while the same study also found that even when outside, 56 percent of activities were still sedentary. One factor believed to contribute to the lack of activity found was little teacher motivation,[67] but when toys, such as balls were made available, the children were more likely to play.[67] ### Home environment Children's food choices are also influenced by family meals. Researchers provided a household eating questionnaire to 18,177 children, ranging in ages 11–21, and discovered that four out of five parents let their children make their own food decisions. They also discovered that compared to adolescents who ate three or fewer meals per week, those who ate four to five family meals per week were 19% less likely to report poor consumption of vegetables, 22% less likely to report poor consumption of fruits, and 19% less likely to report poor consumption of dairy foods. Adolescents who ate six to seven family meals per week, compared to those who ate three or fewer family meals per week, were 38% less likely to report poor consumption of vegetables, 31% less likely to report poor consumption of fruits, and 27% less likely to report poor consumption of dairy foods.[68] The results of a survey in the UK published in 2010 imply that children raised by their grandparents are more likely to be obese as adults than those raised by their parents.[69] An American study released in 2011 found the more mothers work the more children are more likely to be overweight or obese.[70] ### Developmental factors Various developmental factors may affect rates of obesity. Breast-feeding for example may protect against obesity in later life with the duration of breast-feeding inversely associated with the risk of being overweight later on.[71] A child's body growth pattern may influence the tendency to gain weight. Researchers measured the standard deviation (SD [weight and length]) scores in a cohort study of 848 babies. They found that infants who had an SD score above 0.67 had catch up growth (they were less likely to be overweight) compared to infants who had less than a 0.67 SD score (they were more likely to gain weight).[72] Additionally, breastfeeding for less than 6 months, compared to 6 months or more, has been shown to result in a higher growth rate and higher zBMI at 18, 36, and 72 months of age.[73] A child's weight may be influenced when he/she is only an infant. Researchers also did a cohort study on 19,397 babies, from their birth until age seven and discovered that high weight babies at four months were 1.38 times more likely to be overweight at seven years old compared to normal weight babies. High weight babies at the age of one were 1.17 times more likely to be overweight at age seven compared to normal weight babies.[74] ### Medical illness Cushing's syndrome (a condition in which the body contains excess amounts of cortisol) may also influence childhood obesity. Researchers analyzed two isoforms (proteins that have the same purpose as other proteins, but are programmed by different genes) in the cells of 16 adults undergoing abdominal surgery. They discovered that one type of isoform created oxo-reductase activity (the alteration of cortisone to cortisol) and this activity increased 127.5 pmol mg sup when the other type of isoform was treated with cortisol and insulin. The activity of the cortisol and insulin can possibly activate Cushing's syndrome.[75] Hypothyroidism is a hormonal cause of obesity, but it does not significantly affect obese people who have it more than obese people who do not have it. In a comparison of 108 obese patients with hypothyroidism to 131 obese patients without hypothyroidism, researchers discovered that those with hypothyroidism had only 0.077 points more on the caloric intake scale than did those without hypothyroidism.[76] ### Psychological factors Main article: Psychological aspects of childhood obesity Researchers surveyed 1,520 children, ages 9–10, with a four-year follow up and discovered a positive correlation between obesity and low self-esteem in the four-year follow up. They also discovered that decreased self-esteem led to 19% of obese children feeling sad, 48% of them feeling bored, and 21% of them feeling nervous. In comparison, 8% of normal weight children felt sad, 42% of them felt bored, and 12% of them felt nervous.[77] Stress can influence a child's eating habits. Researchers tested the stress inventory of 28 college females and discovered that those who were binge eating had a mean of 29.65 points on the perceived stress scale, compared to the control group who had a mean of 15.19 points.[78] This evidence may demonstrate a link between eating and stress. Feelings of depression can cause a child to overeat. Researchers provided an in-home interview to 9,374 adolescents, in grades seven through 12 and discovered that there was not a direct correlation with children eating in response to depression. Of all the obese adolescents, 8.2% had said to be depressed, compared to 8.9% of the non-obese adolescents who said they were depressed.[79] Antidepressants, however, seem to have very little influence on childhood obesity. Researchers provided a depression questionnaire to 487 overweight/obese subjects and found that 7% of those with low depression symptoms were using antidepressants and had an average BMI score of 44.3, 27% of those with moderate depression symptoms were using antidepressants and had an average BMI score of 44.7, and 31% of those with major depression symptoms were using antidepressants and had an average BMI score of 44.2.[80] Several studies have also explored the connection between Attention-deficit Hyperactivity Disorder (ADHD) and obesity in children. A study in 2005 concluded that within a subgroup of children who were hospitalized for obesity, 57.7% had co-morbid ADHD.[81] This relationship between obesity and ADHD may seem counter-intuitive, as ADHD is typically associated with higher level of energy expenditure, which is thought of as a protective factor against obesity.[82] However, these studies determined that children exhibited more signs of predominantly inattentive-type ADHD rather than combined-type ADHD. It is possible, however, that the symptoms of hyperactivity typically present in individuals with combined-type ADHD are simply masked in obese children with ADHD due to their decreased mobility.[81] The same correlation between obesity and ADHD is also present in adult populations.[83] Existing underlying explanations for the relationship between ADHD and obesity in children include but are not limited to abnormalities in the hypo-dopaminergic pathway, ADHD creating abnormal eating behaviors which leads to obesity, or impulsivity associated with binge eating leading to ADHD in obese patients.[83][84] A systematic review of the literature on the relationship between obesity and ADHD concluded that all reviewed studies reported ADHD patients were heavier than expected.[84] However, the same systematic review also claimed that all the evidence supporting this connection was still limited and further research is still necessary to learn more about this connection.[84] Given the prevalence rates of both obesity and ADHD in children, understanding the possible relationship between the two is important for public health, particularly when exploring treatment and management options. Direct intervention for psychological treatment of childhood obesity has become more prevalent in recent years. A meta-analysis of the psychological treatment of obesity in children and adolescents found family-based behavioral treatment (FBT) and Parent-Only Behavior treatment to be the most effective practices in treating obesity in children within a psychological framework.[85] ## Management Obesity in children is treated with dietary changes and physical activity. Dieting and missing meals should; however, be discouraged.[86] The benefit of tracking BMI and providing counselling around weight is minimal.[87] ### Lifestyle Exclusive breast-feeding is recommended in all newborn infants for its nutritional and other beneficial effects.[71] Parents changing the diet and lifestyle of their offspring by offering appropriate food portions, increasing physical activity, and keeping sedentary behaviors at a minimum may also decrease the obesity levels in children.[88] If children were more mobile and less sedentary, the rate of obesity would decrease. Parents should recognize the signs and encourage their children to be more physically active. By walking or riding a bike, instead of using motorised transport or watching television, will reduce sedentary activity.[89] ### Medications There are no medications currently approved for the treatment of obesity in children. The American Academy of Pediatrics recommends medications for obesity be discourage.[86] Orlistat and sibutramine may be helpful in managing moderate obesity in adolescence.[71] Metformin is minimally useful.[90] A Cochrane review in 2016 concluded that medications might reduce BMI and bodyweight to a small extent in obese children and adolescents. This conclusion was based only on low quality evidence.[91] ### Surgery As of 2015 there is not good evidence comparing surgery to lifestyle change for obesity in children, though there are a number of high quality ongoing studies looking at this issue.[92] Bariatric surgical procedures are increasingly used amongst adolescents with severe adolescent obesity to promote weight loss.[93] ## Epidemiology Main article: Epidemiology of childhood obesity Rates of overweight among children 2 to 19 years in the USA. From 1980 to 2013, the prevalence of overweight and obesity in children increased by nearly 50%.[94] Currently 10% of children worldwide are either overweight or obese.[2] In 2014, the World Health Organization established a high-level commission to end childhood obesity.[95] With more than 42 million overweight children around the world, childhood obesity is increasing worldwide.[5] Since 1980, the number of obese children has doubled in all three North American countries, Mexico, the United States, and Canada.[96] Although the rate of childhood obesity in the United States has stopped increasing, the current rate remains high. In 2010, 32.6 percent of 6- to 11-year-olds were overweight, and 18 percent of 6- to 9-year-olds were obese.[96] ### Canada The rate of overweight and obesity among Canadian children has increased dramatically in recent years. In boys, the rate increased from 11% in the 1980s to 30% in the 1990s.[97] ### Brazil The rate of overweight and obesity in Brazilian children increased from 4% in the 1980s to 14% in the 1990s.[97] In 2007 the prevalence of children overweight and childhood obesity was 11.1% and 2.7% in girls, 8.2% and 1.5% in boys, respectively.[98] ### United States The rate of obesity among children and adolescents in the United States has nearly tripled between the early 1980s and 2000. It has however not changed significantly between 2000 and 2006 with the most recent statistics showing a level just over 17 percent.[99] In 2008, the rate of overweight and obese children in the United States was 32%, and had stopped climbing.[100] In 2011, a national cohort study of infants and toddlers found that nearly one-third of US children were overweight or obese at 9 months and 2 years old.[101] In a follow-up study, infant weight status (healthy and obese) was strongly associated with preschool weight status.[102] ### Australia Main article: Childhood obesity in Australia Since the onset of the 21st century, Australia has found that childhood obesity has followed trend with the United States. Information garnered has concluded that the increase has occurred in the lower socioeconomic areas where poor nutritional education has been blamed. ## Research A study of 1800 children aged 2 to 12 in Colac, Australia tested a program of restricted diet (no carbonated drinks or sweets) and increased exercise. Interim results included a 68% increase in after school activity programs, 21% reduction in television viewing, and an average of 1 kg weight reduction compared to a control group.[103] A survey carried out by the American Obesity Association into parental attitudes towards their children's weight showed the majority of parents think that recess should not be reduced or replaced. Almost 30% said that they were concerned with their child's weight. 35% of parents thought that their child's school was not teaching them enough about childhood obesity, and over 5% thought that childhood obesity was the greatest risk to their child's long-term health.[104] A Northwestern University study indicates that inadequate sleep has a negative impact on a child's performance in school, their emotional and social welfare, and increases their risk of being overweight. This study was the first nationally represented, longitudinal investigation of the correlation between sleep, Body Mass Index (BMI) and overweight status in children between the ages of 3 and 18. The study found that an extra hour of sleep lowered the children's risk of being overweight from 36% to 30%, while it lessened older children's risk from 34% to 30%.[105] A 2018 Cochrane review on the impact of physical activity, diet and other behavioral interventions for improving cognition and school achievement in children and adolescents found that school and community-based programs as part of an overall prevention program were beneficial.[106] Obese children and adolescents are more likely to become obese as adults. For example, one study found that approximately 80% of children who were overweight at aged 10–15 years were obese adults at age 25 years. Another study found that 25% of obese adults were overweight as children. The latter study also found that if overweight begins before 8 years of age, obesity in adulthood is likely to be more severe.[107] A study has also found that tackling childhood obesity will not necessarily lead to eating disorders later in life.[108] A review of secular trends in the number of overweight or obese children have come to the conclusion that prevalence had increased during the past two decades in the most industrialised countries, apart from Russia and Poland, and in several low-income countries, especially in urban areas. Prevalence doubled or tripled between the early 1970s and late 1990s in Australia, Brazil, Canada, Chile, Finland, France, Germany, Greece, Japan, the UK, and the USA. By 2010, more than 40% of children in the North American and eastern Mediterranean WHO regions, 38% in Europe, 27% in the western Pacific, and 22% in southeast Asia were predicted to be overweight or obese. However, that 2006 review pre-dates recent data, which, although still too soon to be certain, suggest that the increase in childhood obesity in the US, the UK, and Sweden might be abating.3–5 [109] A British longitudinal study has found that obesity restricted to childhood has minimal influence on adult outcomes at age 30. The study also found that, while obesity that continues into adulthood has little influence on men's outcomes, it makes women less likely to have ever been employed or to currently have a romantic partner.[110] A 2017 National Bureau of Economic Research paper found that childhood obesity in the United States increases medical costs by $1,354 a year (in 2013 dollars).[111] ## See also * International Journal of Pediatric Obesity * Task Force on Childhood Obesity * Classification of childhood obesity * Obesity and walking * Social stigma of obesity * Sugary drink tax * EPODE International Network ## Footnotes 1. ^ a b Kopelman, Peter G (2005). 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"Child Obesity". The Lancet. 375 (9727): 1737–1748. doi:10.1016/s0140-6736(10)60171-7. PMC 3073855. PMID 20451244. 110. ^ Viner, RM; Cole, TJ (11 June 2005). "Adult socioeconomic, educational, social, and psychological outcomes of childhood obesity: a national birth cohort study". BMJ (Clinical Research Ed.). 330 (7504): 1354. doi:10.1136/bmj.38453.422049.e0. PMC 558281. PMID 15901644. 111. ^ Biener, Adam I.; Cawley, John; Meyerhoefer, Chad (August 2017). "The Medical Care Costs of Youth Obesity: An Instrumental Variables Approach". NBER Working Paper No. 23682. doi:10.3386/w23682. ## Further reading * Laura Dawes, Childhood Obesity in America: Biography of an Epidemic. Cambridge, MA: Harvard University Press, 2014. ## External links Classification D * ICD-10: E66 * ICD-9-CM: 278 * MeSH: D063766 * DiseasesDB: 9099 External resources * MedlinePlus: 003101 * eMedicine: med/1653 * Patient UK: Childhood obesity * "North American Society for Pediatric Gastroenterology, Hepatology and Nutrition" (PDF). Archived from the original (PDF) on 2016-03-03. Retrieved 2008-08-27. * v * t * e Obesity * Overweight * Childhood obesity * Abdominal obesity * Weight gain * Obesity hypoventilation syndrome * Bariatric surgery * Obesity and walking * Overnutrition [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	Childhood obesity	c2362324	8,372	wikipedia	https://en.wikipedia.org/wiki/Childhood_obesity	2021-01-18T18:51:39	{"mesh": ["D063766"], "icd-9": ["278"], "icd-10": ["E66"], "wikidata": ["Q3241451"]}
Type of hemorrhage Cephalhematoma Other namesCephalhematoma Newborn scalp haematomata SpecialtyPediatrics A cephalohaematoma is a hemorrhage of blood between the skull and the periosteum of any age human, including a newborn baby secondary to rupture of blood vessels crossing the periosteum. Because the swelling is subperiosteal, its boundaries are limited by the individual bones, in contrast to a caput succedaneum. ## Contents * 1 Symptoms and signs * 2 Causes * 3 Management * 4 See also * 5 References * 6 External links ## Symptoms and signs[edit] Swelling appears after 2-3 days after birth. If severe the child may develop jaundice, anemia or hypotension. In some cases it may be an indication of a linear skull fracture or be at risk of an infection leading to osteomyelitis or meningitis. The swelling of a cephalohematoma takes weeks to resolve as the blood clot is slowly absorbed from the periphery towards the centre. In time the swelling hardens (calcification) leaving a relatively softer centre so that it appears as a 'depressed fracture'. Cephalohematoma should be distinguished from another scalp bleeding called subgaleal hemorrhage (also called subaponeurotic hemorrhage), which is blood between the scalp and skull bone (above the periosteum) and is more extensive. It is more prone to complications, especially anemia and bruising.[citation needed] ## Causes[edit] The usual causes of a cephalohematoma are a prolonged second stage of labor or instrumental delivery, particularly forceps delivery. Ventouse application does not increase the incidence of cephalhematoma.[citation needed] Vitamin C deficiency has been reported to possibly be associated with development of cephalhematomas.[citation needed] ## Management[edit] Skull x-ray or CT scanning is used if neurological symptoms appear. These measurements are also used if concomitant depressed skull fracture is a possibility. Usual management is mainly observation. Phototherapy may be necessary if blood accumulation is significant leading to jaundice. Rarely, anaemia can develop needing blood transfusion. The presence of a bleeding disorder should be considered but is rare.[citation needed] Cephalohematomas typically resolve spontaneously within weeks or months of birth, however calcification can occur in 3-5% of cases.[1] While aspiration to remove accumulated blood and prevent calcification has generally been recommended against due to risk of infection, modern surgical standards and antibiotics may make this concern unfounded, and needle aspiration can be considered a safe intervention for significantly-sized cephalohematomas that do not resolve spontaneously after one month.[1] ## See also[edit] * Caput succedaneum * Cephal * Chignon * Hematoma * Subgaleal hemorrhage ## References[edit] 1. ^ a b Wong, Chin-Ho; Foo, Chee-Liam; Seow, Wan-Tiew (2006). "Calcified cephalohematoma: classification, indications for surgery and techniques". The Journal of Craniofacial Surgery. 17 (5): 970–979. doi:10.1097/01.scs.0000229552.82081.de. PMID 17003628. ## External links[edit] Classification D * ICD-10: P12 * ICD-9-CM: 767.19 * Differentiating Cephalhematoma from Caput Succedaneum * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [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	Cephalohematoma	c0007722	8,373	wikipedia	https://en.wikipedia.org/wiki/Cephalohematoma	2021-01-18T18:48:48	{"umls": ["C0007722"], "icd-9": ["767.19"], "icd-10": ["P12"], "wikidata": ["Q419938"]}
Chronic intestinal pseudo-obstruction (CIPO) is a rare disease characterized by repetitive episodes or continuous symptoms of bowel obstruction when no blockage exists. Problems with nerves, muscles, or interstitial cells of Cajal (the cells that set the pace of intestinal contractions) prevent normal contractions and cause problems with the movement of food, fluid, and air through the intestines. The most common symptoms are abdominal swelling or bloating (distention), vomiting, abdominal pain, failure to thrive, diarrhea, constipation, feeding intolerance and urinary symptoms. CIPO can occur in people of any age. It may be primary or secondary. Primary or idiopathic (where the cause is unknown) CIPO occurs by itself. Secondary CIPO develops as a complication of another medical condition. In some people with CIPO, the condition is caused by variations (mutations) affecting the FLNA or ACTG2 gene. Before making the diagnosis other conditions with similar symptoms should be ruled out. Treatment aims to restore the normal bowel movements and to correct nutritional deficiencies. Treatment may include antibiotics, prokinetic medications (metoclopramide, cisapride), surgical excision of intestinal segments in cases of localized disease, and parenteral nutrition. Intestinal transplantation has been successful in some cases. Several specialists may be needed for better management of the disease. [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	Chronic intestinal pseudoobstruction	c0238062	8,374	gard	https://rarediseases.info.nih.gov/diseases/12744/chronic-intestinal-pseudoobstruction	2021-01-18T18:01:18	{"orphanet": ["2978"], "synonyms": ["CIPO"]}
