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Find sources: "Fazio–Londe disease" – news · newspapers · books · scholar · JSTOR (July 2008) (Learn how and when to remove this template message) Fazio–Londe disease Other namesProgressive bulbar palsy of childhood This condition has a autosomal recessive mode of inheritance SpecialtyNeurology Fazio–Londe disease (FLD), also called progressive bulbar palsy of childhood,[1][2][3] is a very rare inherited motor neuron disease of children and young adults and is characterized by progressive paralysis of muscles innervated by cranial nerves. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 History * 7 Eponym * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] FLD produces rapidly progressive weakness of tongue, face and pharyngeal muscles in a clinical pattern similar to myasthenia. Neuromuscular transmission may be abnormal in these muscles because of rapid denervation and immature reinnervation. Paralysis occurs secondary to degeneration of the motor neurons of the brain stem. It causes progressive bulbar paralysis due to involvement of motor neurons of the cranial nerve nuclei. The most frequent symptoms at onset of progressive bulbar paralysis of childhood has been a unilateral facial paralysis. It is followed in frequency by dysarthria due to facial weakness or by dysphagia. Palatal weakness and palpebral ptosis also have been reported in few patients. Both sexes can be affected. ## Genetics[edit] Fazio–Londe disease is linked to a genetic mutation in the SLC52A3 gene on chromosome 20 (locus: 20p13).[1] It is allelic and phenotypically similar to Brown–Vialetto–Van Laere syndrome.[1][4] The condition is inherited in an autosomal recessive manner.[1] The gene encodes the intestinal riboflavin transporter (hRFT2). ## Diagnosis[edit] Symptoms of Fazio-Londe include bulbar palsy, hearing loss, facial weakness, and difficulty breathing. The disease is caused by mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) genes which code for hRFT3 and hRFT1, human riboflavin transporters. Only muscle biopsy and examination of the transporter genes is considered to provide a definitive diagnosis. However, because the disease is so often fatal without treatment, and because the treatment is so inexpensive and with little risk, it is recommended that if the disease is suspected that riboflavin therapy be started immediately while testing is in progress.[5] ## Treatment[edit] The condition is treatable.[6] High doses of oral riboflavin 5 phosphate may work.[7] If that didn't work sublingual FAD may work. ## Prognosis[edit] Onset of first symptom has been reported between 1–12 years, with a mean age of onset at 8 years. Clinical course can be divided into early (< 6 yrs age, predominance of respiratory symptoms) and late course (6–20 years of age, predominance of motor symptoms on superior limbs). Progression to involve other cranial nerve muscles occurs over a period of months or years. In the Gomez review facial nerve was affected in all cases while hypoglossal nerve was involved in all except one case. Other cranial nerves involved were vagus, trigeminal, spinal accessory nerve, abducent, occulomotor and glossopharyngeal in this order. Corticospinal tract signs were found in 2 of the 14 patients. The disease may progress to patient's death in a period as short as 9 months or may have a slow evolution or may show plateaus. Post mortem examination of cases have found depletion of nerve cells in the nuclei of cranial nerves. The histologic alterations found in patient with Fazio–Londe disease were identical to those seen in infantile-onset spinal muscular atrophy.[citation needed] Strength may improve with administration of cholinesterase inhibitors.[citation needed] ## History[edit] Berger, in 1876, first reported a case of 12-year-old child with progressive bulbar paralysis ## Eponym[edit] It is named for the Italian pathologist, Eugenio Fazio (1849–1902) and for the French physician, Paul Frederic Louis Londe (1864–1944).[8][9] ## See also[edit] * Brown–Vialetto–Van Laere syndrome ## References[edit] 1. ^ a b c d Online Mendelian Inheritance in Man (OMIM): 211500 2. ^ McShane, MA; Boyd, S; Harding, B; Brett, EM; Wilson, J (December 1992). "Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease". Brain : A Journal of Neurology. 115 (Pt 6): 1889–900. doi:10.1093/brain/115.6.1889. PMID 1486466. 3. ^ "progressive bulbar palsy of childhood" at Dorland's Medical Dictionary[dead link] 4. ^ Dipti S, Childs AM, Livingston JH, et al. (September 2005). "Brown–Vialetto–Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio–Londe disease". Brain Dev. 27 (6): 443–446. doi:10.1016/j.braindev.2004.10.003. PMID 16122634. S2CID 32223440. 5. ^ Bosch, Annet M; Stroek, Kevin; Abeling, Nico G; Waterham, Hans R; IJIst, Loedijk; Wanders, Ronald JA (2012). "The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives". Orphanet Journal of Rare Diseases. BMC. 7: 83. doi:10.1186/1750-1172-7-83. PMC 3517535. PMID 23107375. 6. ^ Varadarajan, Poovazhagi; Thayanathi, Vimal; Pauline, LeemaC (2014). "Fazio Londe syndrome: A treatable disorder". Annals of Indian Academy of Neurology. 0 (1): 87–9. doi:10.4103/0972-2327.144283. PMC 4350224. PMID 25745320. 7. ^ Bosch, Annet M; Stroek, Kevin; Abeling, Nico G; Waterham, Hans R; IJlst, Lodewijk; Wanders, Ronald JA (2012-10-29). "The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives". Orphanet Journal of Rare Diseases. 7 (1): 83. doi:10.1186/1750-1172-7-83. ISSN 1750-1172. PMC 3517535. PMID 23107375. 8. ^ synd/1909 at Who Named It? 9. ^ Londe, P. Paralysie bulbaire progressive, infantile et familiale. Rev. Med. 14: 212–254, 1894. ## External links[edit] Classification D * ICD-10: G12.1 * ICD-9-CM: 335.2 * OMIM: 211500 * MeSH: D010244 * DiseasesDB: 29491 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis [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	Fazio–Londe disease	c0015708	5,900	wikipedia	https://en.wikipedia.org/wiki/Fazio%E2%80%93Londe_disease	2021-01-18T18:58:38	{"mesh": ["D010244"], "umls": ["C0015708"], "icd-9": ["335.2"], "icd-10": ["G12.1"], "orphanet": ["56965"], "wikidata": ["Q1399155"]}
Nystagmus Horizontal optokinetic nystagmus, a normal (physiological) form of nystagmus SpecialtyNeurology, ophthalmology Nystagmus is a condition of involuntary (or voluntary, in some cases)[1] eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.[2] Due to the involuntary movement of the eye, it has been called "dancing eyes".[3][a] In normal eyesight, while the head rotates about an axis, distant visual images are sustained by rotating eyes in the opposite direction of the respective axis.[4] The semicircular canals in the vestibule of the ear sense angular acceleration, and send signals to the nuclei for eye movement in the brain. From here, a signal is relayed to the extraocular muscles to allow one's gaze to fix on an object as the head moves. Nystagmus occurs when the semicircular canals are stimulated (e.g., by means of the caloric test, or by disease) while the head is stationary. The direction of ocular movement is related to the semicircular canal that is being stimulated.[5] There are two key forms of nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorder or sleep deprivation, acquired or central nervous system disorders, toxicity, pharmaceutical drugs, alcohol, or rotational movement. Previously considered untreatable, in recent years several drugs have been identified for treatment of nystagmus. Nystagmus is also occasionally associated with vertigo. ## Contents * 1 Causes * 1.1 Early-onset nystagmus * 1.2 Acquired nystagmus * 1.2.1 General diseases and conditions * 1.2.2 Toxicity or intoxication, metabolic disorders and combination * 1.2.3 Thiamine deficiency * 1.2.4 Central nervous system (CNS) diseases and disorders * 1.3 Other causes * 2 Diagnosis * 2.1 Pathologic nystagmus * 2.1.1 Variations * 2.2 Physiological nystagmus * 2.2.1 Variations * 3 Treatment * 4 Epidemiology * 5 Law enforcement * 6 See also * 7 Notes * 8 References * 9 External links ## Causes[edit] The cause of pathological nystagmus may be congenital, idiopathic, or secondary to a pre-existing neurological disorder. It also may be induced temporarily by disorientation (such as on roller coaster rides) or by some drugs (alcohol, lidocaine, and other central nervous system depressants, inhalant drugs, stimulants, psychedelics, and dissociative drugs). ### Early-onset nystagmus[edit] Early-onset nystagmus occurs more frequently than acquired nystagmus. It can be insular or accompany other disorders (such as micro-ophthalmic anomalies or Down syndrome). Early-onset nystagmus itself is usually mild and non-progressive. The affected persons are usually unaware of their spontaneous eye movements, but vision can be impaired depending on the severity of the eye movements. Types of early-onset nystagmus include the following, along with some of their causes: * Infantile: * Albinism * Aniridia * Bilateral congenital cataract * Bilateral optic nerve hypoplasia * Idiopathic * Leber's congenital amaurosis * Optic nerve or macular disease * Persistent tunica vasculosa lentis * Rod monochromatism * Visual-motor syndrome of functional monophthalmus * Latent nystagmus * Noonan syndrome * Nystagmus blockage syndrome X-linked infantile nystagmus is associated with mutations of the gene FRMD7, which is located on the X chromosome.[6][7] Infantile nystagmus is also associated with two X-linked eye diseases known as complete congenital stationary night blindness (CSNB) and incomplete CSNB (iCSNB or CSNB-2), which are caused by mutations of one of two genes located on the X chromosome. In CSNB, mutations are found in NYX (nyctalopin).[8][9] CSNB-2 involves mutations of CACNA1F, a voltage-gated calcium channel that, when mutated, does not conduct ions.[10] ### Acquired nystagmus[edit] Nystagmus that occurs later in childhood or in adulthood is called acquired nystagmus. The cause is often unknown, or idiopathic, and thus referred to as idiopathic nystagmus. Other common causes include diseases and disorders of the central nervous system, metabolic disorders and alcohol and drug toxicity. In the elderly, stroke is the most common cause. #### General diseases and conditions[edit] Some of the diseases that present nystagmus as a pathological sign or symptom are as follows: * Aniridia * Benign paroxysmal positional vertigo[11] * Brain tumors (medulloblastoma, astrocytoma, or other tumors in the posterior fossa.) * Canavan disease * Head trauma * Lateral medullary syndrome * Ménière's disease and other balance disorders * Multiple sclerosis * Optic nerve hypoplasia * Pelizaeus–Merzbacher disease * Superior canal dehiscence syndrome * Tullio phenomenon * Whipple's disease #### Toxicity or intoxication, metabolic disorders and combination[edit] Sources of toxicity that could lead to nystagmus: * Alcohol intoxication * Amphetamines * Barbiturates * Benzodiazepines * Ketamine * Pregabalin * Lithium * MDMA * Nitrous Oxide * Phencyclidine (PCP) * Phenytoin (Dilantin) * Salicylates * Selective serotonin reuptake inhibitors (SSRIs) * Other anticonvulsants or sedatives * Thiamine deficiency * Wernicke's encephalopathy * Wernicke–Korsakoff syndrome #### Thiamine deficiency[edit] Risk factors for thiamine deficiency, or beri beri, in turn include a diet of mostly white rice, as well as alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics.[12][13] Rarely it may be due to a genetic condition that results in difficulties absorbing thiamine found in food.[12] Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi.[13] #### Central nervous system (CNS) diseases and disorders[edit] Central nervous system disorders such as with a cerebellar problem, the nystagmus can be in any direction including horizontal. Purely vertical nystagmus usually originates in the central nervous system, but it is also an adverse effect commonly seen in high phenytoin toxicity. Other causes of toxicity that may result in nystagmus include: * Cerebellar ataxia * Chiari Malformation * Multiple sclerosis * Stroke * Thalamic hemorrhage * Trauma * Tumor ### Other causes[edit] * Non-physiological * Trochlear nerve malfunction[14] * Vestibular Pathology (Ménière's disease, SCDS (superior canal dehiscence syndrome), BPPV, Labyrinthitis) * Exposure to strong magnetic fields (as in MRI machines)[15] * A slightly different form of nystagmus may be produced voluntarily by some people.[16] ## Diagnosis[edit] fast-phase horizontal eye movement vision fast-phase vertical eye movement vision Nystagmus is highly noticeable but rarely recognized. Nystagmus can be clinically investigated by using a number of non-invasive standard tests. The simplest one is the caloric reflex test, in which one ear canal is irrigated with warm or cold water or air. The temperature gradient provokes the stimulation of the horizontal semicircular canal and the consequent nystagmus. Nystagmus is often very commonly present with Chiari malformation. The resulting movement of the eyes may be recorded and quantified by a special devices called an electronystagmograph (ENG), a form of electrooculography (an electrical method of measuring eye movements using external electrodes),[17] or an even less invasive device called a videonystagmograph (VNG),[18] a form of video-oculography (VOG) (a video-based method of measuring eye movements using external small cameras built into head masks), administered by an audiologist. Special swinging chairs with electrical controls can be used to induce rotatory nystagmus.[19] Over the past forty years, objective eye-movement-recording techniques have been applied to the study of nystagmus, and the results have led to greater accuracy of measurement and understanding of the condition. Orthoptists may also use an optokinetic drum, or electrooculography to assess a patient's eye movements. Nystagmus can be caused by subsequent foveation of moving objects, pathology, sustained rotation or substance use. Nystagmus is not to be confused with other superficially similar-appearing disorders of eye movements (saccadic oscillations) such as opsoclonus or ocular flutter that are composed purely of fast-phase (saccadic) eye movements, while nystagmus is characterized by the combination of a smooth pursuit, which usually acts to take the eye off the point of focus, interspersed with the saccadic movement that serves to bring the eye back on target. Without the use of objective recording techniques, it may be very difficult to distinguish among these conditions. In medicine, the presence of nystagmus can be benign, or it can indicate an underlying visual or neurological problem.[20] ### Pathologic nystagmus[edit] Pathological nystagmus is characterized by "excessive drifts of stationary retinal images that degrades vision and may produce illusory motion of the seen world: oscillopsia (an exception is congenital nystagmus)".[21] When nystagmus occurs without fulfilling its normal function, it is pathologic (deviating from the healthy or normal condition). Pathological nystagmus is the result of damage to one or more components of the vestibular system, including the semicircular canals, otolith organs, and the vestibulocerebellum.[contradictory] Pathological nystagmus generally causes a degree of vision impairment, although the severity of such impairment varies widely. Also, many blind people have nystagmus, which is one reason that some wear dark glasses.[22] #### Variations[edit] * Central nystagmus occurs as a result of either normal or abnormal processes not related to the vestibular organ. For example, lesions of the midbrain or cerebellum can result in up- and down-beat nystagmus. * Gaze induced nystagmus occurs or is exacerbated as a result of changing one's gaze toward or away from a particular side which has an affected central apparatus.[23] * Peripheral nystagmus occurs as a result of either normal or diseased functional states of the vestibular system and may combine a rotational component with vertical or horizontal eye movements and may be spontaneous, positional, or evoked. * Positional nystagmus occurs when a person's head is in a specific position.[24] An example of disease state in which this occurs is Benign paroxysmal positional vertigo (BPPV). * Post rotational nystagmus occurs after an imbalance is created between a normal side and a diseased side by stimulation of the vestibular system by rapid shaking or rotation of the head. * Spontaneous nystagmus is nystagmus that occurs randomly, regardless of the position of the patient's head. ### Physiological nystagmus[edit] Physiological nystagmus is a form of involuntary eye movement that is part of the vestibulo-ocular reflex (VOR), characterized by alternating smooth pursuit in one direction and saccadic movement in the other direction. #### Variations[edit] The direction of nystagmus is defined by the direction of its quick phase (e.g. a right-beating nystagmus is characterized by a rightward-moving quick phase, and a left-beating nystagmus by a leftward-moving quick phase). The oscillations may occur in the vertical,[25] horizontal or torsional planes, or in any combination. The resulting nystagmus is often named as a gross description of the movement, e.g. downbeat nystagmus, upbeat nystagmus, seesaw nystagmus, periodic alternating nystagmus. These descriptive names can be misleading, however, as many were assigned historically, solely on the basis of subjective clinical examination, which is not sufficient to determine the eyes' true trajectory. * Optokinetic (syn. opticokinetic) nystagmus: a nystagmus induced by looking at moving visual stimuli, such as moving horizontal or vertical lines, and/or stripes. For example, if one fixates on a stripe of a rotating drum with alternating black and white, the gaze retreats to fixate on a new stripe as the drum moves. This is first a rotation with the same angular velocity, then returns in a saccade in the opposite direction. The process proceeds indefinitely. This is optokinetic nystagmus, and is a source for understanding the fixation reflex.[26] * Postrotatory nystagmus: if one spins in a chair continuously and stops suddenly, the fast phase of nystagmus is in the opposite direction of rotation, known as the "post-rotatory nystagmus", while slow phase is in the direction of rotation.[26] ## Treatment[edit] Congenital nystagmus has long been viewed as untreatable, but medications have been discovered in recent years that show promise in some patients. In 1980, researchers discovered that a drug called baclofen could stop periodic alternating nystagmus. Subsequently, gabapentin, an anticonvulsant, was led to improvement in about half the patients who took it. Other drugs found to be effective against nystagmus in some patients include memantine,[27] levetiracetam, 3,4-diaminopyridine (available in the US to eligible patients with downbeat nystagmus at no cost under an expanded access program[28][29]), 4-aminopyridine, and acetazolamide.[30] Several therapeutic approaches, such as contact lenses,[31] drugs, surgery, and low vision rehabilitation have also been proposed. For example, it has been proposed that mini-telescopic eyeglasses suppress nystagmus.[32] Surgical treatment of congenital nystagmus is aimed at improving head posture, simulating artificial divergence, or weakening the horizontal recti muscles.[33] Clinical trials of a surgery to treat nystagmus (known as tenotomy) concluded in 2001. Tenotomy is now being performed regularly at numerous centres around the world. The surgery aims to reduce the eye oscillations, which in turn tends to improve visual acuity.[34] Acupuncture tests have produced conflicting evidence on its beneficial effects on the symptoms of nystagmus. Benefits have been seen in treatments in which acupuncture points of the neck were used, specifically points on the sternocleidomastoid muscle.[35][36] Benefits of acupuncture for treatment of nystagmus include a reduction in frequency and decreased slow phase velocities, which led to an increase in foveation duration periods both during and after treatment.[36] By the standards of evidence-based medicine, the quality of these studies is poor (for example, Ishikawa's study had sample size of six subjects, was unblinded, and lacked proper controls), and given high quality studies showing that acupuncture has no effect beyond placebo,[citation needed] the results of these studies have to be considered clinically irrelevant until higher quality studies are performed. Physical or occupational therapy is also used to treat nystagmus. Treatment consists of learning strategies to compensate for the impaired system.[citation needed] A Cochrane Review on interventions for eye movement disorders due to acquired brain injury, updated in June 2017, identified three studies of pharmacological interventions for acquired nystagmus but concluded that these studies provided insufficient evidence to guide treatment choices.[37] ## Epidemiology[edit] Nystagmus is a relatively common clinical condition, affecting one in several thousand people. A survey conducted in Oxfordshire, United Kingdom found that by the age of two, one in every 670 children had manifested nystagmus.[2] Authors of another study in the United Kingdom estimated an incidence of 24 in 10,000 (c. 0.240%), noting an apparently higher rate amongst white Europeans than in individuals of Asian origin.[38] ## Law enforcement[edit] Main article: Field sobriety testing § Horizontal Gaze Nystagmus Test (HGN) See also: Positional alcohol nystagmus In the United States, testing for horizontal gaze nystagmus is one of a battery of field sobriety tests used by police officers to determine whether a suspect is driving under the influence of alcohol. The test involves observation of the suspect's pupil as it follows a moving object, noting 1. lack of smooth pursuit, 2. distinct and sustained nystagmus at maximum deviation, and 3. the onset of nystagmus prior to 45 degrees. The horizontal gaze nystagmus test has been highly criticized and major errors in the testing methodology and analysis found.[39][40] However, the validity of the horizontal gaze nystagmus test for use as a field sobriety test for persons with a blood alcohol level between 0.04 and 0.08 is supported by peer reviewed studies and has been found to be a more accurate indication of blood alcohol content than other standard field sobriety tests.[41] ## See also[edit] * Bruns nystagmus * Myoclonus * Oscillopsia * Opsoclonus * Optokinetic nystagmus ## Notes[edit] 1. ^ Note however that "dancing eyes" is also a common term for opsoclonus myoclonus syndrome. ## References[edit] 1. ^ Zahn JR (July 1978). "Incidence and characteristics of voluntary nystagmus". Journal of Neurology, Neurosurgery, and Psychiatry. 41 (7): 617–23. doi:10.1136/jnnp.41.7.617. PMC 493105. PMID 690639. 2. ^ a b "General Information about Nystagmus". American Nystagmus Network. February 21, 2002. Retrieved 2011-11-09. 3. ^ Weil A (2013). "Dealing with dancing eyes". Weil Lifestyle, LLC. Retrieved 2014-04-16. 4. ^ [1]"Nystagmus". Medline Plus. February 27, 2013. Retrieved 2012-12-12. 5. ^ Saladin K (2012). Anatomy and Physiology: The Unity of Form and Function. New York: McGraw-Hill. pp. 597–609. ISBN 978-0-07-337825-1. 6. ^ Self J, Lotery A (December 2007). "A review of the molecular genetics of congenital Idiopathic Nystagmus (CIN)". Ophthalmic Genetics. 28 (4): 187–91. doi:10.1080/13816810701651233. PMID 18161616. S2CID 46052164. 7. ^ Li N, Wang L, Cui L, Zhang L, Dai S, Li H, et al. (April 2008). "Five novel mutations of the FRMD7 gene in Chinese families with X-linked infantile nystagmus". Molecular Vision. 14: 733–8. PMC 2324116. PMID 18431453. 8. ^ Poopalasundaram S, Erskine L, Cheetham ME, Hardcastle AJ (December 2005). "Focus on molecules: nyctalopin". Experimental Eye Research. 81 (6): 627–8. doi:10.1016/j.exer.2005.07.017. PMID 16157331. 9. ^ Leroy BP, Budde BS, Wittmer M, De Baere E, Berger W, Zeitz C (May 2009). "A common NYX mutation in Flemish patients with X linked CSNB". The British Journal of Ophthalmology. 93 (5): 692–6. doi:10.1136/bjo.2008.143727. hdl:1854/LU-940940. PMID 18617546. S2CID 22631306. 10. ^ Peloquin JB, Rehak R, Doering CJ, McRory JE (December 2007). "Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W". Neuroscience. 150 (2): 335–45. doi:10.1016/j.neuroscience.2007.09.021. PMID 17949918. S2CID 22643376. 11. ^ Dorigueto RS, Ganança MM, Ganança FF (2005). "The number of procedures required to eliminate positioning nystagmus in benign paroxysmal positional vertigo" [The number of procedures required to eliminate positioning nystagmus in benign paroxysmal positional vertigo]. Brazilian Journal of Otorhinolaryngology (in Portuguese). 71 (6): 769–75. doi:10.1590/S0034-72992005000600013. PMID 16878247. 12. ^ a b "Beriberi". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2015. Archived from the original on 11 November 2017. Retrieved 11 November 2017. 13. ^ a b "Nutrition and Growth Guidelines \| Domestic Guidelines - Immigrant and Refugee Health". CDC. March 2012. Archived from the original on 11 November 2017. Retrieved 11 November 2017. 14. ^ Lindgren S (1993). Kliniska färdigheter: Informationsutbytet mellan patient och läkare (in Swedish). Lund: Studentlitteratur. ISBN 978-91-44-37271-6.[page needed] 15. ^ Roberts DC, Marcelli V, Gillen JS, Carey JP, Della Santina CC, Zee DS (October 2011). "MRI magnetic field stimulates rotational sensors of the brain". Current Biology. 21 (19): 1635–40. doi:10.1016/j.cub.2011.08.029. PMC 3379966. PMID 21945276. 16. ^ Tusa RJ (June 1999). "Nystagmus: diagnostic and therapeutic strategies". Seminars in Ophthalmology. 14 (2): 65–73. doi:10.3109/08820539909056066. PMID 10758214. 17. ^ Markley BA (September 2007). "Introduction to electronystagmography for END technologists". American Journal of Electroneurodiagnostic Technology. 47 (3): 178–89. doi:10.1080/1086508X.2007.11079629. PMID 17982846. S2CID 40334544. 18. ^ Mosca F, Sicignano S, Leone CA (April 2003). "Benign positional paroxysmal vertigo: videonystagmographic study using rotatory test". Acta Otorhinolaryngologica Italica. 23 (2): 67–72. PMID 14526552. 19. ^ Eggert T (2007). "Eye movement recordings: methods". Developments in Ophthalmology. 40: 15–34. doi:10.1159/000100347. ISBN 978-3-8055-8251-3. PMID 17314477. 20. ^ Serra A, Leigh RJ (December 2002). "Diagnostic value of nystagmus: spontaneous and induced ocular oscillations". Journal of Neurology, Neurosurgery, and Psychiatry. 73 (6): 615–8. doi:10.1136/jnnp.73.6.615. PMC 1757336. PMID 12438459. 21. ^ "Differences Between Physiologic and Pathologic Nystagmus". Spencer S. Eccles Health Sciences Library. Retrieved 22 November 2016. 22. ^ "nystagmus". Retrieved 2007-06-07. 23. ^ Gold D. "Gaze-evoked and rebound nystagmus in a cerebellar syndrome". Neuro-Ophthalmology Virtual Education Library (NOVEL): Daniel Gold Collection. Spencer S. Eccles Health Sciences Library. Retrieved 9 September 2019. 24. ^ Anagnostou E, Mandellos D, Limbitaki G, Papadimitriou A, Anastasopoulos D (June 2006). "Positional nystagmus and vertigo due to a solitary brachium conjunctivum plaque". Journal of Neurology, Neurosurgery, and Psychiatry. 77 (6): 790–2. doi:10.1136/jnnp.2005.084624. PMC 2077463. PMID 16705203. 25. ^ Pierrot-Deseilligny C, Milea D (June 2005). "Vertical nystagmus: clinical facts and hypotheses". Brain. 128 (Pt 6): 1237–46. doi:10.1093/brain/awh532. PMID 15872015. 26. ^ a b "Sensory Reception: Human Vision: Structure and function of the Human Eye" vol. 27, p. 179 Encyclopædia Britannica, 1987 27. ^ Corbett J (September 2007). "Memantine/Gabapentin for the treatment of congenital nystagmus". Current Neurology and Neuroscience Reports. 7 (5): 395–6. doi:10.1007/s11910-007-0061-z. PMID 17764629. S2CID 40249108. 28. ^ Muscular Dystrophy Association Press Release 29. ^ Clinical trial number NCT02189720 for "Expanded Access Study of Amifampridine Phosphate in LEMS, Congenital Myasthenic Syndrome, or Downbeat Nystagmus Patients (EAP-001)" at ClinicalTrials.gov 30. ^ Groves N (March 15, 2006). "Many options to treat nystagmus, more in development". Ophthalmology Times. 31. ^ Biousse V, Tusa RJ, Russell B, Azran MS, Das V, Schubert MS, et al. (February 2004). "The use of contact lenses to treat visually symptomatic congenital nystagmus". Journal of Neurology, Neurosurgery, and Psychiatry. 75 (2): 314–6. doi:10.1136/jnnp.2003.010678. PMC 1738913. PMID 14742616. 32. ^ Cerman E. "Mini-telescopic eyeglasses suppress nystagmus". World Society of Pediatric Ophthalmology and Strabismus Conference in Barcelona 2015. Retrieved 26 January 2016. 33. ^ Kumar A, Shetty S, Vijayalakshmi P, Hertle RW (Nov–Dec 2011). "Improvement in visual acuity following surgery for correction of head posture in infantile nystagmus syndrome". Journal of Pediatric Ophthalmology and Strabismus. 48 (6): 341–6. doi:10.3928/01913913-20110118-02. PMID 21261243. 34. ^ Wang Z, Dell'Osso LF, Jacobs JB, Burnstine RA, Tomsak RL (December 2006). "Effects of tenotomy on patients with infantile nystagmus syndrome: foveation improvement over a broadened visual field". Journal of AAPOS. 10 (6): 552–60. doi:10.1016/j.jaapos.2006.08.021. PMID 17189150. 35. ^ Ishikawa S, et al. (1987). "Treatment of nystagmus by acupuncture". Highlights in Neuro-ophthalmology (6th ed.): 227–232. 36. ^ a b Blekher T, Yamada T, Yee RD, Abel LA (February 1998). "Effects of acupuncture on foveation characteristics in congenital nystagmus". The British Journal of Ophthalmology. 82 (2): 115–20. doi:10.1136/bjo.82.2.115. PMC 1722486. PMID 9613375. 37. ^ Rowe FJ, Hanna K, Evans JR, Noonan CP, Garcia-Finana M, Dodridge CS, et al. (Cochrane Eyes and Vision Group) (March 2018). "Interventions for eye movement disorders due to acquired brain injury". The Cochrane Database of Systematic Reviews. 3: CD011290. doi:10.1002/14651858.CD011290.pub2. PMC 6494416. PMID 29505103. 38. ^ Sarvananthan N, Surendran M, Roberts EO, Jain S, Thomas S, Shah N, et al. (November 2009). "The prevalence of nystagmus: the Leicestershire nystagmus survey". Investigative Ophthalmology & Visual Science. 50 (11): 5201–6. doi:10.1167/iovs.09-3486. PMID 19458336. 39. ^ Booker JL (2004). "The Horizontal Gaze Nystagmus test: fraudulent science in the American courts". Science & Justice. 44 (3): 133–9. doi:10.1016/S1355-0306(04)71705-0. PMID 15270451. 40. ^ Booker JL (2001). "End-position nystagmus as an indicator of ethanol intoxication". Science & Justice. 41 (2): 113–6. doi:10.1016/S1355-0306(01)71862-X. PMID 11393940. 41. ^ McKnight AJ, Langston EA, McKnight AS, Lange JE (May 2002). "Sobriety tests for low blood alcohol concentrations". Accident Analysis and Prevention. 34 (3): 305–11. doi:10.1016/S0001-4575(01)00027-6. PMID 11939359. ## External links[edit] Classification D * ICD-10: H55, H81.4 * ICD-9-CM: 379.50, 794.14 * MeSH: D009760 * DiseasesDB: 23470 External resources * MedlinePlus: 003037 * Patient UK: Nystagmus * GeneReviews: NBK3822 * 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 * t * e Multiple sclerosis and other demyelinating diseases of the central nervous system Signs and symptoms * Ataxia * Depression * Diplopia * Dysarthria * Dysphagia * Fatigue * Incontinence * Nystagmus * Optic neuritis * Pain * Uhthoff's phenomenon Investigations and diagnosis * Multiple sclerosis diagnosis * McDonald criteria * Poser criteria * Clinical * Clinically isolated syndrome * Expanded Disability Status Scale * Serological and CSF * Oligoclonal bands * Radiological * Radiologically isolated syndrome * Lesional demyelinations of the central nervous system * Dawson's fingers Approved[by whom?] treatment * Management of multiple sclerosis * Alemtuzumab * Cladribine * Dimethyl fumarate * Fingolimod * Glatiramer acetate * Interferon beta-1a * Interferon beta-1b * Mitoxantrone * Natalizumab * Ocrelizumab * Ozanimod * Siponimod * Teriflunomide Other treatments * Former * Daclizumab * Multiple sclerosis research Demyleinating diseases Autoimmune * Multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis Inflammatory * Acute disseminated encephalomyelitis * MOG antibody disease * Balo concentric sclerosis * Marburg acute multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis * Tumefactive multiple sclerosis * Experimental autoimmune encephalomyelitis Hereditary * Adrenoleukodystrophy * Alexander disease * Canavan disease * Krabbe disease * Metachromatic leukodystrophy * Pelizaeus–Merzbacher disease * Leukoencephalopathy with vanishing white matter * Megalencephalic leukoencephalopathy with subcortical cysts * CAMFAK syndrome Other * Central pontine myelinolysis * Marchiafava–Bignami disease * Mitochondrial DNA depletion syndrome Other * List of multiple sclerosis organizations * List of people with multiple sclerosis * Multiple sclerosis drug pipeline * Pathophysiology * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry Authority control * NDL: 00562242 [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	Nystagmus	c0271390	5,901	wikipedia	https://en.wikipedia.org/wiki/Nystagmus	2021-01-18T18:37:26	{"mesh": ["D009760"], "icd-9": ["379.50", "794.14"], "icd-10": ["H55", "H81.4"], "wikidata": ["Q220989"]}
Pityriasis lichenoides et varioliformis acuta (PLEVA) is the acute form of an inflammatory skin condition called pityriasis lichenoides. People with PLEVA may develop a few to more than one hundred scaling papules which may become filled with blood and/or pus, or erode into crusted red-brown spots. Papules may itch or burn, and some people may experience fever or joint pain. Although PLEVA may occur at any age (including infancy), it most commonly affects children and young adults. A skin biopsy is needed to confirm the diagnosis. The exact underlying cause is unknown, but some scientists suspect that it may occur due to an exaggerated immune response to an infection or an overproduction of certain white blood cells (a lymphoproliferative disorder). If treatment is necessary, recommended therapies may include oral antibiotics, sun exposure, topical steroids, immunomodulators (medications used to help regulate or normalize the immune system), phototherapy and/or systemic steroids. PLEVA may last for a few weeks to years, and may fluctuate between getting better and worse before going away on its own. [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	Pityriasis lichenoides et varioliformis acuta	c0162852	5,902	gard	https://rarediseases.info.nih.gov/diseases/9768/pityriasis-lichenoides-et-varioliformis-acuta	2021-01-18T17:58:18	{"mesh": ["D017514"], "umls": ["C0162852"], "synonyms": ["PLEVA", "Mucha-Habermann disease"]}
The 2p21 microdeletion syndrome consists of cystinuria, neonatal seizures, hypotonia, severe growthand developmental delay, facial dysmorphism, and lactic acidemia. ## Epidemiology It has been described in seven patients from three families of a small Bedouin clan. ## Clinical description Dysmorphic features include frontal bossing, almond-shaped eyes, long eyelashes, depressed nasal bridge, and large, posteriorly rotated ears. Renal lithiasis occurs at an early age in all patients. Reduced activity of the respiratory chain complexes I, III, IV and V was found in patients examined. ## Etiology The syndrome is caused by homozygous deletion of at least four contiguous genes on chromosome 2: SLC3A1, PREPL, PPM1B and C2orf34 (2p21). [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	2p21 microdeletion syndrome	c1848030	5,903	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163693	2021-01-23T19:09:39	{"mesh": ["C564710"], "omim": ["606407"], "icd-10": ["Q93.5"], "synonyms": ["2p21 deletion syndrome", "Del(2)(p21)", "Monosomy 2p21"]}
Surgically correctable forms of primary aldosteronism (also known as primary hyperaldosteronism; see this term) are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. ## Epidemiology The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. ## Etiology nilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma (see these terms). In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. ## Diagnostic methods Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. ## Differential diagnosis The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, exposure to glycyrrhizic acid and apparent mineralocorticoid excess caused by mutations in the HSD11B2 gene and pseudo-hypermineralocorticoidism in Liddle syndrome (see these terms). ## Management and treatment If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. ## Prognosis Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension. [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	Rare surgically correctable form of primary aldosteronism	None	5,904	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231637	2021-01-23T17:25:20	{}
## Clinical Features Graves et al. (1979) described 2 brothers with identical HLA haplotypes and allergic bronchopulmonary aspergillosis. A barn near the residence of the brothers was identified as the probable source. Vithayasai et al. (1973) also reported familial allergic aspergillosis. However, in 35 unrelated cases no HLA association was found (Flaherty et al., 1978). Immunology \- Allergic bronchopulmonary aspergillosis 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	ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS, FAMILIAL	c0004031	5,905	omim	https://www.omim.org/entry/103920	2019-09-22T15:41:17	{"doid": ["13166"], "mesh": ["D001229"], "omim": ["103920"], "orphanet": ["1164"]}
Branchiootorenal (BOR) syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition vary widely, even among members of the same family. Branchiootic (BO) syndrome includes many of the same features as BOR syndrome, but affected individuals do not have kidney abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders). "Branchio-" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with BOR/BO syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected people have abnormal holes or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause health problems if they become infected, so they are often removed surgically. "Oto-" and "-otic" refer to the ear; most people with BOR/BO syndrome have hearing loss and other ear abnormalities. The hearing loss can be sensorineural, meaning it is caused by abnormalities in the inner ear; conductive, meaning it results from changes in the small bones in the middle ear; or mixed, meaning it is caused by a combination of inner ear and middle ear abnormalities. Some affected people have tiny holes in the skin or extra bits of tissue just in front of the ear. These are called preauricular pits and preauricular tags, respectively. "Renal" refers to the kidneys; BOR syndrome (but not BO syndrome) causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively. ## Frequency Researchers estimate that BOR/BO syndrome affects about 1 in 40,000 people. ## Causes Mutations in three genes, EYA1, SIX1, and SIX5, have been reported in people with BOR/BO syndrome. About 40 percent of people with this condition have a mutation in the EYA1 gene. SIX1 gene mutations are a much less common cause of the disorder. SIX5 gene mutations have been found in a small number of people with BOR syndrome, although researchers question whether mutations in this gene cause the condition. Some affected individuals originally reported to have SIX5 gene mutations were later found to have EYA1 gene mutations as well, and researchers suspect that the EYA1 gene mutations may be the actual cause of the condition in these people. The proteins produced from the EYA1, SIX1, and SIX5 genes play important roles in development before birth. The EYA1 protein interacts with several other proteins, including SIX1 and SIX5, to regulate the activity of genes involved in many aspects of embryonic development. Research suggests that these protein interactions are essential for the normal formation of many organs and tissues, including the second branchial arch, ears, and kidneys. Mutations in the EYA1, SIX1, or SIX5 gene may disrupt the proteins' ability to interact with one another and regulate gene activity. The resulting genetic changes affect the development of organs and tissues before birth, which leads to the characteristic features of BOR/BO syndrome. Some people with BOR/BO syndrome do not have an identified mutation in any of the genes listed above. In these cases, the cause of the condition is unknown. ### Learn more about the genes associated with Branchiootorenal/branchiootic syndrome * EYA1 * SIX1 * SIX5 ## Inheritance Pattern BOR/BO syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 90 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [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	Branchiootorenal/branchiootic syndrome	c1865143	5,906	medlineplus	https://medlineplus.gov/genetics/condition/branchiootorenal-branchiootic-syndrome/	2021-01-27T08:25:18	{"gard": ["10148", "10147"], "mesh": ["C537104"], "omim": ["602588", "120502", "608389", "113650", "610896"], "synonyms": []}
A rare, aggressive, malignant, epithelial carcinoma of the esophagus characterized, macroscopically, by an exophytic mass with central ulceration located on the esophagus and, histologically, by a sheet-like growth of neoplastic cells without significant glandular, squamous or neuroendocrine differentiation. Patients may present with progressive dysphagia, long-standing history of gastroesophageal reflux, weight loss, anemia, abdominal or chest pain/pressure, dyspnea, and/or hematemesis. Presence or history of Barrett esophagus is frequently associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Undifferentiated carcinoma of esophagus	c2188058	5,907	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=418951	2021-01-23T17:46:31	{"icd-10": ["C15.0", "C15.1", "C15.2", "C15.3", "C15.4", "C15.5", "C15.8"], "synonyms": ["Undifferentiated esophageal carcinoma"]}
A rare X-linked syndromic intellectual disability characterized by congenital sensorineural hearing loss, varying degrees of intellectual disability, short stature, and dysmorphic facial features (such as telecanthus, epicanthic folds, broad nasal root, malar hypoplasia, low-set ears, dental anomalies, and micrognathia). Additional reported manifestations include microcephaly, renal and genitourinary abnormalities, widely spaced, hypoplastic nipples, and adult onset of progressive pancytopenia. [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	Deafness-intellectual disability syndrome, Martin-Probst type	c1845285	5,908	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85321	2021-01-23T18:58:15	{"mesh": ["C564495"], "omim": ["300519"], "umls": ["C1845285"], "icd-10": ["Q87.8"], "synonyms": ["Hearing loss-intellectual disability syndrome, Martin-Probst type", "Martin-Probst syndrome", "X-linked deafness-intellectual disability syndrome syndrome", "X-linked hearing loss-intellectual disability syndrome syndrome"]}
Lowry and MacLean (1977) reported the case of a 29-month-old Caucasian girl with mental retardation, cleft palate, eventration of diaphragm, congenital heart defect, glaucoma, craniosynostosis, and growth failure. Cohen (1978) dubbed this cleft syndrome as Lowry-MacLean syndrome and classified it as a previously unreported multiple congenital anomalies-mental retardation (MCA/MR) syndrome. Kousseff and Ranells (1994) described an African American boy with multiple congenital anomalies and developmental delay from birth. Meconium staining, unusual facial appearance, and multiple congenital anomalies were noted at birth. Like the patient reported by Lowry and MacLean (1977), the second patient had intrauterine growth retardation, microcephaly, craniosynostosis, glaucoma, cleft palate, delayed dentition, preauricular tag/pit, beaked nose, congenital heart defect, and developmental delay. Chromosomes were normal. The genetic basis of this seemingly distinctive syndrome is unclear. It may be due to an autosomal dominant mutation. Al-Torki et al. (1997) described the disorder in a father and daughter in a Kuwaiti Bedouin family. The proposita was born at 39 weeks' gestation after an uneventful pregnancy to nonconsanguineous parents. The 25-year-old father had bilateral congenital glaucoma that led to blindness despite surgery. A paternal aunt also had congenital glaucoma. The proposita had congenital heart disease (via ventricular septal defect and coarctation of the aorta). She also had congenital microcephaly, developmental delay, growth failure, clinically evident craniosynostosis, and Crouzon-like facial appearance. She also had osteoporosis. Neuro \- Mental retardation \- Developmental delay Inheritance \- ? Autosomal dominant Head \- Craniosynostosis \- Microcephaly Nose \- Beaked nose Teeth \- Delayed dentition Ears \- Preauricular tag/pit Eyes \- Glaucoma Lab \- Normal chromosomes Growth \- Intrauterine growth retardation Mouth \- Cleft palate Cardiac \- Congenital heart defect Thorax \- Eventration of diaphragm ▲ 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	LOWRY-MACLEAN SYNDROME	c0796020	5,909	omim	https://www.omim.org/entry/600252	2019-09-22T16:16:28	{"mesh": ["C537037"], "omim": ["600252"], "orphanet": ["2409"]}
A number sign (#) is used with this entry because of evidence that myopia-25 (MYP25) is caused by heterozygous mutation in the P4HA2 gene (600608) on chromosome 5q31. Description Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700. Clinical Features Guo et al. (2015) studied a 3-generation Chinese family segregating autosomal dominant high myopia. The 9 affected individuals had refractive errors ranging from -6.25 to -10.00 diopters in the left eye and from -6.00 to -20.00 diopters in the right eye, with axial lengths of the eye globes ranging from 26.14 to 27.45 mm in the left eye and 26.03 to 31.01 mm in the right eye. All affected individuals had onset of myopia before 10 years of age. The authors also studied another 186 cases of high myopia, all with early onset (before 10 years of age) and refractive errors ranging from -6.0 to -29.0 diopters. Mapping In a 3-generation Chinese family segregating autosomal dominant high myopia, Guo et al. (2015) performed whole-genome multipoint parametric linkage analysis and identified 4 candidate regions on chromosomes 1, 5, 6, and 21, with a maximum multipoint lod score of 2.405. Molecular Genetics In a 3-generation Chinese family segregating autosomal dominant high myopia, Guo et al. (2015) performed whole-exome sequencing and identified a heterozygous missense mutation in the P4HA2 gene (E291K; 600608.0001), located within a linkage region on chromosome 5, that segregated fully with disease in the family and was not found in 626 population-matched controls or in public variant databases. Sequencing of P4HA2 in 186 additional Chinese probands with high myopia revealed 4 more mutations in 5 patients (see, e.g., 600608.0002 and 600608.0003). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- High myopia \- Increased axial lengths of eye globes MISCELLANEOUS \- Onset of myopia by age 10 years MOLECULAR BASIS \- Caused by mutation in the procollagen-proline, 2-oxoglutarate-4-dioxygenase, alpha-subunit, isoform-2 gene (P4HA2, 600608.0001 ) ▲ 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	MYOPIA 25, AUTOSOMAL DOMINANT	c4310655	5,910	omim	https://www.omim.org/entry/617238	2019-09-22T15:46:23	{"omim": ["617238"]}
A number sign (#) is used with this entry because microphthalmia with brain and digital anomalies (MCOPS6) is caused by heterozygous mutation in the gene encoding bone morphogenetic protein-4 (BMP4; 112262) on chromosome 14q22. Clinical Features Bennett et al. (1991) described a 21-week female fetus with histologically confirmed bilateral anophthalmia, retrognathia, brachycephaly, fleshy low-set angular ears, bilateral in-curving of the fifth digit with short middle phalanges and flexion of the thumbs, underdeveloped external genitalia, and hypoplastic kidneys. Brain anomalies included a small cerebellum and the absence of optic nerves, chiasma and tracts, geniculate bodies, and pituitary stalk and gland. Elliott et al. (1993) reported a 4-year-old boy with bilateral clinical anophthalmia and dysmorphic features including micrognathia, extremely small tongue, high-arched palate, developmental and growth retardation, undescended testes with micropenis, and hypothyroidism believed to be secondary to a pituitary abnormality. Phadke et al. (1994) reported a 5-day-old male infant with bilateral clinical anophthalmia, micrognathia, cleft palate, hypospadias, and bifid scrotum. Lemyre et al. (1998) described a 21-month-old girl with bilateral clinical anophthalmia, absent left auditory canal, facial asymmetry, microretrognathia, hypotonia, and psychomotor retardation. X-rays revealed lambdoid craniosynostosis, a very small sella turcica, and cervical vertebral anomalies, and MRI revealed absence of the optic chiasm, hypoplasia of the pituitary gland, and cortical atrophy. Bakrania et al. (2008) reported 2 patients with bilateral clinical anophthalmia, partial callosal agenesis, and other developmental anomalies including hypothyroidism and central vermis hypoplasia in 1 patient and microcephaly, sensorineural deafness, cryptorchidism, and cerebellar and pituitary abnormalities in the other. They also described 2 additional patients with anophthalmia-microphthalmia and digital and brain anomalies. One had right clinical anophthalmia and left microanterior segment, iris and chorioretinal coloboma, retinal dystrophy of both rods and cones, learning difficulties, partial callosal agenesis, and postaxial polydactyly of feet. This patient's grandmother had a similar brain phenotype, polydactyly, and finger webbing; both the grandmother and mother had high myopia but no anophthalmia-microphthalmia. The other had bilateral microphthalmia, broad hands, low thumbs, dysplastic nails, simple prominent ears, cryptorchidism, brain anomalies, seizures, and developmental delay. The patient's father did not have anophthalmia-microphthalmia but demonstrated some mild inferior pigmentation of both retinas, which was considered a possible forme fruste coloboma. Cytogenetics Using cultured tissue from a female fetus with bilateral anophthalmia and pituitary anomalies, Bennett et al. (1991) identified a small deletion of chromosome 14q22-q23. Using a fibroblast cell line from the female fetus reported by Bennett et al. (1991), Gallardo et al. (1999) localized the deletion to chromosome 14q22.3-q23 and showed that regulatory and coding regions of the SIX6 gene (606326) were included within the deletion. Analysis of microsatellite markers and sequencing data were compatible with SIX6 haploinsufficiency. In a 4-year-old boy with bilateral clinical anophthalmia, hypogonadism, and suspected pituitary abnormality, Elliott et al. (1993) identified an interstitial deletion on chromosome 14, del14(q22.1-q22.3). The findings suggested that haploinsufficiency of genes in this region might account for the phenotype. Lemyre et al. (1998) identified an interstitial deletion of the long arm of chromosome 14, del(14)(q22.1q23.2), in a 21-month-old girl with bilateral anophthalmia and pituitary hypoplasia. Noting that 2 other patients had been reported with similar deletions (Bennett et al., 1991 and Elliott et al., 1993), Lemyre et al. (1998) suggested that the region 14q22 is important for eye and pituitary development and noted that the BMP4 gene may play a role. Ahmad et al. (2003) described a family in which the proband, his 3 sisters, and 2 of his 3 sons had uni- or bilateral clinical anophthalmia and preaxial polydactyly in the right hand. Karyotyping of the proband and 1 affected son showed deletion of 14q22-q23; the deletion was not present in his unaffected son. No pituitary anomaly was found in the proband or his affected son. Nolen et al. (2006) reported a 5-year-old boy with clinical anophthalmia and absence of the optic nerves, chiasm, and tracts as well as pituitary gland hypoplasia on MRI who had an apparently balanced de novo chromosomal translocation t(3,14)(q28;q23.2). Translocation breakpoint analysis revealed a 9.66-Mb deletion at chromosome 14q22-q23. At birth the patient exhibited facial dysmorphism and abnormal ears, with small, triangular pinnae, small external auditory canals, and uplifted earlobes; he also had undescended testes, small scrotum, hypoplastic foreskin, and syndactyly of the hands and feet. Echocardiogram and renal sonograms were normal. Audiologic assessment at age 2 years revealed high frequency hearing loss bilaterally. At 5 years of age, the patient exhibited hypotonia and global developmental delay, with no expressive language. Nolen et al. (2006) noted that several genes are located within the 9.66-Mb deleted region, including OTX2 (600037), SIX6 (606326), and BMP4 (112262). In 2 patients with bilateral clinical anophthalmia and partial callosal agenesis, Bakrania et al. (2008) detected interstitial deletion of 14q22-q23. One deletion, del(14)(q22.3q23.2), was found in a female patient with the additional features of hypothyroidism and cerebellar vermis hypoplasia. The other deletion, del(14)(q22.2-q23.1), was carried by a male patient with sensorineural deafness, cryptorchidism, and cerebellar and pituitary anomalies. MLPA analysis showed that both the BMP4 and OTX2 genes were deleted. No anomalies of the digits were reported for these 2 patients. Molecular Genetics Deletions in 14q22-q23 are associated with anophthalmia-microphthalmia, brain, pituitary, and ear anomalies including structural defects and hearing loss, hypothyroidism, poly- and/or syndactyly, clinodactyly, high-arched palate, cryptorchidism, and developmental delay (e.g., Ahmad et al., 2003, Bennett et al., 1991). Although the OTX2 gene (600037) had been identified as a causative gene for anophthalmia-microphthalmia within this region (see MCOPS5, 610125), Bakrania et al. (2008) suggested that it may not account for all cases and did not appear to explain a complex phenotype that includes hypopituitarism and digital anomalies because OTX2 is not expressed in the pituitary gland or digits during development. Bakrania et al. (2008) considered BMP4 (112262), also located at 14q22-q23, as a candidate gene and screened 215 individuals with ocular defects, mainly microphthalmia, for cytogenetic defects by chromosomal analysis, for gene deletions by multiplex ligation-dependent probe amplification (MLPA), and for mutations in the BMP4 gene by direct sequencing. They identified 2 individuals with a 14q22-q23 deletion associated with anophthalmia-microphthalmia, 1 with associated pituitary anomaly. Sequence analysis of the BMP4 gene identified 2 mutations: a frameshift mutation (112262.0001) in a family with anophthalmia-microphthalmia, retinal dystrophy, myopia, poly- and syndactyly, and brain anomalies, and a missense mutation (112262.0002) in an individual with anophthalmia-microphthalmia and brain and digital anomalies. Bakrania et al. (2008) remarked that although the SIX6 gene, which resides in the same 14q22-q23 region as BMP4 and OTX2, is expressed in pituitary and so could potentially explain the hypopituitarism in a contiguous gene syndrome, it does not appear to be important in human anophthalmia-microphthalmia (Aijaz et al., 2004). Reis et al. (2011) analyzed the BMP4 coding region in 133 patients with various ocular conditions, including 60 with clinical anophthalmia/microphthalmia (34 syndromic), 38 with anterior segment anomalies, 16 with cataract, 4 with coloboma, 5 with high myopia, and 10 with other disorders. In 3 probands with syndromic microphthalmia, they identified heterozygosity for a 158-kb deletion involving only the BMP4 gene (112262.0006), a nonsense mutation (R198X; 112262.0007), and a frameshift mutation (112262.0008), respectively; the affected sister of the proband with the frameshift mutation carried both the frameshift and a missense mutation (H121R; 112262.0009). Nomenclature The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.' INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Plagiocephaly \- Brachycephaly Face \- High forehead \- Midface hypoplasia \- Facial asymmetry \- Retrognathia \- Micrognathia Ears \- Large ears \- Flat ears \- Posteriorly rotated ears \- Low-set ears \- Fleshy ears \- Angular ears \- Small triangular pinnae \- Small external auditory canals \- Uplifted earlobes Eyes \- Anophthalmia, true \- Anophthalmia, clinical \- Microphthalmia Mouth \- Small tongue \- High-arched palate \- Cleft palate \- Bifid uvula GENITOURINARY External Genitalia (Male) \- Micropenis \- Small scrotum \- Bifid scrotum \- Hypoplastic foreskin \- Hypospadias External Genitalia (Female) \- Underdeveloped genitalia Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Absent uterine horn Kidneys \- Hypoplastic kidneys \- Hypoplastic adrenal glands SKELETAL Skull \- Craniosynostosis, lambdoid Spine \- Cervical vertebral anomalies Hands \- Single palmar crease \- Clinodactyly \- Short middle phalanges \- Flexion of thumbs \- Preaxial polydactyly \- Syndactyly \- Brachydactyly Feet \- Syndactyly NEUROLOGIC Central Nervous System \- Hypotonia, severe \- Cortical atrophy \- Small cerebellum \- Absent optic nerves, chiasm, and tracts \- Psychomotor retardation ENDOCRINE FEATURES \- Hypopituitarism \- Pituitary anomalies \- Hypothyroidism, secondary MOLECULAR BASIS \- Caused by mutation in the bone morphogenetic protein 4 (BMP4, 112262.0001 ) ▲ 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	MICROPHTHALMIA, SYNDROMIC 6	c1864689	5,911	omim	https://www.omim.org/entry/607932	2019-09-22T16:08:30	{"doid": ["10629"], "mesh": ["C566440"], "omim": ["607932"], "orphanet": ["139471"], "synonyms": ["Alternative titles", "MICROPHTHALMIA AND PITUITARY ANOMALIES", "MICROPHTHALMIA WITH BRAIN AND DIGIT DEVELOPMENTAL ANOMALIES", "ANOPHTHALMIA, CLINICAL, WITH MICROGNATHIA, MALFORMED EARS, DIGITAL ANOMALIES, AND ABNORMAL EXTERNAL GENITALIA"]}
Eccrine mucinosis SpecialtyDermatology Eccrine mucinosis is a cutaneous condition characterized by mucinosis, and described in HIV-infected patients.[1] ## See also[edit] * Perifollicular mucinosis * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. This dermatology 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	Eccrine mucinosis	None	5,912	wikipedia	https://en.wikipedia.org/wiki/Eccrine_mucinosis	2021-01-18T18:29:39	{"wikidata": ["Q5332315"]}
An acute arboviral infection caused by a virus of the Flaviviridae family transmitted by an infected mosquito, and characterized by the onset of flulike symptoms such as fever, malaise, headache, cough, and sore throat that can progress to meningitis or encephalitis with symptoms like nausea, vomiting, confusion, stiff neck, disorientation, irritability, tremors, and convulsions. Photophobia, cranial nerve palsies, and even coma may occur. [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	St. Louis encephalitis	c0014060	5,913	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83484	2021-01-23T17:34:23	{"mesh": ["D004674"], "umls": ["C0014060"], "icd-10": ["A83.3"], "synonyms": ["Saint Louis encephalitis"]}
A number sign (#) is used with this entry because of evidence that catecholaminergic polymorphic ventricular tachycardia-4 (CPVT4) is caused by heterozygous mutation in the calmodulin gene (CALM1; 114180) on chromosome 14q32. For a general phenotypic description and a discussion of genetic heterogeneity of CPVT, see 604772. Clinical Features Nyegaard et al. (2012) studied a large 4-generation Swedish family with a history of ventricular arrhythmias, syncope, and sudden death, predominantly in association with physical exercise or stress. The proband was a 42-year-old man who first developed syncope at 12 years of age while playing football; electrocardiogram (ECG) at that time showed bradycardia with a prominent U-wave in leads V2 and V3, without evidence of QT prolongation. He had a history of loss of consciousness on at least 4 occasions during physical activity and once in connection with a fire alarm. A 24-hour ECG recording revealed premature ventricular contractions (PVCs), bigeminy, and paired PVCs during football training, but no symptoms were reported. An older brother with a history of repeated syncope during exercise was reported to show polymorphic ventricular tachycardia on an exercise ECG; a follow-up ECG while on a beta-1 adrenergic receptor blocker showed PVCs at high loads. He had a son with syncope. The proband also had a brother who had drowned at 15 years of age during a swimming competition after prior episodes of syncope, and an older sister who had episodic syncope and was later found to have ventricular fibrillation, but stabilized on a beta-1 adrenergic receptor blocker and became asymptomatic. In addition, a younger sister presented at 7 years of age with repeated syncope during intense physical activity, and she also had a son with syncope. Their mother, who died at age 60, had multiple episodes of syncope in her youth for which she received medication. The proband's older sister had 6 children, 4 of whom were affected, including a son who died suddenly at 13 years of age while on a beta-1 adrenergic receptor blocker for syncopal episodes that had started at 2.5 years of age. A daughter, who began having syncope at 4 years of age and was asymptomatic on a beta-1 adrenergic receptor blocker, suffered cardiac arrest at age 16, was resuscitated, and received an implantable cardiac defibrillator (ICD). Two more daughters also presented with syncope within the first decade of life, and 1 had a son with syncope. Mapping In a large 4-generation Swedish family segregating autosomal dominant catecholaminergic polymorphic ventricular tachycardia, in which the proband was negative for mutation in known arrhythmia-associated genes, including RYR2 (180902) and CASQ2 (114251), Nyegaard et al. (2012) performed genomewide linkage analysis and obtained a lod score of 3.9 for a 21-cM interval on chromosome 14, from SNP rs9323782 to SNP rs721403. The disease haplotype was present in all affected members but not in any unaffected members of the family, suggesting 100% penetrance of the mutation in the family. Molecular Genetics In a large 4-generation Swedish family with CPVT mapping to chromosome 14q31-q32, Nyegaard et al. (2012) identified a heterozygous missense mutation in the candidate gene calmodulin (CALM1; 114180.0001) that segregated fully with the disease and was not found in 1,200 Danish controls. Analysis of CALM1 in 61 additional arrhythmia patients who were negative for mutation in the RYR2 gene revealed another heterozygous missense mutation (114180.0002), in an Iraqi woman with a history of syncope beginning at 4 years of age who ultimately underwent implantation of an ICD after cardiac arrest at age 15. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Polymorphic ventricular tachycardia induced by physical activity or stress \- Dizziness \- Syncope \- Cardiac arrest \- Sudden death \- Prominent U-waves in anterior leads on electrocardiogram \- Premature ventricular contractions, including couplets and triplets of variable morphology MISCELLANEOUS \- Onset within the first decade of life MOLECULAR BASIS \- Caused by mutation in the calmodulin-1 gene (CALM1, 114180.0001 ) ▲ 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	VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4	c1631597	5,914	omim	https://www.omim.org/entry/614916	2019-09-22T15:53:45	{"doid": ["0060678"], "mesh": ["C536334"], "omim": ["614916"], "orphanet": ["3286"], "genereviews": ["NBK1289"]}
A number sign (#) is used with this entry because autosomal recessive mental retardation-39 (MRT39) is caused by homozygous mutation in the TTI2 gene (614426) on chromosome 8p12. Clinical Features Langouet et al. (2013) reported 3 sibs, born of consanguineous Algerian parents, with mental retardation and behavioral problems. All had a normal neonatal period, but showed delayed psychomotor development and severe speech delay. Examination at ages 30 to 36 years revealed microcephaly (-3 to -4 SD), short stature, kyphoscoliosis, and dysmorphic facial features, including sloping forehead, deep-set eyes, synophrys, prominent nose, anteverted large ears, and dental anomalies. Behavioral abnormalities included hyperactivity, aggression, and stereotypic movements. Seizures were not reported. Laboratory analysis showed mild lymphopenia of naive T cells, but increased susceptibility to infection was not reported. Inheritance The transmission pattern in the family with mental retardation reported by Langouet et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arabic) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. In family M100, they identified homozygosity for a missense mutation in the TTI2 gene (P367L; 614426.0001) in 4 sibs with moderate nonsyndromic mental retardation. The parents were first cousins and had 4 healthy children. In 3 sibs, born of consanguineous Algerian parents, with mental retardation and dysmorphic features, Langouet et al. (2013) identified a homozygous missense mutation in the TTI2 gene (I436N; 614426.0002). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed almost undetectable levels of mutant TTI2 compared to controls, although mRNA levels were normal. Patient cells also showed decreased levels of the other 2 components of the Triple T complex (TTI1, 614425 and TELO2, 611140), indicating impaired stability of the complex, as well as decreased amounts of ATM (607585), PRKDC (600899), and MTOR (601231) (less than 50% of controls for all 3 proteins). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly (-3 to -4 SD) Face \- Sloping forehead Ears \- Anteverted ears \- Large ears Eyes \- Deep-set eyes \- Strabismus \- Synophrys Nose \- Prominent nose Teeth \- Malposition of the teeth SKELETAL Spine \- Kyphoscoliosis NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation, moderate to severe \- Speech delay, severe Behavioral Psychiatric Manifestations \- Hyperactivity \- Aggression \- Stereotyped behavior IMMUNOLOGY \- Decreased circulating naive T cells (1 family) MISCELLANEOUS \- Onset in infancy \- Dysmorphic facial features reported in 1 family \- Two unrelated families have been reported (last curated November 2013) MOLECULAR BASIS \- Caused by mutation in the TELO2-interacting protein 2 gene (TTI2, 614426.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	c3809853	5,915	omim	https://www.omim.org/entry/615541	2019-09-22T15:51:47	{"doid": ["0060308"], "omim": ["615541"], "orphanet": ["391307"], "synonyms": []}
Persistent thyroglossal duct Origin of Thyroglossal duct (Thyroid diverticulum) SpecialtyMedical genetics A persistent thyroglossal duct is a usually benign medical condition in which the thyroglossal duct, a structure usually only found during embryonic development, fails to atrophy. The duct persists as a midline structure forming an open connection between the back of the tongue and the thyroid gland. This opening can lead to fluid accumulation and infection, which necessitate the removal of the duct. ## Contents * 1 Signs and symptoms * 2 Anatomy * 2.1 Embryological origin * 3 Histology * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Signs and symptoms[edit] Studies done on cadavers claim persistent thyroglossal ducts can be completely asymptomatic and found in 7% of the human adult population.[1] However, the continued presence of the duct can often lead to complications due to infections and fluid buildup. The glands in the mucosa of the duct will continue their secretions until the fluid forms a cyst or exit the duct via the opening in the foramen cecum. Local infections, such as colds, tonsillitis, or inflammation of the lymph nodes in the area can also lead to the accumulation of fluid within the duct.[2] Even if the cyst forms as secondary to another infection and improved after antibiotics, it will often reoccur and require treatment.[citation needed] Example of Thyroglossal duct cyst. Three-fourths of abnormalities within a persistent thyroglossal duct involve the formation of a cyst.[2] If a persistent thyroglossal duct becomes fluid filled it will form a thyroglossal duct cyst, which accounts for 70% of congenital neck masses and is the most likely diagnosis if the mass is along the midline of the neck.[3] These cysts are often diagnosed in children under the age of ten and have no particular gender prevalence. The cysts are normally asymptomatic at this age and are noticed because of the swelling that will move if the patient swallows. Over 80% of these cysts are located at or below the hyoid bone.[4] Very rarely, the persistent duct can become cancerous, called thyroglossal duct carcinoma. In the case of thyroglossal duct carcinoma, the cancerous cells are ectopic thyroid tissue that has been deposited along the thyroglossal duct and will present as a papillary carcinoma.[4] However, the cells are less likely to metastasize in the cyst, than if they were present in the actual thyroid gland.[citation needed] The other fourth of abnormalities presents as draining abscess. This is from an infection that will rupture through the skin to allow for adequate drainage of the infected area.[2] ## Anatomy[edit] The tongue develops after the thyroid primordium so the foramen cecum becomes buried at the base of the tongue. The thyroglossal duct then continues through the neck and lies anterior to the laryngeal cartilage. The duct then passes anteriorly to the developing hyoid bone; however, as the bone continues to grow it can continue to grow posteriorly, become anterior, or even grow to surround the duct. The duct is found very close to the medial line of the neck. The duct continues in front of the thyrohyoid membrane, sternothyroid muscle, and sternohyoid muscle, before terminating in the inferior segment of the neck at the thyroid.[4] Failures of duct removal surgeries have proven that the suprahyoid region of the duct can have many microscopic branches that connect to the base of the tongue. They exhibit variability between different cases; however, it is believed they are associated with the pharyngeal mucosa and muscles of the tongue.[citation needed] ### Embryological origin[edit] During the third week of development, the thyroid gland begins to develop from the floor of the pharynx. This primordium begins as an evagination between the first and second pharyngeal grooves, relatively where the anterior two-thirds of the tongue ends.[4] This area is known as the foramen cecum and marks the origin of the thyroglossal duct. As the developing thyroid begins to travel to its intended destination, it remains connected to the tongue via the thyroglossal duct. By the seventh week of fetal development, the thyroid reaches its final position in the neck after growing through the mesoderm and musculature of the tongue, mouth, and neck. During the eighth to tenth week, the cells of the duct normally begin growing inwards and fill the previously hollow tube, beginning from the inferior end. This inferior end of the duct will then become the pyramidal lobe of the thyroid gland. The dividing cellular cords of the tubular duct become the isthmus and lateral lobes of the gland to complete the formation of the rest of the gland.[5] Once the thyroglossal duct involutes, the cells will begin to degenerate and disappear. However, in the case of a persistent thyroglossal duct, the tube remains hollow and continues to connect the foramen cecum to the thyroid gland.[citation needed] ## Histology[edit] The cells of the thyroglossal duct are epithelial in origin. The cell shapes can range from columnar, to squamous, to transitional epithelium. Thyroid-like masses can also be seen in close relation along the duct. Enclosed vesicles and cysts can also be seen while studying the tissue of the duct. A persistent thyroglossal duct in a rabbit showed resemblance to the layout of the alimentary canal; with its external fibrous connective tissue, muscular layers, submucosal glands, and convoluted epithelium.[5] ## Diagnosis[edit] Ultrasound is the often chosen to examine the duct and determine the presence and size of any cysts or abnormalities. Fine-needle aspiration cytology can also be used to confirm the diagnosis.[6] ## Treatment[edit] In order to prevent further cysts and infections from forming, the thyroglossal duct and all of its branches are removed from the throat and neck area. A procedure, known as the Sistrunk procedure, is considered to be the standard procedure and involves removal of portions of the hyoid bone and core tissue of the suprahyoid region. Cysts will often reoccur if the entire duct is not removed, so reoccurrence requires a wider range of tissue to be removed in a subsequent surgery.[4] Delaying the surgical procedure almost always leads to recurrent infections, which will continue to delay the needed treatment. The Sistrunk procedure has a reoccurrence rate of less than 5%, proving it is extremely effective at removing the majority of traces of the persistent thyroglossal duct.[6] ## References[edit] 1. ^ Kurt A, Ortug C, Aydar Y, Ortug G (April 2007). "An incidence study on thyroglossal duct cysts in adults". Saudi Medical Journal. 28 (4): 593–7. PMID 17457484. 2. ^ a b c "Thyroglossal Duct Cysts and Sinuses". American Pediatric Surgical Association. 3. ^ Singh S, Rosenthal DI, Ginsberg LE (April 2009). "Enlargement and transformation of thyroglossal duct cysts in response to radiotherapy: imaging findings". AJNR. American Journal of Neuroradiology. 30 (4): 800–2. doi:10.3174/ajnr.A1448. PMC 7051746. PMID 19131415. 4. ^ a b c d e Koeller KK, Alamo L, Adair CF, Smirniotopoulos JG (1999). "Congenital cystic masses of the neck: radiologic-pathologic correlation". Radiographics. 19 (1): 121–46, quiz 152–3. doi:10.1148/radiographics.19.1.g99ja06121. PMID 9925396. 5. ^ a b Pal RK (April 1934). "Persistent Thyroglossal Duct in a Rabbit". Journal of Anatomy. 68 (Pt 3): 354–6. PMC 1249038. PMID 17104487. 6. ^ a b Manzano JA, Meseguer EL, Banegas AM, Santos JM (November 2005). "Total persistence of thyroglossal duct with direct communication between cyst and foramen caecum". European Archives of Oto-Rhino-Laryngology. 262 (11): 884–6. doi:10.1007/s00405-004-0753-9. PMID 16273414. S2CID 195073036. ## External links[edit] * ent/323 at eMedicine Classification D * ICD-10: Q89.2 * ICD-9-CM: 759.2 * v * t * e Congenital endocrine disorders Pituitary * Congenital hypopituitarism Thyroid * Thyroid disease * Persistent thyroglossal duct * Thyroglossal cyst * Congenital hypothyroidism * Thyroid dysgenesis * Thyroid dyshormonogenesis * Pendred syndrome Parathyroid * Congenital absence of parathyroid Adrenal * Absent adrenal gland [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	Persistent thyroglossal duct	c0266286	5,916	wikipedia	https://en.wikipedia.org/wiki/Persistent_thyroglossal_duct	2021-01-18T18:59:45	{"umls": ["C0266286"], "icd-9": ["759.2"], "icd-10": ["Q89.2"], "wikidata": ["Q7170423"]}
A rare, genetic, multiple congenital malformation syndrome, characterized by cleidocranial dysplasia (wide fontanelles, calvaria dysostosis, absent or hypoplastic clavicles), absent thumbs and halluces, hypoplastic distal and medial phalanges of fingers, pelvic dysplasia with hip dislocations. Dysmorphic features include sparse scalp hair, protruding eyes, low-set ears, anteverted nares, midfacial hypoplasia, tented upper lip, high arched palate, and micrognathia. Brain malformations are frequently associated. From birth, affected individuals tend to be significantly hypotonic and present with global developmental delay, and respiratory, feeding and swallowing difficulties. [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	Yunis-Varon syndrome	c1857663	5,917	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3472	2021-01-23T17:33:06	{"gard": ["331"], "mesh": ["C536719"], "omim": ["216340"], "umls": ["C1857663"], "icd-10": ["Q87.8"], "synonyms": ["Cleidocranial dysplasia-micrognathia-absent thumbs syndrome"]}
Conduplicato corpore is a condition that occurs during birth if the fetus is quite small and the pelvis is large. Spontaneous delivery may occur despite persistence of the abnormal lie.[1] In such cases, the fetus is compressed with the head forced against the abdomen.[2] A portion of the thoracic wall below the shoulder thus becomes the most dependent part, appearing at the vulva. The head and thorax then pass through the pelvic cavity at the same time, and the fetus, which is doubled upon itself (Conduplicato Corpore), is expelled.[3] Such a mechanism is obviously possible only in the case of very small infant and occasionally when the second preterm fetus in a twin pregnancy is born. ## References[edit] 1. ^ ARUP KUMAR MAJHI (2016-08-16). BEDSIDE CLINICS IN OBSTETRICS. Academic Publishers. p. 194. ISBN 978-93-83420-87-2. 2. ^ Ronald S. Gibbs (2008). Danforth's Obstetrics and Gynecology. Lippincott Williams & Wilkins. p. 412. ISBN 978-0-7817-6937-2. 3. ^ Rajeev Kumar; Prakash Nayak (2014-07-16). Elsevier Comprehensive Guide to Combined Medical Services (UPSC) - E-Book. Elsevier Health Sciences. p. 200. ISBN 978-81-312-3892-9. [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	Conduplicato corpore	None	5,918	wikipedia	https://en.wikipedia.org/wiki/Conduplicato_corpore	2021-01-18T19:04:44	{"wikidata": ["Q5159418"]}
CATSPER1-related nonsyndromic male infertility is a condition that affects the function of sperm, leading to an inability to father children. Males with this condition produce sperm that have decreased movement (motility). Affected men may also produce a smaller than usual number of sperm cells or sperm cells that are abnormally shaped. Men with CATSPER1-related nonsyndromic male infertility do not have any other symptoms related to this condition. ## Frequency The prevalence of CATSPER1-related nonsyndromic male infertility is unknown. ## Causes Mutations in the CATSPER1 gene cause CATSPER1-related nonsyndromic male infertility. The CATSPER1 gene provides instructions for producing a protein that is found in the tail of sperm cells. The CATSPER1 protein is involved in the movement of the sperm tail, which propels the sperm forward and is required for sperm cells to push through the outside membrane of the egg cell during fertilization. CATSPER1 gene mutations result in the production of a CATSPER1 protein that may be altered, nonfunctional, or quickly broken down (degraded) by the cell. Sperm cells missing a functional CATSPER1 protein have decreased motion in their tails and move more slowly than normal. Sperm cells lacking functional CATSPER1 protein cannot push through the outside membrane of the egg cell. As a result, sperm cells cannot reach the inside of the egg cell to achieve fertilization. ### Learn more about the gene associated with CATSPER1-related nonsyndromic male infertility * CATSPER1 ## 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 symptoms of the condition. Males with two CATSPER1 gene mutations in each cell have CATSPER1-related nonsyndromic male infertility. Females with two CATSPER1 gene mutations in each cell have no symptoms because the mutations only affect sperm function, and women do not produce sperm. [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	CATSPER1-related nonsyndromic male infertility	c2751811	5,919	medlineplus	https://medlineplus.gov/genetics/condition/catsper1-related-nonsyndromic-male-infertility/	2021-01-27T08:25:09	{"mesh": ["C567832"], "omim": ["612997"], "synonyms": []}