A number sign (#) is used with this entry because the slow and fast acetylation phenotypes are due to polymorphisms in the gene encoding N-acetyltransferase-2 (NAT2; 612182). Clinical Features The antituberculosis agent isoniazid (INH) is rendered therapeutically inactive by acetylation. Most or perhaps all populations of the world are polymorphic for 'rapid inactivation' versus 'slow inactivation.' As shown by the study of Evans et al. (1960), the 'slow inactivator' person is homozygous for a slow inactivator allele; the 'rapid inactivator' person may be either homozygous or heterozygous for a rapid inactivator allele. The method described by Sunahara et al. (1961) permitted separation of the homozygotes and heterozygotes, i.e., 3 genotypes in all. The rapid versus slow acetylation of sulfadiazine in rabbits (Frymoyer and Jacox, 1963) is similar. The polymorphism in acetylation extends to the acetylation of sulfamethazine, which can be used as a test (Parker, 1969). Isoniazid, hydralazine, and some sulfa drugs are acetylated by a common mechanism (Evans and White, 1964). Administration of INH with phenytoin (Dilantin) results in high, even toxic levels of the anticonvulsant (Kutt et al., 1970), and the effects of the drug interaction are greater in slow acetylators. Hydralazine (Apresoline) is acetylated through the INH-type mechanism, as is procainamide (Pronestyl). INH hepatotoxicity is more frequent in slow inactivators (Timbrell et al., 1977). McLaren et al. (1977) found a significantly higher proportion of fast acetylators in a group of diabetics without neuropathy than in those with neuropathy (see 603933) or in the normal population. Using dapsone (anti-leprosy drug) acetylation rate, Vansant et al. (1978) found a normal distribution of phenotypes in idiopathic systemic lupus erythematosus (SLE; see 152700). Drug-induced SLE has been thought to be more frequent in slow acetylators and several workers have reported the same for spontaneous SLE. Sonnhag et al. (1979) could find no relation between acetylator phenotype and proneness to develop SLE-like syndrome. Reidenberg et al. (1980) found an excess of slow acetylator phenotype in SLE. On the other hand, Baer et al. (1986) could find no association between acetylator phenotype and SLE and from a review of the literature concluded that most workers have had similar results. Harmer et al. (1986) found no correlation between the acetylator and the sparteine hydroxylation phenotypes. This is perhaps not surprising inasmuch as the N-acetyltransferase enzyme is cytosolic in liver and jejunal mucosa, whereas the polymorphic enzyme that governs hydroxylation of sparteine, debrisoquine, and other drugs is a liver P450 (124030). In addition to isoniazid, Harmer et al. (1986) listed the following drugs as being acetylated by the polymorphic enzyme: sulfadimidine, hydralazine, dapsone, procaine amide, sulfapyridine, a reduced metabolite of nitrazepam, and a metabolite of caffeine. Nhachi (1988) found bimodality for percent urinary sulfamethazine acetylated in a 6-hour sample in a Zimbabwe population. The allele for slow acetylation was estimated to have a frequency of 0.72. Roberts-Thomson et al. (1996) found that the fast acetylator phenotype was associated with odds ratios of 1.1 and 1.8 for adenoma and colorectal cancer, respectively. The highest risk occurred in the youngest tertile (less than 64 years) of cases. There was no difference between the sexes. The risk of adenoma or cancer increased with increasing intake of meat in fast but not in slow acetylators. The findings suggested that acetylator status modulates the risk of colorectal neoplasia associated with meat intake. Schnakenberg et al. (1998) analyzed the NAT2 gene of blood and tumor DNA from 60 patients with primary bladder cancer and DNA of blood samples from 154 healthy individuals. They found that 70% of patients with bladder cancer were slow acetylators, while genotyping of controls resulted in 61% with slow acetylation. In addition, dividing bladder cancer patients in males and females, the genotype NAT25B/NAT26A occurred with much higher frequencies in males. Furthermore, investigating bladder cancer tissues, they detected loss of heterozygosity in slow and rapid acetylator genotypes. In 11 of 60 tumor samples (18.3%), they observed allelic loss at the NAT2 locus, while in control DNA of blood from the same patients both alleles were still detectable. Biochemical Features In cultured rabbit hepatocytes, McQueen et al. (1982) found a relationship between acetylator phenotype and DNA damage by chemicals that undergo N-acetylation. DNA repair, an index of DNA damage, was produced by hydralazine in hepatocytes from slow acetylator rabbits but not in those from rapid acetylators. In contrast, hepatocytes from rapid acetylators were more sensitive to toxicity from the carcinogen 2-aminofluorene and displayed greater amounts of DNA repair. The amount of DNA repair measured with each chemical was dose dependent. Thus, McQueen et al. (1982) concluded that the acetylation polymorphism may be a factor in susceptibility to toxicity and perhaps carcinogenicity of these chemicals. The polymorphic enzyme responsible for the acetylator phenotype is arylamine N-acetyltransferase (EC 2.3.1.5). In the New Zealand white rabbit, which is a widely used animal model for the human acetylation polymorphism, Blum et al. (1989) showed that the defective arylamine N-acetylation is caused by a gene deletion. Reviews were provided by Weber (1987) and Evans (1989). Grant et al. (1990) concluded that the slow acetylator phenotype is the result of decreased or absent arylamine N-acetyltransferase in the liver. In a study of the acetylator phenotype of 26 surgical patients, they used caffeine as the probe drug and the measurement of the 5-acetyl-amino-6-formylamino-3-methyluracil to 1-methylxanthine molar ratio in urine. Liver wedge biopsies taken from these patients were used for a measurement of N-acetyltransferase activity with the substrate sulfamethazine and for quantitation of immunoreactive N-acetyltransferase protein. The ratio of caffeine metabolites in urine and in vitro sulfamethazine acetylation showed a correlation of 0.98. Furthermore, slow acetylation was associated with a decrease in the quantity of immunodetectable N-acetyltransferase protein. They isolated 2 kinetically distinct enzyme activities, designated NAT1 (108345) and NAT2, from low- and high-activity livers. Low acetylation was related to decreases in the liver content of both of these immunologically related proteins. Grant et al. (1990) concluded that parallel decrease in the 2 enzymes is involved. Unlike the rabbit, in which gene deletion is responsible for slow acetylation, Southern analyses of genomic DNA from slow and rapid acetylator humans suggested that in man the deletion mechanism is either unlikely or uncommon. Mapping The slow and rapid acetylation phenotypes are caused by polymorphisms in the NAT2 gene, which maps to chromosome 8p23.1-p21.3 (Hickman et al., 1994). Molecular Genetics The highly homologous human genes for N-acetyltransferase, NAT1 and NAT2, appear to code for the genetically invariant and variant NAT proteins, respectively. NAT1, which is responsible for N-acetylation of certain arylamine drugs, displays no genetic variation, whereas the rapid or slow acetylation of therapeutic and carcinogenic agents is due to variation at the NAT2 locus. Vatsis et al. (1991) generated 1.9-kb genomic EcoRI fragments by PCR with liver and leukocyte DNA from 7 subjects phenotyped as homozygous or heterozygous acetylators. Direct sequencing demonstrated multiple point mutations in a coding region of 2 distinct NAT2 variants. One of these, derived from leukocytes of a slow acetylator, showed a G-to-A transition at nucleotide 590 leading to replacement of arginine-197 by glutamine; the mutated guanine was part of a CpG dinucleotide and a TaqI site (612182.0001). A second NAT2 variant originated from liver with low N-acetylation activity. It was characterized by 3 nucleotide transitions giving rise to a silent mutation and 2 amino acid substitutions: ile114-to-thr (612182.0002) and lys268-to-arg (612182.0003). The results show conclusively that the genetically variant NAT is encoded by NAT2. Mashimo et al. (1992) described a method for determining the polymorphic N-acetyltransferase phenotype from Southern blot analysis of genomic DNA from leukocytes. Abe et al. (1993) described a rapid and simple method for genotyping the N-acetyl transferase polymorphism using a PCR-based RFLP. They determined 10 different genotypes reliably. Lin et al. (1994) found that 4 mutations--191A, 481T, 590A (612182.0001), and 857A (612182.0004)--accounted for nearly all slow acetylator alleles among blacks, whites, Asian Indians, Hispanics, Koreans, Japanese, Hong Kong Chinese, Taiwanese, Filipinos, and Samoans. The ethnic distribution supported an interpretation that the acetylation polymorphism existed before Paleolithic splitting of human populations from Africa. Cascorbi et al. (1995) identified 7 different alleles of the NAT2 gene coding for the slow acetylation phenotype. They found a slow acetylation genotype in 58.9% of the 844 unrelated German subjects studied. In vivo acetylation capacity of homozygous wildtype subjects was significantly higher than in heterozygous genotypes. All mutant alleles showed low in vivo acetylation capacities, including the newly defined alleles. Moreover, distinct slow genotypes differed significantly among each other, as reflected in lower acetylation capacity of some alleles as compared with others. Lee et al. (1998) studied the frequencies of NAT2 alleles and genotypes in 216 colorectal cancer patients and 187 controls among Chinese in Singapore. Their results confirmed the findings of Roots et al. (1989) and were contrary to earlier reports that the rapid N-acetylation phenotype was associated with an increased risk of colorectal cancer in Caucasians (Lang et al., 1986; Ilett et al., 1987). The frequency of rapid acetylator genotypes in patients with right-sided cancer, however, was significantly greater as compared to that of controls (odds ratio = 1.899). On the other hand, the frequency of the NAT27A allele, commonly associated with the slow acetylator status, was increased among colorectal cancer patients. The NAT27A genotypes, however, were more frequent among patients with cancer on the left side (odds ratio = 2.872) and along the sigmoid/rectal region (odds ratio = 2.642). Population Genetics To investigate the role of population history and natural selection in shaping variation in the closely clustered NAT1 and NAT2 genes on chromosome 8p, Patin et al. (2006) characterized genetic diversity through the resequencing and genotyping of NAT1, NAT2, and the pseudogene NATP in 13 different populations with distinct ethnic backgrounds and demographic pasts. They defined a detailed map of linkage disequilibrium of the NAT region as well as performed a number of sequence-based neutrality tests and the long-range haplotype (LRH) test. The data showed distinctive patterns of variability for the 2 genes: the reduced diversity observed at NAT1 was consistent with the action of purifying selection, whereas NAT2 functional variation contributed to high levels of diversity. The LRH test identified a particular NAT2 haplotype (NAT25B; 612182.0002) under recent positive selection in western/central Eurasians. This haplotype harbors the mutation 341T-C and encodes the 'slowest-acetylator' NAT2 enzyme, suggesting a general selective advantage for the slow acetylator phenotype. The NAT25B haplotype, which seemed to have conferred a selective advantage during the previous 6,500 years, exhibits today the strongest association with susceptibility to bladder cancer and adverse drug reactions. The patterns observed for NAT2 illustrate how geographically and temporally fluctuating xenobiotic environments may have influenced not only our genome diversity but also our present day susceptibility to disease. The diversity patterns observed in the NAT region illustrate the current vision of the human genome as a 'mosaic of segments,' each with its own individual evolutionary history (Paabo, 2003). Magalon et al. (2008) genotyped 138 unrelated individuals from 6 populations in central Asia, including long-term sedentary agriculturalists (2 Tajik populations) and recent sedentary agriculturalists (Kazakhs and Uzbeks), whose diets are less dominated by meat, and nomad pastoralists (2 Kirghiz populations), whose diet is dominated by meat. The Tajiks and Kazakhs exhibited the highest frequency of the slow acetylator haplotype NAT25B (612182.0002), ranging from 22 to 26%. The NAT26A haplotype (612182.0001) was present at high frequencies in the Tajik populations (39 to 45%), whereas it was at the lowest frequency in Kazakhs (13%). The Kazakhs exhibited the highest frequency (23%) of NAT27B (612182.0004), which is mainly restricted to East Eurasian populations. The 'fast' haplotype NAT24, defined as the ancestral state of the gene and the reference NAT2 haplotype, was found at high frequency in the Kirghizs (46 to 48%) and in the Uzbeks (42%), but at nearly 2-fold lower frequencies in the Tajiks (23 to 26%), and intermediate frequency in the Kazakhs (38%). Overall, the Tajiks exhibited significantly higher proportions of slow acetylators (55 to 63%; p less than 0.05) as compared to the Uzbeks, Kirghizs, and Kazakhs, who presented proportions of slow acetylators ranging from 26 to 35%. Magalon et al. (2008) suggested that being a slow acetylator confers an advantage in long-term agriculturalist populations in central Asia, and indicated that selective natural environmental pressures can affect the evolution of genetic diversity. Animal Model The rapid versus slow acetylation of sulfadiazine in rabbits (Frymoyer and Jacox, 1963) is similar to the human isoniazid inactivation phenotype. In cultured rabbit hepatocytes, McQueen et al. (1982) found a relationship between acetylator phenotype and DNA damage by chemicals that undergo N-acetylation. DNA repair, an index of DNA damage, was produced by hydralazine in hepatocytes from slow acetylator rabbits but not in those from rapid acetylators. In contrast, hepatocytes from rapid acetylators were more sensitive to toxicity from the carcinogen 2-aminofluorene and displayed greater amounts of DNA repair. The amount of DNA repair measured with each chemical was dose dependent. The polymorphic enzyme responsible for the 'acetylator phenotype' is arylamine N-acetyltransferase (EC 2.3.1.5). In the New Zealand white rabbit, which is a widely used animal model for the human acetylation polymorphism, Blum et al. (1989) showed that the defective arylamine N-acetylation is caused by a gene deletion. A mouse model for the human acetylation polymorphism was developed by Glowinski and Weber (1982), Mattano and Weber (1987), and Tannen and Weber (1980). The model involves the A/J (slow acetylator) and C57BL/6J (rapid acetylator) inbred strains. Mattano et al. (1988) demonstrated linkage between the Nat and the esterase (Es-1) genes, located on mouse chromosome 8. A recombination frequency of about 12% was observed between the 2 loci. History The finding in the late 1950s that an impairment of a phase I reaction, hydrolysis of the muscle relaxant succinylcholine by butyrylcholinesterase (177400), was inherited served as an early stimulus for the development of pharmacogenetics (Kalow, 1962). At almost the same time, Evans et al. (1960) observed that a common genetic variation in a phase II pathway of drug metabolism, N-acetylation, could result in striking differences in the half-life and plasma concentrations of drugs metabolized by N-acetyltransferase. Weinshilboum (2003) reviewed the subject of inheritance and drug response beginning from these 2 historic examples. Evans and McLeod (2003) discussed pharmacogenomics more broadly, from the standpoints of drug disposition, drug targets, and side effects. Misc \- Variation in drug therapy response \- Arylamine N-acetyltransferase polymorphism \- Susceptibility to chemical toxicity or carcinogenicity Lab \- Polymorphic rapid or slow acetylation of: Isoniazid (INH), Sulfadimidine, Hydralazine, Dapsone, Procaine amide, Sulfapyridine, Reduced metabolite of nitrazepam, Metabolite of caffeine 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	ACETYLATION, SLOW	c2673470	8,375	omim	https://www.omim.org/entry/243400	2019-09-22T16:26:16	{"omim": ["243400"], "synonyms": ["Alternative titles", "SLOW ACETYLATOR PHENOTYPE", "ISONIAZID INACTIVATION, SLOW", "INH INACTIVATION, SLOW"]}
Poikiloderma People with varying manifestations of poikiloderma SpecialtyDermatology Poikiloderma is a skin condition that consists of areas of hypopigmentation, hyperpigmentation, telangiectasias and atrophy. Poikiloderma of Civatte is most frequently seen on the chest or the neck, characterized by red colored pigment on the skin that is commonly associated with sun damage.[1] ## Contents * 1 Types * 2 Causes * 3 Pathogenesis * 4 Diagnosis * 5 Treatment * 6 See also * 7 References ## Types[edit] * Poikiloderma vasculare atrophicans * Poikiloderma of Civatte * Hereditary sclerosing poikiloderma ## Causes[edit] * Congenital 1. Rothmund-Thompson syndrome 2. Dyskeratosis congenita 3. Mendes da Costa syndrome * Other hereditary causes 1. Degos-Touraine syndrome 2. Diffuse and macular atrophic dermatosis 3. Hereditary sclerosing poikiloderma of weary 4. Kindler syndrome 5. Weary-Kindler syndrome 6. Xeroderma pigmentosum * Acquired 1. Injury to cold, heat, ionizing radiation, exposure to sensitizing chemicals 2. Lichen planus 3. Dermatomyositis 4. Lupus erythematosus 5. Systemic sclerosis 6. Cutaneous T cell lymphomas ## Pathogenesis[edit] The exact cause of poikiloderma of Civatte is unknown; however, extended sun exposure, namely the ultraviolet light emitted by the sun, is the primary factor.[2] ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2018) ## Treatment[edit] Albeit difficult, treatment of poikiloderma of Civatte involves the delivery of multiple wavelengths of intense pulsed light (IPL) to the affected area.[3] ## See also[edit] * Osteopoikilosis * List of cutaneous conditions ## References[edit] 1. ^ Raulin, Christian; Karsai, Syrus (2011). Laser and IPL Technology in Dermatology and Aesthetic Medicine. Springer Science & Business Media. p. 236. ISBN 9783642034381. Retrieved 7 March 2018. 2. ^ American Osteopathic College of Dermatology "Dermatologic Disease Database", aocd.org, referenced July 22, 2011. 3. ^ PubMed.gov "Treatment of poikiloderma of Civatte with an intense pulsed light source", PubMed.gov, referenced July 22, 2011. * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation 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 [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	Poikiloderma	c0392777	8,376	wikipedia	https://en.wikipedia.org/wiki/Poikiloderma	2021-01-18T18:59:17	{"wikidata": ["Q1307866"]}