HIV/AIDS is considered the deadliest epidemic in the 21st century. It is transmitted through sex, intravenous drug use and mother-to-child transmission. Zambia is experiencing a generalized HIV/AIDS epidemic, with a national HIV prevalence rate of 11.3% among adults ages 15 to 49 as of 2018.[1] Per the 2000 Zambian census, the people affected by HIV/AIDS constituted 15% of the total population, amounting to one million, of which 60% were women.[citation needed] The pandemic results in increased number of orphans, with an estimated 600,000 orphans in the country. It was prevalent more in urban areas compared to rural and among all provinces, Copperbelt Province and Lusaka Province had higher occurrence. The government of Zambia created an AIDS surveillance committee as early as 1986, and created an emergency plan to control the spread by 1987. By 2005, the government made antiretroviral therapy free for every individual. There are several UN and NGO voluntary organizations that are helping combat the disease. ## Contents * 1 Background * 2 Statistics * 3 Causes * 4 Measures * 5 See also * 6 Notes * 7 References * 8 Further reading ## Background[edit] Prevalence of AIDS in Africa over the years. Zambia in 10–20% band Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a set of conditions caused by infection with the human immunodeficiency virus (HIV).[2][3] HIV is transmitted by three main ways: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission). There is no risk of acquiring HIV if exposed to feces, Nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood.[4] It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.[5] Zambia is a landlocked, economically backward county in Africa. It is rated 166th in Human Development Index in 2006 out of a total of 177 countries based on the Human Development Report of the United Nations. By the end of 2006, a total of 39.5 million people in the world were infected by HIV and 2.9 million people died on account of ailments arising out of AIDS. Africa is the leader in AIDS with close to 60% of HIV victims and has been the leading cause of death in Africa.[6] ## Statistics[edit] As per the 2000 Zambian census, the people affected by HIV or AIDS constituted 15 per cent of the population, amounting to one million, of which 60% estimated were women. The pandemic results in increased number of orphans, with an estimated 600,000 orphans in the country. It is estimated that by 2014, 974,000 children would be orphaned.[7] The victims are high in Lusaka and Copperbelt provinces in spite of the provinces being the most urban. As per the estimate from 2006, the HIV positive cases is 5 per cent in the age group 15–19 years, 25 per cent from 30–34 years and 17% from 45–49 years. HIV was more prevalent in urban areas compared to rural areas.[8] HIV infected people in provinces of Zambia[9] Infected with HIV Central Copperbelt Eastern Luapula Lusaka Northern North-Western Southern Western Grand Total 1985 1,448 6,719 779 427 1,518 539 250 23,960 1,067 36,707 1990 12,516 154,131 11,864 6,971 23,828 6,529 3,104 65,467 9,171 293,581 1995 49,682 235,586 49,750 32,447 111,753 32,452 15,855 103,202 35,208 665,935 2000 79,902 265,518 76,213 46,293 155,729 56,050 25,735 117,477 54,123 877,040 2003 86,654 270,590 81,509 48,988 159,409 62,430 27,418 120,425 57,844 915,267 2001 83,080 270,781 78,511 47,465 158,506 58,683 26,517 120,188 55,919 899,650 2002 85,490 270,945 80,157 48,426 160,240 60,802 27,045 120,347 57,252 910,704 2004 87,435 270,525 81,785 49,462 157,997 63,812 27,587 120,768 58,347 917,718 2005 87,144 268,790 81,680 49,798 155,687 65,020 27,676 120,672 58,224 914,691 2006 86,734 266,706 81,504 50,127 153,187 65,385 27,738 120,309 58,015 909,705 2007 86,238 264,358 81,228 50,435 150,408 65,567 27,772 119,829 57,673 903,508 2008 85,637 261,807 80,938 50,685 147,584 65,749 27,769 119,200 57,298 896,667 2009 84,993 259,111 80,560 50,959 144,640 65,772 27,795 118,417 56,861 889,108 2010 84,321 256,374 80,193 51,211 141,663 65,787 27,815 117,471 56,308 881,143 Estimated people killed by AIDS in provinces of Zambia[9] Estimated killed in AIDS Central Copperbelt Eastern Luapula Lusaka Northern North-Western Southern Western Grand Total 1985 028 107 012 006 024 010 004 635 019 845 1990 410 4,664 384 198 640 207 087 3,690 314 10,594 1995 2,306 17,485 2,688 1,478 4,786 1,476 655 8,397 1,684 40,955 2000 5,833 26,801 6,721 3,682 12,188 4,166 1,848 11,379 4,097 76,715 2003 7,877 27,704 8,818 4,761 15,597 5,712 2,522 12,143 5,438 90,572 2001 6,648 27,549 7,597 4,141 13,658 4,727 2,119 12,075 4,641 83,155 2002 7,311 27,798 8,316 4,486 14,758 5,247 2,336 12,331 5,076 87,659 2004 8,399 27,609 9,319 4,995 16,274 6,103 2,684 12,524 5,763 93,670 2005 8,747 27,553 9,614 5,131 16,569 6,418 2,792 12,578 5,971 95,373 2006 8,978 27,477 9,730 5,204 16,617 6,657 2,856 12,586 6,097 96,202 2007 9,098 27,405 9,719 5,232 16,468 6,807 2,887 12,574 6,150 96,340 2008 9,133 27,275 9,627 5,234 16,211 6,901 2,892 12,541 6,150 95,964 2009 9,097 27,094 9,481 5,224 15,849 6,949 2,880 12,485 6,109 95,168 2010 9,016 26,799 9,338 5,209 15,429 6,958 2,859 12,403 6,044 94,055 ## Causes[edit] The primary modes of HIV transmission are through sex, intravenous drug use and mother-to-child transmission. HIV prevalence rates vary considerably within the country. Infection rates are highest in cities and towns along major transportation routes and lower in rural areas with low population density. HIV prevalence among pregnant women can range from less than 10 percent in some areas to 30 percent in others. In general, however, young women ages 25 to 34 are at much higher risk of being infected by HIV than young men in the same age group. The prevalence rates are 12.7 and 3.8 percent, respectively.[10] Risk for the disease is higher for people with sensory, intellectual, physical and psychosocial disabilities, despite the 2012 Persons with Disabilities Act.[11] Other at-risk populations include military personnel, people in prostitution, truck drivers, and people who work in fisheries. Although men who have sex with men have a higher risk of HIV transmission than those who do not, the government-operated National AIDS Control Program does not address same-sex relationships.[10] While Zambia's national prevalence rate remains high and shows no sign of declining, the country has been noted for its significant increases in antiretroviral treatment (ART) access.[12] ## Measures[edit] The government of Zambia created an AIDS surveillance committee as early as 1986 and created an emergency plan to control the spread by 1987. As per the plan, all blood transfusion should be screened for HIV. By 2002, the government created a mission to make antiretroviral therapy available for every individual. By 2005, the government made antiretroviral therapy free for every individual.[13] With about one million Zambians living with HIV/AIDS and 200,000 of these persons requiring ART, the Government of the Republic of Zambia has prioritized making ART available to all Zambians in need. A 2006 rapid assessment of the Zambian ART program identified several important constraints including: inadequate human resources for counseling, testing, and treatment-related care; gaps in supply of drugs in the public sector; increase in value of the Zambian kwacha; lack of adequate logistic/supply chain systems; stigma that hinders people from seeking treatment and care; lack of information on the availability of treatment services; a high level of misinformation about ART; need for a continuous funding stream as an accumulation of patients on ART results in a growing need for support; high cost of ART to patients, despite subsidies from the public sector; lack of referral between counseling and testing services and ART; and lack of referral between home-based care services, testing and ART.[12] ## See also[edit] * ZAMBART Project ## Notes[edit] 1. ^ "Zambia UNAIDS". UNAIDS. 2018. Retrieved 14 October 2020. 2. ^ Sepkowitz KA (June 2001). "AIDS—the first 20 years". N. Engl. J. Med. 344 (23): 1764–72. doi:10.1056/NEJM200106073442306. PMID 11396444. 3. ^ editors, Alexander Krämer, Mirjam Kretzschmar, Klaus Krickeberg (2010). Modern infectious disease epidemiology concepts, methods, mathematical models, and public health (Online-Ausg. ed.). New York: Springer. p. 88. ISBN 9780387938356.CS1 maint: extra text: authors list (link) 4. ^ Kripke, C (1 August 2007). "Antiretroviral prophylaxis for occupational exposure to HIV". American Family Physician. 76 (3): 375–6. PMID 17708137. 5. ^ van der Kuyl, AC; Cornelissen, M (24 September 2007). "Identifying HIV-1 dual infections". Retrovirology. 4: 67. doi:10.1186/1742-4690-4-67. PMC 2045676. PMID 17892568. 6. ^ Kapungwe 2009, pp. 1–2 7. ^ Land Tenure, Housing Rights and Gender in Zambia Volume 3 of Land Tenure, Housing Rights, and Gender in [name of Country], United Nations Human Settlements Programme Law, land tenure and gender review: Southern Africa. UN-HABITAT. 2005. pp. 36–37. ISBN 9789211317749. 8. ^ Kapungwe 2009, p. 3 9. ^ a b "AIDS and HIV statistics". Central Statistical Office of Zambia. 2011. Retrieved 17 October 2016. 10. ^ a b LGBT in Zambia (PDF) (Report). Huachen.org. 2011. Archived from the original (PDF) on 1 October 2008. Retrieved 15 October 2016. 11. ^ "Zambia: People With Disabilities Left Behind in HIV Response". Human Rights Watch. 15 July 2014. Retrieved 19 July 2014. 12. ^ a b "2008 Country Profile: Zambia". U.S. Department of State. 2008. Retrieved 25 August 2008. This article incorporates text from this source, which is in the public domain. 13. ^ Kapungwe 2009, p. 9 ## References[edit] * Kapungwe, Augustus Kasumpa (2009). Youth and Government's Fight Against HIV/AIDS in Zambia: A Closer Look at Some Underlying Assumptions. African Books Collective. ISBN 9789994455393. ## Further reading[edit] * Children as Caregivers: The Global Fight Against Tuberculosis and HIV in Zambia by Jean Hunleth, 2017, Rutgers University Press * v * t * e HIV/AIDS in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) * 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 Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by 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	HIV/AIDS in Zambia	None	5,920	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Zambia	2021-01-18T18:31:32	{"wikidata": ["Q5629895"]}
## Description Body mass index (BMI), which reflects the amount of fat, lean mass, and body build, is a heterogeneous trait influenced by both genetic and environmental factors. Several studies have estimated the heritability of body mass index to be 40 to 55% (Bouchard et al., 1998; Rice et al., 1999). For discussion of genetic heterogeneity of BMI quantitative trait loci and their known or possible associations with variation in specific genes, see MAPPING and MOLECULAR GENETICS sections. Clinical Features BMI is an informative and useful indicator of total fat mass, and a high BMI has been validated as an independent risk factor for coronary heart disease (Van Itallie and Abraham, 1985). Inheritance ### Association With Asthma In a study of 1,001 monozygotic and 383 dizygotic same-sex twin pairs, Hallstrand et al. (2005) analyzed self-reports of a physician diagnosis of asthma (see 600807) and BMI calculated using self-reported height and weight, and found a strong association between asthma and BMI (p less than 0.001). Substantial heritability was detected for asthma (53%) and obesity (77%), indicating additive genetic influences on each disorder. The best-fitting model of shared components of variance indicated that 8% of the genetic component of obesity is shared with asthma. Mapping ### BMIQ1 on Chromosome 7q31 Hsueh et al. (2001) performed a genomewide scan of obesity-related traits in 672 Amish individuals. For the trait BMI-adjusted leptin (164160) levels, they observed a lod score of 1.77 (P = 0.0022) on chromosome 7q (164 cM). To identify regions that are likely to harbor quantitative trait loci (QTLs) for body mass index, Feitosa et al. (2002) conducted an autosomal genome scan for BMI through use of a variance components-based linkage analysis in families participating in the National Heart, Lung, and Blood Institute Family Heart Study. They found strong evidence for linkage on 7q32.3 in each of 2 samples and in the samples combined (maximum multipoint lod scores of 4.7 at marker GATA43C11 and 3.2 at marker D7S1804). The location of maximal linkage was near the reported location of the leptin gene (LEP; 164160) at 7q31.3. Platte et al. (2003) performed a linkage association study of BMI in the Old Order Amish of southeastern Pennsylvania and concluded that a region of 7q distal to the leptin locus was responsible, at least in part, for variation in this measure of obesity. ### BMIQ2 on Chromosome 13q14 See BMIQ2 (606643), which maps to chromosome 13q14. ### BMIQ3 on Chromosome 6q23-q25 See BMIQ3 (607446), which maps to chromosome 6q23-q25. ### BMIQ4 on Chromosome 11q24 See BMIQ4 (607447), which maps to chromosome 11q24. This locus is associated with variation in the UCP2 gene (601693). ### BMIQ5 on Chromosome 16p13 See BMIQ5 (608558), which maps to chromosome 16p13. ### BMIQ6 on Chromosome 20pter-p11.2 See BMIQ6 (608559), which maps to chromosome 20pter-p11.2. ### BMIQ7 on Chromosome 4p15-p14 See BMIQ7 (608410), which maps to chromosome 4p15-p14. ### BMIQ8 on Chromosome 10p See BMIQ8 (603188), which maps to chromosome 10p. ### BMIQ9 on Chromosome 20q See BMIQ9 (602025), which maps to chromosome 20q. This locus is associated with variation in the MC3R gene (155540). ### BMIQ10 on Chromosome 10q See BMIQ10 (607514), which maps to chromosome 10q. This locus is associated with variation in the FFAR4 gene (609044). ### BMIQ11 on Chromosome Xq24 See BMIQ11 (300306), which maps to chromosome Xq24. ### BMIQ12 on Chromosome 5q15-q21 See BMIQ12 (612362), which maps to chromosome 5q15-q21. This locus is associated with variation in the PCSK1 gene (162150). ### BMIQ13 on Chromosome 2q14.1 See BMIQ13 (612459), which maps to chromosome 2q14.1. ### BMIQ14 on Chromosome 16q12.2 See BMIQ14 (612460), which maps to chromosome 16q12.2. This locus is associated with variation in the FTO gene (610966). ### BMIQ15 on Chromosome 17q23.2-q25.1 See BMIQ15 (612967), which maps to chromosome 17q23.2-q25.1. This locus is associated with variation in the PRKCA gene (176960). ### BMIQ16 on Chromosome 16p11.2 See BMIQ16 (see 613444), which maps to chromosome 16p11.2. This locus is associated with variation in the SH2B1 gene (608937), which is involved in a 220-kb chromosome 16p11.2 deletion syndrome (613444). ### BMIQ17 on Chromosome 9p13.3 See BMIQ17 (614411), which is associated with variation in the AQP7 gene (602974) on chromosome 9p13.3. ### BMIQ18 on Chromosome 6q14.2 See BMIQ18 (615457), which is associated with variation in the MRAP2 gene (615410) on chromosome 6q14.2. ### BMIQ19 on Chromosome 2p23 See BMIQ19 (617885), which is associated with variation in the ADCY3 gene (600291) on chromosome 2p23. ### BMIQ20 on Chromosome 18q21 See BMIQ20 (618406), which is associated with mutation in the MC4R gene (155541) on chromosome 18q21. BMIQ20 is a monogenic disorder characterized by severe obesity with hyperphagia or by resistance to obesity. ### Genomewide Association Studies Atwood et al. (2002) performed a genomewide linkage analysis of 6 separate measurements of body mass index taken over 28 years, from 1971 to 1998, in the Framingham Heart Study. There was substantial evidence for linkage on chromosome 11q24 in the area of markers D11S1998, D11S4464, and D11S912. (The location of these markers was incorrectly cited as 11q14 in the article.) The 6 measurements of BMI in that region showed maximum lod scores of 0.61, 3.27, 1.30, 0.68, 1.30, and 2.29. There was also evidence for linkage to 6q23-q25 (BMIQ3; 607446). Both of these regions had been implicated in previous studies (Feitosa et al., 2002; Hanson et al., 1998). Yanagiya et al. (2007) analyzed 62,663 gene-based SNPs in 3 sequential case-control obesity studies and found a replicated association between obesity, defined as a BMI greater than or equal to 30 kg per meter squared, and a SNP (rs2293855) in the MTMR9 gene on chromosome 8p23-p22 (overall p value = 0.0000005). Meyre et al. (2009) analyzed genomewide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls, with further evaluation of the 38 markers showing the strongest association in 14,186 European individuals. They identified novel associations with rs1805081 in the NPC1 gene (607623) on chromosome 18q11 (p = 2.9 x 10(-7)) and with rs1424233 near the MAF gene (177075) on chromosome 16q22-q23 (p = 3.8 x 10(-13)). Walley et al. (2009) reviewed the genetic contribution to nonsyndromic human obesity, stating that despite the clear genetic component underlying obesity, genomewide association studies will not suffice to elucidate the genetic architecture of common obesity; they suggested that alternative study designs and additional obesity-related phenotype data will be required. Speliotes et al. (2010) examined associations between body mass index and approximately 2.8 million SNPs in up to 123,865 individuals with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. Speliotes et al. (2010) confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P less than 5 x 10(-8)), one of which includes a copy number variant near GPRC5B (605948) on chromosome 16p12. Some loci, at MC4R (155541), POMC (176830), SH2B1, and BDNF (113505), mapped near key hypothalamic regulators of energy balance, and one of these loci was near GIPR (137241), an incretin (see 138030) receptor, on chromosome 19q13. Kilpelainen et al. (2011) noted that while GWAS had identified 32 loci influencing body mass index to that time, this measure does not distinguish lean from fat mass. To identify adiposity loci, Kilpelainen et al. (2011) performed a metaanalysis of associations between 2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (p less than 10(-6)) independent loci in 39,576 individuals. They confirmed the established adiposity locus in FTO (see BMIQ14, 612460) and identified 2 new loci associated with body fat percentage, one near IRS1 (147545) (rs2943650, effect allele T, combined p = 3.8 x 10(-11)) and one near SPRY2 (602466) (rs534870, effect allele A, combined p = 6.5 x 10(-8)). Kilpelainen et al. (2011) noted that the body fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes, and coronary artery disease, and decreased adiponectin levels. Shungin et al. (2015) conducted genomewide association metaanalyses of traits related to waist and hip circumferences in up to 224,459 individuals and identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for BMI, as well as an additional 19 loci newly associated with related waist and hip circumference measures (p less than 5 x 10(-8)). In total, 20 of the 49 BMI-adjusted waist-to-hip ratio-associated loci showed significant sexual dimorphism; 19 of these displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution. Locke et al. (2015) conducted a genomewide association study and custom genotype array metaanalysis of BMI in up to 339,224 individuals. Their analysis identified 97 BMI-associated loci (p less than 5 x 10(-8)). Five loci demonstrated clear evidence of several independent association signals, and many loci had significant effects on other metabolic phenotypes. The 97 loci accounted for approximately 2.7% of BMI variation, and genomewide estimates suggested that common variation accounts for greater than 20% of BMI variants. Pathway analyses provided strong support for a role of the central nervous system in obesity susceptibility and implicated new genes and pathways, including those related to synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology, and adipogenesis. Molecular Genetics For a discussion of an association between variation in the ADIPOQ gene (605441) on chromosome 3q27 and BMI, see ADIPQTL1 (612556). ### Modifier Loci Several groups have presented evidence suggesting that a polymorphism in the PPARG2 gene (601487.0002) may modify BMI (Deeb et al., 1998; Valve et al., 1999; Masud and Ye, 2003). [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	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 1	c3888010	5,921	omim	https://www.omim.org/entry/606641	2019-09-22T16:10:17	{"omim": ["606641"], "synonyms": ["Alternative titles", "BODY MASS INDEX"]}
## Description Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1985). Clinical Features Carson et al. (1968) reported saccharopinuria in a 22-year-old moderately retarded, somewhat short girl with EEG abnormalities but no history of seizures; her urine also contained lysine, citrulline, and histidine. No other family members were affected. Simell et al. (1972) described a 3.5-year-old girl with spastic diplegia who had lysinuria and saccharopinuria, but normal plasma levels of citrulline. Somatically and mentally she was normal. Simell et al. (1973) demonstrated deficiency of the saccharopine-degrading enzyme aminoadipic semialdehyde-glutamate reductase in cultured fibroblasts and in muscle. The enzyme was reduced to 40% of normal. Cederbaum et al. (1979) reported a 7-year-old boy with mild developmental delay, hyperactivity, and speech delay who was found to have increased serum and urinary lysine and saccharopine. Saccharopine was also present in cerebrospinal fluid. Initial studies suggested cystinuria, but further analysis indicated that the amino acid was saccharopine. Patient fibroblasts showed undetectable activities of both lysine ketoglutarate reductase and saccharopine dehydrogenase. Reexamination of the urine of previously studied cases of this double enzyme deficiency (Dancis et al., 1976) suggested that saccharopinuria of variable degree is the rule and not the exception in patients with hyperlysinemia. Growth \- Short stature Neuro \- Mental retardation \- Spastic diplegia Lab \- Abnormal EEG \- Lysinuria \- Citrullinuria \- Histidinuria \- Saccharopinuria \- Aminoadipic semialdehyde-glutamate reductase deficiency 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	SACCHAROPINURIA	c0268556	5,922	omim	https://www.omim.org/entry/268700	2019-09-22T16:22:30	{"mesh": ["D020167"], "omim": ["268700"], "orphanet": ["3124"], "synonyms": ["Alternative titles", "HYPERLYSINEMIA, TYPE II", "SACCHAROPINE DEHYDROGENASE DEFICIENCY", "ALPHA-AMINOADIPIC SEMIALDEHYDE SYNTHASE DEFICIENCY"]}
Attention deficit hyperactivity disorder predominantly inattentive Other namesAttention deficit disorder (without hyperactivity)[1][2] SpecialtyPsychiatry MedicationStimulant medication Attention deficit hyperactivity disorder predominantly inattentive (ADHD-PI or ADHD-I),[3] is one of the three presentations of attention deficit hyperactivity disorder (ADHD).[4] In 1987–1994, there were no subtypes and thus it was not distinguished from hyperactive ADHD in the Diagnostic and Statistical Manual (DSM-III-R). The 'predominantly inattentive subtype' is similar to the other presentations of ADHD except that it is characterized primarily by problems with inattention or a deficit of sustained attention, such as procrastination, hesitation, and forgetfulness. It differs in having fewer or no typical symptoms of hyperactivity or impulsiveness. Lethargy and fatigue are sometimes reported, but ADHD-PI is a separate condition from the proposed cluster of symptoms known as sluggish cognitive tempo (SCT). ## Contents * 1 Classification * 2 Signs and symptoms * 2.1 DSM-5 criteria * 3 Treatment * 3.1 Medication * 4 Prognosis * 4.1 Self-esteem * 4.2 Coping and age * 4.3 Comparisons between subtypes * 5 Epidemiology * 6 History * 7 References * 8 External links ## Classification[edit] ADHD-PI is an attention-concentration deficit that has everything in common with other forms of ADHD except that it has fewer hyperactivity or impulsivity symptoms and has more directed attention fatigue symptoms.[5] ## Signs and symptoms[edit] ### DSM-5 criteria[edit] The DSM-5 allows for diagnosis of the predominantly inattentive presentations of ADHD (ICD-10 code F90.0) if the individual presents six or more (five for adults) of the following symptoms of inattention for at least six months to a point that is disruptive and inappropriate for developmental level: * Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities. * Often has trouble keeping attention on tasks or play activities. * Often does not seem to listen when spoken to directly. * Often does not follow instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions). * Often has trouble organizing activities. * Often avoids, dislikes, or doesn't want to do things that take a lot of mental effort for a long period (such as schoolwork or homework). * Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools). * Is often easily distracted. * Is often forgetful in daily activities.[6] An ADHD diagnosis is contingent upon the symptoms of impairment presenting themselves in two or more settings (e.g., at school or work and at home). There must also be clear evidence of clinically significant impairment in social, academic, or occupational functioning. Lastly, the symptoms must not occur exclusively during the course of a pervasive developmental disorder, schizophrenia, or other psychotic disorder, and are not better accounted for by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder).[citation needed] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2016) (Learn how and when to remove this template message) Life Period Examples of Observed Symptoms Children Failing to pay close attention to details or making careless mistakes when doing school-work or other activities Trouble keeping attention focused during play or tasks Appearing not to listen when spoken to (often being accused of "daydreaming") Failing to follow instructions or finish tasks Avoiding tasks that require a high amount of longer-term mental effort and organization, such as school projects Frequently losing items required to facilitate tasks or activities, such as school supplies Excessive distractibility Forgetfulness Procrastination, inability to begin an activity, such as completing homework Adults Procrastination; delaying or avoiding starting projects that require vigilant mental effort Difficulty sustaining concentration on conversations or briefly losing attention on someone speaking Hesitation to sustain concentration in planning and organizing for the completion of tasks Hesitative responses, doubt, and delayed execution due to inattention remembering information Difficulty finishing projects or completing assignments because many tasks are simultaneously on the go Forgetting to complete tasks and details after temporarily switching to more stimulating tasks Difficulty finding misplaced tools after task switching due to bypassing adequate memory storage Sustained information processing is slower than others causing information gaps that inhibit execution Problems remembering appointments, obligations, or instructions Difficulty learning new projects when concentration deficits cause desire to multitask or daydream Distracted from persevering during work; difficulty holding onto a job for a significant amount of time Changing plans, to the inconvenience of others, due to forgetting or not fully aware of the bigger scenario Maintaining excessive personal items such as storing old items of diminished usefulness Obsessive behavior as compensation or coping mechanism for a perseverance deficit Difficulty transitioning to new task or activity due to obsessive behavior Higher rate of vigilant concentration fatigue after inhibiting many distractions from greater effort required ## Treatment[edit] Main article: Attention deficit hyperactivity disorder management Although ADHD has most often been treated with medication, medications do not cure ADHD. They are used solely to treat the symptoms associated with this disorder and the symptoms will come back once the medication stops.[7] ### Medication[edit] Stimulants are typically formulated in fast and slow-acting as well as short and long-acting formulations. The fast-acting amphetamine mixed salts (Adderall) and its derivatives, with short and long-acting formulations bind to the trace amine associated receptor and triggers the release of dopamine into the synaptic cleft.[8] They may have a better cardiovascular disease profile than methylphenidate and potentially better tolerated.[9] The fast-acting methylphenidate (well known under the trade name Ritalin) is a dopamine reuptake inhibitor.[10] In the short term, methylphenidate is well tolerated. However, long-term studies have not been conducted in adults, and concerns about long-term effects like increases in blood pressure have not been established.[11] The slow and long-acting nonstimulant atomoxetine (Strattera), is primarily a norepinephrine reuptake inhibitor and, to a lesser extent, a dopamine reuptake inhibitor. It may be more effective for those with predominantly inattentive concentration.[12] It is sometimes prescribed in adults who do not get enough vigilant concentration response from mixed amphetamine salts (Adderall) or get too many side effects.[13][unreliable medical source] It is also approved for ADHD by the US Food and Drug Administration. The use of cholinergic adjunctive medications is uncommon and their clinical effects are poorly researched;[14][15][16][unreliable medical source][17] consequently, cholinergics such as galantamine or varenicline would be off label use for ADHD.[18][19][20] New nicotinic cholinergic medications in development for ADHD are pozanicline,[21][non-primary source needed][22] ABT-418,[23][non-primary source needed] and ABT-894.[24][non-primary source needed] ## Prognosis[edit] ### Self-esteem[edit] In some cases, children who enjoy learning may develop a sense of fear when faced with structured or planned work, especially long or group-based assignments that require extended focus, even if they thoroughly understand the topic. Children with ADHD-PI may be at greater risk of academic failures and early withdrawal from school.[25] Teachers and parents may make incorrect assumptions about the behaviors and attitudes of a child with ADHD-PI, and may provide them with frequent and erroneous negative feedback (e.g. "careless", "you're irresponsible", "you're immature", "you're lazy", "you don't care/show any effort", "you just aren't trying", etc.).[26] The inattentive children may realize on some level that they are somehow different internally from their peers. However, they are also likely to accept and internalize the continuous negative feedback, creating a negative self-image that becomes self-reinforcing. If these children progress into adulthood undiagnosed or untreated, their inattentiveness, ongoing frustrations, and poor self-image frequently create numerous and severe problems maintaining healthy relationships, succeeding in postsecondary schooling, or succeeding in the workplace. These problems can compound frustrations and low self-esteem, and will often lead to the development of secondary pathologies including anxiety disorders, mood disorders, and substance abuse.[25] ### Coping and age[edit] It has been suggested[5] that some of the symptoms of ADHD present in childhood appear to be less overt in adulthood. This is likely due to an adult's ability to make cognitive adjustments and develop compensating or coping skills to minimize the impact of inattentive or hyperactive symptoms. However, the core problems of ADHD do not disappear with age.[25] Some researchers have suggested that individuals with reduced or less overt hyperactivity symptoms should receive the ADHD-combined diagnosis. Hallowell and Ratey (2005) suggest[27] that the manifestation of hyperactivity simply changes with adolescence and adulthood, becoming a more generalized restlessness or tendency to fidget. ### Comparisons between subtypes[edit] A meta-analysis of 37 studies on cognitive differences between those presenting ADHD-Predominantly Inattentive presentations and ADHD-Combined type found that "the ADHD-C presenting performed better than the ADHD-PI presenting in the areas of processing speed, attention, performance IQ, memory, and fluency. The ADHD-PI presenting performed better than the ADHD-C group on measures of flexibility, working memory, visual/spatial ability, non-verbal IQ, motor ability, and language. Both the ADHD-C and ADHD-PI groups were found to perform more poorly than the control group on measures of inhibition, however, there was no difference found between the two groups. Furthermore, the ADHD-C and ADHD-PI presenting did not differ on measures of sustained attention."[28] ## Epidemiology[edit] It is difficult to say exactly how many children or adults worldwide have ADHD because different countries have used different ways of diagnosing it, while some do not diagnose it at all. In the UK, diagnosis is based on quite a narrow set of symptoms, and about 0.5–1% of children are thought to have attention or hyperactivity problems. In comparison, professionals in the U.S. used a much broader definition of the term ADHD until recently.[citation needed] This meant up to 10% of children in the U.S. were described as having ADHD. Current estimates suggest that ADHD is present internationally in about 7.2% of children.[29] About five times more boys than girls are diagnosed with ADHD. Boys are seen as the prototypical ADHD child, therefore they are more often diagnosed with ADHD than girls.[30][non-primary source needed] This may be partly because of the particular ways they express their difficulties. Boys and girls both have attention problems, but boys are more likely to be overactive and difficult to manage.[citation needed] Children from all cultures and social groups are diagnosed with ADHD. However, children from certain backgrounds may be particularly likely to be diagnosed with ADHD, because of different expectations about how they should behave.[citation needed] It is, therefore, important to ensure that a child's cultural background is understood and taken into account as part of the assessment. ## History[edit] In 1980, the DSM-III changed the name of the condition from "hyperkinetic reaction of childhood" to "attention deficit disorder" (ADD). That happened because research by Virginia Douglas had suggested that the attention deficits were more important than the hyperactive behaviour for understanding the disorder. The new label also reflected the observation of clinicians that attention deficits could also exist without hyperactivity. For the first time, two subtypes were introduced: ADD with hyperactivity (ADD+H) and ADD without hyperactivity (ADD-H). While the ADD+H category was fairly consistent with previous definitions, the latter subtype represented essentially a new category. Thus, almost everything that is known about the predominantly inattentive subtype is based on research conducted since 1980.[31] ## References[edit] 1. ^ Biederman J, Faraone SV, Weber W, Russell RL, Rater M, Park KS (December 1997). "Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry. 36 (12): 1682–7. doi:10.1097/00004583-199712000-00016. PMID 9401329. Archived from the original on 1 November 2013. 2. ^ Lange KW, Reichl S, Lange KM, Tucha L, Tucha O (December 2010). "The history of attention deficit hyperactivity disorder". Attention Deficit and Hyperactivity Disorders. 2 (4): 241–55. doi:10.1007/s12402-010-0045-8. PMC 3000907. PMID 21258430. 3. ^ Weiss, Lawrence G. (2005). WISC-IV clinical use and interpretation scientist-practitioner perspectives (1st ed.). Amsterdam: Elsevier Academic Press. p. 237. ISBN 9780125649315. 4. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Publishing. pp. 59–65. ISBN 978-0890425558. 5. ^ a b Quinn, Patricia (1994). ADD and the College Student: A Guide for High School and College Students with Attention Deficit Disorder. New York, NY: Magination Press. pp. 2–3. ISBN 1-55798-663-0. 6. ^ "Attention-Deficit/Hyperactivity Disorder". BehaveNet. Retrieved 17 April 2013. 7. ^ "Attention deficit hyperactivity disorder". National Institute of Mental health. 2008. Archived from the original on 19 January 2013. Retrieved 9 January 2013. 8. ^ Retz W, Retz-Junginger P, Thome J, Rösler M (September 2011). "Pharmacological treatment of adult ADHD in Europe". The World Journal of Biological Psychiatry. 12 (Suppl 1): 89–94. doi:10.3109/15622975.2011.603229. PMID 21906003. S2CID 34871481. 9. ^ Kolar D, Keller A, Golfinopoulos M, Cumyn L, Syer C, Hechtman L (April 2008). "Treatment of adults with attention-deficit/hyperactivity disorder". Neuropsychiatric Disease and Treatment. 4 (2): 389–403. doi:10.2147/ndt.s6985. PMC 2518387. PMID 18728745. 10. ^ Volkow, N. D.; Fowler, J. S.; Wang, G.; Ding, Y.; Gatley, S. J. (1 January 2002). "Mechanism of action of methylphenidate: insights from PET imaging studies". Journal of Attention Disorders. 6 Suppl 1: S31–43. doi:10.1177/070674370200601s05. ISSN 1087-0547. PMID 12685517. S2CID 9132302. 11. ^ Godfrey J (March 2009). "Safety of therapeutic methylphenidate in adults: a systematic review of the evidence". Journal of Psychopharmacology. 23 (2): 194–205. doi:10.1177/0269881108089809. PMID 18515459. S2CID 5390805. 12. ^ Simpson D, Plosker GL (2004). "Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder". CNS Drugs. 18 (6): 397–401. doi:10.2165/00023210-200418060-00011. PMID 15089111. S2CID 23171429. 13. ^ Messer, Tess (December 2009). "The Best Medicine for Inattentive ADHD". Primarily Inattentive ADHD (blog). Retrieved 25 December 2013. 14. ^ Wilens TE, Decker MW (October 2007). "Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition". Biochemical Pharmacology. 74 (8): 1212–23. doi:10.1016/j.bcp.2007.07.002. PMC 2974320. PMID 17689498. 15. ^ Sarter M, Givens B, Bruno JP (April 2001). "The cognitive neuroscience of sustained attention: where top-down meets bottom-up". Brain Research Reviews. 35 (2): 146–60. doi:10.1016/S0165-0173(01)00044-3. PMID 11336780. S2CID 7338299. 16. ^ Levin ED, Simon BB (August 1998). "Nicotinic acetylcholine involvement in cognitive function in animals". Psychopharmacology. 138 (3–4): 217–30. doi:10.1007/s002130050667. PMID 9725745. S2CID 12099416. 17. ^ Demeter E, Sarter M (January 2013). "Leveraging the cortical cholinergic system to enhance attention". Neuropharmacology. 64: 294–304. doi:10.1016/j.neuropharm.2012.06.060. PMC 3445745. PMID 22796110. 18. ^ Lehmann, Christine (21 November 2003). "ADHD Symptoms Respond To Cholinergic Drugs". Psychiatric News. 38 (22): 25. doi:10.1176/pn.38.22.0025. 19. ^ Snyder, Bill (11 December 2009). "Genetics may explain three types of ADHD". Reporter: Vanderbilt University Medical Center's Weekly Newspaper. 20. ^ Potter AS, Newhouse PA, Bucci DJ (December 2006). "Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder?". Behavioural Brain Research. 175 (2): 201–11. doi:10.1016/j.bbr.2006.09.015. PMID 17081628. S2CID 9994841. 21. ^ Apostol G, Abi-Saab W, Kratochvil CJ, Adler LA, Robieson WZ, Gault LM, Pritchett YL, Feifel D, Collins MA, Saltarelli MD (February 2012). "Efficacy and safety of the novel α4β2 neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study". Psychopharmacology. 219 (3): 715–25. doi:10.1007/s00213-011-2393-2. PMID 21748252. S2CID 18882095. 22. ^ Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP (2004). "ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders". CNS Drug Reviews. 10 (2): 167–82. doi:10.1111/j.1527-3458.2004.tb00011.x. PMC 6741767. PMID 15179445. 23. ^ Wilens TE, Biederman J, Spencer TJ, Bostic J, Prince J, Monuteaux MC, Soriano J, Fine C, Abrams A, Rater M, Polisner D (December 1999). "A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder". The American Journal of Psychiatry. 156 (12): 1931–7. doi:10.1176/ajp.156.12.1931 (inactive 14 January 2021). PMID 10588407.CS1 maint: DOI inactive as of January 2021 (link) 24. ^ Bain EE, Robieson W, Pritchett Y, Garimella T, Abi-Saab W, Apostol G, McGough JJ, Saltarelli MD (February 2013). "A randomized, double-blind, placebo-controlled phase 2 study of α4β2 agonist ABT-894 in adults with ADHD". Neuropsychopharmacology. 38 (3): 405–13. doi:10.1038/npp.2012.194. PMC 3547191. PMID 23032073. 25. ^ a b c Triolo, Santo (1998). Attention Deficit Hyperactivity Disorder in Adulthood: A Practitioner's Handbook. Philadelphia, PA: Brunner-Routledge. pp. 65–69. ISBN 0-87630-890-6.[permanent dead link] 26. ^ Kelly, Kate; Ramundo, Peggy (2006). You Mean I'm Not Lazy, Stupid or Crazy?! The Classic Self-Help Book For Adults with Attention Deficit Disorder. New York, NY: Scribner. pp. 11–12. ISBN 0-7432-6448-7. 27. ^ Hallowell, Edward M.; Ratey, John J. (2005). Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder. New York: Ballantine Books. pp. 253–5. ISBN 0-345-44231-8. 28. ^ Lane, Brittany Ann (2003). The differential neuropsychological/cognitive profiles of ADHD presentations: A meta-analysis (PhD Thesis). University of Northern Colorado. OCLC 56479200.[page needed] 29. ^ Thomas, Rae; Sanders, Sharon; Doust, Jenny; Beller, Elaine; Glasziou, Paul (1 April 2015). "Prevalence of Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis". Pediatrics. 135 (4): e994–e1001. doi:10.1542/peds.2014-3482. ISSN 0031-4005. PMID 25733754. S2CID 2457397. 30. ^ Bruchmüller K, Margraf J, Schneider S (February 2012). "Is ADHD diagnosed in accord with diagnostic criteria? Overdiagnosis and influence of client gender on diagnosis". Journal of Consulting and Clinical Psychology. 80 (1): 128–38. doi:10.1037/a0026582. PMID 22201328. 31. ^ Wheeler, Jennifer; Carlson, Caryn (3 July 1996). "Attention Deficit Disorder without Hyperactivity (ADHD, Predominantly Inattentive Type)". KidSource Online. Archived from the original on 6 July 2016. Retrieved 30 June 2016. ## External links[edit] Classification D Look up ADHD-PI or ADHD in Wiktionary, the free dictionary. * v * t * e Attention deficit hyperactivity disorder Main articles * History of ADHD * ADHD in adults * ADHD controversies * ADHD management * Social construct theory of ADHD * ADHD coaching * Epidemiology of ADHD * Diet and ADHD * Major characteristics: Attention * Hyperactivity * Impulsivity Sub-types * ADHD predominantly inattentive (ADHD-I, formerly ADD) * ADHD predominantly hyperactive (ADHD-H, formerly ADHD) * ADHD combined type (ADHD-C) Medications Stimulants: * Methylphenidate (Ritalin, Concerta, and others) * Dexmethylphenidate (Focalin, Focalin XR) * Amphetamine (Evekeo, Adderall, Adzenys XR, Dyanavel XR) * Dextroamphetamine (Dexedrine, Zenzedi, ProCentra, and others) * Lisdexamfetamine (Vyvanse) Non-stimulant: * Atomoxetine (Strattera) * Guanfacine (Tenex (off-label), Intuniv) * Clonidine (Catapres (off-label), Kapvay) Related or outdated topics * Deferred gratification * Auditory processing disorder * Deficits in attention, motor control and perception * Developmental coordination disorder * Low arousal theory * Sluggish cognitive tempo * Sensory processing disorder * Hunter vs. farmer hypothesis * Category * v * t * e Amphetamine Main articles and pharmaceuticals Amphetamine * Adzenys ER * Adzenys XR-ODT * Dyanavel XR * Evekeo * Evekeo ODT * Mixed amphetamine salts * Adderall * Adderall XR * Mydayis Levoamphetamine N/A Dextroamphetamine * Dexedrine * ProCentra * Zenzedi Lisdexamfetamine * Vyvanse Neuropharmacology Biomolecular targets * TAAR1 (full agonist) * CART (mRNA inducer) * 5-HT1A receptor (low affinity ligand) * MAO (weak competitive inhibitor) * Carbonic anhydrases hCA4, hCA5A, hCA5B, hCA7, hCA12, hCA13, and hCA14 (enzyme activator) Inhibited transporters * DAT * NET * SERT * VMAT1 * VMAT2 * EAAT3 * SLC22A3 * SLC22A5 Active metabolites * 4-Hydroxyamphetamine * 4-Hydroxynorephedrine * Norephedrine Related articles * ADHD * ADHD management * Amphetamine psychosis * Benzedrine in popular culture * Dopamine * Doping in sport * Executive functions * Formetorex * ΔFosB * History and culture of substituted amphetamines * Methamphetamine * Methylphenidate * N-Methylphenethylamine * Motivational salience * Incentive salience * Narcolepsy * Neurobiological effects of physical exercise § Attention deficit hyperactivity disorder * Nootropic * Norepinephrine * Obesity * Performance-enhancing substance * Phenethylamine * Phentermine * Phenylacetone * Recreational drug use * Serotonin * Substituted amphetamine * Trace amine * Category [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	Attention deficit hyperactivity disorder predominantly inattentive	None	5,923	wikipedia	https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder_predominantly_inattentive	2021-01-18T18:33:02	{"icd-10": ["F90.0"], "wikidata": ["Q1993146"]}
Corneal perforation SpecialtyOphthalmology SymptomsDifficulty seeing, eye pain Diagnostic methodSeidel test TreatmentTissue adhesive, pressure bandage, or lamellar keratoplasty Corneal perforation is an anomaly in the cornea resulting from damage to the corneal surface. A corneal perforation means that the cornea has been penetrated, thus leaving the cornea damaged. The cornea is a clear part of the eye which controls and focuses the entry of light into the eye. Damage to the cornea due to corneal perforation can cause decreased visual acuity. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 References * 6 Further reading ## Signs and symptoms[edit] Corneal perforation may cause difficulty in seeing and persistent eye pain. Physical examination may reveal discoloration of the cornea. ## Causes[edit] Perforation of the cornea may occur due to diseases of the cornea, injury during eye surgery, or infection of the eye, which may occur after surgery or procedures. Pellucid marginal degeneration may cause corneal thinning, leading to perforation.[1] ## Diagnosis[edit] Corneal perforation can be diagnosed by using the Seidel test. Any aqueous leakage is revealed during the Seidel test confirms corneal perforation. A fluorescence strip is wiped over the wound. If the clear aqueous humor from the eye runs through the yellow stain, the patient tests positive for corneal perforation. ## Treatment[edit] The treatment of corneal perforation depends on the location, severity and the cause of damage * Tissue adhesive can be used to seal small perforation, but this method cannot be used to treat perforations larger than 1 mm. * Non infected corneal perforation generally heals when a pressure bandage is used. * For certain types of corneal perforations, lamellar keratoplasty is used as treatment. ## References[edit] 1. ^ Jinabhai, Amit; Radhakrishnan, Hema; o’Donnell, Clare (2011). "Pellucid corneal marginal degeneration: A review". Contact Lens and Anterior Eye. 34 (2): 56–63. doi:10.1016/j.clae.2010.11.007. PMID 21185225. ## Further reading[edit] * http://www.haematologica.org/cgi/reprint/90/3/ECR15.pdf * http://www.lasermyeye.org/patients/learning/cornealperf.html * http://www.ijo.in/article.asp?issn=0301-4738;year=1983;volume=31;issue=5;spage=667;epage=668;aulast=Raju [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	Corneal perforation	c0339293	5,924	wikipedia	https://en.wikipedia.org/wiki/Corneal_perforation	2021-01-18T19:09:28	{"mesh": ["D057112"], "umls": ["C0339293", "C0948060"], "icd-10": ["S05.3"], "wikidata": ["Q5171111"]}
The globulomaxillary cyst is a cyst that appears between a maxillary lateral incisor and the adjacent canine. It exhibits as an "inverted pear-shaped radiolucency" on radiographs, or X-ray films. The globulomaxillary cyst often causes the roots of adjacent teeth to diverge. This cyst should not be confused with a nasopalatine cyst. The developmental origin has been disputed. Today, most literature agree based on overwhelming evidence that the cyst is predominantly of tooth origin (odontogenic), demonstrating findings consistent with periapical cysts, odontogenic keratocysts or lateral periodontal cysts.[1] ## Treatment[edit] Treatment is usually by enucleation. ## References[edit] 1. ^ Developmental defects of the oral and maxillofacial region. In Neville, B, et al. editors: Oral & Maxillofacial Pathology, 2nd Ed. Saunders 2002, page 27. * v * t * e Developmental Cysts of the Oral Cavity * Globulomaxillary cyst * Median alveolar cyst * Median palatal cyst * Nasolabial cyst * Nasopalatine duct cyst [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	Globulomaxillary cyst	c0266102	5,925	wikipedia	https://en.wikipedia.org/wiki/Globulomaxillary_cyst	2021-01-18T18:37:36	{"umls": ["C0266102"], "wikidata": ["Q5571105"]}
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: "Glycogen storage disease type I" – news · newspapers · books · scholar · JSTOR (February 2009) (Learn how and when to remove this template message) This article is written like a research paper or scientific journal that may use overly technical terms or may not be written like an encyclopedic article. Please help improve it by rewriting it in an encyclopedic style. (April 2020) (Learn how and when to remove this template message) GSD Type I Other namesvon Gierke disease Symbol for Glycogen Storage Disease Type I Pronunciation * /ˈglaɪkədʒən ˈstoʊrɪdʒ dɪˈziz/ SpecialtyEndocrinology, genetics, hematology, immunology ComplicationsLactic acidosis, hyperlipidemia, non-alcoholic fatty liver disease, hepatocellular adenoma, inflammatory bowel disease DurationLifetime TypesType Ia, type Ib CausesAutosomal recessive inheritance Diagnostic methodGenetic testing, hypoglycemia, hepatomegaly Type Ib: neutropenia TreatmentCornstarch, diet MedicationFilgrastim Frequency1 in 100,000 live births Glycogen storage disease type I (GSD I) is an inherited disease that results in the liver being unable to properly break down stored glycogen. This impairment disrupts the liver's ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while GSD Ib is caused a deficiency in the enzyme glucose-6-phosphate translocase. Since glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during periods of fasting, both deficiencies cause severe low blood sugar and, over time, excess glycogen storage in the liver and (in some cases) the kidneys. GSD I patients typically present with an enlarged liver from non-alcoholic fatty liver disease as the result of this glycogen buildup.[1] Other functions of the liver and kidneys are initially intact in GSD I, but are susceptible to a variety of other problems.[vague] Without proper treatment, GSD I gives rise to chronic low blood sugar, which can result in derangements including excessive levels of lactic acid and abnormally high levels of lipids in the bloodstream. Frequent feedings of cornstarch or other carbohydrates are the principal treatment for all forms of GSD I. GSD Ib also features chronic neutropenia due to a dysfunction in the production of neutrophils in the bone marrow. This immunodeficiency, if untreated, makes GSD Ib patients susceptible to infection.[2] The principal treatment for this feature of GSD Ib is filgrastim; however, patients often still require treatment for frequent infections, and a chronically enlarged spleen is a common side effect.[3] GSD Ib patients often present with inflammatory bowel disease.[4] It is the most common of the glycogen storage diseases. GSD I has an incidence of approximately 1 in 100,000 births in the American population, and approximately 1 in 20,000 births among Ashkenazi Jews.[5] The disease was named after German doctor Edgar von Gierke, who first described it in 1929.[6][7] ## Contents * 1 Signs and symptoms * 1.1 Hypoglycemia * 2 Genetics * 3 Pathophysiology * 3.1 Normal carbohydrate balance and maintenance of blood glucose levels * 3.2 Pathophysiology * 3.3 Elevated lactate and lactic acidosis * 3.4 Elevated urate and complications * 3.5 Hyperlipidemia and plasma effects * 3.6 Hepatomegaly * 3.7 Hepatic adenomas * 3.8 Portal hypertension * 3.9 Osteopenia * 3.10 Kidney effects * 3.11 Splenomegaly * 3.12 Bowel effects * 3.13 Infection risk * 3.14 Thrombocytopenia and blood clotting problems * 3.15 Developmental effects * 4 Diagnosis * 5 Treatment * 5.1 Avoidance of other sugars * 5.2 Other therapeutic measures * 5.3 Treatment of acute metabolic acidosis episodes * 5.4 Metabolic control * 6 Prognosis * 7 Epidemiology * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Early research into GSD I identified numerous clinical manifestations falsely thought to be primary features of the genetic disorder. However, continuing research has revealed that these clinical features are the consequences of only one (in GSD Ia) or two (in GSD Ib) fundamental abnormalities: * impairment in the liver's ability to convert stored glycogen into glucose through glycogenolysis[8] * in GSD Ib, impairment of the neutrophil's ability to take up glucose, resulting in neutrophil dysfunction and neutropenia[9] These fundamental abnormalities give rise to a small number of primary clinical manifestations, which are the features considered in diagnosis of GSD I: * Low blood sugar (hypoglycemia), due to impairment of glycogen breakdown (glycogenolysis) causing insufficient fasting blood glucose[10] * hepatomegaly of non-alcoholic fatty liver disease, due to impairment of glycogenolysis causing glycogen accumulation in the liver[1] * in GSD Ib, increased infection risk, due to neutropenia and neutrophil dysfunction[2] Affected people commonly present with secondary clinical manifestations, linked to one or more of the primary clinical manifestations: * High levels of uric acid in the blood and attendant risk of gout or kidney damage, caused by low serum insulin levels in prolonged hypoglycemia * High levels of lactic acid in the blood, in extreme cases leading to lactic acidosis, caused by prolonged hypoglycemia[10] * hepatic adenomas developing in adulthood[11] and attendant risk of anemia,[12] suspected to be caused by blood glucose dysregulation in the presence of non-alcoholic fatty liver disease * in GSD Ib, inflammatory bowel disease and attendant risk of anemia,[12] caused by neutrophil dysfunction and exacerbated by the increased carbohydrate intake required to prevent hypoglycemia[2] In addition, there are several clinical manifestations that often result from the treatment of the primary clinical manifestations: * pancreatic hypertrophy, due to increased carbohydrate intake causing frequent engagement of the insulin response[13] * in GSD Ib, splenomegaly, due to the long-term use of filgrastim to treat neutropenia causing sequestration of blood factors in the spleen[3] * in GSD Ib, an abnormally low number of platelets in the blood may occur, due to long-term use of filgrastim causing sequestration of platelets in the spleen[14] * in GSD Ib, anemia, due to long-term use of filgrastim causing sequestration of hemoglobin in the spleen, potentially exacerbated by uncontrolled inflammatory bowel disease[15] ### Hypoglycemia[edit] Medical diagram showing hypoglycemia compared with normal blood glucose level. Low blood sugar (hypoglycemia) is the primary clinical symptom common to both GSD Ia and GSD Ib and most often prompts initial diagnosis of the disease. During fetal development in utero, maternal glucose transferred across the placenta prevents hypoglycemia. However, after birth, the inability to maintain blood glucose from stored glycogen in the liver causes measurable hypoglycemia in no more than 1–2 hours after feedings. Without proper dietary treatment after birth, prolonged hypoglycemia often leads to sudden lactic acidosis that can induce primary respiratory distress in the newborn period, as well as ketoacidosis. Neurological manifestations of hypoglycemia are less severe in GSD I than in other instances. Rather than acute hypoglycemia, GSD I patients experience persistent mild hypoglycemia. The diminished likelihood of neurological manifestations is due to the habituation of the brain to mild hypoglycemia. Given the reduced blood glucose level, the brain adapts to using alternative fuels like lactate. These gradual metabolic adaptations during infancy make severe symptoms like unconsciousness or seizure uncommon before diagnosis. In the early weeks of life, undiagnosed infants with GSD I tolerate persistent hypoglycemia and compensated lactic acidosis between feedings without symptoms. Without consistent carbohydrate feeding, infant blood glucose levels typically measure between 25 and 50 mg/dL (1.4 to 2.8 mmol/L). After weeks to months without treatment with consistent oral carbohydrates, infants will progress to show clear symptoms of hypoglycemia and lactic acidosis. Infants may present with paleness, clamminess, irritability, respiratory distress, and an inability to sleep through the night even in the second year of life. Developmental delay is not an intrinsic effect of GSD I, but is common if the diagnosis is not made in early infancy. ## Genetics[edit] Glycogen storage disease type I has an autosomal recessive pattern of inheritance. GSD I is inherited in an autosomal recessive manner. People with one copy of the faulty gene are carriers of the disease and have no symptoms. As for other autosomal recessive diseases, each child born to two carriers of the disease has a 25% chance of inheriting both copies of the faulty gene and manifesting the disease. Unaffected parents of a child with GSD I can be assumed to be carriers. Prenatal diagnosis has been made by fetal liver biopsy at 18–22 weeks of gestation, but no fetal treatment has been proposed. Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus sampling when a fetus is known to be at risk. The most common forms of GSD I are designated GSD Ia and GSD Ib, the former accounting for over 80% of diagnosed cases and the latter for less than 20%. A few rarer forms have been described. * GSD Ia results from mutations of G6PC, the gene for glucose-6-phosphatase,[16] located on chromosome 17q21.[17] * GSD Ib results from mutations of the gene for SLC37A4 or "G6PT1", the glucose-6-phosphate transporter.[17][18] * GSD Ic results from mutations of SLC17A3 or SLC37A4.[19] Glucose-6-phosphatase is an enzyme located on the inner membrane of the endoplasmic reticulum. The catalytic unit is associated with a calcium binding protein, and three transport proteins (T1, T2, T3) that facilitate movement of glucose-6-phosphate (G6P), phosphate, and glucose (respectively) into and out of the enzyme. ## Pathophysiology[edit] ### Normal carbohydrate balance and maintenance of blood glucose levels[edit] Glycogen in liver and (to a lesser degree) kidneys serves as a form of stored, rapidly accessible glucose, so that the blood glucose level can be maintained between meals. For about 3 hours after a carbohydrate-containing meal, high insulin levels direct liver cells to take glucose from the blood, to convert it to glucose-6-phosphate (G6P) with the enzyme glucokinase, and to add the G6P molecules to the ends of chains of glycogen (glycogen synthesis). Excess G6P is also shunted into production of triglycerides and exported for storage in adipose tissue as fat. When digestion of a meal is complete, insulin levels fall, and enzyme systems in the liver cells begin to remove glucose molecules from strands of glycogen in the form of G6P. This process is termed glycogenolysis. The G6P remains within the liver cell unless the phosphate is cleaved by glucose-6-phosphatase. This dephosphorylation reaction produces free glucose and free PO 4 anions. The free glucose molecules can be transported out of the liver cells into the blood to maintain an adequate supply of glucose to the brain and other organs of the body. Glycogenolysis can supply the glucose needs of an adult body for 12–18 hours. When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA. Amino acids and lactic acid are used to synthesize new G6P in liver cells by the process of gluconeogenesis. The last step of normal gluconeogenesis, like the last step of glycogenolysis, is the dephosphorylation of G6P by glucose-6-phosphatase to free glucose and PO 4. Thus glucose-6-phosphatase mediates the final, key, step in both of the two main processes of glucose production during fasting. The effect is amplified because the resulting high levels of glucose-6-phosphate inhibit earlier key steps in both glycogenolysis and gluconeogenesis. ### Pathophysiology[edit] The principal metabolic effects of deficiency of glucose-6-phosphatase are hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia. Map of effects in GSDIa from non-functioning glucose-6-phosphatase. The hypoglycemia of GSD I is termed "fasting", or "post-absorptive", usually about 4 hours after the complete digestion of a meal. This inability to maintain adequate blood glucose levels during fasting results from the combined impairment of both glycogenolysis and gluconeogenesis. Fasting hypoglycemia is often the most significant problem in GSD I, and typically the problem that leads to the diagnosis. Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol. Lactic acidosis arises from impairment of gluconeogenesis. Lactic acid is generated both in the liver and muscle and is oxidized by NAD+ to pyruvic acid and then converted via the gluconeogenic pathway to G6P. Accumulation of G6P inhibits conversion of lactate to pyruvate. The lactic acid level rises during fasting as glucose falls. In people with GSD I, it may not fall entirely to normal even when normal glucose levels are restored. Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately acetyl-CoA is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control". Hyperuricemia results from a combination of increased generation and decreased excretion of uric acid, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway. It is also a byproduct of purine degradation. Uric acid competes with lactic acid and other organic acids for renal excretion in the urine. In GSD I increased availability of G6P for the pentose phosphate pathway, increased rates of catabolism, and diminished urinary excretion due to high levels of lactic acid all combine to produce uric acid levels several times normal. Although hyperuricemia is asymptomatic for years, kidney and joint damage gradually accrue. ### Elevated lactate and lactic acidosis[edit] High levels of lactic acid in the blood are observed in all people with GSD I, due to impaired gluconeogenesis. Baseline elevations generally range from 4 to 10 mol/mL, which will not cause any clinical impact. However, during and after an episode of low blood sugar, lactate levels will abruptly rise to exceed 15 mol/mL, the threshold for lactic acidosis. Symptoms of lactic acidosis include vomiting and hyperpnea, both of which can exacerbate hypoglycemia in the setting of GSD I. In cases of acute lactic acidosis, patients need emergency care to stabilize blood oxygen, and restore blood glucose. Proper identification of lactic acidosis in undiagnosed children presents a challenge, since the first symptoms are typically vomiting and dehydration, both of which mimic childhood infections like gastroenteritis or pneumonia. Moreover, both of these common infections can precipitate more severe hypoglycemia in undiagnosed children, making diagnosis of the underlying cause difficult. As elevated lactate persists, uric acid, ketoacids, and free fatty acids further increase the anion gap. In adults and children, the high concentrations of lactate cause significant discomfort in the muscles. This discomfort is an amplified form of the burning sensation a runner may feel in the quadriceps after sprinting, which is caused by a brief buildup of lactic acid. Proper control of hypoglycemia in GSD I entirely eliminates the possibility for lactic acidosis. ### Elevated urate and complications[edit] High levels of uric acid often present as a consequence of elevated lactic acid in GSD I patients. When lactate levels are elevated, blood-borne lactic acid competes for the same kidney tubular transport mechanism as urate, limiting the rate that urate can be cleared by the kidneys into the urine. If present, increased purine catabolism is an additional contributing factor. Uric acid levels of 6 to 12 mg/dl (530 to 1060 umol/L) are common among GSD I patients, if the disease is not properly treated. In some affected people, the use of the medication allopurinol is necessary to lower blood urate levels. Consequences of hyperuricemia among GSD I patients include the development of kidney stones and the accumulation of uric acid crystals in joints, leading to kidney disease and gout, respectively. ### Hyperlipidemia and plasma effects[edit] Elevated triglycerides in GSD I result from low serum insulin in patients with frequent prolonged hypoglycemia. It may also be caused by intracellular accumulation of glucose-6-phosphate with secondary shunting to pyruvate, which is converted into Acetyl-CoA, which is transported to the cytosol where the synthesis of fatty acids and cholesterol occurs. Triglycerides above the 3.4 mmol/L (300 mg/dL) range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the blood plasma. In GSD I, cholesterol is typically only mildly elevated compared to other lipids. ### Hepatomegaly[edit] Hepatomegaly with enlarged liver visible in red crosshairs and extending downward. Impairment in the liver's ability to perform gluconeogenesis leads to clinically apparent hepatomegaly. Without this process, the body is unable to liberate glycogen from the liver and convert it into blood glucose, leading to an accumulation of stored glycogen in the liver. Hepatomegaly from the accumulation of stored glycogen in the liver is considered a form of non-alcoholic fatty liver disease. GSD I patients present with a degree of hepatomegaly throughout life, but severity often relates to the consumption of excess dietary carbohydrate. Reductions in the mass of the liver are possible, since most patients retain residual hepatic function that allows for the liberation of stored glycogen at a limited rate. GSD I patients often present with hepatomegaly from the time of birth. In fetal development, maternal glucose transferred to the fetus prevents hypoglycemia, but the storage of glucose as glycogen in the liver leads to hepatomegaly. There is no evidence that this hepatomegaly presents any risk to proper fetal development. Hepatomegaly in GSD type I generally occurs without sympathetic enlargement of the spleen. GSD Ib patients may present with splenomegaly, but this is connected to the use of filgrastim to treat neutropenia in this subtype, not comorbid hepatomegaly. Hepatomegaly will persist to some degree throughout life, often causing the abdomen to protrude, and in severe cases may be palpable at or below the navel. In GSD-related non-alcoholic fatty liver disease, hepatic function is usually spared, with liver enzymes and bilirubin remaining within the normal range. However, liver function may be affected by other hepatic complications in adulthood, including the development of hepatic adenomas. ### Hepatic adenomas[edit] The specific etiology of hepatic adenomas in GSD I remains unknown, despite ongoing research. The typical GSD I patient presenting with at least one adenoma is an adult, though lesions have been observed in patients as young as fourteen. Adenomas, composed of heterogeneous neoplasms, may occur individually or in multiples. Estimates on the rate of conversion of a hepatocellular adenoma into hepatocellular carcinoma in GSD I range from 0% to 11%, with the latter figure representing more recent research. One reason for the increasing estimate is the growing population of GSD I patients surviving into adulthood, when most adenomas develop. Treatment standards dictate regular observation of the liver by MRI or CT scan to monitor for structural abnormalities. Hepatic adenomas may be misidentified as focal nodular hyperplasia in diagnostic imaging, though this condition is rare. However, hepatic adenomas in GSD I uniquely involve diffuse Mallory hyaline deposition, which is otherwise commonly observed in focal nodular hyperplasia. Unlike common hepatic adenomas related to oral contraception, hemorrhaging in GSD I patients is rare. While the reason for the high prevalence of adenomas in GSD I is unclear, research since the 1970s has implicated serum glucagon as a potential driver. In studies, patients that have been put on a dietary regimen to keep blood sugar in a normal range spanning 72 to 108 mg/dL (4.0 to 6.0 mmol/L) have shown a decreased likelihood of developing adenomas. Moreover, patients with well controlled blood glucose have consistently seen a reduction in the size and number of hepatic adenomas, suggesting that adenomas may be caused by imbalances of hepatotropic agents like serum insulin and especially serum glucagon in the liver.[20] ### Portal hypertension[edit] This section is empty. You can help by adding to it. (April 2020) ### Osteopenia[edit] Patients with GSD I will often develop osteopenia. The specific etiology of low bone mineral density in GSD is not known, though it is strongly associated with poor metabolic control. Osteopenia may be directly caused by hypoglycemia, or the resulting endocrine and metabolic sequelae. Improvements in metabolic control have consistently been shown to prevent or reverse clinically relevant osteopenia in GSD I patients.[21] In cases where osteopenia progresses with age, bone mineral density in the ribs is typically more severe than in the vertebrae.[22] In some cases bone mineral density T-score will drop below -2.5, indicating osteoporosis. There is some evidence that osteopenia may be connected with associated kidney abnormalities in GSD I, particularly glomular hyperfiltration.[23] The condition also seems responsive to calcium supplementation. In many cases bone mineral density can increase and return to the normal range given proper metabolic control and calcium supplementation alone, reversing osteopenia. ### Kidney effects[edit] The kidneys are usually 10 to 20% enlarged with stored glycogen. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to kidney failure. GSD I may present with various kidney complications. Renal tubular abnormalities related to hyperlactatemia are seen early in life, likely because prolonged lactic acidosis is more likely to occur in childhood. This will often present as Fanconi syndrome with multiple derangements of renal tubular reabsorption, including tubular acidosis with bicarbonate and phosphate wasting. These tubular abnormalities in GSD I are typically detected and monitored by urinary calcium. Long term these derangements can exacerbate uric acid nephropathy, otherwise driven by hyperlactatemia. In adolescence and beyond, glomerular disease may independently develop, initially presenting as glomerular hyperfiltration indicated by elevated urinary eGFR. ### Splenomegaly[edit] Enlargement of the spleen (splenomegaly) is common in GSD I and has two primary causes. In GSD Ia, splenomegaly may be caused by a relation between the liver and the spleen which causes either to grow or shrink to match the relative size of the other, to a lessened degree. In GSD Ib, it is a side effect of the use of filgrastim to treat neutropenia. ### Bowel effects[edit] Intestinal involvement can cause mild malabsorption with greasy stools (steatorrhea), but usually requires no treatment. ### Infection risk[edit] Neutropenia is a distinguishing feature of GSD Ib, absent in GSD Ia. The microbiological cause of neutropenia in GSD Ib is not well understood. Broadly, the problem arises from compromised cellular metabolism in the neutrophil, resulting in accelerated neutrophil apoptosis. The neutropenia in GSD is characterized by both a decrease in absolute neutrophil count and diminished neutrophil function. Neutrophils use a specific G6P metabolic pathway which relies on the presence of G6Pase-β or G6PT to maintain energy homeostasis within the cell. The absence of G6PT in GSD Ib limits this pathway, leading to endoplasmic reticulum stress, oxidative stress within the neutrophil, triggering premature apoptosis.[24] Granulocyte colony-stimulating factor (G-CSF), available as filgrastim, can reduce the risk of infection. In some cases, G-CSF formulated as pegfilgrastim, sold under the trade name Neulasta, may be used as a slow-acting alternative, requiring less frequent dosing. ### Thrombocytopenia and blood clotting problems[edit] Impaired platelet aggregation is an uncommon consequence of chronic hypoglycemia, seen in GSD I patients. Research has demonstrated decreased platelet function, characterized by decreased prothrombin consumption, abnormal aggregation reactions, prolonged bleeding time, and low platelet adhesiveness. Severity of platelet dysfunction typically correlates with clinical condition, with the most severe cases correlating with lactic acidosis and severely lipidemia.[25] It may cause clinically significant bleeding, especially epistaxis. Additionally, GSD I patients may present with thrombocytopenia as a consequence of splenomegaly. In the setting of splenomegaly various hematologic factors may be sequestered in the tissues of the spleen as blood is filtered through the organ. This can diminish levels of platelets available in the bloodstream, leading to thrombocytopenia. ### Developmental effects[edit] Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Normal neuronal and muscle cells do not express glucose-6-phosphatase, and are thus not impacted by GSD I directly. However, without proper treatment of hypoglycemia, growth failure commonly results from chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, and calorie insufficiency (or malabsorption). The most dramatic developmental delays are often the cause of severe (not just persistent) episodes of hypoglycemia. ## Diagnosis[edit] Several different problems may lead to the diagnosis, usually by two years of age: * seizures or other manifestations of severe fasting hypoglycemia * hepatomegaly with abdominal protuberance * hyperventilation and apparent respiratory distress due to metabolic acidosis * episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia Once the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, GSD I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5)[citation needed], but none are likely to produce all of the features of GSD I. The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar. The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years. ## Treatment[edit] The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65–70% carbohydrate, 10–15% protein, and 20–25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3–4 hours without carbohydrate intake. Once a diagnosis is made, the priority in GSD I treatment is to maintain an adequate blood glucose. Patients aim to maintain a blood glucose above the 72 mg/dL (4.0 mmol/L) cutoff for hypoglycemia. GSD Ib patients have an additional treatment priority relating to neutropenia. Proper management of blood glucose in GSD I is critical in avoiding the more severe effects of high leves of lactic acid and uric acid in the blood, and the development of hepatic adenomas. In the last 30 years, two methods have been used to achieve this goal in young children: (1) continuous nocturnal gastric infusion of glucose or starch; and (2) night-time feedings of uncooked cornstarch. An elemental formula, glucose polymer, and/or cornstarch can be infused continuously through the night at a rate supplying 0.5–0.6 g/kg/h of glucose for an infant, or 0.3–0.4 for an older child. This method requires a nasogastric or gastrostomy tube and pump. Sudden death from hypoglycemia has occurred due to malfunction or disconnection, and periodic cornstarch feedings are now preferred to continuous infusion. Cornstarch is an inexpensive way to provide gradually digested glucose. One tablespoon contains nearly 9 g carbohydrate (36 calories). Although it is safer, less expensive, and requires no equipment, this method does require that parents arise every 3–4 hours to administer the cornstarch. A typical requirement for a young child is 1.6 g/kg every 4 hours. Long-term management should eliminate hypoglycemic symptoms and maintain normal growth. Treatment should achieve normal glucose, lactic acid, and electrolyte levels, and only mild elevations of uric acid and triglycerides. ### Avoidance of other sugars[edit] Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy. ### Other therapeutic measures[edit] Persistent elevation of uric acid above 6.5 mg/dl warrants treatment with allopurinol to prevent uric acid deposition in kidneys and joints. Because of the potential for impaired platelet function, coagulation ability should be checked and the metabolic state normalized before surgery. Bleeding time may be normalized with 1–2 days of glucose loading, and improved with ddavp. During surgery, IV fluids should contain 10% dextrose and no lactate. A patient with GSD, type 1b was treated with a liver transplant at UCSF Medical Center in 1993 that resulted in the resolution of hypoglycemic episodes and the need for the patient to stay away from natural sources of sugar. Other patients have undergone this procedure as well with positive results. Although a liver transplant resulted in the resolution of hypoglycemia it did not however resolve the chronic neutropenia and the risk of infection among patients. ### Treatment of acute metabolic acidosis episodes[edit] The most significant acute problem in childhood is a vulnerability to episodes of metabolic acidosis precipitated by minor illnesses. If a vomiting illness persists longer than 2–4 hours, the child should be seen and assessed for dehydration, acidosis, and hypoglycemia. If these are developing, intravenous fluids should be provided at a rate above maintenance. For mild acidosis, an effective fluid is 10% dextrose in ½ normal saline with 20 mEq/l KCl, but if acidosis is severe, 75–100 mEq/l NaHCO 3 and 20 mEq/l of K acetate can be substituted for the NaCl and KCl. ### Metabolic control[edit] Metabolic control often diminishes during and after puberty, as a result of a patient outgrowing their dietary treatment plan.[26] ## Prognosis[edit] Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Intellectual disability resulting from recurrent, severe hypoglycemia is considered preventable with appropriate treatment. Liver complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation. Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic kidney failure. Despite hyperlipidemia, atherosclerotic complications are uncommon. With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited. ## Epidemiology[edit] In the United States, GSD I has an incidence of approximately 1 in 50,000[27] to 100,000[28] births. None of the glycogenoses are currently detected by standard or extended newborn screening. The disease is more common in people of Ashkenazi Jewish, Mexican, Chinese, and Japanese descent.[29] ## References[edit] 1. ^ a b Kneeman, Jacob M.; Misdraji, Joseph; Corey, Kathleen E. (May 2012). "Secondary causes of nonalcoholic fatty liver disease". Therapeutic Advances in Gastroenterology. 5 (3): 199–207. doi:10.1177/1756283X11430859. ISSN 1756-283X. PMC 3342568. PMID 22570680. 2. ^ a b c Chou, Janice Y.; Jun, Hyun Sik; Mansfield, Brian C. (January 2010). "Neutropenia in type Ib glycogen storage disease". Current Opinion in Hematology. 17 (1): 36–42. doi:10.1097/MOH.0b013e328331df85. ISSN 1065-6251. PMC 3099242. PMID 19741523. 3. ^ a b Dale, David C.; Bolyard, Audrey Anna; Marrero, Tracy M.; Phan, Lan; Boxer, Laurence A.; Kishnani, Priya S.; Kurtzberg, Joanne; Weinstein, David A. (2011-11-18). "Neutropenia in Glycogen Storage Disease 1b (GSD1b)". Blood. 118 (21): 4791. doi:10.1182/blood.V118.21.4791.4791. ISSN 0006-4971. 4. ^ Visser, Gepke; Rake, Jan Peter; Labrune, Philippe; Leonard, James V.; Moses, Shimon; Ullrich, Kurt; Wendel, Udo; Groenier, Klaas H.; Smit, G. Peter A. (October 2002). "Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1". European Journal of Pediatrics. 161 Suppl 1: S83–87. doi:10.1007/s00431-002-1010-0. ISSN 0340-6199. PMID 12373578. 5. ^ "Glycogen Storage Disease Type I". NORD (National Organization for Rare Disorders). Retrieved 2019-09-29. 6. ^ Gierke's syndrome at Who Named It? 7. ^ von Gierke, E. (1929). "Hepato-nephromegalia glykogenica (Glykogenspeicherkrankheit der Leber und Nieren)". Beiträge zur Pathologischen Anatomie und zur Allgemeinen Pathologie. Jena. 82: 497–513. 8. ^ Parikh, Nirzar S.; Ahlawat, Rajni (2019), "Glycogen Storage Disease Type I (Von Gierke Disease)", StatPearls, StatPearls Publishing, PMID 30480935, retrieved 2019-11-01 9. ^ Jun, Hyun Sik; Weinstein, David A.; Lee, Young Mok; Mansfield, Brian C.; Chou, Janice Y. (2014-05-01). "Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib". Blood. 123 (18): 2843–2853. doi:10.1182/blood-2013-05-502435. ISSN 0006-4971. PMC 4007611. PMID 24565827. 10. ^ a b Kishnani, Priya S.; Austin, Stephanie L.; Abdenur, Jose E.; Arn, Pamela; Bali, Deeksha S.; Boney, Anne; Chung, Wendy K.; Dagli, Aditi I.; Dale, David; Koeberl, Dwight; Somers, Michael J. (November 2014). "Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics". Genetics in Medicine. 16 (11): e1. doi:10.1038/gim.2014.128. ISSN 1530-0366. PMID 25356975. 11. ^ Labrune, P.; Trioche, P.; Duvaltier, I.; Chevalier, P.; Odièvre, M. (March 1997). "Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature". Journal of Pediatric Gastroenterology and Nutrition. 24 (3): 276–279. doi:10.1097/00005176-199703000-00008. ISSN 0277-2116. PMID 9138172. 12. ^ a b Wang, David Q.; Carreras, Caroline T.; Fiske, Laurie M.; Austin, Stephanie; Boree, Danielle; Kishnani, Priya S.; Weinstein, David A. (September 2012). "Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib". Genetics in Medicine. 14 (9): 795–799. doi:10.1038/gim.2012.41. ISSN 1098-3600. PMC 3808879. PMID 22678084. 13. ^ David, Weinstein (2019-09-04). "Ultragenyx DTX401 Phase 1/2 Cohort 2 Data Conference Call". edge.media-server.com. Retrieved 2019-10-30. 14. ^ Takamatsu, Yasushi; Jimi, Shiro; Sato, Tomohito; Hara, Shuuji; Suzumiya, Junji; Tamura, Kazuo (January 2007). "Thrombocytopenia in association with splenomegaly during granulocyte-colony-stimulating factor treatment in mice is not caused by hypersplenism and is resolved spontaneously". Transfusion. 47 (1): 41–49. doi:10.1111/j.1537-2995.2007.01061.x. ISSN 0041-1132. PMID 17207228. 15. ^ Chen, Tzu-Lin; Chiang, Ya-Wen; Lin, Guan-Ling; Chang, Hsin-Hou; Lien, Te-Sheng; Sheh, Min-Hua; Sun, Der-Shan (2018-05-02). "Different effects of granulocyte colony-stimulating factor and erythropoietin on erythropoiesis". Stem Cell Research & Therapy. 9 (1): 119. doi:10.1186/s13287-018-0877-2. ISSN 1757-6512. PMC 5930863. PMID 29720275. 16. ^ "Glycogen storage disease type I". Genetics Home Reference from U.S. National Library of Medicine & National Institutes of Health. Retrieved 6 July 2013. 17. ^ a b Bali, DS; Chen, YT; Goldstein, JL; Pagon, RA; Adam, MP; Bird, TD; Dolan, CR; Fong, CT; et al. (1993). "Glycogen Storage Disease Type I". PMID 20301489. Cite journal requires `\|journal=` (help) 18. ^ Online Mendelian Inheritance in Man (OMIM): Glycogen Storage Disease Ib - 232220 19. ^ Online Mendelian Inheritance in Man (OMIM): Glycogen Storage Disease Ic - 232240 20. ^ PARKER, PAUL (1981). "Regression of hepatic adenomas in type Ia glycogen storage disease with dietary therapy". Gastroenterology. 81 (3): 534–536. doi:10.1016/0016-5085(81)90606-5. 21. ^ Minarich, Laurie A.; Kirpich, Alexander; Fiske, Laurie M.; Weinstein, David A. (2013). "Bone mineral density in glycogen storage disease type Ia and Ib". Genetics in Medicine. 14 (8): 737–741. doi:10.1038/gim.2012.36. ISSN 1098-3600. PMC 3884026. PMID 22481133. 22. ^ Soejima, K.; Landing, B. H.; Roe, T. F.; Swanson, V. L. (1985). "Pathologic studies of the osteoporosis of Von Gierke's disease (glycogenosis 1a)". Pediatric Pathology. 3 (2–4): 307–319. doi:10.3109/15513818509078791. ISSN 0277-0938. PMID 3867867. 23. ^ Pan, Bo-Lin; Loke, Song-Seng (2018-01-10). "Chronic kidney disease associated with decreased bone mineral density, uric acid and metabolic syndrome". PLOS ONE. 13 (1): e0190985. Bibcode:2018PLoSO..1390985P. doi:10.1371/journal.pone.0190985. ISSN 1932-6203. PMC 5761949. PMID 29320555. 24. ^ Chou, Janice Y.; Jun, Hyun Sik; Mansfield, Brian C. (January 2010). "Neutropenia in type Ib glycogen storage disease". Current Opinion in Hematology. 17 (1): 36–42. doi:10.1097/MOH.0b013e328331df85. ISSN 1065-6251. PMC 3099242. PMID 19741523. 25. ^ Czapek, Emily E.; Deykin, Daniel; Salzman, Edwin W. (1973-02-01). "Platelet Dysfunction in Glycogen Storage Disease Type I". Blood. 41 (2): 235–247. doi:10.1182/blood.V41.2.235.235. ISSN 0006-4971. 26. ^ Derks, Terry G. J.; van Rijn, Margreet (2015). "Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions". Journal of Inherited Metabolic Disease. 38 (3): 537–543. doi:10.1007/s10545-015-9811-2. ISSN 0141-8955. PMC 4432100. PMID 25633903. 27. ^ Glycogen-Storage Disease Type I at eMedicine 28. ^ https://rarediseases.org/rare-diseases/glycogen-storage-disease-type-i/ Nation Organization for Rare Disorders 29. ^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. pp. 1356. ISBN 978-1437727883. ## Further reading[edit] * GeneReview/NIH/UW entry on Glycogen Storage Disease Type I ## External links[edit] * Media related to Glycogen storage disease type I at Wikimedia Commons Classification D * ICD-10: E74.0 * ICD-9-CM: 271.0 * OMIM: 232200 232240 * MeSH: D005953 * DiseasesDB: 5284 External resources * MedlinePlus: 000338 * eMedicine: ped/2416 * GeneReviews: Glycogen Storage Disease Type I * v * t * e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders Including glycogen storage diseases (GSD) Sucrose, transport (extracellular) Disaccharide catabolism * Congenital alactasia * Sucrose intolerance Monosaccharide transport * Glucose-galactose malabsorption * Inborn errors of renal tubular transport (Renal glycosuria) * Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose: * Essential fructosuria * Fructose intolerance Galactose / galactosemia: * GALK deficiency * GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis * GSD type 0 (glycogen synthase deficiency) * GSD type IV (Andersen's disease, branching enzyme deficiency) * Adult polyglucosan body disease (APBD) Glycogenolysis Extralysosomal: * GSD type III (Cori's disease, debranching enzyme deficiency) * GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency) * GSD type V (McArdle's disease, myophosphorylase deficiency) * GSD type IX (phosphorylase kinase deficiency) Lysosomal (LSD): * GSD type II (Pompe's disease, glucosidase deficiency) Glucose ⇄ CAC Glycolysis * MODY 2/HHF3 * GSD type VII (Tarui's disease, phosphofructokinase deficiency) * Triosephosphate isomerase deficiency * Pyruvate kinase deficiency Gluconeogenesis * PCD * Fructose bisphosphatase deficiency * GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency) Pentose phosphate pathway * Glucose-6-phosphate dehydrogenase deficiency * Transaldolase deficiency * 6-phosphogluconate dehydrogenase deficiency Other * Hyperoxaluria * Primary hyperoxaluria * Pentosuria * Aldolase A deficiency * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical 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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	Glycogen storage disease type I	c0017920	5,926	wikipedia	https://en.wikipedia.org/wiki/Glycogen_storage_disease_type_I	2021-01-18T18:33:56	{"mesh": ["D005953"], "umls": ["C0017920"], "icd-9": ["271.0"], "wikidata": ["Q630090"]}