Central neurocytoma Axial T1-weighted gadolinium-enhanced MRI image showing an enhancing mass with cystic changes consistent with central neurocytoma in the right lateral ventricle. SpecialtyOncology, neurosurgery Central neurocytoma (CNC) is an extremely rare, ordinarily benign intraventricular brain tumour that typically forms from the neuronal cells of the septum pellucidum.[1] The majority of central neurocytomas grow inwards into the ventricular system forming interventricular neurocytomas. This leads to two primary symptoms of CNCs, blurred vision and increased intracranial pressure. Treatment for a central neurocytoma typically involves surgical removal, with an approximate 1 in 5 chance of recurrence.[2] Central neurocytomas are classified as a grade II tumor under the World Health Organization's classification of tumors of the nervous system.[3] ## Contents * 1 Signs and symptoms * 2 Pathology * 3 Treatment * 3.1 Surgery * 3.2 Radiotherapy * 3.3 Chemotherapy * 3.4 Outcome and recurrence * 4 History * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] There is a wide range of symptoms that patients show. Symptoms can lie dormant, but come about due to Obstructive hydrocephalus. These symptoms include:[4] * Intracranial pressure * Headache * Papilledema * Vomiting * Light headedness * Impaired mental activity * Gait instability In rare and extreme cases, more severe symptoms can be observed: * Memory disturbance * Dementia * Hemiparesis[5] * Seizures * Hemorrhage * Psychosis[6] ## Pathology[edit] Micrograph of a central neurocytoma. H&E stain. On the macroscopic scale, CNC tumors are grayish in color, resembling the gray matter that comes with areas of hemorrhage. The tumors are soft, ovid, lobulated to nodular masses that are generally well circumscribed. When dissecting the tumor, scientists experienced some grittiness, which they attribute to the presence of calcification. Tumor samples stained using H&E stain and examined under the microscope revealed that CNC is a well-differentiated tumor with benign histological features. The tumor is composed of “uniform, small-to-medium-sized cells with rounded nuclei, finely stippled chromatin and inconspicuous nucleoli, along with scant cytoplasm.” CNC are characterized by perivascular pseudorosettes, circular/flower-like arrangements of cells with a small blood vessel at the centre, and polygonal small cells with a clear perinuclear halo, sometimes called the ‘fried egg’ appearance, and is clear or slightly eosinophilic. The main histomorphologic differential diagnosis is oligodendroglioma. While the tumor cells are dense in some areas, areas with anuclear, less dense tumor parts were dispersed throughout. The anuclear areas may have a fine fibrillary matrix, like that of neuropil regions. Long, thin-walled, capillary-sized vessels represent the vascularity of CNC. These vessels are arranged in a linear branching pattern, with an endocrine appearance. Thin-walled dilated vascular channels, as well as foci of calcification, were readily identified in many cases.[4] * Very high mag. * High mag. * Very high mag. ## Treatment[edit] The mainstay of treatment is surgical excision.[7] Two adjuvant therapeutic strategies are Stereotactic surgery (SRS) and fractionated convention radiotherapy (FCRT). Both are highly effective means of treatment.[8] ### Surgery[edit] Surgical excision of the central neurocytoma is the primary consensus among practicing physicians. The surgeons perform a craniotomy to remove the tumor. The ability to remove the tumor and to what extent it is removed is dependent upon the location of the tumor and surgeon experience and preference. The extent of the disease plays a large part in determining how effective the surgery will be. The main goal of a complete surgical resection, of the tumor, can also be hindered by the adherence of the tumor to adjoining structures or hemorrhages.[5] If there is a recurrence of the central neurocytoma, surgery is again the most notable treatment. ### Radiotherapy[edit] There is not much evidence supporting the claim that radiotherapy is a beneficial and effective means of treatment. Typically, radiotherapy is used postoperatively in respect to whether or not a partial or complete excision of the tumor has been accomplished.[9] The histopathological features of CNC, neuronal differentiation, low mitotic activity, absence of vascular endothelial proliferation, and tumor necrosis, suggest that the tumor may be resistant to ionizing radiation. However, when radiotherapy is used, whole brain or involved-field treatment is given. This method utilizes a standard fractionation schedule and a total tumor dose of 50-55 Gy.[5] Gamma knife surgery is a form of radiotherapy, more specifically radiosurgery that uses beams of gamma rays to deliver a certain dosage of radiation to the tumor. Gamma knife surgery is incredibly effective at treating neurocytoma and maintaining tumor control after the procedure when a complete excision has been performed. Some studies have found that the success rate of tumor control is around 90% after the first five years and 80% after the first ten years.[2][10] Gamma knife surgery is the most recorded form of radiotherapy performed to treat remnants of the CNC tumor after surgery.[10] ### Chemotherapy[edit] Chemotherapy is typically limited to patients with recurrent central neurocytoma. The course of chemotherapy used for CNC is one of two platinum-based regimes. The two regimes are: * Carboplatin + VP-16 + ifosfamide * cisplatin + VP-16 + cyclophosphamide Because chemotherapy is used in rare cases there is still information to be gathered as to the efficacy of chemotherapy to treat benign CNC. Therefore, recommendations must be viewed as limited and preliminary.[5] ### Outcome and recurrence[edit] The majority of patients can be expected to be cured of their disease and become long-term survivors of central neurocytoma. As with any other type of tumor, there is a chance for recurrence. The chance of recurrence is approximately 20%.[2] Some factors that predict tumor recurrence and death due to progressive states of disease are high proliferative indices, early disease recurrence, and disseminated disease with or without the spread of disease through the cerebral spinal fluid.[5] Long-term follow up examinations are essential for the evaluation of the outcomes that each treatment brings about. It is also essential to identify possible recurrence of CN. It is recommended that a cranial MRI is performed between every 6–12 months.[2] ## History[edit] It was first described in 1982 by Hassoun.[11] Central neurocytomas are rare brain tumors that are located most of the times in the lateral ventricles near the Monro foramina. They were first discovered by Hassoun and co-workers in 1982, and were classified as grade II tumors.[12] In 1985, Wilson had also described a rare case of "differentiated neuroblastoma" in the lateral ventricle that resembles oligondendroglioma on light microscopy. However, the name central neurocytoma was given by Hassoun.[13] Primary neuronal tumors occurring in the ventricular system were considered to be rare. Most cases described were of non-neuronal origin such as oligodendroglioma, ependymoma, meningioma, choroid plexus papilloma and giant cell. Neurocytomas were probably historically misdiagnosed as intraventricular oligondedronglioma or clear cell ependymoma prior to this. With its non-aggressive behavior the tumor has often been called "benign central neurocytoma". It is believed to occur in young adults from the neuronal cells of the septum pullicidum and the subependymal cells of the lateral ventricles. Most of the initial incidents reported in the lateral ventricle were benign. However, as more information was gathered the name benign central neurocytoma was started to be seen as a double misnomer because these tumors are not always benign nor centrally located. Many recent studies suggest that their location, biological potential and clinical behavior are observed be more variable than previously thought. Recent studies indicate their uncommon location, aggressive biological behavior and frequent recurrences following after surgical resection have generated significant interest in various treatment modalities and also in their terminology, lineage potential and molecular regulation.[13] ## Epidemiology[edit] CNC represent 0.1-0.5% of primary brain tumours.[14][8] There is a genetic component to the formation of these tumors, causing a larger proportion of tumors to form in people of Asian descent than of other ethnic groups.[15] Central neurocytomas predominantly form in young adults, most commonly during the second or third decade of life.[16] There is no evidence that the sex of a person is a determinant in the frequency of central neurocytomas.[15] ## See also[edit] * Neurocytoma ## References[edit] 1. ^ Kerkeni, A.; Ben Lakhdher, Z.; Rkhami, M.; Sebai, R.; Belguith, L.; Khaldi, M.; Ben Hamouda, M. (Oct 2010). "[Central neurocytoma: Study of 32 cases and review of the literature]". Neurochirurgie. 56 (5): 408–14. doi:10.1016/j.neuchi.2010.07.001. PMID 20692674. 2. ^ a b c d Kim JW, Kim DG, Chung HT, Choi SH, Han JH, Park CK, Kim CY, Paek SH, Jung HW (December 2013). "Radiosurgery for central neurocytoma: long-term outcome and failure pattern". J. Neurooncol. 115 (3): 505–11. doi:10.1007/s11060-013-1253-9. PMID 24065568. 3. ^ Louis David N.; Ohgaki Hiroko; Wiestler Otmar D.; Cavenee Webster K.; Burger Peter C.; Jouvet Anne; Scheithauer Bernd W.; Kleihues Paul (2007). "The 2007 WHO Classification of Tumours of the Central Nervous System". Acta Neuropathol. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. PMC 1929165. PMID 17618441. 4. ^ a b Li Y, Ye XF, Qian G, Yin Y, Pan QG (2012). "Pathologic features and clinical outcome of central neurocytoma: analysis of 15 cases". Chin J Cancer Res. 24 (4): 284–290. doi:10.1007/s11670-012-0265-x. PMC 3551323. PMID 23358787. 5. ^ a b c d e Chamberlain, Marc C. Treatment of Central Neurocytoma. USC/Norris Cancer Center. Seattle Cancer Care Alliance. <https://www.seattlecca.org/client/Chamberlain_Treatment%20of%20Central%20Neurocytomas.pdf Archived 2014-03-24 at the Wayback Machine> Feb. 20 2014. 6. ^ Ouma, JR (2004). "Psychotic manifestations in brain tumour patients: 2 case reports from South Africa". Afr Health Sci. 4 (3): 190–194. PMC 2688330. PMID 15687074. 7. ^ Schmidt, MH.; Gottfried, ON.; von Koch, CS.; Chang, SM.; McDermott, MW. (Feb 2004). "Central neurocytoma: a review". J Neurooncol. 66 (3): 377–84. doi:10.1023/b:neon.0000014541.87329.3b. PMID 15015671. 8. ^ a b Garcia RM.; Ivan ME.; Oh T.; Barani I.; Parsa AT. (2014). "Intraventricular neurocytomas: A systematic review of stereotactic radiosurgery and fractionated conventional radiotherapy for residual or recurrent tumors". Clinical Neurology and Neurosurgery. 117: 55–64. doi:10.1016/j.clineuro.2013.11.028. PMID 24438806. 9. ^ Chen H, Zhou R, Liu J, Tang J (June 2012). "Central neurocytoma". J Clin Neurosci. 19 (6): 849–53. doi:10.1016/j.jocn.2011.06.038. PMID 22537657. 10. ^ a b Karlsson Bengt; Guo Wan-Yuo; Kejia Teo; Dinesh Nivedh; Pan David Hung-Chi; Jokura Hidefumi; Kawagishi Jun; van Eck Albertus; Horstmann Gerhard A.; Yeo Tseng Tsai; Yamamoto Masaaki (2012). "Gamma Knife surgery for central neurocytomas". J Neurosurg. 117 (Suppl): 96–101. doi:10.3171/2012.6.GKS12214. PMID 23205795. 11. ^ Hassoun, J.; Gambarelli, D.; Grisoli, F.; Pellet, W.; Salamon, G.; Pellissier, JF.; Toga, M. (1982). "Central neurocytoma. An electron-microscopic study of two cases". Acta Neuropathol. 56 (2): 151–6. doi:10.1007/bf00690587. PMID 7064664. 12. ^ Qian H.; Lin S.; Zhang M.; Cao Y. (2012). "Surgical management of intraventricular central neurocytoma: 92 cases". Acta Neurochirurgica. 154 (11): 1951–60. doi:10.1007/s00701-012-1446-6. PMID 22941394. 13. ^ a b Choudhari K. A.; Kaliaperumal C.; Jain A.; Sarkar C.; Soo M.; Rades D.; Singh J. (2009). "Central neurocytoma: A multi-disciplinary review". British Journal of Neurosurgery. 23 (6): 585–595. doi:10.3109/02688690903254350. PMID 19922271. 14. ^ Chuang, MT.; Lin, WC.; Tsai, HY.; Liu, GC.; Hu, SW.; Chiang, IC. (2005). "3-T proton magnetic resonance spectroscopy of central neurocytoma: 3 case reports and review of the literature". J Comput Assist Tomogr. 29 (5): 683–8. doi:10.1097/01.rct.0000171240.95430.29. PMID 16163043. 15. ^ a b Sharma, Mehar Chand; Deb, Prabal; Sharma, Suash; Sarkar, Chitra (August 2006). "Neurocytoma: a comprehensive review". Neurosurgical Review. 29 (4): 270–285. doi:10.1007/s10143-006-0030-z. PMID 16941163. 16. ^ Hassoun J, Soylemezoglu F, Gambarelli D, Figarella-Branger D, von Ammon K, Kleihues P (1993). "Central neurocytoma: a synopsis of clinical and histological features". Brain Pathology. 3 (3): 297–306. doi:10.1111/j.1750-3639.1993.tb00756.x. ## External links[edit] Classification D * ICD-O: ICD-O 9506/1 * MeSH: D018306 External resources * eMedicine: med/1346305 Wikimedia Commons has media related to Central neurocytoma. * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). [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 neurocytoma	c0206719	8,377	wikipedia	https://en.wikipedia.org/wiki/Central_neurocytoma	2021-01-18T18:28:56	{"gard": ["10641"], "mesh": ["D018306"], "umls": ["C0206719"], "orphanet": ["73256"], "wikidata": ["Q5062123"]}
Sebaceoma Sebaceous epithelioma SpecialtyDermatology Sebaceoma (also known as a "sebaceous epithelioma") is a cutaneous condition that appears as a yellow or orange papule.[1]:662 ## See also[edit] * Sebaceous carcinoma * Sebaceous adenoma * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts 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	Sebaceoma	c2939441	8,378	wikipedia	https://en.wikipedia.org/wiki/Sebaceoma	2021-01-18T18:34:35	{"umls": ["C2939441", "C1275210"], "wikidata": ["Q7442318"]}
For a discussion of the genetic heterogeneity in age at menarche, see MENAQ1 (610873). Mapping Perry et al. (2009) conducted a metaanalysis of 17,510 females from 8 different population-based cohorts and found significant association with rs7759938 on chromosome 6q21, within a recombination interval that includes only 1 gene, LIN28B (611044). Each T allele of this SNP was associated with approximately a 5-week reduction in menarchal age (p = 7 x 10(-9)). Perry et al. (2009) noted that a common variant in the LIN28B gene, rs314277, previously associated with normal variation in adult height (Lettre et al., 2008; see stature as a quantitative trait, 606255), lies within 28.7 kb of rs7759938 and suggested that the 2 SNPs likely represent the same signal. In a genomewide association study of 17,438 women, He et al. (2009) found significant association with age at menarche for 6 SNPs on chromosome 6q21: rs314277 (p = 2.7 x 10(-13)), rs314263 (p = 3.2 x 10(-13)), rs369065 (p = 2.4 x 10(-11)), rs314280 (p = 2.3 x 10(-8)), rs4946651 (p = 3.1 x 10(-8)), and rs314262 (p = 9.7 x 10(-8)). He et al. (2009) stated that the nearest gene to all 6 SNPs is LIN28B. Ong et al. (2009) conducted a genomewide association study for age at menarche in 4,714 women and found significant association with only 1 SNP, rs314276 in intron 2 of the LIN28B gene (p = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major C allele of rs314276 was associated with 0.12 years earlier menarche (combined p = 3.6 x 10(-16)). This allele was also associated with earlier breast development (p = 0.001) and a faster tempo of height growth (p = 0.00008) in girls, and shorter adult height in women (p = 3.6 x 10(-7)). The authors also analyzed rs314276 in 1,027 men and 4,588 boys and found that the common C allele was associated with earlier voice breaking (p = 0.006), more advanced pubic hair development (p = 0.01), and faster tempo of height growth (p = 0.03) in boys. In a sample of 9,840 men, the C allele was also associated with shorter adult height in men (p = 0.006). Ong et al. (2009) concluded that variation in LIN28B is a genetic determinant regulating the timing of human pubertal growth and development. Sulem et al. (2009) conducted a genomewide association study of age at menarche in 15,297 Icelandic women and found significant association with SNPs within a 135-kb LD block on chromosome 6q21; the 3 most strongly associated SNPs were fully correlated and rs314280, located near the LIN28B gene, was used to tag the signals from those SNPs. Combined analysis with replication sets from Iceland, Denmark, and the Netherlands involving a total of 10,040 women yielded a significant association between the T allele of rs314280 and age at menarche (1.2 months later per allele; p = 1.8 x 10(-14)). A second SNP within the same LD block, rs314277, created 2 haplotypes with different effects (0.9 months and 1.9 months per allele, respectively). Sulem et al. (2009) noted that these 2 variants had previously been associated with greater adult height (Gudbjartsson et al., 2008; Lettre et al., 2008), but stated that the association with adult height did not account for the association with age at menarche or vice versa, and that other variants previously associated with height did not associate significantly with age at menarche. Widen et al. (2010) identified strong association between pubertal height growth (see STQTL, 606255) and the 5-prime LIN28B SNP rs7759938, previously associated with age at menarche. Multiple regression analysis suggested that the timing of pubertal growth and age of menarche may be mediated through a common underlying mechanism. Widen et al. (2010) tested both rs7759938 and rs314277 for independent effects on postnatal growth and found that the pubertal timing-associated marker rs7759938 affected prepubertal growth in females (p = 7 x 10(-5)) and final height in males (p = 5 x 10(-4)), whereas rs314277 had sex-specific effects on growth (p for interaction = 0.005) that were distinct from those observed at rs7759938. Widen et al. (2010) concluded that partially correlated variants in the LIN28B region tag distinctive, complex, and sex-specific height- and growth-regulating effects, influencing the entire period of postnatal growth, thus implying a critical role for LIN28B in the regulation of human growth. To identify loci for age at menarche, Elks et al. (2010) performed a metaanalysis of 32 genomewide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (p = 5.4 x 10(-60)) and 9q31.2 (MENAQ3; 612883) (p = 2.2 x 10(-33)), they identified 30 new menarche loci (all p less than 5 x 10(-8)) and found suggestive evidence for a further 10 loci (p less than 1.9 x 10(-6)). The new loci included 4 previously associated with body mass index (in or near FTO, 610966; SEC16B 612855; TRA2B 602719; or TMEM18, 613220), 3 in or near other genes implicated in energy homeostasis (BSX, 611074; CRTC1, 607536; and MCHR2, 606111) and 3 in or near genes implicated in hormonal regulation (INHBA, 147290; PCSK2, 162151; and RXRG, 180247). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. Perry et al. (2014) performed a metaanalysis using genomewide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, and found robust evidence (p less than 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. The menarche locus at LIN28B on chromosome 6 (rs7759938) showed the largest effect size (p = 1.23 x 10(-69)) for rs7759938. This age-raising allele was also associated with taller adult height (p = 8.69 x 10(-18)), which is directionally concordant with epidemiologic observations. [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	MENARCHE, AGE AT, QUANTITATIVE TRAIT LOCUS 2	c2752070	8,379	omim	https://www.omim.org/entry/612882	2019-09-22T16:00:25	{"omim": ["612882"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-23 (MCPH23) is caused by homozygous mutation in the NCAPH gene (602332) on chromosome 2q11. One such patient has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). Clinical Features Martin et al. (2016) reported a 42-year-old Portuguese man (P3) with primary microcephaly (-4.2 SD). He had a sloping forehead and moderate intellectual disability. Inheritance The transmission pattern of MCPH23 in the family reported by Martin et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In a 42-year-old man (P3) with MCPH23, Martin et al. (2016) identified a homozygous missense mutation in the NCAPH gene (P243L; 602332.0001). The mutation, which was found by screening of a panel of genes involved in the condensin I and II complexes in 198 patients with microcephaly, was confirmed by Sanger sequencing and segregated with the disorder in the family. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls, consistent with decatenation failure at mitosis. These abnormalities could potentially reduce neuronal cell proliferation, viability, and survival, resulting in microcephaly. The findings suggested that the mutation disrupted condensin-dependent mitotic chromosome integrity. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (-4.2 SD) Face \- Sloping forehead NEUROLOGIC Central Nervous System \- Intellectual disability, moderate MISCELLANEOUS \- One man of Portuguese descent has been reported (last curated May 2018) MOLECULAR BASIS \- Caused by mutation in the non-SMC condensin I complex subunit H (NCAPH, 602332.0001 ) ▲ 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	MICROCEPHALY 23, PRIMARY, AUTOSOMAL RECESSIVE	c4693843	8,380	omim	https://www.omim.org/entry/617985	2019-09-22T15:44:08	{"omim": ["617985"]}
Choroid plexus carcinoma is a rare and highly aggressive malignant type of choroid plexus tumor (see this term) occurring almost exclusively in children, presenting with cerebrospinal fluid obstruction in the lateral ventricles (most common), the fourth and third ventricles or in multiple ventricles, leading to hydrocephalus and increased intracranial pressure, and manifesting with nausea, vomiting, abnormal eye movements, gait impairment, seizures and enlarged head circumference. [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	Choroid plexus carcinoma	c0431109	8,381	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251899	2021-01-23T17:56:28	{"gard": ["8238"], "mesh": ["C562943"], "omim": ["260500"], "umls": ["C0431109"], "icd-10": ["C71.7"]}
Microcystic adnexal carcinoma A microscopic view of microcystic adnexal carcinoma SpecialtyDermatology/oncology Microcystic adnexal carcinoma (MAC) is a rare sweat gland cancer,[1] which often appears as a yellow spot or bump in the skin. It usually occurs in the neck or head, although cases have been documented in other areas of the body. Most diagnosis occur past the age of 50. Although considered an invasive cancer, metastasis rarely occurs. If the tumor spreads, it can grow and invade fat, muscles, and other types of tissue.[2] Main treatments are wide local excision or Mohs micrographic surgery, which ensures that most, if not all, cancer cells are removed surgically.[3] ## Contents * 1 Presentation * 2 Causes * 3 Treatment * 4 See also * 5 References ## Presentation[edit] MACs usually present as a smooth, flesh or yellow colored, slow-growing nodule or bump somewhere on the face or neck with typical development being 3–5 years. The most common location is the mouth (occurring in 74% of cases), however cases have been documented on the scalp, tongue, trunk, upper extremities, and genitals. Patients are more likely to be white, female, and middle aged or elderly, although cases have been documented in children. Although usually presenting with no visual or physical symptoms, some patients do experience numbness, paresthesia, burning, or tingling. This may be due to the invasive nature of MACs, which can burrow deep into underlying tissues and nerves in the face. MAC is very difficult to recognize and differentiate from other conditions. Specialists may suggest a series of tests including a biopsy, an MRI, or a CT scan.[4] The average tumor size is less than 2 cm, however cases have been documented where tumor size exceeds 7.9 cm.[1] While death is rare among MAC patients, it can occasionally metastasize to local lymph nodes.[5] The 10 year overall survival rate is 86.4%, however this is exceedingly close to many 10 year survival rates of populations without MACs present.[6] ## Causes[edit] Little is known about the causes of MACs, although some evidence has shown that ultraviolet light, radiation, and genes may be causation factors. A genetic role might also be plausible, according to some studies. [7]In several cases, patients developed a MAC after immunosuppression.[1] ## Treatment[edit] Due to the invasive nature of MACs, most cases are treated with wide local excision in order to decrease the rate of reoccurrence. Increasingly however, Mohs micrographic surgery is being employed as it allows more specific margins to be removed, along with decreasing the size of postoperative scars and disfigurement. In rare cases, tumors can be deemed inoperable due to their size and location under vital structures of the face. Chemotherapy and radiation treatment have been used when metastasis has occurred or when an excision cannot be performed,[8] but results have been inconclusive about their effectiveness. In some cases, radiation therapy has been shown to increase tumor size. While in other cases, it implies that it will decrease the success of the tumor regrowing.[9] Long term follow-up is necessary, as some cases of local recurrence have been documented 30 years after the original diagnosis.[1] ## See also[edit] * Syringofibroadenoma * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ a b c d Hamed, Nouran S.; Khachemoune, Amor (2015-07-01). "Microcystic adnexal carcinoma: A focused review and updates". Journal of Dermatology & Dermatologic Surgery. 19 (2): 80–85. doi:10.1016/j.jdds.2015.03.001. ISSN 2352-2410. 2. ^ "Microcystic Adnexal Carcinoma". Retrieved 4 December 2020. 3. ^ "Microcystic adnexal carcinoma \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-02-03. 4. ^ "Microcystic Adnexal Carcinoma". Retrieved 4 December 2020. 5. ^ Kitajima, Yasuo; Kamiya, Hideki; Sugie, Shigeyuki; Ban, Masanori (2003). "Microcystic Adnexal Carcinoma with Lymph Node Metastasis". Dermatology. 207 (4): 395–397. doi:10.1159/000074122. ISSN 1018-8665. PMID 14657634. 6. ^ Yu, James B.; Blitzblau, Rachel C.; Patel, Sonya C.; Decker, Roy H.; Wilson, Lynn D. (August 2009). "Surveillance, Epidemiology, and End Results (SEER) Database Analysis of Microcystic Adnexal Carcinoma (Sclerosing Sweat Duct Carcinoma) of the Skin". American Journal of Clinical Oncology. 33 (2): 125–7. doi:10.1097/coc.0b013e31819791eb. ISSN 0277-3732. PMID 19675445. 7. ^ Lountzis, Nektarios. "Microcystic Adnexal Carcinoma". Medscape. Retrieved 4 December 2020. 8. ^ "Microcystic adnexal carcinoma of the face treated with radiation therapy: a case report and review of the literature". Retrieved 4 December 2020. 9. ^ "Microcystic adnexal carcinoma of the face treated with radiation therapy: a case report and review of the literature". Retrieved 4 December 2020. * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts 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	Microcystic adnexal carcinoma	c0346027	8,382	wikipedia	https://en.wikipedia.org/wiki/Microcystic_adnexal_carcinoma	2021-01-18T18:29:18	{"gard": ["10438"], "umls": ["C0346027"], "wikidata": ["Q6839434"]}