Anemia caused by medical interventions Iatrogenic anemia Other namesNosocomial anemia, hospital-acquired anemia Excessive blood draws are a major cause of iatrogenic anemia.[1] CausesRepeated blood draws; surgical and medical procedures; intravenous fluid administration[2] PreventionDrawing smaller volumes of blood; using blood conservation devices; limiting laboratory test ordering[1][3] Iatrogenic anemia, also known as nosocomial anemia or hospital-acquired anemia, is a condition in which a person develops anemia due to medical interventions, most frequently repeated blood draws.[1][2][4] Other factors that contribute to iatrogenic anemia include bleeding from medical procedures and dilution of the blood by intravenous fluids.[2] People may receive blood transfusions to treat iatrogenic anemia, which carries risks for complications like transfusion reactions and circulatory overload.[3][5] ## Contents * 1 Incidence and cause * 2 Complications * 3 Prevention * 4 References ## Incidence and cause[edit] A 2013 study of over 400,000 people admitted to US hospitals found that 74% developed anemia at some point during their hospital stay.[5] Iatrogenic anemia is of particular concern in intensive care medicine,[6]:629 because people who are critically ill require frequent blood tests and have a higher risk of developing anemia due to lower hemoglobin levels and impaired production of red blood cells (erythropoesis) at baseline. The average intensive care unit (ICU) patient loses up to 660 mL of blood per week to laboratory testing.[3] For each day in the ICU, it is estimated that a person's hemoglobin level falls by 5 g/L (0.5 g/dL), 80% of which is due to phlebotomy.[7]:20 On the second day of admission to the ICU, more than 70% of adults exhibit anemia, over half of whom will go on to require a blood transfusion.[3] In the neonatal intensive care unit (NICU), the issue is exacerbated by the patients' low body weight: it is estimated that during their first six weeks of life, infants in NICUs may lose 15−30% of their blood volume to blood draws.[3][8] Premature babies often suffer from anemia of prematurity, which is caused by low production of erythropoietin (a hormone that stimulates red blood cell production) and the short lifespan of neonates' red blood cells, and is worsened by blood loss through phlebotomy.[9] People who are receiving dialysis lose blood not only through sampling for laboratory tests, but from the dialysis process itself and from bleeding caused by accessing veins to attach the dialysis equipment. This iatrogenic anemia often occurs alongside the anemia caused by kidney disease.[6]:629 Another factor that contributes to anemia in hospitalized people is the use of intravenous fluids. Infusion with large volumes of intravenous fluids dilutes the blood, causing a decreased hemoglobin and hematocrit level. This is not a true anemia, as no red blood cells are lost and the body eventually compensates for the effects of the infusion. However, the decreased hemoglobin and hematocrit may lead to unnecessary transfusion. Blood loss through surgery and through medical procedures such as central line placement also play a role, as does the use of certain drugs which can suppress the bone marrow's ability to produce red blood cells.[2] ## Complications[edit] People who develop iatrogenic anemia spend a longer amount of time in the hospital and have an increased risk of mortality. They are also more likely to receive blood transfusions,[1] which carries risks for various conditions, including transfusion reactions, lung injury, circulatory overload and alloimmunization.[2][3] After the initial development of anemia, further testing may be ordered to monitor and investigate the condition, which worsens the anemia and the attendant risks for complications.[1] ## Prevention[edit] The volume of blood needed for most laboratory tests is lower than the amount that is commonly drawn; a 2008 study found that only 9% of the blood in standard sized blood tubes was used for testing. Using smaller tubes for blood tests can decrease the risk of anemia, but it may increase the risk of laboratory errors.[3] Point-of-care testing, meaning testing performed at a patient's bedside rather than in a medical laboratory, typically uses much smaller blood volumes than conventional testing; [7]:20 however, as of 2019, there is insufficent evidence regarding the effects of point-of-care testing on iatrogenic anemia. The use of closed blood sampling devices, which return excess blood from blood draws or line flushes to the person's circulation, can decrease the amount of blood loss in hospitalized patients.[3] Strategies to decrease the amount of blood tests ordered, such as clinician education and auditing, or restricting test orders through the electronic health record, have also been investigated.[1] ## References[edit] 1. ^ a b c d e f Eaton, Kevin P.; Levy, Kathryn; Soong, Christine; Pahwa, Amit K.; Petrilli, Christopher; Ziemba, Justin B.; Cho, Hyung J.; Alban, Rodrigo; Blanck, Jaime F.; Parsons, Andrew S. (2017). "Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing". JAMA Internal Medicine. 177 (12): 1833–1839. doi:10.1001/jamainternmed.2017.5152. ISSN 2168-6106. PMID 29049500. 2. ^ a b c d e Martin, Niels D.; Scantling, Dane (2015). "Hospital-Acquired Anemia". Journal of Infusion Nursing. 38 (5): 330–338. doi:10.1097/NAN.0000000000000121. ISSN 1533-1458. PMID 26339939. 3. ^ a b c d e f g h Whitehead, Nedra S.; Williams, Laurina O.; Meleth, Sreelatha; Kennedy, Sara M.; Ubaka-Blackmoore, Nneka; Geaghan, Sharon M.; Nichols, James H.; Carroll, Patrick; McEvoy, Michael T.; Gayken, Julie; Ernst, Dennis J.; Litwin, Christine; Epner, Paul; Taylor, Jennifer; Graber, Mark L. (2019). "Interventions to prevent iatrogenic anemia: a Laboratory Medicine Best Practices systematic review". Critical Care. 23 (1). doi:10.1186/s13054-019-2511-9. ISSN 1364-8535. PMID 31399052. 4. ^ Patricia O'Malley (17 August 2017). Hematologic Issues in Critical Care, an Issue of Critical Nursing Clinics. Elsevier Health Sciences. p. 285. ISBN 978-0-323-54549-5. 5. ^ a b Koch, Colleen G.; Li, Liang; Sun, Zhiyuan; Hixson, Eric D.; Tang, Anne; Phillips, Shannon C.; Blackstone, Eugene H.; Henderson, J. Michael (2013). "Hospital-acquired anemia: Prevalence, outcomes, and healthcare implications". Journal of Hospital Medicine. 8 (9): 506–512. doi:10.1002/jhm.2061. ISSN 1553-5592. PMID 23873739. 6. ^ a b Kenneth Kaushansky; Marshall A. Lichtman; Josef Prchal; Marcel M. Levi; Oliver W. Press; Linda J. Burns; Michael Caligiuri (23 December 2015). Williams Hematology, 9E. McGraw-Hill Education. ISBN 978-0-07-183301-1. 7. ^ a b Toby L. Simon; Jeffrey McCullough; Edward L. Snyder; Bjarte G. Solheim; Ronald G. Strauss (15 March 2016). Rossi's Principles of Transfusion Medicine. John Wiley & Sons. ISBN 978-1-119-01301-3. 8. ^ Carroll, Patrick D.; Widness, John A. (2012). "Nonpharmacological, Blood Conservation Techniques for Preventing Neonatal Anemia—Effective and Promising Strategies for Reducing Transfusion". Seminars in Perinatology. 36 (4): 232–243. doi:10.1053/j.semperi.2012.04.003. ISSN 0146-0005. PMC 3703659. PMID 22818543. 9. ^ Cassady, George (8 January 2016). "Anemia of Prematurity". Medscape. Archived from the original on 24 March 2019. Retrieved 22 May 2020. * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia * v * t * e Medical harm Concepts * Iatrogenesis * Medical malpractice * Medical error * Patient safety * Medical debt * Unnecessary health care * Adverse effect * Patient abuse Related concerns * Adverse drug reaction * Hospital-acquired pneumonia * Hospital-acquired infection * Iatrogenic anemia * Hand washing Records and histories * Drug pollution (List) [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	Iatrogenic anemia	c4524091	5,927	wikipedia	https://en.wikipedia.org/wiki/Iatrogenic_anemia	2021-01-18T19:07:46	{"umls": ["CL525512"], "wikidata": ["Q96381887"]}
A number sign (#) is used with this entry because of evidence that familial hypertrophic cardiomyopathy-3 (CMH3) is caused by heterozygous mutation in the alpha-tropomyosin gene (TPM1; 191010) on chromosome 15q22. For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). Mapping By linkage analysis, Thierfelder et al. (1993) identified a form of familial hypertrophic cardiomyopathy that mapped to chromosome 15q2. This was designated CMH3, CMH1 (192600) being the locus on chromosome 14 and CMH2 (115195) being the locus on chromosome 1. At least one more form of familial CMH is thought to exist because there are families that do not show linkage to any of these 3 locations. Although the gene for cardiac actin (ACTC; 102540) maps to 15q, it was excluded as a candidate gene on the basis of recombination with the CMH3 clinical phenotype (Thierfelder et al., 1993). Schleef et al. (1993) mapped the murine alpha-tropomyosin (TPM1; 191010) gene to a region that is syntenic to human chromosome 15. Because alpha-tropomyosin is an important component of muscle thin filaments, it became a candidate gene for CMH3. Molecular Genetics In affected members of 2 families with hypertrophic cardiomyopathy mapping to chromosome 15q2, Thierfelder et al. (1994) screened the candidate gene TPM1 and identified heterozygosity for 2 missense mutations, E180G (191010.0001) and D175N (191010.0002), respectively. Watkins et al. (1995) concluded that mutations in the TPM1 gene are a rare cause of CMH, accounting for approximately 3% of cases. These mutations, like those in the cardiac troponin T gene (TNNT2; 191045) that cause CMH2 (115195), are characterized by relatively mild and sometimes subclinical hypertrophy but a high incidence of sudden death. Genetic testing may therefore be especially important in this group. In a large Spanish American family with multiple members affected with hypertrophic cardiomyopathy, Karibe et al. (2001) identified a heterozygous missense mutation in the TPM1 gene (V95A; 191010.0003) that segregated with disease. The authors noted that this mutation was associated with the same mild degree of left ventricular hypertrophy as seen in some CMH1 families harboring specific mutations in MYH7 (160760.0010, 160760.0012, 160760.0001). Penetrance was estimated at 53% on the basis of an abnormal echocardiogram; however, 2 mutation carriers with normal echocardiograms and normal ECGs were only in their mid-thirties at the time of the study. Penetrance could not be accurately assessed by ECG, since 6 older mutation-negative family members had minor T-wave changes. Cumulative survival rates in this family were 73% +/- 10% at 40 years and 32% +/- 13% at 60 years. In a 36-year-old woman of Italian extraction with cardiomyopathy, in whom a transthoracic echocardiogram was consistent with a restrictive phenotype (RCM), Caleshu et al. (2011) sequenced the exons and exon-intron boundaries of 8 known cardiomyopathy-associated genes and identified homozygosity for a missense mutation (N279H) in the TPM1 gene. The patient's cardiac catheterization pattern was consistent with a restrictive phenotype, although the dip-plateau ('square-root sign') was absent. Her first-cousin parents were each heterozygous for the mutation. Her affected 75-year-old father had been diagnosed with hypertrophic cardiomyopathy at 42 years of age, and had a history of heart failure but was currently asymptomatic. His most recent echocardiogram showed moderate asymmetric hypertrophy, mild pulmonary hypertension, mild left ventricular systolic dysfunction, and moderate biatrial enlargement, suggesting a chronic restrictive physiology. The asymptomatic 67-year-old mother underwent echocardiography after her daughter's diagnosis that revealed septal and posterior wall thicknesses that were at the upper limit of normal, with mild biatrial enlargement with normal systolic function and no significant evidence of restrictive physiology. Animal Model Muthuchamy et al. (1999) generated a transgenic mouse model of CMH3. They employed site-directed mutagenesis to convert the wildtype murine GAC sequence at codon 175 to AAC, thus introducing the missense mutation asp175 to asn (191010.0002). S1 nuclease mapping and Western blot analysis demonstrated an increase in mutant alpha-tropomyosin mRNA and protein and a concomitant decrease in endogenous mRNA and protein. In vivo studies demonstrated a significant impairment of left ventricular systolic function, and in vitro analysis of papillary muscle fibers showed a decrease in contractile function. Histologic examination of transgenic cardiac tissue showed patchy ventricular myocyte disarray and hypertrophy. This mild and patchy phenotype was in agreement with the clinical features of patients with the asp175-to-asn mutation (Coviello et al., 1997). Cardiac \- Hypertrophic cardiomyopathy Inheritance \- Autosomal dominant (15) \- other forms at loci on chromosomes 1, 11, 14, and at least one other locus ▲ 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	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 3	c1861863	5,928	omim	https://www.omim.org/entry/115196	2019-09-22T16:43:42	{"mesh": ["C566170"], "omim": ["115196"], "genereviews": ["NBK1768"]}
For a phenotypic description and a discussion of genetic heterogeneity of infantile hypertrophic pyloric stenosis (IHPS), see 179010. Mapping By genomewide linkage analysis of a large pedigree in which 7 individuals had infantile hypertrophic pyloric stenosis, Everett et al. (2008) identified a candidate locus on chromosome 16q24 (maximum lod score of 3.7 at SNP rs7197068). Haplotype analysis delineated a 4.2-Mb critical region between rs7197068 and rs750740. Linkage to IHPS2 (610260) on chromosome 16p13-p12 was excluded, as were mutations in the SLC7A5 gene (600182) on chromosome 16q24.3. [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	PYLORIC STENOSIS, INFANTILE HYPERTROPHIC, 5	c2675862	5,929	omim	https://www.omim.org/entry/612525	2019-09-22T16:01:18	{"mesh": ["C567283"], "omim": ["612525"]}
A rare, genetic form of hypophosphatasia (HPP) characterized by markedly impaired bone mineralization in utero due to reduced activity of serum alkaline phosphatase (ALP) and causing stillbirth or respiratory failure within days of birth. ## Epidemiology Incidence of Perinatal lethal hypophosphatasia (PL-HPP) is not known. However, the birth prevalence for severe HPP (both perinatal-lethal and infantile forms) is estimated at 1/300,000in North and West Europe. ## Clinical description Affected infants may have characteristic skin-covered osteochondral spurs protruding from the forearms or legs and often a small thoracic cavity. They may have hypercalcemia associated with apnea or seizures, and marked shortening of the long bones. Patients rarely survive for more than a few days due to inadequate chest size, hypoplastic lungs and rachitic deformities, leading to respiratory failure. ## Etiology Loss of function mutations in the ALPL gene (1p36.12) are known to cause hypophosphatasia. The specific mechanisms underlying PL-HPP have not been elucidated. ## Diagnostic methods Diagnosis is suspected either on prenatal ultrasound findings or clinical presentation at birth, and confirmed by genetic testing (Sanger or next generetation sequencing of ALPL). ## Differential diagnosis A benign form of HPP (prenatal benign HPP) has been described in which skeletal abnormalities resolve spontaneously and patients subsequently develop nonlethal HPP, often adult or childhood HPP. Osteogenesis Imperfecta is the most frequent differential diagnosis of this severe form of HPP. Other differential diagnoses include campomelic dysplasia, chondrodysplasia and Stuve Wiedemann syndrome. ## Antenatal diagnosis Suspicious ultrasound findings include short and/or bowed limbs, skeletal hypomineralization, osteochondral spurs and, sometimes, the absence of certain bones (skull, ribs, vertebrae, pubis). Confirmation by genetic testing is indispensable, although correlation between the genotype and the prognosis remains a challenge. Genetic prenatal testing is also possible in at risk families with a previous index case and where at least one mutation has been identified. ## Genetic counseling The reported pattern of inheritance in this form of HPP is autosomal recessive but is not necessarily predictive of the lethal form of HPP. ## Management and treatment Ventilation support is initiated shortly after birth. Prompt diagnosis is essential in order to start targeted therapy. Asfotase alfa is approved (Europe and USA) for enzyme replacement therapy (ERT) in patients with pediatric-onset hypophosphatasia and is associated with improvement of the skeletal manifestations as well as respiratory and motor function. ## Prognosis Perinatal HPP is of poor prognosis when not treated with ERT; however, long term prognosis with ERT is currently unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA	Perinatal lethal hypophosphatasia	c2673477	5,930	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247623	2021-01-23T17:15:42	{"mesh": ["C567107"], "omim": ["241500"], "umls": ["C2673477"], "icd-10": ["E83.3"], "synonyms": ["Perinatal lethal Rathbun disease", "Perinatal lethal phosphoethanolaminuria"]}
A number sign (#) is used with this entry because it represents a contiguous gene syndrome caused by duplication at chromosome 2q31.1 (chr2:176.7-177.7 Mb, NCBI36). Clinical Features Cho et al. (2010) described a 3-generation Korean family segregating autosomal dominant mesomelic dysplasia and a 2q31.1 duplication (see MOLECULAR GENETICS). A brother and sister and their mother and maternal grandmother all had short stature and distinctively short forearms, although they displayed some clinical variability: the maternal grandmother had relatively mild forearm shortening and less severe short stature, and had normal-looking, well-functioning hands, whereas the mother had complex hand anomalies, including 5 fingers and a hypoplastic triphalangeal thumb on the left hand and 5 fingers without a thumb on the right hand. The mesomelic pattern was not grossly evident in the lower extremities, but radiologic measurements showed relative shortening of the tibia and fibula compared to the femur. Feet and ankles were normal in all affected family members, except for the brother, who was born with right congenital clubfoot. No abnormality was observed in the spine. Cho et al. (2010) noted that the phenotype in this family resembled that of the Kantaputra type of mesomelic dysplasia (MMDK; 156232) in terms of marked radial and ulnar shortening associated with relatively mild tibial or fibular shortening; however, affected members of the Korean family did not have calcaneofibular fusion, carpotarsal synostoses, or tibiofibular synostosis, features that are characteristically seen in MMDK. Ghoumid et al. (2011) reported a father and his 6-year-old daughter with a 2q31.1 duplication who had pendular nystagmus and bilateral cutaneous syndactyly of the third and fourth fingers with normal radiologic findings. Ophthalmologic and neurologic examinations were also normal. Mapping In a 3-generation Korean family segregating autosomal dominant mesomelic dysplasia, Cho et al. (2010) performed genomewide copy number variation analysis and found DNA amplifications of a 1.0-Mb region at chromosome 2q31.1 (chr2:176,659,417-177,679,909, NCBI36) in affected family members that was not found in unaffected individuals. The microduplicated region contains 9 HOXD genes (see, e.g., HOXD3, 142980) and the MTX2 gene (608555). Real-time PCR confirmed the heterozygous microduplication and indicated that the maternal grandmother, who had a milder phenotype, was most likely a somatic mosaic for the microduplication. Cho et al. (2010) noted that the Kantaputra type of mesomelic dysplasia had also been mapped to a chromosomal region comprising 2q31.1, and suggested that MMDK and the condition seen in the Korean family might be allelic. In a father and daughter with pendular nystagmus and bilateral cutaneous syndactyly of the third and fourth fingers, Ghoumid et al. (2011) identified a 3.8-Mb duplication at 2q31.1-q31.2, which involved 27 genes including the entire HOXD cluster. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Eyes \- Nystagmus, pendular (in one family) SKELETAL Limbs \- Radial shortening \- Ulnar shortening \- Tibial shortening \- Fibula shortening Hands \- Hand anomalies, complex (in some patients) \- Triphalangeal thumb, hypoplastic (in 1 patient) \- Cutaneous syndactyly, bilateral, fingers 3-4 (in one family) Feet \- Clubfoot (in some patients) MISCELLANEOUS \- Contiguous gene duplication syndrome \- One 3-generation Korean family and one father daughter have been reported (last curated August 2013) MOLECULAR BASIS \- Caused by 1 to 3.8-Mb duplication on chromosome 2q31.1 ▲ 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	CHROMOSOME 2q31.1 DUPLICATION SYNDROME	c1835009	5,931	omim	https://www.omim.org/entry/613681	2019-09-22T15:57:59	{"doid": ["0060458"], "mesh": ["C535547"], "omim": ["613681"], "orphanet": ["1836"], "synonyms": ["Alternative titles", "MESOMELIC DYSPLASIA, 2q31.1 DUPLICATION-RELATED"]}
Distal myopathy, Tateyama type is a rare, genetic, slowly progressive, distal myopathy disorder characterized by muscle atrophy and weakness limited to the small muscles of the hands and feet (in particular, thenar and hypothenar muscle atrophy), increased serum creatine kinase, and severely reduced caveolin-3 expression on muscle biopsy. Some patients may also show calf hypertrophy, pes cavus, and signs of muscle hyperexcitability. [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	Distal myopathy, Tateyama type	c3280443	5,932	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=488650	2021-01-23T18:09:12	{"omim": ["614321"]}
A number sign (#) is used with this entry because of evidence that immunodeficiency-60 (IMD60) is caused by heterozygous mutation in the BACH2 gene (605394) on chromosome 6q15. Description Immunodeficiency-60 (IMD60) is an autosomal dominant primary immunologic disorder characterized by inflammatory bowel disease and recurrent sinopulmonary infections. The age at symptom onset is highly variable, ranging from infancy to mid-adulthood. Laboratory studies show dysregulation of both B and T cells, with variably decreased immunoglobulin production, decreased T-regulatory cells, and overall impaired lymphocyte maturation (summary by Afzali et al., 2017). Clinical Features Afzali et al. (2017) reported a 19-year-old woman (family A) and adult father and daughter (family B) with a similar immunologic disorder with autoimmune features. All had inflammatory intestinal disease with chronic diarrhea, as well as recurrent sinopulmonary infections. The 19-year-old woman had onset of colitis in infancy, but did not become seriously ill until age 19, when she presented with ongoing colitis, fever, pancytopenia, lymphopenia, immunoglobulin deficiency, recurrent respiratory infections with lung infiltrates, and massive splenomegaly. Colonic biopsy showed inflammatory changes with crypt branching and lymphocytic infiltrates with decreased numbers of FOXP3+ T-regulatory cells. She was treated with high-dose corticosteroids with some response for the acute episode, but laboratory studies showed persistent low B-cell memory subsets and nearly absent B class switch recombination. She was treated with immunoglobulin therapy. In the second family, the father presented in his fifties with recurrent chest infections and sinusitis, and later developed recurrent diarrhea believed to have an inflammatory component, although biopsy was not performed. He had low memory B cells and profoundly decreased immunoglobulin levels. His daughter was diagnosed with ulcerative colitis at age 10 years and underwent colectomy at age 14. At age 32, she was diagnosed with Crohn disease (see 266600); she also had a history of recurrent sinopulmonary infections. She had low B-cell memory subsets and undetectable IgA. Afzali et al. (2017) noted that the immunologic phenotype in these patients was reminiscent of common variable immunodeficiency (CVID). Inheritance The transmission pattern of IMD60 in the families reported by Afzali et al. (2017) was consistent with autosomal dominant inheritance. Molecular Genetics In a woman with IMD60, Afzali et al. (2017) identified a de novo heterozygous missense mutation in the BACH2 gene (L24P; 605394.0001). A father and daughter from a second family with a similar disorder were heterozygous for a different missense mutation (E788K; 605394.0002). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Patient cells showed decreased BACH2 protein expression despite normal mRNA levels, suggesting decreased stability of the mutant proteins. There were also increased levels of PRDM1 (603423), suggesting a release from BACH2 repression. The mutations were demonstrated to result in haploinsufficiency rather than a dominant-negative effect. Patient T lymphocytes showed several abnormalities, including decreased expression of FOXP3 (300292) compared to controls, enhanced T-helper cell differentiation with cells expressing the gut-homing receptors CCR9 (604738) and ITGB7 (147559), and impaired proliferation of CD4+ T cells. Patient B cells showed a marked decrease in memory and IgG class-switched cells as well as an increase in transitional B cells. The findings indicated a defect in B-cell maturation toward memory and plasma cells, similar to that seen in Bach2-null mice (see ANIMAL MODEL). Afzali et al. (2017) emphasized that the BACH2 gene is associated with an archetypal super-enhancer (SE) structural element, which may have broader implications for genetic disorders. Animal Model Afzali et al. (2017) found that heterozygous haploinsufficient Bach2 +/- mice had a reduction in the number of T(reg) cells, increased numbers of gut-specific CD4+ T cells, and impaired B cell antibody class-switching, similar to the phenotype observed in patients with BACH2 haploinsufficiency. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Otitis media, recurrent RESPIRATORY \- Recurrent sinopulmonary infections Lung \- Bronchiectasis \- Lung infiltrates ABDOMEN Spleen \- Splenomegaly Gastrointestinal \- Inflammatory bowel disease \- Colitis \- Recurrent diarrhea Crypt branching \- Inflammatory infiltrate IMMUNOLOGY \- Recurrent infections \- Hypogammaglobulinemia, variable \- Decreased regulatory T cells \- Impaired B cell class switching \- Low memory B cells \- Impaired lymphocyte maturation MISCELLANEOUS \- Variable age at onset (range infancy to adult) \- Variable severity \- Three patients from 2 unrelated families have been reported (last curated April 2019) MOLECULAR BASIS \- Caused by mutation in the BTB and CNC homology 2 gene (BACH2, 605394.0001 ) ▲ 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	IMMUNODEFICIENCY 60	None	5,933	omim	https://www.omim.org/entry/618394	2019-09-22T15:42:10	{"omim": ["618394"], "synonyms": ["Alternative titles", "IMMUNODEFICIENCY AND AUTOIMMUNITY, BACH2-RELATED"]}
## Description Tibial torsion (twisting of the tibia) can cause toeing in or out, depending on whether it is internal or external torsion. Although some degree of internal tibial torsion is present in almost all infants because of the intrauterine position, it usually corrects spontaneously. Persistence of internal tibial torsion may be inherited as an autosomal dominant trait (summary by Fitch, 1974). Clinical Features Blumel et al. (1957) reported a family in which 8 persons in 4 generations had bilateral medial tibial torsion. Bowing of the legs was the main clinical feature. No male-to-male transmission was observed. Inheritance Fitch (1974) observed 6 affected persons in 3 generations, with 1 instance of father-to-son transmission, suggesting autosomal dominant inheritance. Limbs \- Tibial torsion \- Bowlegs \- Tibial scoliosis 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	TIBIAL TORSION, BILATERAL MEDIAL	c1861097	5,934	omim	https://www.omim.org/entry/188800	2019-09-22T16:32:31	{"mesh": ["C566045"], "omim": ["188800"]}
Subtype of a delusional disorder This article is about a delusional disorder. For an abnormally strong or persistent sexual desire, see hypersexuality. Erotomania M.S.P. "Female patient suffering from erotomania," from Alexander Morison's The Physiognomy of Mental Diseases SpecialtyPsychiatry Erotomania is listed in the DSM-5 as a subtype of a delusional disorder.[1] It is a relatively uncommon paranoid condition that is characterized by an individual's delusions of another person being infatuated with them.[2] This disorder is most often seen (though not exclusively) in female patients who are shy, dependent and sexually inexperienced. The object of the delusion is typically a male who is unattainable due to high social or financial status, marriage or disinterest.[2][3] The object of obsession may also be imaginary, deceased or someone the patient has never met. Delusions of reference are common, as the erotomanic individual often perceives that they are being sent messages from the secret admirer through innocuous events such as seeing license plates from specific states, but has no research development proof.[3] Commonly, the onset of erotomania is sudden, and the course is chronic.[3] ## Contents * 1 Presentation * 2 Cause * 3 Treatment * 4 History * 5 Well-known cases * 6 See also * 7 Notes * 8 References * 8.1 Notes * 8.2 Bibliography ## Presentation[edit] Erotomania is more common in women, but men are more likely to exhibit violent and stalker-like behaviors.[3] The core symptom of the disorder is that the sufferer holds an unshakable belief that another person is secretly in love with them. In some cases, the sufferer may believe several people at once are "secret admirers". Most commonly, the individual has delusions of being loved by an unattainable person who is usually an acquaintance or someone the person has never met. The sufferer may also experience other types of delusions concurrently with erotomania, such as delusions of reference, wherein the perceived admirer secretly communicates their love by subtle methods such as body posture, arrangement of household objects, colors, license plates on cars from specific states, and other seemingly innocuous acts (or, if the person is a public figure, through clues in the media). Some delusions may be extreme such as the conception, birth, and kidnapping of children that never existed. The delusional objects may be replaced by others over time, and some may be chronic in fixed forms.[3] Denial is characteristic with this disorder as the patients do not accept the fact that their object of delusion may be married, unavailable, or uninterested. The phantom lover may also be imaginary or deceased. Erotomania has two forms: primary and secondary. Primary erotomania is also commonly referred to as de Clerambault's syndrome and Old Maid's Insanity[4] and it exists alone without comorbidities, has a sudden onset and a chronic outcome.[3] The secondary form is found along with mental disorders like paranoid schizophrenia, often includes persecutory delusions, hallucinations, and grandiose ideas, and has a more gradual onset.[3] Patients with a "fixed" condition are more seriously ill with constant delusions and are less responsive to treatment. These individuals are usually timid, dependent women that are often sexually inexperienced.[3] In those with a more mild, recurrent condition, delusions are shorter-lived and the disorder can exist undetected by others for years.[4] Problematic behaviors include actions like calling, sending letters and gifts, making unannounced house visits and other persistent stalking behaviors.[3] ## Cause[edit] Erotomania may present as a primary mental disorder, or as a symptom of another psychiatric illness. With secondary erotomania, the erotomanic delusions are due to other mental disorders such as bipolar I disorder or schizophrenia. Symptoms may also be precipitated by alcoholism and the use of antidepressants.[5] There may be a potential genetic component involved as family histories of first degree relatives with histories of psychiatric disorders are common. Sigmund Freud explained erotomania as a defense mechanism to ward off homosexual impulses which can lead to strong feelings of paranoia, denial, displacement and projection. Similarly, it has been explained as a way to cope with severe loneliness or ego deficit following a major loss.[3] Erotomania may also be linked to unsatiated urges dealing with homosexuality or narcissism.[4] Some research shows brain abnormalities occurring in patients with erotomania such as heightened temporal lobe asymmetry and greater volumes of lateral ventricles than those with no mental disorders.[4] ## Treatment[edit] Prognosis differs from person to person, and the ideal treatment is not completely understood. Treatment for this disorder gains the best results when tailored specifically for each individual. To date, the mainline pharmacological treatments have been pimozide (a typical antipsychotic which was also approved for treating Tourette's Syndrome),[3][4] and atypical antipsychotics like risperidone and clozapine.[3][4] Non-pharmacologic treatments that have shown some degree of efficacy are electroconvulsive therapy (ECT), supportive psychotherapy, family and environment therapy,[3] rehousing, risk management and treating underlying disorders in cases of secondary erotomania.[4] ECT may provide temporary remission of delusional beliefs; antipsychotics help attenuate delusions and reduce agitation or associated dangerous behaviors, and SSRIs may be used to treat secondary depression.[3] In delusional disorder there is some evidence that pimozide has superior efficacy compared with other antipsychotics. Psychosocial psychiatric interventions can enhance the quality of life through allowing some social functioning, and treating comorbid disorders is a priority for secondary erotomania.[4] Family therapy, adjustment of socio-environmental factors, and replacing delusions with something positive may be beneficial to all. In most cases, harsh confrontation should be avoided.[3] Structured risk assessment helps to manage risky behaviors in those individuals more likely to engage in actions that include violence, stalking, and crime.[4] For particularly troublesome cases, neuroleptics and enforced separation may be moderately effective.[2] ## History[edit] Early references to the condition can be found in the work of Hippocrates, Freud (1911), G.G. de Clérambault (1942),[3] Erasistratus, Plutarch and Galen. Parisian physician, Bartholomy Pardoux (1545-1611) covered the topics of nymphomania and erotomania.[3] In 1623, erotomania was referred to in a treatise by Jacques Ferrand[3] (Maladie d'amour ou Mélancolie érotique) and has been called "erotic paranoia" and "erotic self-referent delusion" until the common usage of the terms erotomania and de Clérambault's syndrome. In 1971 and 1977, M.V. Seeman referred to the disorder as "phantom lover syndrome" and "psychotic erotic transference reaction and delusional loving".[3] Emil Kraepelin and Bernard also wrote of erotomania and more recently, Winokur, Kendler, and Munro have contributed to knowledge on the disorder.[4] G. E. Berrios and N. Kennedy outlined in 'Erotomania: a conceptual history' (2002)[6] several periods of history through which the definition of erotomania has changed considerably: * Classical times – early eighteenth century: General disease caused by unrequited love * Early eighteenth-beginning of nineteenth century: Practice of excess physical love (akin to nymphomania or satyriasis) * Early nineteenth century – beginning twentieth century: Unrequited love as a form of mental disease * Early twentieth century – present: Delusional belief of "being loved by someone else" In one case, erotomania was reported in a patient who had undergone surgery for a ruptured cerebral aneurysm.[7] ## Well-known cases[edit] In his paper that described the syndrome, de Clérambault referenced a patient he had counselled who was obsessed with British monarch George V.[8] She had stood outside Buckingham Palace for hours at a time, believing that the king was communicating his desire for her by moving the curtains.[8] Parallels were drawn between this and a 2011 case where the body of a homeless American man was found on a secluded island in St James Park, within sight of Buckingham Palace. The man had sent hundreds of "strange and offensive" packages to Queen Elizabeth II over the previous 15 years.[8] The assassination attempt on the US President Ronald Reagan by John Hinckley, Jr. has been reported to have been driven by an erotomanic fixation on Jodie Foster, whom Hinckley was attempting to impress. Late night TV entertainer David Letterman and former astronaut Story Musgrave were both stalked by Margaret Mary Ray, who suffered from erotomania.[8] Michael David Barrett allegedly suffered from erotomania, stalking ESPN correspondent Erin Andrews across the country, trying to see her and taking lewd videos.[8] Many cases of obsession or stalking can be linked to erotomania but do not always necessarily go hand in hand. ## See also[edit] * Gaëtan Gatian de Clérambault * Adèle Hugo * Case of Aimée * Delusion * Delusional disorder * Erotolepsy * Limerence * Love addiction * Monomania * Psychosis * Schizophrenia * Stalking * Yandere ## Notes[edit] This section may require cleanup to meet Wikipedia's quality standards. The specific problem is: it appears to be a static and copy-pasted reference section, of possibly no present worth. Please help improve this section if you can. (February 2020) (Learn how and when to remove this template message) * Remington GJ, Jeffries JJ (1994). "Erotomanic delusions and electroconvulsive therapy: a case series". J Clin Psychiatry. 55 (7): 306–8. PMID 8071292. * Anderson CA, Camp J, Filley CM (1998). "Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review". J Neuropsychiatry Clin Neurosci. 10 (3): 330–7. doi:10.1176/jnp.10.3.330. PMID 9706541.CS1 maint: multiple names: authors list (link) * http://www.history.com/news/when-royal-watching-becomes-royal-stalking * https://www.telegraph.co.uk/news/uknews/theroyalfamily/8802614/Royal-family-obsessives-body-lay-near-Buckingham-Palace-for-years.html * Frank Bruni, Behind the Jokes, a Life Of Pain and Delusion; For Letterman Stalker, Mental Illness Was Family Curse and Scarring Legacy, New York Times, November 22, 1998 * Foster, David & Levinson, Arlene. Suicide on a railroad track ends a celebrity-stalker's inner agony Archived 2011-06-14 at the Wayback Machine., Associated Press, October 11, 1998 * Berrios GE, Kennedy N (2002). "Erotomania: a conceptual history". Hist Psychiatry. 13: 381–400. doi:10.1177/0957154X0201305202. PMID 12638595. * Helen K. Gediman (14 December 2016). Stalker, Hacker, Voyeur, Spy: A Psychoanalytic Study of Erotomania, Voyeurism, Surveillance, and Invasions of Privacy. Karnac Books. pp. 21–34. ISBN 978-1-78181-706-3. ## References[edit] ### Notes[edit] 1. ^ Oliveira, C.; Alves, S.; Ferreira, C.; Agostinho, C.; Avelino, M.J. (2016). "Erotomania-A review of De Clerambault's Syndrome". The Journal of the European Psychiatric Association. 33: 664. 2. ^ a b c Segal, J.H. (1989). "Erotomania revisited: From Kraepelin to DSM-III-R". The American Journal of Psychiatry. 146 (10): 1261–1266. doi:10.1176/ajp.146.10.1261. PMID 2675641. 3. ^ a b c d e f g h i j k l m n o p q r s Jordan, H.W.; Lockert, E.W.; Johnson-Warren, M.; Cabell, C.; Cooke, T.; Greer, W.; Howe, G. (2006). "Erotomania revisisted: Thirty-four years later". Journal of the National Medical Association. 98: 787–793. 4. ^ a b c d e f g h i j Kelly, B.D. (2005). "Erotomania: Epidemiology and management". CNS Drugs. 19: 657–669. doi:10.2165/00023210-200519080-00002. 5. ^ Seeman, M.V. (2016). "Erotomania and recommendations for treatment". Psychiatric Quarterly. 87 (2): 355–364. doi:10.1007/s11126-015-9392-0. 6. ^ Berrios GE, Kennedy N (2002). "Erotomania: a conceptual history". History of Psychiatry. 13 (52, pt4): 381–400. 7. ^ Anderson, CA; Camp, J; Filley, C.M. (1998). "Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review". J Neuropsychiatry Clin Neurosci. 10 (3): 330–337. doi:10.1176/jnp.10.3.330. PMID 9706541. 8. ^ a b c d e McDonnell; Margaux; McPadden. (2013). "9 Stalkers That Make Us Glad We're Not Famous". ### Bibliography[edit] * Anderson CA, Camp J, Filley CM (1998). "Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review". J Neuropsychiatry Clin Neurosci. 10 (3): 330–70. doi:10.1176/jnp.10.3.330. PMID 9706541.CS1 maint: multiple names: authors list (link) * Berrios GE, Kennedy N (2002). "Erotomania: a conceptual history". History of Psychiatry. 13: 381–400. doi:10.1177/0957154X0201305202. PMID 12638595. * Helen K. Gediman (14 December 2016). Stalker, Hacker, Voyeur, Spy: A Psychoanalytic Study of Erotomania, Voyeurism, Surveillance, and Invasions of Privacy. Karnac Books. pp. 21–34. ISBN 978-1-78181-706-3. * Jordan H.W., Lockert E.W., Johnson-Warren M., Cabell C., Cooke T., Greer W., Howe G. (2006). "Erotomania revisisted: Thirty-four years later". Journal of the National Medical Association. 98 (5): 787–93.CS1 maint: multiple names: authors list (link) * Kelly B.D. (2005). "Erotomania: Epidemiology and management". CNS Drugs. 19 (8): 657–669. doi:10.2165/00023210-200519080-00002. * McDonnell, Margaux, and Mike McPadden. “9 Stalkers That Make Us Glad We're Not Famous.” CrimeFeed, 12 Nov. 2013, crimefeed.com/2013/10/9-stalkers-that-make-us-glad-were-not-famous/. * Oliveira C., Alves S., Ferreira C., Agostinho C., Avelino M.J. (2016). "Erotomania-A review of De Clerambault's Syndrome". The Journal of the European Psychiatric Association. 33: S664.CS1 maint: multiple names: authors list (link) * Seeman M.V. (2016). "Erotomania and recommendations for treatment". Psychiatric Quarterly. 87: 355–364. doi:10.1007/s11126-015-9392-0. * Segal J.H. (1989). "Erotomania revisited: From Kraepelin to DSM-III-R". The American Journal of Psychiatry. 146 (10): 1261–6. doi:10.1176/ajp.146.10.1261. PMID 2675641. [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	Erotomania	c0022492	5,935	wikipedia	https://en.wikipedia.org/wiki/Erotomania	2021-01-18T18:40:53	{"mesh": ["D019965"], "wikidata": ["Q252185"]}
Methylmalonic acidemia Other namesMMA Methylmalonic acid SpecialtyEndocrinology Methylmalonic acidemia, also called methylmalonic aciduria,[help 1] is an autosomal recessive[1] metabolic disorder that disrupts normal amino acid metabolism.[2] It is a classical type of organic acidemia.[3] The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.[4] Methylmalonic acidemia stems from several genotypes,[5] all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult.[4] Methylmalonic acidemias are found with an equal frequency across ethnic boundaries.[6] ## Contents * 1 Symptoms and signs * 2 Cause * 2.1 Genetic * 2.2 Nutritional * 3 Mechanism * 3.1 Pathophysiology * 3.1.1 Methylmalonyl CoA mutase * 3.1.2 Methylmalonyl CoA epimerase * 3.1.3 Adenosylcobalamin * 3.2 Progression * 4 Diagnosis * 4.1 Types * 5 Treatment * 5.1 Dietary * 5.2 Surgical * 6 Prognosis * 7 Research * 7.1 Nosologic history * 7.2 Neurologic effects * 7.3 Mitochondrial dysfunction * 7.4 Benign mut phenotype * 8 Notable cases * 9 See also * 10 Notes * 11 References * 12 Further reading * 13 External links ## Symptoms and signs[edit] Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening. * Stroke[4] * Progressive encephalopathy[4] * Seizure[4][7] * Kidney failure[4][8] * Vomiting[4][7][8] * Dehydration[4][7][8] * Failure to thrive and developmental delays[4][7][8] * Lethargy[4][7][8] * Repeated Yeast infections[4] * Acidosis[7] * Hepatomegaly[7][8] * Hypotonia[7][8] * Pancreatitis[8] * Respiratory distress[7] ## Cause[edit] ### Genetic[edit] Methylmalonic acidemia has an autosomal recessive pattern of inheritance. Methylmalonic acidemia is caused by a defect in the vitamin B12-dependent enzyme methylmalonyl CoA mutase. The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.[9] Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia. This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder. ### Nutritional[edit] Though not always grouped together with the inherited versions, a severe nutritional deficiency of vitamin B12 can also result in syndrome with identical symptoms and treatments as the genetic methylmalonic acidemias.[10] Methylmalonyl CoA requires vitamin B12 to form succinyl-CoA. When the amount of B12 is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B12 deficiency in serum.[11] ## Mechanism[edit] ### Pathophysiology[edit] In methylmalonic acidemia, the body is unable to break down the amino acids methionine, threonine, isoleucine and valine; as a result methylmalonic acid builds up in the blood and tissues. Those afflicted with this disorder are either lacking functional copies or adequate levels of one or more of the following enzymes: methylmalonyl CoA mutase, methylmalonyl CoA epimerase, or those involved in adenosylcobalamin synthesis.[7][8] #### Methylmalonyl CoA mutase[edit] It is estimated that as many as 60% of cases are the result of a mutated MUT gene which encodes the protein methylmalonyl CoA mutase. This enzyme is responsible for the digestion of potentially toxic derivatives of the breakdown of the above-mentioned amino acids and fats, primarily cholesterol,[8] particularly this enzyme converts methylmalonyl-CoA into succinyl-CoA.[12] Without this enzyme, the body has no means to neutralize or remove methylmalonic acid and related compounds. The action of this enzyme can also be crippled by mutations in the MMAA, MMAB, and MMADHC genes, each of which encodes a protein required for normal functioning of methylmalonyl CoA mutase.[8] #### Methylmalonyl CoA epimerase[edit] Mutations in the MCEE gene, which encodes the methylmalonyl CoA epimerase protein, also referred to as methylmalonyl racemase, will cause a much more mild form of the disorder than the related methymalonyl CoA mutase variant. Like the mutase, the epimerase also functions in breaking down the same substances, but to a significantly lesser extent than the mutase does.[8] The phenotypic differences caused by a deficiency of the epimerase as opposed to the mutase are so mild that there is debate within the medical community as to whether or not this genetic deficiency can be considered a disorder or clinical syndrome.[13] #### Adenosylcobalamin[edit] Also known as vitamin B12, this form of cobalamin is a required cofactor of methylmalonyl CoA mutase. Even with a functional version of the enzyme at physiologically normal levels, if B12 cannot be converted to this active form, the mutase will be unable to function.[8] ### Progression[edit] Though there are not distinct stages of the disease, Methylmalonic acidemia is a progressive condition; the symptoms of this disorder are compounded as the concentration of methylmalonic acid increases. If the triggering proteins and fats are not removed from the diet, this buildup can lead to irreparable kidney or liver damage and eventually death.[4] ## Diagnosis[edit] One of, if not the most common form of organic acidemia,[14] methylmalonic acidemia is not apparent at birth as symptoms usually do not present themselves until proteins are added to the infant's diet.[4] Because of this, symptoms typically manifest anytime within the first year of life.[14] Due to the severity and rapidity in which this disorder can cause complications when left undiagnosed, screening for methylmalonic acidemia is often included in the newborn screening exam.[4][15] Because of the inability to properly break down amino acids completely, the byproduct of protein digestion, the compound methylmalonic acid, is found in a disproportionate concentration in the blood and urine of those afflicted. These abnormal levels are used as the main diagnostic criteria for diagnosing the disorder. This disorder is typically determined through the use of a urine analysis or blood panel.[14] The presence of methylmalonic acidemia can also be suspected through the use of a CT or MRI scan or ammonia test, however these tests are by no means specific and require clinical and metabolic/correlation.[4] Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine.[7] ### Types[edit] Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder.[5] The following are the known genotypes responsible for methylmalonic acidemia: OMIM Name Gene 251100 cblA type MMAA 251110 cblB type MMAB 277400 cblC type MMACHC 277410 cblD type MMADHC[16] 277380 cblF type LMBRD1[17] 251000 mut type MUT The mut type can further be divided in mut0 and mut- subtypes, with mut0 characterized by a complete lack of methylmalonyl CoA mutase and more severe symptoms and mut- characterized by a decreased amount of mutase activity.[6] Mut-, cblB, and cblA versions of methylmalonic acidemia have been found to be cobalamin responsive. Mut0 is a nonresponsive variant.[6] ## Treatment[edit] ### Dietary[edit] Treatment for all forms of this condition primarily relies on a low-protein diet, and depending on what variant of the disorder the individual suffers from, various dietary supplements. All variants respond to the levo isomer of carnitine as the improper breakdown of the affected substances results in sufferers developing a carnitine deficiency. The carnitine also assists in the removal of acyl-CoA, buildup of which is common in low-protein diets by converting it into acyl-carnitine which can be excreted in urine. Though not all forms of methylmalonyl acidemia are responsive to cobalamin, cyanocobalamin supplements are often used in first line treatment for this disorder.[12] If the individual proves responsive to both cobalamin and carnitine supplements, then it may be possible for them to ingest substances that include small amounts of the problematic amino acids isoleucine, threonine, methionine, and valine without causing an attack.[4] ### Surgical[edit] A more extreme treatment includes kidney or liver transplant from a donor without the condition. The foreign organs will produce a functional version of the defective enzymes and digest the methylmalonic acid, however all of the disadvantages of organ transplantation are of course applicable in this situation.[4] There is evidence to suggest that the central nervous system may metabolize methylmalonic-CoA in a system isolated from the rest of the body. If this is the case, transplantation may not reverse the neurological effects of methylmalonic acid previous to the transplant or prevent further damage to the brain by continued build up.[18][12] ## Prognosis[edit] The prognosis will vary depending on the severity of the condition and the individual's response to treatment. Prognosis is typically better for those with cobalamin-responsive variants and not promising in those suffering from noncobalamin-responsive variants.[12] Milder variants have a higher frequency of appearance in the population than the more severe ones.[14] Even with dietary modification and continued medical care, it may not be possible to prevent neurological damage in those with a nonresponsive acidemia.[12] Without proper treatment or diagnosis, it not uncommon for the first acidemic attack to be fatal.[4] Despite these challenges, since it was first identified in 1967, treatment and understanding of the condition has improved to the point where it is not unheard of for even those with unresponsive forms of methylmalonic acidemia to be able to reach adulthood and even carry and deliver children safely.[18] ## Research[edit] ### Nosologic history[edit] MMA was first characterized by Oberholzer et al.[19] in 1967.[18] ### Neurologic effects[edit] That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined. Published on June 15, 2015, research performed on the effects of methylmalonic acid on neurons isolated from fetal rats in an in vitro setting using a control group of neurons treated with an alternate acid of similar pH. These tests have suggested that methylmalonic acid causes decreases in cellular size and increase in the rate of cellular apoptosis in a concentration dependent manner with more extreme effects being seen at higher concentrations. Furthermore, micro-array analysis of these treated neurons have also suggested that on an epigenetic-level methylmalonic acid alters the transcription rate of 564 genes, notably including those involved in the apoptosis, p53, and MAPK signaling pathways.[20] ### Mitochondrial dysfunction[edit] As the conversion of methylmalonyl-CoA to succinyl-CoA takes place inside the mitochondria, mitochondrial dysfunction as a result of diminished electron transport chain function has long been suspected as a feature in MMA. Recent[when?] research has found that in rat models mitochondria of rats affected by the disorder grow to unusual size, dubbed megamitochondria. These megamitochondria also appear to have deformed internal structures and a loss in electron richness in their internal matrix. These megamitochondria also showed signs of decreased respiratory chain function, particularly in respiratory complex IV which only functioned at about 50% efficiency. Similar changes were identified in the mitochondria of a liver sample removed during transplant from a 5-year-old boy suffering from MMA.[21] ### Benign mut phenotype[edit] Recent[when?] case studies in several patients presenting nonresponsive mut0 MMA with a specific mutation designated p.P86L have suggest the possibility of further subdivision in mut type MMA might exist. Though currently unclear if this is due to the specific mutation or early detection and treatment, despite complete nonresponse to cobalamin supplements, these individuals appeared to develop a largely benign and near completely asymptomatic version of MMA. Despite consistently showing elevated methylmalonic acid in the blood and urine, these individuals appeared for the large part developmentally normal.[22] ## Notable cases[edit] * Ryan Stallings, a St. Louis infant, was mistakenly diagnosed with ethylene glycol poisoning instead of MMA in 1989, leading to a wrongful murder conviction and life sentence for his mother, Patricia Stallings.[18] ## See also[edit] * Isovaleric acidemia * Propionic acidemia * Maple syrup urine disease ## Notes[edit] 1. ^ The names methylmalonic acidemia and methylmalonic aciduria, which are also sometimes written as solid compounds (methylmalonicacidemia and methylmalonicaciduria), use the suffixes -emia and -uria and literally mean "[excess] methylmalonic acid in the blood" and "[excess] methylmalonic acid in the urine", respectively; they are used to label both the fluid analysis findings and the disease entity that causes them. ## References[edit] 1. ^ Radmanesh, A; Zaman, T; Ghanaati, H; Molaei, S; Robertson, Rl; Zamani, Aa (July 2008). "Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature". Pediatric Radiology. 38 (10): 1054–61. doi:10.1007/s00247-008-0940-8. PMID 18636250. S2CID 24915585. 2. ^ "MMA Study: FAQ About Our Study". genome.gov. Retrieved April 26, 2016. 3. ^ Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2–3): 383–389. doi:10.1007/s10545-006-0278-z. PMID 16763906. S2CID 19710669. 4. ^ a b c d e f g h i j k l m n o p q r "Methylmalonic acidemia: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-10-27. 5. ^ a b Matsui, Sm; Mahoney, Mj; Rosenberg, Le (April 1983). "The natural history of the inherited methylmalonic acidemias" (Free full text). The New England Journal of Medicine. 308 (15): 857–61. doi:10.1056/NEJM198304143081501. ISSN 0028-4793. PMID 6132336. 6. ^ a b c "MMA Study: General Information". www.genome.gov. Retrieved 2015-11-03. 7. ^ a b c d e f g h i j k "Acidemia, Methylmalonic - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2015-10-29. 8. ^ a b c d e f g h i j k l m "Methylmalonic acidemia". Genetics Home Reference. 2015-10-26. Retrieved 2015-11-02. 9. ^ Sakomoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S (2007). "Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia". Journal of Human Genetics. 52 (1): 48–55. doi:10.1007/s10038-006-0077-2. PMID 17075691. 10. ^ Higginbottom MC, Sweetman L, Nyhan WL (1978). "A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurological abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian". N Engl J Med. 299 (7): 317–323. doi:10.1056/NEJM197808172990701. PMID 683264. 11. ^ http://www.biology.arizona.edu/biochemistry/problem_sets/b12/04t.html Vitamin B12 deficiency - The methylmalonic aciduria connection 12. ^ a b c d e "Methylmalonic Acidemia: Brief Overview of Methylmalonic Acidemia, Etiology and Neuropathology, Evaluation of Methylmalonic Acidemia". 2019-03-05. Cite journal requires `\|journal=` (help) 13. ^ "OMIM Entry- # 251120 - METHYLMALONYL-CoA EPIMERASE DEFICIENCY". www.omim.org. Retrieved November 11, 2015. 14. ^ a b c d Saini, N (March 2015). "Methylmalonic acidemia mimicking diabetic ketoacidosis and septic shock in infants". Indian Journal of Critical Care Medicine. 19 (3): 183–185. doi:10.4103/0972-5229.152776. PMC 4366921. PMID 25810618. 15. ^ Kimberly G Lee. "Newborn screening tests". nih.gov. Division of Neonatology, Medical University of South Carolina, Charleston, SC. Review provided VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Retrieved April 26, 2016. 16. ^ Coelho D, Suormala T, Stucki M, Lerner-Ellis JP, Rosenblatt DS, Newbold RF, Baumgartner MR, Fowler B (2008). "Gene identification for the cblD defect of vitamin B12 metabolism". N Engl J Med. 358 (14): 1454–64. doi:10.1056/NEJMoa072200. PMID 18385497.CS1 maint: multiple names: authors list (link) 17. ^ Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P (Feb 2009). "Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism". Nat Genet. 41 (2): 234–9. doi:10.1038/ng.294. PMID 19136951. S2CID 28006539. 18. ^ a b c d "OMIM Entry - # 251000 - METHYLMALONIC ACIDURIA DUE TO METHYLMALONYL-CoA MUTASE DEFICIENCY". www.omim.org. Retrieved 2015-11-03. 19. ^ Oberholzer VG, Levin B, Burgess EA, Young WF (1967). "Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis". Arch Dis Child. 42 (225): 492–504. doi:10.1136/adc.42.225.492. PMC 2019805. PMID 6061291. 20. ^ Han, L. (Jun 15, 2015). "Insights into the molecular mechanisms of methylmalonic acidemia using microarray technology". International Journal of Clinical and Experimental Medicine. 8 (6): 8866–8879. PMC 4538064. PMID 26309541. Retrieved November 5, 2015. 21. ^ Chandler, Randy j. (December 16, 2008). "Mitochondrial dysfunction in mut methylmalonic acidemia". The FASEB Journal. 23 (4): 1252–1261. doi:10.1096/fj.08-121848. PMC 2660647. PMID 19088183. 22. ^ Underhill, H (December 2013). "Asymptomatic methylmalonic acidemia in a homozygous MUT mutation (p.P86L)". Pediatrics International. 55 (6): e156-8. doi:10.1111/ped.12195. PMID 24330302. ## Further reading[edit] * GeneReviews article on Methylmalonic Acidemia * GeneReviews article on Disorders of Intracellular Cobalamin Metabolism ## External links[edit] Classification D * ICD-10: E71.1 * ICD-10-CM: E71.120 * ICD-9-CM: 270.3 * OMIM: 251000 251100 251110 277380 277400 277410 606169 * DiseasesDB: 29509 External resources * MedlinePlus: 001162 * eMedicine: neuro/576 * v * t * e Inborn error of amino acid metabolism K→acetyl-CoA Lysine/straight chain * Glutaric acidemia type 1 * type 2 * Hyperlysinemia * Pipecolic acidemia * Saccharopinuria Leucine * 3-hydroxy-3-methylglutaryl-CoA lyase deficiency * 3-Methylcrotonyl-CoA carboxylase deficiency * 3-Methylglutaconic aciduria 1 * Isovaleric acidemia * Maple syrup urine disease Tryptophan * Hypertryptophanemia G G→pyruvate→citrate Glycine * D-Glyceric acidemia * Glutathione synthetase deficiency * Sarcosinemia * Glycine→Creatine: GAMT deficiency * Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine * Carnosinemia * Histidinemia * Urocanic aciduria Proline * Hyperprolinemia * Prolidase deficiency Glutamate/glutamine * SSADHD G→propionyl-CoA→ succinyl-CoA Valine * Hypervalinemia * Isobutyryl-CoA dehydrogenase deficiency * Maple syrup urine disease Isoleucine * 2-Methylbutyryl-CoA dehydrogenase deficiency * Beta-ketothiolase deficiency * Maple syrup urine disease Methionine * Cystathioninuria * Homocystinuria * Hypermethioninemia General BC/OA * Methylmalonic acidemia * Methylmalonyl-CoA mutase deficiency * Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria * 6-Pyruvoyltetrahydropterin synthase deficiency * Tetrahydrobiopterin deficiency Tyrosinemia * Alkaptonuria/Ochronosis * Tyrosinemia type I * Tyrosinemia type II * Tyrosinemia type III/Hawkinsinuria Tyrosine→Melanin * Albinism: Ocular albinism (1) * Oculocutaneous albinism (Hermansky–Pudlak syndrome) * Waardenburg syndrome Tyrosine→Norepinephrine * Dopamine beta hydroxylase deficiency * reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine * aspartate) * Argininemia * Argininosuccinic aciduria * Carbamoyl phosphate synthetase I deficiency * Citrullinemia * N-Acetylglutamate synthase deficiency * Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT * Solute carrier family: Cystinuria * Hartnup disease * Iminoglycinuria * Lysinuric protein intolerance * Fanconi syndrome: Oculocerebrorenal syndrome * Cystinosis Other * 2-Hydroxyglutaric aciduria * Aminoacylase 1 deficiency * Ethylmalonic encephalopathy * Fumarase deficiency * Trimethylaminuria * v * t * e Metabolic disorders of vitamins, coenzymes, and cofactors B7 Biotin/MCD * Biotinidase deficiency * Holocarboxylase synthetase deficiency Other B * B5 (Pantothenate kinase-associated neurodegeneration) * B12 (Methylmalonic acidemia) Other vitamin * Familial isolated vitamin E deficiency Nonvitamin cofactor * Tetrahydrobiopterin deficiency * Molybdenum cofactor 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	Methylmalonic acidemia	c0268583	5,936	wikipedia	https://en.wikipedia.org/wiki/Methylmalonic_acidemia	2021-01-18T18:49:36	{"gard": ["7033"], "mesh": ["C537358"], "umls": ["C0268583"], "icd-9": ["270.3"], "icd-10": ["E71.1"], "wikidata": ["Q742500"]}
Closeup of the female navel Navel fetishism, belly button fetishism, or alvinophilia[1][2][3][4] is a partialism in which an individual is attracted to the human navel.[5][6][7][8][9][10][11] According to a study, it is a moderately prevalent fetish among individuals.[12] In 2012, it was the second most popular fetish search on Google as per their global monthly averages.[13] ## Contents * 1 Stimuli * 1.1 Physical activity * 1.2 Viewing and fantasizing activity * 1.3 Literature * 1.4 Erotica * 2 Connections to other fetishes * 3 Prevalence on the Internet * 4 Celebrities * 5 Controversy * 6 See also * 7 References ## Stimuli[edit] Licking the navel is arousing for some A navel fetishist can be sexually aroused by a variety of stimuli, including key words, thoughts or specific forms of physical interaction with the navel.[1][2][14][15][16][17] ### Physical activity[edit] Some navel fetishists find physical acts involving the navel to be turn-ons.[1][14][18][19] Physical acts can include licking the navel with the tongue or rubbing body lotion or suntan oil. Some fetishists get a turn-on from pouring drops of champagne, honey, chocolate sauce, whipped cream, etc., into and around the navel and then licking or sucking it up.[20][21] Similarly, licking or rolling the tongue into the navel while underwater can produce erotic sensations.[16][22][23][24] An ice cube when rubbed over or rested over the navel can produce erotic sensations.[16][25] The navel is an erogenous zone with a heightened sensitivity.[2][26][27] The navel and the region below when touched by the finger or the tip of the tongue result in the production of erotic sensations,[16][27][28][29] and some people are very ticklish to touch in that area.[30] Some people can be aroused by tickling, lickling, blowing raspberries/zerberts (blowing air with lips), and teasing with a feather, flower or a piece of grass, especially when the person is ticklish in the navel.[2][31][32] Fingering the navel is also a common act.[22][23][33] A Belly dancer with a navel piercing. Some prefer to perform navel torture, a series of pain-inflicting acts such as sucking or pulling the navel out (often with a syringe), dripping hot oil or wax into the navel, poking pins into the navel,[34] and stabbing the navel.[1][2][7][35][36] This attention is usually directed at a partner's navel,[34][37] but may include a fixation on the fetishist's own navel.[38][39][40][41] A sex worker in Turkey stated that some men have attempted to have sexual intercourse by inserting their penis into her navel.[42][43] ### Viewing and fantasizing activity[edit] Some navel fetishists can be aroused by viewing a navel. In the case of a heterosexual man, women in bikini is one such example. Also women dressed in low-rise clothing like jeans, shorts etc., that reveals the navel is also considered sexually arousing.[44] Indian journalist Bachi Karkaria once commented, "The navel is an erogenous zone. This is the reason why its exposure is always in fashion. Women have flashed it through the ages because men are turned on by it. It is shown because it wants to be seen".[45] Videos featuring above said physical acts are very common and are viewed worldwide. Their popularity has become more compared to regular porn videos.[46][47] Fetish model Wonderhussy stated in her blog that she had performed in belly button fetish videos in which she laid back and played with her belly button, poking her finger in it and stretching it out.[48] Other models such as Elan kane,[49] Indica[50] etc., have also featured in similar videos. Belly dancers often have navel piercings or insert sequins into their navels to make it look attractive when they perform.[45] Not only them, many young everyday women also have them to add a charm to their navels.[51] Such decorations also arouse when seen.[31] Sometimes just the thought of the navel is enough to stimulate.[52] Some navel fetishists sexually fantasize about the above physical acts on a person's navel to attain sexual pleasure.[53] The Samoan tribe people find the sight of the navel sexually arousing.[54] ### Literature[edit] Sometimes literary works focusing on navels or which sexually symbolize navels can also act as stimuli to navel fetishists. One such work is Navel Revue by author Jay Hahn-Lonne which is an autobiographical study of a man's obsession with navels.[55] In the Song of Songs, a book in the Hebrew Bible, there are allusions to exotic things in nature, with frequent interweaving of nature with erotic imagery. In Solomon's lavish praise of his love – the country girl, Sulaimi – the navel is mentioned as follows: "thy navel is like a round goblet, which wanteth not liquor: thy belly is like a heap of wheat set about with lilies." (7:2).[56][57][58] American poet May Swenson in her poem "Little Lion Face" wrote, "Now I'm bold to touch your swollen neck, put careful lips to slick petals, snuff up gold pollen in your navel cup."[59] and poem "August Night" wrote, "Your navel a little pool in pulsing tide an aura round your knees".[60] Czech-born writer Milan Kundera in his 2015 book The Festival of Insignificance conveys about the eroticism of exposed female navels.[61][62][63] Alain, one of the characters in the book, observes to his friend how most of the young women in Paris wear T-shirts or blouses that expose their midriffs, displaying their navels for all to see. The navel has become, in effect, the new locus of desire.[64][65][66] Robert W. Service in his short poem "Navels" wrote, "Men have navels more or less;....Woman's is a pearly ring,....So dear ladies, recognise The dimpling of your waist Has approval in my eyes,Favour in my taste......How a rosebud navel would Be sweet to kiss!"[67][68][69] In Ancient Indian Sanskrit literature, writers like Adi Shankara, Kālidāsa etc., have symbolized and referred to the navel while describing the beauty of Hindu Goddesses.[70] ### Erotica[edit] During 1970, a short lived "Belly Button Magazine" having only two issues recovered by The Kinsey Institute had descriptions of penetrative belly button intercourse and sexual images of physical acts towards belly buttons.[71][72] In 2011, MTJ Publishing which publishes adult comics released a bellybutton focused series, "Navel Maneuvers 1: Bellybutton-Tickling Erotica"[73] In 2014, a Kindle erotica eBook titled "Bellybutton Fetish: Erotic and naughty stories for bellybutton lovers" was published online through Amazon Digital Services, Inc.[74][75][76] In the same year, MTJ Publishing released a second edition of the Navel Maneuvers series.[77] ## Connections to other fetishes[edit] Navel fetishism often co-exists with stomach fetishism or alvinolagnia.[1][78] Navel fetishism may co-exist with sadomasochism since some navel fetishists prefer to perform or receive navel torture.[79] Some prefer to engage in physical intercourse, which is commonly linked to weight-related stomach fetishes like BBW, feederism, and belly expansion.[80] ## Prevalence on the Internet[edit] During the late nineties, there was a small but thriving online group of belly button fetish sites. These sites were maintained by individuals and usually hosted on third-party forum sites like ProBoards or InsideTheWeb. Each forum catered to a unique variation on the fetish, but were mostly the same in that they had individual boards for celebrity photos, candids, erotica, and personal stories. As the internet outgrew forums in favor of social networks and corporate porn sites, these sites began shutting down one by one. Subsequently, the site The Original Bellybutton Forum (OBF) became popular but got shut down due to admin-related problems. It reconvened with the name BellyLove but met the same fate as OBF.[80] ## Celebrities[edit] Madonna Billie Piper Rebecca Romijn The following are some celebrities who have a fixation for navels. * Renowned singer Madonna in an interview for the May 1985 edition of Spin had said, "My favorite button is my belly button. I have the most perfect belly button: an inny, and there's no lint in it. When I stick my finger in my belly button, I feel a nerve in the center of my body shoot up my spine. If 100 belly buttons were lined up against a wall, I could definitely pick out which one is mine."[81][82] Displaying her bare navel during performances became her trademark.[83] * American actor Sal Mineo had a fetish for navels. His partner Courtney Burr had once commented in an interview that he came to know about Sal Mineo's navel fetish.[84] In the book Sal Mineo: A Biography, author Michael Gregg Michaud wrote, "Sal had an insatiable sex appetite. We were physically opposite," Courtney explained, "but we were completely compatible sexually. We'd go at it for the longest time, take a 20-minute break, and do it again. When we had the chance, we'd do it all day. I discovered his fetish for navels. He loved mine. And he had a strange recurring dream that he was being chased and then stabbed in the navel."[85][86] * British actress Billie Piper stated that her bellybutton is one of her favorite erogenous zones. In an interview for the June 2000 edition of Maxim, she is quoted as saying, "My bellybutton is also very sensitive and ticklish, which is quite a turn-on too."[87] * American actress Rebecca Romijn stated her bellybutton was ticklish in the popular TV show The Tonight Show with Jay Leno during 1999. She was quoted as saying, "Yeah, actually it tickles a lot on my belly button. That is all I am saying. It tickles around my belly button. It did."[88] * British actress Keira Knightley claimed that her navel piercing won her a role in the film Love Actually since its director Richard Curtis was obsessed with her navel. She once commented in an interview, "My mum always wanted it to be my little secret, but it's become a bit of a trademark. Apparently Richard Curtis fell in love with it when he saw BEND IT LIKE BECKHAM. That's how I got to be in his film Love Actually. So when my character got married in Love Actually the wedding dress was designed to expose my bellybutton."[89][90][91] * Geordie Shore star Gary 'Gaz' Beadle's girlfriend Lillie Gregg in an interview said, "Gary's so sweet, considerate and really patient. Oh, and I love his bellybutton."[92] * Lisa Donahue, the winner of Big Brother 3 (U.S.) had once commented in the show, "I can orgasm just from my navel being touched the right way"[93] and later in an interview had said, "Many ask if I can really orgasm with my navel..well, no I can't....I just really like my navel played with!!".[94] * Chilean writer Isabel Allende in a chapter on eggs on one of her books had said, "I like a raw egg served on my lover's navel, with chopped onions, salt, pepper, lemon and a drop of Tobasco".[95][96] * Bollywood yesteryear actress Rati Agnihotri has mentioned in a couple of interviews that the "top spinning on the navel" scene from her 1981 Hindi film Ek Duuje Ke Liye was one of her most memorable filming moments.[97][98] In an interview she stated, "I remember hot rocks, my concave belly and that shot of Kamal spinning the top on my belly. It was so ticklish that I would squeal and squirm, and nearly ruin the shot!".[99] * Telugu movie director Raghavendra Rao has a huge fetish for the navel since his movies always have guaranteed navel show of the heroines.[100][101] He used to include the navel of the heroine in every possible frame[102] and exploit it in song sequences such as dropping of water, flowers, fruits, ice cubes etc., on the navel.[103][104][105][106][107][108][109][110] Legendary Telugu actor and director Dasari Narayana Rao had once commented, "When you see a heroine slightly removing her pallu to show her inside assets, you don't feel ashamed of it because of the artistic way in which Ragahvendra Rao projects it on the screen. Especially heroines' navels look most beautiful in his movies".[111][112][113] * Australian celebrity Tania Zaetta in an interview for the January 1999 edition of FHM Magazine said, "I can't believe the hoo-ha over my goddamn bellybutton. The navel gazing! It went on for over a year."[114] ## Controversy[edit] Maria Menounos American TV personality Maria Menounos said on The Howard Stern Show on June 11, 2012 that she had been sexually abused by multiple doctors during medical examinations and specified about a male gynecologist who had touched her belly button after commenting on how "hot" her belly button piercing was. She had said that she did not want to press charges and make the situation worse.[115][116] ## See also[edit] Main article: Sexual fetishism * Alvinolagnia * Belly dance * Clothing * Bikini * Crop top * Low-rise jeans * Midriff * Navel in popular culture * Navel piercing * Partialism * Omphalomancy * Umbilicoplasty ## References[edit] Wikimedia Commons has media related to Navel fetishism. 1. ^ a b c d e Aggrawal, Anil (2009). Forensic and medico-legal aspects of sexual crimes and unusual sexual practices. Boca Raton, Florida: CRC Press. p. 121. ISBN 978-1420043099. Retrieved 6 July 2014. 2. ^ a b c d e Katie Tandy. 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Retrieved 11 August 2013. * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [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	Navel fetishism	None	5,937	wikipedia	https://en.wikipedia.org/wiki/Navel_fetishism	2021-01-18T18:40:35	{"wikidata": ["Q6982257"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Tracheoinnominate Fistula Other namesTracheal-innominate artery fistula Depicts the anatomical relationships in the formation of a fistula between the trachea and the innominate artery. SpecialtyVascular surgery Tracheoinnominate fistula (TIAF or TIF) is an abnormal connection (fistula) between the innominate artery (brachiocephalic trunk or brachiocephalic artery) and the trachea. A TIF is a rare but life-threatening iatrogenic injury, usually the sequela of a tracheotomy.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Prevention * 5 Treatment * 5.1 Surgery * 6 Prognosis * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms include hemoptysis, and/or massive hemorrhage which result from the formation of a fistula between the trachea and the brachiocephalic artery.[1] The primary threat is respiratory compromise leading to dyspnea and cyanosis. Patients can later present with hypovolemic shock which include symptoms of tachycardia, cyanosis, cold and clammy skin, dizziness, confusion, and fatigue.[2][3] Patients may also develop sepsis.[2][3] ## Causes[edit] The innominate artery usually crosses the trachea at the ninth cartilage ring, however this can vary from the sixth to the thirteenth cartilage ring in patients.[1] A TIF runs between the trachea and the innominate artery. Through this connection blood from within the artery may pass into the trachea or alternatively air from within the trachea may cross into the artery. TIF is a late complication of a tracheotomy and is associated with prolonged endotracheal intubation, as a result of cuff over inflation or a poorly positioned tracheostomy tube.[1][4] Over inflation of the cuff causes the tracheostomy tube to erode into the posterior aspect of the innominate artery leading to the formation of a fistula.[2] The pathogenesis of an TIF by the aforementioned method is pressure necrosis by tracheostomy tube on the tracheal wall.[2] An TIF can also occur due to innominate artery injury as a result of an bronchoscopy.[5] Patients whose tracheotomies are placed beneath the third tracheal ring cartilage and patients with innominate arteries crossing higher on the trachea have an increased risk of developing an TIF.[2] Other factors contributing to the development of TIF include steroids, which weaken the endotracheal mucosa, episodes of hypotension in which the pressure in the tracheostomy tube exceeds that of the endotracheal mucosa, and radiation therapy.[2] An endotracheal tumor can mimic a TIF and present with massive bleeding during a rigid bronchoscopy.[5] ## Diagnosis[edit] Two-thirds of TIF occurs within three weeks of a tracheotomy.[2] A TIF should be on the top of the differential diagnosis in patients with a tracheostomy followed by bleeding.[2][3] Most effective diagnostic tool is a rigid bronchoscopy, although this may be unnecessary as a massive arterial hemorrhage from the tracheostomy likely indicates the formation of an TIF.[1][2] However, a rigid brochoscopy can clear the tracheobronchial tree of aspirated blood and may be used to terminate blood flow.[3] Only 35% of TIF patients exhibit the pathognomonic warning signs which include sentinel bleeding, a small bleed from the tracheostomy in the preceding the TIF, and pulsations of the tracheostomy tube that coincides with the heartbeat.[2][6] ## Prevention[edit] To prevent an TIF, intubation time should be limited to less than 2 weeks and proper techniques should be used when performing tracheotomies.[1] The occurrence of an TIF can be reduced by using more flexible and blunt tracheostomy tubes and insuring that the tubes are properly aligned in the patients.[1] Placing the tracheostomy between the second and third tracheal rings can minimize the risk of an TIF.[1] Repetitive head movements, especially, hyperextension of the neck should be avoided as since this movement results in contact between the innominate artery and the underside of the tube.[4][2] ## Treatment[edit] The formation of a TIF is a medical emergency and requires immediate intervention.[4] Blood volume control, management of the hemorrhage, and adequate oxygenation should be insured in these patients.[3] In a majority of TIF cases (85%), hyperinflation of the tracheostomy cuff will control the bleeding, while the patient is prepared for surgery.[1][2] However, if this fails the tracheostomy cuff must be removed, and the patient must be intubated from above. Next, pressure from the index finger can be applied on the bleeding site from within the tracheostomy to control the bleeding.[2] In addition, the "Utley Maneuver", which involves digital compression of the artery against the posterior wall of the manubrium of the sternum following a right infraclavicular incision, may be used to urgently control the bleeding[1][2] When the bleeding is controlled the patient should be immediately transferred on the operating room.[1][2] ### Surgery[edit] A sternal saw and a rigid bronchoscopy is used during the operation. During the operation, a median sternotomy is performed in order to expose and ligate the involved artery above and below the fistula. Division of the thymus and superior retraction of the innominate vein exposes the innominate artery.[5] The innominate artery should be debrided to healthy tissue and closed with a monofilament suture.[5] Next, the damaged segments of the trachea and the artery should be excised followed by reconstruction with a primary end to end anastomosis of the trachea. Innominate artery ligation leaves the carotid and subclavian circulations intact.[4] Pulsatile back-bleeding from distal innominate artery stump should be checked to insure collateral circulation.[5] In patients with poor pulsatile back-bleeding, an aorta-axillary artery bypass graft can be considered in patients with severe occlusion of the left common carotid artery, severe atherosclerosis, and brain ischemic or hemorrhagic insults.[6] In addition, an autologous vein bypass between the aorta and the carotid artery or the opposite carotid artery and the subclavian artery may be performed to restore normal circulation.[2] The interposition of viable tissue facilitates tracheal wall repair. Thus, vascularized tissues such as the thymus, strap muscles, the sternocleidomastoid, or the pectoralis major muscle should be interposed between tracheal defect and the vessel stumps to prevent bleeding, seal the mediastinum, fill dead space, cover major vital structures, provide a blood supply and venous drainage, and increase the concentration of antibiotics.[2][5] Innominate artery ligation has a 10% risk of neurological deficit.[4] ## Prognosis[edit] TIF is a rare condition with a .7% frequency, and an mortality rate approaching 100% without surgical intervention.[4] Immediate diagnosis and intervention of an TIF is critical for the surgical intervention success.[4][2] 25-30% of TIF patients who reach the operating room survive.[1][2] Recently, the incidence of TIF may have declined due to advances in tracheostomy tube technology and the introduction of the bedside percutaneous dilatational tracheostomy (PDT).[6] ## References[edit] 1. ^ a b c d e f g h i j k l Zervos, Michael D; Melville, H; Prokopakis, E; Bizekis, C (2012). "Chapter 37 Benign & Malignant Disorders of the Trachea.". CURRENT Diagnosis & Treatment in Otolaryngology—Head & Neck Surgery. New York, NY: McGraw-Hill – via Access Medicine. 2. ^ a b c d e f g h i j k l m n o p q r s Ridley, R. W.; Zwischenberger, J. B. (2006-08-01). "Tracheoinnominate fistula: surgical management of an iatrogenic disaster". The Journal of Laryngology & Otology. 120 (8): 676–680. doi:10.1017/S0022215106001514. ISSN 1748-5460. PMID 16709270. 3. ^ a b c d e Grant, C. A.; Dempsey, G.; Harrison, J.; Jones, T. (2006-01-01). "Tracheo-innominate artery fistula after percutaneous tracheostomy: three case reports and a clinical review". British Journal of Anaesthesia. 96 (1): 127–131. doi:10.1093/bja/aei282. ISSN 0007-0912. PMID 16299043. 4. ^ a b c d e f g Fernandez-Bussy, Sebastian; Mahajan, Bob; Folch, Erik; Caviedes, Ivan; Guerrero, Jorge; Majid, Adnan (2015-10-01). "Tracheostomy Tube Placement: Early and Late Complications". Journal of Bronchology & Interventional Pulmonology. 22 (4): 357–364. doi:10.1097/LBR.0000000000000177. ISSN 1948-8270. PMID 26348694. 5. ^ a b c d e f Lu, Chien-Chih; Huang, Yao-Kuang; Liu, Yun-Hen (2006-07-21). "Tracheoinnominate fistula mimicking an endotracheal mass and rupture during rigid bronchoscopy". European Archives of Oto-Rhino-Laryngology. 263 (11): 1051–1054. doi:10.1007/s00405-006-0106-y. ISSN 0937-4477. PMID 16858579. 6. ^ a b c Seung, Won Bae; Lee, Hae Young; Park, Yong Seok (2016-12-10). "Successful Treatment of Tracheoinnominate Artery Fistula Following Tracheostomy in a Patient with Cerebrovascular Disease". Journal of Korean Neurosurgical Society. 52 (6): 547–550. doi:10.3340/jkns.2012.52.6.547. ISSN 2005-3711. PMC 3550423. PMID 23346327. ## External links[edit] Classification D * ICD-10: J95.01 * ICD-9-CM: 519.09 [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	Tracheoinnominate fistula	None	5,938	wikipedia	https://en.wikipedia.org/wiki/Tracheoinnominate_fistula	2021-01-18T18:39:54	{"wikidata": ["Q28449227"]}