A number sign (#) is used with this entry because autosomal dominant bone marrow failure syndrome-1 (BMFS1) is caused by heterozygous mutation in the SRP72 gene (602122) on chromosome 4q12. ### Genetic Heterogeneity of Bone Marrow Failure Syndrome See also BMFS2 (615715), caused by mutation in the ERCC6L2 gene (615667) on chromosome 9q22; BMSF3 (617052), caused by mutation in the DNAJC21 gene (617048) on chromosome 5p13; BMFS4 (618116), caused by mutation in the MYSM1 gene (612176) on chromosome 1p32; and BMFS5 (618165), caused by mutation in the TP53 gene (191170) on chromosome 17p13. Clinical Features Kirwan et al. (2012) reported a family in which 3 sibs, aged 11 to 14 years, had early-onset aplastic anemia or pancytopenia and their mother had myelodysplasia. All also had congenital nerve deafness. None were treated for the hematologic abnormalities. In a second family, both a mother and daughter had adult-onset myelodysplasia. Neither had deafness, but the daughter had possible labyrinthitis. Neither received treatment. Inheritance The transmission pattern of bone marrow failure in the families reported by Kirwan et al. (2012) was consistent with autosomal dominant inheritance. Molecular Genetics By whole-exome sequencing, Kirwan et al. (2012) identified a truncating mutation in the SRP72 gene (602122.0001) in 4 affected members of a family with autosomal dominant aplastic anemia/myelodysplasia and congenital deafness. Screening of this gene in 96 additional individuals with bone marrow failure identified 1 woman with myelodysplasia who had a heterozygous missense mutation (R207H; 602122.0002); her mother with myelodysplasia also carried the mutation. In vitro functional expression studies showed that both mutant proteins had reduced colocalization with ER markers compared to wildtype. The truncating mutation showed a marked reduction in coprecipitation with 7SL RNA (see, e.g., RN7SL1, 612177), whereas the R207H mutant protein had increased interaction with 7SL RNA. These defects were predicted to interfere with normal functioning of the signal recognition particle, with a failure to arrest cytoplasmic translation or properly translocate peptides within the cell. However, it was unclear how a defect in protein translocation would result in the phenotype. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Deafness (in 1 of 2 families) HEMATOLOGY \- Aplastic anemia \- Pancytopenia \- Myelodysplasia MISCELLANEOUS \- Onset in childhood \- Two unrelated families have been reported (last curated June 2012) MOLECULAR BASIS \- Caused by mutation in the 72-kD signal recognition particle gene (SRP72. 602122.0001 ) ▲ 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	BONE MARROW FAILURE SYNDROME 1	c3808553	8,383	omim	https://www.omim.org/entry/614675	2019-09-22T15:54:33	{"mesh": ["C536572"], "omim": ["614675"], "orphanet": ["314399"], "synonyms": ["Autosomal dominant aplastic anemia and myelodysplasia"]}
Isolated bilateral hemispheric cerebellar hypoplasia is a rare cerebellar malformation characterized by hypoplasia of both cerebellar hemispheres with no other cerebellar/cerebral anomaly or other associated clinical feature. Affected patients present with mild hypotonia with motor delay, mild cognitive impairment, language delay, visuospatial and verbal memory deficits, dysdiadochokinesis, intentional tremor, and possible presence of emotional fragility and mild depression. [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	Isolated bilateral hemispheric cerebellar hypoplasia	None	8,384	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=269221	2021-01-23T17:27:38	{"icd-10": ["Q04.3"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant hypercarotenemia and vitamin A deficiency (HCVAD) is caused by heterozygous mutation in the BCMO1 gene (BCO1; 605748) on chromosome 16q23. One such patient has been reported. See also 277350 for possible autosomal recessive inheritance. Clinical Features Sharvill (1970) described very high levels of blood carotene in a woman, her mother, a sib and her son. Low levels of vitamin A were also found at times. He postulated a defect in the conversion of carotene to vitamin A. Frenk (1966) described 3 patients with yellow-colored keratoderma associated with a lowered level of serum vitamin A and a raised level of carotenes. Attard-Montalto et al. (1992) described a 5-year-old girl with intermittent orange discoloration of her palms, soles, and face. There were persistently low levels of both vitamin A and serum-specific retinol-binding protein (RBP4; 180250). Attard-Montalto et al. (1992) postulated that the low serum RBP concentration resulted in slow uptake and release of vitamin A by the liver. The conversion of carotene to vitamin A was consequently inhibited, resulting in hypercarotenemia. Vitamin A supplements were unable to raise the serum vitamin A concentration and did not relieve the carotenemia. Mapping ### Plasma Level of Carotenoids Quantitative Trait Locus 1 In a genomewide association study of 1,190 Italians, Ferrucci et al. (2009) found significant associations between plasma levels of the carotenoids beta-carotene and lutein and several SNPs mapping to chromosome 16q (rs6420424, rs8044334, rs11645428, and rs6564851). The findings were replicated in additional cohorts of 615 and 2,136 individuals, respectively. Metaanalysis of all 3 studies showed that the G allele of rs6564851 had the highest association with increased plasma beta-carotene (p = 1.6 x 10(-24)). This allele was also associated with lower plasma lutein (p = 7.3 x 10(-15)). This SNP is located 7.7-kb from the BCMO1 gene, which encodes an enzyme that catalyzes the first step in the conversion of dietary provitamin carotenoids to vitamin A in the small intestine. Ferrucci et al. (2009) estimated that rs6564851 could explain 1.9% of the variance in plasma beta-carotene levels. There was no association with plasma retinol levels. Molecular Genetics In a patient with hypercarotenemia and vitamin A deficiency reported by Sharvill (1970), Lindqvist et al. (2007) identified a heterozygous mutation in the BCOM1 gene (605748.0001). The BCMO1 gene encodes beta-carotene 15,15-prime-monooxygenase, which converts carotenoids into vitamin A. Thus, deficiency of this enzyme results in hypercarotenemia and secondary vitamin A deficiency. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Yellow-orange colored skin LABORATORY ABNORMALITIES \- Increased serum beta-carotene \- Decreased serum vitamin A \- Decreased conversion of beta-carotene to vitamin A (retinol) MOLECULAR BASIS \- Caused by mutation in the beta-carotene 15,15-prime-monooxygenase 1 gene (BCMO1, 605748.0001 ). ▲ 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	HYPERCAROTENEMIA AND VITAMIN A DEFICIENCY, AUTOSOMAL DOMINANT	c2676023	8,385	omim	https://www.omim.org/entry/115300	2019-09-22T16:43:41	{"mesh": ["C567296"], "omim": ["115300"], "orphanet": ["199285"], "synonyms": []}
Persistent aura without infarction SpecialtyNeurology, Neuro-ophthalmology Differential diagnosisVisual snow Persistent aura without infarction (PAWOI) is a little-known condition, first described under the designation prolonged migraine aura status,[1] that is not yet fully understood. PAWOI is said to be a possible cause of a variety of neurological symptoms, including visual snow, loss of vision, increased afterimages, tinnitus, and others. However, the pathogenesis of PAWOI is unknown; in other words, it is not known exactly what causes these symptoms. Furthermore, it is not clear which medical examinations are useful in diagnosing PAWOI. At present, PAWOI is usually diagnosed solely based on the patient's present and past symptoms. It may be possible that an overactive brain or a chemical imbalance is partly to blame for the disorder. Different medication has been tried as treatment, notably acetazolamide,[2] valproate,[3] lamotrigine,[4] topiramate, and furosemide.[5] ## References[edit] 1. ^ Haas, David C. (February 1982). "Prolonged migraine aura status". Annals of Neurology. 11 (2): 197–9. doi:10.1002/ana.410110217. PMID 7073253. 2. ^ Haan, J; Sluis, P; Sluis, LH; Ferrari, MD (28 November 2000). "Acetazolamide treatment for migraine aura status". Neurology. 55 (10): 1588–9. doi:10.1212/WNL.55.10.1588. PMID 11094126. 3. ^ Rothrock, JF (January 1997). "Successful treatment of persistent migraine aura with divalproex sodium". Neurology. 48 (1): 261–2. doi:10.1212/WNL.48.1.261. PMID 9008529. 4. ^ Chen, WT; Fuh, JL; Lu, SR; Wang, SJ (September 2001). "Persistent migrainous visual phenomena might be responsive to lamotrigine". Headache. 41 (8): 823–5. doi:10.1046/j.1526-4610.2001.01150.x. PMID 11576209. 5. ^ Rozen, Todd D. (12 September 2000). "Treatment of a prolonged migrainous aura with intravenous furosemide". Neurology. 55 (5): 732–3. doi:10.1212/WNL.55.5.732. PMID 10980751. This article about a medical condition affecting the nervous system 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	Persistent aura without infarction	c2349465	8,386	wikipedia	https://en.wikipedia.org/wiki/Persistent_aura_without_infarction	2021-01-18T18:56:55	{"umls": ["C2349465"], "icd-9": ["346.5"], "icd-10": ["G43.5"], "wikidata": ["Q7170403"]}
A number sign (#) is used with this entry because of evidence that susceptibility to dilated cardiomyopathy is associated with variation in the desmoglein-2 gene (DSG2; 125671). For a phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics In a man with dilated cardiomyopathy who had severely decreased cardiac function and underwent cardiac transplantation at 44 years of age, Posch et al. (2008) identified homozygosity for the V55M mutation in the DSG2 gene (125671.0009). The proband's father, who had less severe disease with a later onset, was heterozygous for the mutation, as was his asymptomatic mother; his paternal grandfather had died of heart failure at 57 years of age. The proband had no abnormalities of skin or hair. Posch et al. (2008) subsequently screened 538 CMD patients for the DSG2 V55M variant and identified 13 unrelated carriers (2.4%); the variant was also found in 1 (0.23%) of 432 individuals without CMD (p less than 0.006). In a total of 1,228 cases and controls, the authors found significant association between the DSG2 V55M variant and CMD (p less than 0.007). Immunostaining and electron microscopy of explanted left ventricular wall myocardium from the homozygous proband revealed pale, irregularly shaped intercalated discs with an indistinct inner structure and significantly shorter desmosomes compared to wildtype. [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	CARDIOMYOPATHY, DILATED, 1BB	c0340427	8,387	omim	https://www.omim.org/entry/612877	2019-09-22T16:00:26	{"doid": ["0110458"], "mesh": ["C536231"], "omim": ["612877"], "orphanet": ["154"], "genereviews": ["NBK1309"]}
This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: Writing style needs fixing Please help improve this article if you can. (October 2012) (Learn how and when to remove this template message) Brain delivery trauma Position of the child is important for normal birthing procedure. Head-first birth is preferred. SpecialtyObstetrics, pediatrics Birth trauma refers to damage of the tissues and organs of a newly delivered child, often as a result of physical pressure or trauma during childbirth. The term also encompasses the long term consequences, often of cognitive nature, of damage to the brain or cranium.[1] Medical study of birth trauma dates to the 16th century, and the morphological consequences of mishandled delivery are described in Renaissance-era medical literature. Birth injury occupies a unique area of concern and study in the medical canon. In ICD-10 "birth trauma" occupied 49 individual codes (P10-Р15). However, there are often clear distinctions to be made between brain damage caused by birth trauma and that induced by intrauterine asphyxia. It is also crucial to distinguish between "birth trauma" and "birth injury". Birth injuries encompass any systemic damages incurred during delivery (hypoxic, toxic, biochemical, infection factors, etc.), but "birth trauma" focuses largely on mechanical damage. Caput succedaneum, bruises, bleeding along the displacements of cranial bones, and subcapsular hematomas of the liver are among reported birth injuries. Birth trauma, on the other hand, encompasses the enduring side effects of physical birth injuries, including the ensuing compensatory and adaptive mechanisms and the development of pathological processes (pathogenesis) after the damage.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Epidemiology * 4 References * 5 External links ## Signs and symptoms[edit] Complications from birth trauma can include damage to the head, spinal cord, soft tissues, and organs. [2] Trauma to the head of the infant can manifest as Caput Succedaneum, skull fractures, extracranial and intracranial hemorrhages, and cranial nerve injuries. Caput Succeedaneum is seen as edema in the scalp due to squeezing of the veins from increase pressure while passing through the birth canal. [2] Birth trauma is uncommon in the Western world in relation to rates in the third world. In the West injury occurs in 1.1% of C-sections.[3][4] ## Causes[edit] * Cephalo-pelvic disproportion, * the quick and rapid delivery, * delayed and prolonged delivery, * the abnormal birth position, * Asynclitic birth (asinclitismus), * abnormal fetal attitude (extensor inserting head), * obstetric turn, * acceleration and stimulation of the birth, * breech presentation, * forceps and vacuum extraction.[5] While any number of injuries may occur during the birthing process, a number of specific conditions are well described. Brachial plexus palsy occurs in 0.4 to 5.1 infants per 1000 live birth.[6] Head trauma and brain damage during delivery can lead to a number of conditions include: caput succedaneum, cephalohematoma, subgaleal hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, and intraventricular hemorrhage.[citation needed] The most common fracture during delivery is that of the clavicle (0.5%).[7] ## Epidemiology[edit] Disability-adjusted life year for birth asphyxia and birth trauma per 100,000 inhabitants in 2002[8] no data less than 150 150-300 300-450 450-600 600-750 750-900 900-1050 1050-1200 1200-1350 1350-1500 1500-1750 more than 1750 ## References[edit] 1. ^ V.V.Vlasyuk Birth trauma and perinatal disorders of cerebral circulation. St. Petersburg, "Nestor History, 2009 - 252 p. ISBN 978-5-98187-373-7. 2. ^ a b c V, Dumpa; R, Kamity (2020). "Birth Trauma". PubMed. PMID 30969653. Retrieved 2020-07-27. 3. ^ Alexander JM, Leveno KJ, Hauth J, et al. (October 2006). "Fetal injury associated with cesarean delivery". Obstet Gynecol. 108 (4): 885–90. doi:10.1097/01.AOG.0000237116.72011.f3. PMID 17012450. 4. ^ "רשלנות רפואית בהריון". Saturday, May 2, 2020 5. ^ Demissie K, Rhoads GG, Smulian JC, et al. (July 2004). "Operative vaginal delivery and neonatal and infant adverse outcomes: population based retrospective analysis". BMJ. 329 (7456): 24–9. doi:10.1136/bmj.329.7456.24. PMC 443446. PMID 15231617. 6. ^ Andersen J, Watt J, Olson J, Van Aerde J (February 2006). "Perinatal brachial plexus palsy". Paediatr Child Health. 11 (2): 93–100. PMC 2435328. PMID 19030261. 7. ^ Beall MH, Ross MG (December 2001). "Clavicle fracture in labor: risk factors and associated morbidities". J Perinatol. 21 (8): 513–5. doi:10.1038/sj.jp.7210594. PMID 11774010. 8. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002. ## External links[edit] Classification D * ICD-10: P10–P15 * ICD-9-CM: 767 * MeSH: D001720 External resources * eMedicine: article/980112 * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [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	Birth trauma (physical)	c0005604	8,388	wikipedia	https://en.wikipedia.org/wiki/Birth_trauma_(physical)	2021-01-18T18:31:37	{"mesh": ["D001720"], "icd-9": ["767"], "icd-10": ["P10-P15"], "wikidata": ["Q1235888"]}
For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300. Mapping In an extended multiplex family, ascertained in a population-based study of early-onset AD in the northern Netherlands, Rademakers et al. (2005) obtained conclusive evidence of linkage of AD with a candidate region of 19.7 cM at 7q36. They identified a shared haplotype at 7q36 between the index family and 3 of 6 multiplex AD-affected families from the same geographic region, which was indicative of a founder effect and defined a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified only an exonic silent mutation in the PAXIP1 gene (608254), 38030G-C in the exon 10 genomic sequence, which affected codon 626. It remained to be determined whether PAXIP1 has a functional role in the expression of AD in the index family or whether another mutation at this locus explained the observed linkage and sharing. Association data in a population-based early-onset AD patient-control sample strongly supported the linkage data from the informative index family indicating a novel AD locus at 7q36. The genetic heterogeneity of AD was emphasized. It is noteworthy that another gene in the 7q36 region, NOS3 (163729), has also been associated with Alzheimer disease. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Memory impairment \- Dementia \- Praxis \- Speech impairment \- Neuroimaging shows cortical atrophy Behavioral Psychiatric Manifestations \- Personality changes MISCELLANEOUS \- Mean age at onset 66.8 years (range 47-77) ▲ 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	ALZHEIMER DISEASE 10	c0276496	8,389	omim	https://www.omim.org/entry/609636	2019-09-22T16:05:45	{"doid": ["0110043"], "mesh": ["D000544"], "omim": ["609636"], "orphanet": ["1020"], "synonyms": ["Alternative titles", "ALZHEIMER DISEASE, FAMILIAL, 10", "AD10"]}
A rare diving disorder caused by inhaling a mist of seawater This article needs editing for compliance with Wikipedia's Manual of Style. In particular, it has problems with not using MEDMOS. Please help improve it if you can. (August 2017) (Learn how and when to remove this template message) Salt water aspiration syndrome is a rare diving disorder suffered by scuba divers who inhale a mist of seawater from a faulty demand valve causing irritation of the lungs. It is not the same thing as aspiration of salt water as a bulk liquid, i.e. drowning.[1][2] It can be treated by rest for several hours. If severe, medical assessment is required. ## Contents * 1 Symptoms * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Symptoms[edit] Symptoms of salt water aspiration syndrome include:[2] * Post-dive cough, with or without sputum, usually suppressed during the dive. * In serious cases the sputum may be bloodstained, frothy and copious. * Over time further symptoms may develop, including: * rigors, tremors or shivering; * nausea or vomiting; * hot or cold sensations; * dyspnoea; cough; sputum; shortness of breath; * headaches; malaise; and generalised aches. * Cyanosis * Mild fever ## Diagnosis[edit] This section is empty. You can help by adding to it. (February 2018) ## Treatment[edit] ## See also[edit] * Pulmonary aspiration ## References[edit] 1. ^ Edmonds C (September 1970). "A salt water aspiration syndrome". Mil Med. 135 (9): 779–85. doi:10.1093/milmed/135.9.779. PMID 4991232. 2. ^ a b Edmonds, C. (1998). "Drowning syndromes: the mechanism". South Pacific Underwater Medicine Society Journal. 28 (1). ISSN 0813-1988. OCLC 16986801. Archived from the original on 2011-01-28. Retrieved 2008-07-04. ## External links[edit] * Diving Medicine Online — Salt Water Aspiration Syndrome * v * t * e Underwater diving * Diving modes * Atmospheric pressure diving * Freediving * Saturation diving * Scuba diving * Snorkeling * Surface oriented diving * Surface-supplied diving * Unmanned diving Diving equipment * Cleaning and disinfection of personal diving equipment * Human factors in diving equipment design Basic equipment * Diving mask * Snorkel * Swimfin Breathing gas * Bailout gas * Bottom gas * Breathing air * Decompression gas * Emergency gas supply * Heliox * Nitrox * Oxygen * Travel gas * Trimix Buoyancy and trim equipment * Buoyancy compensator * Power inflator * Dump valve * Diving weighting system * Ankle weights * Integrated weights * Trim weights * Weight belt Decompression equipment * Decompression buoy * Decompression cylinder * Decompression trapeze * Dive computer * Diving shot * Jersey upline * Jonline Diving suit * Atmospheric diving suit * Dry suit * Sladen suit * Standard diving suit * Rash vest * Wetsuit * Dive skins * Hot-water suit Helmets and masks * Anti-fog * Diving helmet * Free-flow helmet * Lightweight demand helmet * Orinasal mask * Reclaim helmet * Shallow water helmet * Standard diving helmet * Diving mask * Band mask * Full-face mask * Half mask Instrumentation * Bottom timer * Depth gauge * Dive computer * Dive timer * Diving watch * Helium release valve * Pneumofathometer * Submersible pressure gauge Mobility equipment * Diving bell * Closed bell * Wet bell * Diving stage * Swimfin * Monofin * PowerSwim * Towboard Diver propulsion vehicle * Advanced SEAL Delivery System * Cosmos CE2F series * Dry Combat Submersible * Human torpedo * Motorised Submersible Canoe * Necker Nymph * R-2 Mala-class swimmer delivery vehicle * SEAL Delivery Vehicle * Shallow Water Combat Submersible * Siluro San Bartolomeo * Wet Nellie * Wet sub Safety equipment * Alternative air source * Octopus regulator * Pony bottle * Bolt snap * Buddy 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recovery system * Wet bell * Diving chamber * Diving stage * Recreational Dive Planner * Saturation system Platforms * Dive boat * Canoe and kayak diving * Combat Rubber Raiding Craft * Liveaboard * Subskimmer * Diving support vessel * HMS Challenger (K07) Underwater habitat * Aquarius Reef Base * Continental Shelf Station Two * Helgoland Habitat * Jules' Undersea Lodge * Scott Carpenter Space Analog Station * SEALAB * Tektite habitat Remotely operated underwater vehicles * 8A4-class ROUV * ABISMO * Atlantis ROV Team * CURV * Deep Drone * Épaulard * Global Explorer ROV * Goldfish-class ROUV * Kaikō ROV * Kaşif ROUV * Long-Term Mine Reconnaissance System * Mini Rover ROV * OpenROV * ROV KIEL 6000 * ROV PHOCA * Scorpio ROV * Sea Dragon-class ROV * Seabed tractor * Seafox drone * Seahorse ROUV * SeaPerch * SJT-class ROUV * T1200 Trenching Unit * VideoRay UROVs Safety equipment * Diver down flag * Diving shot * Hyperbaric lifeboat * Hyperbaric stretcher * Jackstay * Jonline * Reserve gas supply General * Diving spread * Air spread * Saturation spread * Hot water system * Sonar * Underwater acoustic positioning system * Underwater acoustic communication Freediving Activities * Aquathlon * Apnoea finswimming * Freediving * Haenyeo * Pearl hunting * Ama * Snorkeling * Spearfishing * Underwater football * Underwater hockey * Underwater ice hockey * Underwater rugby * Underwater target shooting Competitions * Nordic Deep * Vertical Blue * Disciplines * Constant weight (CWT) * Constant weight without fins (CNF) * Dynamic apnea (DYN) * Dynamic apnea without fins (DNF) * Free immersion (FIM) * No-limits apnea (NLT) * Static apnea (STA) * Skandalopetra diving * Variable weight apnea (VWT) * Variable weight apnea without fins Equipment * Diving mask * Diving suit * Hawaiian sling * Polespear * Snorkel (swimming) * Speargun * Swimfins * Monofin * Water polo cap Freedivers * Deborah Andollo * Peppo Biscarini * Sara Campbell * Derya Can Göçen * Goran Čolak * Carlos Coste * Robert Croft * Mandy-Rae Cruickshank * Yasemin Dalkılıç * Leonardo D'Imporzano * Flavia Eberhard * Şahika Ercümen * Emma Farrell * Francisco Ferreras * Pierre Frolla * Flavia Eberhard * Mehgan Heaney-Grier * Elisabeth Kristoffersen * Loïc Leferme * Enzo Maiorca * Jacques Mayol * Audrey Mestre * Karol Meyer * Stéphane Mifsud * Alexey Molchanov * Natalia Molchanova * Dave Mullins * Patrick Musimu * Guillaume Néry * Herbert Nitsch * Umberto Pelizzari * Annelie Pompe * Michal Risian * Stig Severinsen * Tom Sietas * Aharon Solomons * Martin Štěpánek * Walter Steyn * Tanya Streeter * William Trubridge * Devrim Cenk Ulusoy * Danai Varveri * Alessia Zecchini * Nataliia Zharkova Hazards * Barotrauma * Drowning * Freediving blackout * Deep-water blackout * Shallow-water blackout * Hypercapnia * Hypothermia Historical * Ama * Octopus wrestling * Swimming at the 1900 Summer Olympics – Men's underwater swimming Organisations * AIDA International * Scuba Schools International * Australian Underwater Federation * British Freediving Association * Confédération Mondiale des Activités Subaquatiques * Fédération Française d'Études et de Sports Sous-Marins * Performance Freediving International Professional diving Occupations * Ama * Commercial diver * Commercial offshore diver * Hazmat diver * Divemaster * Diving instructor * Diving safety officer * Diving superintendent * Diving supervisor * Haenyeo * Media diver * Police diver * Public safety diver * Scientific diver * Underwater archaeologist Military diving * Army engineer diver * Clearance diver * Frogman * List of military diving units * Royal Navy ships diver * Special Boat Service * United States military divers * U.S. Navy diver * U.S.Navy master diver * United States Navy SEALs * Underwater Demolition Team Underwater work * Commercial offshore diving * Dive leader * Diver training * Recreational diver training * Hyperbaric welding * Media diving * Nondestructive testing * Pearl hunting * Police diving * Potable water diving * 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revolvers * AAI underwater revolver * Underwater rifles * ADS amphibious rifle * APS underwater rifle * ASM-DT amphibious rifle Recreational diving Specialties * Altitude diving * Cave diving * Deep diving * Ice diving * Muck diving * Open-water diving * Rebreather diving * Sidemount diving * Solo diving * Technical diving * Underwater photography * Wreck diving Diver organisations * British Sub-Aqua Club (BSAC) * Cave Divers Association of Australia (CDAA) * Cave Diving Group (CDG) * Comhairle Fo-Thuinn (CFT) * Confédération Mondiale des Activités Subaquatiques (CMAS) * Federación Española de Actividades Subacuáticas (FEDAS) * Fédération Française d'Études et de Sports Sous-Marins (FFESSM) * International Association for Handicapped Divers (IAHD) * National Association for Cave Diving (NACD) * Woodville Karst Plain Project (WKPP) Diving tourism industry * Dive center * Environmental impact of recreational diving * Scuba diving tourism * Shark tourism * Sinking ships for wreck diving sites Diving events and festivals * Diversnight * Underwater Bike Race Recreational dive sites Reef diving regions * Aliwal Shoal Marine Protected Area * Arrecifes de Cozumel National Park * Edmonds Underwater Park * Great Barrier Reef * iSimangaliso Marine Protected Area * Poor Knights Islands * Table Mountain National Park Marine Protected Area Reef dive sites * Artificial reef * Gibraltar Artificial Reef * Shark River Reef * Osborne Reef * Fanadir * Gamul Kebir * Palancar Reef * Underwater artworks * Cancún Underwater Museum * Christ of the Abyss * Molinere Underwater Sculpture Park Wreck diving regions * Chuuk Lagoon * Edmonds Underwater Park * Finger Lakes Underwater Preserve Association * Maritime Heritage Trail – Battle of Saipan * Michigan Underwater Preserves * Robben Island Marine Protected Area * Table Mountain National Park Marine Protected Area * Tulagi * Tulamben * Whitefish Point Underwater Preserve * Wreck Alley, San Diego Wreck dive sites * HMS A1 * HMS A3 * USS Aaron 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Field * Andrea Doria * Antilla * Antilles * Aquila * USS Arkansas * Bianca C. * SS Binnendijk * HMS Boadicea * Booya * HMSAS Bloemfontein * Breda * HMAS Brisbane * HMHS Britannic * Bungsberg * HMAS Canberra * Carl D. Bradley * Carnatic * SMS Dresden * Dunraven * Eastfield * HMT Elk * Ellengowan * RMS Empress of Ireland * HMS Falmouth * Fifi * SS Francisco Morazan * Fujikawa Maru * Fumizuki * SATS General Botha * USNS General Hoyt S. Vandenberg * HMS Ghurka * Glen Strathallan * SAS Good Hope * Gothenburg * Herzogin Cecilie * Hilma Hooker * Hispania * HMS Hood * HMAS Hobart * Igara * James Eagan Layne * Captain Keith Tibbetts * King Cruiser * SMS Kronprinz * Kyarra * HMS Laforey * USAT Liberty * Louis Sheid * USS LST-507 * SMS Markgraf * Mikhail Lermontov * HMS M2 * Maine * Maloja * HMS Maori * Marguerite * SS Mauna Loa * USAT Meigs * Mendi * USCGC Mohawk * Mohegan * RMS Moldavia * HMS Montagu * MV RMS Mulheim * Nagato * Oceana * USS Oriskany * Oslofjord * P29 * P31 * Pedernales * Persier * HMAS Perth * SAS Pietermaritzburg * Piłsudski * Pool Fisher * HMS Port Napier * Preußen * President Coolidge * PS Queen Victoria * Radaas * Rainbow Warrior * RMS Rhone * Rondo * Rosehill * Rotorua * Royal Adelaide * Royal Charter * Rozi * HMS Safari * Salem Express * USS Saratoga * USS Scuffle * HMS Scylla * HMS Sidon * USS Spiegel Grove * Stanegarth * Stanwood * Stella * HMAS Swan * USS Tarpon * Thesis * Thistlegorm * Toa Maru * Torrey Canyon * SAS Transvaal * U-40 * U-352 * U-1195 * Um El Faroud * Varvassi * Walter L M Russ * Washingtonian (1913) * HMNZS Wellington * USS Yancey * Yongala * Zenobia * Zealandia * Zingara Cave diving sites * Blauhöhle * Chinhoyi Caves * Devil's Throat at Punta Sur * Engelbrecht Cave * Fossil Cave * Jordbrugrotta * Piccaninnie Ponds * Pluragrotta * Pollatoomary * Sistema Ox Bel Ha * Sistema Sac Actun * Sistema Dos Ojos * Sistema Nohoch Nah Chich Freshwater dives * Dutch Springs * Ewens Ponds * Little Blue Lake Training sites * Capernwray Dive Centre * Deepspot * National Diving and Activity Centre * Stoney Cove Open ocean diving * Blue-water diving * Black-water diving Diving safety * Human factors in diving equipment design * Human factors in diving safety * Life-support system * Safety-critical system * Scuba diving fatalities Diving hazards * List of diving hazards and precautions * Environmental * Current * Delta-P * Entanglement hazard * Overhead * Silt out * Wave action * Equipment * Freeflow * Use of breathing equipment in an underwater environment * Failure of diving equipment other than breathing apparatus * Single point of failure * Physiological * Cold shock response * Decompression * Nitrogen narcosis * Oxygen toxicity * Seasickness * Uncontrolled decompression * Diver behaviour and competence * Lack of competence * Overconfidence effect * Panic * Task loading * Trait anxiety * Willful violation Consequences * Barotrauma * Decompression sickness * Drowning * Hypothermia * Hypoxia * Hypercapnia * Hyperthermia Diving procedures * Ascending and descending * Emergency ascent * Boat diving * Canoe and kayak diving * Buddy diving * buddy check * Decompression * Decompression practice * Pyle stop * Ratio decompression * Dive briefing * Dive log * Dive planning * Scuba gas planning * Diver communications * Diving hand signals * Diving line signals * Diver voice communications * Diver rescue * Diver training * Doing It Right * Drift diving * Gas blending for scuba diving * Night diving * Solo diving * Water safety Risk management * Checklist * Hazard identification and risk assessment * Hazard analysis * Job safety analysis * Risk assessment * Risk control * Hierarchy of hazard controls * Incident pit * Lockout–tagout * Permit To Work * Redundancy * Safety data sheet * Situation awareness Diving team * Bellman * Chamber operator * Diver medical technician * Diver's attendant * Diving supervisor * Diving systems technician * Gas man * Life support technician * Stand-by diver Equipment safety * Breathing gas quality * Testing and inspection of diving cylinders * Hydrostatic test * Sustained load cracking * Diving regulator * Breathing performance of regulators Occupational safety and health * Approaches to safety * Job safety analysis * Risk assessment * Toolbox talk * Housekeeping * Association of Diving Contractors International * Code of practice * Contingency plan * Diving regulations * Emergency procedure * Emergency response plan * 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Thalmann * Jacques Triger Diving medical research organisations * Aerospace Medical Association * Divers Alert Network (DAN) * Diving Diseases Research Centre (DDRC) * Diving Medical Advisory Council (DMAC) * European Diving Technology Committee (EDTC) * European Underwater and Baromedical Society (EUBS) * National Board of Diving and Hyperbaric Medical Technology * Naval Submarine Medical Research Laboratory * Royal Australian Navy School of Underwater Medicine * Rubicon Foundation * South Pacific Underwater Medicine Society (SPUMS) * Southern African Underwater and Hyperbaric Medical Association (SAUHMA) * Undersea and Hyperbaric Medical Society (UHMS) * United States Navy Experimental Diving Unit (NEDU) Law * Civil liability in recreational diving * Diving regulations * Duty of care * List of legislation regulating underwater diving * Investigation of diving accidents * UNESCO Convention on the Protection of the Underwater Cultural Heritage History of underwater diving * History of decompression research and development * History of scuba diving * List of researchers in underwater diving * Timeline of diving technology * Underwater diving in popular culture Archeological sites * SS Commodore * USS Monitor * Queen Anne's Revenge * Whydah Gally Underwater art and artists * The Diver * Jason deCaires Taylor Engineers and inventors * William Beebe * Georges Beuchat * John R. 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Marketing Association * Divers Alert Network * Green Fins * Historical Diving Society * Karst Underwater Research * Nautical Archaeology Program * Nautical Archaeology Society * Naval Air Command Sub Aqua Club * Project AWARE * Reef Check * Reef Life Survey * Rubicon Foundation * Save Ontario Shipwrecks * SeaKeys * Sea Research Society * Society for Underwater Historical Research * Society for Underwater Technology * Underwater Archaeology Branch, Naval History & Heritage Command Submarine escape and rescue * Escape trunk * International Submarine Escape and Rescue Liaison Office * McCann Rescue Chamber * Submarine Escape and Rescue system (Royal Swedish Navy) * Submarine escape training facility * Submarine Escape Training Facility (Australia) * Submarine rescue ship Neutral buoyancy facilities for Astronaut training * Neutral Buoyancy Laboratory * Neutral buoyancy pool * Neutral buoyancy simulation as a training aid * Neutral Buoyancy Simulator * Space Systems Laboratory * Yuri Gagarin Cosmonaut Training Center Other * Nautilus Productions * Category * Commons * * Glossary * Indexes: dive sites * divers * diving * * Outline * Portal [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	Salt water aspiration syndrome	None	8,390	wikipedia	https://en.wikipedia.org/wiki/Salt_water_aspiration_syndrome	2021-01-18T18:36:47	{"wikidata": ["Q7406013"]}
## Description Intracranial berry aneurysms are saccular outpouchings of the intracranial arteries, most commonly at arterial bifurcations, characterized by arterial wall remodeling. Most cases of ruptured intracranial berry aneurysms result in a subarachnoid hemorrhage, associated with high morbidity and mortality (summary by van der Voet et al., 2004). For a discussion of genetic heterogeneity of intracranial berry aneurysm, see ANIB1 (105800). Mapping In a genomewide scan of 48 affected sib pairs from a Finnish population, Olson et al. (2002) identified a locus for intracranial aneurysms on chromosome 19q13, with a maximum multipoint lod score of 2.6 between markers D19S245 and D19S246. In a follow-up study with a total of 222 affected Finnish relative pairs, van der Voet et al. (2004) refined the ANIB2 locus to a 6.6-cM region on 19q13.3 between markers D19S545 and D19S246 (lod scores greater than 3.0). Families with nonsaccular aneurysms or with predisposing conditions, such as polycystic kidney disease (173900), Ehlers-Danlos syndrome (130000), or Marfan syndrome (154700), were excluded from the study. [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	ANEURYSM, INTRACRANIAL BERRY, 2	c1837894	8,391	omim	https://www.omim.org/entry/608542	2019-09-22T16:07:40	{"doid": ["0060228"], "mesh": ["C536360"], "omim": ["608542", "105800"], "orphanet": ["231160"], "synonyms": ["Familial berry aneurysm", "Familial intracranial saccular aneurysm"]}
## Description Limb-girdle muscular dystrophy type 1H (LGMD1H) is an autosomal dominant disorder characterized by adult onset of progressive proximal muscle weakness affecting both the upper and lower limbs (Bisceglia et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511). Clinical Features Bisceglia et al. (2010) reported a 4-generation family from southern Italy segregating limb-girdle muscular dystrophy in an autosomal dominant pattern of inheritance. Five family members presented with slowly progressive muscle weakness, initially affecting the lower limbs and later involving the upper limbs, with onset between 39 and 50 years of age. There was hypotrophy of upper and lower limb-girdle muscles, hyporeflexia, calf hypertrophy, and increased serum creatine kinase. A second group of younger family members had a possibly less severe phenotype with calf hypertrophy, but no muscle weakness and normal serum creatine kinase when examined. These individuals were considered affected for linkage analysis. EMG studies in 2 older patients showed a myopathic pattern with decreased duration of motor unit potentials and no evidence of denervation. Skeletal muscle biopsies of 4 older affected individuals showed abnormal fiber type size and shape variation, increased connective tissues, and occasional centralized nuclei. One biopsy showed ragged-red fibers with subsarcolemmal accumulation of mitochondria, and 2 biopsies showed absence of cytochrome c oxidase staining as well as evidence of mtDNA deletions. Overall, the biopsy results suggested a defect in mitochondrial function. Mapping By genomewide linkage analysis, followed by haplotype analysis, of a 4-generation Italian family with LGMD, Bisceglia et al. (2010) identified a candidate disease locus, which the authors termed LGMD1H, within a 25-cM region on chromosome 3p25.1-p23 between markers D3S1263 and D3S1277 (2-point lod score of 3.23 at markers D3S3613 and D3S1286; nonparametric p value of 0.0004). Two unaffected individuals, aged 14 and 30 years, respectively, shared the disease haplotype. Four candidate genes in the region, CAV3 (601253), CAPN7 (606300), MGC15763, and CMYA1 (609777), were analyzed but no pathogenic mutations were found. INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Proximal muscle weakness, upper and lower limbs \- Hip girdle muscle atrophy \- Shoulder girdle muscle atrophy \- Calf hypertrophy \- EMG shows myopathic pattern \- Muscle biopsy shows abnormal fiber size and variation \- Increased connective tissue \- Centralized nuclei, rare \- Ragged red fibers \- Subsarcolemmal mitochondrial accumulation \- Cytochrome c oxidase-negative fibers \- Mitochondrial DNA deletions NEUROLOGIC Peripheral Nervous System \- Hyporeflexia LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset of muscle weakness in fifth decade \- Onset of calf hypotrophy may occur earlier \- Slowly progressive \- Incomplete penetrance \- Variable expressivity \- One family has been reported (as of August 2010) ▲ 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 DYSTROPHY, LIMB-GIRDLE, TYPE 1H	c3150786	8,392	omim	https://www.omim.org/entry/613530	2019-09-22T15:58:21	{"doid": ["0110303"], "omim": ["613530"], "orphanet": ["238755"], "synonyms": ["LGMD1H"]}
Ameloblastoma Micrograph of an ameloblastoma showing the characteristic palisading and stellate reticulum. H&E stain. SpecialtyOncology, oral and maxillofacial surgery Ameloblastoma is a rare, benign tumor of odontogenic epithelium (ameloblasts, or outside portion, of the teeth during development) much more commonly appearing in the lower jaw than the upper jaw.[1] It was recognized in 1827 by Cusack.[2] This type of odontogenic neoplasm was designated as an adamantinoma in 1885 by the French physician Louis-Charles Malassez.[3] It was finally renamed to the modern name ameloblastoma in 1930 by Ivey and Churchill.[4][5] While these tumors are rarely malignant or metastatic (that is, they rarely spread to other parts of the body), and progress slowly, the resulting lesions can cause severe abnormalities of the face and jaw leading to severe disfiguration. Additionally, as abnormal cell growth easily infiltrates and destroys surrounding bony tissues, wide surgical excision is required to treat this disorder. If an aggressive tumor is left untreated, it can obstruct the nasal and oral airways making it impossible to breathe without oropharyngeal intervention. The term "ameloblastoma" is from the early English word amel, meaning enamel and the Greek word blastos, meaning germ.[6] ## Contents * 1 Types * 1.1 Conventional ameloblastoma * 1.2 Unicystic ameloblastoma * 1.3 Metastasising ameloblastoma * 1.4 Peripheral ameloblastoma * 2 Presentation * 3 Histopathology * 3.1 Solid structure * 3.1.1 Follicular * 3.1.2 Plexiform * 3.2 Cystic structure * 3.3 Desmoplastic ameloblastoma * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 5.1 Surgical resection * 5.2 Enucleation * 5.3 Radiation and chemotherapy * 5.4 Follow-up and recurrence * 5.5 Molecular biology * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Types[edit] Four types of ameloblastoma have been described by the WHO 2017 classification:[7] * Conventional (solid/multicystic) type ameloblastoma * Unicystic ameloblastoma * Peripheral/extraosseous ameloblastoma * Metastasising ameloblastoma ### Conventional ameloblastoma[edit] Previously known as solid/multicystic ameloblastoma. Usually presents with multiple large cystic areas. ### Unicystic ameloblastoma[edit] Ameloblastoma with a single cyst cavity account for around 10% of ameloblastomas. Present in younger patients in their second and third decades of life, often in relation to unerupted third molar.