## Summary ### Clinical characteristics. Leber hereditary optic neuropathy (LHON) is characterized by bilateral, painless, subacute visual failure that develops during young adult life. Males are four to five times more likely than females to be affected. Affected individuals are usually entirely asymptomatic until they develop visual blurring affecting the central visual field in one eye; similar symptoms appear in the other eye an average of two to three months later. In about 25% of cases, visual loss is bilateral at onset. Visual acuity is severely reduced to counting fingers or worse in the majority of cases, and visual field testing shows an enlarging dense central or centrocecal scotoma. After the acute phase, the optic discs become atrophic. Significant improvement in visual acuity is rare and most persons qualify for registration as legally blind (visual acuity ≤20/200). Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in the general population. Some individuals with LHON, usually women, may also develop a multiple sclerosis-like illness. ### Diagnosis/testing. The diagnosis of LHON is established in a proband with bilateral, painless, subacute visual failure that develops during young adult life and/or by the identification of one of three common mtDNA pathogenic variants (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4, or m.14484T>C in MT-ND6) on molecular genetic testing. ### Management. Treatment of manifestations: Management of affected individuals is largely supportive, with the provision of visual aids, help with occupational rehabilitation, and registration with the relevant social services. ECG may reveal a pre-excitation syndrome in individuals harboring a mtDNA LHON-causing pathogenic variant; referral to cardiology can be considered and treatment for symptomatic individuals is the same as that in the general population. A multidisciplinary approach for those affected individuals with extraocular neurologic features (ataxia, peripheral neuropathy, nonspecific myopathy, and movement disorders) should be considered to minimize the functional consequences of these complications. Prevention of primary manifestations: Treatment for raised intraocular pressure in individuals who have a LHON-causing pathogenic variant. Agents/circumstances to avoid: Individuals harboring a mtDNA LHON-causing pathogenic variant should be strongly advised to moderate their alcohol intake and not to smoke. Avoiding exposure to other putative environmental triggers for visual loss, in particular industrial toxins and drugs with mitochondrial-toxic effects, also seems reasonable. ### Genetic counseling. Leber hereditary optic neuropathy is caused by pathogenic variants in mtDNA and transmitted by mitochondrial (maternal) inheritance. Genetic counseling for LHON is complicated by the gender- and age-dependent penetrance of the primary mtDNA LHON-causing pathogenic variants. The mother of a proband usually has the mtDNA pathogenic variant and may or may not have symptoms. In most cases a history of visual loss affecting maternal relatives at a young age is present, but up to 40% of cases are simplex (i.e., occur in a single individual in a family). A male (affected or unaffected) with a primary LHON-causing mtDNA pathogenic variant cannot transmit the variant to any of his offspring. A female (affected or unaffected) with a primary LHON-causing mtDNA pathogenic variant transmits the variant to all of her offspring. Prenatal diagnosis for mitochondrial pathogenic variants is possible if the variant in a family is known; however, accurate interpretation of a positive prenatal test result is difficult because the mtDNA mutational load in amniocytes and chorionic villi may not correspond to that of other fetal or adult tissues, and the presence of the mtDNA pathogenic variant does not predict the occurrence of disease, age of onset, severity, or rate of disease progression. ## Diagnosis ### Suggestive Findings Leber hereditary optic neuropathy (LHON) should be suspected in individuals with the following ophthalmologic, extraocular, neuroimaging, biochemical, and family history findings: Ophthalmologic * Bilateral, painless subacute visual failure that develops during young adult life * Visual acuity is severely reduced to counting fingers or worse in the majority of cases. * Visual field testing by kinetic or static perimetry shows an enlarging dense central or centrocecal scotoma. * Disk hyperemia, edema of the peripapillary retinal nerve fiber layer, retinal telangiectasia, and increased vascular tortuosity Note: Approximately 20% of affected individuals show no fundal abnormalities in the acute stage. * Optic disc atrophy * Electrophysiologic studies (pattern electroretinogram and visual evoked potentials) demonstrating optic nerve dysfunction and the absence of retinal disease Extraocular * Neurologic abnormalities * Postural tremor * Peripheral neuropathy * Movement disorders * Multiple sclerosis-like illness * Nonspecific myopathy * Cardiac arrhythmias Neuroimaging. Magnetic resonance imaging (MRI) is often normal, but may reveal white matter lesions and/or a high signal within the optic nerves [Matthews et al 2015]. Biochemical studies show respiratory chain defect that is more subtle than that seen in other mitochondrial genetic disorders. The m.3460G>A pathogenic variant in MT-ND1 is associated with the most severe biochemical phenotype (see Table 1). ### Table 1. Respiratory Chain Dysfunction in LHON View in own window Mitochondrial DNA VariantIn VitroIn Vivo Complex I ActivityRespiratory Rate 1MRS 1 m.3460G>A60%-80% less than controls30%-35%0% m.11778G>A0%-50% less than controls30%-50%75% m.14484T>C0%-65% less than controls10%-20%50% See references in Yu-Wai-Man et al [2002]. MRS = magnetic resonance spectroscopy 1\. % of decrease relative to controls Family history of similarly affected individuals is seen in up to 60% of probands. Note: Absence of a family history of LHON does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of LHON is established in a proband with the ocular manifestations listed in Suggestive Findings and/or by the identification of one of three common mtDNA pathogenic variants on molecular genetic testing (see Table 2). Molecular testing approaches can include targeted testing, a multigene panel, or complete mtDNA sequencing. Targeted testing. Three common mtDNA pathogenic variants account for 90%-95% of LHON. Targeted analysis for one of these three variants should be performed first. * m.3460G>A in MT-ND1 * m.11778G>A in MT-ND4, present in 70% of affected individuals of northern European descent and 90% of affected individuals of Asian descent [Mackey et al 1996, Mashima et al 1998, Jia et al 2006] * m.14484T>C in MT-ND6, commonly found among French Canadians due to a founder effect [Mackey et al 1996, Macmillan et al 1998, Chinnery et al 2001, Yu-Wai-Man et al 2003] A multigene panel that includes the mitochondrial genes that encode subunits of NADH dehydrogenase, MT-ND1, MT-ND2, MT-ND4, MT-ND4L, MT-ND5, and MT-ND6, which are known to cause LHON (see Table 5 [pdf]) and other genes of interest (see Differential Diagnosis) may also be considered. Note: The genes included and the sensitivity of multigene panels vary by laboratory and over time. Complete mtDNA sequencing may be considered if use of targeted testing and/or a multigene panel did not identify a pathogenic variant, clinical suspicion remains high, and there is no evidence of paternal transmission. ### Table 2. Molecular Genetic Testing Used in Leber Hereditary Optic Neuropathy (LHON) View in own window Gene 1Proportion of LHON Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detected by Method Targeted analysis for pathogenic variantsSequence analysis 3Gene-targeted deletion/duplication analysis 4 MT-ND4, MT-ND6, MT-ND1~90% 5, 6See footnote 790% 6None reported 6 Select mitochondrial genes~10% 6, 810% 6None reported 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 5\. Mackey et al [1996] 6\. Mitomap 7\. The three most common pathogenic variants are: m.11778G>A (MT-ND4), accounting for approximately 70% of cases among northern European populations [Wallace et al 1988, Mackey et al 1996]; m.14484T>C (MT-ND6), most common among French Canadians as a result of a founder effect [Johns et al 1992a, Macmillan et al 1998]; and m.3460G>A (MT-ND1) [Howell et al 1992]. 8\. Achilli et al [2012] Interpretation of test results. Heteroplasmy, a mixture of mutated and wild type mtDNA in leukocytes, occurs in approximately 10%-15% of individuals with LHON [Smith et al 1993, Yu-Wai-Man et al 2003]. * Heteroplasmy does not influence the sensitivity of molecular genetic testing for LHON because affected individuals generally have more than 70% mutated mtDNA in leukocytes, which is easily detected by standard techniques. * It is likely that the level of heteroplasmy may have a bearing on the risk of developing LHON in the asymptomatic individual and on the risk for transmission [Chinnery et al 2001]; however, no rigorous prospective studies have been performed to clarify this possibility. ## Clinical Characteristics ### Clinical Description Leber hereditary optic neuropathy (LHON) typically presents in young adults as bilateral, painless, subacute visual failure. The peak age of onset in LHON is in the second and third decades of life, with 95% of those who lose their vision doing so before age 50 years. Very rarely, individuals first manifest LHON in the seventh and eighth decades of life [Dimitriadis et al 2014]. Males are four to five times more likely to be affected than females, but neither gender nor mutational status significantly influences the timing and severity of the initial visual loss. In the presymptomatic phase, fundal abnormalities including peripapillary telangiectatic vessels and variable degrees of retinal nerve fiber layer edema have been previously documented; these can vary with time [Nikoskelainen 1994]. Using optical coherence tomography imaging, thickening of the temporal retinal nerve fiber layer was confirmed in clinically unaffected individuals with a LHON-causing mtDNA pathogenic variant, providing further evidence that the papillomacular bundle is particularly vulnerable in LHON [Savini et al 2005]. On more detailed investigation, some individuals with a LHON-causing mtDNA pathogenic variant can also exhibit subtle impairment of optic nerve function including: (a) loss of color vision affecting mostly the red-green system, (b) reduced contrast sensitivity, and (c) subnormal electroretinogram and visual evoked potential [Sadun et al 2006]. Affected individuals are usually entirely asymptomatic until they develop visual blurring affecting the central visual field in one eye (acute phase); similar symptoms appear in the other eye an average of two to three months later, so that both eyes are affected in the majority of cases within six months. Unilateral optic nerve involvement in LHON is exceptionally rare; if it is present, another underlying pathologic process should be actively excluded. In about 25% of cases, visual loss is bilateral at onset. The most characteristic feature is an enlarging central or centrocecal scotoma and as the field defect increases in size and density, visual acuity deteriorates to the level of counting fingers or worse. Following the nadir, visual acuity may improve; such improvement is more likely in individuals with the m.14484T>C pathogenic variant than in those with the m.11778G>A or m.3460G>A pathogenic variant (see Genotype-Phenotype Correlations). Other positive prognostic factors have been identified including an earlier age of onset (<10 years), a subacute presentation with slow visual deterioration, and a relatively large optic disc [Barboni et al 2006, Ramos et al 2009]. The atrophic phase is characterized by optic atrophy (which typically develops within six weeks of the onset of visual loss) and a dense central or centrocecal scotoma. Most persons remain severely visually impaired and are within the legal requirements for blind registration [Kirkman et al 2009]. Other neurologic features associated with LHON. Some neurologic abnormalities (e.g., postural tremor, peripheral neuropathy, nonspecific myopathy, movement disorders, and Leigh syndrome) have been reported to be common in individuals with LHON [McFarland et al 2007, Martikainen et al 2016]. Some individuals with LHON, usually women, may develop a progressive multiple sclerosis (MS)-like illness. The pattern of visual loss in LHON-MS appears distinct from classic LHON, being marked by recurrent episodes of visual loss that can be associated with ocular pain, but with incomplete visual recovery and progression to legal blindness in half of all affected persons [Pfeffer et al 2013]. In addition to a severe bilateral optic neuropathy, these individuals manifest disseminated central nervous system demyelination, with characteristic periventricular white matter lesions and unmatched cerebrospinal fluid oligoclonal bands [Bhatti & Newman 1999, Horváth et al 2000, Palace 2009]. Cardiac conduction defects and LHON. A Finnish study showed an increased incidence of cardiac arrhythmias secondary to accessory pathways in association with LHON [Nikoskelainen 1994]; this finding has not been replicated in other populations [Bower et al 1992]. ### Genotype-Phenotype Correlations Some broad categorization can be made with regard to specific LHON-causing pathogenic variants: * m.3460G>A is associated with the worst impairment in visual function. * m.11778G>A has an intermediate phenotype. * m.14484T>C is associated with the best long-term visual outcome. It must be emphasized that recovery of visual function in LHON, if it does occur, is usually incomplete. Reported visual recovery rates among persons with LHON are summarized in Table 3; the lifetime risk for visual failure in individuals with a homoplasmic primary LHON-causing pathogenic variant by sex and age is summarized in Table 4. ### Table 3. Visual Recovery Rates by Pathogenic Variant in Individuals with LHON View in own window Mitochondrial DNA VariantVisual Recovery 1References m.11778G>A4%-25%Newman et al [1991], Harding et al [1995], Lam et al [2014] m.14484T>C37%-64%Johns et al [1993], Macmillan et al [1998], Spruijt et al [2006] m.3460G>A15%-25% 2Johns et al [1992b], Harding et al [1995], Spruijt et al [2006] 1\. Different criteria have been used to define visual recovery; the range partly reflects this variability. 2\. Although published reports would appear to indicate otherwise, the m.3460G>A pathogenic variant is generally accepted among experts as having the worst visual recovery rate [Author, personal communication]. ### Table 4. Lifetime Risk for Visual Failure in Individuals with a Homoplasmic Primary LHON-Causing Mitochondrial DNA Pathogenic Variant by Study View in own window Mitochondrial DNA Pathogenic VariantRisk of Developing SymptomsMedian Age at Onset (Males)Male/Female RatioReference MalesFemales m.3460G>A32%15%20 yrs4.3:1Nikoskelainen [1994] m.3460G>A49%28%22 yrs1.7:1Yu-Wai-Man et al [2003] m.11778G>A43%11%24 yrs3.7:1Harding et al [1995] m.11778G>A51%9%22 yrs5.1:1Yu-Wai-Man et al [2003] m.14484T>C47%8%20 yrs7.7:1Macmillan et al [1998] A multiple sclerosis-like illness has been reported in association with all three primary mtDNA LHON-causing pathogenic variants (m.3460G>A, m.11778G>A, and m.14484T>C), but with a female bias [Pfeffer et al 2013]. ### Penetrance LHON-causing mtDNA pathogenic variants are characterized by reduced penetrance. An individual can only develop LHON if a pathogenic mtDNA LHON-causing variant is present, but approximately 50% of males and 90% of females who harbor a primary LHON-causing mtDNA pathogenic variant do not develop blindness. It must be stressed that penetrance can vary markedly in different branches of the same family and between families harboring the same LHON-causing mtDNA pathogenic variants, which complicates genetic counseling at the individual level. Additional environmental and genetic factors interact with the primary mtDNA pathogenic variant and determine whether an individual ultimately develops optic nerve dysfunction and visual failure. The two most important risk factors for visual loss are sex and age (see Table 4) [Yu-Wai-Man et al 2009]. * Age-related penetrance of LHON. The penetrance of LHON is age specific. The 95th centile for age at onset is 50 years for all three primary pathogenic variants. Thus, a clinically unaffected male age 50 years has less than a 1/20 chance of losing his vision [Yu-Wai-Man et al 2003]. * Heteroplasmy. Many mitochondria (and thus many mtDNA molecules) are present in each cell. Some individuals with a pathogenic LHON-causing mtDNA variant have a mixture of mutated and wild type species of mtDNA, a finding referred to as heteroplasmy. Heteroplasmy is present in 10%-15% of individuals with a LHON-causing mtDNA variant. In one study, individuals with a m.11778G>A pathogenic variant load of less than 75% in their leukocytes were unaffected [Smith et al 1993]. In a retrospective analysis of 17 families heteroplasmic for the m.11778G>A pathogenic variant, males with a mutational load greater than 60% in their leukocytes had an increased frequency of optic neuropathy than did those with lower mutational loads [Chinnery et al 2001]. However, quantifying the level of heteroplasmy for the purpose of presymptomatic testing is limited as the majority of individuals with a LHON-causing mtDNA variant are homoplasmic. ### Anticipation Anticipation has not been seen in LHON. ### Nomenclature In the past, LHON was sometimes referred to as Leber hereditary optic neuroretinopathy; this term is outdated and should not be used. ### Prevalence In the North East of England, 1:8,500 individuals were found to harbor a pathogenic LHON-causing variant; 1:31,000 had experienced visual loss as a result of LHON [Yu-Wai-Man et al 2003, Gorman et al 2015]. Fairly similar figures have been reported in other northern European populations, with a disease prevalence of 1:39,000 in the Netherlands and 1:50,000 in Finland [Spruijt et al 2006, Puomila et al 2007]. ## Differential Diagnosis If the ophthalmologic assessment (including an assessment of visual acuity, color vision, visual fields, and electrophysiology) and molecular genetic testing leave any uncertainty about the diagnosis of Leber hereditary optic neuropathy (LHON), further investigations are appropriate to exclude other potentially reversible causes of bilateral optic neuropathy and to allow for the initiation of prompt treatment before visual loss becomes irreversible. Depending on the clinical presentation and evolution, autoantibody testing and an infectious or vasculitic screen may be warranted. A lumbar puncture should be performed when clinically indicated to evaluate for unmatched oligoclonal bands in suspected cases of demyelination or to exclude infectious and neoplastic causes. The appropriate neuroimaging modality should be requested and the films should ideally be reviewed with an experienced neuroradiologist. Acute phase. A wide range of non-genetic causes of bilateral visual failure must be excluded during the acute phase. Atrophic phase. If an individual is only seen at this stage, it can be difficult to exclude other possible causes of optic atrophy, especially if there is no clear maternal family history. In these cases, neuroimaging of the anterior visual pathways is mandatory while awaiting the results of molecular genetic testing. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Leber hereditary optic neuropathy (LHON), the following evaluations are recommended: * Measurement of best corrected visual acuity * Assessment of visual fields with static or kinetic perimetry * ECG. Although a relatively rare finding, an ECG may reveal a pre-excitation syndrome in both symptomatic and asymptomatic individuals who have a LHON-causing mtDNA variant. Even when present, such an ECG finding does not necessitate further intervention in the absence of cardiac symptoms. * Screening for possible associated neurologic complications, which can further compound the visual impairment among individuals with LHON * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Management of affected individuals is supportive and includes provision of visual aids, occupational rehabilitation, and registration with the relevant local social services. A minority of individuals with LHON develop neurologic features including ataxia, peripheral neuropathy, nonspecific myopathy, and movement disorders. This group of affected individuals should be managed by a multidisciplinary team of physicians and allied professionals to minimize the functional consequences of these neurologic complications. In those individuals who are found to have pre-excitation syndrome on ECG, referral to a cardiologist can be considered; treatment for symptomatic individuals with pre-excitation syndrome is the same as in the general population. ### Prevention of Primary Manifestations There is evidence that raised intraocular pressure could be a risk factor triggering visual loss in individuals at risk for developing LHON. Until further evidence becomes available, it is reasonable to set a lower threshold for initiating treatment for raised intraocular pressure in individuals with a LHON-causing variant given the possible deleterious consequences of raised intraocular pressure on mitochondrial function and retinal ganglion cell survival [Thouin et al 2013]. ### Surveillance Ongoing surveillance of asymptomatic individuals harboring LHON-causing mtDNA variants is not necessary; however, they should be advised to seek immediate medical attention should they experience any visual disturbance. The frequency of follow-up for affected individuals varies depending on the individual's personal circumstances and the availability of health care locally. ### Agents/Circumstances to Avoid Individuals harboring established LHON-causing mtDNA variants should be strongly advised not to smoke and to moderate their alcohol intake, avoiding binge-drinking episodes. Although based largely on anecdotal evidence, avoidance of other environmental factors that have been implicated in precipitating visual loss in LHON (e.g., head trauma, industrial toxins, drugs with mitochondrial toxic effects) would seem reasonable. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Idebenone. Small case series have reported that oral administration of idebenone (a short-chain synthetic benzoquinone; 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone) and/or vitamin supplementation (B12 and C) can accelerate visual recovery and improve final visual outcome in patients with LHON [Mashima et al 2000, Carelli et al 2001]. A subsequent report of two individuals with LHON showed no visual benefit from idebenone and multivitamin supplementation [Barnils et al 2007]. To address these conflicting anecdotal findings, a Phase II double-blind randomized placebo-controlled trial was conducted to investigate the efficacy, safety, and tolerability of oral idebenone in LHON: RHODOS (Rescue of Hereditary Optic Disease Outpatient Study). In total, 85 affected individuals harboring one of the three primary mtDNA LHON-causing variants (m.3460G>A, m.11778G>A, and m.14484T>C) were successfully enrolled in this multicenter study [Klopstock et al 2013]. Research subjects were assigned in a two-to-one randomization ratio to receive either idebenone (at a dose of 300 mg/3x/day) or placebo. This dose of idebenone was found to be safe with no significant drug-related adverse events. Affected individuals with discordant visual acuities (defined as a difference of >0.2 LogMAR between the two eyes) and at highest risk for further visual loss in the least affected eye were more likely to benefit from treatment with idebenone [Klopstock et al 2011]. In the follow-up study (RHODOS-OFU), the beneficial effect of six months of treatment with idebenone appeared to persist despite discontinuation of the active medication at the end of the trial [Klopstock et al 2013]. In a large retrospective study involving 103 individuals with LHON, 44 with visual loss of one year's duration or less were treated with idebenone and followed up for at least five years. A greater proportion of those in the treated group recovered vision compared with the untreated group, and the most consistent factor associated with visual recovery was an early initiation of treatment during the acute phase of the disease process [Carelli et al 2011]. It must be stressed that idebenone will not completely reverse the significant damage already sustained to the optic nerve, but in those affected individuals who do respond, there is an increased rate and likelihood of visual recovery compared with the known natural history. There is no evidence to support the prophylactic use of idebenone among asymptomatic individuals with LHON-causing mtDNA variants. EPI-743. In an open-label study of five individuals with acute LHON treated within 90 days of disease conversion, the antioxidant α-tocotrienol-quinone (EPI-743), a vitamin E derivative, has shown early promise [Sadun et al 2012]. An adequately powered, double-blind, randomized placebo-controlled trial is needed to confirm the visual benefit of this agent in both acute and chronic LHON [Sadun et al 2012]. Gene therapy. Targeted gene therapy for LHON is being actively explored for affected individuals harboring the m.11778G>A pathogenic variant [Qi et al 2003, Qi et al 2004, Qi et al 2007, Ellouze et al 2008, Lam et al 2010]. Promising pre-clinical data based on in vitro and rodent models have resulted in the recent launch of pivotal clinical trials for affected individuals with the m.11778G>A pathogenic variant involving the intravitreal injection of a modified adeno-associated virus (AAV2) vector carrying the replacement MTND4 subunit (see ClinicalTrials.gov). Hormone therapy. The marked male bias in LHON could reflect a protective influence of female sex hormones, and this hypothesis was recently investigated using LHON cybrid cell lines. Treatment with estrogens was found to reduce reactive oxygen species levels in these LHON cybrids, with increased activity of the antioxidant enzyme superoxide dismutase. These beneficial estrogenic effects translated into more efficient mitochondrial oxidative phosphorylation [Giordano et al 2011]. Further research is needed to determine whether females with a LHON-causing variant are at increased risk for visual loss in the perimenopausal period and following the onset of menopause. Mitochondrial replacement. In vitro fertilization (IVF) techniques aimed at preventing the maternal transmission of mtDNA pathogenic variants from mother to child are being developed. Pronuclear transfer and metaphase II spindle transfer are the two approaches that are being investigated, and further experimental work to validate the safety and potential clinical applicability of these IVF strategies is currently ongoing [Tachibana et al 2009, Craven et al 2010, Chinnery et al 2014]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. [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	Leber Hereditary Optic Neuropathy	c0917796	5,939	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1174/	2021-01-18T21:15:19	{"mesh": ["D029242"], "synonyms": ["LHON", "Leber's Disease", "Leber's Optic Atrophy", "Leber's Optic Neuropathy"]}
A rare neurologic disease characterized by unpredictable, transient and spontaneous unresponsiveness lasting from hours to days, with a frequency of three to seven attacks per year, in the absence of readily discernible toxic, metabolic or structural causes. [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	Idiopathic recurrent stupor	c4706562	5,940	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276174	2021-01-23T18:15:44	{}
Condition where a certain body part grows larger than normal size Local gigantism affecting second toe of a child Local gigantism or localised gigantism is a condition in which a certain part of the body acquires larger than normal size due to excessive growth of the anatomical structures or abnormal accumulation of substances. It is more common in fingers and toes, where it is termed macrodactyly. However, sometimes an entire limb may be enlarged. ## Contents * 1 Causes * 1.1 Congenital * 1.2 Acquired * 2 Treatment * 3 References * 4 External links ## Causes[edit] Local gigantism may be caused by a heterogeneous group of both congenital and acquired conditions. ### Congenital[edit] Congenital causes include: * Klippel Trenaunay Weber syndrome * Maffucci syndrome * macrodystrophia lipomatosa[1] * neurofibromatosis,[2][3] * lipoatrophic diabetes.[4] * Proteus syndrome, which by one theory accounts for the deformities of the Elephant Man ### Acquired[edit] There are a number of acquired causes of local gigantism. A body part can attain bigger size from causes as common as the following: * inflammation, due to trauma or infection * tumors like osteoid osteoma, melorheostosis, and lipofibromatous hamartoma[5] * Arteriovenous malformations occurring on a limb, before the closure of epiphyses in long bones[6] * Elephantiasis, which is quite common in south-east asia due to prevalence of filariasis. * Still's disease * amyloidosis * acromegaly ## Treatment[edit] As the causes of local gigantism are varied, treatment depends on the particular condition. Treatment may range from antibiotics and other medical therapy, to surgery in order to correct the anatomical anomaly. ## References[edit] 1. ^ Letter to the Indian Journal of Radiology and Imaging Archived September 7, 2015, at the Wayback Machine 2. ^ Lassmann H, Gebhart W, Mamoli B, Niebauer G (1977). "Nervous lesions in a case of local gigantism". Acta Neuropathol. 38 (2): 109–15. doi:10.1007/BF00688556. PMID 878849. 3. ^ Chung IH, Kim NH, Choi IY (1973). "Macrodactylism associated with neurofibroma of the median nerve. A case report". Yonsei Med. J. 14: 49–52. PMID 4804132. 4. ^ Some case reports[permanent dead link] 5. ^ Razzaghi A, Anastakis DJ (2005). "Lipofibromatous hamartoma: review of early diagnosis and treatment". Canadian Journal of Surgery. 48 (5): 394–9. PMC 3211895. PMID 16248139. 6. ^ Case report Archived May 14, 2006, at the Wayback Machine ## External links[edit] * "Gigantism". Medcyclopaedia. GE. Archived from the original on 4 February 2012. Retrieved 6 March 2006. [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	Local gigantism	None	5,941	wikipedia	https://en.wikipedia.org/wiki/Local_gigantism	2021-01-18T18:44:19	{"orphanet": ["294953"], "synonyms": [], "wikidata": ["Q6664372"]}
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600). Mapping In a genomewide association study involving DNA samples from 988 patients with ileal Crohn disease and 1,007 controls, Rioux et al. (2007) found significant association with rs224136, located in an intergenic region on chromosome 10q21. Two independent replication cohorts, involving 530 patients with ileal CD and their parents and 353 individuals with CD and 207 controls, respectively, confirmed the association (combined p less than 10(-10)). Using an array custom-made for the Wellcome Trust Case Control Consortium (2007) and a staged experimental design, Fisher et al. (2008) genotyped a total of 3,133 unrelated patients with ulcerative colitis and 4,494 controls and found association at rs10761659 in what the authors described as a 'gene desert' on chromosome 10q21. Franke et al. (2008) investigated 50 previously reported susceptibility loci in a German sample of 1,850 individuals with Crohn disease, 1,103 with ulcerative colitis, and 1,817 controls and observed a significant association with rs10761659 for both CD (p = 8.25l x 10(-5)) and UC (p = 0.0052). In a study involving 2,731 Dutch and Belgian IBD patients (including 1,656 CD patients and 1,075 UC patients) and 1,086 controls, Weersma et al. (2009) replicated association at rs10761659 for CD (corrected p = 3.58 x 10(-3); odds ratio, 0.75) but did not find significant association with UC. In a metaanalysis of data from 3 studies of Crohn disease involving a total of 3,230 cases and 4,829 controls (Rioux et al., 2007, the Wellcome Trust Case Control Consortium, 2007, and Libioulle et al., 2007) with replication in 3,664 independent cases, Barrett et al. (2008) identified significant association with rs10995271 at 10q21 (combined p = 4.46 x 10(-20); case-control odds ratio, 1.25). Glas et al. (2009) attempted to replicate the findings of the North American genomewide ileal Crohn disease association study by Rioux et al. (2007) in a European cohort involving 854 German patients with CD, 476 with ulcerative colitis, and 1,503 healthy controls. Glas et al. (2009) found no association between CD and rs224136, a SNP in the intergenic region on chromosome 10q21.1, even after subanalysis of 529 German patients with an ileal CD phenotype; they concluded that these findings were likely due to ethnic differences between the North American and European IBD populations. ### Possible Role in Inflammatory Bowel Disease For discussion of a possible role of the SIRT1 gene in inflammatory bowel disease mapping to chromosome 10q21, see 604479.0001. [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	INFLAMMATORY BOWEL DISEASE 15	c2677094	5,942	omim	https://www.omim.org/entry/612255	2019-09-22T16:02:02	{"mesh": ["C567381"], "omim": ["612255"]}
## Description The designation 'antiphospholipid syndrome' was proposed for the association of arterial and venous thrombosis, recurrent fetal loss, and immune thrombocytopenia with a spectrum of autoantibodies directed against cellular phospholipid components. Anticardiolipin antibodies may react with cardiolipin and with other negatively charged phospholipids, including beta-2-glycoprotein I (B2GPI, APOH; 138700). The term 'lupus anticoagulant' refers to a heterogeneous group of antibodies, most commonly of the IgG type, that are detected by their inhibitory effect on coagulant-active phospholipid components of in vitro coagulation tests (summary by Matthey et al., 1989). Shoenfeld et al. (2008) noted that antiphospholipid syndrome is characterized by up to 30 different autoantibodies, including those against platelets, glycoproteins, coagulation factors, lamins, mitochondrial antigens, and cell surface markers. Some of these may have an additive effect on the prothrombotic tendency of the syndrome. Ruiz-Irastorza et al. (2010) reviewed pathophysiologic, clinical, diagnostic, and therapeutic advances related to the antiphospholipid syndrome. Various autoimmune disorders that cluster in families, including autoimmune thrombocytopenia (188030), are discussed elsewhere (e.g., 109100, 269200). Clinical Features Hellan et al. (1998) described a brother and sister with lupus anticoagulant, elevated anticardiolipin-immunoglobulin G levels, and systemic lupus erythematosus (SLE; 152700) or related autoimmune disorder. Both patients experienced venous thrombotic complications at an early age. The woman first presented with symptoms of spontaneous deep vein thrombosis of the right leg at the age of 22 years. The brother had been hospitalized at the age of 13 years for symptoms of arthritis of multiple joints and hepatosplenomegaly. He was found to have serologic and histologic evidence for lupus. At the age of 17 years, he presented with deep vein thrombosis of the right leg after a minor trauma. An association between the presence of lupus anticoagulant and the development of abnormalities of the heart valves was suggested by Hoshide et al. (1998), who described typical mitral stenosis in a patient with SLE associated with lupus anticoagulant. Brenner et al. (1996) observed a 23-year-old female and her 19-year-old sister, the offspring of a first-cousin marriage, who presented with unusual recurrent severe thromboembolic phenomenon and were found to have familial antiphospholipid syndrome and also to be heterozygous for the R506Q mutation of factor V (612309.0001). The coexistence of hereditary and acquired APC-resistance was thought to explain the severity of the thromboembolism. The older sib presented with deep vein thrombosis of the proximal left leg and intrauterine fetal death at 20 weeks of gestation in her third pregnancy. During her fourth pregnancy she received enoxaparine from the tenth week of gestation, but intrauterine fetal death occurred at 20 weeks of gestation. Three weeks later she developed right popliteal deep vein thrombosis. The younger sister was admitted to hospital with infarction of lumbar vertebra L4 demonstrated by bone scan, first-trimester abortion, and pancytopenia. Akiguchi et al. (1999) reported a 2-generation family with 3 generations of cousin marriages that was segregating lupus anticoagulant and Binswanger disease. The 60-year-old proband began insidious decline at age 57. Lupus anticoagulant was positive but anticardiolipin antibodies were negative. Multiple lacunes were present in a younger brother, in a younger sister, who also had venous thrombosis, and in 1 daughter, who also had SLE. Gelfand et al. (1999) reported the systemic and ophthalmic involvement in 39 consecutive patients with primary antiphospholipid syndrome. The first 20 consecutive patients underwent retinal fluorescein angiography. The most common forms of systemic involvement included fetal loss (46%), central nervous system involvement (44%), and venous thrombosis (41%). Thirty-three percent of patients had ocular symptoms; these were usually visual disturbances and were most often transient. Pathologic ocular findings directly related to the disease were found in 13% of the patients, and only 5% had intraocular pathology, which consisted of very mild retinopathy. Ocular findings were present in only 6% of the asymptomatic patients. Routine retinal angiography did not reveal any additional information. The authors concluded that ocular involvement in the primary antiphospholipid syndrome is uncommon. Transient visual disturbances are common, although most of them are related to central nervous system rather than ocular ischemia. Miserocchi et al. (2001) evaluated the ophthalmic features in 13 patients presenting with ocular inflammation in the presence of anticardiolipin antibodies. All patients had abnormal titers of anticardiolipin antibodies, predominantly the IgG isotype; 46% had markers of immune activation. Systemic symptoms were frequently present in association with ocular disease. The most common ocular symptom at presentation was blurred vision (62%), followed by pain (23%) and visual loss (15%). Seventy-six percent of patients had anterior segment abnormalities, including iritis (62%), scleritis (15%), and filamentary keratitis (7%). The most common posterior segment feature was retinal vasculitis (60%), followed by vitritis (38%), retinal detachment (15%), scleritis (7%), and central retinal artery occlusion (7%). Mapping Hudson et al. (1997) found a possible linkage between the HLA-DRB114 allele on chromosome 6p21.3 and familial antiphospholipid syndrome. Inheritance Familial occurrence of lupus anticoagulant was reported by Exner et al. (1980) and Mackie et al. (1987). In these reports, the index cases had systemic lupus erythematosus or related immune disorders, while many of their family members had a variety of clinical serologic features suggestive of a lupus-like syndrome. Matthey et al. (1989) described a family in which several members had anticardiolipin antibodies and 2 had lupus anticoagulant, but all were asymptomatic. To develop diagnostic criteria for a familial form of antiphospholipid syndrome, Goel et al. (1999) studied families with more than one affected member, examined possible modes of inheritance, and determined linkage to potential candidate genes. In 7 families, 30 of 101 family members met diagnostic criteria for the syndrome. Segregation studies rejected both environmental and autosomal recessive models, and the data were fitted best by either a dominant or codominant model. Linkage analysis showed independent segregation of antiphospholipid syndrome and several candidate genes. Pathogenesis McNeil et al. (1990) identified beta-2-glycoprotein I (B2GPI, APOH; 138700) as a cofactor required for antiphospholipid antibodies (APA) to bind to cardiolipin. These findings suggested that APA are directed against a complex antigen that includes B2GPI. In addition, B2GPI bound to anionic phospholipids in the absence of anticardiolipin antibodies. McNeil et al. (1990) hypothesized that anticardiolipin APA may interfere with the function of apoH in vivo, which may explain the association of these antibodies with thrombotic tendencies. Molecular Genetics Hirose et al. (1999) found that a polymorphism in the APOH gene (V247L) was significantly associated with decreased levels of anti-beta-2-glycoprotein I (B2GPI) antibodies in Asian patients with antiphospholipid syndrome in a study of 370 healthy controls from different racial backgrounds and 149 patients with APS. The V allele and the VV genotype were found more frequently among Asian patients with antiphospholipid syndrome than among controls (p = 0.0028 and p = 0.0023, respectively). There were no significant differences in allele or genotype frequencies when comparing Caucasian or African American APS patients with appropriate controls. The differences in allele and genotype frequencies seen in Asian APS patients were restricted to those with anti-B2GPI antibodies. Animal Model In a mouse model of antiphospholipid syndrome induced by passive transfer of human antiphospholipid antibodies, Girardi et al. (2003) showed that complement activation plays an essential and causative role in fetal loss and tissue injury. Specifically, they identified the proinflammatory sequelae of the interaction of C5a and C5a receptor (C5R1; 113995) and the recruitment of neutrophils as the critical intermediates linking pathogenic antiphospholipid antibodies to fetal damage. Their conclusions were based on the fetal protective effects of C5a receptor deficiency and C5a receptor antagonist peptide, the similar findings with anti-C5 mouse antibody and in C5 -/- mice, where C5a generation is prevented, and the effects of neutrophil depletion. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Blurred vision \- Ocular redness and pain \- Visual loss \- Iritis \- Anterior scleritis \- Filamentary keratitis \- Retinal vasculitis \- Vitritis \- Retinal detachment \- Posterior scleritis \- Central retinal artery occlusion CARDIOVASCULAR Vascular \- Arterial thrombosis \- Venous thrombosis HEMATOLOGY \- Immune thrombocytopenia IMMUNOLOGY \- Autoantibodies against cellular phospholipid components \- Anticardiolipin antibodies \- Lupus anticoagulant antibodies PRENATAL MANIFESTATIONS Delivery \- Recurrent fetal loss MISCELLANEOUS \- Variable ocular phenotype ▲ 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	ANTIPHOSPHOLIPID SYNDROME, FAMILIAL	c2930802	5,943	omim	https://www.omim.org/entry/107320	2019-09-22T16:44:57	{"mesh": ["C531622"], "omim": ["107320"], "synonyms": ["Alternative titles", "LUPUS ANTICOAGULANT, FAMILIAL"]}
Granulomatous lobular mastitis is a rare inflammatory disease of the breast. This disease usually affects women of child-bearing age or those who use oral contraceptive medication. It can be confused with breast cancer, so it is often misdiagnosed and proper treatment is delayed. The main symptoms include a palpable mass, skin or nipple retraction, and pain and swelling in the breast. Core needle biopsy is the recommended method for diagnosis and must be made in all cases, to rule-out breast cancer and other causes of granulomatous mastitis (such as infections (bacterial, fungal, mycobacterial), sarcoidosis, and other systemic granulomatous diseases). After ruling-out these diseases, the diagnosis of idiopathic “granulomatous lobular mastitis” is made. The cause is unknown, but may be autoimmune. Some cases are associated with Corynebacterium infection (when it is known as cystic neutrophilic granulomatous mastitis). There is no established treatment, but antibiotics, corticosteroids, drainage, excision, and surgical removal of the lesion have been tried with variable success. [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	Granulomatous lobular mastitis	c0405469	5,944	gard	https://rarediseases.info.nih.gov/diseases/13119/granulomatous-lobular-mastitis	2021-01-18T18:00:12	{"mesh": ["D058890"], "orphanet": ["64722"], "synonyms": ["Idiopathic granulomatous lobular mastitis"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Stigmatic-eligibilic paraphilia" – news · newspapers · books · scholar · JSTOR (December 2006) (Learn how and when to remove this template message) Stigmatic-eligibilic paraphilias are desires whose objects "become eligible" to be desired because of, rather than despite, a stigma which they bear. The manifold manifestations of these paraphilias cover the broadest range of physical, intimate and social circumstance. In the context of a stigmatic-eligibilic paraphilia, what is considered repulsive, unsuitable, prohibited, abnormal or taboo by most people turns into something attractive, suitable, permitted, normal and licensed. Thus, in paedophilia, necrophilia and zoophilia, children, corpses and animals are desired despite being incapable of forming sexual (or, indeed, any) relationships. In the attraction to disability, disabled people are desired despite deviating from the physical standard. In gerontophilia and ephebophilia, significantly older or younger people are desired despite being generally considered unsuitable due to great difference in age. In hybristophilia, notorious criminals are desired despite being generally considered objectionable. In urolagnia, coprophilia and emetophilia, urinating, defecating and vomiting in intimate circumstances are seen as arousing despite the general views that they are repulsive. In this sense, stigmatic-eligibilic paraphilias can seem 'non-conformist' and 'taboo-busting.' Stigmatic-eligibilic paraphilias are generally thought to result from intense and memorable childhood experiences ("sexuoerotic tragedies," though they may not be distressing) which "deform" the future adult's idea of what is and what is not attractive (their "lovemap"). Attempting to accommodate the extraordinary experience into an acceptable mental frame of reference, the future adult may "triumph" over it by use of a logic whereby the terms of reference commonly associated with it are reversed. ## References[edit] This abnormal psychology–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA	Stigmatic-eligibilic paraphilia	None	5,945	wikipedia	https://en.wikipedia.org/wiki/Stigmatic-eligibilic_paraphilia	2021-01-18T18:33:55	{"wikidata": ["Q7616497"]}
A number sign (#) is used with this entry because distal hereditary motor neuronopathy type VA (dHMN5A or HMN5A), sometimes referred to as distal spinal muscular atrophy type V (DSMAVA), can be caused by heterozygous mutation in the GARS gene (600287) on chromosome 7p14 or by heterozygous mutation in the BSCL2 gene (606158) on chromosome 11q12. Charcot-Marie-Tooth disease type 2D (CMT2D; 601472), also caused by mutation in the GARS gene, has a similar phenotype. Silver syndrome (SPG17; 270685), also caused by mutation in the BSCL2 gene, is a similar disorder with an overlapping phenotype characterized by spasticity. For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN, see HMN type I (HMN1; 182960). Clinical Features Meadows and Marsden (1969) reported 3 sibs with a form of distal muscular atrophy confined largely to the upper extremities. All had weakness of the hands since early childhood, manifest by difficulty writing. The condition worsened significantly much later in life, in the sixth and seventh decades. Hand weakness and atrophy were apparent in all, and 2 sibs had lower limb weakness with hyporeflexia/areflexia; the remaining sib had hyporeflexia/areflexia without lower limb weakness. EMG and muscle biopsy confirmed a neurogenic disorder. The mode of inheritance was unclear. Christodoulou et al. (1995) identified a large 5-generation Bulgarian family from Burgass with an autosomal dominant distal spinal muscular atrophy (dSMA) with upper limb predominance. Afflicted members had weakness and wasting which was more prominent in the upper limbs and more selectively involved the thenar muscles and the first dorsal interossei. They had clinical information on 114 family members, of whom 30 were affected. The disease commenced with hand involvement at a mean age of 17 years (median 16 years). In 40% of patients, symptoms subsequently developed in their feet within about 2 years. In 1 branch of the family, mild pyramidal features and, rarely, up-going plantar responses were observed. There were not sensory symptoms or signs except for slightly reduced vibratory sense in the feet in 10% of the patients. Progression of the disease was very slow, with patients still ambulant at the age of 64. Electrophysiologic investigations showed reduced or, in severely wasted muscles, unobtainable compound motor action potentials. Motor conduction velocities and distal latencies were normal, except in severely wasted muscles, where the former were reduced. Christodoulou et al. (1995) concluded that the family fell into the type V category of distal spinal muscular atrophy according to Harding (1993), who proposed a classification into 7 types of distal SMA according to their clinical and genetic features. The family was similar to the one reported by Lander et al. (1976), but differed in that weakness and wasting were more severe in the thenar muscles and first dorsal interossei. The family was considered to be different from the families with Silver syndrome described by Silver (1966) and by van Gent et al. (1985) in that most of their patients also had brisk reflexes and signs of spasticity in addition to hand weakness. Sambuughin et al. (1998) reported a family in which autosomal dominant CMT2D and distal spinal muscular atrophy type V segregated in the same kindred. All 17 affected members had bilateral weakness and wasting in thenar and first dorsal interossei muscles starting commonly with cold-induced cramps in the hands in their late teens. The mean age at onset was 18 years (range 12 to 36) and progression of illness was very slow. DSMAV was diagnosed in 11 patients based on the presence of hand and peroneal muscle weakness and atrophy without sensory deficits. CMT2D was diagnosed in 6 other patients based on the presence of weakness and atrophy in the same muscle groups, hypoactive knee and ankle reflexes, stocking and glove distribution sensory loss, and reduced sensory nerve action potential amplitudes. Antonellis et al. (2003) reported an Algerian Sephardic Jewish family with autosomal dominant DSMAV. A father and daughter had bilateral hand amyotrophy and weakness, particularly in the thenar and dorsal interosseus muscles. Motor and sensory nerve conduction velocities were normal. Van de Warrenburg et al. (2006) reported 2 unrelated Dutch families with overlapping Silver syndrome and distal motor neuropathy caused by the same BSCL2 mutation (N88S; 606158.0013). The first family contained 5 affected individuals spanning 3 generations. All presented with pes cavus and foot of leg muscle weakness and atrophy between 11 and 26 years of age. There was slow progression, with gradually evolving lower limb hypertonia and hyperreflexia with extensor plantar responses without prominent spasticity. Two patients also developed weakness and atrophy of the first dorsal interosseus and abductor pollicis brevis muscles without involvement of the hypothenar muscles. In the second family, there were multiple affected individuals spanning 3 generations. Age at onset was before age 20 years. About half of the patients presented with foot or leg muscle weakness and atrophy, whereas the other half presented with hand muscle weakness and atrophy. Most developed hyperreflexia with extensor plantar responses; spasticity was observed in older patients. Van de Warrenburg et al. (2006) emphasized the phenotypic variability and incomplete penetrance of some symptoms. Brusse et al. (2009) reported 12 members of a large 3-generation Dutch family with phenotypic overlap between Silver syndrome and distal HMN5 who carried a heterozygous N88S mutation in the BSCL2 gene. The phenotype was variable, and the distribution of muscle weakness and atrophy included predominantly the feet (in 4), the hands (in 1), or both upper and lower extremities (in 4). Three individuals showed evidence of pyramidal features, including spasticity, hyperrflexia, and extensor plantar responses. Severity of the disease ranged from adolescent patients with disabling muscle weakness to an elderly patient with only mild weakness of the ankle dorsiflexors and bilateral pes cavus. Brusse et al. (2009) noted the extreme phenotypic variability associated with the N88S mutation in their family and in those reported by Auer-Grumbach et al. (2005) and van de Warrenburg et al. (2006), who also carried the N88S mutation, and suggested the presence of other genetic or environmental factors. In their family, Brusse et al. (2009) used genomewide linkage analysis to identify a candidate disease modifier on chromosome 16p13.3-p13.12 that was shared by all 12 affected individuals (maximum lod score of 3.28). One family member without the N88S mutation but with the chromosome 16p haplotype showed mild electrophysiologic abnormalities. Brusse et al. (2009) postulated that a locus on chromosome 16p may contain a disease modifier in their family. Mapping Linkage studies in the Bulgarian family reported by Christodoulou et al. (1995) excluded the SMA locus (253300) on chromosome 5. Using more than 140 microsatellite polymorphic markers for a genome screen, Christodoulou et al. (1995) found a maximum lod score of 5.99 at theta = 0.007 for locus D7S795 located on 7p. Sambuughin et al. (1998) mapped the disorder in their family to a region on 7p15 between markers D7S2496 and D7S1514. Ellsworth et al. (1999) performed a more detailed linkage analysis of the region on 7p and found overlap between the areas defined by Christodoulou et al. (1995) and Sambuughin et al. (1998) and the area defined by Ionasescu et al. (1996) in a CMT2D family. Ellsworth et al. (1999) determined that the most likely location of the CMT2D gene is between markers D7S2496 and D7S632. They suggested that defects in a single gene account for the disease in all of the families. ### Genetic Heterogeneity In a large 4-generation Austrian family with autosomal dominant DSMAV, Auer-Grumbach et al. (2000) excluded linkage to the DSMAV locus on 7p, indicating genetic heterogeneity of the disorder. Linkage was also excluded from the adult spinal muscular atrophy locus on chromosome 12q (158590) and the juvenile ALS locus on 9q (ALS4; 602433). Twenty-one family members were affected with a highly variable phenotype. Most affected members had onset before age 20 years of a progressive asymmetric wasting of the thenar and the first dorsal interosseus muscles. Twenty patients had foot deformity, ranging from mild to severe, and about half had peroneal muscular atrophy. A subset of patients also had brisk tendon reflexes. Sensory abnormalities were virtually absent. Molecular Genetics Irobi et al. (2004) reviewed the molecular genetics of the distal motor neuropathies. ### Mutations in the GARS Gene In the families with DSMAV reported by Christodoulou et al. (1995) and Antonellis et al. (2003) and the family with both DSMAV and CMT2D reported by Sambuughin et al. (1998), Antonellis et al. (2003) identified mutations in the GARS gene (600287.0002-600287.0004). Dubourg et al. (2006) identified a mutation in the GARS gene (G526R; 600287.0004) in 12 affected members from 3 French families of Sephardic Jewish origin with HMN type V. Four mutation carriers were clinically asymptomatic, suggesting incomplete penetrance. Most presented with distal upper limb involvement between the second and fourth decades; none had sensory involvement. Haplotype analysis suggested a founder effect. ### Mutations in the BSCL2 Gene In affected members of 1 Italian, 1 English, and 8 Austrian families with DSMAV, including the one reported by Auer-Grumbach et al. (2000), Windpassinger et al. (2004) identified a heterozygous asn88-to-ser mutation in the BSCL2 gene (N88S; 606158.0013). In the same study, Windpassinger et al. (2004) also identified mutations in the BSCL2 gene in patients with Silver syndrome, indicating that the 2 disorders are extreme phenotypes with the same genetic etiology. The large affected Austrian kindred comprised 4 family branches with Silver syndrome and 8 family branches with DSMAV; all affected Austrian patients had the N88S mutation in the BSCL2 gene. By in vitro functional expression analysis, Ito and Suzuki (2007) demonstrated that the N88S and S90L mutations in the BSCL2 gene disrupt glycosylation of the seipin protein. Overexpressed mutant seipin was highly ubiquitinated and degraded by the proteasome, and improper glycosylation exacerbated endoplasmic reticulum (ER) retention. Mutant proteins activated the unfolded protein response (UPR), resulting in apoptotic cell death through ER stress. Ito and Suzuki (2007) concluded that the N88S and S90L mutations, which result in motor neuron disease, have a gain-of-function effect, resulting in conformational protein changes, activation of the UPR, cell death, and neurodegeneration. Ito and Suzuki (2009) provided a review. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus in some \- Pes planus in some \- Hammertoes in some NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Upper limb weakness and atrophy predominates \- Thenar muscle weakness \- Thenar muscle atrophy \- First dorsal interossei muscle weakness \- First dorsal interossei muscle atrophy \- Cold-induced hand cramps \- Mildly reduced vibratory sense in 10% of patients \- Normal motor nerve conduction velocity (except in severely wasted muscles) \- Hyperreflexia in some MISCELLANEOUS \- Mean age of onset 18 years \- Slow disease progression \- Allelic disorder to Charcot-Marie-Tooth disease type 2D (CMT2D, 601472 ), but distinguished by less severe distal sensory involvement \- Allelic disorder to Silver syndrome ( 270685 ), but distinguished by lack of spasticity MOLECULAR BASIS \- Caused by mutation in the glycyl tRNA synthetase gene (GARS, 600287.0002 ) \- Caused by mutation in the seipin gene (BSCL2, 606158.0013 ) ▲ 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	NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE VA	c1833308	5,946	omim	https://www.omim.org/entry/600794	2019-09-22T16:15:48	{"doid": ["0111204"], "mesh": ["C563443"], "omim": ["600794"], "orphanet": ["139536"], "synonyms": ["Alternative titles", "HMN VA", "NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE V", "NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE VA", "DHMN VA", "SPINAL MUSCULAR ATROPHY, DISTAL, TYPE VA", "SPINAL MUSCULAR ATROPHY, DISTAL, TYPE V", "SPINAL MUSCULAR ATROPHY, DISTAL, WITH UPPER LIMB PREDOMINANCE"], "genereviews": ["NBK1307", "NBK1358", "NBK1242"]}
A number sign (#) is used with this entry because of evidence that torsion dystonia-1 (DYT1) is caused by heterozygous mutation in the TOR1A gene (605204), encoding the ATP-binding protein torsin-A, on chromosome 9q34. Description 'Dystonia' describes a neurologic condition characterized by involuntary, sustained muscle contractions affecting one or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in dystonia. Dystonia has been classified as primary (dystonia as the sole or major symptom) or secondary (a symptom of another disorder), and by age of onset, muscle groups affected, and mode of inheritance (Muller and Kupke, 1990; Nemeth, 2002). Clinical Features Primary torsion dystonia (also known as 'idiopathic' torsion dystonia; ITD) usually begins in childhood or adolescence with involuntary posturing of the trunk, neck, or limbs (Marsden et al., 1976; Nemeth, 2002). Some patients have a myostatic picture, such as was described by Wechsler and Brock (1922). Johnson et al. (1962) described an extensively affected French-Canadian family. Age of onset of affected family members ranged from 6 to 42 years and severity of the disease varied considerably, with early-onset cases being severely affected. Minor manifestations interpreted as 'formes frustes' were found in some family members. In a large North American family of non-Jewish ancestry, Brin et al. (1989) found that age of onset ranged from 4 to 43 years (mean 14.4, median 10.0). Generalization occurred within a median time of 3 years and occurred earlier in cases with onset in the leg. One 6.5-year-old was unable to walk within 3 months of onset. Batshaw et al. (1985) described a patient with severe simulated torsion dystonia as the main feature of Munchausen syndrome. Bressman et al. (1994) analyzed the haplotype of 174 Ashkenazi Jewish individuals affected with torsion dystonia. In this group, there were 90 carriers of the haplotype and 70 noncarriers. The authors found very striking differences in the phenotype between carriers and noncarriers. The age of onset in carriers was 12.5 years versus 36.5 years in the noncarriers. In 94% of carriers, symptoms began in a limb but only rarely in the neck and larynx. In contrast, the neck, larynx, or other cranial muscles were the site of onset in 79% of noncarriers. Discriminant analysis of limb onset, leg involvement, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In 23 of the 70 noncarriers, the disease was familial and included brachial, cervical, laryngeal, and facial dystonia. Cheng et al. (1996) studied 49 probands with cervical or cranial dystonia with age of onset greater than 12 years and with a positive family history. They found that age of onset of clinical symptoms was earlier by an average of 21.25 years in the second generation than in the first, and suggested that an unstable trinucleotide repeat may be involved in adult-onset primary cranial or cervical dystonia. Grundmann et al. (2003) stated that most cases of early-onset generalized dystonia are caused by a 3-bp deletion in the DYT1 gene (delE302/303; 605204.0001). They reported 6 patients with dystonia caused by the 3-bp deletion who exhibited wide phenotypic variability: 2 had classic early-onset primary generalized dystonia, 2 had multifocal dystonia (1 with cranial and cervical muscle involvement), and 2 had only writer's cramp with mild progression. Kostic et al. (2006) reported a large Serbian family in which 7 members carried the delE302/303 DYT1 mutation (605204.0001). However, only 2 were affected by dystonia, indicating a penetrance of 29%. One of the affected individuals had late-onset mild torticollis, and the other had generalized jerky dystonia. In addition, 3 family members with dystonia did not carry the DYT1 mutation, indicating genetic heterogeneity or possibly a psychogenic origin. Kostic et al. (2006) commented on the phenotypic variability in this family. Zirn et al. (2008) reported an 18-year-old girl with a severe form of early-onset dystonia. She had mildly delayed early motor development with stalling of further development during the second year of life. She never learned to walk independently and became wheelchair-bound at age 5 years. At age 13, she could no longer eat or drink without assistance. At age 18, she had dysphagia, severe dysarthria, facial palsy with reduced tongue mobility, dystonic movements, multiple joint contractures, increased muscle tone, hyperreflexia, and extensor plantar responses. Cognition was normal. ### Neuroradiologic Studies In 12 nonmanifesting carriers of a DYT1 mutation (605204.0001), Ghilardi et al. (2003) found decreased learning of new motor sequence tasks, compared to controls. PET scans during the tasks showed some areas of brain overactivity in the carriers, including in the premotor and supplemental motor cortices. The authors concluded that clinically unaffected DYT1 mutation carriers exhibit mild abnormalities in motor behavior and brain functioning, suggesting an innate compensation for mild striatal dysfunction. Using diffusion tensor magnetic resonance imaging (DTI) to assess axonal integrity and coherence in the brain, Carbon et al. (2004) found that 4 clinically affected DYT1 patients and 8 nonmanifesting DYT1 carriers had microstructural disturbances of the white matter pathways that carry afferents and efferents to the primary sensorimotor cortex compared to controls. The changes were more severe in the clinically affected patients. Using PET scans, Carbon et al. (2004) found that manifesting gene carriers of DYT1 and DYT6 (602629) had bilateral hypermetabolism in the presupplementary motor area and parietal association cortices compared to their respective nonmanifesting gene carriers. DYT1 carriers as a whole showed increased metabolism in the inferior cerebellum and putamen, with decreases in the anterior cingulate. In contrast, DYT6 carriers as a whole showed hypometabolism in the putamen and hypermetabolism in the temporal cortex. Carbon et al. (2004) concluded that dystonia in general is a disease of 'movement preparation' driven by a disruption of sensorimotor integration, but that unique metabolic abnormalities, particularly in subcortical structures, may represent genotype-specific differences. Using PET scans and radiolabeled raclopride, Asanuma et al. (2005) found that 9 nonmanifesting carriers of DYT1 mutations had significantly reduced striatal D2 receptor (DRD2; 126450)-binding compared to 13 control individuals. DYT1 carriers had a reduction in D2 binding in the caudate and ventral putamen. Although Asanuma et al. (2005) were not able to distinguish between D2 receptor loss and increased dopamine turnover, the findings implicated abnormal dopaminergic transmission in the pathogenesis of primary dystonia. Using PET scans and radiolabeled raclopride, Carbon et al. (2009) found significant reductions in caudate and putamen DRD2 availability in 21 individuals with DYT1, including 12 nonmanifesting and 9 manifesting carriers, and 12 individuals with DYT6, including 4 nonmanifesting and 8 manifesting carriers, compared to 13 controls. There was no significant difference between manifesting and nonmanifesting mutation carriers within either group, but those with DYT6 mutations had greater reductions than those with DYT1 mutations. Voxel-based analysis using stringent thresholds showed that the lateral putamen and right ventrolateral thalamus were most affected, with DYT6 carriers again more affected than DYT1 carriers. In addition, DYT6 carriers showed significantly greater reduction in the posterior putamen than DYT1 carriers. Carbon et al. (2009) emphasized that there was no difference between manifesting and nonmanifesting mutation carriers, suggesting that alterations in dopamine neurotransmission are susceptibility factors for the development of clinical symptoms, but that there likely needs to be an additional insult for manifestation. ### Neuropathologic Features McNaught et al. (2004) found perinuclear inclusion bodies in cholinergic neurons of the midbrain reticular formation, particularly in the pedunculopontine nuclei (PPN), and periaqueductal gray matter in 4 clinically affected patients with genetically confirmed DYT1. The inclusions stained positively for ubiquitin (191339), torsin-A, and lamin A/C (LMNA; 150330). No inclusion bodies were identified in the substantia nigra, striatum, hippocampus, or selected regions of the cerebral cortex. McNaught et al. (2004) concluded that DYT1 dystonia is associated with impaired protein handling and possible disruption of the nuclear envelope, and that alterations in the brainstem may underlie the motor abnormalities in DYT1. ### Clinical Variability Calakos et al. (2010) reported a man with late-onset focal torsion dystonia of the oromandibular region occurring in the fifth decade that was associated with a heterozygous mutation (F205I; 605204.0004) in the TOR1A gene. The dystonia was characterized by involuntary jaw movements and grimacing. Neurologic examination showed cogwheel tone without rigidity and mild action tremor in the upper limbs, as well as absent ankle reflexes. He had a history of bipolar disorder, treated with lithium, and remote history of treatment with a dopamine receptor blocking agent. There was a family history of tremor and depression, but no family history of dystonia. In vitro functional expression studies in cultured cells showed that the F205I-mutant protein produced TOR1A inclusion bodies that colocalized with the endoplasmic reticulum in about 44% of cells, suggesting impaired function. Other Features Heiman et al. (2004) administered a standard psychiatric interview to 96 manifesting carriers of the DYT1 deletion mutation (605204.0001), 60 nonmanifesting carriers of the mutation, and 65 noncarriers. The risk for early-onset (before 30 years) recurrent major depression (see 608516) was increased in both manifesting mutation carriers (relative risk of 3.62) and nonmanifesting mutation carriers (relative risk of 4.95) compared to noncarriers. The severity of dystonia in manifesting carriers was not associated with the likelihood of major depression, and mutation carriers did not have an increased risk for other affective disorders. Heiman et al. (2004) concluded that early-onset recurrent major depression is a clinical expression of the DYT1 gene mutation that is independent of dystonia. Biochemical Features Some groups have found elevation of plasma dopamine-beta-hydroxylase, the enzyme that converts dopamine to norepinephrine, in the dominant form of dystonia (Wooten et al., 1973; Ziegler et al., 1976; Askenasy et al., 1980). Hornykiewicz et al. (1986) performed histologic and biochemical studies on the brains of 2 patients with a generalized childhood-onset form of dystonia. No important histologic change was found, but levels of norepinephrine and serotonin were decreased in some areas and elevated in others. The authors concluded that some of these changes may represent a basic abnormality of the disorder. They pointed to elevated norepinephrine levels found in an inherited dystonia of the Sprague-Dowley rat with no obvious neuropathologic changes (Lorden et al., 1984). In this model, the alpha-2-adrenergic receptor agonist clonidine has antidystonic effects. Inheritance Zeman et al. (1959, 1960) traced the disorder through 4 generations and Larsson and Sjogren (1963) traced it through 5 generations. Zilber et al. (1984) analyzed data from a nationwide survey of idiopathic torsion dystonia in Israel. Assuming that all cases fit the same genetic model, an X-linked or simple autosomal recessive model could be rejected. An autosomal dominant model with low penetrance could have accounted for the observations. Paternal age was increased (33.8 vs 30.1, p = 0.01) for isolated cases. Bundey et al. (1975) had also observed paternal age effect. Risch et al. (1989, 1990) ascertained 43 Ashkenazi Jewish probands with idiopathic torsion dystonia with onset before age 28 years and studied all available first- and second-degree relatives. The findings were considered consistent with autosomal dominant inheritance with about 30% penetrance; recessive inheritance was strongly rejected. Risch et al. (1989, 1990) concluded that torsion dystonia in Ashkenazi Jews may be largely homogeneous. Bressman et al. (1989) studied 39 kindreds derived from 43 independently ascertained probands of Ashkenazi ancestry. The age-adjusted risk for all first-degree relatives was 15.5% and for all second-degree relatives 6.5%, with no significant sex differences; parent, offspring, and sib risks did not differ significantly. The risks were consistent with autosomal dominant inheritance with a penetrance estimated at 29.4% using definite cases only, and 32.2% using definite and probable cases. Assuming a disease frequency of 1 in 15,000, the gene frequency was estimated to be 1 in 9,000. Penetrance in this disorder is usually low (approximately 30%), but varies considerably between families; the particularly large French-Canadian family first described by Johnson et al. (1962) showed a penetrance greater than 90%. Muller and Kupke (1990) reviewed the genetics of primary torsion dystonia and noted there are multiple forms of autosomal dominant torsion dystonia. They also listed genetic and nongenetic causes of secondary dystonia. Heterogeneity In 1 French and 26 British families with torsion dystonia, 3 of which were Ashkenazi Jewish, Warner et al. (1993) found that nearly half of the dystonia families may be of a variety unlinked to 9q34, supporting the existence of genetic heterogeneity. Gasser et al. (1996) found no common haplotypes in the DYT1 region on chromosome 9q in 10 Ashkenazi Jewish patients with focal hand dystonia, indicating separate etiology for this disorder. In a review of primary dystonias, Muller et al. (1998) indicated that at least 8 clinically distinct autosomal dominant and 2 X-linked recessive forms had been identified. In addition, pedigree analyses suggested the occurrence of an autosomal recessive variant. They tabulated the primary dystonias, numbered 1 through 12, and proposed that most of them can be distinguished by genetic criteria. Contarino et al. (2008) reported a large consanguineous family with adult-onset primary focal dystonia from a small Dutch village on a former island. There were 8 affected and 4 possibly affected individuals, with a mean age at onset of 45.5 years. Common clinical features included cervical dystonia, blepharospasm, writer's cramp, and mild arm tremor. The symptoms overall were quite mild in all patients. Contarino et al. (2008) noted that the transmission pattern could be consistent with autosomal recessive inheritance, given the consanguinity, or with autosomal dominant inheritance with reduced penetrance, because there was an instance of father-to-son transmission. Genetic analysis excluded mutations in the TOR1A and SGCE (604149) genes, and linkage analysis excluded several DYT loci. Mapping In the large non-Jewish kindred studied by Kramer et al. (1987), Ozelius et al. (1989) found tight linkage with the gene encoding gelsolin (137350); maximum lod score = 3.51 at theta = 0.0 cM. Ozelius et al. (1989) concluded from multipoint linkage analysis that the DYT1 locus lies in the 9q32-q34 region between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase, a possible candidate gene. In a study of 12 multiplex Ashkenazi Jewish families, Kramer et al. (1989, 1990) confirmed the assignment to 9q32-q34. Kramer et al. (1990) demonstrated close linkage with the gene encoding argininosuccinate synthetase (ASS; 603470). This suggests that the mutation causing the Ashkenazi Jewish disease is in the same gene as that causing dystonia in the non-Jewish kindred in which linkage to gelsolin was demonstrated. In a large non-Jewish family and in a group of Ashkenazi Jewish families, Kwiatkowski et al. (1991) used GT repeat polymorphisms from the 9q32-q34 region to demonstrate that the causative gene in both groups was in this region, in an 11-cM interval between AK1 (103000) and D9S10. Using (GT)n and RFLP markers from the region 9q32-q34, Ozelius et al. (1992) delineated the area containing the DYT1 gene to a 6-cM region bounded by loci AK1 and ASS. Warner et al. (1993) determined that association observed between ABL/ASS and idiopathic torsion dystonia in Ashkenazi families in the U.S. was also present in some British Jewish kindreds. Kramer et al. (1994) studied 7 non-Jewish families of northern European and French-Canadian descent and found evidence for linkage to the DYT1 region in 5 of these families. Estimates of penetrance in the non-Jewish families ranged from 0.40 to 0.75. None of these families carried the Ashkenazi Jewish haplotype, suggesting that in these populations there was a different mutation in the DYT1 gene. Ozelius et al. (1997) used a YAC contig spanning 600 kb of chromosome 9q34 and several new polymorphic loci to expand the linkage disequilibrium analysis of the torsion dystonia mutation in Ashkenazi Jewish families. They concluded that the most likely location of the DYT1 gene is within a 150-kb region between D9S2161 and D9S63. ### Exclusion Studies Kramer et al. (1985) used the 'candidate gene' approach to show that the proopiomelanocortin gene (POMC; 176830) is not linked to torsion dystonia in a kindred with the autosomal dominant form reported by Johnson et al. (1962). Using the same approach, Breakefield et al. (1986) excluded the POMC and glutamate decarboxylase (GAD; see 605363) genes as the site of the mutation. Kramer et al. (1987) excluded 11p, 13q, and 21q as the location of the mutation in a single non-Jewish pedigree with torsion dystonia. Molecular Genetics Ozelius et al. (1997) identified a heterozygous 3-bp deletion in the DYT1 gene (delE302/303; 605204.0001) in all affected and obligate carrier individuals with chromosome 9-linked primary dystonia, regardless of ethnic background and surrounding haplotype. In a man with focal torsion dystonia of the oromandibular region occurring in the fifth decade, Calakos et al. (2010) identified a heterozygous mutation (F205I; 605204.0004) in the TOR1A gene. In an 18-year-old girl with severe early-onset torsion dystonia, Zirn et al. (2008) identified a heterozygous missense mutation in the DYT1 gene (R288Q; 605204.0005). The mutation was inherited from the patient's unaffected mother, but was not found in 500 German control individuals. Transfection of the mutation into HEK293 cells resulted in a focally enlarged perinuclear space filled with membrane remnants; these abnormal findings were also observed in cells transfected with the common delE302/303 mutation, but were not observed in cells transfected with wildtype DYT1. The presence of the mutation in the unaffected mother was consistent with incomplete penetrance, which has been observed in DYT1. ### Modifier Alleles Although a GAG deletion in the DYT1 gene (605204.0001) is the major cause of early-onset dystonia, expression as clinical disease occurs in only 30% of mutation carriers. To gain insight into genetic factors that may influence penetrance, Risch et al. (2007) evaluated 3 DYT1 SNPs including D216H (605204.0003), a coding-sequence variation that moderates the effects of the DYT1 GAG deletion in cellular models. The D216H polymorphism encodes aspartic acid (D) in 88% and histidine (H) in 12% of control-population alleles (Ozelius et al., 1997: Leung et al., 2001). Risch et al. (2007) tested 119 DYT1 GAG-deletion carriers with clinical signs of dystonia and 113 mutation carriers without signs of dystonia as well as 197 control individuals; they found a frequency of the his216 allele to be increased in GAG-deletion carriers without dystonia and to be decreased in carriers with dystonia, compared with the control individuals. Analysis of haplotypes demonstrated a highly protective effect of the H allele in trans with the GAG deletion; there was also suggestive evidence that the asp216 allele in cis is required for the disease to be penetrant. The findings established, for the first time, a clinically relevant gene modifier of DYT1. Kamm et al. (2008) found that none of 42 symptomatic patients from 35 European families with dystonia carried the D216H variant, whereas 6 (12.5%) of 48 chromosomes from 24 asymptomatic mutation carriers had the D216H SNP. The findings indicated that deletion carriers with the his216 allele have a greatly reduced risk of developing symptoms of dystonia: the disease penetrance of those with the his216 allele is about 3% compared to about 35% in deletion carriers with the asp216 allele. The authors noted that although the his216 allele is generally rare, with a maximum frequency of 19% in Europeans, it should be included in molecular genetic testing for the disorder. ### Associations Pending Confirmation For discussion of a possible association between primary cervical focal dystonia and variation in the DRD5 gene, see 126453.0001. Genotype/Phenotype Correlations Among 147 DYT1 deletion (605204.0001) carriers and 113 blood-related noncarriers from 43 families, Bressman et al. (2002) assessed the validity of the diagnostic categories of 'definite,' 'probable,' and 'possible' dystonia often used in genetic research studies. The category of 'definite' dystonia, defined as characteristic overt twisting or directional movements and postures that are consistently present, was 100% specific: all patients classified as 'definite' carried the deletion mutation. 'Probable' dystonia was significantly increased in carriers compared with noncarriers, and 'possible' dystonia was not significantly different. Bressman et al. (2002) recommended that only patients with definite signs of dystonia be considered affected in linkage and other genetic studies. Population Genetics Zilber et al. (1984) found that the frequency of the disease in European Jews was about 1:23,000 live births or about 5 times greater than in Jews of Afro-Asian origin. Risch et al. (1989, 1990) reported a high incidence of the disease among Ashkenazi Jews. In 52 unrelated, affected Ashkenazi Jewish persons, Ozelius et al. (1992) found highly significant linkage disequilibrium between a particular extended haplotype at the ABL-ASS loci and the DYT1 gene. Most affected individuals were heterozygous for the particular haplotype, a finding supporting autosomal dominant inheritance of the DYT1 gene. Of the 53 definitely affected individuals typed, 13 appeared to be sporadic, with no family history of dystonia. Ozelius et al. (1992) concluded that many sporadic cases are in fact hereditary, that the disease gene frequency is greater than 1 in 15,000, and that the penetrance is lower than 30% (the previously estimated value for this population). Risch et al. (1995) examined data on 6 closely linked microsatellite loci on 9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia. The data indicated that more than 90% of early-onset cases in the Ashkenazi population are due to a single founder mutation, which the authors estimated first appeared approximately 350 years ago. They showed that carriers preferentially originated from the northern part of the historic Jewish Pale, Lithuania and Byelorussia. The recent origin of this dominant mutation and its current high frequency, between 1 in 6,000 and 1 in 2,000, suggested that the Ashkenazi population descended from a limited number of founders and emphasized the importance of genetic drift in determining disease allele frequencies in this population. Zoossmann-Diskin (1995) challenged the significance of genetic drift in determining the high frequency of the DYT1 gene in Ashkenazim. He questioned the accuracy of the small population numbers before 1600 and the rapid expansion thereafter and favored heterozygote advantage as the explanation for the high gene frequency. In a long reply, Risch et al. (1995) defended the population statistics and cited a number of reasons that the claim of heterozygote advantage for this dominant disorder is untenable. They suggested that genetic drift provides a general explanation for the high frequency of at least a dozen genetic diseases that occur at high frequency uniquely to the Ashkenazi population. None of these mutations is common among the non-Jews living in proximity to the Jews. Founder effect of recent mutations in a rapidly expanding population from a limited number of founders offers a simple, parsimonious solution, in their view. Motulsky (1995) gave a useful review of 10 'Ashkenazi Jewish diseases,' including torsion dystonia. Valente et al. (1999) analyzed the haplotypes surrounding the DYT1 gene in 9 Ashkenazi Jewish and 15 non-Jewish British patients carrying the GAG deletion. They found that all Ashkenazi-Jewish British patients carried the same haplotype as the North American Jews, sustaining the theory that the current British Ashkenazi community descends from the same small group of individuals as the North American Jewry. Furthermore, in the non-Jewish British patients, only a limited number of distinct founder mutations were observed. This supported the hypothesis that the GAG deletion in the DYT1 gene (605204.0001) is not a very frequent mutation, and that it has arisen only a limited number of times throughout the centuries. Ikeuchi et al. (1999) noted that Yanagisawa et al. (1972) had described families with the clinical diagnosis of dystonia musculorum deformans. Because of the high frequency in Japanese of hereditary progressive dystonia with marked diurnal fluctuations (128230), which has symptoms similar to those of primary torsion dystonia, Ikeuchi et al. (1999) concluded that it is important to document the GAG deletion in the DYT1 gene (605204.0001) in the Japanese population. Hjermind et al. (2002) examined 107 unrelated Danish probands with primary torsion dystonia. The clinical examinations showed that 22 probands had generalized dystonia (20 of whom had early limb-onset), 2 had hemidystonia, 5 had multifocal dystonia, 15 had segmental dystonia, and 63 had focal dystonia. Among the 107 probands investigated, the GAG deletion (605204.0001) in the DYT1 gene was detected in 3 (2.8%). This corresponded to 15% of the 20 probands with early limb-onset generalized dystonia. Of the 3 probands with the GAG deletion, only 1 had familial dystonia, with the mutation detected in the affected father and in 6 asymptomatic adult relatives. In the second proband the DYT1 mutation was also encountered in the asymptomatic mother, while in the third case none of the parents had the GAG deletion and therefore represented a de novo mutation. Hjermind et al. (2002) pointed out that the difficulties in genetic counseling concerning dystonia are due to the low penetrance of many of the hereditary forms of dystonia, the variable phenotype within the same type of dystonia, and the occurrence of de novo DYT1 mutations. Frederic et al. (2008) found that DYT1 was rare in France, with an estimated disease frequency of 0.13 in 100,000 and an estimated mutation frequency of 0.17 in 100,000. Eleven (20.7%) of 53 families carried the Ashkenazi Jewish haplotype, suggesting that independent mutational events occurred in the other families. Animal Model Shashidharan et al. (2005) generated 4 independent lines of transgenic mice by overexpressing human delE-torsin-A using a neuron-specific enolase promoter. Approximately 40% of the transgenic mice developed abnormal involuntary movements with dystonic-appearing self-clasping of limbs, hyperkinesia, and rapid bidirectional circling. Neurochemical analyses revealed decreased striatal dopamine in affected transgenic mice, and immunohistochemical studies demonstrated perinuclear inclusions and aggregates that stained positively for ubiquitin (UBB; 191339), torsin-A, and lamin (LMNA; 150330). Inclusions were detected in neurons of the pedunculopontine nucleus and in other brain stem regions in a pattern similar to that described in DYT1 patients. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial grimace Eyes \- Blepharospasm Neck \- Torticollis SKELETAL Spine \- Lordosis \- Kyphosis \- Scoliosis NEUROLOGIC Central Nervous System \- Torsion dystonia (involuntary sustained muscle contractions, twisting and repetitive movements, abnormal posturing) \- Begins in limbs, later generalized (childhood onset) \- Focal dystonia (adult onset) \- Dysarthria \- Tremor \- Hypotonia \- Hypertonia \- Writer's cramp \- Isolated focal dystonia may occur Behavioral Psychiatric Manifestations \- Depression MISCELLANEOUS \- Onset in mid to late childhood \- Occasional adult onset \- Wide phenotypic variability \- High incidence among Ashkenazi Jews \- Incomplete penetrance (as low as 30% in some cases) MOLECULAR BASIS \- Caused by mutations in the torsion dystonia-1 gene (DYT1, 605204.0001 ). ▲ 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	DYSTONIA 1, TORSION, AUTOSOMAL DOMINANT	c1851945	5,947	omim	https://www.omim.org/entry/128100	2019-09-22T16:42:03	{"doid": ["0060730"], "omim": ["128100"], "orphanet": ["256"], "synonyms": ["Alternative titles", "DYSTONIA MUSCULORUM DEFORMANS 1", "EARLY-ONSET TORSION DYSTONIA"], "genereviews": ["NBK1492"]}
"NBTE" redirects here. For educational board, see National Board for Technical Education. Nonbacterial thrombotic endocarditis SpecialtyCardiology Nonbacterial thrombotic endocarditis (NBTE) is a form of endocarditis in which small sterile vegetations are deposited on the valve leaflets. Formerly known as marantic endocarditis, which comes from the Greek marantikos, meaning "wasting away".[1] The term "marantic endocarditis" is still sometimes used to emphasize the association with a wasting state[2] such as cancer.[3] ## Contents * 1 Risk factors * 1.1 Valve predilection * 2 Histopathology * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Risk factors[edit] Marantic vegetations are often associated with previous rheumatic fever. Other risk factors include: * hypercoagulable states * malignant cancers, especially mucin-producing adenocarcinomas (most commonly associated with pancreatic adenocarcinomas) * systemic lupus erythematosus: Referred to as Libman-Sacks endocarditis * trauma (e.g., catheters) ### Valve predilection[edit] The disease affects the valves with following predilection: mitral valve > aortic valve > tricuspid valve > pulmonary valve [4] ## Histopathology[edit] Grossly, vegetations form along lines of valve closure and are generally symmetric with a smooth or verrucoid (warty) texture. Histologically, lesions are composed of fibrin[5] (eosinophilic) and platelets but, unlike bacterial etiologies, contain little evidence of PMNs, microorganisms or inflammation. ## Diagnosis[edit] Due to the non-invasive nature of NBTE, clinical examination may or may not reveal a new murmur. An embolic stroke may be the first feature to suggest diagnosis of NBTE. An echocardiograph may be used to further assess for valvular lesions. ## Treatment[edit] This section is empty. You can help by adding to it. (October 2017) ## References[edit] 1. ^ Neurological Sequelae of Infectious Endocarditis at eMedicine 2. ^ "Noninfective Endocarditis: Endocarditis: Merck Manual Professional". Retrieved 2008-12-22. 3. ^ "Marantic endocarditis". Online Medical Dictionary. Retrieved 2008-12-22. 4. ^ "UpToDate". 5. ^ "nonbacterial thrombotic endocarditis" at Dorland's Medical Dictionary ## External links[edit] Classification D * MeSH: D059905 * DiseasesDB: 29250 External resources * eMedicine: article/155230 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * t * e Paraneoplastic syndromes Endocrine * Hypercalcaemia * SIADH * Zollinger–Ellison syndrome * Cushing's syndrome Hematological * Multicentric reticulohistiocytosis * Nonbacterial thrombotic endocarditis Neurological * Paraneoplastic cerebellar degeneration * Encephalomyelitis * Limbic encephalitis * Opsoclonus * Polymyositis * Transverse myelitis * Lambert–Eaton myasthenic syndrome * Anti-NMDA receptor encephalitis Musculoskeletal * Dermatomyositis * Hypertrophic osteopathy Mucocutaneous reactive erythema * Erythema gyratum repens * Necrolytic migratory erythema papulosquamous * Acanthosis nigricans * Ichthyosis acquisita * Acrokeratosis paraneoplastica of Bazex * Extramammary Paget's disease * Florid cutaneous papillomatosis * Leser-Trélat sign * Pityriasis rotunda * Tripe palms Other * Febrile neutrophilic dermatosis * Pyoderma gangrenosum * Paraneoplastic pemphigus [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	Nonbacterial thrombotic endocarditis	c3202971	5,948	wikipedia	https://en.wikipedia.org/wiki/Nonbacterial_thrombotic_endocarditis	2021-01-18T18:39:07	{"mesh": ["D059905"], "icd-9": ["424.90"], "icd-10": ["I38"], "wikidata": ["Q73518"]}
Felid alphaherpesvirus 1 Virus classification (unranked): Virus Realm: Duplodnaviria Kingdom: Heunggongvirae Phylum: Peploviricota Class: Herviviricetes Order: Herpesvirales Family: Herpesviridae Genus: Varicellovirus Species: Felid alphaherpesvirus 1 Synonyms * Felid herpesvirus 1[1] * Feline rhinotracheitis virus[2] Feline viral rhinotracheitis infection Feline viral rhinotracheitis (FVR) is an upper respiratory or pulmonary infection of cats caused by Felid alphaherpesvirus 1 (FeHV-1), of the family Herpesviridae. It is also commonly referred to as feline influenza, feline coryza, and feline pneumonia but, as these terms describe other very distinct collections of respiratory symptoms, they are misnomers for the condition. Viral respiratory diseases in cats can be serious, especially in catteries and kennels. Causing one-half of the respiratory diseases in cats,[3] FVR is the most important of these diseases and is found worldwide. The other important cause of feline respiratory disease is feline calicivirus. FVR is very contagious and can cause severe disease, including death from pneumonia in young kittens. It can cause flat-chested kitten syndrome, but most evidence for this is anecdotal. All members of the family Felidae are susceptible to FVR; in fact, FHV-1 has caused a fatal encephalitis in lions in Germany.[4] ## Contents * 1 History * 2 Transmission * 3 Clinical signs * 4 Diagnosis * 5 Treatment and prevention * 5.1 Vaccine * 5.2 Preventing spread of virus * 6 See also * 7 References * 8 External links ## History[edit] FHV-1 was first isolated from cats in 1958 in the United States.[5] ## Transmission[edit] FVR is transmitted through direct contact only.[6] It replicates in the nasal and nasopharyngeal tissues and the tonsils. Viremia (the presence of the virus in the blood) is rare. The virus is shed in saliva and eye and nasal secretions, and can also be spread by fomites. FVR has a two- to five-day incubation period.[3] The virus is shed for one to three weeks postinfection.[4] Latently infected cats (carriers) will shed FHV-1 intermittently for life, with the virus persisting within the trigeminal ganglion. Stress and use of corticosteroids precipitate shedding. Most disinfectants, antiseptics and detergents are effective against the virus.[6] ## Clinical signs[edit] Chronic epiphora in a carrier of FVR Initial signs of FVR include coughing, sneezing, nasal discharge, conjunctivitis, and sometimes fever (up to 106) and loss of appetite. These usually resolve within four to seven days, but secondary bacterial infections can cause the persistence of clinical signs for weeks.[4] Frontal sinusitis and empyema can also result. FHV-1 also has a predilection for corneal epithelium, resulting in corneal ulcers, often pinpoint or dendritic in shape. Other ocular signs of FHV-1 infection include conjunctivitis, keratitis, keratoconjunctivitis sicca (decreased tear production), and corneal sequestra.[7] Infection of the nasolacrimal duct can result in chronic epiphora (excess tearing). Ulcerative skin disease can also result from FHV-1 infection.[8] FHV-1 can also cause abortion in pregnant queens, usually at the sixth week of gestation,[3] although this may be due to systemic effects of the infection rather than the virus directly. In chronic nasal and sinus disease of cats, FHV-1 may play more of an initiating role than an ongoing cause. Infection at an early age may permanently damage nasal and sinus tissue, causing a disruption of ciliary clearance of mucus and bacteria, and predispose these cats to chronic bacterial infections.[9] ## Diagnosis[edit] Diagnosis of FVR is usually by clinical signs, especially corneal ulceration. Definitive diagnosis can be done by direct immunofluorescence or virus isolation. However, many healthy cats are subclinical carriers of feline herpes virus, so a positive test for FHV-1 does not necessarily indicate that signs of an upper respiratory tract infection are due to FVR. Early in the course of the disease, histological analysis of cells from the tonsils, nasal tissue, or nictitating membrane (third eyelid) may show inclusion bodies (a collection of viral particles) within the nucleus of infected cells.[10] ## Treatment and prevention[edit] Polyprenyl Immunostimulant is the only currently-approved treatment in the US for feline rhinotracheitis caused by herpesvirus.[11] Effectiveness was demonstrated in a clinical study with cats experimentally infected with feline herpesvirus: 20 cats were treated with Polyprenyl Immunostimulant and 20 received a placebo; the study established that the severity of the disease was lower in the group treated with Polyprenyl Immunostimulant.[12] Safety was demonstrated in 390 personally-owned cats from 2 days to 16 years of age, residing in 10 states (ibid). Antibiotics are commonly used to prevent secondary bacterial infection. There are no specific antiviral drugs in common use at this time for FVR, although one study has shown that ganciclovir, PMEDAP, and cidofovir hold promise for treatment.[13] More recent research has indicated that systemic famciclovir is effective at treating this infection in cats without the side effects reported with other anti-viral agents.[14] More severe cases may require supportive care such as intravenous fluid therapy, oxygen therapy, or even a feeding tube. Conjunctivitis and corneal ulcers are treated with topical antibiotics for secondary bacterial infection. Lysine is commonly used as a treatment, however in a 2015 systematic review, where the authors investigated all clinical trials with cats as well as in vitro studies, concluded that lysine supplementation is likely not effective for the treatment or prevention of feline herpesvirus 1 infection.[15] ### Vaccine[edit] There is a vaccine for FHV-1 available (ATCvet code: QI06AA08 (WHO), plus various combination vaccines), but although it limits or weakens the severity of the disease and may reduce viral shedding, it does not prevent infection with FVR.[16] Studies have shown a duration of immunity of this vaccine to be at least three years.[17] The use of serology to demonstrate circulating antibodies to FHV-1 has been shown to have a positive predictive value for indicating protection from this disease.[18] ### Preventing spread of virus[edit] Most household disinfectants will inactivate FHV-1. The virus can survive up to 18 hours in a damp environment, but less in a dry environment and only shortly as an aerosol.[16] ## See also[edit] * Feline vaccination ## References[edit] 1. ^ "ICTV Taxonomy history: Felid alphaherpesvirus 1". International Committee on Taxonomy of Viruses (ICTV). Retrieved 9 January 2019. 2. ^ "ICTV 9th Report (2011) Herpesviridae". International Committee on Taxonomy of Viruses (ICTV). Retrieved 9 January 2019. "Felid herpesvirus 1 Felid herpesvirus 1 [FJ478159=NC_013590] (FeHV-1) (Feline rhinotracheitis virus)" 3. ^ a b c Carter, G.R.; Flores, E.F.; Wise, D.J. (2006). "Herpesviridae". A Concise Review of Veterinary Virology. Retrieved 2006-06-08. 4. ^ a b c Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 978-0-7216-6795-9.[page needed] 5. ^ Maeda, Ken; Horimoto, Taisuke; Mikami, Takeshi (1998). "Properties and Functions of Feline Herpesvirus Type 1 Glycoproteins". Journal of Veterinary Medical Science. 60 (8): 881–8. doi:10.1292/jvms.60.881. PMID 9764399. 6. ^ a b Thiry, Etienne; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; et al. (2009). "Feline herpesvirus infection. ABCD guidelines on prevention and management". Journal of Feline Medicine & Surgery. 11 (7): 547–55. doi:10.1016/j.jfms.2009.05.003. PMC 7129359. PMID 19481034. 7. ^ Stiles, J (1995). "Treatment of cats with ocular disease attributable to herpesvirus infection: 17 cases (1983–1993)". Journal of the American Veterinary Medical Association. 207 (5): 599–603. PMID 7649774. 8. ^ Holland, Jessica L.; Outerbridge, Catherine A.; Affolter, Verena K.; Maggs, David J. (2006). "Detection of feline herpesvirus 1 DNA in skin biopsy specimens from cats with or without dermatitis". Journal of the American Veterinary Medical Association. 229 (9): 1442–6. doi:10.2460/javma.229.9.1442. PMID 17078806. 9. ^ Johnson, Lynelle R.; Foley, Janet E.; De Cock, Hilde E. V.; Clarke, Heather E.; Maggs, David J. (2005). "Assessment of infectious organisms associated with chronic rhinosinusitis in cats". Journal of the American Veterinary Medical Association. 227 (4): 579–85. doi:10.2460/javma.2005.227.579. PMID 16117066. 10. ^ "Feline Respiratory Disease Complex". The Merck Veterinary Manual. 2006. Retrieved 2007-04-01. 11. ^ [1] 12. ^ Legendre, Al (2017). "Polyprenyl Immunostimulant in Feline Rhinotracheitis: Randomized Placebo-Controlled Experimental and Field Safety Studies". Front. Vet. Sci. 4: 24. doi:10.3389/fvets.2017.00024. PMC 5326765. PMID 28289684. 13. ^ Van Der Meulen, K; Garré, B; Croubels, S; Nauwynck, H (2006). "In vitro comparison of antiviral drugs against feline herpesvirus 1". BMC Veterinary Research. 2: 13. doi:10.1186/1746-6148-2-13. PMC 1475582. PMID 16640781. 14. ^ Malik, R.; Lessels, N. S.; Webb, S.; Meek, M.; Graham, P. G.; Vitale, C.; Norris, J. M.; Power, H. (2009). "Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs". Journal of Feline Medicine & Surgery. 11 (1): 40–48. doi:10.1016/j.jfms.2008.11.012. PMID 19154974. 15. ^ Bol, Sebastiaan; Bunnik, Evelien M. (2015). "Lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats: a systematic review". BMC Veterinary Research. 11: 284. doi:10.1186/s12917-015-0594-3. PMC 4647294. PMID 26573523. 16. ^ a b Gaskell, Rosalind; Dawson, Susan; Radford, Alan; Thiry, Etienne (2007). "Feline herpesvirus" (PDF). Veterinary Research. 38 (2): 337–54. doi:10.1051/vetres:2006063. PMID 17296160. 17. ^ Gore, TC; Lakshmanan, N; Williams, JR; Jirjis, FF; Chester, ST; Duncan, KL; Coyne, MJ; Lum, MA; Sterner, FJ (2006). "Three-year duration of immunity in cats following vaccination against feline rhinotracheitis virus, feline calicivirus, and feline panleukopenia virus". Veterinary Therapeutics : Research in Applied Veterinary Medicine. 7 (3): 213–22. PMID 17039444. 18. ^ Lappin, Michael R. (2006). Use of serological tests to determine vaccine needs. Proceedings of the North American Veterinary Conference. ## External links[edit] Wikimedia Commons has media related to Feline viral rhinotracheitis. * Feline Upper Respiratory Disease from The Pet Health Library * v * t * e Taxonomy of the Herpesvirales Higher taxonomy: Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales Malacoherpesviridae Aurivirus * AbHV-1 Ostreavirus * OsHV-1 Alloherpesviridae Batrachovirus * RaHV-1 * 2 * 3 Cyprinivirus * AngHV-1 * CyHV-1 * 2 * 3 Ictalurivirus * AciHV-2 * IcHV-1 * 2 Salmonivirus * SalHV-1 * 2 * 3 Herpesviridae IgHV-2 α ChHV-6 Iltovirus * GaHV-1 * PsHV-1 Mardivirus * AnHV-1 * CoHV-1 * GaHV-2 * 3 * MeHV-1 * SpAHV-1 Scutavirus * ChHV-5 * TeHV-3 Simplexvirus * AtHV-1 * BoHV-2 * CeHV-2 * HHV-1 * 2 * LeHV-4 * McHV-1 * MaHV-1 * 2 * PnHV-3 * PaHV-2 * PtHV-1 * SaHV-1 Varicellovirus * BoHV-1 * 5 * BuHV-1 * CaHV-1 * CpHV-1 * CeHV-9 * CvHV-1 * 2 * EHV-1 * 3 * 4 * 8 * 9 * FeHV-1 * HHV-3 * MoHV-1 * PhHV-1 * SuHV-1 β CaHV-2 TuHV-1 Cytomegalovirus * AoHV-1 * CbHV-1 * CeHV-5 * HHV-5 * McHV-3 * 8 * MnHV-1 * PnHV-2 * PaHV-3 * 4 * SaHV-4 Muromegalovirus * MuHV-1 * 2 * 8 Proboscivirus * ElHV-1 * 4 * 5 Roseolovirus * HHV-6A * 6B * 7 * McHV-9 * MuHV-3 * SuHV-2 γ EHV-7 PhHV-2 SgHV-1 Lymphocryptovirus * CalHV-3 * CeHV-14 * GoHV-1 * HHV-4 * McHV-4 * 10 * PnHV-1 * PaHV-1 * PoHV-2 Macavirus * AlHV-1 * 2 * BoHV-6 * CpHV-2 * HiHV-1 * OvHV-2 * SuHV-3 * 4 * 5 Percavirus * EHV-2 * 5 * FeHV-1 * MusHV-1 * PhHV-3 * VeHV-1 Rhadinovirus * AtHV-2 * 3 * BoHV-4 * CrHV-2 * HHV-8 * McHV-5 * 8 * 11 * 12 * MuHV-4 * 7 * SaHV-2 Unassigned species listed below parent taxon –– Source: ICTV –– Wikispecies * v * t * e Domestic cats Felinology * Anatomy * Genetics * Dwarf cat * Kitten * Odd-eyed cat * Squitten Coat genetics Bicolor cat Black cat Calico cat Tabby cat Tortoiseshell cat Health * Aging * Declawing * Diet * dental health * senior * Neutering * Spaying * Vaccination Behavior * Body language * Catfight * Catnip * valerian * Communication * Meow * Purr * Kneading * Intelligence * Play and toys * Righting reflex * Senses Human–cat interaction * Ailurophobia * Animal-assisted therapy * Bodega cat * Cat cafés * Cat massage * Cat meat * Cat-scratch disease * Cat show * Cats in ancient Egypt * Cultural depictions * Internet * Farm cat * Feral cat * Cats and Islam * Lolcat * National Cat Day * Puppy cat * Ship's cat * Zoonosis Registries * American Cat Fanciers Association * Associazione Nazionale Felina Italiana * Canadian Cat Association * Cat Aficionado Association * Cat Fanciers' Association * Fédération Internationale Féline * Governing Council of the Cat Fancy * Southern Africa Cat Council * The International Cat Association * World Cat Congress * World Cat Federation Breeds (full list) (experimental) Fully domestic Abyssinian American Curl American Shorthair Balinese Brazilian Shorthair British Shorthair Birman Bombay Burmese Burmilla California Spangled Chartreux Chinese Li Hua Colorpoint Shorthair Cornish Rex Cymric Devon Rex Donskoy Egyptian Mau European Shorthair Exotic Shorthair German Rex Himalayan Japanese Bobtail Javanese Khao Manee Korat Kurilian Bobtail Lykoi Maine Coon Manx Munchkin Norwegian Forest Ocicat Ojos Azules Oriental Shorthair Persian Peterbald Pixie-bob Raas Ragdoll Ragamuffin Russian Blue Scottish Fold Selkirk Rex Siamese Siberian Singapura Snowshoe Somali Sphynx Thai Traditional Persian Tonkinese Toyger Turkish Angora Turkish Van Hybrid Bengal Chausie Highlander Savannah Serengeti Landraces * Aegean * Cyprus * Domestic long-haired * Domestic short-haired * Kellas * Sokoke * Van Diseases and disorders * Acne * Asthma * Calicivirus * Congenital sensorineural deafness * Feline corneal sequestrum * Flea * Heartworm * Hepatic lipidosis * Hypertrophic cardiomyopathy * Immunodeficiency virus * Infectious peritonitis * Leukemia virus * Lower urinary tract disease * Panleukopenia * Polydactyly * Rabies * Ringworm * Roundworm * Skin disorders * Tick * Toxoplasmosis * Viral rhinotracheitis * Book * Category Taxon identifiers Felid herpesvirus 1 * Wikidata: Q11752015 * Wikispecies: Felid alphaherpesvirus 1 * IRMNG: 11459794 Felid alphaherpesvirus 1 * Wikidata: Q24808714 * NCBI: 10334 [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	Feline viral rhinotracheitis	c0276243	5,949	wikipedia	https://en.wikipedia.org/wiki/Feline_viral_rhinotracheitis	2021-01-18T18:52:21	{"wikidata": ["Q15660578"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (December 2012) Entomopia (from the Greek roots for "insect" and "eye"), is a form of polyopia in which a grid-like pattern of multiple copies of the same visual image is seen.[1] Entomopia may be due to disease of the occipital lobe, defects in visual integration and fixation or incomplete visual processing due to poor visuospatial localisation in the hemianopic field,[2] although its causes are unknown.[3] Reassurance may be the only treatment.[3] ## See also[edit] * Diplopia ## References[edit] 1. ^ Jaime R. Lopez; Bruce T. Adornato; W. F. Hoyt (1993). ""Entomopia": a remarkable case of cerebral polyopia". Neurology. 43 (10): 2145–2146. doi:10.1212/wnl.43.10.2145. PMID 8413985. 2. ^ M. B. Bender (1945). "Polyopia and monocular diplopia of cerebral origin". Archives of Neurology and Psychiatry. 54 (5): 323–328. doi:10.1001/archneurpsyc.1945.02300110007002. 3. ^ a b Andrew J. Larner (2006). "Entomopia" (PDF). Advances in Clinical Neuroscience and Rehabilitation. 6 (4): 30. This medical sign 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	Entomopia	None	5,950	wikipedia	https://en.wikipedia.org/wiki/Entomopia	2021-01-18T18:35:50	{"wikidata": ["Q5380627"]}
Severe intellectual disability-progressive spastic diplegia syndrome is a rare condition that has been described in a few people with severe intellectual disability . Other signs and symptoms include progressive microcephaly (very small head); ataxia (lack of coordination); spasticity; and/or skin, hair and mild facial anomalies. It is caused by changes (mutations) in the CTNNB1 gene and it is inherited in an autosomal dominant fashion. Treatment is based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA	Severe intellectual disability-progressive spastic diplegia syndrome	c3554449	5,951	gard	https://rarediseases.info.nih.gov/diseases/3505/severe-intellectual-disability-progressive-spastic-diplegia-syndrome	2021-01-18T17:57:44	{"omim": ["615075"], "orphanet": ["404473"], "synonyms": ["Intellectual disability, autosomal dominant 19", "CTNNB1 syndrome", "CTNNB1-related intellectual disability"]}
Osteochondromatosis SpecialtyMedical genetics Osteochondromatosis is a condition involving a proliferation of osteochondromas.[1] Types include: * Hereditary multiple exostoses * Synovial osteochondromatosis ## References[edit] 1. ^ "osteochondromatosis" at Dorland's Medical Dictionary ## External links[edit] Classification D * ICD-10: Q78.6 * ICD-9-CM: 238.0 * ICD-O: M9210/1 * MeSH: D018216 * DiseasesDB: 29635 * SNOMED CT: 66467005 * 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 * t * e Tumours of bone and cartilage Diaphysis * Multiple myeloma * Epithelia * Adamantinoma * Primitive neuroectodermal tumor * Ewing family * Ewing's sarcoma Metaphysis Osteoblast * Osteoid osteoma * Osteoblastoma * Osteoma/osteosarcoma Chondroblast * Chondroma/ecchondroma/enchondroma * Enchondromatosis * Extraskeletal chondroma * Chondrosarcoma * Mesenchymal chondrosarcoma * Myxoid chondrosarcoma * Osteochondroma * Osteochondromatosis * Chondromyxoid fibroma Fibrous * Ossifying fibroma * Fibrosarcoma Epiphysis Chondroblast * Chondroblastoma Myeloid * Giant-cell tumor of bone Other Notochord * Chordoma * v * t * e Osteochondrodysplasia Osteodysplasia// osteodystrophy Diaphysis * Camurati–Engelmann disease Metaphysis * Metaphyseal dysplasia * Jansen's metaphyseal chondrodysplasia * Schmid metaphyseal chondrodysplasia Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia * Opsismodysplasia * Polyostotic fibrous dysplasia * McCune–Albright syndrome Chondrodysplasia/ chondrodystrophy (including dwarfism) Osteochondroma * osteochondromatosis * Hereditary multiple exostoses Chondroma/enchondroma * enchondromatosis * Ollier disease * Maffucci syndrome Growth factor receptor FGFR2: * Antley–Bixler syndrome FGFR3: * Achondroplasia * Hypochondroplasia * Thanatophoric dysplasia COL2A1 collagen disease * Achondrogenesis * type 2 * Hypochondrogenesis SLC26A2 sulfation defect * Achondrogenesis * type 1B * Autosomal recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia Chondrodysplasia punctata * Rhizomelic chondrodysplasia punctata * Conradi–Hünermann syndrome Other dwarfism * Fibrochondrogenesis * Short rib – polydactyly syndrome * Majewski's polydactyly syndrome * Léri–Weill dyschondrosteosis This article about a neoplasm 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	Osteochondromatosis	c0206641	5,952	wikipedia	https://en.wikipedia.org/wiki/Osteochondromatosis	2021-01-18T18:56:03	{"mesh": ["D018216"], "icd-9": ["238.0"], "icd-10": ["Q78.6"], "wikidata": ["Q7107610"]}
A cystic teratoma with a small Rokitansky nodule — region of thickened cyst wall (bottom part of image). In gynecology, a Rokitansky nodule is a mass or lump in an ovarian teratomatous cyst.[1] ## See also[edit] * Baron Carl von Rokitansky * Rokitansky-Aschoff sinuses ## References[edit] 1. ^ Outwater EK, Siegelman ES, Hunt JL (2001). "Ovarian teratomas: tumor types and imaging characteristics". Radiographics. 21 (2): 475–90. doi:10.1148/radiographics.21.2.g01mr09475. PMID 11259710. ## External links[edit] * Image of a Rokitansky nodule \- geocities.com [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	Rokitansky nodule	None	5,953	wikipedia	https://en.wikipedia.org/wiki/Rokitansky_nodule	2021-01-18T18:36:26	{"wikidata": ["Q7360009"]}
Human and animal disease This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (September 2020) (Learn how and when to remove this template message) Brucellosis Other namesundulant fever, undulating fever, Mediterranean fever, Malta fever, Cyprus fever, rock fever (Micrococcus melitensis)[1] SpecialtyInfectious disease Symptomscoughing Brucellosis[2][3] is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions.[4] It is also known as undulant fever, Malta fever, and Mediterranean fever.[5] Brucella species are small, Gram-negative, nonmotile, nonspore-forming, rod-shaped (coccobacilli) bacteria. They function as facultative intracellular parasites, causing chronic disease, which usually persists for life. Four species infect humans: B. abortus, B. canis, B. melitensis, and B. suis. B. abortus is less virulent than B. melitensis and is primarily a disease of cattle. B. canis affects dogs. B. melitensis is the most virulent and invasive species; it usually infects goats and occasionally sheep. B. suis is of intermediate virulence and chiefly infects pigs. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized in animals and humans since the early 20th century. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Epidemiology * 7.1 Argentina * 7.2 Australia * 7.3 Canada * 7.4 China * 7.5 Europe * 7.5.1 Malta * 7.5.2 Republic of Ireland * 7.5.3 UK * 7.6 New Zealand * 7.7 United States * 8 History * 8.1 Biological warfare * 9 Other animals * 9.1 Cattle * 9.2 Dogs * 9.3 Aquatic wildlife * 9.4 Terrestrial wildlife * 9.5 Effects on hunters * 10 See also * 11 References * 12 Further reading * 13 External links ## Signs and symptoms[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (November 2020) (Learn how and when to remove this template message) A graph of the cases of brucellosis in humans in the United States from the years 1993–2010 surveyed by the Centers for Disease Control and Prevention through the National Notifiable Diseases Surveillance System[6] The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years. In the first stage of the disease, bacteremia occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic foul, moldy smell sometimes likened to wet hay), and migratory arthralgia and myalgia (joint and muscle pain).[citation needed] Blood tests characteristically reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes such as aspartate aminotransferase and alanine aminotransferase, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen.[citation needed] This complex is, at least in Portugal, Israel, Syria, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations[clarification needed] or become chronic. The focalizations of brucellosis occur usually in bones and joints, and osteomyelitis or spondylodiscitis of the lumbar spine accompanied by sacroiliitis is very characteristic of this disease. Orchitis is also common in men. The consequences of Brucella infection are highly variable and may include arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis. ## Cause[edit] Granuloma and necrosis in the liver of a guinea pig infected with Brucella suis Brucellosis in humans is usually associated with consumption of unpasteurized milk and soft cheeses made from the milk of infected animals—primarily goats, infected with B. melitensis and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers.[7] Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, miscarriage, sweating, weakness, anemia, headaches, depression, and muscular and bodily pain. The other strains, B. suis and B. canis, cause infection in pigs and dogs, respectively. Overall findings support that brucellosis poses an occupational risk to goat farmers with specific areas of concern including weak awareness of disease transmission to humans and lack of knowledge on specific safe farm practices such as quarantine practices.[8] ## Diagnosis[edit] The diagnosis of brucellosis relies on: 1. Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures: The growth of brucellae is extremely slow (they can take up to two months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae. 2. Demonstration of antibodies against the agent either with the classic Huddleson, Wright, and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease 3. Histologic evidence of granulomatous hepatitis on hepatic biopsy 4. Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of the anterosuperior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis. Definite diagnosis of brucellosis requires the isolation of the organism from the blood, body fluids, or tissues, but serological methods may be the only tests available in many settings. Positive blood culture yield ranges between 40 and 70% and is less commonly positive for B. abortus than B. melitensis or B. suis. Identification of specific antibodies against bacterial lipopolysaccharide and other antigens can be detected by the standard agglutination test (SAT), rose Bengal, 2-mercaptoethanol (2-ME), antihuman globulin (Coombs’) and indirect enzyme-linked immunosorbent assay (ELISA). SAT is the most commonly used serology in endemic areas.[9][10] An agglutination titre greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas. Due to the similarity of the O polysaccharide of Brucella to that of various other Gram-negative bacteria (e.g. Francisella tularensis, Escherichia coli, Salmonella urbana, Yersinia enterocolitica, Vibrio cholerae, and Stenotrophomonas maltophilia), the appearance of cross-reactions of class M immunoglobulins may occur. The inability to diagnose B. canis by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies (the prozone phenomenon) in the α2-globulin (IgA) and in the α-globulin (IgG) fractions. Dipstick assays are new and promising, based on the binding of Brucella IgM antibodies, and are simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with better sensitivity and specificity than the SAT in most recent comparative studies.[11] The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-Brucella antibodies, is an increasingly used adjunctive test when resources permit. PCR is fast and should be specific. Many varieties of PCR have been developed (e.g. nested PCR, realtime PCR, and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment.[12] Unfortunately, these are not standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis. Other laboratory findings include normal peripheral white cell count, and occasional leucopenia with relative lymphocytosis. The serum biochemical profiles are commonly normal.[13] ## Prevention[edit] Surveillance using serological tests, as well as tests on milk such as the milk ring test, can be used for screening and play an important role in campaigns to eliminate the disease. Also, individual animal testing both for trade and for disease-control purposes is practiced. In endemic areas, vaccination is often used to reduce the incidence of infection. An animal vaccine is available that uses modified live bacteria. The World Organisation for Animal Health Manual of Diagnostic Test and Vaccines for Terrestrial Animals provides detailed guidance on the production of vaccines. As the disease is closer to being eliminated, a test and eradication program is required to completely eliminate it. The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by pasteurizing all milk that is to be ingested by human beings, either in its unaltered form or as a derivative, such as cheese. ## Treatment[edit] Antibiotics such as tetracyclines, rifampin, and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells. The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or contraindicated.[14] Another widely used regimen is doxycycline plus rifampin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampin and co-trimoxazole, has been used successfully to treat neurobrucellosis.[15] Doxycycline plus streptomycin regimen (for 2 to 3 weeks) is more effective than doxycycline plus rifampicin regimen (for 6 weeks).[16] Doxycycline is able to cross the blood–brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5 to 10% of patients with Malta fever. ## Prognosis[edit] The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was endocarditis. Recent advances in antibiotics and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement.[citation needed] Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. Exposure of diagnostic laboratory personnel to Brucella organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient.[17] After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for 6 months.[18] Recently published experience confirms that prolonged and frequent serological follow-up consumes significant resources without yielding much information, and is burdensome for the affected staff, who often fail to comply. The side effects of the usual recommended regimen of rifampicin and doxycycline for 3 weeks also reduces treatment adherence. As no evidence shows treatment with two drugs is superior to monotherapy, British guidelines now recommend doxycycline alone for 3 weeks and a less onerous follow-up protocol.[19] ## Epidemiology[edit] ### Argentina[edit] According to a study published in 2002, an estimated 10–13% of farm animals are infected with Brucella species.[20] Annual losses from the disease were calculated at around $60 million. Since 1932, government agencies have undertaken efforts to contain the disease. Currently, all cattle of ages 3–8 months must receive the Brucella abortus strain 19 vaccine.[21] ### Australia[edit] Australia is free of cattle brucellosis, although it occurred in the past. Brucellosis of sheep or goats has never been reported. Brucellosis of pigs does occur. Feral pigs are the typical source of human infections.[22][23] ### Canada[edit] On 19 September 1985, the Canadian government declared its cattle population brucellosis-free. Brucellosis ring testing of milk and cream, and testing of cattle to be slaughtered ended on 1 April 1999. Monitoring continues through testing at auction markets, through standard disease-reporting procedures, and through testing of cattle being qualified for export to countries other than the United States.[24] ### China[edit] An outbreak infecting humans took place in Lanzhou in 2020 after the Lanzhou Biopharmaceutical Plant, which was involved in vaccine production, accidentally pumped out the bacteria into the atmosphere in exhaust air due to use of expired disinfectant. The outbreak affected over 6,000 people.[25][26] ### Europe[edit] Disease incidence map of B. melitensis infections in animals in Europe during the first half of 2006 never reported not reported in this period confirmed clinical disease confirmed infection no information #### Malta[edit] Until the early 20th century, the disease was endemic in Malta to the point of it being referred to as "Maltese fever". Since 2005, due to a strict regimen of certification of milk animals and widespread use of pasteurization, the illness has been eradicated from Malta.[27] #### Republic of Ireland[edit] Ireland was declared free of brucellosis on 1 July 2009. The disease had troubled the country's farmers and veterinarians for several decades.[28][29] The Irish government submitted an application to the European Commission, which verified that Ireland had been liberated.[29] Brendan Smith, Ireland's then Minister for Agriculture, Food and the Marine, said the elimination of brucellosis was "a landmark in the history of disease eradication in Ireland".[28][29] Ireland's Department of Agriculture, Food and the Marine intends to reduce its brucellosis eradication programme now that eradication has been confirmed.[28][29] #### UK[edit] Mainland Britain has been free of brucellosis since 1979, although there have been episodic re-introductions since.[30] The last outbreak of brucellosis in Great Britain was in cattle in Cornwall in 2004.[30][31] Northern Ireland was declared officially brucellosis-free in 2015.[30] ### New Zealand[edit] Brucellosis in New Zealand is limited to sheep (B. ovis). The country is free of all other species of Brucella.[32] ### United States[edit] Dairy herds in the USA are tested at least once a year to be certified brucellosis-free.[33] with the Brucella milk ring test.[34] Cows confirmed to be infected are often killed. In the United States, veterinarians are required[citation needed] to vaccinate all young stock, to further reduce the chance of zoonotic transmission. This vaccination is usually referred to as a "calfhood" vaccination. Most cattle receive a tattoo in one of their ears, serving as proof of their vaccination status. This tattoo also includes the last digit of the year they were born.[35] The first state–federal cooperative efforts towards eradication of brucellosis caused by B. abortus in the U.S. began in 1934. Brucellosis was originally imported to North America with non-native domestic cattle (Bos taurus), which transmitted the disease to wild bison (Bison bison) and elk (Cervus canadensis). No records exist of brucellosis in ungulates native to America until the early 19th century.[36] ## History[edit] David Bruce (centre), with members of the Mediterranean Fever Commission (Brucellosis) The lab in which Sir Themistocles Zammit and the Mediterranean Fever Commission carried out research about brucellosis from 1904 to 1906 is located within the Castellania in Valletta, Malta. Brucellosis first came to the attention of British medical officers in the 1850s in Malta during the Crimean War, and was referred to as Malta Fever. Jeffery Allen Marston (1831–1911) described his own case of the disease in 1861. The causal relationship between organism and disease was first established in 1887 by David Bruce.[37][38] The agent that Bruce identified was classed as a coccus. In 1897, Danish veterinarian Bernhard Bang isolated a bacillus as the agent of heightened spontaneous abortion in cows, and the name "Bang's disease" was assigned to this condition. At the time, no one knew that this bacillus had anything to do with the causative agent in Malta fever. Maltese scientist and archaeologist Themistocles Zammit identified unpasteurized goat milk as the major etiologic factor of undulant fever in June 1905.[39] In the late 1910s, American bacteriologist Alice C. Evans was studying the Bang bacillus and gradually realized that it was virtually indistinguishable from the Bruce coccus.[40] The short-rod versus oblong-round morphologic borderline explained the leveling of the erstwhile bacillus/coccus distinction (that is, these "two" pathogens were not a coccus versus a bacillus but rather were one coccobacillus).[40] The Bang bacillus was already known to be enzootic in American dairy cattle, which showed itself in the regularity with which herds experienced contagious abortion.[40] Having made the discovery that the bacteria were certainly nearly identical and perhaps totally so, Evans then wondered why Malta fever was not widely diagnosed or reported in the United States.[40] She began to wonder whether many cases of vaguely defined febrile illnesses were in fact caused by the drinking of raw (unpasteurized) milk.[40] During the 1920s, this hypothesis was vindicated. Such illnesses ranged from undiagnosed and untreated gastrointestinal upset to misdiagnosed[40] febrile and painful versions, some even fatal. This advance in bacteriological science sparked extensive changes in the American dairy industry to improve food safety. The changes included making pasteurization standard and greatly tightening the standards of cleanliness in milkhouses on dairy farms. The expense prompted delay and skepticism in the industry,[40] but the new hygiene rules eventually became the norm. Although these measures have sometimes struck people as overdone in the decades since, being unhygienic at milking time or in the milkhouse, or drinking raw milk, are not a safe alternative. In the decades after Evans's work, this genus, which received the name Brucella in honor of Bruce, was found to contain several species with varying virulence. The name "brucellosis" gradually replaced the 19th-century names Mediterranean fever and Malta fever.[41] In 1989, neurologists in Saudi Arabia discovered "neurobrucellosis", a neurological involvement in brucellosis.[42][43] These obsolete names have previously been applied to brucellosis:[41][44] * Crimean fever * Cyprus fever * Gibraltar fever * Goat fever * Italian fever * Neapolitan fever ### Biological warfare[edit] Brucella species were weaponized by several advanced countries by the mid-20th century. In 1954, B. suis became the first agent weaponized by the United States at its Pine Bluff Arsenal near Pine Bluff, Arkansas. Brucella species survive well in aerosols and resist drying. Brucella and all other remaining biological weapons in the U.S. arsenal were destroyed in 1971–72 when the American offensive biological warfare program was discontinued by order of President Richard Nixon.[45] The experimental American bacteriological warfare program focused on three agents of the Brucella group: * Porcine brucellosis (agent US) * Bovine brucellosis (agent AA) * Caprine brucellosis (agent AM) Agent US was in advanced development by the end of World War II. When the United States Air Force (USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet, based on the four-pound bursting bomblet developed for spreading anthrax during World War II. Though the capability was developed, operational testing indicated the weapon was less than desirable, and the USAF designed it as an interim capability until it could eventually be replaced by a more effective biological weapon. The main drawback of using the M114 with Agent US was that it acted mainly as an incapacitating agent, whereas the USAF administration wanted weapons that were deadly. Also, the stability of M114 in storage was too low to allow for storing it at forward air bases, and the logistical requirements to neutralize a target were far higher than was originally planned. Ultimately, this would have required too much logistical support to be practical in the field. Agents US and AA had a median infective dose of 500 organisms/person, and for Agent AM it was 300 organisms/person. The time-of-incubation was believed to be about 2 weeks, with a duration of infection of several months. The lethality estimate was based on epidemiological information at 1 to 2%. Agent AM was believed to be a somewhat more virulent disease, with a fatality rate of 3% being expected. ## Other animals[edit] Species infecting domestic livestock are B. abortus (cattle, bison, and elk), B. canis (dogs), B. melitensis (goats and sheep), B. ovis (sheep), and B. suis (caribou and pigs). Brucella species have also been isolated from several marine mammal species (cetaceans and pinnipeds). ### Cattle[edit] B. abortus is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calving or abortion. Once exposed, the likelihood of an animal becoming infected is variable, depending on age, pregnancy status, and other intrinsic factors of the animal, as well as the number of bacteria to which the animal was exposed.[46] The most common clinical signs of cattle infected with B. abortus are high incidences of abortions, arthritic joints, and retained placenta. The two main causes for spontaneous abortion in animals are erythritol, which can promote infections in the fetus and placenta, and the lack of anti-Brucella activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely seminal vesicles, ampullae, testicles, and epididymes. ### Dogs[edit] The causative agent of brucellosis in dogs, B. canis, is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans who come in contact with infected aborted tissue or semen. The bacteria in dogs normally infect the genitals and lymphatic system, but can also spread to the eyes, kidneys, and intervertebral discs. Brucellosis in the intervertebral disc is one possible cause of discospondylitis. Symptoms of brucellosis in dogs include abortion in female dogs and scrotal inflammation and orchitis in males. Fever is uncommon. Infection of the eye can cause uveitis, and infection of the intervertebral disc can cause pain or weakness. Blood testing of the dogs prior to breeding can prevent the spread of this disease. It is treated with antibiotics, as with humans, but it is difficult to cure.[47] ### Aquatic wildlife[edit] Brucellosis in cetaceans is caused by the bacterium B. ceti. First discovered in the aborted fetus of a bottlenose dolphin, the structure of B. ceti is similar to Brucella in land animals. B. ceti is commonly detected in two suborders of cetaceans, the Mysticeti and Odontoceti. The Mysticeti include four families of baleen whales, filter-feeders, and the Odontoceti include two families of toothed cetaceans ranging from dolphins to sperm whales. B. ceti is believed to transfer from animal to animal through sexual intercourse, maternal feeding, aborted fetuses, placental issues, from mother to fetus, or through fish reservoirs. Brucellosis is a reproductive disease, so has an extreme negative impact on the population dynamics of a species. This becomes a greater issue when the already low population numbers of cetaceans are taken into consideration. B. ceti has been identified in four of the 14 cetacean families, but the antibodies have been detected in seven of the families. This indicates that B. ceti is common amongst cetacean families and populations. Only a small percentage of exposed individuals become ill or die. However, particular species apparently are more likely to become infected by B. ceti. The harbor porpoise, striped dolphin, white-sided dolphin, bottlenose dolphin, and common dolphin have the highest frequency of infection amongst ondontocetes. In the mysticetes families, the northern minke whale is by far the most infected species. Dolphins and porpoises are more likely to be infected than cetaceans such as whales. With regard to sex and age biases, the infections do not seem influenced by the age or sex of an individual. Although fatal to cetaceans, B. ceti has a low infection rate for humans.[48] ### Terrestrial wildlife[edit] The disease in its various strains can infect multiple wildlife species, including elk (Cervus canadensis), bison (Bison bison), African buffalo (Syncerus caffer), European wild boar (Sus scrofa), caribou (Rangifer tarandus), moose (Alces alces), and marine mammals (see section on aquatic wildlife above).[49][50] While some regions use vaccines to prevent the spread of brucellosis between infected and uninfected wildlife populations, no suitable brucellosis vaccine for terrestrial wildlife has been developed.[51] This gap in medicinal knowledge creates more pressure for management practices that reduce spread of the disease.[51] Wild bison and elk in the greater Yellowstone area are the last remaining reservoir of B. abortus in the US. The recent transmission of brucellosis from elk back to cattle in Idaho and Wyoming illustrates how the area, as the last remaining reservoir in the United States, may adversely affect the livestock industry. Eliminating brucellosis from this area is a challenge, as many viewpoints exist on how to manage diseased wildlife. However, the Wyoming Game and Fish Department has recently begun to protect scavengers (particularly coyotes and red fox) on elk feedgrounds, because they act as sustainable, no-cost, biological control agents by removing infected elk fetuses quickly.[52] Purebred bison in the Henry Mountains of southern Utah are free of brucellosis.[53] The National Elk Refuge in Jackson, Wyoming asserts that the intensity of the winter feeding program affects the spread of brucellosis more than the population size of elk and bison.[49] Since concentrating animals around food plots accelerates spread of the disease, management strategies to reduce herd density and increase dispersion could limit its spread.[49] ### Effects on hunters[edit] Hunters may be at additional risk for exposure to brucellosis due to increased contact with susceptible wildlife, including predators that may have fed on infected prey. Hunting dogs can also be at risk of infection.[54] Exposure can occur through contact with open wounds or by directly inhaling the bacteria while cleaning game.[55] In some cases, consumption of undercooked game can result in exposure to the disease.[55] Hunters can limit exposure while cleaning game through the use of precautionary barriers, including gloves and masks, and by washing tools rigorously after use.[51][56] By ensuring that game is cooked thoroughly, hunters can protect themselves and others from ingesting the disease.[55] Hunters should refer to local game officials and health departments to determine the risk of brucellosis exposure in their immediate area and to learn more about actions to reduce or avoid exposure. ## See also[edit] * Brucella suis, also referred to as swine brucellosis ## References[edit] 1. ^ Wyatt HV (2014). "How did Sir David Bruce forget Zammit and his goats ?" (PDF). Journal of Maltese History. 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Retrieved 2016-10-03. 56. ^ "Zoonoses – Brucellosis". www.who.int/en/. World Health Organization. 2016. Retrieved 2016-10-03. ## Further reading[edit] * Fact sheet on Brucellosis from World Organisation for Animal Health * Brucella genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID * Prevention about Brucellosis from Centers for Disease Control * Capasso L (August 2002). "Bacteria in two-millennia-old cheese, and related epizoonoses in Roman populations". The Journal of Infection. 45 (2): 122–7. doi:10.1053/jinf.2002.0996. PMID 12217720. – re high rate of brucellosis in humans in ancient Pompeii * Brucellosis, factsheet from European Centre for Disease Prevention and Control ## External links[edit] Classification D * ICD-10: A23 * ICD-9-CM: 023 * MeSH: D002006 * DiseasesDB: 1716 External resources * MedlinePlus: 000597 * eMedicine: med/248 * Patient UK: Brucellosis * Orphanet: 1304 * v * t * e United States biological weapons program Weaponized agents * Anthrax * Botulism * Brucellosis * Q fever * Enterotoxin type B * Rice blast * Tularemia * VEE * Wheat stem rust Researched agents * AHF * BHF * Bird flu * CHIKV * Dengue fever * EEE * Glanders * Hantavirus * Lassa fever * Melioidosis * Newcastle disease * Plague * Potato blight * Psittacosis * Ricin * RVF * Rinderpest * Smallpox * Typhus * WEE * Yellow fever Munitions * E120 bomblet * E133 cluster bomb * E14 munition * E23 munition * E48 particulate bomb * E61 bomb * E77 balloon bomb * E86 cluster bomb * E96 cluster bomb * Flettner rotor bomblet * M114 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* t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis Authority control * GND: 4146716-4 * NDL: 00561086 [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	Brucellosis	c0006309	5,954	wikipedia	https://en.wikipedia.org/wiki/Brucellosis	2021-01-18T18:42:22	{"gard": ["5966"], "mesh": ["D002006"], "umls": ["C0006309"], "orphanet": ["1304"], "wikidata": ["Q156050"]}
A number sign (#) is used with this entry because glycogen storage disease IXd (GDS9D), also known as X-linked muscle phosphorylase kinase deficiency, is caused by mutation in the PHKA1 gene (311870), which encodes the alpha subunit of muscle phosphorylase kinase, on chromosome Xq13. See also hepatic PHK deficiency (GSD9A; 306000). Description Glycogen storage disease type IXd is an X-linked recessive, relatively mild metabolic disorder characterized by variable exercise-induced muscle weakness or stiffness. Most patients have adult-onset of symptoms, and some can remain asymptomatic even in late adulthood. The phenotype is usually only apparent with intense exercise (summary by Preisler et al., 2012). Clinical Features Abarbanel et al. (1986) reported a 35-year-old man with severe exercise intolerance and muscle cramps. Muscle biopsy showed subsarcolemmal and intermyofibrillar accumulation of glycogen. Muscle phosphorylase kinase activity was 12% of control values. Clemens et al. (1990) reported 2 unrelated patients with muscle phosphorylase kinase deficiency. Patient 1 was a 58-year-old man who had predominantly distal weakness beginning at age 46 years, but no cramps on exertion. Patient 2 was a 26-year-old man who had had cramps on exertion since age 6, but no muscle weakness. Muscle lactate production during ischemic exercise was impaired only in the first patient. In both patients, serum creatine kinase level was elevated, muscle phosphorylase kinase activity was low, and red cell activity was normal. Liver-specific phosphorylase kinase (300798) activity, measured in patient 1, was also normal. Wehner et al. (1994) provided follow-up on patient 1 reported by Clemens et al. (1990). He had slowly progressive, predominantly distal muscle weakness and atrophy beginning at age 46. He showed symptoms of hypoglycemia upon exertion. At age 64 years, he had weakness of the leg, arm, and abdominal muscles, rapid fatigue on exercise, and requirement for ankle braces. Phosphorylase kinase activity was 0.3% of normal in muscle, but normal in red blood cells and liver. Muscle biopsy showed mild glycogenosis with subsarcolemmal accumulations of glycogen and focal muscle fiber necrosis. The patient's mother, who died at the age of about 26 years, and his daughter, aged 33 at the time of the report, were reportedly asymptomatic. Burwinkel et al. (2003) reported follow-up on patient 2 reported by Clemens et al. (1990). At follow-up, he was a 36-year-old man with exercise-induced cramps, pain, and early fatigue since age 6 years, and occasional pigmenturia after intense exertion. Muscle glycogen concentration was elevated, and subsarcolemmal glycogen accumulation was observed in muscle histology. Total phosphorylase was normal in muscle, and phosphorylase kinase activity was markedly reduced in muscle, but normal in red blood cells. Wuyts et al. (2005) reported a man with muscle phosphorylase kinase deficiency confirmed by genetic analysis (311870.0004). He first presented at age 43 years with pain and weakness of the quadriceps muscle. Creatine kinase was mildly elevated. Over the subsequent 8 years, he had slowly progressive weakness of the pelvic girdle muscles without pyramidal or cerebellar signs. Muscle biopsy and ultrastructural analysis showed large amounts of subsarcolemmal free glycogen accumulation and a few mitochondrial paracrystalline inclusions. Biochemical analysis showed normal total muscle phosphorylase activity, but absence of phosphorylase kinase activity. Orngreen et al. (2008) reported a 50-year-old man with muscle phosphorylase kinase deficiency confirmed by genetic analysis (311870.0005). He reported progressive exercise intolerance, muscle stiffness on exercise, and nighttime muscle cramps since childhood. Serum creatine kinase levels were mildly elevated on several occasions, and there was low muscle PHK activity and high muscle glycogen content. During a cycle ergonometry test, the patient showed low-normal maximum oxidative capacity that was higher than that of 12 patients with McArdle disease, or myophosphorylase deficiency (232600). Peak serum lactate of the patient with PHK deficiency was decreased compared to 5 healthy men, but higher than that of the those with McArdle disease, indicating impaired oxidation of carbohydrate in the disease groups. The patient with PHK deficiency showed mild improvement of exercise tolerance with intravenous glucose infusion. There was a normal increase in serum lactate in the forearm ischemic exercise test, suggesting a discrepancy in glycogen breakdown impairment during anaerobic and aerobic exercise in PHK deficiency that may result from different activation pathways for myophosphorylase. Overall, the findings demonstrated that X-linked PHK deficiency is a mild metabolic myopathy characterized by impaired lactate production during moderate-intensity dynamic exercise and mild elevations of plasma creatine kinase and muscle glycogen content. Orngreen et al. (2008) noted that the clinical severity of PHK deficiency resembles another partial glycolytic defect, phosphoglycerate mutase deficiency (261670). Preisler et al. (2012) reported 2 unrelated adult men with genetically confirmed GSD IXd: a 39-year-old with mild exercise-induced forearm pain and a 69-year-old with persistently increased serum creatine kinase after statin treatment (see 311870.0004), but no other symptoms. Both patients had increased glycogen levels in muscle and PHK activity less than 11% of normal. Both had a normal increase in plasma lactate on anaerobic exercise, but showed an exaggerated 5-fold increase in ammonia levels. An incremental exercise test revealed a blunted lactate response compared to controls; fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. Glucose infusion did not improve work capacity. Preisler et al. (2012) concluded that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis was explained by activation of myophosphorylase (PYGM; 608455) at high exercise intensities. Molecular Genetics In patient 1 with phosphorylase kinase deficiency reported by Clemens et al. (1990), Wehner et al. (1994) identified a nonsense mutation in the PHKA1 gene (311870.0001). The findings confirmed that the condition in this patient was a human homolog of the X-linked muscle Phk deficiency of the I-strain mouse (Schneider et al., 1993). In patient 2 of Clemens et al. (1990), Burwinkel et al. (2003) identified a missense mutation in the PHKA1 gene (311870.0003). Burwinkel et al. (2003) screened 5 other patients with decreased muscle PHK activity for mutations in 6 genes that contribute to muscle PHK, in the muscle isoform of glycogen phosphorylase (PYGM; 608455), and in a muscle-specific regulatory subunit of protein kinase (PRKAG3; 604976). Two patients were heterozygous for single amino acid replacements of unclear significance in the beta subunit of phosphorylase kinase (PHKB; 172490). Bruno et al. (1998) reported a splice junction mutation in the PHKA1 gene (311870.0002) in a 28-year old Caucasian male with exercise intolerance, myoglobinuria, and muscle phosphorylase kinase deficiency. The patient, reported as patient 1 of Wilkinson et al. (1994), had been diagnosed with PHK deficiency at age 15 years. INHERITANCE \- X-linked recessive MUSCLE, SOFT TISSUES \- Muscle weakness \- Muscle atrophy \- Muscle pain, exercise-induced \- Muscle stiffness, exercise-induced \- Exercise intolerance \- Muscle biopsy shows increased subsarcolemmal vacuolar glycogen accumulation \- Muscle biopsy shows mitochondrial paracrystalline inclusions \- Muscle biopsy shows decreased muscle-specific phosphorylase kinase activity LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Myoglobinuria, exercise-induced MISCELLANEOUS \- Variable age at onset (childhood to adult) \- Most patients have adult onset of symptoms MOLECULAR BASIS \- Caused by mutation in the muscle-specific phosphorylase kinase subunit A1 gene (PHKA1, 311870.0001 ) ▲ 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	GLYCOGEN STORAGE DISEASE, TYPE IXd	c1845151	5,955	omim	https://www.omim.org/entry/300559	2019-09-22T16:20:06	{"doid": ["0111040"], "mesh": ["C564485"], "omim": ["300559"], "orphanet": ["715"], "synonyms": ["Alternative titles", "GSD IXd", "MUSCLE PHOSPHORYLASE KINASE DEFICIENCY", "MUSCLE GLYCOGENOSIS, X-LINKED"], "genereviews": ["NBK55061"]}
Mercury poisoning is a condition that occurs in people who are exposed to toxic levels of the element, mercury. There are three different forms of mercury that can cause health problems: * Elemental mercury (also known as liquid mercury or quicksilver) can be found in glass thermometers, electrical switches, dental fillings and fluorescent light bulbs. This form of mercury is generally only harmful when small droplets become airborne and are inhaled. If this occurs, signs and symptoms of poisoning may include metallic taste, vomiting, difficulty breathing, coughing, and/or swollen, bleeding gums. In severe cases, long-term brain damage, permanent lung damage and even death may occur. * Inorganic mercury is found in batteries, chemistry labs, and some disinfectants. This form of mercury is harmful when swallowed. Signs and symptoms of inorganic mercury poisoning vary based on the amount consumed, but may include burning in the stomach and throat; vomiting; and/or bloody diarrhea. Inorganic mercury can also affect the kidneys and brain if it enters the blood stream. * Organic mercury can be found in fish. Some organisms convert fumes from burning coal into organic mercury. This form of mercury is harmful if inhaled, eaten, or placed on the skin for long periods of time. Long-term exposure to organic mercury may result in skin numbness or pain; tremor; inability to walk well; blindness; double vision; memory problems; seizures; or even death. Treatment is generally supportive and based on the signs and symptoms present in each person. Medications called chelators, which remove mercury and heavy metals from the body, are generally prescribed. [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	Mercury poisoning	c0025427	5,956	gard	https://rarediseases.info.nih.gov/diseases/7021/mercury-poisoning	2021-01-18T17:59:08	{"mesh": ["D008630"], "umls": ["C0025427"], "synonyms": ["Mercury toxicity"]}
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: "Amyotrophy" – news · newspapers · books · scholar · JSTOR (October 2020) (Learn how and when to remove this template message) Amyotrophy SpecialtyNeurology Amyotrophy is progressive wasting of muscle tissues. Muscle pain is also a symptom. It can occur in middle-aged males with type 2 diabetes. It also occurs with motor neuron disease. ## Contents * 1 Differential Diagnosis * 2 Treatment * 3 See also * 4 References * 5 External links ## Differential Diagnosis[edit] The following are considered differential diagnosis for Amyotrophy:[1] * compressive and infective causes of polyradiculopathy * structural disc diseases * chronic demyelinating neuropathies ## Treatment[edit] This section is empty. You can help by adding to it. (October 2020) ## See also[edit] * Diabetic amyotrophy * Monomelic amyotrophy * Amyotrophic lateral sclerosis ## References[edit] 1. ^ Zaidi, Syed Amir; Chhetri, Suresh Kumar; Lekwuwa, Godwin; Majeed, Tahir (2013-02-04). "An unusual presentation of diabetic amyotrophy: myoclonus". BMJ Case Reports. 2013: bcr2012008245. doi:10.1136/bcr-2012-008245. ISSN 1757-790X. PMC 3604390. PMID 23386493. ## External links[edit] Classification D * ICD-10: G71.8 * ICD-9-CM: 728.2 * MeSH: D009133 * DiseasesDB: 29472 * v * t * e Symptoms and conditions relating to muscle Pain * Myalgia * Fibromyalgia * Acute * Delayed onset Inflammation * Myositis * Pyomyositis Destruction * Muscle weakness * Rhabdomyolysis * Muscle atrophy/Amyotrophy Other * Myositis ossificans * Fibrodysplasia ossificans progressiva * Compartment syndrome * Anterior * Diastasis of muscle * Diastasis recti * Muscle spasm 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	Amyotrophy	c0026846	5,957	wikipedia	https://en.wikipedia.org/wiki/Amyotrophy	2021-01-18T18:53:00	{"mesh": ["D009133"], "umls": ["C0026846"], "icd-9": ["728.2"], "icd-10": ["G71.8"], "wikidata": ["Q2844600"]}
BRCA1 hereditary breast and ovarian cancer syndrome (BRCA1 HBOC) is an inherited condition that is characterized by an increased risk for a variety of different cancers. Women with this condition have a 57-60% risk of developing breast cancer, a 40-59% risk of developing ovarian cancer and an 83% risk of developing contralateral breast cancer by age 70. Men have a 1% lifetime risk of breast cancer and an increased risk for prostate cancer. BRCA1 HBOC may also be associated with an elevated risk for cancers of the cervix, uterus, pancreas, esophagus, stomach, fallopian tube, and primary peritoneum; however, these risks are not well defined. This condition is caused by changes (mutations) in the BRCA1 gene and is inherited in an autosomal dominant manner. Management may include high risk cancer screening, chemoprevention and/or prophylactic surgeries. [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	BRCA1 hereditary breast and ovarian cancer syndrome	c0677776	5,958	gard	https://rarediseases.info.nih.gov/diseases/12351/brca1-hereditary-breast-and-ovarian-cancer-syndrome	2021-01-18T18:01:43	{"mesh": ["D061325"], "orphanet": ["145"], "synonyms": ["BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1, INCLUDED", "OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1, INCLUDED", "Familial susceptibility to breast-ovarian cancer 1", "BROVCA1"]}