[8] ### Metastasising ameloblastoma[edit] Histologically atypical ameloblastoma can, rarely, lead to metastasis, usually in the lung. 'Metastasis' look histologically identical to the primary tumour and are benign in nature.[8] ### Peripheral ameloblastoma[edit] The peripheral subtype composes 2% of all ameloblastomas.[1] ## Presentation[edit] Ameloblastomas can be found both in the maxilla and mandible. Although, 80% are situated in the mandible with the posterior ramus area being the most frequent site.[9] The neoplasms are often associated with the presence of unerupted teeth, displacement of adjacent teeth and resorption of roots.[10] Symptoms include a slow-growing, painless swelling leading to facial deformity. As the swelling gets progressively larger it can impinge on other structures resulting in loose teeth and malocclusion. Bone can also be perforated leading to soft tissue involvement.[9] The lesion has a tendency to expand the bony cortices because the slow growth rate of the lesion allows time for the periosteum to develop a thin shell of bone ahead of the expanding lesion. This shell of bone cracks when palpated. This phenomenon is referred to as "Egg Shell Cracking" or crepitus, an important diagnostic feature. Maxillary ameloblastomas can be dangerous and even lethal. Due to thin bone and weak barriers, the neoplasm can extend into the sinonasal passages, pterygomaxillary fossa and eventually into the cranium and brain.[8] Rare orbital invasion of the neoplasm has also been reported.[11] ## Histopathology[edit] A CT scan of a patient with an ameloblastoma. The resected left half of a mandible containing an ameloblastoma, initiated at the third molar Conventional ameloblastomas have both cystic and solid neoplastic structures. ### Solid structure[edit] Solid areas contain fibrous tissue islands or epithelium that interconnect through strands and sheets. The epithelial cells tend to move the nucleus away from the basement membrane to the opposite pole of the cell. This process is called reverse polarization. Two main histological patterns most often occur: follicular and plexiform. Other less common histological variants include acanthomatous, basal cell, and granular cell patterns.[8] #### Follicular[edit] The most common follicular type has an outer arrangement of columnar or palisaded ameloblasts-like cells and inner zone of triangular shaped cells resembling stellate reticulum from the bell stage of tooth development.[8] #### Plexiform[edit] The plexiform type has epithelium that proliferates in a "Fish Net Pattern". The plexiform ameloblastoma shows epithelium proliferating in a 'cord like fashion', hence the name 'plexiform'. There are layers of cells in between the proliferating epithelium with well-formed desmosomal junctions, simulating spindle cell layers. The ameloblasts cells can be less prominent.[8] ### Cystic structure[edit] Large cysts up to a few centimetres in diameter can be found. In follicular type, cysts develop in the stellate reticulum and in the plexiform type, cysts are caused by degeneration of connective tissue stroma.[8] ### Desmoplastic ameloblastoma[edit] A distinctive histological variant of conventional ameloblastoma. Found in near equal frequencies in both maxilla and mandible. Resemble a fibro-osseous lesion with no obvious ameloblasts whilst dominated by dense collagenous tissue (desmoplastic).[8] In one center, desmoplastic ameloblastomas represented about 9% of all ameloblastomas encountered.[12] A systematic review showed a predilection for males and predominance in fourth and fifth decades in life. 52% desmoplastic ameloblastomas showed mandibular involvement, with a tendency to anterior region. Majority of tumours were found to have ill-defined margins radiographically.[13] Ameloblastoma ## Diagnosis[edit] Ameloblastoma is tentatively diagnosed through radiographic examination and must be confirmed by histological examination through biopsy.[8] Radiographically, the tumour area appears as a rounded and well-defined lucency in the bone with varying size and features. Numerous cyst-like radiolucent areas can be seen in larger tumours (multi-locular) giving a characteristic "soap bubble" appearance. A single radiolucent area can be seen in smaller tumours (unilocular).[8] The radiodensity of an ameloblastoma is about 30 Hounsfield units, which is about the same as keratocystic odontogenic tumours. However, ameloblastomas show more bone expansion and seldom show high density areas.[14] Lingual plate expansion is helpful in diagnosing ameloblastoma as cysts rarely do this. Resorption of roots of involved teeth can be seen in some cases, but is not unique to ameloblastoma.[10] ### Differential diagnosis[edit] * Keratocystic odontogenic tumour * Central giant-cell granuloma * Odontogenic myxoma ## Treatment[edit] Tracheal intubation is difficult in this child with a large ameloblastoma. While chemotherapy, radiation therapy, curettage and liquid nitrogen have been effective in some cases of ameloblastoma, surgical resection or enucleation remains the most definitive treatment for this condition. However, in a detailed study of 345 patients, chemotherapy and radiation therapy was contraindicated for the treatment of ameloblastomas.[1] Thus, surgery is the most common treatment of this neoplasm. Conservative treatment requires very careful case selection.[8] ### Surgical resection[edit] The aim of treatment and surgery is to remove the entire tumour with a margin of surrounding tissue (block resection) for a good prognosis.[10] Preferable removal includes 10mm of normal bone around the neoplasm. Larger ameloblastomas can require partial resection of the jaw bone followed by bone grafting.[8] There is evidence that the treatment of conventional ameloblastoma is best done by bone resection.[15] A systematic review found that 79% of desmoplastic ameloblastoma cases were treated by resection.[13] ### Enucleation[edit] Smaller mandibular neoplasms have been enucleated where the cavity of the tumour is curetted, allowing preservation of the bone cortex and the lower border of the mandible. Although, recurrence rate for this type of treatment is higher. Unicystic ameloblastomas—called intraluminal unicystic or plexiform unicystic ameloblstomas can be enucleated, as the epithelium is only limited to the inner cyst wall and lumen.[8] ### Radiation and chemotherapy[edit] Radiation is ineffective in many cases of ameloblastoma.[1] There have also been reports of sarcoma being induced as the result of using radiation to treat ameloblastoma.[16] Chemotherapy is also often ineffective.[16] However, there is some controversy regarding this[17] and some indication that some ameloblastomas might be more responsive to radiation that previously thought.[18][5] ### Follow-up and recurrence[edit] Persistent follow-up examination including radiographs is essential for managing ameloblastoma.[19][8] Follow-up should occur at regular intervals for at least 10 years.[20] Follow up is important, because 50% of all recurrences occur within 5 years postoperatively.[1] Recurrence is common, although the recurrence rates for block resection followed by bone graft are lower than those of enucleation and curettage.[21] Follicular variants appear to recur more than plexiform variants.[1] Unicystic lesions recur less frequently than "non-unicystic" lesions.[1] A low recurrence rate of around 10% can be seen in unicystic ameloblastomas.[8] Recurrence within a bone graft (following resection of the original tumor) does occur, but is less common.[22] Seeding to the bone graft is suspected as a cause of recurrence.[19] The recurrences in these cases seem to stem from the soft tissues, especially the adjacent periosteum.[23] Recurrence has been reported to occur as many as 36 years after treatment.[24] To reduce the likelihood of recurrence within grafted bone, meticulous surgery[22] with attention to the adjacent soft tissues is required.[23][19] ### Molecular biology[edit] BRAF V600E gene and SMO gene mutations have been found in ameloblastomas. V600E mutation is also seen in other malignant and benign neoplasms, which activate the MAP kinase pathway required for cell division and differentiation but is the most commonly seen mutation in ameloblastoma.[8][7] 72% of BRAF mutations are found in the mandible.[7] A recent study discovered a high frequency of BRAF V600E mutations (15 of 24 samples, 63%) in conventional ameloblastoma. These data suggests drugs targeting mutant BRAF as potential novel therapies for ameloblastoma.[25] SMO mutations lead to the activation of the hedgehog pathway giving similar results as V600E but is less frequently seen.[8] 55% of SMO mutations are found in the maxilla.[7] Evidence shows that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro.[26] There is also some research suggesting that α5β1 integrin may participate in the local invasiveness of ameloblastomas.[27] ## Epidemiology[edit] People with African heritage have been shown to have a higher incidence compared to Caucasians, with the site often being in the midline of the mandible.[10] The annual incidence rates per million for ameloblastomas are 1.96, 1.20, 0.18 and 0.44 for black males, black females, white males and white females respectively.[28] Ameloblastomas account for about one percent of all oral tumors[16] and about 18% of odontogenic tumors.[29] Men and women are equally affected, though women average four years younger than men when tumors first occur, and tumors run larger in females.[1] ## See also[edit] * Ameloblastic fibroma * Bone grafting * Epithelial cell rests of Malassez * List of cutaneous conditions * Matrix Metalloproteinase-2 * Tooth development and Odontogenesis ## References[edit] 1. ^ a b c d e f g h Reichart PA, Philipsen HP, Sonner S (March 1995). "Ameloblastoma: biological profile of 3677 cases". European Journal of Cancer, Part B. 31B (2): 86–99. doi:10.1016/0964-1955(94)00037-5. PMID 7633291. 2. ^ Cusack JW (1827). "Report of the amputations of the lower jaw". Dublin Hosp Rec. 4: 1–38. 3. ^ Malassez L (1885). "Sur Le role des debris epitheliaux papdentaires". Arch Physiol Norm Pathol. 5: 309–340 6:379–449. 4. ^ Ivey RH, Churchill HR (1930). "The need of a standardized surgical and pathological classification of tumors and anomalies of dental origin". Am Assoc Dent Sch Trans. 7: 240–245. 5. ^ a b Madhup R, Kirti S, Bhatt ML, Srivastava M, Sudhir S, Srivastava AN (January 2006). "Giant ameloblastoma of jaw successfully treated by radiotherapy". Oral Oncology Extra. 42 (1): 22–25. doi:10.1016/j.ooe.2005.08.004. 6. ^ Brazis PW, Miller NR, Lee AG, Holliday MJ (1995). "Neuro-ophthalmologic Aspects of Ameloblastoma". Skull Base Surgery. 5 (4): 233–44. doi:10.1055/s-2008-1058921. PMC 1656531. PMID 17170964. 7. ^ a b c d Soluk-Tekkeşin M, Wright JM (2018). "The World Health Organization Classification of Odontogenic Lesions: A Summary of the Changes of the 2017 (4th) Edition". Turk Patoloji Dergisi. 34 (1). doi:10.5146/tjpath.2017.01410. PMID 28984343. 8. ^ a b c d e f g h i j k l m n o p q W., Odell, E. (2017-06-28). Cawson's essentials of oral pathology and oral medicine. Preceded by (work): Cawson, R. A. (Ninth ed.). [Edinburgh]. ISBN 9780702049828. OCLC 960030340. 9. ^ a b Crispian S (2013). Oral and maxillofacial medicine : the basis of diagnosis and treatment (3rd ed.). Edinburgh: Churchill Livingstone/Elsevier. ISBN 9780702049484. OCLC 830037239. 10. ^ a b c d Coulthard P, Heasman PA (2008). Master dentistry (2nd ed.). Edinburgh: Churchill Livingstone/Elsevier. ISBN 9780702040047. OCLC 324993231. 11. ^ Abtahi MA, Zandi A, Razmjoo H, Ghaffari S, Abtahi SM, Jahanbani-Ardakani H, Kasaei Z, Kasaei-Koupaei S, Sajjadi S, Sonbolestan SA, Abtahi SH (March 2018). "Orbital invasion of ameloblastoma: A systematic review apropos of a rare entity". Journal of Current Ophthalmology. 30 (1): 23–34. doi:10.1016/j.joco.2017.09.001. PMC 5859465. PMID 29564405. 12. ^ Keszler A, Paparella ML, Dominguez FV (September 1996). "Desmoplastic and non-desmoplastic ameloblastoma: a comparative clinicopathological analysis". Oral Diseases. 2 (3): 228–31. doi:10.1111/j.1601-0825.1996.tb00229.x. PMID 9081764. 13. ^ a b Anand R, Sarode GS, Sarode SC, Reddy M, Unadkat HV, Mushtaq S, Deshmukh R, Choudhary S, Gupta N, Ganjre AP, Patil S (February 2018). "Clinicopathological characteristics of desmoplastic ameloblastoma: A systematic review". Journal of Investigative and Clinical Dentistry. 9 (1): e12282. doi:10.1111/jicd.12282. PMID 28707772. 14. ^ Ariji Y, Morita M, Katsumata A, Sugita Y, Naitoh M, Goto M, Izumi M, Kise Y, Shimozato K, Kurita K, Maeda H, Ariji E (March 2011). "Imaging features contributing to the diagnosis of ameloblastomas and keratocystic odontogenic tumours: logistic regression analysis". Dento Maxillo Facial Radiology. 40 (3): 133–40. doi:10.1259/dmfr/24726112. PMC 3611454. PMID 21346078. 15. ^ Almeida RD, Andrade ES, Barbalho JC, Vajgel A, Vasconcelos BC (March 2016). "Recurrence rate following treatment for primary multicystic ameloblastoma: systematic review and meta-analysis". International Journal of Oral and Maxillofacial Surgery. 45 (3): 359–67. doi:10.1016/j.ijom.2015.12.016. PMID 26792147. 16. ^ a b c Randall S, Zane MD (3 January 2009). "Maxillary Ameloblastoma". Archived from the original on 2008-07-06. 17. ^ Atkinson CH, Harwood AR, Cummings BJ (February 1984). "Ameloblastoma of the jaw. A reappraisal of the role of megavoltage irradiation". Cancer. 53 (4): 869–73. doi:10.1002/1097-0142(19840215)53:4<869::AID-CNCR2820530409>3.0.CO;2-V. PMID 6420036. 18. ^ Miyamoto CT, Brady LW, Markoe A, Salinger D (June 1991). "Ameloblastoma of the jaw. Treatment with radiation therapy and a case report". American Journal of Clinical Oncology. 14 (3): 225–30. doi:10.1097/00000421-199106000-00009. PMID 2031509. 19. ^ a b c Choi YS, Asaumi J, Yanagi Y, Hisatomi M, Konouchi H, Kishi K (January 2006). "A case of recurrent ameloblastoma developing in an autogenous iliac bone graft 20 years after the initial treatment". Dento Maxillo Facial Radiology. 35 (1): 43–6. doi:10.1259/dmfr/13828255. PMID 16421264. 20. ^ Su T, Liu B, Zhao JH, Zhang WF, Zhao YF (February 2006). "[Ameloblastoma recurrence in the grafted iliac bone: report of three cases]". Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. 15 (1): 109–11. PMID 16525625. 21. ^ Vasan NT (March 1995). "Recurrent ameloblastoma in an autogenous bone graft after 28 years: a case report". The New Zealand Dental Journal. 91 (403): 12–3. PMID 7746553. 22. ^ a b Dolan EA, Angelillo JC, Georgiade NG (April 1981). "Recurrent ameloblastoma in autogenous rib graft. Report of a case". Oral Surgery, Oral Medicine, and Oral Pathology. 51 (4): 357–60. doi:10.1016/0030-4220(81)90143-2. PMID 7015222. 23. ^ a b Martins WD, Fávaro DM (December 2004). "Recurrence of an ameloblastoma in an autogenous iliac bone graft". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 98 (6): 657–9. doi:10.1016/j.tripleo.2004.04.020. PMID 15583536. 24. ^ Zachariades N (October 1988). "Recurrences of ameloblastoma in bone grafts. Report of 4 cases". International Journal of Oral and Maxillofacial Surgery. 17 (5): 316–8. doi:10.1016/S0901-5027(88)80011-0. PMID 3143780. 25. ^ Kurppa KJ, Catón J, Morgan PR, Ristimäki A, Ruhin B, Kellokoski J, Elenius K, Heikinheimo K (April 2014). "High frequency of BRAF V600E mutations in ameloblastoma". The Journal of Pathology. 232 (5): 492–8. doi:10.1002/path.4317. PMC 4255689. PMID 24374844. 26. ^ Wang A, Zhang B, Huang H, Zhang L, Zeng D, Tao Q, Wang J, Pan C (June 2008). "Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro". BMC Cancer. 8 (182): 182. doi:10.1186/1471-2407-8-182. PMC 2443806. PMID 18588710. 27. ^ Souza Andrade ES, da Costa Miguel MC, Pinto LP, de Souza LB (June 2007). "Ameloblastoma and adenomatoid odontogenic tumor: the role of alpha2beta1, alpha3beta1, and alpha5beta1 integrins in local invasiveness and architectural characteristics". Annals of Diagnostic Pathology. 11 (3): 199–205. doi:10.1016/j.anndiagpath.2006.04.005. PMID 17498594. 28. ^ Shear M, Singh S (July 1978). "Age-standardized incidence rates of ameloblastoma and dentigerous cyst on the Witwatersrand, South Africa". Community Dentistry and Oral Epidemiology. 6 (4): 195–9. doi:10.1111/j.1600-0528.1978.tb01149.x. PMID 278703. 29. ^ Gordon J (2004). "Clinical Quiz: Painless Mass". Medscape. 3 (8). ## External links[edit] Classification D * ICD-10: D16.4-D16.5 * ICD-9-CM: 213.0-213.1 * ICD-O: 9310/0 * MeSH: D000564 * DiseasesDB: 31676 * SNOMED CT: 20462008 External resources * Orphanet: 314419 Wikimedia Commons has media related to Ameloblastoma. * v * t * e Dental tumors Cementoblast * Cementoblastoma * Cementoma Ameloblast * Ameloblastoma Mixed/hamartoma * Odontoma Other * Adenomatoid odontogenic tumor * Keratocystic odontogenic tumour [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	Ameloblastoma	c0002448	8,393	wikipedia	https://en.wikipedia.org/wiki/Ameloblastoma	2021-01-18T18:32:49	{"gard": ["5747"], "mesh": ["D000564"], "umls": ["C0002448"], "icd-9": ["213.1"], "icd-10": ["D16.5"], "orphanet": ["314419"], "wikidata": ["Q461857"]}
Subacromial bursitis Shoulder joint SpecialtyRheumatology Subacromial bursitis is a condition caused by inflammation of the bursa that separates the superior surface of the supraspinatus tendon (one of the four tendons of the rotator cuff) from the overlying coraco-acromial ligament, acromion, and coracoid (the acromial arch) and from the deep surface of the deltoid muscle.[1] The subacromial bursa helps the motion of the supraspinatus tendon of the rotator cuff in activities such as overhead work. Musculoskeletal complaints are one of the most common reasons for primary care office visits, and rotator cuff disorders are the most common source of shoulder pain.[2] Primary inflammation of the subacromial bursa is relatively rare and may arise from autoimmune inflammatory conditions such as rheumatoid arthritis; crystal deposition disorders such as gout or pseudogout; calcific loose bodies, and infection.[1] More commonly, subacromial bursitis arises as a result of complex factors, thought to cause shoulder impingement symptoms. These factors are broadly classified as intrinsic (intratendinous) or extrinsic (extratendinous). They are further divided into primary or secondary causes of impingement. Secondary causes are thought to be part of another process such as shoulder instability or nerve injury.[3] In 1983 Neer described three stages of impingement syndrome.[4] He noted that "the symptoms and physical signs in all three stages of impingement are almost identical, including the 'impingement sign'..., arc of pain, crepitus, and varying weakness". The Neer classification did not distinguish between partial-thickness and full-thickness rotator cuff tears in stage III.[4] This has led to some controversy about the ability of physical examination tests to accurately diagnose between bursitis, impingement, impingement with or without rotator cuff tear and impingement with partial versus complete tears. In 2005, Park et al. published their findings which concluded that a combination of clinical tests were more useful than a single physical examination test. For the diagnosis of impingement disease, the best combination of tests were "any degree (of) a positive Hawkins–Kennedy test, a positive painful arc sign, and weakness in external rotation with the arm at the side", to diagnose a full thickness rotator cuff tear, the best combination of tests, when all three are positive, were the painful arc, the drop-arm sign, and weakness in external rotation.[5] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Imaging * 3.2 Special considerations * 4 Treatment * 4.1 Early / initial * 4.2 Middle / intermittent * 4.3 Late / return to function * 5 Prognosis * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] Subacromial bursitis often presents with a constellation of symptoms called impingement syndrome. Pain along the front and side of the shoulder is the most common symptom and may cause weakness and stiffness.[3] If the pain resolves and weakness persists other causes should be evaluated such as a tear of the rotator cuff or a neurological problem arising from the neck or entrapment of the suprascapular nerve. The onset of pain may be sudden or gradual and may or may not be related to trauma. Night time pain, especially sleeping on the affected shoulder, is often reported. Localized redness or swelling are less common and suggest an infected subacromial bursa. Individuals affected by subacromial bursitis commonly present with concomitant shoulder problems such as arthritis, rotator cuff tendinitis, rotator cuff tears, and cervical radiculopathy (pinched nerve in neck).[citation needed] Impingement may be brought on by sports activities, such as overhead throwing sports and swimming, or overhead work such as painting, carpentry, or plumbing. Activities that involve repetitive overhead activity, or directly in front, may cause shoulder pain. Direct upward pressure on the shoulder, such as leaning on an elbow, may increase pain.[citation needed] ## Pathophysiology[edit] The literature on the pathophysiology of bursitis describes inflammation as the primary cause of symptoms. Inflammatory bursitis is usually the result of repetitive injury to the bursa. In the subacromial bursa, this generally occurs due to microtrauma to adjacent structures, particularly the supraspinatus tendon. The inflammatory process causes synovial cells to multiply, increasing collagen formation and fluid production within the bursa and reduction in the outside layer of lubrication.[6] Less frequently observed causes of subacromial bursitis include hemorrhagic conditions, crystal deposition and infection. Many causes have been proposed in the medical literature for subacromial impingement syndrome. The bursa facilitates the motion of the rotator cuff beneath the arch, any disturbance of the relationship of the subacromial structures can lead to impingement. These factors can be broadly classified as intrinsic such as tendon degeneration, rotator cuff muscle weakness and overuse. Extrinsic factors include bone spurs from the acromion or AC joint, shoulder instability and neurologic problems arising outside of the shoulder.[3] ## Diagnosis[edit] It is often difficult to distinguish between pain caused by bursitis or that caused by a rotator cuff injury as both exhibit similar pain patterns in the front or side of the shoulder.[7] Subacromial bursitis can be painful with resisted abduction due to the pinching of the bursa as the deltoid contracts.[8] If the therapist performs a treatment direction test and gently applies joint traction or a caudal glide during abduction (MWM), the painful arc may reduce if the problem is bursitis or adhesive capsulitis (as this potentially increases the subacromial space).[citation needed] The following clinical tests, if positive, may indicate bursitis: * The patient actively abducts the arm and a painful arc occurs between 60° and 120°. This is due to the compression of the supraspinatus tendon or subacromial bursa between the anterior acromial arch and humeral head. When lowering from full abduction there is often a painful "catch" at midrange. If the patient can achieve adequate muscle relaxation, passive motion tends to be less painful.[9] * The patient performs an isometric flexion contraction against resistance of the therapist (Speed’s Test). When the therapist’s resistance is removed, a sudden jerking motion results and latent pain indicates a positive test for bursitis.[8] * Neer’s Sign: If pain occurs during forward elevation of the internally rotated arm above 90°. This will identify impingement of the rotator cuff but is also sensitive for subacromial bursitis.[9] Irritation or entrapment of the lower subscapular nerve, which innervates the subscapularis and teres major muscles, will produce muscle guarding at the shoulder that will restrict motion into external rotation, abduction, or flexion. The aforementioned tests will assist in diagnosing bursitis over other conditions. The diagnosis of impingement syndrome should be viewed with caution in people who are less than forty years old, because such individuals may have subtle glenohumeral instability.[10] ### Imaging[edit] X-rays may help visualize bone spurs, acromial anatomy and arthritis. Further, calcification in the subacromial space and rotator cuff may be revealed. Osteoarthritis of the acromioclavicular (AC) joint may co-exist and is usually demonstrated on radiographs.[citation needed] MRI imagining can reveal fluid accumulation in the bursa and assess adjacent structures. In chronic cases caused by impingement tendinosis and tears in the rotator cuff may be revealed. At US, an abnormal bursa may show 1. fluid distension, 2. synovial proliferation, and/or 3. thickening of the bursal walls.[11] In any case, the magnitude of pathological findings does not correlate with the magnitude of the symptoms.[11] ### Special considerations[edit] In patients with bursitis who have rheumatoid arthritis, short term improvements are not taken as a sign of resolution and may require long term treatment to ensure recurrence is minimized. Joint contracture of the shoulder has also been found to be at a higher incidence in type two diabetics, which may lead to frozen shoulder (Donatelli, 2004). ## Treatment[edit] Many non-operative treatments have been advocated, including rest; oral administration of non-steroidal anti-inflammatory drugs; physical therapy; chiropractic; and local modalities such as cryotherapy, ultrasound, electromagnetic radiation, and subacromial injection of corticosteroids.[12] Shoulder bursitis rarely requires surgical intervention and generally responds favorably to conservative treatment. Surgery is reserved for patients who fail to respond to non-operative measures. Minimally invasive surgical procedures such as arthroscopic removal of the bursa allows for direct inspection of the shoulder structures and provides the opportunity for removal of bone spurs and repair of any rotator cuff tears that may be found.[citation needed] ### Early / initial[edit] Initial phase of physiotherapy rehabilitation Goals of treatment * Reduce inflammation * Reduce pain * Prevent weakness and atrophy of muscles as a result of disuse * Increase the patient’s awareness of bursitis * Prevent/reduce impingement and further tissue damage Treatment Justification Advice and education Educate the patient about their condition and advise to avoid painful activities and the importance of relative rest of the shoulder Prevention of pain and impingement which delays the healing process Educate the patient about the importance of correct posture Puts muscles in the optimal length tension relationship, reducing impingement Manual therapy Grade 1 and 2 accessory mobilisations of the glenohumeral joint Has a neurophysiological effect reducing pain and improving synovial fluid flow, improving healing Soft tissue massage Lengthens tight muscles and reduces muscle spasm Therapeutic exercise Gentle pendulum range of motion exercises Maintenance of range of motion and prevention of adhesive capsulitis Scapular exercises such as shoulder shrugs and shoulder retraction exercises Improve muscular control and scapular coordination Centering of humeral head Helps to facilitate adequate muscle timing and recruitment Stretching of tight muscles such as the levator scapulae, pectoralis major, subscapularis and upper trapezius muscle To lengthen tight muscles which may improve scapulohumeral rhythm, posture and increase the subacromial space Rotator cuff strengthening - isometric contractions in neutral and 30 degrees abduction Improves rotator cuff strength which is integral to the stability of the shoulder and functional activities Electrophysical modalities Ice To reduce inflammation and pain elevate Low intensity pulsed ultrasound (3 megaHz) To reduce inflammation and facilitate healing External physical aids May use head of humerus repositioning tape To maintain the head of humerus in its central position for optimal muscle recruitment ### Middle / intermittent[edit] Intermittent phase of physiotherapy rehabilitation Goals of treatment * Improve muscle control * Improve scapulohumeral rhythm * Improve active and passive range of motion * Restore strength of scapular and rotator cuff muscles Treatment Justification Advice and education Advise the patient that they must perform all activities and exercises pain free To prevent reinjury and damage to the bursa Manual therapy Grade 3 and 4 accessory mobilizations of the glenohumeral joint Improves range of motion and increases synovial fluid movement, improving healing Proprioceptive neuromuscular facilitation (PNF) in functional diagonal patterns Strengthens muscles, improves motor control and scapulohumeral rhythm Mobilization with movement e.g. caudal glide with active abduction Improves range of motion and decreases pain Therapeutic exercise Specific muscle strengthening exercises especially for scapular stabilization (serratus anterior, rhomboids and lower trapezius muscles) e.g. strengthening lower trapezius muscle - bilateral external rotation using a theraband, strengthening of serratus anterior, punching with theraband resistance Improves stability during scapular motion which may decrease impingement of the bursa in the subacromial space. Active assisted range of motion - creeping the hand up the wall in abduction, scaption and flexion and door pulley manoeuvre Help to improve active range of motion and gravity assists with shoulder depression Active internal and external rotator exercises with the use of a bar or a theraband Improves strength of rotator cuff and improves mobility in internal and external rotation Electrophysical modalities Heat Improves muscle extensibility Low intensity pulsed ultrasound (3 megaHz) Facilitates healing External physical aids May use head of humerus repositioning tape if necessary To maintain the head of humerus in its optimal position for optimal muscle recruitment ### Late / return to function[edit] Return to function phase of physiotherapy rehabilitation Goals of treatment * Return the patient to their previous level of function * Achieve full active and passive range of motion Treatment Justification Education and advice Education about the importance of a home based exercise program in the late stage of rehabilitation Ensures patient compliance Correction of techniques performed Ensures that the correct target muscles are being used Education to ensure that the patient performs activities and exercises within pain free limits This reduces the chance that the patient may work too hard and cause reinjury Manual therapy PNF functional patterns with increasing resistance Continues to strengthen muscles, improves motor control and scapulohumeral rhythm Therapeutic exercise Exercises specific for the patient’s functional needs e.g. functional reaching To improve the patients functional ability Proprioception exercises e.g. Wall push ups with the hands resting on medicine balls or dura disks Improves proprioception important to reduce reinjury as return to function/sport Strengthen the shoulder elevators – deltoid, flexors and also latissimus dorsi. Important in this phase of the rehabilitation following strengthening of the shoulder depressors Progress strengthening exercises to incorporate speed and load to make more functional Adding speed and load to exercises ensures that the patient is prepared for more functional tasks and activities Electrophysical modalities Ice after exercise May assist to reduce any inflammation post exercise External physical aids May use head of humerus repositioning tape if necessary May assist with return to function ## Prognosis[edit] In 1997 Morrison et al.[13] published a study that reviewed the cases of 616 patients (636 shoulders) with impingement syndrome (painful arc of motion) to assess the outcome of non-surgical care. An attempt was made to exclude patients who were suspected of having additional shoulder conditions such as, full-thickness tears of the rotator cuff, degenerative arthritis of the acromioclavicular joint, instability of the glenohumeral joint, or adhesive capsulitis. All patients were managed with anti-inflammatory medication and a specific, supervised physical-therapy regimen. The patients were followed up from six months to over six years. They found that 67% (413 patients) of the patients improved, while 28% did not improve and went to surgical treatment. 5% did not improve and declined further treatment.[citation needed] Of the 413 patients who improved, 74 had a recurrence of symptoms during the observation period and their symptoms responded to rest or after resumption of the exercise program.[citation needed] The Morrison study shows that the outcome of impingement symptoms varies with patient characteristics. Younger patients (20 years or less) and patients between 41 and 60 years of age, fared better than those who were in the 21 to 40 years age group. This may be related to the peak incidence of work, job requirements, sports and hobby related activities, that may place greater demands on the shoulder. However, patients who were older than sixty years of age had the "poorest results". It is known that the rotator cuff and adjacent structures undergo degenerative changes with ageing.[citation needed] The authors were unable to posit an explanation for the observation of the bimodal distribution of satisfactory results with regard to age. They concluded that it was "unclear why (those) who were twenty-one to forty years old had less satisfactory results". The poorer outcome for patients over 60 years old was thought to be potentially related to "undiagnosed full-thickness tears of the rotator cuff".[13] ## References[edit] 1. ^ a b Salzman KL, Lillegard WA, Butcher JD (1997). "Upper extremity bursitis". Am Fam Physician. 56 (7): 1797–806, 1811–2. PMID 9371010. 2. ^ Arcuni SE (2000). "Rotator cuff pathology and subacromial impingement". Nurse Pract. 25 (5): 58, 61, 65–6 passim. doi:10.1097/00006205-200025050-00005. PMID 10826138. 3. ^ a b c Bigliani LU, Levine WN (1997). "Subacromial impingement syndrome". J Bone Joint Surg Am. 79 (12): 1854–68. doi:10.2106/00004623-199712000-00012. PMID 9409800. 4. ^ a b Neer CS (1983). "Impingement lesions". Clin. Orthop. Relat. Res. (173): 70–7. PMID 6825348. 5. ^ Park HB, Yokota A, Gill HS, El Rassi G, McFarland EG (2005). "Diagnostic accuracy of clinical tests for the different degrees of subacromial impingement syndrome". J Bone Joint Surg Am. 87 (7): 1446–55. doi:10.2106/JBJS.D.02335. PMID 15995110. 6. ^ Ishii et al., 1997. 7. ^ Hartley, 1990 8. ^ a b Buschbacher & Braddom, 1994. 9. ^ a b Starr & Harbhajan, 2001. 10. ^ Jobe FW, Kvitne RS, Giangarra CE (1989). "Shoulder pain in the overhand or throwing athlete. The relationship of anterior instability and rotator cuff impingement". Orthop Rev. 18 (9): 963–75. PMID 2797861. 11. ^ a b Arend CF. Ultrasound of the Shoulder. Master Medical Books, 2013. Free chapter on ultrasound findings of subacromial-subdeltoid bursitis at ShoulderUS.com 12. ^ Blair B, Rokito AS, Cuomo F, Jarolem K, Zuckerman JD (1996). "Efficacy of injections of corticosteroids for subacromial impingement syndrome". J Bone Joint Surg Am. 78 (11): 1685–9. doi:10.2106/00004623-199611000-00007. PMID 8934482. S2CID 36977069. 13. ^ a b Morrison DS, Frogameni AD, Woodworth P (1997). "Non-operative treatment of subacromial impingement syndrome". J Bone Joint Surg Am. 79 (5): 732–7. doi:10.2106/00004623-199705000-00013. PMID 9160946. S2CID 30707675. * Anderson, D., M, (2000), Dorland’s Illustrated Medical Dictionary, 29th ed, W.B. Saunders Company, Canada, 965-967. * Buschbacher, R., M, Braddom, R., L. (1994). Sports medicine & rehabilitation: A sport-specific approach. Hanley and Belfus Inc, Philadelphia. * Hartley, A. (1990). Practical joint assessment: A sports medicine manual, St Louis, Sydney. ## Further reading[edit] * Arend CF. Ultrasound of the Shoulder. Master Medical Books, 2013. Free chapter on bursae around the shoulder joint. * Wilk, Kevin E.; Andrews, James R. (1994). The Athlete's shoulder. Edinburgh: Churchill Livingstone. ISBN 978-0-443-08847-6. * Blaine TA, Kim YS, Voloshin I, et al. (2005). "The molecular pathophysiology of subacromial bursitis in rotator cuff disease". J Shoulder Elbow Surg. 14 (1 Suppl S): 84S–89S. doi:10.1016/j.jse.2004.09.022. PMID 15726092. * Brox JI, Gjengedal E, Uppheim G, et al. (1999). "Arthroscopic surgery versus supervised exercises in patients with rotator cuff disease (stage II impingement syndrome): a prospective, randomized, controlled study in 125 patients with a 21⁄2-year follow-up". J Shoulder Elbow Surg. 8 (2): 102–11. doi:10.1016/S1058-2746(99)90001-0. PMID 10226960. * Butcher JD, Salzman KL, Lillegard WA (1996). "Lower extremity bursitis". Am Fam Physician. 53 (7): 2317–24. PMID 8638508. * Donatelli, Robert (2004). Physical therapy of the shoulder. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06614-6. * Handa A, Gotoh M, Hamada K, et al. (2003). "Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease". J. Orthop. Res. 21 (6): 1138–44. doi:10.1016/S0736-0266(03)00102-5. PMID 14554230. S2CID 29665718. * Hartley, Anne (1990). Practical joint assessment: a sports medicine manual. St. Louis, MO: Mosby Year Book. ISBN 978-0-8016-2050-8. * editors (1994). Sports Medicine and Rehabilitation: A Sport-Specific Approach. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 978-1-56053-133-3.CS1 maint: extra text: authors list (link) * Lo IK, Boorman R, Marchuk L, Hollinshead R, Hart DA, Frank CB (2005). "Matrix molecule mRNA levels in the bursa and rotator cuff of patients with full-thickness rotator cuff tears". Arthroscopy. 21 (6): 645–51. doi:10.1016/j.arthro.2005.03.008. PMID 15944617. * Ishii H, Brunet JA, Welsh RP, Uhthoff HK (1997). ""Bursal reactions" in rotator cuff tearing, the impingement syndrome, and calcifying tendinitis". J Shoulder Elbow Surg. 6 (2): 131–6. doi:10.1016/S1058-2746(97)90033-1. PMID 9144600. * McAfee JH, Smith DL (1988). "Olecranon and prepatellar bursitis. Diagnosis and treatment". West. J. Med. 149 (5): 607–10. PMC 1026560. PMID 3074561. * Perry J (1983). "Anatomy and biomechanics of the shoulder in throwing, swimming, gymnastics, and tennis". Clin Sports Med. 2 (2): 247–70. doi:10.1016/S0278-5919(20)31406-X. PMID 9697636. * Reilly JP, Nicholas JA (1987). "The chronically inflamed bursa". Clin Sports Med. 6 (2): 345–70. doi:10.1016/S0278-5919(20)31035-8. PMID 3319205.Trojian T, Stevenson JH, Agrawal N (2005). "What can we expect from nonoperative treatment options for shoulder pain?". J Fam Pract. 54 (3): 216–23. PMID 15755374. * Shamus, Jennifer; Shamus, Eric (2001). Sports injury: prevention & rehabilitation. New York: McGraw-Hill Medical Pub. Div. ISBN 978-0-07-135475-2. * Starr M, Harbhajan K (June 2001). "Recognition and Management of Common Forms of Tendinitis and Bursitis" (PDF). The Canadian Journal of Continuing Medical Education: 155–63. ISSN 0843-994X. * Trojian T, Stevenson JH, Agrawal N (2005). "What can we expect from nonoperative treatment options for shoulder pain?". J Fam Pract. 54 (3): 216–23. PMID 15755374. * van Holsbeeck M, Strouse PJ (1993). "Sonography of the shoulder: evaluation of the subacromial-subdeltoid bursa". AJR Am J Roentgenol. 160 (3): 561–4. doi:10.2214/ajr.160.3.8430553. PMID 8430553. * Yanagisawa K, Hamada K, Gotoh M, et al. (2001). "Vascular endothelial growth factor (VEGF) expression in the subacromial bursa is increased in patients with impingement syndrome". J. Orthop. Res. 19 (3): 448–55. doi:10.1016/S0736-0266(00)90021-4. PMID 11398859. S2CID 20098903. ## External links[edit] Classification D * ICD-10: M75.5 * ICD-9-CM: 726.19 * v * t * e Soft tissue disorders Capsular joint Synoviopathy * Synovitis/Tenosynovitis * Calcific tendinitis * Stenosing tenosynovitis * Trigger finger * De Quervain syndrome * Transient synovitis * Ganglion cyst * osteochondromatosis * Synovial osteochondromatosis * Plica syndrome * villonodular synovitis * Giant-cell tumor of the tendon sheath Bursopathy * Bursitis * Olecranon * Prepatellar * Trochanteric * Subacromial * Achilles * Retrocalcaneal * Ischial * Iliopsoas * Synovial cyst * Baker's cyst * Calcific bursitis Noncapsular joint Symptoms * Ligamentous laxity * Hypermobility Enthesopathy/Enthesitis/Tendinopathy upper limb * Adhesive capsulitis of shoulder * Impingement syndrome * Rotator cuff tear * Golfer's elbow * Tennis elbow lower limb * Iliotibial band syndrome * Patellar tendinitis * Achilles tendinitis * Calcaneal spur * Metatarsalgia * Bone spur other/general: * Tendinitis/Tendinosis Nonjoint Fasciopathy * Fasciitis: Plantar * Nodular * Necrotizing * Eosinophilic Fibromatosis/contracture * Dupuytren's contracture * Plantar fibromatosis * Aggressive fibromatosis * Knuckle pads [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	Subacromial bursitis	c0546953	8,394	wikipedia	https://en.wikipedia.org/wiki/Subacromial_bursitis	2021-01-18T18:39:44	{"icd-9": ["726.19"], "icd-10": ["M75.5"], "wikidata": ["Q7630699"]}
The newly described 2q23.1 microdeletion syndrome includes severe intellectual deficit with pronounced speech delay, behavioral abnormalities including hyperactivity and inappropriate laughter, short stature and seizures. ## Epidemiology To date, fifteen patients have been reported. ## Clinical description Dysmorphic features include microcephaly, wide and open mouth, a tented upper lip, and prominent incisors. The majority of cases present with stereotypic repetitive behavior, a disturbed sleep pattern and a broad-based gait. Skeletal abnormalities include generalized brachydactyly with small hands and feet. ## Etiology The microdeletion was identified by microarray based comparative genomic hybridization (aCGH). The size of the deletions is variable; the critical region includes a single gene, MBD5. Another gene, EPC2, is deleted in patients who have a broader phenotype than those with a deletion of MBD5 only. [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	2q23.1 microdeletion syndrome	c1969562	8,395	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228402	2021-01-23T19:09:42	{"gard": ["10998"], "mesh": ["C566947"], "omim": ["156200"], "icd-10": ["Q93.5"], "synonyms": ["Del(2)(q23.1)", "Monosomy 2q23.1", "Pseudo-Angelman syndrome"]}
A number sign (#) is used with this entry because of evidence that X-linked deafness-7 (DFNX7) is caused by hemizygous mutation in the GPRASP2 gene (300969) on chromosome Xq26. One such family has been reported. Description DFNX7 is a congenital form of bilateral mixed or conductive hearing loss, which may be progressive. It is not associated with vestibular symptoms (Xing et al., 2017). Clinical Features Xing et al. (2017) reported a 5-generation Chinese family in which 6 males had congenital bilateral hearing loss. The proband (V-4) exhibited symmetric and conductive hearing loss, whereas the 3 other affected men who were examined (IV-9, III-6, III-13) had mixed hearing loss. All had ear anomalies, including canal atresia in 4 and abnormal auricular shape and inner ear malformations in 3. Hearing loss was described as progressive in 3 and as nonprogressive in 1. None of the patients complained of vestibular symptoms. All of the patients had facial dysmorphism, including telecanthus in 4 and bilateral ptosis, heavy eyebrows, and broad nasal root in 3. None had developmental delay or intellectual disability. Molecular Genetics In affected male members of a Chinese family with congenital hearing loss, Xing et al. (2017) identified a hemizygous mutation in the GPRASP2 gene (A573N; 300969.0001) that segregated with hearing loss in the family. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in 300 ethnically matched controls. No functional studies were performed. INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Hearing loss, bilateral mixed or conductive \- Canal atresia/stenosis \- Abnormal auricular shape \- Antitragus formation \- Incomplete antihelix \- Dilatation of internal auditory canal Eyes \- Ptosis \- Telecanthus \- Heavy eyebrows Nose \- Broad nasal root MISCELLANEOUS \- Congenital onset \- Progressive in some patients \- Based on 1 Chinese family (last curated November 15, 2018) MOLECULAR BASIS \- Caused by mutation in the G protein-coupled receptor-associated sorting protein 2 gene (GPRASP2, 300969.0001) ▲ 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	DEAFNESS, X-LINKED 7	None	8,396	omim	https://www.omim.org/entry/301018	2019-09-22T16:19:00	{"omim": ["301018"], "orphanet": ["500188"], "synonyms": []}