## Clinical Features Gershoni-Baruch et al. (1990) reported a male infant with a giant omphalocele containing liver and intestines, diaphragmatic hernia, hepatic cyst, bilateral radioulnar synostosis, absent left thumb, and triphalangeal right thumb. Radiographically, there was absence of the right metacarpal and phalanges, and 3 normal first phalanges. The face was unusual, with short, downslanting palpebral fissures, bushy eyebrows, high nasal bridge, short pointed nose, anteverted nostrils, malar hypoplasia, and micrognathia. The ears were low set and posteriorly angulated; the right ear was small and dysplastic. The upper lip was thin, long, and downturned with a midline beak. The neck was short, with a low hairline and a tongue-like extension of hair onto the cheeks; the skin was thick and hirsute. The chest was bell-shaped. The G-banded karyotype was normal. The patient died at 12 days of age after 2 operations to repair the omphalocele. Devriendt et al. (1999) described a female infant with a large omphalocele containing approximately half the liver and small intestine, severe cervicothoracic scoliosis, narrow thorax with thin ribs, agenesis of the right radius and thumb, normal left hand with transverse palmar crease, and normal lower limbs. The child required artificial ventilation and died after 3 days. Postmortem examination revealed lung hypoplasia due to bilateral eventration of the diaphragm, absence of the right umbilical artery, intestinal malrotation, 2 small accessory spleens, and hypoplastic ovaries. The face was triangular with horizontal palpebral fissures and mild retrognathia. Devriendt et al. (1999) noted that their patient strongly resembled the sibs reported by Bird et al. (1994) (see DK phocomelia syndrome, 223340). Franceschini et al. (2003) reported 2 sibs, a female fetus and a male fetus, delivered through termination at 23 and 9 weeks of gestation, respectively. The female fetus had an omphalocele containing the liver and small intestine, a 6.5 cm thoracolumbar rachischisis, a posterior diaphragmatic hernia, absent left kidney, and a single umbilical artery. Upper and lower extremities were normal. The male fetus had multiple limb malformations with bilateral generalized syndactyly with hypoplasia and radial deviation of the thumbs and numerical reduction of the toes. There was no omphalocele, but the abdominal wall was interrupted in the right hypochondrium with liver protrusion; there was a single umbilical artery. Inheritance Franceschini et al. (2003) noted that the familial cases he described supported the hypothesis of autosomal recessive inheritance. [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	OMPHALOCELE, DIAPHRAGMATIC HERNIA, AND RADIAL RAY DEFECTS	c1836007	5,959	omim	https://www.omim.org/entry/609545	2019-09-22T16:05:52	{"mesh": ["C563701"], "omim": ["609545"], "orphanet": ["496693"], "synonyms": ["Alternative titles", "GERSHONI-BARUCH SYNDROME", "Gershoni-Baruch syndrome"]}
Subcutaneous emphysema Other namesSurgical emphysema, tissue emphysema, sub Q air An abdominal CT scan of a patient with subcutaneous emphysema (arrows) SpecialtyEmergency medicine Subcutaneous emphysema (SCE, SE) occurs when gas or air travels under the skin. Subcutaneous refers to the tissue beneath the skin, and emphysema refers to trapped air. Since the air generally comes from the chest cavity, subcutaneous emphysema usually occurs on the chest, neck and face, where it is able to travel from the chest cavity along the fascia.[1] Subcutaneous emphysema has a characteristic crackling-feel to the touch, a sensation that has been described as similar to touching Rice Krispies;[2] This sensation of air under the skin is known as subcutaneous crepitation, a form of Crepitus. Numerous etiologies of subcutaneous emphysema have been described. Pneumomediastinum was first recognized as a medical entity by Laennec, who reported it as a consequence of trauma in 1819. Later, in 1939, at The Johns Hopkins Hospital, Dr. Louis Hamman described it in postpartum woman; indeed, subcutaneous emphysema is sometimes known as Hamman's syndrome. However, in some medical circles, it can instead be more commonly known as Macklin's Syndrome after L. Macklin, in 1939, and M.T. and C.C. Macklin, in 1944, who cumulatively went on to describe the pathophysiology in more detail.[3] Subcutaneous emphysema can result from puncture of parts of the respiratory or gastrointestinal systems. Particularly in the chest and neck, air may become trapped as a result of penetrating trauma (e.g., gunshot wounds or stab wounds) or blunt trauma. Infection (e.g., gas gangrene) can cause gas to be trapped in the subcutaneous tissues. Subcutaneous emphysema can be caused by medical procedures and medical conditions that cause the pressure in the alveoli of the lung to be higher than that in the tissues outside of them.[4] Its most common causes are pneumothorax and a chest tube that has become occluded by a blood clot or fibrinous material. It can also occur spontaneously due to rupture of the alveoli with dramatic presentation.[5] When the condition is caused by surgery it is called surgical emphysema.[6] The term spontaneous subcutaneous emphysema is used when the cause is not clear.[5] Subcutaneous emphysema is not typically dangerous in and of itself, however it can be a symptom of very dangerous underlying conditions, such as pneumothorax.[7] Although the underlying conditions require treatment, subcutaneous emphysema usually does not; small amounts of air are reabsorbed by the body. However, subcutaneous emphysema can be uncomfortable and may interfere with breathing, and is often treated by removing air from the tissues, for example by using large bore needles, skin incisions or subcutaneous catheterization. ## Contents * 1 Symptoms and signs * 2 Causes * 2.1 Trauma * 2.2 Medical treatment * 2.3 Infection * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 History * 8 References * 9 External links ## Symptoms and signs[edit] Signs and symptoms of spontaneous subcutaneous emphysema vary based on the cause, but it is often associated with swelling of the neck and chest pain, and may also involve sore throat, neck pain, difficulty swallowing, wheezing and difficulty breathing.[5] Chest X-rays may show air in the mediastinum, the middle of the chest cavity.[5] A significant case of subcutaneous emphysema is easy to detect by touching the overlying skin; it feels like tissue paper or Rice Krispies.[8] Touching the bubbles causes them to move and sometimes make a crackling noise.[9] The air bubbles, which are painless and feel like small nodules to the touch, may burst when the skin above them is palpated.[9] The tissues surrounding SCE are usually swollen. When large amounts of air leak into the tissues, the face can swell considerably.[8] In cases of subcutaneous emphysema around the neck, there may be a feeling of fullness in the neck, and the sound of the voice may change.[10] If SCE is particularly extreme around the neck and chest, the swelling can interfere with breathing. The air can travel to many parts of the body, including the abdomen and limbs, because there are no separations in the fatty tissue in the skin to prevent the air from moving.[11] ## Causes[edit] ### Trauma[edit] Conditions that cause subcutaneous emphysema may result from both blunt and penetrating trauma;[5] SCE is often the result of a stabbing or gunshot wound.[12] Subcutaneous emphysema is often found in car accident victims because of the force of the crash. Chest trauma, a major cause of subcutaneous emphysema, can cause air to enter the skin of the chest wall from the neck or lung.[9] When the pleural membranes are punctured, as occurs in penetrating trauma of the chest, air may travel from the lung to the muscles and subcutaneous tissue of the chest wall.[9] When the alveoli of the lung are ruptured, as occurs in pulmonary laceration, air may travel beneath the visceral pleura (the membrane lining the lung), to the hilum of the lung, up to the trachea, to the neck and then to the chest wall.[9] The condition may also occur when a fractured rib punctures a lung;[9] in fact, 27% of patients who have rib fractures also have subcutaneous emphysema.[11] Rib fractures may tear the parietal pleura, the membrane lining the inside of chest wall, allowing air to escape into the subcutaneous tissues.[13] Subcutaneous emphysema is frequently found in pneumothorax (air outside of the lung in the chest cavity)[14][15] and may also result from air in the mediastinum, pneumopericardium (air in the pericardial cavity around the heart).[16] A tension pneumothorax, in which air builds up in the pleural cavity and exerts pressure on the organs within the chest, makes it more likely that air will enter the subcutaneous tissues through pleura torn by a broken rib.[13] When subcutaneous emphysema results from pneumothorax, air may enter tissues including those of the face, neck, chest, armpits, or abdomen.[1] Pneumomediastinum can result from a number of events. For example, foreign body aspiration, in which someone inhales an object, can cause pneumomediastinum (and lead to subcutaneous emphysema) by puncturing the airways or by increasing the pressure in the affected lung(s) enough to cause them to burst.[17] Subcutaneous emphysema of the chest wall is commonly among the first signs to appear that barotrauma, damage caused by excessive pressure, has occurred,[1][18] and it is an indication that the lung was subjected to significant barotrauma.[19] Thus the phenomenon may occur in diving injuries.[5][20] Trauma to parts of the respiratory system other than the lungs, such as rupture of a bronchial tube, may also cause subcutaneous emphysema.[13] Air may travel upward to the neck from a pneumomediastinum that results from a bronchial rupture, or downward from a torn trachea or larynx into the soft tissues of the chest.[13] It may also occur with fractures of the facial bones, neoplasms, during asthma attacks, when the Heimlich maneuver is used, and during childbirth.[5] Injury with pneumatic tools, those that are driven by air, is also known to cause subcutaneous emphysema, even in extremities (the arms and legs).[21] It can also occur as a result of rupture of the esophagus; when it does, it is usually as a late sign.[22] ### Medical treatment[edit] Subcutaneous emphysema is a common result of certain types of surgery; for example it is not unusual in chest surgery.[8] It may also occur from surgery around the esophagus, and is particularly likely in prolonged surgery.[7] Other potential causes are positive pressure ventilation for any reason and by any technique, in which its occurrence is frequently unexpected. It may also occur as a result of oral surgery,[23] laparoscopy,[7] and cricothyrotomy. In a pneumonectomy, in which an entire lung is removed, the remaining bronchial stump may leak air, a rare but very serious condition that leads to progressive subcutaneous emphysema.[8] Air can leak out of the pleural space through an incision made for a thoracotomy to cause subcutaneous emphysema.[8] On infrequent occasions, the condition can result from dental surgery, usually due to use of high-speed tools that are air driven.[24] These cases result in usually painless swelling of the face and neck, with an immediate onset, the crepitus (crunching sound) typical of subcutaneous emphysema, and often with subcutaneous air visible on X-ray.[24] One of the main causes of subcutaneous emphysema, along with pneumothorax, is an improperly functioning chest tube.[2] Thus subcutaneous emphysema is often a sign that something is wrong with a chest tube; it may be clogged, clamped, or out of place.[2] The tube may need to be replaced, or, when large amounts of air are leaking, a new tube may be added.[2] Since mechanical ventilation can worsen a pneumothorax, it can force air into the tissues; when subcutaneous emphysema occurs in a ventilated patient, it is an indication that the ventilation may have caused a pneumothorax.[2] It is not unusual for subcutaneous emphysema to result from positive pressure ventilation.[25] Another possible cause is a ruptured trachea.[2] The trachea may be injured by tracheostomy or tracheal intubation; in cases of tracheal injury, large amounts of air can enter the subcutaneous space.[2] An endotracheal tube can puncture the trachea or bronchi and cause subcutaneous emphysema.[12] ### Infection[edit] Air can be trapped under the skin in necrotizing infections such as gangrene, occurring as a late sign in gas gangrene,[2] of which it is the hallmark sign. Subcutaneous emphysema is also considered a hallmark of fournier gangrene.[26] Symptoms of subcutaneous emphysema can result when infectious organisms produce gas by fermentation. When emphysema occurs due to infection, signs that the infection is systemic, i.e. that it has spread beyond the initial location, are also present.[9][21] ## Pathophysiology[edit] Air is able to travel to the soft tissues of the neck from the mediastinum and the retroperitoneum (the space behind the abdominal cavity) because these areas are connected by fascial planes.[4] From the punctured lungs or airways, the air travels up the perivascular sheaths and into the mediastinum, from which it can enter the subcutaneous tissues.[17] Spontaneous subcutaneous emphysema is thought to result from increased pressures in the lung that cause alveoli to rupture.[5] In spontaneous subcutaneous emphysema, air travels from the ruptured alveoli into the interstitium and along the blood vessels of the lung, into the mediastinum and from there into the tissues of the neck or head.[5] ## Diagnosis[edit] Significant cases of subcutaneous emphysema are easy to diagnose because of the characteristic signs of the condition.[1] In some cases, the signs are subtle, making diagnosis more difficult.[13] Medical imaging is used to diagnose the condition or confirm a diagnosis made using clinical signs. On a chest radiograph, subcutaneous emphysema may be seen as radiolucent striations in the pattern expected from the pectoralis major muscle group. Air in the subcutaneous tissues may interfere with radiography of the chest, potentially obscuring serious conditions such as pneumothorax.[18] It can also reduce the effectiveness of chest ultrasound.[27] On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury.[13] Subcutaneous emphysema can also be seen in CT scans, with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues.[13] In 1994, M.T. Macklin and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklin's Syndrome occurring from a severe asthmatic attack. The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bout of vomiting followed by left chest pain is very suggestive of the diagnosis of Boerhaave's syndrome, which is a life-threatening emergency caused by rupture of the distal esophagus. Subcutaneous emphysema can be a complication of CO2 insufflation with laparoscopic surgery. A sudden rise in end-tidal CO2 following the initial rise that occurs with insufflation (first 15-30 min) should raise suspicion of subcutaneous emphysema.[4] Of note, there are no changes in the pulse oximetry or airway pressure in subcutaneous emphysema, unlike in endobronchial intubation, capnothorax, pneumothorax, or CO2 embolism. Bubbles of air in the subcutaneous tissue (arrow) feel like mobile nodules that move around easily A chest X-ray of a right sided pulmonary contusion associated with flail chest and subcutaneous emphysema Subcutaneous air (arrows) can be seen as black areas on this pelvic CT scan. ## Treatment[edit] Subcutaneous emphysema is usually benign.[1] Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable.[28] It occasionally progresses to a state "Massive Subcutaneous Emphysema" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to positive pressure ventilation, the eyelids swell so much that the patient cannot see. Also the pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia. This can lead to necrosis of the skin in these areas. The latter are urgent situations requiring rapid, adequate decompression.[29][30][31] Severe cases can compress the trachea and do require treatment.[32] In severe cases of subcutaneous emphysema, catheters can be placed in the subcutaneous tissue to release the air.[1] Small cuts, or "blow holes", may be made in the skin to release the gas.[16] When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space.[2] If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one.[8] Suction may also be applied to the tube to remove air faster.[8] The progression of the condition can be monitored by marking the boundaries with a special pencil for marking on skin.[32] Since treatment usually involves dealing with the underlying condition, cases of spontaneous subcutaneous emphysema may require nothing more than bed rest, medication to control pain, and perhaps supplemental oxygen.[5] Breathing oxygen may help the body to absorb the subcutaneous air more quickly.[10] ## Prognosis[edit] Air in subcutaneous tissue does not usually pose a lethal threat;[4] small amounts of air are reabsorbed by the body.[8] Once the pneumothorax or pneumomediastinum that causes the subcutaneous emphysema is resolved, with or without medical intervention, the subcutaneous emphysema will usually clear.[18] However, spontaneous subcutaneous emphysema can, in rare cases, progress to a life-threatening condition,[5] and subcutaneous emphysema due to mechanical ventilation may induce ventilatory failure.[25] ## History[edit] The first report of subcutaneous emphysema resulting from air in the mediastinum was made in 1850 in a patient who had been coughing violently.[5] In 1900, the first recorded case of spontaneous subcutaneous emphysema was reported in a bugler for the Royal Marines who had had a tooth extracted: playing the instrument had forced air through the hole where the tooth had been and into the tissues of his face.[5] Since then, another case of spontaneous subcutaneous emphysema was reported in a submariner for the US Navy who had had a root canal in the past; the increased pressure in the submarine forced air through it and into his face. In recent years a case was reported at the University Hospital of Wales of a young man who had been coughing violently causing a rupture in the esophagus resulting in SE.[5] The cause of spontaneous subcutaneous emphysema was clarified between 1939 and 1944 by Macklin, contributing to the current understanding of the pathophysiology of the condition.[5] ## References[edit] 1. ^ a b c d e f Papiris SA, Roussos C (2004). "Pleural disease in the intensive care unit". In Bouros D (ed.). Pleural Disease (Lung Biology in Health and Disease). Florida: Bendy Jean Baptiste. pp. 771–777. ISBN 978-0-8247-4027-6. Retrieved 2008-05-16. 2. ^ a b c d e f g h i Lefor, Alan T. (2002). Critical Care on Call. New York: Lange Medical Books/McGraw-Hill, Medical Publishing Division. pp. 238–240. ISBN 978-0-07-137345-6. Retrieved 2008-05-09. 3. ^ Macklin, M. T; C. C Macklin (1944). "Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: an interpretation of the clinical literature in the light of laboratory experiment". Medicine. 23 (4): 281–358. doi:10.1097/00005792-194412000-00001. S2CID 56803581. 4. ^ a b c d Maunder RJ, Pierson DJ, Hudson LD (July 1984). "Subcutaneous and mediastinal emphysema. Pathophysiology, diagnosis, and management". Arch. Intern. Med. 144 (7): 1447–53. doi:10.1001/archinte.144.7.1447. PMID 6375617. 5. ^ a b c d e f g h i j k l m n o Parker GS, Mosborg DA, Foley RW, Stiernberg CM (September 1990). "Spontaneous cervical and mediastinal emphysema". Laryngoscope. 100 (9): 938–940. doi:10.1288/00005537-199009000-00005. PMID 2395401. S2CID 21114664. 6. ^ Oxford Concise Medical Dictionary (6th ed.). Oxford, UK: Oxford University Press. 2003. ISBN 978-0-19-860753-3. 7. ^ a b c Brooks DR (1998). Current Review of Minimally Invasive Surgery. Philadelphia: Current Medicine. p. 36. ISBN 978-0-387-98338-7. 8. ^ a b c d e f g h Long BC, Cassmeyer V, Phipps WJ (1995). Adult Nursing: Nursing Process Approach. St. Louis: Mosby. p. 328. ISBN 978-0-7234-2004-0. Retrieved 2008-05-12. 9. ^ a b c d e f g DeGowin RL, LeBlond RF, Brown DR (2004). DeGowin's Diagnostic Examination. New York: McGraw-Hill Medical Pub. Division. pp. 388, 552. ISBN 978-0-07-140923-0. Retrieved 2008-05-12. 10. ^ a b NOAA (1991). NOAA Diving Manual. US Dept. of Commerce – National Oceanic and Atmospheric Administration. p. 3.15. ISBN 978-0-16-035939-2. Retrieved 2008-05-09. 11. ^ a b Schnyder P, Wintermark M (2000). Radiology of Blunt Trauma of the Chest. Berlin: Springer. pp. 10–11. ISBN 978-3-540-66217-4. Retrieved 2008-05-06. 12. ^ a b Peart O (2006). "Subcutaneous emphysema". Radiologic Technology. 77 (4): 296. PMID 16543482. 13. ^ a b c d e f g Wicky S, Wintermark M, Schnyder P, Capasso P, Denys A (2000). "Imaging of blunt chest trauma". European Radiology. 10 (10): 1524–1538. doi:10.1007/s003300000435. PMID 11044920. S2CID 22311233. 14. ^ Hwang JC, Hanowell LH, Grande CM (1996). "Peri-operative concerns in thoracic trauma". Baillière's Clinical Anaesthesiology. 10 (1): 123–153. doi:10.1016/S0950-3501(96)80009-2. 15. ^ Myers JW, Neighbors M, Tannehill-Jones R (2002). Principles of Pathophysiology and Emergency Medical Care. Albany, N.Y: Delmar Thomson Learning. p. 121. ISBN 978-0-7668-2548-2. Retrieved 2008-06-16. 16. ^ a b Grathwohl KW, Miller S (2004). "Anesthetic implications of minimally invasive urological surgery". In Bonnett R, Moore RG, Bishoff JT, Loenig S, Docimo SG (eds.). Minimally Invasive Urological Surgery. London: Taylor & Francis Group. p. 105. ISBN 978-1-84184-170-0. Retrieved 2008-05-11. 17. ^ a b Findlay CA, Morrissey S, Paton JY (July 2003). "Subcutaneous emphysema secondary to foreign-body aspiration". Pediatric Pulmonology. 36 (1): 81–82. doi:10.1002/ppul.10295. PMID 12772230. S2CID 33808524. 18. ^ a b c Criner GJ, D'Alonzo GE (2002). Critical Care Study Guide: text and review. Berlin: Springer. p. 169. ISBN 978-0-387-95164-5. Retrieved 2008-05-12. 19. ^ Rankine JJ, Thomas AN, Fluechter D (July 2000). "Diagnosis of pneumothorax in critically ill adults". Postgraduate Medical Journal. 76 (897): 399–404. doi:10.1136/pmj.76.897.399. PMC 1741653. PMID 10878196. 20. ^ Raymond LW (June 1995). "Pulmonary barotrauma and related events in divers". Chest. 107 (6): 1648–52. doi:10.1378/chest.107.6.1648. PMID 7781361. Retrieved 2009-07-05. 21. ^ a b van der Molen AB, Birndorf M, Dzwierzynski WW, Sanger JR (May 1999). "Subcutaneous tissue emphysema of the hand secondary to noninfectious etiology: a report of two cases". Journal of Hand Surgery. 24 (3): 638–41. doi:10.1053/jhsu.1999.0638. PMID 10357548. 22. ^ Kosmas EN, Polychronopoulos VS (2004). "Pleural effusions in gastrointestinal tract diseases". In Bouros D (ed.). Pleural Disease (Lung Biology in Health and Disease). New York, N.Y: Marcel Dekker. p. 798. ISBN 978-0-8247-4027-6. Retrieved 2008-05-16. 23. ^ Pan PH (1989). "Perioperative subcutaneous emphysema: Review of differential diagnosis, complications, management, and anesthetic implications". Journal of Clinical Anesthesia. 1 (6): 457–459. doi:10.1016/0952-8180(89)90011-1. PMID 2696508. 24. ^ a b Monsour PA, Savage NW (October 1989). "Cervicofacial emphysema following dental procedures". Australian Dental Journal. 34 (5): 403–406. doi:10.1111/j.1834-7819.1989.tb00695.x. PMID 2684113. 25. ^ a b Conetta R, Barman AA, Iakovou C, Masakayan RJ (September 1993). "Acute ventilatory failure from massive subcutaneous emphysema". Chest. 104 (3): 978–980. doi:10.1378/chest.104.3.978. PMID 8365332. 26. ^ Levenson RB, Singh AK, Novelline RA (2008). "Fournier gangrene: Role of imaging". Radiographics. 28 (2): 519–528. doi:10.1148/rg.282075048. PMID 18349455. 27. ^ Gravenstein N, Lobato E, Kirby RM (2007). Complications in Anesthesiology. Hagerstown, MD: Lippincott Williams & Wilkins. p. 171. ISBN 978-0-7817-8263-0. Retrieved 2008-05-12. 28. ^ Abu-Omar Y, Catarino PA (February 2002). "Progressive subcutaneous emphysema and respiratory arrest". Journal of the Royal Society of Medicine. 95 (2): 90–91. doi:10.1258/jrsm.95.2.90. PMC 1279319. PMID 11823553. 29. ^ Maunder, R J; D J Pierson; L D Hudson (July 1984). "Subcutaneous and mediastinal emphysema. Pathophysiology, diagnosis, and management". Archives of Internal Medicine. 144 (7): 1447–1453. doi:10.1001/archinte.144.7.1447. ISSN 0003-9926. PMID 6375617. 30. ^ Romero, Kleber J; Máximo H Trujillo (2010-04-21). "Spontaneous pneumomediastinum and subcutaneous emphysema in asthma exacerbation: The Macklin effect". Heart & Lung: The Journal of Critical Care. 39 (5): 444–7. doi:10.1016/j.hrtlng.2009.10.001. ISSN 1527-3288. PMID 20561891. 31. ^ Ito, Takeo; Koichi Goto; Kiyotaka Yoh; Seiji Niho; Hironobu Ohmatsu; Kaoru Kubota; Kanji Nagai; Eishi Miyazaki; Toshihide Kumamoto; Yutaka Nishiwaki (July 2010). "Hypertrophic pulmonary osteoarthropathy as a paraneoplastic manifestation of lung cancer". Journal of Thoracic Oncology. 5 (7): 976–980. doi:10.1097/JTO.0b013e3181dc1f3c. ISSN 1556-1380. PMID 20453688. S2CID 2989121. 32. ^ a b Carpenito-Moyet LJ (2004). Nursing Care Plans and Documentation: Nursing Diagnoses and Collaborative Problems. Hagerstown, MD: Lippincott Williams & Wilkins. p. 889. ISBN 978-0-7817-3906-1. Retrieved 2008-05-12. ## External links[edit] Classification D * ICD-10: T79.7, T81.8 * ICD-9-CM: 958.7, 998.81 * MeSH: D013352 * DiseasesDB: 29756 External resources * MedlinePlus: 003286 * v * t * e Consequences of external causes Temperature Elevated Hyperthermia Heat syncope Reduced Hypothermia Immersion foot syndromes Trench foot Tropical immersion foot Warm water immersion foot Chilblains Frostbite Aerosol burn Cold intolerance Acrocyanosis Erythrocyanosis crurum Radiation Radiation poisoning Radiation burn Chronic radiation keratosis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Radiation acne Radiation-induced cancer Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Air * Hypoxia/Asphyxia * Barotrauma * Aerosinusitis * Decompression sickness * High altitude * Altitude sickness * Chronic mountain sickness * Death zone * HAPE * HACE Food * 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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 [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	Subcutaneous emphysema	c0038536	5,960	wikipedia	https://en.wikipedia.org/wiki/Subcutaneous_emphysema	2021-01-18T19:09:28	{"mesh": ["D013352"], "icd-9": ["958.7", "998.81"], "icd-10": ["T79.7", "T81.8"], "wikidata": ["Q1412866"]}
Prion disease affecting the deer family Chronic wasting disease Other namesZombie deer disease Deer with signs of chronic wasting disease SpecialtyVeterinary medicine Chronic wasting disease (CWD), sometimes called zombie deer disease, is a transmissible spongiform encephalopathy (TSE) affecting deer. TSEs are a family of diseases thought to be caused by misfolded proteins called prions and includes similar diseases such as BSE (mad cow disease) in cattle, Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep.[1] In the US, CWD affects mule deer, white-tailed deer, red deer, sika deer, elk, caribou, and moose.[2] Natural infection causing CWD affects members of the deer family.[2] Experimental transmission of CWD to other species such as squirrel monkeys, and genetically modified mice has been shown.[3] In 1967, CWD was first identified in mule deer at a government research facility in northern Colorado, United States.[2] It was initially recognized as a clinical "wasting" syndrome and then in 1978, it was identified more specifically as a TSE disease. Since then, CWD has been found in free-ranging and captive animal populations in 26 US states and three Canadian provinces.[4] In addition, CWD has been found in one Minnesota red deer farm, one wild reindeer herd in Norway (March 2016) as well as in wild moose. Single cases of CWD in moose have been found in Finland (March 2018) and in Sweden (March and May 2019, September 2020). CWD was found in South Korea in some deer imported from Canada.[5] CWD is typified by chronic weight loss and clinical signs compatible with brain lesions, aggravated over time, always leading to death. No relationship is known between CWD and any other TSEs of animals or people. Although reports in the popular press have been made of humans being affected by CWD, by 2004 a study for the Centers for Disease Control and Prevention (CDC) suggested, "[m]ore epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions".[6] The epidemiological study further concluded, "[a]s a precaution, hunters should avoid eating deer and elk tissues known to harbor the CWD agent (e.g., brain, spinal cord, eyes, spleen, tonsils, lymph nodes) from areas where CWD has been identified".[6] ## Contents * 1 History * 2 Signs and symptoms * 3 Cause * 3.1 Genetics * 3.2 Spread * 3.2.1 Direct * 3.2.2 Experimental transmission * 3.2.3 Indirect * 4 Prevention * 5 Diagnosis * 6 Epidemiology * 6.1 North America * 6.2 Europe * 7 Research * 8 References * 9 External links ## History[edit] Chronic wasting disease was first discovered by American wildlife veterinarian Beth S. Williams. Williams performed necropsies on deer and elk that had died of an unknown syndrome. She recognized that the brain lesions in these animals were consistent with transmissible spongiform encephalopathy (TSE).[7] In 1978, she and neuropathologist Stuart Young cowrote the first scientific paper that named the disease and described it as a TSE.[8] ## Signs and symptoms[edit] Most cases of CWD occur in adult animals; the youngest animal to exhibit clinical symptoms of the disease was 15 months.[9] The disease is progressive and always fatal. The first signs are difficulties in movement. The most obvious and consistent clinical sign of CWD is weight loss over time. Behavioral changes also occur in the majority of cases, including decreased interactions with other animals, listlessness, lowering of the head, tremors, repetitive walking in set patterns, and nervousness. Excessive salivation and grinding of the teeth also are observed. Most deer show increased drinking and urination; the increased drinking and salivation may contribute to the spread of the disease.[10] Loss of fear of humans and appearance of confusion are also common.[11] The APHIS summarized it as:[2] > Behavioral changes, emaciation, weakness, ataxia, salivation, aspiration pneumonia, progressive death. ## Cause[edit] The cause of CWD (like other TSEs, such as scrapie and bovine spongiform encephalopathy) is a prion, a misfolded form of a normal protein, known as prion protein (PrP), that is most commonly found in the central nervous system (CNS) and peripheral nervous system (PNS). The misfolded form has been shown to be capable of converting normally folded prion protein, PrPC ("C" for cellular) into an abnormal form, PrPSc ("Sc" for scrapie), thus leading to a chain reaction. CWD is thought to be transmitted by this mechanism. The abnormality in PrP has its genetic basis in a particular variant of the protein-coding gene PRNP that is highly conserved among mammals and has been found and sequenced in deer. The build-up of PrPd in the brain is associated with widespread neurodegeneration.[2][10][12] ### Genetics[edit] The allele which encodes leucine, codon 132 in the family of Elks, is either homozygous LL, homozygous MM, or heterozygous ML. Individuals with the first encoding seem to resist clinical signs of CWD, whereas individuals with either of the other two encodings have much shorter incubation periods.[2] In white-tailed deer, polymorphisms at codons 95(Q->H) and 96 (G->S) dramatically affect CWD progression and prion strain specification. Deer containing the 96S allele have delayed progression to clinical disease onset.[13] When deer with the 95H polymorphism become infected, they select for altered strains of CWD.[14] ### Spread[edit] As of 2013, no evidence has been found of transmission to humans from deer, nor by eating animals in the deer family, but both channels remain a subject of public health surveillance and research.[2] Researchers in July 2019 that "with all the research on the malignity of prions, and the permanence of prions in the wider environment, and their resistance to destruction and degradation, it is necessary to reduce the potential sources of exposure to CWD."[15] In fact an APHIS scientist observed that, while the longevity of CWD prion is unknown, the scrapie prion has been measured to endure for 16 years.[2][16] The PrPCWD protein is insoluble in all but the strongest solvents, and highly resistant to digestion by proteases.[2] PrPCWD converts the normal protein PrPC into more of itself upon contact, and binds together forming aggregates.[2][16] Prusiner noted in 2001 that[16] > In the prion diseases, the initial formation of PrPSc leads to an exponential increase in the protein, which can be readily transmitted to another host but it is noted that as of 2013, although CWD prions were transmissible within the cervidae family, CWD was not transmissible to humans or to cattle.[2] How the prions that cause CWD spread is unknown, but recent research indicates that prions can be excreted by deer and elk, and are transmitted by eating grass growing in contaminated soil.[17] Animals born in captivity and those born in the wild have been affected with the disease. Transmission of CWD is thought to be lateral (from animal to animal). Maternal transmission may occur, although it appears to be relatively unimportant in maintaining epidemics. An infected deer's saliva is able to spread the CWD prions.[18] Exposure between animals is associated with sharing food and water sources contaminated with CWD prions shed by diseased deer.[19] #### Direct[edit] CWD may be directly transmitted by contact with infected animals, their bodily tissues, and their bodily fluids.[20] Spread may result from contact with infected deer regardless of if they are symptomatic.[21] Recent research on Rocky Mountain elk found that with CWD-infected cows, many subclinical, a high rate (80%) of maternal-to-offspring transmission of CWD prions occurred, regardless of gestational period.[21] While not dispositive relative to disease development in the fetus, this does suggest that maternal transmission may be yet another important route of direct CWD transmission. #### Experimental transmission[edit] In addition to the cervid species in which CWD is known to naturally occur, black-tailed deer and European red deer have been demonstrated to be naturally susceptible to CWD.[22] Other cervid species, including caribou, are also suspected to be naturally vulnerable to this disease.[20] Many other noncervid mammalian species have been experimentally infected with CWD, either orally or by intracerebral inoculation.[20] These species include monkeys, sheep, cattle, prairie voles, mice, and ferrets.[23] An experimental case study of oral transmission of CWD to reindeer shows certain reindeer breeds may be susceptible to CWD, while other subpopulations may be protective against CWD in free-ranging populations. None of the reindeer in the study showed symptoms of CWD, potentially signifying resistance to different CWD strains.[24] #### Indirect[edit] Environmental transmission has been linked to contact with infected bodily fluids and tissues, as well as contact with contaminated environments. Once in the environment, CWD prions may remain infectious for many years. Thus, decomposition of diseased carcasses, infected "gut piles" from hunters who field dress their cervid harvests, and the urine, saliva, feces, and antler velvet of infected individuals that are deposited in the environment, all have the potential to create infectious environmental reservoirs of CWD.[10] In 2013, researchers at the National Wildlife Research Center in Fort Collins, Colorado successfully inoculated white-tailed deer with the misfolded prion via the nasal passage, when the prions were mixed with clay.[25] This was important because the prions had already been shown by 2006 to bind with sandy quartz clay minerals.[2] One avian scavenger, the American crow, was recently evaluated as a potential vector for CWD.[26] As CWD prions remain viable after passing through the bird's digestive tract, crows represent a possible mechanism for the creation of environmental reservoirs of CWD.[26][27] Additionally, the crows' extensive geographic range presents ample opportunities for them to come in contact with CWD. This, coupled with the population density and longevity of communal roosting sites in both urban and rural locations, suggests that the fecal deposits at roosting sites may represent a CWD environmental reservoir.[26] Conservative estimates for crows' fecal deposits at one winter roosting site for one winter season ranged from 391,552 to 599,032 kg.[26] CWD prions adhere so tightly to soil surface particles that the ground becomes a source of infection and may be a major route of transmission due to frequent ground contact when animals in the deer family graze.[10] ## Prevention[edit] This section is missing information about predation. Please expand the section to include this information. Further details may exist on the talk page. (December 2020) By 2012, a voluntary system of control was published by APHIS in the US Federal Register. It depended on voluntary minimum standards methodology, and herd certification programs to avoid interstate movement of the disease vector. It was based on a risk management framework.[2] As of August 2019, APHIS law in 9 CFR Part 55 - CONTROL OF CHRONIC WASTING DISEASE dealt with this problem. The MFFP ministry in Quebec practiced 9500 tests in the period between 2007 and autumn 2018 before they detected a seropositive case in September 2018.[28] The September 2018 discovery of CWD on a managed operation in Grenville-sur-la-Rouge Quebec prompted a wholesale slaughter of 3500 animals in two months before the enterprise shut its doors for good.[29] The CFIA ordered the cull, as well as the decontamination of 10 inches of soil in certain places on the 1000-acre operation.[28] Post-discovery, each animal was tested for CWD by the CFIA before it was released onto the market. Other Quebec producers lamented the glut of supply.[29] A 400 km quarantine area was declared, in which all hunting and trapping activities were banned.[30] Government massacred hundreds of wild beasts over a two-month period. The routine cull for market was between 70 and 100 animals per week. When the producer was forced to close, the weekly slaughter neared 500 beasts per week.[29] One year later, 750 wild specimens had been culled in the 45 km-radius "enhanced monitoring area", and none tested positive for CWD.[31] It came to light in August 2019 that prior to 2014 in Canada, all animals on CWD-infected farms were buried or incinerated. But in a mysterious change of policy, since then the CFIA has allowed animals from CWD-infected farms to enter the food chain because there is "no national requirement to have animals tested for the disease". From one CWD-infected herd in Alberta, 131 elk were sold for human consumption.[32] For the fall 2019 hunting season in western Quebec, the provincial ministry relaxed the rules for the annual white-tailed deer (WTD) hunt, in an effort to curb the spread of CWD. Any WTD can be hunted with any weapon in certain municipalities in the Outaouais valley and the Laurentides. The MFFP hopes thereby to receive more samples to test for CWD.[31] The quarantine around Grenville was still in place, and the ministry specifically prohibited (only) the "removal" from the quarantine "enhanced monitoring area" zone of "the head, more specifically any part of the brain, the eyes, the retropharyngeal lymph nodes and the tonsils, any part of the spinal column, the internal organs (including the liver and the heart), and the testicles."[33] Introduced for the 2019 Minnesota hunting season, a no-cost deer carcass-incineration program was rolled out by Crow Wing County officials hoping to stem the spread of CWD in the region. CWD was found among wild deer in Crow Wing County for the first time in January 2019. The voluntary program encourages both residents and visiting hunters to bring harvested deer carcasses to the county landfill east of Brainerd, Minnesota for incineration and disposal.[11] ## Diagnosis[edit] Diagnosis is based on post mortem examination (necropsy) and testing; examination of the dead body is not definitive, as many animals die early in the course of the disease and conditions found are nonspecific; general signs of poor health and aspiration pneumonia, which may be the actual cause of death, are common. On microscopic examination, lesions of CWD in the CNS resemble those of other TSEs. In addition, scientists use immunohistochemistry to test brain, lymph, and neuroendocrine tissues for the presence of the abnormal prion protein to diagnose CWD; positive IHC findings in the obex is considered the gold standard.[10] Conventional CWD diagnostic strategies and seeded amplification methods for amplifying CWD prions in vitro include: immunohistochemistry (IHC), western blotting (WB), enzyme immunoassay (EIA), protein misfolding cyclic amplification (PMCA), and real time quaking-induced conversion (RT-QuIC).[34] Available tests, as of July 2019, at the CFIA were not sensitive enough to detect the prion in specimens from animals younger than a year old.[15] Strategies are being developed to allow for the quantification of prion burden in a tissue, body fluid, or environmental sample.[34] As of 2015, no commercially feasible diagnostic tests could be used on live animals.[10] As early as 2001 an antemortem test was deemed urgent.[35] Running a bioassay, taking fluids from animals in the deer family suspected of infection and incubating them in transgenic mice that express the cervid prion protein, can be used to determine whether the cervid is infected, but ethical issues exist with this, and it is not scalable.[10] A tonsillar biopsy technique has been a reliable method of testing for CWD in live deer,[36] but it only seems to be effective on mule deer and white-tailed deer, not elk.[37] Biopsies of the rectal mucosa have also been effective at detecting CWD in live mule deer, white-tailed deer, and elk, though detection efficacy may be influenced by numerous factors including animal age, genotype, and disease stage.[38][39][40][41] It is possible for CWD prions to survive sterilization procedures involving an autoclave. ## Epidemiology[edit] Reported cases of chronic wasting disease in North America, as of 2018 ### North America[edit] The disease was first identified in 1967 in a closed herd of captive mule deer in contiguous portions of northeastern Colorado. In 1980, the disease was determined to be a TSE. It was first identified in wild elk and mule deer and white-tailed deer in the early 1980s in Colorado and Wyoming, and in farmed elk in 1997.[2][10][12] Canada was not affected by the disease until 1996.[15] In May 2001, CWD was also found in free-ranging deer in the southwestern corner of Nebraska (adjacent to Colorado and Wyoming) and later in additional areas in western Nebraska. The limited area of northern Colorado, southern Wyoming, and western Nebraska in which free-ranging deer, moose, and/or elk positive for CWD have been found is referred to as the endemic area. The area in 2006 has expanded to six states, including parts of eastern Utah, southwestern South Dakota, and northwestern Kansas. Also, areas not contiguous (to the endemic area) areas in central Utah and central Nebraska have been found. The limits of the affected areas are not well defined, since the disease is at a low incidence and the amount of sampling may not be adequate to detect it. In 2002, CWD was detected in wild deer in south-central Wisconsin and northern Illinois and in an isolated area of southern New Mexico. In 2005, it was found in wild white-tailed deer in New York and in Hampshire County, West Virginia.[42] In 2008, the first confirmed case of CWD in Michigan was discovered in an infected deer on an enclosed deer-breeding facility. It is also found in the Canadian provinces of Alberta and Saskatchewan. In February 2011, the Maryland Department of Natural Resources reported the first confirmed case of the disease in that state. The affected animal was a white-tailed deer killed by a hunter.[43] CWD has also been diagnosed in farmed elk and deer herds in a number of states and in two Canadian provinces. The first positive farmed-elk herd in the United States was detected in 1997 in South Dakota. Since then, additional positive elk herds and farmed white-tailed deer herds have been found in South Dakota (7), Nebraska (4), Colorado (10), Oklahoma (1), Kansas (1), Minnesota (3), Montana (1), Wisconsin (6), and New York (2). As of fall of 2006, four positive elk herds in Colorado and a positive white-tailed deer herd in Wisconsin remain under state quarantine. All of the other herds have been depopulated or have been slaughtered and tested, and the quarantine has been lifted from one herd that underwent rigorous surveillance with no further evidence of disease. CWD also has been found in farmed elk in the Canadian provinces of Saskatchewan and Alberta. A retrospective study also showed mule deer exported from Denver to the Toronto Zoo in the 1980s were affected. In June 2015, the disease was detected in a male white-tailed deer on a breeding ranch in Medina County, Texas. State officials euthanized 34 deer in an effort to contain a possible outbreak. In February 2018, the Mississippi Department of Wildlife, Fisheries, and Parks announced that a Mississippi deer tested positive for chronic wasting disease.[44] Another Mississippi whitetail euthanized in Pontotoc County on 8 October 2018 tested positive for CWD. The disease was confirmed by the National Veterinary Services Laboratory in Ames, Iowa on 30 October 2018.[45] Species that have been affected with CWD include elk, mule deer, white-tailed deer, black-tailed deer, and moose. Other ruminant species, including wild ruminants and domestic cattle, sheep, and goats, have been housed in wildlife facilities in direct or indirect contact with CWD-affected deer and elk, with no evidence of disease transmission. However, experimental transmission of CWD into other ruminants by intracranial inoculation does result in disease, suggesting only a weak molecular species barrier exists. Research is ongoing to further explore the possibility of transmission of CWD to other species. By April 2016, CWD had been found in captive animals in South Korea; the disease arrived there with live elk that were imported from Canada for farming in the late 1990s.[2][46] In the summer of 2018, cases were discovered in the Harpur Farm herd in Grenville-sur-la-Rouge, Quebec.[28] Over the course of 2018 fully 12% of the mule deer that were tested in Alberta, had a positive result. More than 8% of Alberta deer were deemed seropositive.[32] ### Europe[edit] In 2016, the first case of CWD in Europe was from the Nordfjella wild reindeer herd in southern Norway. Scientists found the diseased female reindeer as it was dying, and routine CWD screening at necropsy was unexpectedly positive. The origin of CWD in Norway is unknown, whereas import of infected deer from Canada was the source of CWD cases in South Korea. Norway has strict legislation and rules not allowing importation of live animals and deer into the country. Norway has a scrapie surveillance program since 1997; while no reports of scrapie within the range of Nordfjella reindeer population have been identified, sheep are herded through that region and are a potential source of infection.[47] In May and June 2016, two infected wild moose (Alces alces) were found around 300 km north from the first case, in Selbu.[48][49] By the end of August, a fourth case had been confirmed in a wild reindeer shot in the same area as the first case in March.[50] In 2017, the Environment Agency of the Norwegian government released guidelines for hunters hunting reindeer in the Nordfjella areas. The guidelines contain information on identifying animals with CWD symptoms and instructions for minimizing the risk of contamination, as well as a list of supplies given to hunters to be used for taking and submitting samples from shot reindeer.[51] In March 2018, Finnish Food Safety Authority EVIRA stated that the first case of CWD in Finland had been diagnosed in a 15-year-old moose (Alces alces) that had died naturally in the municipality of Kuhmo in the Kainuu region. Before this case in Kuhmo, Norway was the only country in the European Economic Area where CWD has been diagnosed. The moose did not have the transmissible North American form of the disease, but similar to the Norwegian variant of CWD, an atypical or sporadic form which occurs incidentally in individual animals of the deer family. In Finland, CWD screening of fallen wild deer has been done since 2003. None of the roughly 2,500 samples analyzed so far have tested positive for the disease. The export of live animals of the deer family to other countries has been temporarily banned as a precautionary measure to stop the spread of the CWD, and moose hunters are going to be provided with more instructions before the start of the next hunting season, if appropriate. The export and sales of meat from deer will not be restricted and moose meat is considered safe to eat as only the brain and nervous tissue of infected moose contains prions.[52] In March 2019, the Swedish National Veterinary Institute (SVA) diagnosed the first case of CWD in Sweden. A 16-year old emaciated female moose was found in the municipality of Arjeplog in the county of Norrbotten, circling and with loss of shyness towards humans, possibly blind. The moose was euthanized and the head was sent for CWD screening in the national CWD surveillance program. The brainstem tissue, but not lymph nodes, was positive for CWD (confirmed with Western Blot). A second case of CWD was diagnosed in May 2019, with very similar case history, about 70 km east of the first case. This second case, in the municipality of Arvidsjaur, was also an emaciated and apathic 16-year-old female moose that was euthanized. The circumstances of these Swedish cases are similar to the CWD cases in moose in both Norway and Finland. The EU regulated CWD surveillance runs between 2018 - 2020. A minimum of 6 000 deer are to be tested, both free-ranging animals in the deer family, farmed red deer, and semi-domesticated reindeer.[53] The finding of CWD-positive moose initiated an intensified surveillance in the affected municipalities. Adult hunter-harvested moose and slaughtered semi-domesticated reindeer from the area are tested for CWD. In September 2019, a third moose was found positive for CWD, a hunter-harvested 10-year-old apparently healthy female moose from Arjeplog.[54] A fourth case of CWD in moose was verified in September 2020, in a euthanized 14-year-old lame and unshy female moose in the municipality of Robertsfors, in the county of Västerbotten, approximately 200 km from the previous moose cases in the neighboring county of Norrbotten.[55] ## Research[edit] Research is focused on better ways to monitor disease in the wild, live animal diagnostic tests, developing vaccines, better ways to dispose of animals that died from the disease and to decontaminate the environment, where prions can persist in soils, and better ways to monitor the food supply. Deer harvesting and management issues are intertwined.[56] ## References[edit] 1. ^ "Chronic Wasting Disease (CWD)". USDA. APHIS. 1 August 2017. 2. ^ a b c d e f g h i j k l m n o Patrice N Klein, CWD Program Manager USDA/APHIS. 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"Could avian scavengers translocated infectious prions to disease-free areas initiating new foci of chronic wasting disease?". Prion. 7 (4): 263–266. doi:10.4161/pri.25621. PMC 3904308. PMID 23822910. 27. ^ Vercauteren, K.C.; Pilon, J.L.; Nash, P.B.; Phillips, G.E.; Fischer, J.W. (2012). "Prion remains infectious after passage through digestive system of American crows (Corvus brachyrhynchos)". PLOS ONE. 7 (10): e45774. Bibcode:2012PLoSO...745774V. doi:10.1371/journal.pone.0045774. PMC 3474818. PMID 23082115. 28. ^ a b c Lorange, Simon-Olivier. "Pourquoi avoir abattu 3000 cerfs dans les Laurentides? \| Simon-Olivier Lorange \| Environnement". La Presse. Lapresse.ca. Retrieved 2019-02-12. 29. ^ a b c "DU CERF DE BOILEAU, IL N'Y EN AURA PLUS". La Presse, ltée. 21 December 2018. 30. ^ "Une maladie fatale affectant les cerfs arrive au Québec". La Presse (2018) Inc. 1 October 2018. 31. ^ a b "Deer hunting rules relaxed to curb deadly disease". CBC. 9 September 2019. 32. ^ a b "Critics warn of 'totally unacceptable' risk to humans after meat from 21 tainted elk herds enters food supply". CBC. 15 August 2019. 33. ^ "Operation to control and monitor chronic wasting disease in cervids". mffp.gouv.qc.ca. 29 August 2019. 34. ^ a b Haley, Nicholas; Richt, Jurgen (September 2017). "Evolution of Diagnostic Tests for Chronic Wasting Disease, a Naturally Occurring Prion Disease of Cervids". Pathogens. 6(3). PMID 28783058. Retrieved 23 August 2020. 35. ^ Prusiner, Stanley B. (2001). "Neurodegenerative Diseases and Prions". New England Journal of Medicine. 344 (20): 1516–1526. doi:10.1056/NEJM200105173442006. PMID 11357156. 36. ^ Wolfe, Lisa L.; Conner, Mary M.; Baker, Thomas H.; Dreitz, Victoria J.; Burnham, Kenneth P.; Williams, Elizabeth S.; Hobbs, N. Thompson; Miller, Michael W. (2002). "Evaluation of Antemortem Sampling to Estimate Chronic Wasting Disease Prevalence in Free-Ranging Mule Deer". The Journal of Wildlife Management. 66 (3): 564. doi:10.2307/3803124. JSTOR 3803124. S2CID 16353279. 37. ^ "Chronic Wasting Disease" (PDF). Archived from the original (PDF) on 2006-09-12. 38. ^ Geremia, Chris; Hoeting, Jennifer A.; Wolfe, Lisa L.; Galloway, Nathan L.; Antolin, Michael F.; Spraker, Terry R.; Miller, Michael W.; Hobbs, N. Thompson (2015). "Age and Repeated Biopsy Influence Antemortem PRPCWD Testing in Mule Deer (Odocoileus Hemionus) in Colorado, USA". Journal of Wildlife Diseases. 51 (4): 801–810. doi:10.7589/2014-12-284. ISSN 0090-3558. PMID 26251986. 39. ^ Thomsen, Bruce V.; Schneider, David A.; O’Rourke, Katherine I.; Gidlewski, Thomas; McLane, James; Allen, Robert W.; McIsaac, Alex A.; Mitchell, Gordon B.; Keane, Delwyn P. (September 2012). "Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer ( Odocoileus virginianus ) herds in North America: Effects of age, sex, polymorphism at PRNP codon 96, and disease progression". Journal of Veterinary Diagnostic Investigation. 24 (5): 878–887. doi:10.1177/1040638712453582. ISSN 1040-6387. PMID 22914819. 40. ^ Spraker, Terry R.; VerCauteren, Kurt C.; Gidlewski, Thomas; Schneider, David A.; Munger, Randy; Balachandran, Aru; O'Rourke, Katherine I. (2009). "Antemortem Detection of PrP CWD in Preclinical, Ranch-Raised Rocky Mountain Elk ( Cevvus Elaphus Nelsoni ) by Biopsy of the Rectal Mucosa". Journal of Veterinary Diagnostic Investigation. 21 (1): 15–24. doi:10.1177/104063870902100103. ISSN 1040-6387. PMID 19139496. 41. ^ Monello, Ryan J.; Powers, Jenny G.; Hobbs, N. Thompson; Spraker, Terry R.; O’Rourke, Katherine I.; Wild, Margaret A. (April 2013). "Efficacy of Antemortem Rectal Biopsies to Diagnose and Estimate Prevalence of Chronic Wasting Disease in Free-Ranging Cow Elk (Cervus Elaphus Nelsoni)". Journal of Wildlife Diseases. 49 (2): 270–278. doi:10.7589/2011-12-362. ISSN 0090-3558. PMID 23568902. 42. ^ "Chronic Wasting Disease". West Virginia Division of Natural Resources. 2008-08-01. 43. ^ "Wasting Disease Confirmed in State". February 13, 2011. 44. ^ "The Clarion Ledger". The Clarion Ledger. 2018-02-10. Retrieved 2019-02-12. 45. ^ Times Daily Florence, AL 11/12/18 46. ^ Rachel Becker for Nature News. April 18, 2016 Deadly animal prion disease appears in Europe 47. ^ Benestad, Sylvie L.; Mitchell, Gordon; Simmons, Marion; Ytrehus, Bjørnar; Vikøren, Turid (2016-01-01). "First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer". Veterinary Research. 47 (1): 88. doi:10.1186/s13567-016-0375-4. ISSN 0928-4249. PMC 5024462. PMID 27641251. 48. ^ "Chronic Wasting Disease in Norway". Norwegian Food Safety Authority. 15 September 2016. Retrieved 2018-03-12. 49. ^ Norwegian Food Safety Authority. Chronic Wasting Disease in Norway. Published July 13, 2016; updated July 14, 2016 50. ^ "Nytt tilfelle av CWD på villrein". Norwegian Veterinary Institute (in Norwegian). 29 August 2016. Retrieved 2018-03-12. 51. ^ "Informasjon til villreinjegere i Nordfjella" (PDF) (in Norwegian). 2017. Retrieved 2018-03-12. 52. ^ "Moose found dead in forest with chronic wasting disease". Evira. 8 March 2018. Archived from the original on 24 June 2018. Retrieved 2018-03-12. 53. ^ "Aktuellt - SVA". 54. ^ "Aktuellt - SVA". 55. ^ https://www.mynewsdesk.com/se/jordbruksverket/pressreleases/nytt-fall-av-avmagringssjuka-cwd-paa-aelg-3037551 56. ^ Lohrer, Lydia (November 26, 2017). "Hunters must change approach, help stall CWD from spreading to humans". Detroit Free Press. Retrieved November 26, 2017. ## External links[edit] Wikimedia Commons has media related to Chronic wasting disease. * This entry incorporates public domain text originally at What is chronic wasting disease? Animal and Plant Health Inspection Service * Chronic Wasting Disease Alliance * Chronic wasting disease Centers for Disease Control and Prevention * Chronic wasting disease (CWD) of deer and elk, Canadian Food Inspection Agency * Chronic wasting disease (CWD) USGS National Wildlife Health Center * CWD information & testing Colorado Parks and Wildlife * [https://www.dnr.illinois.gov/programs/CWD/Pages/default.aspx Chronic wasting diseas Illinois Department of Natural Resources * Chronic wasting disease management Minnesota Department of Natural Resources * Chronic wasting disease (CWD) Nebraska Game and Parks Commission * Chronic wasting disease New York State Department of Environmental Conservation * Chronic wasting disease Program Pennsylvania Department of Agriculture * Chronic wasting disease Pennsylvania Game Commission * Chronic wasting disease Wisconsin Department of Natural Resources * Chronic wasting disease (CWD) Wyoming Wildlife, Wyoming Game and Fish * v * t * e Prion diseases and transmissible spongiform encephalopathy Prion diseases in humans inherited/PRNP: * fCJD * Gerstmann–Sträussler–Scheinker syndrome * Fatal familial insomnia sporadic: * sCJD * Sporadic fatal insomnia * Variably protease-sensitive prionopathy acquired/ transmissible: * iCJD * vCJD * Kuru Prion diseases in other animals * Bovine spongiform encephalopathy * Camel spongiform encephalopathy * Scrapie * Chronic wasting disease * Transmissible mink encephalopathy * Feline spongiform encephalopathy * Exotic ungulate encephalopathy [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	Chronic wasting disease	c1135993	5,961	wikipedia	https://en.wikipedia.org/wiki/Chronic_wasting_disease	2021-01-18T18:39:14	{"mesh": ["D034081"], "umls": ["C1135993"], "wikidata": ["Q1087811"]}
A rare subtype of autosomal dominant cerebellar ataxia type I characterized by involuntary movements, ataxia, epilepsy, mental disorders, cognitive decline and prominent anticipation. ## Epidemiology Worldwide prevalence is unknown. However, the disease is found most commonly in Japan where the prevalence is estimated to be 1/208,000. ## Clinical description Age of onset ranges from 1 to 60 years (mean age = 28.8 years). Patients with earlier onset (below 20 years of age) tend to show myoclonus epilepsy and intellectual deficit. Patients with late onset (over 40 years of age) tend to present with cerebellar ataxia, choreoathetosis and dementia. Clinical features and the age of onset are significantly correlated with the size of CAG repeats. Head magnetic resonance imaging (MRI) shows atrophy of cerebellum, brainstem, cerebrum and high signal has been shown in periventricular white matter. ## Etiology Unstable expansion of CAG repeats in the ATN1 gene (12p13.31) has been demonstrated. ## Prognosis Prognosis is poor. DRPLA progresses rather rapidly. The mean disease duration is about 13 years. Recurrent seizures and dysphagia with frequent fluid and food aspiration lead to bronchopneumonia and subsequent death. However, some patients can reach 60 years of age or more. [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	Dentatorubral pallidoluysian atrophy	c0751781	5,962	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101	2021-01-23T18:47:52	{"gard": ["5643"], "mesh": ["D020191"], "omim": ["125370"], "umls": ["C0751781"], "icd-10": ["G11.8"], "synonyms": ["DRPLA", "Dentatorubropallidoluysian atrophy", "Naito-Oyanagi disease"]}
Velamentous cord insertion Normal umbilical cord insertion and velamentous umbilical cord insertion in pregnancy, with and without vasa previa. SpecialtyObstetrics SymptomsBlood vessel compression,[1][2] decrease in blood supply to the fetus,[2][3] impaired growth and development of the fetus.[4][5] Risk factorsMultiple gestation,[1][2][6][7][8] placental anomalies [9] previous pregnancy with abnormal cord insertion[2] Diagnostic methodAbdominal ultrasound[3][4] TreatmentCaesarean section[7] Frequency0.1%-1.8% of pregnancies[6] Velamentous cord insertion is a complication of pregnancy where the umbilical cord is inserted in the fetal membranes. In normal pregnancies, the umbilical cord inserts into the middle of the placental mass and is completely encased by the amniotic sac. The vessels are hence normally protected by Wharton's jelly, which prevents rupture during pregnancy and labor.[10] In velamentous cord insertion, the vessels of the umbilical cord are improperly inserted in the chorioamniotic membrane, and hence the vessels traverse between the amnion and the chorion towards the placenta.[1][11] Without Wharton's jelly protecting the vessels, the exposed vessels are susceptible to compression and rupture.[1][9] The exact cause of velamentous cord insertion is unknown, although risk factors include nulliparity,[2][6] the use of assisted reproductive technology,[6][12] maternal obesity,[6][7] and pregnancy with other placental anomalies.[9] Velamentous cord insertion is often diagnosed using an abdominal ultrasound.[3][4] This is most successful in the second trimester,[13] however Color Doppler ultrasound[14] or transvaginal ultrasound[15] can be used in difficult cases, such as when the placenta is located posteriorly. If the woman is diagnosed with velamentous cord insertion, the pregnancy is closely monitored, especially as velamentous cord insertion is a strong risk factor for vasa previa, where the exposed vessels cross the cervix and are at high risk of rupture when during membrane rupture in early labor.[9] Management strategies for velamentous cord insertion also involve determining the presence of vasa previa.[16] Velamentous cord insertion impacts fetal development during pregnancy by impairing the development of the placenta[2] and modifying the efficiency of placental function.[17] This can manifest in a range of adverse perinatal outcomes, such as fetal growth restriction,[4][5] placental abruption,[3][6][16][18] abnormal fetal heart rate patterns,[3][10][19] and fetal death.[6][7][9] Velamentous cord insertion affects between 0.1%-1.8% of pregnancies,[6] though its incidence increases ten-fold in multiple pregnancies.[1][10] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 2.1 Risk factors * 3 Diagnosis * 4 Management * 5 Complications * 5.1 Maternal * 5.2 Fetal * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] Signs and symptoms of velamentous cord insertion during pregnancy include blood vessel compression,[1][2] decrease in blood supply to the fetus,[2][3] and impaired growth and development of the fetus.[4][5] Blood tests taken in the second trimester may reveal increased levels of serum human chorionic gonadotropin and reduced levels of alpha-fetoprotein.[20][21] The mother may also experience vaginal bleeding, particularly in the third trimester.[11] Women with velamentous cord insertion may not experience any symptoms throughout pregnancy.[16] During delivery, there may be slow or abnormal fetal heart rate patterns[3][10][19] and there may be excessive bleeding or hemorrhage, particularly if the fetal vessels rupture.[1][7][9][22] ## Pathophysiology[edit] The exact mechanisms leading to insertion of the umbilical cord in the fetal membranes are unknown, although they are likely to occur in the first trimester.[23] One theory is that velamentous cord insertion may arise from the process of placental trophotropism, which is the phenomenon where the placenta migrates towards areas which have better blood flow with advancing gestation. The placenta grows in regions with better blood supply and portions atrophy in regions of poor blood flow. This process of atrophy may result in the exposure of umbilical blood vessels, causing marginal or peripheral placental insertion to evolve to velamentous insertion over time.[1][10][23] Placentas with velamentous cord insertion have a lower vessel density.[2] As the growth of the fetus is dependent on the organization, mass, and nutrient-transfer capacity of the placenta, fetal development is hence hindered in velamentous cord insertion. This can lead to fetal malformations[2][24] and low birth weight.[2][6][10] The umbilical vessels may also be longer compared to normal,[2] particularly when the site of velamentous cord insertion is in the lower uterine section as the extension of the uterine isthmus as pregnancy advances causes vessel elongation.[3] This results in increased vascular resistance, which impedes nutrient transfer to the fetus.[2] The umbilical vessels experience increased pressure and compression as they are not protected by Wharton's jelly. This can cause decreased or acute cessation of blood flow, decreased cardiac output, and pulmonary complications in the newborn.[2] The elongated, exposed vessels in lower velamentous cord insertion cases are more readily compressed by the fetus, hence there is an even greater risk of non-reassuring fetal heart rate pattern and emergency caesarean section.[2][3] The growth-restricting impacts of placental insufficiency resulting from velamentous cord insertion can also augment the effects of increased pressure to the umbilical vessels.[2] Normally in the second half of pregnancy, one-third of fetal cardiac output is directed towards the placenta. This fraction is reduced to around one-fifth in the last few weeks of pregnancy, while the remaining umbilical blood is recirculated in the fetal body, corresponding with decreased fetal reserves of oxygen.[25] In pregnancies with growth restriction, the fraction of fetal cardiac output distributed to the placenta decreases, further lowering fetal reserves.[2][25] This can result in increased risk of caesarean delivery, fetal hypoxia, and perinatal death in pregnancies with velamentous cord insertion.[2] Damage to the umbilical cord vessels can occur when the amniotic membranes are ruptured, particularly in the case of vasa previa, potentially leading to fetal exsanguination.[3][8][26] If the umbilical vessels are positioned such that their rupture is likely during labor, an elective operative birth at 35–36 weeks gestation may be planned, and corticosteroids may be administered in order to assist with fetal lung maturation.[7][9] Overall, velamentous cord insertion doubles the risk of both preterm birth and acute caesarean section.[2] ### Risk factors[edit] The following have been identified as risk factors for velamentous cord insertion: * Nulliparity[2][6] * Prior termination[6][7] * History of infertility[6] * The use of assisted reproductive technology[6][7][12] * Multiple gestation[1][2][6][7][8] * Maternal smoking[1][2][6][7] * Maternal asthma[2] * Maternal obesity[6] * Chronic hypertension[2] * Type 1 diabetes[2] * Gestational diabetes[2] * Placental anomalies, including low-lying placenta, bilobed placenta, placenta with accessory lobe/s[9] * Previous pregnancy with abnormal cord insertion[2] * Having an umbilical cord with a single umbilical artery[9] * Advanced maternal age[5][27] ## Diagnosis[edit] Abdominal ultrasound can be used to visualize the insertion site of the umbilical cord.[3][4] Overall, visualization is most successful in the second trimester,[13] however routine ultrasound examination in the second trimester may not detect velamentous cord insertion if the condition develops after the remodelling of the placenta as gestation advances.[10] Visualization becomes increasingly difficult in the third trimester as the fetus may obscure the insertion site.[4][13] The umbilical cord and its insertion site may be obscured by the fetus, such as in posterior placenta or in low-lying placenta, or may be difficult to visualise due to conditions such as maternal obesity.[10][15] In these cases, the use of Color Doppler ultrasound or transvaginal ultrasound can enhance the visualization of the umbilical cord, and are able to diagnose velamentous cord insertion at 18–20 weeks.[14][15] ## Management[edit] If velamentous cord insertion is diagnosed, fetal growth is assessed every four weeks using ultrasound beginning at 28 weeks. If intrauterine growth restriction is observed, the umbilical cord is also assessed for signs of compression. Non-stress tests may be performed twice a week to ensure adequate blood flow to the fetus.[16] The amniotic fluid may be frequently assessed for high levels of inflammatory markers such as interleukin-6 which can indicate intra-amniotic inflammation.[28][29] Upon diagnosis of velamentous cord insertion, transvaginal ultrasound with Color Doppler may also be performed to determine whether any of the exposed vessels are within two centimeters of the internal cervical os. If such vessels are identified, vasa previa may be present and cervical length is measured every week to determine the risk of premature rupture of membranes.[16] Women diagnosed with velamentous cord insertion may also receive counselling about the condition, its risks, and potential courses of action, including preterm delivery or caesarean delivery.[7] The newborn may be delivered via normal vagina labor if there are no signs of fetal distress.[2] Fetal heart rate is continuously monitored for slow or abnormal heart rate patterns which may indicate fetal distress during labor.[7] If the exposed blood vessels are near the cervix or are at risk of rupturing, the newborn may be delivered via caesarean section as early as 35 weeks gestation.[7][9] ## Complications[edit] ### Maternal[edit] * Vasa previa[2][3][7][11][16] * Rupture of the vessels and membranes[1][7][9] * Small placenta[2] * Low arterial cord pH[10] * Vascular thrombosis[9] * Intrapartum bleeding[11] * Umbilical cord avulsion[10][27] * Need for caesarean delivery,[2][3] curettage,[22] manual extraction of the placenta[1][27] * Placental abruption[3][6][16][18] * Postpartum hemorrhage[1][7][9][22] ### Fetal[edit] * Prematurity[2][4] * Abnormal heart rate patterns[3][10][19] * Low birth weight[2][6][10] * Newborn/s small for gestational age[4][5][6] * Low Apgar score[3][4][10] * Fetal hypoxia[9][23] * Pulmonary complications[2] * Fetal malformations[1][2] * Fetal bleeding[9][4] * Death[3][5][6][7][9][10] In twins, one or both of the fetuses may have velamentous cord insertion, which can lead to birth-weight discordance, where one twin weighs significantly more at birth than the other,[2][30] and selective fetal growth restriction.[31] These complications particularly arise in the case of monochorionic twins, where identical twins share the same placenta.[2][32] ## Epidemiology[edit] Velamentous cord insertion occurs in between 0.1%-1.8% of all pregnancies,[6] and is eight to ten times more frequent in multiple pregnancies.[1][3][12] This risk is doubled in the case of monochorionic twins, and tripled in the case of fetal growth restriction.[1] It is thought that sex may be a determinant of abnormal cord insertions, however there is conflicting evidence as to whether male or female fetuses are linked to greater risk of velamentous cord insertion.[2][6] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p Ismail K, Hannigan A, ODonoghue K, Cotter A (2017). "Abnormal placental cord insertion and adverse pregnancy outcomes: a systematic review and meta-analysis". Systematic Reviews. 6 (1): 242. doi:10.1186/s13643-017-0641-1. PMC 5718132. PMID 29208042. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al Ebbing C, Kiserud T, Johnsen S, Albrechtsen S, Rasmussen S (2013). "Prevalence, Risk Factors and Outcomes of Velamentous and Marginal Cord Insertions: A Population-Based Study of 634,741 Pregnancies". PLOS ONE. 8 (7): e70380. Bibcode:2013PLoSO...870380E. doi:10.1371/journal.pone.0070380. PMC 3728211. PMID 23936197. 3. ^ a b c d e f g h i j k l m n o p q r Hasegawa J, Matsuoka R, Ichizuka K, Sekizawa A, Okai T (2006). "Velamentous Cord Insertion: Significance of Prenatal Detection to Predict Perinatal Complications". Taiwanese Journal of Obstetrics and Gynecology. 45 (1): 21–25. doi:10.1016/S1028-4559(09)60185-6. PMID 17272203. 4. ^ a b c d e f g h i j k Sepulveda W, Rojas I, Robert J, Schnapp C, Alcalde J (2003). "Prenatal detection of velamentous insertion of the umbilical cord: a prospective color Doppler ultrasound study". Ultrasound in Obstetrics and Gynecology. 21 (6): 564–569. doi:10.1002/uog.132. PMID 12808673. S2CID 1788491. 5. ^ a b c d e f Eddleman K, Lockwood C, Berkowitz G, Lapinski R, Berkowitz R (1992). "Clinical Significance and Sonographic Diagnosis of Velamentous Umbilical Cord Insertion". American Journal of Perinatology. 9 (2): 123–126. doi:10.1055/s-2007-994684. PMID 1590867. 6. ^ a b c d e f g h i j k l m n o p q r s t u v Räisänen S, Georgiadis L, Harju M, Keski-Nisula L, Heinonen S (2012). "Risk factors and adverse pregnancy outcomes among births affected by velamentous umbilical cord insertion: a retrospective population-based register study". European Journal of Obstetrics & Gynecology and Reproductive Biology. 165 (2): 231–234. doi:10.1016/j.ejogrb.2012.08.021. PMID 22944380. 7. ^ a b c d e f g h i j k l m n o p q Wiedaseck S, Monchek R (2014). "Placental and Cord Insertion Pathologies: Screening, Diagnosis, and Management". Journal of Midwifery & Women's Health. 59 (3): 328–335. doi:10.1111/jmwh.12189. PMID 24751147. 8. ^ a b c Furuya S, Kubonoya K, Kubonaya K (2014). "Prevalence of velamentous and marginal umbilical cord insertions; a comparison of term singleton ART and non-ART pregnancies". Fertility and Sterility. 102 (3): e313. doi:10.1016/j.fertnstert.2014.07.1063. 9. ^ a b c d e f g h i j k l m n o p Bohiltea R, Cirstoiu M, Ciuvica A, Munteanu O, Bodean O, Voicu D, Ionescu C (2016). "Velamentous insertion of umbilical cord with vasa praevia: case series and literature review". Journal of Medicine and Life. 9 (2): 126–129. PMC 4863500. PMID 27453740. 10. ^ a b c d e f g h i j k l m n Sinkin J, Craig W, Jones M, Pinette M, Wax J (2018). "Perinatal Outcomes Associated With Isolated Velamentous Cord Insertion in Singleton and Twin Pregnancies". Journal of Ultrasound in Medicine. 37 (2): 471–718. doi:10.1002/jum.14357. PMID 28850682. S2CID 26888548. 11. ^ a b c d Paavonen J, Jouttunpää K, Kangasluoma P, Aro P, Heinonen P (1984). "Velamentous insertion of the umbilical cord and vasa previa". International Journal of Gynecology & Obstetrics. 22 (3): 207–211. doi:10.1016/0020-7292(84)90007-9. PMID 6148278. S2CID 23409481. 12. ^ a b c Delbaere I, Goetgeluk S, Derom C, De Bacquer D, De Sutter P, Temmerman M (2007). "Umbilical cord anomalies are more frequent in twins after assisted reproduction". Human Reproduction. 22 (10): 2763–2767. doi:10.1093/humrep/dem191. PMID 17720701. 13. ^ a b c Pretorius D, Chau C, Poeltler D, Mendoza A, Catanzarite V, Hollenbach K (1996). "Placental cord insertion visualization with prenatal ultrasonography". Journal of Ultrasound in Medicine. 15 (8): 585–593. doi:10.7863/jum.1996.15.8.585. PMID 8839406. S2CID 40093577. 14. ^ a b Nomiyama M, Toyota Y, Kawano H (1998). "Antenatal diagnosis of velamentous umbilical cord insertion and vasa previa with color Doppler imaging". Ultrasound in Obstetrics and Gynecology. 12 (6): 426–429. doi:10.1046/j.1469-0705.1998.12060426.x. PMID 9918092. S2CID 35261375. 15. ^ a b c Baulies S, Maiz N, Muñoz A, Torrents M, Echevarría M, Serra B (2007). "Prenatal ultrasound diagnosis of vasa praevia and analysis of risk factors". Prenatal Diagnosis. 27 (7): 595–599. doi:10.1002/pd.1753. PMID 17497747. S2CID 37634607. 16. ^ a b c d e f g Vintzileos A, Ananth C, Smulian J (2015). "Using ultrasound in the clinical management of placental implantation abnormalities". American Journal of Obstetrics and Gynecology. 213 (4): S70–S77. doi:10.1016/j.ajog.2015.05.059. PMID 26428505. 17. ^ Yampolsky M, Salafia C, Shlakhter O, Haas D, Eucker B, Thorp J (2009). "Centrality of the Umbilical Cord Insertion in a Human Placenta Influences the Placental Efficiency". Placenta. 30 (12): 1058–1064. doi:10.1016/j.placenta.2009.10.001. PMC 2790011. PMID 19879649. 18. ^ a b Toivonen S, Heinonen S, Anttila M, Kosma V, Saarikoski S (2002). "Reproductive Risk Factors, Doppler Findings, and Outcome of Affected Births in Placental Abruption: A Population-Based Analysis". American Journal of Perinatology. 19 (8): 451–460. doi:10.1055/s-2002-36868. PMID 12541219. 19. ^ a b c Hasegawa J, Matsuoka R, Ichizuka K, Kotani M, Nakamura M, Mikoshiba T, Sekizawa A, Okai (2009). "Atypical variable deceleration in the first stage of labor is a characteristic fetal heart-rate pattern for velamentous cord insertion and hypercoiled cord". Journal of Obstetrics and Gynaecology Research. 35 (1): 35–39. doi:10.1111/j.1447-0756.2008.00863.x. PMID 19215545. S2CID 11157923. 20. ^ Heinonen S, Ryynanen M, Kirkinen P, Saarikoski S (1996). "Velamentous umbilical cord insertion may be suspected from maternal serum alpha-fetoprotein and hCG". BJOG. 103 (3): 209–213. doi:10.1111/j.1471-0528.1996.tb09707.x. PMID 8630303. S2CID 74179289. 21. ^ Heinonen S, Ryynanen M, Kirkinen P, Saarikoski S (1996). "Elevated Midtrimester Maternal Serum hCG in Chromosomally Normal Pregnancies is Associated with Preeclampsia and Velamentous Umbilical Cord Insertion". American Journal of Perinatology. 13 (7): 437–441. doi:10.1055/s-2007-994384. PMID 8960614. 22. ^ a b c Ebbing C, Kiserud T, Johnsen S, Albrechtsen S, Rasmussen S (2015). "Third stage of labor risks in velamentous and marginal cord insertion: a population-based study". Acta Obstetricia et Gynecologica Scandinavica. 94 (8): 878–883. doi:10.1111/aogs.12666. PMID 25943426. S2CID 45614777. 23. ^ a b c Sepulveda W (2006). "Velamentous Insertion of the Umbilical Cord". Journal of Ultrasound in Medicine. 25 (8): 963–968. doi:10.7863/jum.2006.25.8.963. PMID 16870889. S2CID 43165100. 24. ^ Yerlikaya G, Pils S, Springer S, Chalubinski K, Ott J (2015). "Velamentous cord insertion as a risk factor for obstetric outcome: a retrospective case–control study". Archives of Gynecology and Obstetrics. 293 (5): 975–981. doi:10.1007/s00404-015-3912-x. PMID 26498602. S2CID 1011746. 25. ^ a b Kiserud T, Ebbing C, Kessler J, Rasmussen S (2006). "Fetal cardiac output, distribution to the placenta and impact of placental compromise". Ultrasound in Obstetrics and Gynecology. 28 (2): 126–136. doi:10.1002/uog.2832. PMID 16826560. S2CID 25954526. 26. ^ Robert J, Sepulveda W (2003). "Fetal exsanguination from ruptured vasa previa: still a catastrophic event in modern obstetrics". Journal of Obstetrics and Gynaecology. 23 (5): 574. doi:10.1080/0144361031000156636. PMID 12963533. S2CID 36906136. 27. ^ a b c Esakoff T, Cheng Y, Snowden J, Tran S, Shaffer B, Caughey A (2014). "Velamentous cord insertion: is it associated with adverse perinatal outcomes?". The Journal of Maternal-Fetal & Neonatal Medicine. 28 (4): 409–412. doi:10.3109/14767058.2014.918098. PMID 24758363. S2CID 1390065. 28. ^ Kenyon A, Abi-Nader K, Pandya P (2010). "Pre-term pre-labour rupture of membranes and the role of amniocentesis". Fertility and Sterility. 21 (2): 75–88. 29. ^ Chaemsaithong P, Romero R, Korzeniewski S, Martinez-Varea A, Dong Z, Yoon B, Hassan S, Chaiworapongsa T, Yeo L (2015). "A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection". The Journal of Maternal-Fetal & Neonatal Medicine. 29 (3): 360–367. doi:10.3109/14767058.2015.1006621. PMC 5703063. PMID 25758620. 30. ^ Kent E, Breathnach F, Gillan J, McAuliffe F, Geary M, Daly S, Higgins J, Dornan J, Morrison J, Burke G, Higgins S, Carroll S, Dicker P, Manning F, Malone F (2011). "Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective EsPRIT trial". American Journal of Obstetrics and Gynecology. 204 (1): S20. doi:10.1016/j.ajog.2010.10.044. 31. ^ Kalafat E, Thilaganathan B, Papageorghiou A, Bhide A, Khalil A (2018). "Significance of placental cord insertion site in twin pregnancys". Ultrasound in Obstetrics & Gynecology. 52 (3): 378–384. doi:10.1002/uog.18914. PMID 28976606. S2CID 10906198. 32. ^ Sato Y (2006). "Increased Prevalence of Fetal Thrombi in Monochorionic-Twin Placentas. Pediatrics". Pediatrics. 117 (1): e113–e117. doi:10.1542/peds.2005-1501. PMID 16361224. S2CID 19061448. ## External links[edit] Classification D * ICD-10: O43.1 * ICD-9-CM: 762.6 * DiseasesDB: 34591 External resources * eMedicine: med/3276 * 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 [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	Velamentous cord insertion	c0266789	5,963	wikipedia	https://en.wikipedia.org/wiki/Velamentous_cord_insertion	2021-01-18T18:29:46	{"icd-9": ["762.6"], "icd-10": ["O43.1"], "wikidata": ["Q490081"]}
For the hair pattern, see Chignon (hairstyle). 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: "Chignon" medical term – news · newspapers · books · scholar · JSTOR (January 2014) (Learn how and when to remove this template message) Chignon A baby's scalp showing the effects of a vacuum extraction. SpecialtyPediatrics A chignon is a temporary swelling left on an infant's head after a ventouse suction cap has been used to deliver him or her.[1] It is not a sign of serious injury and may take as little as two hours or as long as two weeks to disappear. ## See also[edit] * Caput succedaneum * Cephalohematoma ## References[edit] 1. ^ Baston, Helen; Durward, Heather (23 June 2010). Examination of the Newborn: A Practical Guide. Routledge. pp. 72–75. ISBN 978-0-203-84995-8. ## External links[edit] Classification D * ICD-10: P12.1 * ICD-9-CM: 767.19 * 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 This medical sign 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	Chignon (medical term)	None	5,964	wikipedia	https://en.wikipedia.org/wiki/Chignon_(medical_term)	2021-01-18T18:54:45	{"icd-9": ["767.19"], "icd-10": ["P12.1"], "wikidata": ["Q5097223"]}
Double aortic arch Other namesDAA Double aortic arch is a relatively rare congenital cardiovascular malformation. DAA is an anomaly of the aortic arch in which two aortic arches form a complete vascular ring that can compress the trachea and/or esophagus.[1][2] Most commonly there is a larger (dominant) right arch behind and a smaller (hypoplastic) left aortic arch in front of the trachea/esophagus. The two arches join to form the descending aorta which is usually on the left side (but may be right-sided or in the midline). In some cases the end of the smaller left aortic arch closes (left atretic arch) and the vascular tissue becomes a fibrous cord. Although in these cases a complete ring of two patent aortic arches is not present, the term ‘vascular ring’ is the accepted generic term even in these anomalies. The symptoms are related to the compression of the trachea, esophagus or both by the complete vascular ring. Diagnosis can often be suspected or made by chest x-ray, barium esophagram, or echocardiography. Computed tomography (CT) or magnetic resonance imaging (MRI) show the relationship of the aortic arches to the trachea and esophagus and also the degree of tracheal narrowing. Bronchoscopy can be useful in internally assessing the degree of tracheomalacia. Treatment is surgical and is indicated in all symptomatic patients. In the current era the risk of mortality or significant morbidity after surgical division of the lesser arch is low. However, the preoperative degree of tracheomalacia has an important impact on postoperative recovery. In certain patients it may take several months (up to 1–2 years) for the obstructive respiratory symptoms (wheezing) to disappear. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 4.1 Anesthesia and intraoperative monitoring * 4.2 Open division of vascular ring * 4.3 Postoperative care * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms are caused by vascular compression of the airway, esophagus or both. Presentation is often within the first month (neonatal period) and usually within the first 6 months of life. Starting at birth an inspiratory and expiratory stridor (high pitch noise from turbulent airflow in trachea) may be present often in combination with an expiratory wheeze. The severity of the stridor may depend on the patient’s body position. It can be worse when the baby is lying on their back rather than their side. Sometimes the stridor can be relieved by extending the neck (lifting the chin up). Parents may notice that the baby’s cry is hoarse and the breathing noisy. Frequently a persistent cough is present. When the airway obstruction is significant there may be episodes of severe cyanosis (“blue baby”) that can lead to unconsciousness. Recurrent respiratory infections are common and secondary pulmonary secretions can further increase the airway obstruction. Secondary to compression of the esophagus babies often feed poorly. They may have difficulties in swallowing liquids with choking or regurgitating and increased respiratory obstruction during feeding. Older patients might refuse to take solid food, although most infants with severe symptoms nowadays are operated upon before they are offered solid food. Occasionally patients with double aortic arches present late (during later childhood or adulthood). Symptoms may mimic asthma. ## Causes[edit] Little is known regarding the exact causes of aortic arch anomalies. However, the association with chromosome 22q11 deletion (DiGeorge Syndrome) implies that a genetic component is likely in certain cases.[3] Esophageal atresia also occurs in some patients with double aortic arch.[4] ## Diagnosis[edit] Prenatal diagnosis (fetal ultrasound): Today the diagnosis of double aortic arch can be obtained in-utero in experienced centers.[5] Scheduled repair soon after birth in symptomatic patients can relieve tracheal compression early and therefore potentially prevent the development of severe tracheomalacia. Chest X-ray: Plain chest x-rays of patients with double aortic arch may appear normal (often) or show a dominant right aortic arch or two aortic arches . There might be evidence of tracheal deviation and/or compression. Sometimes patients present with radiologic findings of pneumonia. Barium swallow (esophagraphy): Historically the esophagram used to be the gold standard for diagnosis of double aortic arch. In patients with double aortic arch the esophagus shows left- and right-sided indentations from the vascular compression. Due to the blood-pressure related movement of the aorta and the two arches, moving images of the barium-filled esophagus can demonstrate the typical pulsatile nature of the obstruction. The indentation from a dominant right arch is usually deeper and higher compared to the dent from the left arch. Bronchoscopy: Although bronchoscopy is not routinely done in patients with suspected or confirmed double aortic arch, it can visualize sites and severity of pulsatile tracheal compression. Echocardiography: In babies under the age of 12 months, echocardiography is considered to be sensitive and specific in making the diagnosis of double aortic arch when both arches are open. Non-perfused elements of other types of vascular rings (e.g. left arch with atretic (closed) end) or the ligamentum arteriosum might be difficult to visualize by echocardiography. Computed tomography (CT): Computed tomography after application of contrast media is usually diagnostically accurate. It shows the relationship of the arches to the trachea and bronchi. Magnetic resonance imaging (MRI): Magnetic resonance imaging provides excellent images of the trachea and surrounding vascular structures and has the advantage of not using radiation for imaging compared to Computed tomography. Cardiac catherization/aortography: Today patients with double aortic arch usually only undergo cardiac catherization to evaluate the hemodynamics and anatomy of associated congenital cardiac defects. Through a catheter in the ascending aorta contrast media is injected and the resulting aortography may be used to delineate the anatomy of the double aortic arch including sites of narrowing in the left aortic arch. Aortography can also be used to visualize the origin of all head and arm vessels originating from the two arches. ### Classification[edit] Double aortic arch is a subtype of complete vascular ring. There are three types of double aortic arch: * Right dominant arch (about 70% of surgical cases) * Balanced or codominant (about 5%): both arches are of equal size * Left dominant (about 25%) Double aortic arch with right dominant arch: Normally there is only one (left) aortic arch. In patients with double aortic arch the ascending aorta arises normally from the left ventricle but then divides into two arches, a left and a right aortic arch which join posteriorly to become the descending aorta. The smaller left arch passes anteriorly and to the left of the trachea in the usual position. It is often joined by the ligamentum arteriosum (or patent ductus arteriosus) where it forms the descending aorta. The left arch gives first origin to the left common carotid artery and then the left subclavian artery. The right aortic arch is completing the vascular ring by passing to the right and then behind the esophagus and trachea to join the usually left-sided descending aorta. The first vessel coming off the right arch is usually the right common carotid artery followed by the right subclavian artery. Double aortic arch with left dominant arch: In this less common condition, as the name indicates, the left arch is the larger of the two aortic arches. The origins of the arm and head vessels are identical to the anatomy of double aortic arch with right dominant arch Balanced or codominant double aortic arch: In this rare condition both aortic arches are of the same diameter. ## Treatment[edit] Surgical correction is indicated in all double aortic arch patients with obstructive symptoms (stridor, wheezing, pulmonary infections, poor feeding with choking). If symptoms are absent a conservative approach (watchful waiting) can be reasonable. Children with very mild symptoms may outgrow their symptoms but need regular follow-up. ### Anesthesia and intraoperative monitoring[edit] The procedure is performed in general anesthesia. It is useful to place pulse oximeter probes on both hands and one foot so that test occlusion of one arch or its branches will allow confirmation of the anatomy. In addition blood pressure cuffs should also be placed on one leg and both arms to confirm the absence of a pressure gradient when the intended point of division of the lesser arch is temporarily occluded with forceps. ### Open division of vascular ring[edit] Isolated double aortic arch without associated intracardiac defects is a vascular anomaly that can be corrected without the support of cardiopulmonary bypass. For surgical division of the narrower left aortic arch in a typical double arch patient with a dominant right arch, the patient is placed on the right side. After prepping and draping of the left chest a posterolateral thoracotomy is performed. The chest cavity is entered between the fourth and fifth rib (fourth intercostal space, as in the operation for patent ductus arteriosus or coarctation). After pulling the left lung aside, the layer (mediastinal pleura) above the left arch is incised and the left arch and the ligamentum arteriosum are dissected out and separated from the surrounding structures. The ligamentum is divided and two vascular clamps are placed on the junction of the left arch with the descending aorta. After division the two aortic ends are oversewn with 2 running layers of non-absorbable sutures. The end of the left arch is now further dissected from the mediastinal tissues for relief of any remaining constricting mechanism. The medial surface of the descending aorta and the distal end are also carefully dissected away from the esophagus. Additional relief can be obtained by stitching the lateral wall of the aorta to the adjacent rib to pull it away from the esophagus. After insertion of a chest tube to prevent hemothorax and/or pneumothorax, the fourth and fifth rib are approximated by an absorbable suture. The surgery is completed by closure of the left thoracotomy wound in layers. In most centers, the mortality risk for surgery is between zero and 2%.[citation needed] A specific risk of open surgical repair of double aortic arch is injury to the recurrent laryngeal nerve, which can cause vocal cord paralysis. Injury to the lymphatic system can lead to postoperative chylothorax. Additional risks include lung injury, bleeding with the need for blood transfusions and wound infection. ### Postoperative care[edit] After the surgery, some patients require intubation and mechanical ventilation for several days to allow adequate tracheal toilet, but most patients can have the tubes removed soon after the surgery. The obstructive airway symptoms may be worse in the first postoperative weeks. Only a few patients have immediate relief of stridor, but many obtain immediate relief of problems with swallowing (dysphagia). After extubation, it might be necessary to maintain positive airway pressure by appropriate flows of a humidified oxygen/air mixture. ## Epidemiology[edit] Complete vascular rings represent about 0.5-1% of all congenital cardiovascular malformations. The majority of these are double aortic arches. There is no known gender preference, i.e. males and females are about equally affected. There is also no known ethnic or geographic disposition. Associated cardiovascular anomalies are found in 10-15% of patients. These include: * Atrial septal defect (ASD) * Ventricular septal defect (VSD) * Patent ductus arteriosus (PDA) * Tetralogy of Fallot (ToF) * Transposition of the great arteries (D-TGA) ## History[edit] Congenital abnormalities of the aortic arch have been known for a long time. The first postmortem description of double aortic arch was in 1737 by Hommell.[6] In 1837 von Siebold published a case report in the German medical literature entitled "Ringfoermiger Aortenbogen bei einem neugeborenen blausuechtigen Kinde" (Ring-shaped aortic arch in a cyanotic neonate).[7] With the use of barium esophagography it became possible to diagnose aortic arch anomalies during life in the 1930s. The first open surgical correction via thoracotomy was performed by Robert E. Gross at Children’s Hospital Boston in 1945.[8] Gross is one of the pioneers of cardiovascular surgery, who also performed the first successful ligation of a patent ductus arteriosus 7 years earlier. The basis for the radiologic diagnosis by barium swallow (esophagram) of double aortic arch (and other forms of vascular rings) was described in 1946 by Neuhauser from the same institution.[9] Certain types of double aortic arch with a left arch that is small in diameter (less than 2 or 3mm patent) or atretic might be suitable for a so-called minimally invasive video-assisted thoracoscopic surgery (VATS) approach.[10] ## References[edit] 1. ^ Jonas RA. Comprehensive Surgical Management of Congenital Heart Disease, London, Arnold, 2004, p. 497 2. ^ Kirklin JW, Barratt-Boyes BG. Cardiac Surgery, 3rd ed., New York, Churchill Livingstone, 2003, p. 1415 3. ^ Momma K, Matsuoka R, Takao A. Aortic arch anomalies associated with chromosome 22q11 deletion. Pediatr Cardiol. 1999 Mar-Apr;20(2):97-102 4. ^ Hartenberg, M. A.; Salzberg, A. M.; Krummel, T. M.; Bush, J. J. (1989-05-01). "Double aortic arch associated with esophageal atresia and tracheoesophageal fistula". Journal of Pediatric Surgery. 24 (5): 488–490. doi:10.1016/s0022-3468(89)80409-9. ISSN 0022-3468. PMID 2738813. 5. ^ Tuo G, Volpe P, Bava GL, Bondanza S, De Robertis V, Pongiglione G, Marasini M. Prenatal diagnosis and outcome of isolated vascular rings. Am J Cardiol. 2009 Feb 1;103(3):416-9 6. ^ Hommell L. Observationes anatomicae de arcu aortae bifido du dueto thoracico duplica, et de carstidum atque subclaviarum. Holdomas 1737;21:161 7. ^ von Siebold CT. Ringfoermiger Aortenbogen bei einem neugeborenen blausuechtigen Kinde. J Geburtsh Frauenzimmer-Kinderkrank 1837;16:294 8. ^ Gross RE. Surgical relief for tracheal obstruction from a vascular ring. N Engl J Med 1945;233:586 9. ^ Neuhauser EB. The roentgen diagnosis of double aortic arch and other anomalies of the great vessels. Am J Roentgenol Radium Ther Nucl Med 1946;56:1 10. ^ Burke RP, Rosenfeld HM, Wernovsky G, Jonas RA.Video-assisted thoracoscopic vascular ring division in infants and children. J Am Coll Cardiol. 1995;25:943 ## External links[edit] Classification D * DiseasesDB: 33811 External resources * MedlinePlus: 007316 * eMedicine: article/899609 * v * t * e Congenital vascular defects / Vascular malformation Great arteries/ other arteries Aorta * Patent ductus arteriosus * Coarctation of the aorta * Interrupted aortic arch * Double aortic arch * Right-sided aortic arch * Overriding aorta * Aneurysm of sinus of Valsalva * Vascular ring Pulmonary artery * Pulmonary atresia * Stenosis of pulmonary artery Subclavian artery * Aberrant subclavian artery Umbilical artery * Single umbilical artery Great veins Superior/inferior vena cava * Congenital stenosis of vena cava * Persistent left superior vena cava Pulmonary vein * Anomalous pulmonary venous connection (Total, Partial) * Scimitar syndrome Arteriovenous malformation * Cerebral arteriovenous malformation [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	Double aortic arch	c0265883	5,965	wikipedia	https://en.wikipedia.org/wiki/Double_aortic_arch	2021-01-18T18:59:07	{"mesh": ["D000073872"], "umls": ["C0265883"], "wikidata": ["Q5299967"]}
Dental panoramic radiograph showing Stafne defect in the right mandible, below the inferior alveolar nerve canal (arrowed, appears on lower left of image). This x-ray was taken for an unrelated assessment of wisdom teeth, and the Stafne defect was a chance finding. Axial computed tomograph of the same person. The Stafne defect appears as a well corticated 1 cm round defect in the medial cortex of the mandible in the right angle of the jaw (arrowed). Coronal computed tomograph of the same person (Stafne defect arrowed). The Stafne defect (also termed Stafne's idiopathic bone cavity, Stafne bone cavity, Stafne bone cyst (misnomer), lingual mandibular salivary gland depression, lingual mandibular cortical defect, latent bone cyst, or static bone cyst) is a depression of the mandible, most commonly located on the lingual surface (the side nearest the tongue). The Stafne defect is thought to be a normal anatomical variant, as the depression is created by ectopic salivary gland tissue associated with the submandibular gland and does not represent a pathologic lesion as such. ## Contents * 1 Classification * 2 Signs and symptoms * 3 Causes * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 History * 8 References ## Classification[edit] It is a classed as a pseudocyst,[1] since there is no epithelial lining or fluid content. This defect is usually considered with other cysts of the jaws, since it can be mistaken for such on a radiograph. ## Signs and symptoms[edit] There are no symptoms,[2] and no signs can be elicited on examination. Medical imaging such as traditional radiography or computed tomography is required to demonstrate the defect. Usually the defect is unilateral, but occasionally can be bilateral.[3] ## Causes[edit] The Stafne defect is thought to be caused by an ectopic portion of the submandibular salivary gland which causes the bone of the lingual cortical plate to remodel. Rarely, the defect can be completely surrounded by bone, and this has been theorized to be the result of entrapment of embryonic salivary gland tissue within the bone. Similar, but rarer, defects may be present in the anterior portion of the lingual surface of the mandible. These are not termed Stafne defects which specifically refers to the posterior location. The anterior defects may be associated with the sublingual salivary gland. ## Diagnosis[edit] Stafne's defect is usually discovered by chance during routine dental radiography.[4] Radiographically, it is a well-circumscribed, monolocular, round, radiolucent defect, 1–3 cm in size, usually between the inferior alveolar nerve (IAN) and the inferior border of the posterior mandible between the molars and the angle of the jaw. It is one of the few radiolucent lesions that can occur below the IAN. The border is well corticated and it will have no effect on the surrounding structures. Computed tomography (CT) will show a shallow defect through the medial cortex of the mandible with a corticated rim and no soft tissue abnormalities, with the exception of a portion of the submandibular gland. Neoplasms, such as metastatic squamous cell carcinoma to the submandibular lymph nodes or a salivary gland tumour, could create a similar appearance but rarely have such well defined borders and can usually be palpated in the floor of the mouth or submandibular triangle of the neck as a hard mass. CT and clinical exam is typically sufficient to distinguish between this and a Stafne defect. The Stafne defect also tends to not increase in size or change in radiographic appearance over time (hence the term "static bone cyst"), and this can be used to help confirm the diagnosis.[4] Tissue biopsy is not usually indicated, but if carried out, the histopathologic appearance is usually normal salivary gland tissue. Sometimes attempted biopsy of Stafne defects reveals an empty cavity (possibly because the gland was displaced at the time of biopsy), or other contents such as blood vessels, fat, lymphoid or connective tissues. Defects of the anterior lingual mandible may require biopsy for correct diagnosis at this unusual location.[2] The radiolucent defect here may be superimposed on the lower anterior teeth and be mistaken for an odontogenic lesion. Sometimes the defect may interrupt the contour of the lower border of the mandible, and may be palpable. Sialography may be sometimes used to help demonstrate the salivary gland tissue within the bone. ## Treatment[edit] No treatment is required,[2] but neoplastic processes (metastatic malignancy to the submandibular lymph nodes and/or salivary gland tumours) should be ruled out. This is usually done with clinical exam and imaging. Very rarely, since the defect contains salivary gland tissue, salivary gland tumors can occur within an established defect but there is likely no difference in the risk of neoplasia in salivary gland tissue at other sites. ## Epidemiology[edit] Stafne defect is uncommon,[3] and has been reported to develop anywhere between the ages of 11 and 30 years old,[5] (although the defect is developmental, it does not seem to be present from birth, implying that the lesion develops at a later age).[2] Usually the defect is unilateral (on one side only) and most commonly occurs in men. ## History[edit] This entity was first described in 1942 by Edward C. Stafne.[6] It was previously known by many names, including static bone cyst,[7] Stafne idiopathic bone cavity,[8] and salivary gland inclusions in the mandible,[9] An early case of Stafne's defect has been discovered in a 7th-century BC adult male individual from Klazomenai, one of the 12 cities of the Ionian League (now in modern Turkey).[10] ## References[edit] 1. ^ Burket LW, Greenberg MS, Glick M (2003). Burket's oral medicine diagnosis & treatment (10th ed.). Hamilton, Ont.: BC Decker. p. 155. ISBN 978-1550091861. 2. ^ a b c d Bouquot, Brad W. Neville BW, Damm DD, Allen CM, Bouquot JE. (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. p. 23. ISBN 978-072169003-2. 3. ^ a b Soames JV, Southam JC (2003). Oral Pathology. New York: Oxford University Press Inc. p. 89. ISBN 978-0192628947. 4. ^ a b Wray D, Stenhouse D, Lee D, Clark AJE (2003). Textbook of general and oral surgery. Edinburgh [etc.]: Churchill Livingstone. pp. 236–237. ISBN 978-0443070839. 5. ^ White, Stuart C.; Pharoah, Michael J. (2004). Oral radiology principles and interpretation 5th editition. St. Louis, Missouri: Mosby. pp. 651–2. ISBN 978-0-323-02001-5. 6. ^ Stafne, EC. Bone cavities situated near the angle of the mandible. JADA 1942;29:1969–1972. 7. ^ Rushton, MA. Solitary bone cysts in the mandible. Br Dent J 1946;81:37-49 8. ^ Barakat, N; AbouChedid, J. Cavite idiopathic mandibulaires. Rev Dent Liban 1973;23:35-40 9. ^ Seward, GR. Salivary gland inclusions in the mandible. Br Dent J 1960;108:321-325 10. ^ A. Agelarakis and B. Cohen, “Stafne Cavity on a 7th c. BC Klazomenaean Hoplite Warrior”, Book of Abstracts, 37th Annual Meeting of the American Paleopathology Association, Albuquerque, New Mexico, April 13–14, 2010 * 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	Stafne defect	None	5,966	wikipedia	https://en.wikipedia.org/wiki/Stafne_defect	2021-01-18T18:36:47	{"icd-10": ["M27.0"], "wikidata": ["Q7596727"]}
Interstitial lung disease due to ABCA3 deficiency is a rare genetic respiratory disease characterized by a variable clinical outcome ranging from a fatal respiratory distress syndrome in the neonatal period to chronic interstitial lung disease developing in infancy or childhood with chronic cough, rapid breathing, shortness of breath and recurrent pulmonary infections. Clinical manifestations of respiratory failure include grunting, intercostal retractions, nasal flaring, cyanosis, and progressive dyspnea. [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	Interstitial lung disease due to ABCA3 deficiency	c1970456	5,967	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=440402	2021-01-23T17:34:04	{"mesh": ["C567046"], "omim": ["610921"], "icd-10": ["J84.8"], "synonyms": ["Interstitial lung disease due to ATP-binding cassette subfamily A member 3 deficiency"]}
Hypereosinophilic syndrome (HES) refers to a rare group of conditions that are associated with persistent eosinophilia with evidence of organ involvement. Signs and symptoms vary significantly based on which parts of the body are affected. Although any organ system can be involved in HES, the heart, central nervous system, skin, and respiratory tract are the most commonly affected. The condition was originally thought to be "idiopathic" or of unknown cause. However, recent advances in diagnostic testing have allowed a cause to be identified in approximately a quarter of cases. Management varies based on the severity of the condition and whether or not an underlying cause has been identified but generally includes imatinib or corticosteroids as an initial treatment. [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	Hypereosinophilic syndrome	c1540912	5,968	gard	https://rarediseases.info.nih.gov/diseases/2804/hypereosinophilic-syndrome	2021-01-18T17:59:56	{"mesh": ["D017681"], "omim": ["607685", "131400"], "orphanet": ["168956"], "synonyms": ["HES", "Hypereosinophilic syndrome, idiopathic"]}
## Description Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of genetic heterogeneity of restless legs syndrome, see RLS1 (102300). Mapping In a genomewide association study of 393 patients with restless leg syndrome and 1,602 controls, Winkelmann et al. (2007) found a significant association between restless leg syndrome and rs2300478 in the MEIS1 gene (601739) on chromosome 2p14-p13. The findings were confirmed in 2 independent replication studies of 875 and 211 patients, respectively. Combined results of all 3 studies yielded an overall odds ratio of 1.74 for the G allele (p = 8.08 x 10(-23)). The study also showed evidence for an association with several SNPs within a region on chromosome 15q that contains the LBXCOR1 (611273) and MAP2K5 (602520) genes. In a study of 244 patients with restless legs syndrome, including 123 familial probands, Vilarino-Guell et al. (2008) confirmed an association with 2 SNPs in the MEIS1 gene. The most significant association was observed for the G allele of rs12469063 (p = 8.2 x 10(-6)) in familial cases. In a study including 649 RLS patients and 1,230 controls from the Czech Republic, Austria, and Finland, Kemlink et al. (2009) found an association between RLS and rs2300478 in the MEIS1 gene. (p = 1.26 x 10(-5); odds ratio of 1.47). The association was found only in familial and not sporadic cases. Restless legs syndrome can occur in end-stage renal disease (ESRD), with a prevalence ranging between 18.4 and 45.8% in ESRD patients of European descent (summary by Schormair et al., 2011). In a case-control association study of 200 RLS German patients and 443 non-RLS German patients both with ESRD, Schormair et al. (2011) found an association between RLS and rs12469063 and rs2300478 in the MEIS1 gene: an OR of 1.47-1.52, p (corrected) of 0.013-0.026. However, no association was observed with these SNPs among 141 RLS and 393 non-RLS patients both with ESRD of Greek descent. Molecular Genetics Xiong et al. (2009) sequenced all 13 MEIS1 exons and their splice junctions in 285 RLS probands and 285 normal controls and did not identify any causative coding or exon-intron junction mutations. The authors analyzed 2 RLS-associated SNPs, rs12469063 and 2300478, and found a GG/GG risk haplotype (43% vs 25%, p = 0.0095) in 28 RLS and 140 control brain samples. Quantitative real-time PCR analysis detected a significant decrease in MEIS1 expression in lymphoblastoid cell lines (LCLs) and brain tissues from RLS patients with GG/GG risk haplotype compared with RLS patients and controls with the AA/TT nonrisk haplotype. There was significantly decreased MEIS1 protein levels in the same sample of LCLs and brain tissues from GG/GG carriers compared with the AA/TT carriers. Xiong et al. (2009) concluded that reduced expression of the MEIS1 gene, possibly through intronic cis-regulatory elements, predisposes to RLS. Vilarino-Guell et al. (2009) identified an arg272-to-his (R272H; rs61752693) substitution in the MEIS1 gene in 1 of 71 probands with RLS. The variant segregated with the disorder in 3 additional family members, but was also found in 1 unaffected member. The phenotype in this family was highly variable, with different ages at onset and differing severity. The R272H variant was not found among 378 additional RLS cases or 528 controls from North America, but it was found in 1 of 325 European controls, suggesting reduced penetrance. The substitution was predicted to occur in a highly conserved homeobox 'three-amino acid loop extension' (TALE) domain, but no functional studies were performed. Vilarino-Guell et al. (2009) stated that the pathogenicity of the R272H MEIS1 variant warrants replication. Schulte et al. (2014) identified synonymous and nonsynonymous rare coding variants in the MEIS1 gene in 9 of 188 German RLS patients compared to 1 of 182 controls, indicating a significant association (p = 0.021). A follow-up study of 3,262 RLS cases of German or Austrian descent and 2,944 controls yielded similar results, with the association becoming stronger as the allele frequency decreased: nonsynonymous MEIS1 alleles with a minor allele frequency (MAF) less than 1% were found in 39 cases compared to 14 controls (p = 0.0024, OR = 2.46), whereas total and nonsynonymous-only alleles with an MAF less than 0.1% were found in 9 cases and 1 control (p = 0.014, OR = 8.14). The association was driven primarily by a low-frequency variant (rs11693221) in the 3-prime UTR of isoform 1 of MEIS1 (OR = 4.42), implicating the UTRs in disease pathogenesis, perhaps through regulating gene expression or mRNA stability. More detailed analysis of the type of variants showed that RLS cases carried an excess of rare variants in the 3- and 5-prime UTRs as well as of nonsynonymous coding variants compared to controls. Functional analysis of selected coding variants was performed in zebrafish using rescue of morpholino knockouts, which showed defects in neurogenesis. Fourteen cases carried 5 variants in isoform 1 of the MEIS1 gene (R203G, S204T, H239Y, R272H, and Q353H) that were shown to be null alleles in zebrafish assays, whereas only 2 controls carried functionally null alleles (Q147K and R272H) (p = 0.0012, OR = 7.48). The findings suggested that reduced activity of MEIS1 isoform 1 contributes to the development of RLS. Animal Model Spieler et al. (2014) found that the G risk allele of rs12469063 in the MEIS1 gene alters enhancer function in the developing telencephalon. The G risk allele of rs12469063, located in a highly conserved noncoding region (617), showed decreased reporter gene expression in the neural tube compared to the A protective allele. Decreased enhancer function of the risk allele was also observed in embryonic mouse brain, particularly in the ganglionic eminences, but not in the adult brain. Affinity chromatography identified CREB1 (123810) as an upstream binding factor of rs12469063, binding stronger to the risk allele where it may act as a transcriptional repressor. Adult heterozygous Meis1-deficient mice showed hyperactivity, resembling the RLS phenotype. Spieler et al. (2014) postulated a loss-of-function mechanism that causes a neurodevelopmental defect affecting the basal ganglia with possible age-dependent development of RLS. [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	RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 7	c2748506	5,969	omim	https://www.omim.org/entry/612853	2019-09-22T16:00:28	{"omim": ["612853"]}
Bardet-Biedl syndrome (BBS) is an inherited condition that affects many parts of the body. People with this syndrome have progressive visual impairment due to cone-rod dystrophy; extra fingers or toes (polydactyly); truncal obesity; decreased function of the male gonads (hypogonadism); kidney abnormalities; and learning difficulties. Mutations in many genes are known to cause Bardet-Biedl syndrome and inheritance is usually autosomal recessive. Treatment depends on the symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA	Bardet-Biedl syndrome	c0752166	5,970	gard	https://rarediseases.info.nih.gov/diseases/6866/bardet-biedl-syndrome	2021-01-18T18:01:53	{"mesh": ["D020788"], "orphanet": ["110"], "synonyms": ["BBS", "Biedl-Bardet Syndrome"]}
Ectodermal dysplasia with corkscrew hairs SpecialtyDermatology Ectodermal dysplasia with corkscrew hairs is a skin condition with salient features including exaggerated pili torti, scalp keloids, follicular plugging, keratosis pilaris, xerosis, eczema, palmoplantar keratoderma, syndactyly, onychodysplasia and conjunctival neovascularization.[1]:571 ## See also[edit] * Skin lesion ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. ## Further reading[edit] * Argenziano G, Monsurrò MR, Pazienza R, Delfino M (February 1998). "A case of probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis". J. Am. Acad. Dermatol. 38 (2 Pt 2): 344–8. doi:10.1016/S0190-9622(98)70580-8. PMID 9486713. * Trüeb R, Burg G, Bottani A, Schinzel A (February 1994). "Ectodermal dysplasia with corkscrew hairs: observation of probable autosomal dominant tricho-odonto-onychodysplasia with syndactyly". J. Am. Acad. Dermatol. 30 (2 Pt 1): 289–90. doi:10.1016/S0190-9622(08)81934-2. PMID 8141890. * Abramovits-Ackerman W, Bustos T, Simosa-Leon V, Fernandez L, Ramella M (December 1992). "Cutaneous findings in a new syndrome of autosomal recessive ectodermal dysplasia with corkscrew hairs". J. Am. Acad. Dermatol. 27 (6 Pt 1): 917–21. doi:10.1016/0190-9622(92)70287-P. PMID 1479096. This Genodermatoses 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	Ectodermal dysplasia with corkscrew hairs	c2931239	5,971	wikipedia	https://en.wikipedia.org/wiki/Ectodermal_dysplasia_with_corkscrew_hairs	2021-01-18T18:37:53	{"gard": ["5376"], "mesh": ["C536565"], "umls": ["C2931239"], "orphanet": ["3357"], "wikidata": ["Q5333997"]}
Infantile Bartter syndrome with deafness, a phenotypic variant of Bartter syndrome (see this term) is characterized by maternal polyhydramnios, premature delivery, polyuria and sensorineural deafness and is associated with hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure, and vascular resistance to angiotensin II. ## Epidemiology It is the least common of all recessive types of Bartter syndrome. ## Clinical description Infantile Bartter syndrome with deafness is a severe type of Bartter syndrome manifesting prenatally with maternal polyhydramnios (due to fetal polyuria) usually evident by the end of 2nd trimester, often leading to preterm labour and prematurity. Postnatally patients present with polyuria, isosthenuria/hyposthenuria and are at high risk of dehydration, hypovolemic hypotension and shock. Patients are found to have complete sensorineural deafness. Recurrent vomiting, muscle cramps, spasms and failure to thrive are observed. Progression to renal failure is frequent. Hypokalemic alkalosis, hypomagnesemia, hyperprostaglandin E-uria and hypochloremia are noted (hypercalciuria is only transient). ## Etiology Infantile Bartter syndrome with deafness is caused by a defect in chloride transport in thick ascending loop of Henle and distal convoluted tubule as a consequence of inactivating mutations of the gene BSND (1p32.3) encoding for the protein Barttin (Bartter syndrome type 4A), required for the location and proper function of the voltage sensitive, Ka and Kb chloride channels of the basolateral membrane, (ClCKa and ClCKb). In addition to mutations of Barttin, infantile Bartter syndrome with deafness may be caused by digeneic (CLCKA and CLCKB 1p36) mutations inactivating all the 4 alleles of the 2 genes (or Bartter syndrome type 4B). CLCKa is highly expressed in the inner ear and contributes to maintain the high potassium ion concentration in the endolymph necessary for normal hearing, disruption of the function of which thus leads to nerve deafness. ## Genetic counseling The disease is transmitted in an autosomal recessive manner. [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	Infantile Bartter syndrome with sensorineural deafness	c2748440	5,972	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=89938	2021-01-23T19:07:40	{"gard": ["10508"], "mesh": ["C567544"], "omim": ["602522", "613090"], "icd-10": ["E26.8"], "synonyms": ["Bartter syndrome type 4", "Bartter syndrome type IV", "Infantile Bartter syndrome with sensorineural hearing loss"]}
A number sign (#) is used with this entry because of evidence that Greig cephalopolysyndactyly syndrome (GCPS) is caused by heterozygous mutation in the GLI3 gene (165240) on chromosome 7p14. Mutations in the GLI3 gene can also cause Pallister-Hall syndrome (PHS; 146510) and 2 forms of isolated polydactyly: postaxial polydactyly type A1 (174200) and preaxial polydactyly type IV (174700). The acrocallosal syndrome (200990) shows some phenotypic overlap with GCPS. Description Greig cephalopolysyndactyly syndrome is characterized by frontal bossing, scaphocephaly, and hypertelorism associated with pre- and postaxial polydactyly and variable syndactyly. The phenotype shows variable expressivity and can also include craniosynostosis. Affected individuals usually have normal psychomotor development (summary by Gorlin et al., 2001). Clinical Features Greig (1928) described digital malformations and peculiar skull shape in mother and daughter. The mother had syndactyly of both hands. The daughter, of above average intelligence, had polysyndactyly and a peculiar skull shape in the form of expanded cranial vault leading to high forehead and bregma, with no evidence of precocious closure of cranial sutures. The thumbs and great toes had bifid terminal phalanges. Marshall and Smith (1970) reported a family with dominant inheritance of what they termed 'frontodigital syndrome.' Intelligence was normal. Merlob et al. (1981) reported a female infant with postaxial polydactyly of the hands, preaxial polydactyly of the feet, with syndactyly, and craniofacial dysmorphism characterized by frontal bossing. X-ray examination revealed markedly advanced bone age. There was also bilateral hip dislocation. The father of the infant had a high forehead and mild hypertelorism. Fryns et al. (1981) described the disorder in dizygotic 4-month-old twin brothers and their father; the twins had severe affection, the father mild. Chudley and Houston (1982) described the syndrome in 3 generations of a family and perhaps by implication in a fourth. They commented on phenotypic overlap with the acrocallosal syndrome (ACLS; 200990). Baraitser et al. (1983) reported 13 affected persons in 3 kindreds with, curiously, no male-to-male transmission. They also commented on similarity to the acrocallosal syndrome. The main clinical distinction was mental retardation, involving agenesis of the corpus callosum. Legius et al. (1985) proposed that the acrocallosal syndrome is the same as Greig syndrome. Marafie et al. (1996) reported Bedouin father and son with Greig cephalopolysyndactyly syndrome; the son had the rare association of mild mental retardation and dysgenesis of the corpus callosum. They noted that dysgenesis of the corpus callosum with mild mental retardation had been reported in only 1 other patient with GCPS (Hootnick and Holmes, 1972). Baraitser et al. (1983) observed that the facial features of Greig syndrome can be so mild as to be indistinguishable from the normal. Therefore they suggested that type IV preaxial polydactyly, or uncomplicated polysyndactyly (174700), as delineated by Temtamy and McKusick (1978), may be Greig syndrome. The family reported by Ridler et al. (1977) as an example of type II syndactyly (186000) was in fact a family with Greig syndrome, as established by Winter (1989), who revisited the family. ### Clinical Variability Gorlin et al. (2001) noted that there is markedly variable expressivity of Greig cephalopolysyndactyly syndrome, and that craniosynostosis has been rarely reported. Hootnick and Holmes (1972) reported a father with polysyndactyly and his son with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum (McDonald-McGinn et al., 2010). Gorlin et al. (2001) considered the father and son reported by Hootnick and Holmes (1972) had GCPS. Guzzetta et al. (1996) reported a boy with trigonocephaly and digital anomalies, including syndactyly of the third and fourth fingers of both hands with bony fusion, bifid thumbs, preaxial polydactyly of the toes, and syndactyly of the first, second, and third rays of the feet. He also had partial agenesis of the corpus callosum but normal development at age 11 months. Guzzetta et al. (1996) discussed the differential diagnosis as including GCPS and Carpenter syndrome (see 201000), and Fryns et al. (1997) later noted the phenotypic overlap with acrocallosal syndrome (ACLS; 200990). McDonald-McGinn et al. (2010) reported 2 unrelated patients with craniosynostosis of the metopic suture resulting in trigonocephaly and multiple digital anomalies associated with 2 different heterozygous mutations in the GLI3 gene (165240.0020 and 165240.0021, respectively). One patient had full digit postaxial polydactyly of all 4 limbs, whereas the other had bilateral complete cutaneous syndactyly of the third and fourth fingers, duplication of the great toe on the right with soft tissue syndactyly of toes 2 and 3, and medial deviation of the great toe on the left. Neither patient had structural brain anomalies, and both had normal development at ages 14 months and 13 years, respectively. The presence of trigonocephaly expanded the phenotype associated with GLI3 mutations. Kini et al. (2010) also reported a child with Greig syndrome and metopic synostosis resulting from a GLI3 mutation. The child also had speech delay. Biesecker (2008) reviewed GCPS, noting the phenotypic overlap with acrocallosal syndrome (ACLS; 200990). He remarked that in patients with substantial phenotypic overlap, molecular diagnostics are essential to arrive at a correct diagnosis; a mutation in GLI3 denotes GCPS. He classified the patient of Elson et al. (2002), with a phenotype 'indistinguishable from acrocallosal syndrome,' as a case of GCPS (see 165240.0013). Demurger et al. (2015) reported the molecular and clinical results from their study of a cohort of 76 probands with either a GLI3 mutation (49 with GCPS and 21 with PHS) or a large deletion encompassing the GLI3 gene (6 with GCPS). Only 10 patients with GCPS fulfilled all clinical criteria, namely preaxial polydactyly, cutaneous syndactyly, widely spaced eyes, and macrocephaly. Anomalies of the corpus callosum were found in 9 patients, 7 of whom had a truncating mutation in the C-terminal domain of the protein. Macrosomia was observed in at least 13% of individuals diagnosed with GCPS. Craniosynostosis was found in only 2 patients, confirming its rare association with GCPS. Inheritance Temtamy and McKusick (1978) studied a particularly instructive family in which 10 members of 4 generations in 6 sibships were affected in the pattern of a fully penetrant autosomal dominant trait. Fryns (1982) documented the variability and autosomal dominant inheritance on the basis of 7 cases. In 1 family, a mother and son were affected. Gollop and Fontes (1985) described affected mother and 2 of her 3 sons. Cytogenetics In an analysis of reported cases, Baccichetti et al. (1982) suggested that deletion of part of the 7p21 may be critical in GCPS. Tommerup and Nielsen (1983) described a translocation t(3;7)(p21.1;p13) segregating through 4 generations in invariable association with GCPS. High resolution cytogenetic analysis using G- and R-banding did not uncover any imbalance of the affected chromosomes, nor were the late replicating patterns changed. A girl with GCPS died with medulloblastoma. Sage et al. (1987) subjected the breakpoints on chromosome 3 and chromosome 7 to molecular genetic analysis. Drabkin et al. (1989) identified 2 very closely linked DNA sequences that flanked the 3;7 translocation breakpoint; no recombination between the disorder and these sequences was found. A pulsed field analysis showed that the disorder was also linked to the TCRG locus (see 186970), but Drabkin et al. (1989) found no evidence of linkage to EGFR (131550). Motegi et al. (1985) reported an affected boy who had a tiny deletion of 7p21.3-p15.3. From comparison with other cases of 7p deletion, with or without craniosynostosis, they suggested that the critical segment for craniosynostosis may be at 7p21.2 or the proximal part of 7p21.3. In 7 GCPS pedigrees with no chromosome abnormality, Brueton et al. (1988) found linkage to EGFR, which is located at 7p13-p11 (maximum lod score of 3.17 at theta = 0.0). In a patient with Greig cephalopolysyndactyly syndrome and deletion of 7p13-p11.2, Rosenkranz et al. (1989) found molecular evidence of deletion of the EGFR gene. However, the EGFR genes were intact in a second patient with deletion of 7p14.2-p12.3. From the data available, the authors concluded that the EGFR gene is probably in band 7p12.3-p12.1 and the GCPS gene more distally situated in 7p13-p12.3. Pettigrew et al. (1989, 1991) confirmed the assignment to 7p13 by study of the sporadic case of an 11-month-old infant with typical features including macrocephaly, frontal bossing, syndactyly, postaxial polydactyly of the hands, and preaxial polydactyly of the feet. High resolution chromosome analysis showed a 46,XX,del(7)(p13p14)pat chromosome pattern. This was the first report of an interstitial deletion associated with Greig syndrome. Cytogenetic analysis of polymorphisms of the heterochromatin in the pericentromeric region suggested that the deleted chromosome was of paternal origin. Review of clinical features and published reports of patients with a deletion involving 7p13 showed a number to have features overlapping with Greig syndrome. Kruger et al. (1989) reported on cases of Greig syndrome segregating in a large kindred over 4 generations. The disorder was due to reciprocal translocation t(6;7)(q27;p13). One patient in this pedigree had a severe malformation syndrome due to duplication 7pter-p13. Wagner et al. (1990) studied 2 patients with GCPS and a cytogenetically visible microdeletion of 7p with gene probes that had been assigned close to the proposed Greig locus. One patient showed loss of the TCRG gene cluster and both showed hemizygosity for PGAM2 (612931). On the other hand, HOX-1.4 (HOXA4; 142953) and IFNB2 (147620) showed normal gene dosage. This suggested that PGAM2 and GCPS are in 7p13-p12.3; TCRG in the distal part of 7p14.2-p13; and HOX-1.4 and IFNB2 distal to 7p14.2. The findings excluded the HOX-1.4 gene from involvement in the pathogenesis of GCPS. Kroisel et al. (2001) described 5 patients with Greig syndrome, including 3 unrelated patients and a pair of monozygotic twin boys with a de novo microdeletion involving 7p13. Because of the considerable lack of well-defined clinical delineation of reported patients with GCPS and microdeletions involving 7p13, the authors focused on the symptoms not typically related to GCPS, such as moderate psychomotor retardation, seizures, muscle fiber anomalies, cardiac anomalies, hyperglycemia, and hirsutism. Their observations suggested that the presence of a cytogenetically detectable microdeletion or a submicroscopic deletion of 7p13 should be suspected in all cases of atypical GCPS. Molecular Genetics Vortkamp et al. (1991) used a candidate gene approach to test the possible implication of the GLI3 gene in this disorder, since the GLI3 gene had been mapped to 7p13. Vortkamp et al. (1991) demonstrated that 2 of 3 translocations found to be associated with GCPS interrupt the GLI3 gene. The breakpoints were within the first third of the coding sequence. In the third translocation, chromosome 7 was broken at about 10 kb downstream of the 3-prime end of GLI3. In patients with GCPS, Wild et al. (1997) identified heterozygous point mutations in the GLI3 gene (165240.0018 and 165240.0019). Sobetzko et al. (2000) described a newborn infant with an unusual combination of syndactylies, macrocephaly, and severe skeletal dysplasia. A history of digital anomalies in the father and grandfather led to the diagnosis of Greig cephalopolysyndactyly syndrome. The skeletal changes were thought to fit best congenital spondyloepiphyseal dysplasia (SEDC; 183900), a type II collagen disorder. Molecular analysis confirmed the presence of 2 dominant mutations in the infant: a GLI3 mutation (E543X; 165240.0010), which was present also in the father and grandfather, and a de novo COL2A1 mutation leading to a gly973 to arg (G973R; 120140.0031) substitution. Thus, this boy combined the syndactyly-macrocephaly phenotype of Greig syndrome with a severe form of SED caused by de novo mutation in type II collagen. The diagnostic difficulties posed by the combination of 2 genetic disorders and the usefulness of molecular diagnostics were well illustrated. Debeer et al. (2003) presented clinical and radiologic findings of 12 patients with GCPS derived from 4 independent families and 3 sporadic cases with documented GLI3 mutations, with particular emphasis on inter- and intrafamilial variability. In a particularly instructive family in which 9 members of 4 generations could be studied clinically and molecularly, a missense mutation, R625W (165240.0012), was transmitted and showed a partially penetrant pattern. In a branch of the family, the GCPS phenotype skipped a generation via a normal female carrier without clinical signs, providing evidence that GCPS does not always manifest full penetrance. Hurst et al. (2011) studied 5 sporadic patients with trigonocephaly due to metopic synostosis in association with pre- and postaxial polydactyly and cutaneous syndactyly of the hands and feet. In all 5 children, diagnosis of GCPS was confirmed by molecular analysis of GLI3, which revealed heterozygosity for a missense mutation and a nonsense mutation in 2 patients, respectively, as well as 3 complete gene deletions detected by array CGH in the remaining 3 patients. Three of the patients had been referred with a clinical diagnosis of Carpenter syndrome (see 201000), which shows overlapping features with GCPS, including craniosynostosis and polysyndactyly; however, additional features that would point to Carpenter syndrome, such as fusion of the coronal or lambdoid sutures, high birth weight, umbilical hernia, and hypogenitalism in males, were absent in these patients. Hurst et al. (2011) also noted that 1 of these patients had hypoplasia of the corpus callosum, a feature that could cause confusion with acrocallosal syndrome. Genotype/Phenotype Correlations Using FISH and STRP analyses in the study of 34 patients with characteristics of GCPS, Johnston et al. (2003) found that 11 had deletions. Mental retardation or developmental delay was present in 9 patients with deletions in whom the disorder was classified as severe GCPS. These patients had manifestations that overlapped with the acrocallosal syndrome. The deletion breakpoints were analyzed in 6 patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. Johnston et al. (2003) concluded that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and hypothesized that the severe GCPS phenotype is caused by deletion of contiguous genes. Johnston et al. (2005) hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause Pallister-Hall syndrome (PHS; 146510), whereas haploinsufficiency of GLI3 causes GCPS. To test this hypothesis, they screened 46 patients with PHS and 89 patients with GCPS for GLI3 mutations. They detected 47 pathologic mutations (among 60 probands), and when these mutations were combined with previously published mutations, 2 genotype-phenotype correlations were evident. GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/nonsense and splicing mutations. Among the frameshift/nonsense mutations, Johnston et al. (2005) found a clear genotype/phenotype correlation. Mutations in the first third of the gene (from open reading frame nucleotides 1-1997) caused GCPS, and mutations in the second third of the gene (from nucleotides 1998-3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3-prime third of the gene (after open reading frame nucleotide 3481), and no patients with PHS had mutations in this region. These results demonstrated a robust genotype/phenotype correlation for GLI3 mutations and strongly supported the hypothesis that these 2 allelic disorders have distinct modes of pathogenesis. Furniss et al. (2007) identified a heterozygous nonsense mutation in the GLI3 gene (R792X; 165240.0016) in a patient with GCPS. The mutation was demonstrated to result in nonsense-mediated mRNA decay. Furniss et al. (2007) postulated that the relatively mild phenotype in this patient, which was less severe than that observed in Pallister-Hall syndrome, may be due to nonsense-mediated mRNA decay that eliminates a toxic dominant-negative effect of a mutant protein. Demurger et al. (2015) reported the molecular and clinical results from a study of 76 probands from 55 families who had either a mutation in GLI3 (49 with GCPS and 21 with PHS) or a large deletion encompassing GLI3 (6 with GCPS). Most of the mutations they identified were novel and supported previously reported genotype/phenotype correlations. Truncating mutations in the middle third of the gene generally resulted in PHS, whereas exonic deletions and missense and truncating mutations elsewhere in the gene caused GCPS. History D. M. Greig, a Scot, pronounced his name 'Gregg' (Ferguson-Smith, 1996). Animal Model Winter and Huson (1988) called attention to the evidence that, on both morphologic and comparative gene mapping grounds, Greig cephalopolysyndactyly syndrome is homologous to the mouse mutant 'extra toes' (Xt) on mouse chromosome 13. The pattern of polydactyly in the 2 species is very similar and both conditions probably map close to the T-gamma receptor locus (TCRG; see 186970). Vortkamp et al. (1992) reported deletion in the 5-prime end of the Gli3 gene in an Xt mutant, and Schimmang et al. (1992) reported that expression of Gli3 is reduced in this mutant. Hui and Joyner (1993) described the molecular characteristics of the Xt mutation. They found that deficiency of expression of Gli3 in the mutant mouse is due to a deletion within the 3-prime end of the gene. Furthermore, structures affected in the mouse mutant and in the human syndrome were found to correlate with expression domains of Gli3 in the mouse. These findings strongly supported the suggestion that deficiency of GLI3 function leads to human GCPS. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Macrocephaly \- Scaphocephaly \- Trigonocephaly Face \- High forehead \- Frontal bossing Eyes \- Hypertelorism \- Downslanting palpebral fissures Nose \- Broad nasal root ABDOMEN External Features \- Umbilical hernia GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKELETAL \- Advanced bone age Skull \- Broad late closing cranial sutures \- Craniosynostosis \- Metopic synostosis (rare) Hands \- Postaxial polydactyly \- Broad thumbs \- Syndactyly (usually fingers 3 and 4) \- Preaxial polydactyly (variable) \- Camptodactyly Feet \- Preaxial polydactyly \- Broad halluces \- Syndactyly (usually toes 1 to 3) \- Postaxial polydactyly (rare) \- Camptodactyly NEUROLOGIC Central Nervous System \- Normal intelligence \- Mental retardation, mild (rare) \- Hydrocephaly \- Agenesis of corpus callosum LABORATORY ABNORMALITIES \- Translocation or deletions involving 7p13 (severe case reports) MISCELLANEOUS \- Variable expressivity MOLECULAR BASIS \- Caused by mutation in the GLI-Kruppel family member GLI3 gene (GLI3, 165240.0001 ) ▲ 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	GREIG CEPHALOPOLYSYNDACTYLY SYNDROME	c0265306	5,973	omim	https://www.omim.org/entry/175700	2019-09-22T16:35:58	{"doid": ["14761"], "mesh": ["C537300"], "omim": ["175700"], "orphanet": ["380"], "synonyms": ["Alternative titles", "POLYSYNDACTYLY WITH PECULIAR SKULL SHAPE"], "genereviews": ["NBK1446"]}
Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells are called ragged-red fibers. Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). People with this condition may also develop hearing loss or optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy. Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin. ## Frequency MERRF is a rare condition; its prevalence is unknown. MERRF is part of a group of conditions known as mitochondrial disorders, which affect an estimated 1 in 5,000 people worldwide. ## Causes Mutations in the MT-TK gene are the most common cause of MERRF, occurring in more than 80 percent of all cases. Less frequently, mutations in the MT-TL1, MT-TH, and MT-TS1 genes have been reported to cause the signs and symptoms of MERRF. People with mutations in the MT-TL1, MT-TH, or MT-TS1 gene typically have signs and symptoms of other mitochondrial disorders as well as those of MERRF. The MT-TK, MT-TL1, MT-TH, and MT-TS1 genes are contained in mitochondrial DNA (mtDNA). Mitochondria are structures within cells that use oxygen to convert the energy from food into a form cells can use through a process called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. The genes associated with MERRF provide instructions for making molecules called transfer RNAs, which are chemical cousins of DNA. These molecules help assemble protein building blocks called amino acids into full-length, functioning proteins within mitochondria. These proteins perform the steps of oxidative phosphorylation. Mutations that cause MERRF impair the ability of mitochondria to make proteins, use oxygen, and produce energy. These mutations particularly affect organs and tissues with high energy requirements, such as the brain and muscles. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MERRF. A small percentage of MERRF cases are caused by mutations in other mitochondrial genes, and in some cases the cause of the condition is unknown. ### Learn more about the genes and chromosome associated with Myoclonic epilepsy with ragged-red fibers * MT-TH * MT-TK * MT-TL1 * MT-TS1 * mitochondrial dna Additional Information from NCBI Gene: * MT-TF * MT-TP * MT-TS2 * MT-TT ## Inheritance Pattern MERRF is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children. In most cases, people with MERRF inherit an altered mitochondrial gene from their mother, who may or may not show symptoms of the disorder. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MERRF. [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	Myoclonic epilepsy with ragged-red fibers	c0162672	5,974	medlineplus	https://medlineplus.gov/genetics/condition/myoclonic-epilepsy-with-ragged-red-fibers/	2021-01-27T08:24:43	{"gard": ["7144"], "mesh": ["D017243"], "omim": ["545000"], "synonyms": []}
Post-nasal drip Other namesUpper airway cough syndrome, UACS, or Post nasal drip syndrome Post-nasal drip SpecialtyOtorhinolaryngology Post-nasal drip (PND), also known as upper airway cough syndrome (UACS), occurs when excessive mucus is produced by the nasal mucosa. The excess mucus accumulates in the back of the nose, and eventually in the throat once it drips down the back of the throat. It can be caused by rhinitis, sinusitis, gastroesophageal reflux disease (GERD), or by a disorder of swallowing (such as an esophageal motility disorder). Other causes can be allergy, cold, flu, and side effects from medications. However, some researchers argue that the flow of mucus down the back of the throat from the nasal cavity is a normal physiologic process that occurs in all healthy individuals.[1] Post-nasal drip has been challenged as a syndrome and instead is widely viewed as a symptom by various researchers as a result of the wide variation among differing societies. Furthermore, this rebuttal is reinforced because of the lack of an accepted definition, pathologic tissue changes, and available biochemical tests.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Allergic rhinitis * 2.2 Non-allergic rhinitis * 2.3 Rhinosinusitis * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] PND may present itself through the constant presence of discomfort in the upper airways. It is classically described as the sensation of a substance "dripping down the throat" and may also present with rhinorrhea, constant throat clearing, and cough, although its symptoms can be very nonspecific.[2] PND is one of the most common etiologies for chronic cough, defined as a cough persisting beyond 8 weeks.[3] GERD is often associated with a high prevalence of upper-respiratory symptoms similar to those of PND, such as coughing, throat clearing, hoarseness and change in voice. Reflux causes throat irritation, leading to a sensation of increased mucus in the throat, which is believed to aggravate and, in some cases, cause post-nasal drip.[2] Post-nasal drip can be a cause of laryngeal inflammation and hyperresponsiveness, leading to symptoms of vocal cord dysfunction.[4][5][6] ## Causes[edit] There are multiple causes of PND, which can be acute or chronic. ### Allergic rhinitis[edit] Allergic rhinitis (AR) is a common condition where exposure to allergens results in the release of inflammatory mediators, such as histamine, that causes sneezing, rhinorrhea, itchy eyes, and nasal obstruction.[7] The increased rhinorrhea and mucus production can result in PND. ### Non-allergic rhinitis[edit] Non-allergic rhinitis (NAR) is a condition in which there are symptoms of rhinitis, including rhinorrhea and nasal obstruction, but with negative skin and serum allergy testing results.[7] It can be further categorized into:[citation needed] * Non-allergic rhinitis with eosinophilia (NARES) * Hormonal rhinitis (such as during pregnancy) * Medication-induced rhinitis * Atrophic rhinitis * Irritant and occupational rhinitis (including tobacco smoke, cleaning supplies, etc.) * Idiopathic nonallergic rhinitis ### Rhinosinusitis[edit] Rhinosinusitis is inflammation or infection of the sinus cavities. Acute rhinosinusitis has symptoms lasting less than four weeks, while chronic rhinosinusitis lasts greater than 12 weeks.[8] This persistent irritation can lead to increased mucus production as a result of pro-inflammatory pathways, producing symptoms of PND.[7] ## Mechanism[edit] The exact mechanism of PND depends on its etiology, but usually involves increased production of mucus from the nasal mucosa. In addition to providing sense of smell, the nasal cavity serves to filtrate and regulate the temperature and humidity of inspired air.[7] The nasal mucosa can produce secretions, or mucus, that provides lubrication and protection for the nasal cavity. This mucus production is activated by the autonomic nervous system; specifically, cholinergic neuropeptides are responsible for increasing mucus production.[7] Excess mucus can drain posteriorly into the upper and lower airways, which, along with other physical and chemical irritants, can activate receptors in the respiratory tract that results in a protective physiological cough.[9] ## Diagnosis[edit] The "allergic salute" sign common in people with allergic rhinitis. Diagnosis of PND depends on both a detailed history and clinical examination to help determine its etiology. The history may begin with feelings of obstructed nasal breathing or "stuffy nose" with or without nasal discharge.[10] If allergic rhinitis is suspected, a family history of allergic conditions as well as a personal history of other associated conditions such as food allergy, asthma, and atopic dermatitis can be evaluated.[10] Allergic rhinitis classically has more symptoms of sneezing attacks, itchy eyes, and respiratory problems, although it is difficult to distinguish the different types of rhinitis by symptomology alone.[10][7] Visual inspection can reveal mouth breathing, which is suggestive of nasal obstruction, or a horizontal crease across the nose (allergic salute).[10] In the absence of any specific diagnostic tests, it may be difficult to diagnose PND from history of symptoms alone, as the etiology is broad and the symptoms may be very general. As such, suggestive procedures that highlight rhinitis and mucopurulent secretions, such as nasoendoscopy, may instead be utilized because of the vague nature of information available to directly attribute specific symptoms to the syndrome.[11][2] ## Treatment[edit] Treatment options depend on the nature of an individual’s post-nasal drip and its cause. Antibiotics may be prescribed if the PND is the result of bacterial sinusitis.[8] In cases where PND is caused by allergic rhinitis or irritant rhinitis, avoidance of allergens or irritating factors such as dander, cigarette smoke, and cleaning supplies may be beneficial.[7] Antihistamines are particularly useful for allergic rhinitis, and it may be beneficial in some cases of non-allergic rhinitis.[7] First-generation antihistamines such as chlorpheniramine and clemastine are more potent but have greater sedatory effects; later-generation antihistamines may be used to reduce these effects.[7] Azelastine, a topical antihistamine, is approved for both allergic and non-allergic rhinitis due to its unique anti-inflammatory effects separate from its histamine receptor antagonism.[7] Intranasal steroids may also be beneficial in patients who do not respond to antihistamines. In one meta-analysis, intranasal steroids were shown to improve symptoms of non-allergic rhinitis at four weeks better than a placebo.[12] Decongestants such as pseudoephedrine can tighten blood vessels of the nasal mucosa and result in a decrease in mucus production.[7] Anticholinergics such as ipratropium bromide can help reduce secretions by blocking parasympathetic effects on the nasal mucosa.[7][13] Other methods, such as drinking warm fluids and using saline nasal irrigation, may be useful for managing symptoms of PND but its exact efficacy is unclear in medical literature.[citation needed] ## Epidemiology[edit] Because PND is often characterized as a "symptom" rather than a separate condition, the exact incidence is unknown and varies by its etiology. Chronic rhinitis, which includes allergic and non-allergic rhinitis, can affect 30-40% of the population.[12] Non-allergic rhinitis is more common in females than in males.[7] ## References[edit] 1. ^ a b Morice AH (2004). "Post-nasal drip syndrome--a symptom to be sniffed at?". Pulmonary Pharmacology & Therapeutics. 17 (6): 343–5. doi:10.1016/j.pupt.2004.09.005. PMID 15564073. 2. ^ a b c Sylvester DC, Karkos PD, Vaughan C, Johnston J, Dwivedi RC, Atkinson H, Kortequee S (2012). "Chronic cough, reflux, postnasal drip syndrome, and the otolaryngologist". International Journal of Otolaryngology. 2012: 564852. doi:10.1155/2012/564852. PMC 3332192. PMID 22577385. 3. ^ Gibson P, Wang G, McGarvey L, Vertigan AE, Altman KW, Birring SS (January 2016). "Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report". Chest. 149 (1): 27–44. doi:10.1378/chest.15-1496. PMC 5831652. PMID 26426314. 4. ^ Ibrahim WH, Gheriani HA, Almohamed AA, Raza T (March 2007). "Paradoxical vocal cord motion disorder: past, present and future". Postgraduate Medical Journal. 83 (977): 164–72. doi:10.1136/pgmj.2006.052522. PMC 2599980. PMID 17344570. 5. ^ Gimenez LM, Zafra H (April 2011). "Vocal cord dysfunction: an update". Annals of Allergy, Asthma & Immunology. 106 (4): 267–74, quiz 275. doi:10.1016/j.anai.2010.09.004. PMID 21457874. 6. ^ Kenn K, Balkissoon R (January 2011). "Vocal cord dysfunction: what do we know?". The European Respiratory Journal. 37 (1): 194–200. doi:10.1183/09031936.00192809. PMID 21205712. S2CID 12436689. 7. ^ a b c d e f g h i j k l m Flint PW, Haughey BH, Robbins KT, Thomas JR, Niparko JK, Lund VJ, Lesperance MM (2014). Cummings Otolaryngology: Head & Neck Surgery (Sixth ed.). Philadelphia, PA. ISBN 978-0-323-27820-1. OCLC 894112159. 8. ^ a b Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. (April 2015). "Clinical practice guideline (update): adult sinusitis". Otolaryngology–Head and Neck Surgery. 152 (2 Suppl): S1–S39. doi:10.1177/0194599815572097. PMID 25832968. S2CID 30043393. 9. ^ McCallion P, De Soyza A (December 2017). "Cough and bronchiectasis". Pulmonary Pharmacology & Therapeutics. 47: 77–83. doi:10.1016/j.pupt.2017.04.010. PMID 28602999. 10. ^ a b c d Probst R, Grevers G, Iro H (2017). Basic Otorhinolaryngology. Georg Thieme Verlag. doi:10.1055/b-005-148915. ISBN 978-3-13-203472-3. 11. ^ Pratter MR (January 2006). "Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines". Chest. 129 (1 Suppl): 63S–71S. doi:10.1378/chest.129.1_suppl.63s. PMID 16428694. 12. ^ a b Segboer C, Gevorgyan A, Avdeeva K, Chusakul S, Kanjanaumporn J, Aeumjaturapat S, et al. (Cochrane ENT Group) (November 2019). "Intranasal corticosteroids for non-allergic rhinitis". The Cochrane Database of Systematic Reviews. 2019 (11). doi:10.1002/14651858.CD010592.pub2. PMC 6824914. PMID 31677153. 13. ^ Naclerio R (August 2009). "Anticholinergic drugs in nonallergic rhinitis". The World Allergy Organization Journal. 2 (8): 162–5. doi:10.1097/WOX.0b013e3181b35336. PMC 3650956. PMID 24228813. ## External links[edit] Classification D * ICD-10: R09.8 * ICD-9-CM: 784.91 External resources * eMedicine: ent/338 * Medline Plus article on Nasal Discharge * v * t * e Symptoms and signs relating to the respiratory system Auscultation * Stethoscope * Respiratory sounds * Stridor * Wheeze * Crackles * Rhonchi * Stertor * Squawk * Pleural friction rub * Fremitus * Bronchophony * Terminal secretions * Elicited findings * Percussion * Pectoriloquy * Whispered pectoriloquy * Egophony Breathing Rate * Apnea * Prematurity * Dyspnea * Hyperventilation * Hypoventilation * Hyperpnea * Tachypnea * Hypopnea * Bradypnea Pattern * Agonal respiration * Biot's respiration * Cheyne–Stokes respiration * Kussmaul breathing * Ataxic respiration Other * Respiratory distress * Respiratory arrest * Orthopnea/Platypnea * Trepopnea * Aerophagia * Asphyxia * Breath holding * Mouth breathing * Snoring Other * Chest pain * In children * Precordial catch syndrome * Pleurisy * Nail clubbing * Cyanosis * Cough * Sputum * Hemoptysis * Epistaxis * Silhouette sign * Post-nasal drip * Hiccup * COPD * Hoover's sign * asthma * Curschmann's spirals * Charcot–Leyden crystals * chronic bronchitis * Reid index * sarcoidosis * Kveim test * pulmonary embolism * Hampton hump * Westermark sign * pulmonary edema * Kerley lines * Hamman's sign * Golden S sign [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	Post-nasal drip	c0032781	5,975	wikipedia	https://en.wikipedia.org/wiki/Post-nasal_drip	2021-01-18T18:43:10	{"umls": ["C0032781"], "icd-9": ["784.91"], "icd-10": ["R09.82"], "wikidata": ["Q7233562"]}
Diplophonia V̬‼ Diplophonia, also known as diphthongia, is a phenomenon in which a voice is perceived as being produced with two concurrent pitches.[1] Diplophonia is a result of vocal fold vibrations that are quasi-periodic in nature.[2] It has been reported from old days, but there is no uniform interpretation of established mechanisms.[3] It has been established that diplophonia can be caused by various vocal fold pathologies, such as vocal folds polyp, vocal fold nodule, recurrent laryngeal nerve paralysis[3] or vestibular fold hypertrophy.[4] The Voice Quality Symbol for diplophonia is V̬‼. ## References[edit] 1. ^ Ward; Sanders; Goldman; Moore (1969). "Diplophonia". The Annals of Otology, Rhinology, and Laryngology. 78. 2. ^ Kiritani; Hirose; Imagawa (1993). "High-speed digital image analysis of vocal cord vibration in diplophonia". Speech Communication. 13. 3. ^ a b 吉岡博英 (1987). "二重声の成立機序に関する音響的側面について" (in Japanese). 筑波大学. Retrieved 2015-12-26. 4. ^ "仮声帯肥大" (in Japanese). sickness-dictionary.jp. Archived from the original on 2016-03-04. Retrieved 2015-12-26. This medical 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	Diplophonia	c0234760	5,976	wikipedia	https://en.wikipedia.org/wiki/Diplophonia	2021-01-18T19:03:15	{"wikidata": ["Q1227259"]}
Free-living Amoebozoa infection SpecialtyInfectious diseases Free-living amoebae (or "FLA")[1] in the Amoebozoa group are important causes of disease in humans and animals. Naegleria fowleri is sometimes included in the group "free-living amoebae",[2][3] and it causes a condition traditionally called primary amoebic meningoencephalitis. However, Naegleria is now considered part of the Excavata, not the Amoebozoa,[4] and is considered to be much more closely related to Leishmania and Trypanosoma. ## Contents * 1 Presentation * 2 Life cycle * 3 Diagnosis * 4 Treatment * 5 Geographic distribution * 6 See also * 7 References * 8 External links ## Presentation[edit] Acanthamoeba spp. causes mostly subacute or chronic granulomatous amoebic encephalitis (GAE), with a clinical picture of headaches, altered mental status, and focal neurologic deficit, which progresses over several weeks to death. In addition, Acanthamoeba spp. can cause granulomatous skin lesions and, more seriously, keratitis and corneal ulcers following corneal trauma or in association with contact lenses. ## Life cycle[edit] Acanthamoeba spp. and Balamuthia mandrillaris are opportunistic free-living amoebae capable of causing granulomatous amoebic encephalitis (GAE) in individuals with compromised immune systems. * Acanthamoeba spp. have been found in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues. * B. mandrillaris however, has not been isolated from the environment but has been isolated from autopsy specimens of infected humans and animals. Unlike N. fowleri, Acanthamoeba and Balamuthia have only two stages, cysts and trophozoites, in their life cycle. No flagellated stage exists as part of the life cycle. The trophozoites replicate by mitosis (nuclear membrane does not remain intact) . The trophozoites are the infective forms and are believed to gain entry into the body through the lower respiratory tract, ulcerated or broken skin and invade the central nervous system by hematogenous dissemination . Acanthamoeba spp. and Balamuthia mandrillaris cysts and trophozoites are found in tissue. ## Diagnosis[edit] In Acanthamoeba infections, the diagnosis can be made from microscopic examination of stained smears of biopsy specimens (brain tissue, skin, cornea) or of corneal scrapings, which may detect trophozoites and cysts. Cultivation of the causal organism, and its identification by direct immunofluorescent antibody, may also prove useful. Laboratory workers and physicians often mistake the organisms on wet mount for monocytes and a diagnosis of viral meningitis is mistakenly given if the organisms are not motile. Heating a copper penny with an alcohol lamp and placing it on the wet mount slide will activate sluggish trophozoites and more rapidly make the diagnosis. If the person performing the spinal tap rapidly looks at the heated wet mount slide the trophozoites can be seen to swarm while monocytes do not. ## Treatment[edit] Eye and skin infections caused by Acanthamoeba spp. are generally treatable. Topical use of 0.1% propamidine isethionate (Brolene) plus neomycin-polymyxin B-gramicidin ophthalmic solution has been a successful approach; keratoplasty is often necessary in severe infections. Although most cases of brain (CNS) infection with Acanthamoeba have resulted in death, patients have recovered from the infection with proper treatment. ## Geographic distribution[edit] While infrequent, infections appear to occur worldwide. ## See also[edit] * Waterborne diseases ## References[edit] 1. ^ Sarica, F. B.; Tufan, K.; Cekinmez, M.; Erdoğan, B.; Altinörs, M. N. (2009). "A rare but fatal case of granulomatous amebic encephalitis with brain abscess: the first case reported from Turkey". Turkish Neurosurgery. 19 (3): 256–259. PMID 19621290. 2. ^ Da Rocha-Azevedo, B.; Tanowitz, H.; Marciano-Cabral, F. (2009). "Diagnosis of infections caused by pathogenic free-living amoebae". Interdisciplinary Perspectives on Infectious Diseases. 2009: 1–14. doi:10.1155/2009/251406. PMC 2719787. PMID 19657454. 3. ^ Visvesvara, G.; Moura, H.; Schuster, F. (2007). "Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea". FEMS Immunology and Medical Microbiology. 50 (1): 1–26. doi:10.1111/j.1574-695X.2007.00232.x. PMID 17428307. 4. ^ Maruyama, S.; Matsuzaki, M.; Misawa, K.; Nozaki, H. (2009). "Cyanobacterial contribution to the genomes of the plastid-lacking protists". BMC Evolutionary Biology. 9: 197. doi:10.1186/1471-2148-9-197. PMC 3087521. PMID 19664294. ## External links[edit] Classification D * ICD-9-CM: 136.2 * v * t * e Amoebozoal diseases Lobosea (free-living) Centramoebida * Acanthamoeba * Acanthamoeba keratitis * Cutaneous acanthamoebiasis * Granulomatous amoebic encephalitis * Acanthamoeba infection * Balamuthia mandrillaris * Balamuthia amoebic encephalitis * Balamuthia infection Flabellinia * Sappinia diploidea/Sappinia pedata * Sappinia amoebic encephalitis Conosa/Archamoebae * Entamoeba histolytica * Amoebiasis * Amoebic dysentery * Amoebic liver abscess * Cutaneous amoebiasis * Amoebic brain abscess * Amebiasis cutis * Entamoeba gingivalis [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	Free-living Amoebozoa infection	None	5,977	wikipedia	https://en.wikipedia.org/wiki/Free-living_Amoebozoa_infection	2021-01-18T18:34:45	{"icd-9": ["136.2"], "wikidata": ["Q5499617"]}