This syndrome is characterised by severe hypotonia, lactic academia and congenital hyperammonaemia. ## Epidemiology It has been described in three newborns born to consanguineous parents. ## Clinical description Ultrasound examination during the 36th week of pregnancy revealed generalised oedema. Hypertrophic cardiomyopathy and tubulopathy developed within the first week of life and the infants died within the first month. The activities of enzymes in the mitochondrial respiratory chain were reduced in the muscles of the patients. ## Etiology Mutations were identified in the MRPS22 gene, encoding a mitochondrial ribosomal protein. [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	Hypotonia with lactic acidemia and hyperammonemia	c2673642	8,397	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137908	2021-01-23T17:16:41	{"mesh": ["C567126"], "omim": ["611719"], "umls": ["C2673642"], "icd-10": ["E88.8"], "synonyms": ["COXPD5", "Combined oxidative phosphorylation defect type 5"]}
Complete androgen insensitivity syndrome (CAIS) is a form of androgen insensitivity syndrome (AIS; see this term), a disorder of sex development (DSD), characterized by the presence of female external genitalia in a 46,XY individual with normal testis development but undescended testes and unresponsiveness to age-appropriate levels of androgens. ## Epidemiology The estimated incidence is between 1/20,000 and 1/99,000 live male births. ## Clinical description The typical presentation is primary amenorrhea in an adolescent female. CAIS may also present in infancy or childhood with an inguinal hernia or labial swelling containing a testis. Breast development at puberty is normal, but pubic and axillary hair is absent or scanty. The external genitalia are normal female but internal female genitalia are absent. Adult patients are tall. Other presentations may be serendipitous from a mismatch in prenatal sexing (XY) and birth female phenotype, history of an inguinal hernia repair in an older sister, or development of a pelvic tumor in later adult life. ## Etiology The condition is due to mutations in the androgen receptor (AR) gene which is located on the long arm of the X-chromosome (Xq11-12). The AR is a nuclear transcription factor comprising three functional domains. Mutations are distributed throughout the gene, predominantly in 5 of the 8 exons that code for the ligand binding domain. The CAIS phenotype is associated with an AR mutation that completely disrupts AR function; target cells do not respond to testosterone or dihydrostosterone (DHT). An AR mutation is found in more than 95% of patients with CAIS; 30% are de novo mutations. ## Diagnostic methods The diagnosis is based on clinical and biochemical findings in a female with a 46,XY karyotype. The typical hormone profile is increased basal luteinizing hormone (LH) and testosterone levels in adults, and increased testosterone levels in infants following human chorionic gonadotropin (hCG) stimulation. Serum anti-Müllerian hormone (AMH) levels are normal or increased. Pelvic ultrasound or MRI reveal absent Müllerian structures (uterus, Fallopian tubes and upper vagina), due to the action of testicular anti-Müllerian hormone (AMH). Wolffian duct derivatives (vas deferens, epididymis, seminal vesicle) are absent due to androgen resistance. Mutation analysis of the AR gene confirms the diagnosis. ## Differential diagnosis Differential diagnoses include 17-beta-hydroxysteroid dehydrogenase deficiency, Leydig cell hypoplasia, XY complete gonadal dysgenesis (Swyer syndrome), 5-alpha-reductase type 2 deficiency and variants of congenital adrenal hyperplasia (see these terms). ## Antenatal diagnosis Antenatal diagnosis is seldom indicated. ## Genetic counseling he condition is X-linked recessive. Affected families should be offered genetic counseling in order to be informed of the risk of recurrence and to identify other potential carriers in the family. ## Management and treatment Management includes removal of the testes, either after puberty when feminization is complete or before puberty, followed by estrogen replacement therapy at the age of puberty. Vaginal dilatation may be indicated to avoid dyspareunia. Adults require bone mineral density scans every five years. Psychological support is required for disclosure. ## Prognosis Prognosis for patients with CAIS is favorable if support and counseling are appropriate. Adults have normal female gender identity. Patients are infertile and have an increased risk of osteoporosis if hormone replacement is inadequate. The risk of carcinoma in situ (a pre-malignant disorder) and gonadoblastoma is less than 5%. [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	Complete androgen insensitivity syndrome	c0039585	8,398	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99429	2021-01-23T19:00:45	{"gard": ["10597"], "mesh": ["D013734"], "omim": ["300068", "300274"], "icd-10": ["E34.5"], "synonyms": ["CAIS", "Complete androgen resistance syndrome"]}
Fregoli delusion SpecialtyNeuropsychiatry The Fregoli delusion is a rare disorder in which a person holds a delusional belief that different people are in fact a single person who changes appearance or is in disguise. The syndrome may be related to a brain lesion[1][2] and is often of a paranoid nature, with the delusional person believing themselves persecuted by the person they believe is in disguise. A person with the Fregoli delusion can also inaccurately recall places, objects, and events. This disorder can be explained by "associative nodes". The associative nodes serve as a biological link of information about other people with a particular familiar face (to the patient). This means that for any face that is similar to a recognizable face to the patient, the patient will recall that face as the person they know.[3] The Fregoli delusion is classed both as a monothematic delusion, since it only encompasses one delusional topic, and as a delusional misidentification syndrome (DMS), a class of delusional beliefs that involves misidentifying people, places, or objects.[4] Like Capgras delusion, psychiatrists believe it is related to a breakdown in normal face perception. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Levodopa treatment * 2.2 Traumatic brain injury * 2.3 Fusiform gyrus * 2.4 Abnormal P300 * 3 Treatment * 4 History * 4.1 Delusional misidentification syndromes and Fregoli * 4.2 Coexistence of Capgras and Fregoli * 5 Current research * 6 Popular culture * 7 See also * 8 References ## Signs and symptoms[edit] Signs and symptoms of Fregoli's:[5] * delusions * visual memory deficit * deficit in self-monitoring * deficit in self-awareness * hallucinations * deficit in executive functions * deficit in cognitive flexibility * history of seizure activity * epileptogenic activity ## Causes[edit] ### Levodopa treatment[edit] Levodopa, also known as L-DOPA, is the precursor to several catecholamines, specifically of dopamine, epinephrine and norepinephrine. It is clinically used to treat Parkinson's disease and dopamine-responsive dystonia. Clinical studies have shown that the use of levodopa can lead to visual hallucinations and delusions. In most patients, delusions were more salient than hallucinations. With prolonged use of levodopa, the delusions occupy almost all of a patient's attention. In experimental studies, when the concentration of levodopa decreases, the number of reported delusions decreases as well. It has been concluded that delusions related to antiparkinsonian medications are one of the leading causes of Fregoli syndrome.[6] ### Traumatic brain injury[edit] Injury to the right frontal and left temporo-parietal areas can cause Fregoli syndrome. Research by Feinberg, et al. has shown that significant deficits in executive and memory functions follow shortly after damage in the right frontal or left temporoparietal areas. Tests performed on patients that have suffered from a brain injury revealed that basic attention ability and visuomotor processing speed are typically normal. However, these patients made many errors when they were called to participate in detailed attention tasks. Selective attention tests involving auditory targets were also performed, and brain-injured patients had many errors; this meant that they were deficient in their response regulation and inhibition. The most profound finding in Feinberg et al.'s paper is that performance tests on the retrieval process of memory was significantly damaged in brain-injured patients. They found, however, that these patients chose incorrect answers that were related semantically (i.e., chose vegetable instead of fruit). More importantly, tests of visual memory showed that there was a severe inability in visual recollection. Overall, brain-injured patients were severely impaired in many executive functions such as self-monitoring, mental flexibility, and social reasoning. Fregoli syndrome is an illusion of positive doubles where there is an over-familiarity with the environment. This over-familiarity may have four causes: * impaired self monitoring — passive acceptance of inaccurate conclusions * faulty filtering — tendency to select salient associations rather than a relevant one * mnemonic association from routine thoughts * perseveration — unable to come up with an alternate hypothesis Thus, executive dysfunction appears to be necessary to identify one as having Fregoli's syndrome.[7][8] ### Fusiform gyrus[edit] Main article: Fusiform gyrus Current research has shown that lesions in the right temporal lobe and the fusiform gyrus may contribute to DMSs. MRIs of patients exemplifying Fregoli symptoms have shown parahippocampal and hippocampal damage in the anterior fusiform gyrus, as well as the middle and inferior of the right temporal gyri. The inferior and medial of the right temporal gyri are the storage locations for long-term memory in retrieving information on visual recognition, specifically of faces; thus, damage to these intricate connections could be one of the leading factors in face misidentification disorders. Recently, a face-specific area in the fusiform gyrus has been discovered and is close to the anterior fusiform gyrus. MRI studies performed by Hudson, et al. have shown lesions in the anterior fusiform gyrus, which is close to the face specific area (ventral fusiform cortex), may also be associated with Fregoli syndrome and other DMSs. Such damage may cause disruption in long-term visual memory and lead to improper associations of human faces. On another note, our brains interpret visual scenes in two pathways: one is via the Parietal lobe-occipital dorsal pathway (visual spatial material is analyzed here), and the other is via the temporal-occipital ventral pathway (recognizes objects and faces). Thus, lesions in either structures or disruption of delicate connections may produce DMSs.[9][10] ### Abnormal P300[edit] Delusional misidentification syndrome is thought to occur due to a dissociation between identification and recognition processes. The integration of information for further processing is referred to as working memory (WM). The P300 (P stands for positive voltage potential and the 300 for the 300-millisecond poststimulus) is an index of WM and is used during a WM test in DMS patients. In comparison to normal patients, DMS patients generally exhibit an attenuated amplitude of P300 at many abductions. These patients also exhibit prolonged latencies of P300 at all abductions. These implications suggest that DMSs are accompanied by abnormal WM, specifically affecting the prefrontal cortex (both outside and inside). Past studies have shown correlations between DMS and damages to the right-hemispheric function, which has an array of functions (insight, 3D shapes, art awareness, imagination, left-hand control, music awareness, etc.). In recent years, the P300 auditory component, which forms in response to a detection task that occurs a short time after a stimulus, has acquired a great deal of recognition. The P300 component is an index of mental activity in that its amplitude increases highly with increased stimuli. This P300 component is correlated with updating the working memory to what is expected in the environment. Other findings enhance the belief that defects in the working memory are associated with DMS. Papageorgio et al.'s paper, psychological evidence for altered information processing in delusional misidentification syndromes, hypothesized that electrophysiological brain activity in the working memory and P300 component can help identify the mechanisms of DMS. Thus, they concentrated on P300 released during a working memory test in DMS patients. Papageorgio et al. also found that DMS patients had a lower P300 amplitude in the right hemisphere compared to the control group (non-DMS patients). From this result, the researchers implied that shorter P300 amplitudes are highly correlated with gray matter abnormalities; this finding is consistent with the DMS patients' characteristics and the presence of gray-matter deterioration. DMS patients were also found to have prolonged P300 lag, and their memory performance was lower than the control groups. The researchers were, thus, able to imply that DMS patients have trouble in focusing their resources to a stimulus; this was hypothesized to be caused by the neurodegeneration of the right hemisphere. Overall, other research studies have also provided evidence in the correlation of DMS and gray-matter degeneration of the right frontal region, which controls attentional resources. This research is important, because it can help determine the mechanisms of DMS, which can then help conjure a more effective target drug and/or treatment plan for those suffering from DMS.[11] ## Treatment[edit] Once it has been positively identified, pharmacotherapy follows. Antipsychotic drugs are the frontrunners in treatment for Fregoli and other DMSs. In addition to antipsychotics, anticonvulsants and antidepressants are also prescribed in some treatment courses. If a Fregoli patient has other psychological disorders, treatment often results in the use of trifluoperazine.[12][13][14] ## History[edit] The condition is named after the Italian actor Leopoldo Fregoli, who was renowned for his ability to make quick changes of appearance during his stage act. P. Courbon and G. Fail first reported the condition in a 1927 paper (Syndrome d'illusion de Frégoli et schizophrénie).[15] They described a 27-year-old woman living in London who believed she was being persecuted by two actors she often saw at the theatre. She believed these people pursued her closely, taking the form of people she knew or met. ### Delusional misidentification syndromes and Fregoli[edit] Delusional misidentification syndromes (DMS) are rooted in the inability to register the identity of something, whether it is an object, event, place or even a person. There are various forms of DMS, such as the syndrome of subjective doubles, intermetamorphosis, Capgras syndrome and Fregoli syndrome. However, all of these various syndromes have a common denominator: they are all due to malfunctional familiarity processing during information processing. The most common syndromes are Capgras and Fregoli. Capgras syndrome is the delusional belief that a friend, family member, etc., has been replaced by a twin impostor. Fregoli syndrome is the delusional belief that different people are in fact a single person who is in disguise. Other commonalities among these syndromes are that they are discriminatory in which object(s) are misidentified. Lastly, dopamine hyperactivity is evident in all DMSs and thus, all syndromes utilize antipsychotic medications to help control DMS. ### Coexistence of Capgras and Fregoli[edit] Delusional misidentification syndromes (DMSs) are four types of syndromes: the syndrome of subjective doubles, the syndrome of intermetamorphosis, Fregoli delusion and Capgras syndrome. Of the four, Fregoli syndrome is the least frequent, followed by Capgras. Of more rarity is the coexistence of both Fregoli and Capgras syndromes. Coexistence of DMSs are enhanced when coupled with other mental disorders such as schizophrenia, bipolar disorder and other mood disorders. Depersonalization and derealization symptoms are usually manifested in patients exhibiting two misidentification delusions. However, such symptoms have been witnessed to cease once the coexisting DMSs are fully developed.[16] ## Current research[edit] The study of DMS currently remains controversial[citation needed], as they are often coupled with many psychological disorders (i.e. schizophrenia, bipolar disorder, obsessive compulsive disorder, etc.). Although there is a plethora of information on DMS, there are still many mysteries of the physiological and anatomical details of DMS. An accurate semiological analysis of higher visual anomalies and their corresponding topographic sites may help elucidate the aetiology of Fregoli's and other misidentification disorders. ## Popular culture[edit] Charlie Kaufman's 2015 film Anomalisa has several direct and indirect references to the Fregoli delusion. Kaufman adapted the screenplay from his 2005 audio play Anomalisa, written under the pseudonym Francis Fregoli, and the hotel that Michael stays in is called "The Fregoli". [17] The science fiction short story “Liking What You See: A Documentary”, from the collection Stories of Your Life and Others by Ted Chiang, refers to Fregoli syndrome in the context of artificial targeted neurological impairment. [18] In March 2020, the delusion was covered in an episode of the BBC medical soap opera Doctors when Lizzie Milton (Adele James) believes she is being stalked by Joe Pasquale.[19] ## See also[edit] * Schizophrenia * Cotard delusion * Capgras delusion * Erotomania * Psychosis * Paramnesia * Prosopagnosia * Agnosia * Mirrored-self misidentification ## References[edit] 1. ^ Devinsky, Orrin (6 January 2009). "Delusional misidentifications and duplications: Right brain lesions, left brain delusions". Neurology. 72 (1): 80–87. doi:10.1212/01.wnl.0000338625.47892.74. PMID 19122035. 2. ^ Feinberg, Todd; Eaton, Lisa; Roane, David; Giacino, Joseph (1999). "Multiple Fregoli Delusions after Traumatic Brain Injury". Cortex. 35 (3): 373–387. doi:10.1016/S0010-9452(08)70806-2. PMID 10440075. 3. ^ Tibbetts, Paul. " Symbolic Interaction Theory and the Cognitively Disabled: A neglected Dimension." Jstor. Winter 2004. Web. 28 September 2011 Symbolic Interaction Theory and the Cognitively Disabled: A Neglected Dimension 4. ^ Mojtabai R (September 1994). "Fregoli syndrome". Aust N Z J Psychiatry. 28 (3): 458–62. doi:10.3109/00048679409075874. PMID 7893241. 5. ^ https://www.pharmatutor.org/articles/fregoli-syndrome 6. ^ Stewart JT (January 2008). "Frégoli syndrome associated with levodopa treatment". Mov. Disord. 23 (2): 308–9. doi:10.1002/mds.21843. PMID 18044770. 7. ^ Feinberg TE, Eaton LA, Roane DM, Giacino JT (June 1999). "Multiple Fregoli delusions after traumatic brain injury". Cortex. 35 (3): 373–87. doi:10.1016/S0010-9452(08)70806-2. PMID 10440075. 8. ^ Pires-Barata, S., Gois, J. P., & da Silva, M. H. T. (2008). Fregoli's syndrome and traumatic brain injury. 9. ^ Hudson AJ, Grace GM (2000). "Misidentification syndromes related to face specific area in the fusiform gyrus". J. Neurol. Neurosurg. Psychiatry. 69 (5): 645–8. doi:10.1136/jnnp.69.5.645. PMC 1763428. PMID 11032619. 10. ^ Perez-Martinez DA, Porta-Etessam J (2007). "Higher visual integration abnormalities, illusions and visual hallucinations". Neurologia: 34–41. 11. ^ Papageorgiou C, Lykouras L, Ventouras E, Uzunoglu N, Christodoulou GN (May 2002). "Abnormal P300 in a case of delusional misidentification with coinciding Capgras and Frégoli symptoms". Prog. Neuropsychopharmacol. Biol. Psychiatry. 26 (4): 805–10. doi:10.1016/S0278-5846(01)00293-7. PMID 12188110. 12. ^ Silva JA, Leong GB, Miller AL (1996). "Delusional misidentification syndromes — Drug treatment options". CNS Drugs. 5 (2): 89–102. doi:10.2165/00023210-199605020-00002. 13. ^ McAllister TW, Ferrell RB (2002). "Evaluation and treatment of psychosis after traumatic brain injury". NeuroRehabilitation. 17 (4): 357–68. PMID 12547983. 14. ^ Christodoulou GN (1977). "Treatment of the "syndrome of doubles"". Acta Psychiatr Belg. 77 (2): 254–9. PMID 20738. 15. ^ Ellis HD, Whitley J, Luauté JP (March 1994). "Delusional misidentification. The three original papers on the Capgras, Frégoli and intermetamorphosis delusions. (Classic Text No. 17)". Hist Psychiatry. 5 (17 Pt 1): 117–46. doi:10.1177/0957154X9400501708. PMID 11639277. 16. ^ Lykouras L, Typaldou M, Gournellis R, Vaslamatzis G, Christodoulou GN (July 2002). "Coexistence of Capgras and Frégoli syndromes in a single patient. Clinical, neuroimaging and neuropsychological findings". Eur. Psychiatry. 17 (4): 234–5. doi:10.1016/S0924-9338(02)00660-0. PMID 12231272. 17. ^ "Psychiatric Times: Anomalisa: A beautiful, tricky, heartbreaking puppet show from Charlie Kaufman". 18. ^ Chiang, Ted (2016). Stories of Your Life and Others. Vintage Books. p. 257. ISBN 978-1-101-97212-0. 19. ^ Writer: Stephen Keyworth; Director: David Lewis Richardson; Producer: Peter Leslie Wild (12 March 2020). "The Joe Pasquale Problem". Doctors. BBC. BBC One. [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	Fregoli delusion	None	8,399	wikipedia	https://en.wikipedia.org/wiki/Fregoli_delusion	2021-01-18T18:59:37	{"icd-9": ["297.8"], "icd-10": ["F22"], "wikidata": ["Q1453767"]}

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