Not to be confused with Cryptococcosis. Parasitic disease Cryptosporidiosis Micrograph showing cryptosporidiosis. The cryptosporidium are the small, round bodies in apical vacuoles on the surface of the epithelium. H&E stain. Colonic biopsy. SpecialtyInfectious disease SymptomsWatery diarrhea, nausea, abdominal pain, fever CausesCryptosporidium infection Risk factorsImmunocompromisation PreventionAvoid contaminated water TreatmentNitazoxanide Cryptosporidiosis, sometimes informally called crypto,[1] is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS or autoimmune disorders) individuals, resulting in watery diarrhea with or without an unexplained cough.[2] In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water;[2][3] recent evidence suggests that it can also be transmitted via fomites in respiratory secretions.[2] Cryptosporidium is commonly isolated in HIV-positive patients presenting with diarrhea.[4][5] Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The infection begins when a human consumes food or water containing cysts of the Cryptosporidium organism. ## Contents * 1 Signs and symptoms * 1.1 Intestinal cryptosporidiosis * 1.2 Respiratory cryptosporidiosis * 2 Cause * 2.1 Transmission * 2.2 Life cycle * 3 Pathogenesis * 4 Diagnosis * 5 Prevention * 6 Treatment * 6.1 Immunocompetent * 6.2 Immunocompromised * 7 Epidemiology * 8 History * 9 Research * 10 Other animals * 11 Notable cases * 11.1 Before 2000 * 11.2 2001–2009 * 11.3 2010 and later * 12 See also * 13 References * 14 External links ## Signs and symptoms[edit] Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent.[2][6][7][8] It may be fatal in individuals with a severely compromised immune system.[2][6] Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals;[2][6][7] symptoms are usually more severe and persist longer in immunocompromised individuals.[2][6][7] Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection.[6][7][8][9] The likelihood of re-infection is high in immunocompromised adults, and low in those with normal immune systems.[9][10] In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well.[2][7] In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder;[2][7] pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis.[7][11] ### Intestinal cryptosporidiosis[edit] Common signs and symptoms of intestinal cryptosporidiosis include: * Moderate to severe watery diarrhea,[2][6][7] sometimes contains mucus and rarely contains blood or leukocytes[7] * In very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia[7] * Low-grade fever[2][6][7] * Crampy abdominal pain[2][6][7] * Dehydration[2][6] * Weight loss[2][6] * Fatigue[9] * Nausea and vomiting[2][6][7] – suggests upper GI tract involvement[7] and may lead to respiratory cryptosporidiosis[2] * Epigastric or right upper quadrant tenderness[7] Less common or rare signs and symptoms include: * Reactive arthritis (may affect the hands, knees, ankles, and feet)[7] * Jaundice – suggests hepatobiliary involvement[7] * Ascites – suggests pancreatic involvement[7] ### Respiratory cryptosporidiosis[edit] Symptoms of upper respiratory cryptosporidiosis include: * Inflammation of the nasal mucosa, sinuses, larynx, or trachea[2] * Nasal discharge[2] * Voice change[2] (e.g., hoarseness)[7] Symptoms of lower respiratory cryptosporidiosis include: * Cough[2][7] * Shortness of breath[2][7] * Fever[2] * Hypoxemia[2] ## Cause[edit] Life cycle of Cryptosporidium spp. Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis (previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans. Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route. Other vectors of disease transmission also exist.[2][12] The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborder Eimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serving for parasites' spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species. These species possess a number of unusual features: * an endogenous phase of development in microvilli of epithelial surfaces * two morphofunctional types of oocysts * the smallest number of sporozoites per oocyst * a multi-membraneous "feeder" organelle DNA studies suggest a relationship with the gregarines rather than the coccidia.[13] The taxonomic position of this group has not yet been finally agreed upon. The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA.[14] A closely related species, C. hominis, also has its genome sequence available.[15] CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets. ### Transmission[edit] This section needs expansion with: potential for fomite transmission[2]. You can help by adding to it. (January 2016) Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces.[3] The high resistance of Cryptosporidium oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective.[16] Some outbreaks have happened in day care related to diaper changes.[17] The following groups have an elevated risk of being exposed to Cryptosporidium:[3] * Child care workers * Parents of infected children * People who take care of other people with cryptosporidiosis * International travelers * Backpackers, hikers, and campers who drink unfiltered, untreated water * People, including swimmers, who swallow water from contaminated sources * People who handle infected cattle * People exposed to human feces through sexual contact Cases of cryptosporidiosis can occur even in cities that have a properly de-contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have other origins.[3] Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Cryptosporidium is causing serious illness [18] more frequently in immunocompromised than in apparently healthy individuals. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviors can transmit the parasite directly.[3] ### Life cycle[edit] Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage).[1] As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants.[19][20] After being ingested, the sporozoites within oocysts excyst (i.e., are released) in the small intestine. The released sporozoites subsequently attach to the microvilli of the epithelial cells of the small intestine. From there they become trophozoites that reproduce asexually by multiple fission, a process known as schizogony. The trophozoites develop into Type 1 meronts [1] that contain 8 daughter cells.[21] These daughter cells are Type 1 merozoites, which get released by the meronts. Some of these merozoites can cause autoinfection by attaching to epithelial cells. Others of these merozoites become Type II meronts,[22] which contain 4 Type II merozoites.[21] These merozoites get released and they attach to the epithelial cells. From there they become either macrogamonts or microgamonts.[22] These are the female and male sexual forms, respectively.[21] This stage, when sexual forms arise, is called gametogony.[23] Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into oocysts of two types.[22] 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again.[21] The thick-walled oocysts are excreted into the environment.[22] The oocysts are mature and infective upon being excreted.[21] ## Pathogenesis[edit] The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations they appear highly refractile. The oocysts contains up to 4 sporozoites that are bow-shaped.[24] As few as 2 to 10 oocysts can initiate an infection.[25] The parasite is located in the brush border of the epithelial cells of the small intestine.[26] They are mainly located in the jejunum. When the sporozoites attach the epithelial cells’ membrane envelops them. Thus, they are “intracellular but extracytoplasmic”.[21] The parasite can cause damage to the microvilli where it attaches.[24] The infected human excretes the most oocysts during the first week.[21] Oocysts can be excreted for weeks after the diarrhea subsides from infections by C. parvum or C. hominis;[1] however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months.[27] The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts.[21] This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite.[25] Previous infection in immunocompetent individuals produces little resistance to future infection, however it may decrease the severity of disease and the number of oocysts excreted.[28][29] ## Diagnosis[edit] There are many diagnostic tests for Cryptosporidium. They include microscopy, staining, and detection of antibodies. Microscopy[1] can help identify oocysts in fecal matter.[26] To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples.[23] There are several techniques to concentrate either the stool sample or the oocysts. The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool.[24] Both the modified zinc sulfate centrifugal flotation technique and the Sheather's sugar flotation procedure can concentrate the oocysts by causing them to float.[23] Another form of microscopy is fluorescent microscopy done by staining with auramine.[26] Other staining techniques include acid-fast staining,[25] which will stain the oocysts red.[24] One type of acid-fast stain is the Kinyoun stain.[20] Giemsa staining can also be performed.[21] Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.[24] Detecting antigens is yet another way to diagnose the disease. This can be done with direct fluorescent antibody (DFA) techniques.[1] It can also be achieved through indirect immunofluorescence assay.[23] Enzyme-linked immunosorbent assay (ELISA) also detects antigens.[26] Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species of Cryptosporidium.[1] If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography. If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography.[25] ## Prevention[edit] Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes, including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, including slow sand filters, diatomaceous earth filters and membranes will remove 99% of Cryptosporidium.[30] Membranes and bag and cartridge filters remove Cryptosporidium product-specifically. While Cryptosporidium is highly resistant to chlorine disinfection,[31] with high enough concentrations and contact time, Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UV's efficacy in inactivating Cryptosporidium.[32][33] One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory. Real-time monitoring technology is now able to detect Cryptosporidium with online systems, unlike the spot and batch testing methods used in the past. The most reliable way to decontaminate drinking water that may be contaminated by Cryptosporidium is to boil it.[34][35] In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments. These departments then report to the Center for Disease Control and Prevention.[1] The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation.[23] An example would be hand-washing.[1] Prevention is through washing hands carefully after going to the bathroom or contacting stool, and before eating. People should avoid contact with animal feces.[26] They should also avoid possibly contaminated food and water.[1] In addition, people should refrain from engaging in sexual activities that can expose them to feces.[23] Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it. Heating milk at 71.7 °C (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts' ability to infect.[36] Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for “cyst removal” by NSF International National Sanitation Foundation.[1] Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.[36] People with cryptosporidiosis should not swim in communal areas because the pathogen can reside in the anal and genital areas and be washed off. They should wait until at least two weeks after diarrhea stops before entering public water sources, since oocysts can still be shed for a while. Also, they should stay away from immunosuppressed people.[1] Immunocompromised people should take care to protect themselves from water in lakes and streams.[25] They should also stay away from animal stools and wash their hands after touching animals. To be safe, they should boil or filter their water. They should also wash and cook their vegetables.[1] The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3% hydrogen peroxide[clarification needed] (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions.[37] ## Treatment[edit] Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g., loperamide).[38][39] Supplemental zinc may improve symptoms,[38] particularly in recurrent or persistent infections or in others at risk for zinc deficiency. ### Immunocompetent[edit] Immunocompetent individuals with cryptosporidiosis typically suffer a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may require symptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms);[9] however reinfection frequently occurs.[9] As of 2015[update], nitazoxanide is the only antiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals;[9][38][39][40] however, it lacks efficacy in severely immunocompromised patients.[40] Certain agents such as paromomycin and azithromycin are sometimes used as well, but they only have partial efficacy.[38] ### Immunocompromised[edit] In immunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.[41] The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication.[38][39] Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together;[9][38] these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons.[38] A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.[39] Currently, research is being done in molecular-based immunotherapy. For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies. Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro.[42] ## Epidemiology[edit] Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites.[20] In developing countries, 8–19% of diarrheal diseases can be attributed to Cryptosporidium.[43] Ten percent of the population in developing countries excretes oocysts. In developed countries, the number is lower at 1–3%. The age group most affected are children from 1 to 9 years old.[25][44] In Eastern Europe cryptosporidiosis in humans and animals is common, but there are considerable gaps in surveillance and a lack of comparable methods which is limit the understanding of the disease and detection of outbreaks. Research show a rich diversity of zoonotic subtypes of the parasite in animals indicating a rich potential of animal to human transmission. [45][46] Roughly 30% of adults in the United States are seropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives.[9] ## History[edit] The organism was first described in 1907 by Tyzzer, who recognised it was a coccidian.[47] ## Research[edit] A recombinant Cryptosporidium parvum oocyst surface protein (rCP15/60) vaccine has produced an antibody response in a large group of cows and also antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. This is very promising. Human Cryptosporidium parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDS patients. There is no commercially available effective vaccine against Cryptosporidium parvum, although passive immunization utilizing different zoite surface (glyco)proteins has shown promise. Developmental stages of the life cycle of the parasite might act as possible targets for vaccine development. The organism is detected in 65–97% of the surface-water supply in the United States and is resistant to most disinfectants used for the treatment of drinking water. Antibodies in the serum of humans and animals infected with Cryptosporidium parvum react with several antigens, one of which is a 15 kDa protein (CP15) located on the surface of the organism. This protein is a good candidate for use as a molecular vaccine because previous studies have shown that a monoclonal antibody to CP15 confers passive immunity to mice. Currently, there is no vaccine or completely effective drug therapy against Cryptosporidium parvum in HIV/AIDS individuals.[38][39] A summary of discoveries presented at the most recent (June 2019) international symposium on Cryptosporidium has been published in 2020.[48] ## Other animals[edit] The most important zoonotic reservoirs are cattle,[49] sheep and goats. In addition, in recent years, cryptosporidiosis has plagued many commercial leopard gecko breeders. Several species of the Cryptosporidium family (C. serpentes and others) are involved, and outside of geckos it has been found in monitor lizards, iguanas and tortoises, as well as several snake species. ## Notable cases[edit] ### Before 2000[edit] * In 1987, 13,000 people in Carrollton, Georgia, United States, became ill with cryptosporidiosis. This was the first report of its spread through a municipal water system that met all state and federal drinking water standards. * In 1993, a waterborne cryptosporidiosis outbreak occurred in Milwaukee, Wisconsin, US. An estimated 403,000 people became ill, including 4,400 people hospitalized. The source of the Cryptosporidium is believed to be overflow from the Milwaukee area combined sanitary and storm sewer system into Lake Michigan, which was then taken into the Howard Avenue Water Purification Plant and distributed to an estimated 880,000 residents (of the 1.61 million residents in the Milwaukee area who receive their drinking water from Lake Michigan).[50] These residents, who receive their drinking water from Lake Michigan, were told to boil their water before drinking it. More people were affected in this one outbreak than the combined number of people affected in every cryptosporidiosis outbreak in the 24 years since then. An estimated 69 people died during the outbreak, according to the CDC.[51] * The UK's biggest outbreak occurred in Torbay in Devon in 1995. * In the summer of 1996, Cryptosporidium affected approximately 2,000 people in Cranbrook, British Columbia, Canada. Weeks later, a separate incident occurred in Kelowna, British Columbia, where 10,000 to 15,000 people got sick.[52] ### 2001–2009[edit] * In April 2001, an outbreak occurred in the city of North Battleford, Saskatchewan, Canada. Between 5800 and 7100 people suffered from diarrheal illness, and 1907 cases of cryptosporidiosis were confirmed. Equipment failures at the city's antiquated water filtration plant following maintenance were found to have caused the outbreak.[53] * In the summer of 2005, after numerous reports by patrons of gastrointestinal upset, a water park at Seneca Lake State Park, in the Finger Lakes region of upstate New York was found to have two water storage tanks infected with Cryptosporidium. By early September 2005, over 3,800 people reported symptoms of a Cryptosporidium infection.[54] The "Sprayground" was ordered closed for the season on 15 August. * In October 2005, the Gwynedd and Anglesey areas of North Wales, the United Kingdom, suffered an outbreak of cryptosporidiosis. The outbreak may have been linked to the drinking water supply from Llyn Cwellyn, but this is not yet confirmed. As a result, 231 people fell ill and the company Welsh Water (Dwr Cymru) advised 61,000 people to boil their water before use. * In March 2007, a suspected outbreak occurred in Galway, Ireland, after the source of water for much of the county, Lough Corrib, was suspected to be contaminated with the parasite. A large population (90,000 people), including areas of both Galway City and County, were advised to boil water for drinking, food preparation and for brushing teeth. On 21 March 2007, it was confirmed that the city and county's water supply was contaminated with the parasite. The area's water supply was finally given approval on 20 August 2007, five months after Cryptosporidium was first detected. Around 240 people are known to have contracted the disease; experts say the true figure could be up to 5,000.[55] * Hundreds of public pools in 20 Utah counties were closed to young children in 2007, as children under 5 are most likely to spread the disease, especially children wearing diapers. As of 10 September 2007 the Utah Department of Health had reported 1302 cases of cryptosporidiosis in the year; a more usual number would be 30. On 25 September the pools were reopened to those not requiring diapers, but hyperchlorination requirements were not lifted. * On 21 September 2007, a Cryptosporidium outbreak attacked the Western United States: 230 Idaho residents, with hundreds across the Rocky Mountain area; in the Boise and Meridian areas; Utah, 1,600 illnesses; Colorado and other Western states — Montana, decrease.[56] * On 25 June 2008, Cryptosporidium was found in England in water supplies in Northampton, Daventry, and some surrounding areas supplied from the Pitsford Reservoir, as reported on the BBC. People in the affected areas were warned not to drink tap water unless it had been boiled. Anglian Water confirmed that 108,000 households were affected, about 250,000 people. They advised that water might not be fit for human consumption for many weeks.[57] The boil notice was lifted for all the affected customers on 4 July 2008.[58] * Throughout the summer of 2008; many public swimming areas, water parks, and public pools in the Dallas/Fort Worth Metroplex of Texas suffered an outbreak of cryptosporidiosis. Burger's Lake in Fort Worth was the first to report such an outbreak. This prompted some, if not all, city-owned and private pools to close and hyperchlorinate. To the 13 August 2008 there were 400 reported cases of Cryptosporidium.[59] * In September 2008, a gym in Cambridge, the United Kingdom, was forced to close its swimming pool until further notice after health inspectors found an outbreak of cryptosporidiosis. Environmental Health authorities requested that the water be tested after it was confirmed that a young man had been infected.[60] ### 2010 and later[edit] * In May 2010, the Behana creek water supply south of Cairns, Australia, was found to be contaminated by cryptosporidium.[61] * In July 2010, a local sports center in Cumbernauld (Glasgow, UK) detected traces of cryptosporidium in its swimming pools, causing a temporary closure of the swimming pools. * In November 2010, over 4000 cases of cryptosporidiosis were reported in Östersund, Sweden. The source of contamination was the tap water.[62] In mid December 2010 the number of reported cases was 12,400 according to local media.[63] * As of April 2011, there has been an ongoing outbreak in Skellefteå, Sweden. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Several tests have been taken around the water treatment unit "Abborren", but so far no results have turned up positive. Residents are being advised to boil the tap water as they continue to search for the contaminating source. * Since May 2011, there has been an ongoing outbreak in South Roscommon in Ireland. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Testing continues and Roscommon County Council are now considering introducing Ultra Violet Filtration to their water treatment process in the next 12 months. Residents are being advised to boil the tap water and there is no sign of this boil notice being lifted in the near future. * In May 2013, in Roscommon, Ireland, another outbreak of the cryptosporidiosis was reported and a boil water notice was issued. This was the second time the parasite was detected in a month in the Roscommon water supply. The source of one of the outbreaks had been linked to the agricultural community.[64] At least 13 people were treated for Cryptosporidiosis.[65] ## See also[edit] * Cryptosporidium was the basis of the 1998 television film, Thirst,[66] in which it mutates and passes through a town's water filters. * Cryptosporidium was shown on three episodes in three seasons of the television show, Monsters Inside Me ## References[edit] 1. ^ a b c d e f g h i j k l "Cryptosporidiosis". Centers for Disease Control and Prevention. 5 February 2009. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Sponseller JK, Griffiths JK, Tzipori S (2014). "The evolution of respiratory Cryptosporidiosis: evidence for transmission by inhalation". Clin. Microbiol. Rev. 27 (3): 575–86. doi:10.1128/CMR.00115-13. PMC 4135895. PMID 24982322. "Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. ... Upper respiratory cryptosporidiosis may cause inflammation of the nasal mucosa, sinuses, larynx, and trachea, accompanied by nasal discharge and voice change (54, 61, 62). Cryptosporidiosis of the lower respiratory tract typically results in productive cough, dyspnea, fever, and hypoxemia (63,–66). ... While fecal-oral transmission is indisputably the major route of infection, transmission via coughing and fomites is also possible in situations of close contact (20). ... Because they lacked gastrointestinal symptoms and oocyst excretion, the latter cases establish the possibility of primary respiratory infection with Cryptosporidium, which may have been acquired by inhalation of expectorated droplets or by contact with fomites. ... 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Use of partially active antiparasitic drugs (eg, nitazoxanide or paromomycin combined with azithromycin) should be considered along with initiating antiretroviral therapy. ... Symptomatic therapy includes replacement of fluids, provision of appropriate nutrition, and treatment with antimotility agents. ... Replacement of fluids and electrolytes is the critically important first step in the management of cryptosporidiosis, particularly in patients with large diarrheal losses. Fluids should include sodium, potassium, bicarbonate, and glucose." 39. ^ a b c d e Abubakar I, Aliyu SH, Arumugam C, Hunter PR, Usman NK (January 2007). "Prevention and treatment of cryptosporidiosis in immunocompromised patients" (PDF). Cochrane Database Syst Rev (1): CD004932. doi:10.1002/14651858.CD004932.pub2. PMID 17253532. "The results indicate that nitaxozanide reduces the load of parasites and may be useful in immunocompetent individuals. Due to the seriousness of the potential outcomes of cryptosporidiosis, the use of nitaxozanide should be considered in immunocompromised patients. The absence of effective therapy highlights the need to ensure that infection is avoided. ... For HIV-infected persons, highly active antiretroviral therapy (HAART) is the mainstay of preventing and managing cryptosporidiosis. HAART can lead to complete resolution of clinical symptoms and oocysts (Grube 1997; Maggi 2000; Miao 2000). This intervention is not available for HIV patients who are failing HAART or those unable to access HAART in developing countries. Among these immunocompromised persons without the option of an effective treatment for the underlying disease, supportive management, including rehydration therapy, electrolyte replacement, and anti-motility agents will remain the only alternatives for care until better drugs emerge." 40. ^ a b Sparks H, Nair G, Castellanos-Gonzalez A, White AC (2015). "Treatment of Cryptosporidium: What We Know, Gaps, and the Way Forward". Curr Trop Med Rep. 2 (3): 181–187. doi:10.1007/s40475-015-0056-9. PMC 4640180. PMID 26568906. 41. ^ Gilson M.D., Ian; Buggy, Brian P. M.D. (October 1996). "Cryptosporidiosis in Patients with HIV Disease: Is It Safe to Drink the Water?". HIV Newsline. 42. ^ Gargala G (September 2008). "Drug treatment and novel drug target against Cryptosporidium". Parasite. 15 (3): 275–81. doi:10.1051/parasite/2008153275. PMID 18814694. 43. ^ Gatei W, Wamae CN, Mbae C, et al. (July 2006). "Cryptosporidiosis: prevalence, genotype analysis, and symptoms associated with infections in children in Kenya". Am. J. Trop. Med. Hyg. 75 (1): 78–82. doi:10.4269/ajtmh.2006.75.78. PMID 16837712. 44. ^ Lozano, R (15 December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604. S2CID 1541253. 45. ^ Plutzer, J.; Lassen, B.; Jokelainen, P.; Djurković-Djaković, O.; Kucsera, I.; Dorbek-Kolin, E.; Šoba, B.; Sréter, T.; Imre, K.; Omeragić, J.; Nikolić, A.; Bobić, B.; Živičnjak, T.; Lučinger, S.; Lazarić Stefanović, L.; Kučinar, J.; Sroka, J.; Deksne, G.; Keidāne, D.; Kváč, M.; Hůzová, Z.; Panagiotis, K. (2018). "Review of Cryptosporidium and Giardia in the eastern part of Europe, 2016". Euro Surveill. 23 (4). doi:10.2807/1560-7917.ES.2018.23.4.16-00825. PMC 5801338. PMID 29382412. 46. ^ Santoro, A.; Dorbek-Kolin, E.; Jeremejeva, J.; Tummeleht, L.; Orro, T.; Jokelainen, P.; Lassen, B. (2019). "Molecular epidemiology of Cryptosporidium spp. in calves in Estonia: high prevalence of Cryptosporidium parvum shedding and 10 subtypes identified". Parasitology. 146 (2): 261–267. doi:10.1017/S0031182018001348. PMID 30086806. 47. ^ Xiao, L.; Fayer, R.; Ryan, U.; Upton, S. J. (2004). "Cryptosporidium Taxonomy: Recent Advances and Implications for Public Health". Clinical Microbiology Reviews. 17 (1): 72–97. doi:10.1128/CMR.17.1.72-97.2004. ISSN 0893-8512. PMC 321466. PMID 14726456. 48. ^ Widmer, Giovanni; Carmena, David; Kváč, Martin; Chalmers, Rachel M.; Kissinger, Jessica C.; Xiao, Lihua; Sateriale, Adam; Striepen, Boris; Laurent, Fabrice; Lacroix-Lamandé, Sonia; Gargala, Gilles; Favennec, Loïc (2020). "Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference". Parasite. 27: 14. doi:10.1051/parasite/2020011. ISSN 1776-1042. PMC 7069357. PMID 32167464. 49. ^ Lassen B, Ståhl M, Enemark HL (2014). "Cryptosporidiosis - an occupational risk and a disregarded disease in Estonia". Acta Vet. Scand. 56: 36. doi:10.1186/1751-0147-56-36. PMC 4089559. PMID 24902957. 50. ^ Botkin & Keller (2005). Environmental Science, Earth as a Living Planet (5th ed.). p. 441. 51. ^ Corso P, Kramer M, Blair K, Addiss D, Davis J, Haddix A (2003). "Costs of Illness in the 1993 Waterborne Cryptosporidium Outbreak, Milwaukee, Wisconsin". Emerg Infect Dis. 9 (4): 426–31. doi:10.3201/eid0904.020417. PMC 2957981. PMID 12702221. 52. ^ "Cryptosporidium". CBC News. 23 June 2004. Archived from the original on 1 March 2011. Retrieved 19 April 2011. 53. ^ "Waterborne Cryptosporidiosis Outbreak, North Battleford, Ssaskatchewan, Spring 2001". Public Health Agency of Canada. 15 November 2001. Retrieved 25 January 2008. 54. ^ "State Health Department Issues Update on Seneca Lake State Park Gastrointestinal Outbreak". New York State Health Dept. Archived from the original on 11 March 2007. Retrieved 29 September 2006. 55. ^ RTÉ News — Galway water now safer than ever — HSE 56. ^ Yahoo.com, Cryptosporidium outbreak hits the West 57. ^ Northampton Chronicle and Echo[permanent dead link] 58. ^ "Anglian Water-lifting of boil notice". Archived from the original on 1 August 2008. Retrieved 5 July 2008. 59. ^ Crypto spreads to private pools Archived 14 August 2008 at the Wayback Machine — WFAA-TV. Retrieved 13 August 2008. 60. ^ Gym closes pool in danger bug alert 61. ^ Mawer, Jessica (20 May 2010). "Woree, Gordonvale residents advised to boil drinking water". ABC Online. Retrieved 19 April 2011. 62. ^ "Smittskyddsinstitutets arbete med det vattenburna utbrottet av Cryptosporidium i Östersund" (in Swedish). Smittskyddsinstitutet. Archived from the original on 15 May 2011. Retrieved 19 April 2011. 63. ^ Sjöö, Patrick (13 December 2010). "Kommunens parasitenkät avslutas". Östersunds-Posten (in Swedish). Retrieved 19 April 2011. 64. ^ "Boil water notice after Cryptosporidiosis outbreak in Co Roscommon". RTÉ News. 15 May 2013. 65. ^ "13 people treated following Roscommon water pollution". RTÉ News. 17 May 2013. 66. ^ "Thirst (1998) IMDB". Archived from the original on 8 April 2012. Retrieved 29 June 2018. * White, A. Clinton Jr. (2005). "Cryptosporidiosis". In Mandell, G; et al. (eds.). Principles and Practice of Infectious Diseases (6th ed.). Elsevier. pp. 3215–28. * Upton, Steve J. (12 September 2003). "Basic Biology of Cryptosporidium" (Website). Kansas State University: Parasitology Laboratory. * S.J. Brands (Compiler) (2000). "The Taxonomicon & Systema Naturae" (Website database). Taxon: Genus Cryptosporidium. Universal Taxonomic Services, Amsterdam, The Netherlands. * Heymann, David (2015). Control of communicable diseases manual : an official report of the American Public Health Association. APHA Press, the American Public Health Association. ISBN 9780875530185. ## External links[edit] Classification D * ICD-10: A07.2 * ICD-9-CM: 007.4 * MeSH: D003457 * DiseasesDB: 3221 External resources * MedlinePlus: 000617 * eMedicine: med/484 * Patient UK: Cryptosporidiosis * Scholia: Q1359898 * Cryptosporidiosis — Centers for Disease Control and Prevention * Aquatics International Article Regarding Infection via Spray Parks * CryptoDB: The Cryptosporidium Genome Resource * v * t * e Eukaryota: SAR: Alveolata Domain Archaea Bacteria Eukaryota (Supergroup Plant Hacrobia Heterokont Alveolata Rhizaria Excavata Amoebozoa Opisthokonta Animal Fungi) Acavomonidia Acavomonadea Acavomonadida (Acavomonas) Ciliophora Intramacronucleata * Armophorea (Metopus) * Cariacotrichea (Cariacothrix caudata) * Colpodea (Colpoda) * Litostomatea (Balantidium, Dileptus) * Muranotrichea (Muranothrix) * Nassophorea (Nassula) * Oligohymenophorea (Ichthyophthirius, Paramecium, Tetrahymena, Vorticella) * Parablepharismea (Parablepharisma) * Phyllopharyngea (Chilodonella, Tokophrya) * Plagiopylea (Plagiopyla) * Prostomatea (Coleps, Holophrya) * Protocruziea (Protocruzia) * Spirotrichea (Euplotes, Stylonychia) Postciliodesmatophora * Heterotrichea (Stentor, Climacostomum, Blepharisma) * Karyorelictea (Loxodes, Tracheloraphis) Mesodiniea (Mesodinium, Myrionecta) Colponemidia Colponemadea Colponemadida (Colponema) Myzozoa Apicomplexa Aconoidasida Haemospororida * Garniidae (Garnia) * Haemoproteidae (Haemoproteus) * Leucocytozoidae (Leucocytozoon) * Plasmodiidae (Plasmodium) Piroplasmida * Babesiidae (Babesia) * Theileriidae (Theileria) * Cardiosporidium * Nephromyces Conoidasida Coccidia Agamococcidiorida * Gemmocystidae (Gemmocystis) * Rhytidocystidae (Rhytidocystis) Eucoccidiorida Adeleorina * Adeleidae * Dactylosomatidae (Babesiosoma, Dactylosoma) * Haemogregarinidae (Haemogregarina) * Hepatozoidae (Hepatozoon) * Karyolysidae (Karyolysus) * Klossiellidae (Klossiella) * Legerellidae (Legerella) Eimeriorina * Aggregatidae (Aggregata, Grasseella, Merocystis, Ovivora, Pseudoklossia, Selysina) * Atoxoplasmatidae * Barrouxiidae * Calyptosporiidae * Caryotrophidae * Cryptosporidiidae (Cryptosporidium) * Eimeriidae (Cyclospora, Eimeria, Isospora) * Elleipsisomatidae * Lankesterellidae * Selenococcidiidae Sarcocystidae * Sarcocystinae (Frenkelia, Sarcocystis) * Toxoplasmatinae (Besnoitia, Hammondia, Hyaloklossia, Nephroisospora, Neospora, Toxoplasma) Ixorheorida * Ixorheidae (Ixorheis) Protococcidiorida * Angeiocystidae (Angeiocystis) * Eleutheroschizonidae (Coelotropha, Defretinella, Eleutheroschizon) * Grelliidae (Coelotropha, Grellia) * Mackinnoniidae (Mackinnonia) * Myriosporidae (Myriosporides, Myriospora) Gregarinia Archigregarinorida * Exoschizonidae (Exoschizon) * Selenidioididae (Merogregarina, Meroselenidium, Selenidioides, Veloxidium) Eugregarinorida Aseptatorina * Aikinetocystidae * Allantocystidae * Diplocystidae * Enterocystidae * Ganymedidae * Lecudinidae * Monocystidae (Monocystinae, Oligochaetocystinae, Rhynchocystinae, Stomatophorinae, Zygocystinae) * Schaudinnellidae * Selenidiidae * Thiriotiidae * Urosporidae Blastogregarinorina * Siedleckiidae (Siedleckia) Septatorina * Fusionicae (Fusionidae) * Gregarinicae (Cephaloidophoridae, Cephalolobidae, Didymophoridae, Gregarinidae, Hirmocystidae, Metameridae, Uradiophoridae) * Porosporicae (Porosporidae) * Stenophoricae (Acutidae, Amphiplatysporidae, Brustiophoridae, Cnemidosporidae, Dactylophoridae, Leidyanidae, Monoductidae, Monoicidae, Sphaerocystidae, Stenophoridae, Trichorhynchidae) * Stylocephaloidea (Actinocephalidae, Stylocephalidae) * Blabericolidae Neogregarinorida * Schizogregarinina (Caulleryellidae, Ophryocystidae) * Gigaductidae (Gigaductus) * Lipotrophidae (Apicystis, Farinocystis, Lipotropha, Lipocystis, Mattesia, Menzbieria) * Schizocystidae (Lymphotropha, Machadoella, Schizocystis) * Syncystidae (Syncystis) Apicomonadea Chromerida * Chromeraceae (Chromera velia) * Vitrellaceae (Vitrella brassicaformis) Colpodellida * Colpodellidae (Colpodella) Voromonadida * Alphamonadidae (Alphamonas) * Voromonadidae (Voromonas) Dinoflagellata Dinokaryota * With a theca: Dinophysiales (Dinophysis, Histioneis, Ornithocercus, Oxyphysis) * Gonyaulacales (Ceratium, Gonyaulax) * Peridiniales (Pfiesteria, Peridinium) * Prorocentrales (Prorocentrum) * Without theca: Gymnodiniales (Amphidinium, Gymnodinium, Karenia, Karlodinium) * Suessiales (Polarella, Symbiodinium) Noctilucea * Noctilucales (Noctiluca) Syndinea * Syndiniales: Amoebophryaceae (Amoebophyra) * Duboscquellaceae (Duboscquella) * Syndiniaceae (Hematodinium, Syndinium) Other * Acrocoelidae (Acrocoelus) * Ichthyodinium * Oxyrrhinaceae (Oxyrrhis) * Pronoctilucidae (Pronoctiluca) * Psammosidae (Psammosa) Perkinsozoa Perkinsea * Perkinsidae (Perkinsus) * Phagodinida (Phagodinium) * Rastromonadida (Parvilucifera, Rastrimonas) Protoalveolata Ellobiopsea * Ellobiopsidae (Elliobiocystis, Ellobiopsis, Parallobiopsis, Thalassomyces, Rhizellobiopsis) Myzomonadea Algovorida * Algovoridae (Algovora) Chilovorida * Chilovoridae (Chilovora) Squirmidea * Squirmidae (Filipodium, Platyproteum) * v * t * e Protozoan infection: SAR and Archaeplastida SAR Alveolate Apicomplexa Conoidasida/ Coccidia * Coccidia: Cryptosporidium hominis/Cryptosporidium parvum * Cryptosporidiosis * Cystoisospora belli * Isosporiasis * Cyclospora cayetanensis * Cyclosporiasis * Toxoplasma gondii * Toxoplasmosis Aconoidasida * Plasmodium falciparum/vivax/ovale/malariae/knowlesi * Malaria * Blackwater fever * Babesia * Babesiosis Ciliophora * Balantidium coli * Balantidiasis Heterokont * Blastocystis * Blastocystosis * Pythium insidiosum * Pythiosis Archaeplastida * Algaemia: Prototheca wickerhamii * Protothecosis [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	Cryptosporidiosis	c0010418	5,978	wikipedia	https://en.wikipedia.org/wiki/Cryptosporidiosis	2021-01-18T19:09:36	{"gard": ["6219"], "mesh": ["D003457"], "umls": ["C0010418"], "icd-10": ["A07.207.2"], "orphanet": ["1549"], "wikidata": ["Q1359898"]}
Chromosome 20p duplication is a rare chromosome abnormality that occurs when there is an extra copy (duplication) of genetic material on the short arm (p) of chromosome 20. The severity of the condition and the signs and symptoms depend on the size and location of the duplication and which genes are involved. In general, smaller duplications are less severe than larger duplications. Very few cases of chromosome 20p duplication have been reported. The majority of those have been partial duplications (involving only part of the p arm) and have occurred as part of a translocation (along with a deletion on another chromosome). Therefore, it is hard to know which symptoms in people with a 20p duplication have been due to the duplication specifically. Signs and symptoms that have been reported in people with chromosome 20p duplication include intellectual disability, developmental delay, speech delay, poor coordination, dental problems, spinal bone abnormalities, distinctive facial features, and heart problems. Most cases of chromosome 20p duplication have resulted from a healthy parent having a chromosomal balanced translocation or inversion (when a piece of a chromosome is facing the wrong direction). When a parent has one of these, there is an increased risk to have another child with a chromosome abnormality. Some chromosome 20p duplications have resulted from a random genetic error (not inherited), in which both parents have normal chromosomes. In these cases, it is unlikely the parents would have another child with a chromosome abnormality. Treatment for chromosome 20p duplications depends on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Chromosome 20p duplication	c2930888	5,979	gard	https://rarediseases.info.nih.gov/diseases/5333/chromosome-20p-duplication	2021-01-18T18:01:23	{"mesh": ["C535371"], "umls": ["C2930888"], "synonyms": ["Duplication 20p", "Trisomy 20p", "20p duplication", "20p trisomy", "Partial trisomy 20p"]}
Fechtner syndrome Other namesAlport syndrome with leukocyte inclusions and macrothrombocytopenia Fechtner syndrome is inherited in an autosomal dominant manner. Fechtner syndrome is a variant of Alport syndrome characterized by leukocyte inclusions, macrothrombocytopenia,[1] thrombocytopenia, nephritis, and sensorineural hearing loss. [2] Some patients may also develop cataracts. [3] ## References[edit] 1. ^ cause by mutation in the MYH9 gene on chromosome 22q11 AbstractThis study reports a family comprising four generations in whom nephritis, deafness, congenital cataracts, macrothrombocytopenia, and leukocyte inclusions were observed in varying combinations in eight of 17 members. The family differs from others reported in that their hematologic abnormalities include not only macrothrombocytopenia, but also small, pale blue cytoplasmic inclusions in the neutrophils and eosinophils. Light microscopic appearance of the inclusions resembled that of toxic Döhle bodies and inclusions of May-Hegglin anomaly, but their ultrastructural appearance was unique. The inclusions consisted of clusters of ribosomes and small segments of rough endoplasmic reticulum (RER). They lacked the parallel 10-nm filaments characteristic of May-Hegglin anomaly and the parallel strands of RER seen in toxic Döhle bodies. Platelets were large, but their light and ultrastructural appearance was not significantly different from normal platelets. Platelet aggregation in response to epinephrine, arachidonate, thrombin, adenosine diphosphate, collagen, and ristocetin was normal. Levels of nucleotides and serotonin were elevated in proportion to cell volume. The concentration of adenosine triphosphate secreted and the percentage of arachidonic acid converted to thromboxane B2 were proportional to cell number. Deafness was high-tone sensorineural. Renal disease ranged from Peterson LC, Rao KV, Crosson JT, White JG (February 1985). "Fechtner syndrome--a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia". Blood. 65 (2): 397–406. doi:10.1182/blood.V65.2.397.397. PMID 2981587. Retrieved 2013-05-19. 2. ^ Toriello, Helga V.; Smith, Shelley D. (2013). Hereditary Hearing Loss and Its Syndromes. Oxford University Press USA. p. 127. ISBN 9780199731961. 3. ^ Avner, Ellis D.; Harmon, William E.; Niaudet, Patrick; Yoshikawa, Norishige; Emma, Francesco; Goldstein, Stuart L. (2016). Pediatric Nephrology. Springer-Verlag Berlin Heidelberg. p. 632. ISBN 978-3-662-43595-3. ## External links[edit] Classification D * ICD-10: D69.4 * OMIM: 153640 External resources * Orphanet: 1984 [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	Fechtner syndrome	c0403445	5,980	wikipedia	https://en.wikipedia.org/wiki/Fechtner_syndrome	2021-01-18T18:34:49	{"orphanet": ["1984"], "wikidata": ["Q1399440"]}
A rare hereditary optic atrophy characterized by an early onset of bilateral optic nerve degeneration without other systemic features. Clinical manifestations include pallor of the optic disks, severe but slowly progressing visual impairment, and in some patients also paracentral scotoma, photophobia and dyschromatopsia. [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	Autosomal recessive isolated optic atrophy	c1850281	5,981	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98676	2021-01-23T17:00:20	{"mesh": ["C537127"], "omim": ["258500", "616289", "616732", "617302"], "icd-10": ["H47.2"], "synonyms": ["Autosomal recessive non-syndromic optic atrophy"]}
Transvestic fetishism SpecialtyPsychiatry SymptomsExcessive sexual or erotic interest in cross-dressing Cross-dressing History of cross-dressing * In wartime * History of drag * Rebecca Riots * Casa Susanna * Pantomime dame * Principal boy * Travesti Key elements * Passing * Transvestism Modern drag culture * Ball culture * Drag king * Drag pageantry * Drag queen * Faux queen Sexual aspects * Autoandrophilia * Autogynephilia * Feminization * Petticoating * Transvestic fetishism Other aspects * Albanian sworn virgins * Bacha bazi * Bacha posh * Crossplay * En femme * En homme Passing as male * Breast binding * Female urination device * Packing Passing as female * Breast forms * Cleavage enhancement * Hip and buttock padding * Tucking * Gaff Organizations * Tri-Ess * ABGLT Books * My Husband Betty * She's Not The Man I Married * The Boy in the Dress * v * t * e Transvestic fetishism is a psychiatric diagnosis applied to those who are thought to have an excessive sexual or erotic interest in cross-dressing; this interest is often expressed in autoerotic behavior. It differs from cross-dressing for entertainment or other purposes that do not involve sexual arousal. Under the name transvestic disorder, it is categorized as a paraphilia in the DSM-5.[1] Sexual arousal in response to donning sex-typical clothing is homeovestism. ## Contents * 1 Description * 2 Types * 3 See also * 4 References ## Description[edit] The DSM-5 states that adolescent and adult males with late-onset gender dysphoria "frequently engage in transvestic behavior with sexual excitement."[2] "Habitual fetishistic transvestism developing into autogynephilia" is given as a risk factor for gender dysphoria to develop. According to DSM-IV, this fetishism was limited to heterosexual men; however, the DSM-5 does not have this restriction, and opens it to women and men with this interest, regardless of their sexual orientation.[3] It is, however, usually documented in males.[4] There are two key criteria before a psychiatric diagnosis of "transvestic fetishism" is made:[5] 1. Individuals must be sexually aroused by the act of cross-dressing. 2. Individuals must experience significant distress or impairment – socially or occupationally – because of their behavior. ## Types[edit] See also: Clothing fetish Some male transvestic fetishists collect women's clothing, e.g. panties, nightgowns, babydolls, bridal gowns, slips, brassieres, and other types of nightwear, lingerie, stockings, pantyhose, shoes, and boots, items of a distinct feminine look and feel. They may dress in these feminine garments and take photographs of themselves while living out their fantasies. * Some men find the sheer fabric of stockings highly erotic * Transvestic fetishism involving a half slip and stockings ## See also[edit] * Dual-role transvestism * Feminization * Hair fetishism * List of transgender-related topics * List of paraphilias * Pinafore eroticism * Transgender * Transvestism ## References[edit] Citations 1. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 685–705. ISBN 978-0-89042-555-8. 2. ^ Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. 2013. pp. 451–460. ISBN 978-0-89042-554-1. 3. ^ http://www.dsm5.org/Documents/Paraphilic%20Disorders%20Fact%20Sheet.pdf DSM-5 Documents: Paraphilic Disorders Fact Sheet 4. ^ Cowen P, Harrison P, Burns T (2012). Shorter Oxford Textbook of Psychiatry. OUP Oxford. p. 373. ISBN 0191626759. 5. ^ American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). Washington, DC: American Psychiatric Publishing. Sources * Laws, Richard D.; O'Donohue, William T., eds. (2008). Sexual Deviance: Theory, Assessment, and Treatment (2 ed.). New York: Guilford Press. ISBN 978-1-59385-605-2. * v * t * e Paraphilias List * Abasiophilia * Acrotomophilia * Agalmatophilia * Algolagnia * Apotemnophilia * Autassassinophilia * Biastophilia * Capnolagnia * Chremastistophilia * Chronophilia * Coprophagia * Coprophilia * Crurophilia * Crush fetish * Dacryphilia * Dendrophilia * Emetophilia * Eproctophilia * Erotic asphyxiation * Erotic hypnosis * Erotophonophilia * Exhibitionism * Formicophilia * Frotteurism * Gerontophilia * Homeovestism * Hybristophilia * Infantophilia * Kleptolagnia * Klismaphilia * Lactaphilia * Macrophilia * Masochism * Mechanophilia * Microphilia * Narratophilia * Nasophilia * Necrophilia * Object sexuality * Odaxelagnia * Olfactophilia * Omorashi * Paraphilic infantilism * Partialism * Pedophilia * Podophilia * Plushophilia * Pyrophilia * Sadism * Salirophilia * Scopophilia * Somnophilia * Sthenolagnia * Tamakeri * Telephone scatologia * Transvestic fetishism * Trichophilia * Troilism * Urolagnia * Urophagia * Vorarephilia * Voyeurism * Zoophilia * Zoosadism See also * Other specified paraphilic disorder * Erotic target location error * Courtship disorder * Polymorphous perversity * Sexual fetishism * Human sexual activity * Perversion * Sexology * Book * Category * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category * v * t * e Cross-dressing * History Types and practices * Transvestism * Wartime cross-dressing * Crossplay * Forced cross-dressing * Passing * En femme * En homme * Otokonoko * Sissy As performance * Breeches role * Theatrical travesti * Drag * Pantomime dame * Principal boy * Onnagata * Khawal * Köçek * Shirabyōshi Culture * Hybristica * Cross dressing ball * Fantasia Fair * Casa Susanna * Kottankulangara Festival * Womanless wedding Media * In film and television * In literature * In music and opera * In animated series Sexuality * Transvestic fetishism * Dual-role transvestism * Autoandrophilia and Autogynephilia People * List * Sworn virgins * Bacha bazi * Bacha posh * Travesti * Wartime cross-dressers Organizations * Tri-Ess * ABGLT Related articles * Bibliography of works on wartime cross-dressing * Rebecca Riots * Breeching * Trousers as women's clothing * Gender non-conformance * Transgender * Category [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	Transvestic fetishism	None	5,982	wikipedia	https://en.wikipedia.org/wiki/Transvestic_fetishism	2021-01-18T18:45:24	{"icd-10": ["F65.1"], "wikidata": ["Q377402"]}
Perrault syndrome (PS) is characterized by the association of ovarian dysgenesis in females with sensorineural hearing impairment. In more recent PS reports, some authors have described neurologic abnormalities, notably progressive cerebellar ataxia and intellectual deficit. ## Epidemiology Prevalence is unknown but 34 patients with PS (28 females and 6 males) from 15 different families have been reported so far. However, the syndrome is probably underdiagnosed: hypogonadism is not a feature in males and in the absence of an affected sister the syndrome remains undetected. ## Clinical description Mean age at diagnosis is 22 years following presentation with delayed puberty in females with sensorineural deafness. Hearing defects were noted in all but one of the reported cases (mean age at diagnosis of 8 years). The hearing loss is always sensorineural and bilateral but the severity is variable (mild to profound), even in affected patients from the same family. Ovarian dysgenesis has been reported in all female cases but no gonad defects are detected in males. Amenorrhea is generally primary but secondary amenorrhea has also been reported. Delayed growth (height below the third percentile) was reported in half the documented cases. The exact frequency of the neurological abnormalities is unknown, but nine females and two males (16-37 years old) lacking neurological abnormalities have been reported. Neurological signs are progressive and generally appear later in life, however, walking delay or early frequent falls have been noted in young PS patients. Common neurological signs are ataxia, dyspraxia, limited extraocular movements, and polyneuropathy. Some cases with scoliosis have also been reported. ## Etiology Mutations in the following genes have been excluded: GJB2 (responsible for the most frequent form of isolated hearing loss), FOXL2 (involved in premature ovarian failure) and POLG, FRDA, AOA1 (implicated in ataxia or ophthalmoplegia). Karyotype is normal. The variability in the presence of the neurological symptoms may indicate that PS is a heterogeneous disease. ## Diagnostic methods Diagnosis is made on the basis of the clinical signs and further investigations: CT scans revealing that the hearing loss is not associated with temporal bone malformations; hormonal tests revealing hypergonadotropic hypogonadism in females; pelvic examinations revealing absent ovaries or streak gonads, and a very hypoplasic uterus, and neurologic investigations revealing reduced nerve conduction velocities. Cerebral MRI may show a nonspecific white matter hypersignal or cerebellar atrophy. ## Differential diagnosis Turner syndrome is the principle differential diagnosis (see this term). ## Genetic counseling Transmission of PS is probably autosomal recessive but no gene locus or mitochondrial mutations have been identified to date. ## Management and treatment Treatment and follow-up should be multidisciplinary including audiologists, endocrinologists and neurologists. Hearing aids or cochlear implants may be of benefit for the hearing defect. ## Prognosis Life expectancy is normal. Outcome with treatment is very variable, depending on the association with other features, in particular the presence of neurologic 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	Perrault syndrome	c0685838	5,983	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2855	2021-01-23T17:13:23	{"gard": ["2542"], "mesh": ["C537286"], "omim": ["233400", "614129", "614926", "615300", "616138", "617565"], "umls": ["C0685838"], "icd-10": ["Q87.8"], "synonyms": ["XX gonodal dysgenesis-deafness syndrome", "XX gonodal dysgenesis-hearing loss syndrome"]}
A number sign (#) is used with this entry because of evidence that recurrent hydatidiform mole-1 (HYDM1) is caused by homozygous or compound heterozygous mutation in the NLRP7 gene (609661) on chromosome 19q13. Description A hydatidiform mole is an abnormal pregnancy characterized by hydropic placental villi, trophoblastic hyperplasia, and poor fetal development. Familial recurrent hydatidiform mole is an autosomal recessive condition in which women experience recurrent pregnancy losses, predominantly complete hydatidiform mole (CHM). However, unlike sporadic CHMs, which are androgenetic with 2 paternal chromosome complements, CHMs associated with familial recurrence are genetically biparental in origin with both a maternal and a paternal contribution to the genome. Other pregnancy losses in this condition include partial hydatidiform mole, stillbirths, ectopic pregnancies, early neonatal deaths, and miscarriages, some of which may be undiagnosed molar pregnancies. Normal pregnancies are extremely rare in families with this condition (summary by Fallahian et al., 2013). ### Genetic Heterogeneity of Recurrent Hydatidiform Mole Another form of recurrent complete hydatidiform mole (HYDM2; 614293) is caused by mutation in the KHDC3L gene (611687) on chromosome 6q13. HYDM3 (618431) is caused by mutation in the MEI1 gene (608797) on chromosome 22q13. HYDM4 (618432) is caused by mutation in the C11ORF80 gene (616109) on chromosome 11q13. Clinical Features In India, Ambani et al. (1980) observed gestational trophoblastic disease in multiple pregnancies of sisters in 3 unrelated kindreds. In 1 family a first cousin of 2 'affected' sisters also had a mole pregnancy and the 3 husbands of the 'affected' females had a common ancestral couple, i.e., were related as second cousins, although not related to their wives. Kajii and Ohama (1977) presented evidence for solely paternal genome in hydatidiform moles. On the basis of genetic origin, hydatidiform mole can be divided into 3 types. Approximately 25% of hydatidiform moles ascertained clinically are partial moles. They are triploid, the additional set of chromosomes generally being paternally derived. They do not seem to be associated with the development of choriocarcinoma. A second type of mole that can be classified pathologically is the complete mole. These moles are genetically diploid but are unusual in that all chromosomes are paternally derived, although the cytoplasm has been shown to be maternally derived as in normal conceptions. Complete hydatidiform moles may have 1 of 2 different origins. Most, about 90%, are homozygous, arising from duplication of a haploid sperm. More rarely, complete mole arises by dispermy, the fertilization of an anucleate egg by 2 sperm, and are therefore heterozygous. In 1 choriocarcinoma following pregnancy with hydatidiform mole, Fisher et al. (1988) demonstrated homozygosity. Moglabey et al. (1999) found reports of 7 familial cases. Helwani et al. (1999) provided a partial pedigree of a Lebanese family with recurrent hydatidiform moles involving 3 sibships, the offspring of consanguineous parents. They pointed out that the same family had been reported by Vejerslev et al. (1991), Sunde et al. (1993), and Seoud et al. (1995). Using microsatellite markers amplified by PCR, they performed a genetic study on 8 independent molar tissues occurring in 2 sisters. Karyotype and genotype data demonstrated a diploid and biparental constitution in 7 of the analyzed moles, suggesting a common mechanism underlying the etiology of the various molar pregnancies in this family. The data suggested that complete and partial hydatidiform moles are not always separate entities and that women with familial recurrent hydatidiform moles are homozygous for an autosomal recessive mutation. In this pedigree, not only were the parents of the molar pregnancies consanguineous, but the women were in each case the product of a consanguineous mating. One of their patients had had at least 8 molar pregnancies and several abortions but no viable children. Women with recurrent hydatidiform moles usually fail to have normal pregnancies. Helwani et al. (1999) suggested that the defective gene may be required in the fertilized/unfertilized ovum or in the maternal reproductive tract. They noted that the initial development of the mammalian zygote is under the control of maternally inherited proteins and mRNA produced and stored in the oocyte during oogenesis. Moreover, the progression of the fertilized ovum through cleavage, blastocyst formation, and implantation is dependent on the successful interaction between the preimplantation embryo and the maternal reproductive tract. Therefore, a defective maternal gene at any of these levels might deregulate the imprinting process in diploid zygotes and lead to abnormal embryonic development and to a phenotype similar to that observed in androgenetic diploid and diandric triploid conceptuses. In a family in southern Italy, Sensi et al. (2000) confirmed that recurrent familial hydatidiform moles are diploid and biparental and arise from independent conceptions. The 2 sisters were related in each case to their husbands and all 4 were related to each other. One sister experienced 8 reproductive failures, including 6 complete moles. One pregnancy was attempted by ovum donation, but STS analysis and HLA molecular typing of the molar conceptus established that it was originated by the fertilization of a maternal ovum. This mole was persistent and treated with methotrexate. The proband's sister reported the recurrence of 3 molar pregnancies. Slim and Mehio (2007) reviewed the history and genetics of hydatidiform mole. Population Genetics The incidence of hydatidiform mole varies among ethnic groups and reaches 1 in every 250 pregnancies in eastern Asia. The frequency in the US is approximately 1 in every 1,500 pregnancies (summary by Moglabey et al., 1999). Mapping To map the hydatidiform mole locus, Moglabey et al. (1999) performed a genomewide scan on the Lebanese family (MoLb1) reported by Helwani et al. (1999) and on a previously reported German family (MoGe2). They demonstrated that a defective maternal gene is responsible for recurrent hydatidiform moles. This gene mapped to 19q13.3-q13.4 in a 15.2-cM interval flanked by D19S924 and D19S890. They claimed that this was the first genetic mapping of a maternal locus involved in early embryogenesis in mammals. In a family in southern Italy, Sensi et al. (2000) confirmed that recurrent familial hydatidiform moles are diploid and biparental and arise from independent conceptions. A narrowing of the gene interval on chromosome 19q13.3-q13.4 was suggested by haplotype analysis in 2 sisters. Molecular Genetics By fine mapping, Murdoch et al. (2006) narrowed the hydatidiform mole candidate region to a 0.65-Mb region of chromosome 19q13.4. By screening genes in this region, they identified in NLRP7 (609661) 2 different splice site mutations in 2 families (609661.0001 and 609661.0002, respectively). Screening of 2 additional families and a single family member with recurrent moles demonstrated 3 different missense mutations (609661.0003-609661.0005, respectively). NLRP7 is a member of the CATERPILLAR protein family involved in inflammation and apoptosis. Murdoch et al. (2006) pointed out that NLRP7 is the first maternal effect gene identified in humans and is also responsible for recurrent spontaneous abortions, stillbirths, and intrauterine growth retardation. Djuric et al. (2006) analyzed molar tissues from 2 Lebanese sisters, in whom Murdoch et al. (2006) had previously identified a splice site mutation in the NLRP7 gene (609661.0001), and demonstrated normal postzygotic DNA methylation patterns at major repetitive and long interspersed nuclear elements, genes on the inactive X chromosome, 3 cancer-related genes, and CpG-rich areas surrounding the PEG3 (601483) differentially methylated region (DMR). Djuric et al. (2006) concluded that postzygotic DNA methylation and de novo methylation are normal in familial hydatidiform moles with defects in NLRP7, and that abnormal DNA methylation in these tissues is restricted to imprinted DMRs. Deveault et al. (2009) reported 10 novel nonsynonymous variants/mutations and 1 truncation mutation (609661.0006) of the NLRP7 gene in sporadic and familial patients with hydatidiform mole. Diploid biparental, diploid androgenetic, triploid, and tetraploid conceptions were seen in patients. In vitro and in vivo early embryo cleavage abnormalities were documented in 3 patients. The authors proposed a 2-hit mechanism at the origin of androgenetic moles. This mechanism consists of variable degrees of early embryo cleavage abnormalities leading to chaotic mosaic aneuploidies, with haploid, diploid, triploid, and tetraploid blastomeres. Surviving embryonic cells that reach implantation may then be subject to the maternal immune response. Because of the patients' impaired inflammatory response, androgenetic cells, which are complete allograft, may grow and proliferate. Wang et al. (2009) analyzed the NLRP7 gene in affected individuals from 20 families with a confirmed diagnosis of familial recurrent hydatidiform mole and identified 16 different mutations in 17 of the families (see, e.g., 609661.0003-609661.0012), including in 2 Asian sisters previously studied by Fisher et al. (2002) (609661.0009) and in 2 Italian sisters previously reported by Sensi et al. (2000) (609661.0010). Affected members from 14 of the 17 mutation-positive families were homozygous for the identified mutation, even though only 1 family reported consanguinity. Most pregnancies in the affected women were complete hydatidiform mole, although other reproductive losses were reported, including miscarriages, partial hydatidiform mole, and 1 stillbirth. None of the women had pregnancies resulting in normal live births. Fallahian et al. (2013) performed genetic analysis of tissue from the complete hydatidiform mole pregnancies of a woman who was previously studied by Wang et al. (2009) and found to be homozygous for a 14-bp duplication in the NLRP7 gene (609661.0011). Her first and third were diploid biparental CHMs, whereas the second was a digynic triploid conceptus, with 1 paternal and 2 maternal alleles. Fallahian et al. (2013) stated that these findings were consistent with a role for NLRP7 in setting and/or maintaining the maternal imprint. Andreasen et al. (2012) analyzed the NLRP7, NLRP2 (609364), and KHDC3L genes in 11 Danish women with hydatidiform mole, including 8 with mosaic diploid androgenetic/diploid biparental (PP/PM) moles and 3 with diploid biparental (PM) moles. Homozygosity for a splice site mutation in the NLRP7 gene (609661.0001) was identified in 1 woman with a PM mole who had a positive family history for HYDM and who had experienced 7 HYDMs. The 10 other women had no family history of HYDM and had only experienced 1 HYDM. Andreasen et al. (2012) concluded that although NLRP7 and KHDC3L mutations are associated with recurrent diploid biparental HYDMs, these genes and the NLRP2 gene are not associated with diploid HYDMs with biparental contributions to the molar genome in general. Pathogenesis In a series of patients with biparental complete HYDM, Fisher et al. (2002) observed dramatic underexpression of p57(KIP2) (CDKN1C; 600856) identical to the pattern seen in complete HYDM of androgenetic origin. The series included 2 sisters, both of whom had biparental complete HYDM. Genotyping of this family identified a 15-cM region of homozygosity for 19q13.3-q13.4 similar to that found in 3 other families with recurrent biparental complete HYDM. Fisher et al. (2002) concluded that biparental complete HYDM, like HYDM of androgenetic origin, may result from abnormal expression of imprinted genes (such as CDKN1C), and that a locus on 19q13.3-q13.4 may regulate expression of imprinted genes on other chromosomes. Nguyen et al. (2014) found variable expression of CDKN1C in 35 conceptuses from 17 patients with biallelic mutations in the NLRP7 gene. Of the informative samples, 19 (59%) did not express CDKN1C and 13 (41%) displayed variable levels (20-100%) of CDKN1C. All tissue contained a diploid biparental genome. Some NLRP7 missense mutations did not completely repress CDKN1C expression, and these samples were associated with the presence of embryonic tissue of inner cell mass origin, mild trophoblastic proliferation, and low expression of CDKN1C. In contrast, truncating NLRP7 mutations were associated with lack of CDKN1C expression, absence of embryonic tissue of inner cell mass origin, and the presence of excessive trophoblastic proliferation. The findings suggested that NLRP7 regulates the imprinted expression of CDKN1C and consequently the balance between tissue differentiation and proliferation during early human development. El-Maarri et al. (2003) reported the methylation status of 4 imprinted genes in 2 biparental complete HYDMs from 2 sisters, a 16-year-old normal offspring, and 2 sporadic biparental complete HYDMs from unrelated patients. Using 2 bisulfite-based methods, the authors demonstrated a general trend of abnormal hypomethylation at the paternally expressed genes PEG3 (601483) and SNRPN (182279), and hypermethylation at the maternally expressed genes NESP55 (see 139320) and H19 (103280), in 2 to 4 biparental complete HYDMs. Using single-nucleotide polymorphisms, the authors provided evidence that SNRPN, NESP55, and H19 were abnormally methylated on the maternal alleles in biparental complete HYDMs. They showed, in biparental complete HYDMs from the 2 sisters, that the abnormally methylated H19 allele was inherited from a maternal grandparent. These data suggested that the abnormal methylation in biparental complete HYDM may not be due to an error in erasing the parental imprinting marks, but rather in the reestablishment of the new maternal marks during oogenesis or their postzygotic maintenance. The defective 19q13.4 locus may have led to the development of variable degrees of faulty paternal marks on the maternal chromosomes. INHERITANCE \- Autosomal recessive PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Gestational trophoblastic disease \- Hydatidiform mole MOLECULAR BASIS \- Caused by mutation in the NACHT domain-, leucine-rich repeat-, and PYD-containing protein-7 gene (NALP7, 609661.0001 ) ▲ 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	HYDATIDIFORM MOLE, RECURRENT, 1	c0020217	5,984	omim	https://www.omim.org/entry/231090	2019-09-22T16:27:36	{"doid": ["3590"], "mesh": ["D006828"], "omim": ["231090"], "icd-10": ["O01.9", "O01.0"], "orphanet": ["99927", "254688"], "synonyms": ["Alternative titles", "HYDATIDIFORM MOLE", "HYDATIDIFORM MOLE, COMPLETE", "GESTATIONAL TROPHOBLASTIC DISEASE"]}
Diabetic foot Other namesDiabetic foot syndrome Neuropathic diabetic foot ulcer SpecialtyInfectious disease, endocrinology, surgery A diabetic foot is any pathology that results directly from peripheral arterial disease (PAD) and/or sensory neuropathy affecting the feet in diabetes mellitus; it is a long-term (or "chronic") complication of diabetes mellitus.[1][2] Presence of several characteristic diabetic foot pathologies such as infection, diabetic foot ulcer and neuropathic osteoarthropathy is called diabetic foot syndrome. Due to advanced peripheral nerve dysfunction associated with diabetes (diabetic neuropathy), patients' feet have a reduced ability to feel pain. This means that minor injuries may remain undiscovered for a long while, and hence may progress to a full-thickness diabetic foot ulcer. The feet's insensivity to pain can easily be established by 512 mN quantitative pinprick stimulation.[3] Research estimates that the lifetime incidence of foot ulcers within the diabetic community is around 15% and may become as high as 25%.[4] In diabetes, peripheral nerve dysfunction can be combined with peripheral artery disease (PAD) causing poor blood circulation to the extremities (diabetic angiopathy). Around half of patients with a diabetic foot ulcer have co-existing PAD.[5] Vitamin D deficiency has been recently found to be associated with diabetic foot infections and increased risk of amputations and deaths.[6] Where wounds take a long time to heal, infection may set in, spreading to bones and joints, and lower limb amputation may be necessary. Foot infection is the most common cause of non-traumatic amputation in people with diabetes.[7] ## Contents * 1 Prevention * 2 Treatment * 3 References * 4 External links ## Prevention[edit] Prevention of diabetic foot may include optimising metabolic control via the regulation of blood glucose levels; identification and screening of people at high risk for diabetic foot ulceration, especially those with advanced painless neuropathy; and patient education in order to promote foot self-examination and foot care knowledge. Patients would be taught routinely to inspect their feet for hyperkeratosis, fungal infection, skin lesions and foot deformities. Control of footwear is also important as repeated trauma from tight shoes can be a triggering factor,[8] especially where peripheral neuropathy is present. Evidence is limited that low-quality patient education courses have a long-term preventative impact.[9] "Of all methods proposed to prevent diabetic foot ulcers, only foot temperature-guided avoidance therapy was found beneficial in RCTs" according to a meta-analysis.[10] ## Treatment[edit] Treatment of diabetic foot ulceration can be challenging and prolonged; it may include orthopaedic appliances, surgery and antimicrobial drugs and topical dressings.[9] Most diabetic foot infections (DFIs) require treatment with systemic antibiotics. The choice of the initial antibiotic treatment depends on several factors such as the severity of the infection, whether the patient has received another antibiotic treatment for it, and whether the infection has been caused by a micro-organism that is known to be resistant to usual antibiotics (e.g. MRSA). The objective of antibiotic therapy is to stop the infection and ensure it does not spread.[11] It is unclear whether any particular antibiotic is better than any other for curing infection or avoiding amputation. One trial suggested that ertapenem with or without vancomycin is more effective than tigecycline for resolving DFIs. It is also generally unclear whether different antibiotics are associated with more or fewer adverse effects.[7] It is recommended however that the antibiotics used for treatment of diabetic foot ulcers should be used after deep tissue culture of the wound. Tissue culture and not pus swab culture should be done. Antibiotics should be used at correct doses in order to prevent the emergence of drug resistance. It is unclear if local antibiotics improve outcomes after surgery.[12] ## References[edit] 1. ^ Hefni, Abd Al-Hamead; Ibrahim, Al-Metwally R; Attia, Khaled M.; Moawad, Mahmoud M.; El-ramah, Ayman F.; Shahin, Mohamed M.; Al-Molla, Mahmoud; Abd Al-Satar, Lotfi. "Bacteriological study of diabetic foot infection in Egypt". Journal of the Arab Society for Medical Research. 8 (1): 26–32. S2CID 85976195. 2. ^ [1] [2] Boulton in Diabetes, 30;36 2002 3. ^ Ernst-Adolf Chantelau (2020-01-16). "A Novel Diagnostic Test for End-Stage Sensory Failure Associated With Diabetic Foot Ulceration: Proof-of-Principle Study". Journal of Diabetes Science and Technology. doi:10.1177/1932296819900256. PMID 31948277. 4. ^ Singh, N. (2005). "Preventing Foot Ulcers in Patients With Diabetes". JAMA. 293 (2): 217–28. doi:10.1001/jama.293.2.217. PMID 15644549. 5. ^ International Working Group on the Diabetic Foot (2015). "Guidance on the diagnosis, prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes". Retrieved 23 November 2015. 6. ^ Darlington, C., Kumar, S., Jagdish, S., Sridhar, M. Evaluation of Serum Vitamin D Levels in Diabetic Foot Infections: A Cross-Sectional Study in a Tertiary Care Center in South India. Iranian Journal of Medical Sciences, 2019; 44(6): 474-482. doi: 10.30476/ijms.2018.44951 7. ^ a b Selva Olid A, Solà I, Barajas-Nava LA, Gianneo OD, Bonfill Cosp X, Lipsky BA (4 September 2015). "Systemic antibiotics for treating diabetic foot infections". Cochrane Database of Systematic Reviews (9): CD009061. doi:10.1002/14651858.CD009061.pub2. PMID 26337865. 8. ^ Stiegler, H (2004). "Das diabetische Fußsyndrom". Herz. 29 (1): 104–15. doi:10.1007/s00059-004-2534-z. PMID 14968346. 9. ^ a b Dorresteijn JAN, Kriegsman DMW, Assendelft WJJ, Valk GD (2014). "Patient education for preventing diabetic foot ulceration". Cochrane Database of Systematic Reviews (12): CD001488. doi:10.1002/14651858.CD001488.pub5. hdl:2066/108980. PMC 7057029. PMID 25514250. 10. ^ Arad Y, Fonseca V, Peters A, Vinik A (2011). "Beyond the Monofilament for the Insensate Diabetic Foot: A systematic review of randomized trials to prevent the occurrence of plantar foot ulcers in patients with diabetes". Diabetes Care. 34 (4): 1041–6. doi:10.2337/dc10-1666. PMC 3064020. PMID 21447666. 11. ^ Bader MS. "Diabetic Foot Infection". American Family Physician. Retrieved 8 October 2020. 12. ^ Marson, BA; Deshmukh, SR; Grindlay, DJC; Ollivere, BJ; Scammell, BE (November 2018). "A systematic review of local antibiotic devices used to improve wound healing following the surgical management of foot infections in diabetics". The Bone & Joint Journal. 100-B (11): 1409–1415. doi:10.1302/0301-620X.100B11.BJJ-2018-0720. PMID 30418057. S2CID 53280854. ## External links[edit] Classification D * ICD-10: Xxx.x * ICD-9-CM: xxx * MeSH: D017719 Wikimedia Commons has media related to diabetic foot. * MedlinePlus: Diabetic Foot * v * t * e Diabetes Types * Type 1 * Type 2 * LADA * Gestational diabetes * Diabetes and pregnancy * Prediabetes * Impaired fasting glucose * Impaired glucose tolerance * Insulin resistance * KPD * MODY * Neonatal * Transient * Permanent * Type 3c (pancreatogenic) * Type 3 Blood tests * Blood sugar level * Glycosylated hemoglobin * Glucose tolerance test * Postprandial glucose test * Fructosamine * Glucose test * C-peptide * Noninvasive glucose monitor * Insulin tolerance test Management * Diabetic diet * Anti-diabetic drugs * Insulin therapy * intensive * conventional * pulsatile * Cure * Embryonic stem cells * Artificial pancreas * Other * Gastric bypass surgery Complications * Diabetic comas * Hypoglycemia * Ketoacidosis * Hyperosmolar hyperglycemic state * Diabetic foot * ulcer * Neuropathic arthropathy * Organs in diabetes * Blood vessels * Muscle * Kidney * Nerves * Retina * Heart * Diabetic skin disease * Diabetic dermopathy * Diabetic bulla * Diabetic cheiroarthropathy * Neuropathic ulcer * Hyperglycemia * Hypoglycemia Other * Glossary of diabetes * History of diabetes * Notable people with type 1 diabetes [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	Diabetic foot	c0206172	5,985	wikipedia	https://en.wikipedia.org/wiki/Diabetic_foot	2021-01-18T19:03:27	{"mesh": ["D017719"], "umls": ["C0206172"], "wikidata": ["Q52856"]}
Cardiac tamponade Other namesPericardial tamponade A very large pericardial effusion resulting in tamponade as a result of bleeding from cancer as seen on ultrasound. Closed arrow - the heart; open arrow - the effusion SpecialtyCardiac surgery SymptomsShortness of breath, weakness, lightheadedness, cough[1] Usual onsetRapid or more gradual[2] CausesCancer, kidney failure, chest trauma, pericarditis, tuberculosis[2][1] Diagnostic methodSymptoms and ultrasound of the heart[2] TreatmentDrainage (pericardiocentesis, pericardial window, pericardiectomy)[2] Frequency2 per 10,000 per year (US)[3] Cardiac tamponade, also known as pericardial tamponade, is when fluid in the pericardium (the sac around the heart) builds up, resulting in compression of the heart.[2] Onset may be rapid or gradual.[2] Symptoms typically include those of cardiogenic shock including shortness of breath, weakness, lightheadedness, and cough.[1] Other symptoms may relate to the underlying cause.[1] Common causes of cardiac tamponade include cancer, kidney failure, chest trauma, myocardial infarction, and pericarditis.[2][4] Other causes include connective tissues diseases, hypothyroidism, aortic rupture, autoimmune disease, and complications of cardiac surgery.[2][5] In Africa, tuberculosis is a relatively common cause.[1] Diagnosis may be suspected based on low blood pressure, jugular venous distension, or quiet heart sounds (together known as Beck's triad).[2][1][6] A pericardial rub may be present in cases due to inflammation.[2] The diagnosis may be further supported by specific electrocardiogram (ECG) changes, chest X-ray, or an ultrasound of the heart.[2] If fluid increases slowly the pericardial sac can expand to contain more than 2 liters; however, if the increase is rapid, as little as 200 mL can result in tamponade.[2] Tamponade is a medical emergency.[4] When it results in symptoms, drainage is necessary.[7] This can be done by pericardiocentesis, surgery to create a pericardial window, or a pericardiectomy.[2] Drainage may also be necessary to rule out infection or cancer.[7] Other treatments may include the use of dobutamine or in those with low blood volume, intravenous fluids.[1] Those with few symptoms and no worrisome features can often be closely followed.[2] The frequency of tamponade is unclear.[8] One estimate from the United States places it at 2 per 10,000 per year.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Surgery * 3 Pathophysiology * 4 Diagnosis * 4.1 Medical imaging * 4.2 Differential diagnosis * 5 Treatment * 5.1 Pre-hospital care * 5.2 Hospital management * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] Onset may be rapid (acute) or more gradual (subacute).[9][2] Signs of cardiac tamponade typically include those of cardiogenic shock including shortness of breath, weakness, lightheadedness, and cough.[1] Other symptoms may relate to the underlying cause.[1] Other general signs of shock (such as fast heart rate, shortness of breath and decreasing level of consciousness) may also occur. However, some of these signs may not be present in certain cases. A fast heart rate, although expected, may be absent in people with uremia and hypothyroidism.[1] ## Causes[edit] Cardiac tamponade is caused by a large or uncontrolled pericardial effusion, i.e. the buildup of fluid inside the pericardium.[10] This commonly occurs as a result of chest trauma (both blunt and penetrating),[11] but can also be caused by myocardial infarction, myocardial rupture, cancer, uremia, pericarditis, or cardiac surgery,[10] and rarely occurs during retrograde aortic dissection,[12] or while the person is taking anticoagulant therapy.[13] The effusion can occur rapidly (as in the case of trauma or myocardial rupture), or over a more gradual period of time (as in cancer). The fluid involved is often blood, but pus is also found in some circumstances.[10] ### Surgery[edit] One of the most common settings for cardiac tamponade is in the first 7 days after heart surgery.[14] After heart surgery, chest tubes are placed to drain blood. These chest tubes, however, are prone to clot formation. When a chest tube becomes occluded or clogged, the blood that should be drained can accumulate around the heart, leading to tamponade.[15] ## Pathophysiology[edit] Hemopericardium, wherein the pericardium becomes filled with blood, is one cause of cardiac tamponade. The outer layer of the heart is made of fibrous tissue[16] which does not easily stretch, so once fluid begins to enter the pericardial space, pressure starts to increase.[10] If fluid continues to accumulate, each successive diastolic period leads to less blood entering the ventricles. Eventually, increasing pressure on the heart forces the septum to bend in towards the left ventricle, leading to a decrease in stroke volume.[10] This causes the development of obstructive shock, which if left untreated may lead to cardiac arrest (often presenting as pulseless electrical activity).[17] ## Diagnosis[edit] Play media An ultrasound of the heart showing cardiac tamponade.[18] The three classic signs, known as Beck's triad, are low blood pressure, jugular-venous distension, and muffled heart sounds.[19] Other signs may include pulsus paradoxus (a drop of at least 10 mmHg in arterial blood pressure with inspiration),[10] and ST segment changes on the electrocardiogram,[19] which may also show low voltage QRS complexes.[13] ### Medical imaging[edit] Tamponade can often be diagnosed radiographically. Echocardiography, which is the diagnostic test of choice, often demonstrates an enlarged pericardium or collapsed ventricles. A large cardiac tamponade will show as an enlarged globular-shaped heart on chest x-ray. During inspiration, the negative pressure in the thoracic cavity will cause increased pressure into the right ventricle. This increased pressure in the right ventricle will cause the interventricular septum to bulge towards the left ventricle, leading to decreased filling of the left ventricle. At the same time, right ventricle volume is markedly diminished and sometimes it can collapse.[13] * Play media Apical ultrasound image of the heart in a person with cardiac tamponade. Note how the right atrial collapses during systole.[18] * Play media Ultrasound image of the inferior vena cava (IVC) in a person with cardiac tamponade. Note that the IVC is large and changes minimally with breathing.[18] ### Differential diagnosis[edit] Initial diagnosis of cardiac tamponade can be challenging, as there is a broad differential diagnosis.[9] The differential includes possible diagnoses based on symptoms, time course, mechanism of injury, patient history. Rapid onset cardiac tamponade may also appear similary to pleural effusions, shock, pulmonary embolism, and tension pneumothorax.[11][9] If symptoms appeared more gradually, the differential diagnosis includes acute heart failure.[20] In a person with trauma presenting with pulseless electrical activity in the absence of hypovolemia and tension pneumothorax, the most likely diagnosis is cardiac tamponade.[21] In addition to the diagnostic complications afforded by the wide-ranging differential diagnosis for chest pain, diagnosis can be additionally complicated by the fact that people will often be weak or faint at presentation. For instance, a fast rate of breathing and difficulty breathing on exertion that progresses to air hunger at rest can be a key diagnostic symptom, but it may not be possible to obtain such information from people who are unconscious or who have convulsions at presentation.[1] ## Treatment[edit] ### Pre-hospital care[edit] Initial treatment given will usually be supportive in nature, for example administration of oxygen, and monitoring. There is little care that can be provided pre-hospital other than general treatment for shock. Some teams have performed an emergency thoracotomy to release clotting in the pericardium caused by a penetrating chest injury.[citation needed] Prompt diagnosis and treatment is the key to survival with tamponade. Some pre-hospital providers will have facilities to provide pericardiocentesis, which can be life-saving. If the person has already suffered a cardiac arrest, pericardiocentesis alone cannot ensure survival, and so rapid evacuation to a hospital is usually the more appropriate course of action[citation needed]. ### Hospital management[edit] Initial management in hospital is by pericardiocentesis.[11] This involves the insertion of a needle through the skin and into the pericardium and aspirating fluid under ultrasound guidance preferably. This can be done laterally through the intercostal spaces, usually the fifth, or as a subxiphoid approach.[22][23] A left parasternal approach begins 3 to 5 cm left of the sternum to avoid the left internal mammary artery, in the 5th intercostal space.[24] Often, a cannula is left in place during resuscitation following initial drainage so that the procedure can be performed again if the need arises. If facilities are available, an emergency pericardial window may be performed instead,[11] during which the pericardium is cut open to allow fluid to drain. Following stabilization of the person, surgery is provided to seal the source of the bleed and mend the pericardium. Following heart surgery, the amount of chest tube drainage is monitored. If the drainage volume drops off, and the blood pressure goes down, this can suggest a tamponade due to chest tube clogging. In that case, the person is taken back to the operating room for an emergency reoperation. If aggressive treatment is offered immediately and no complications arise (shock, AMI or arrhythmia, heart failure, aneurysm, carditis, embolism, or rupture), or they are dealt with quickly and fully contained, then adequate survival is still a distinct possibility.[citation needed] ## Epidemiology[edit] The frequency of tamponade is unclear.[8] One estimate from the United States places it at 2 per 10,000 per year.[3] It is estimated to occur in 2% of those with stab or gunshot wounds to the chest.[25] ## References[edit] 1. ^ a b c d e f g h i j k Spodick, DH (Aug 14, 2003). "Acute cardiac tamponade". The New England Journal of Medicine. 349 (7): 684–90. doi:10.1056/NEJMra022643. PMID 12917306. 2. ^ a b c d e f g h i j k l m n o Richardson, L (November 2014). "Cardiac tamponade". Journal of the American Academy of Physician Assistants. 27 (11): 50–1. doi:10.1097/01.jaa.0000455653.42543.8a. PMID 25343435. S2CID 205395461. 3. ^ a b c Kahan, Scott (2008). In a Page: Medicine. Lippincott Williams & Wilkins. p. 20. ISBN 9780781770354. Archived from the original on 2016-10-02. 4. ^ a b "Cardiac Tamponade - Injuries and Poisoning". Merck Manuals Consumer Version. Retrieved 1 May 2020. 5. ^ Schiavone, WA (February 2013). "Cardiac tamponade: 12 pearls in diagnosis and management". Cleveland Clinic Journal of Medicine. 80 (2): 109–16. doi:10.3949/ccjm.80a.12052. PMID 23376916. 6. ^ Khandaker, MH; Espinosa, RE; Nishimura, RA; Sinak, LJ; Hayes, SN; Melduni, RM; Oh, JK (June 2010). "Pericardial disease: diagnosis and management". Mayo Clinic Proceedings. 85 (6): 572–93. doi:10.4065/mcp.2010.0046. PMC 2878263. PMID 20511488. 7. ^ a b Sagristà-Sauleda, J; Mercé, AS; Soler-Soler, J (26 May 2011). "Diagnosis and management of pericardial effusion". World Journal of Cardiology. 3 (5): 135–43. doi:10.4330/wjc.v3.i5.135. PMC 3110902. PMID 21666814. 8. ^ a b Bodson, L; Bouferrache, K; Vieillard-Baron, A (October 2011). "Cardiac tamponade". Current Opinion in Critical Care. 17 (5): 416–24. doi:10.1097/mcc.0b013e3283491f27. PMID 21716107. S2CID 25236604. 9. ^ a b c Stashko, Eric; Meer, Jehangir M. (2019), "Cardiac Tamponade", StatPearls, StatPearls Publishing, PMID 28613742, retrieved 2019-08-02 10. ^ a b c d e f Porth, Carol; Carol Mattson Porth (2005). Pathophysiology: concepts of altered health states (7th ed.). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-4988-6. 11. ^ a b c d Gwinnutt CL, Driscoll PA (2003). Trauma Resuscitation: The Team Approach (2nd ed.). Oxford: BIOS. ISBN 978-1-85996-009-7. 12. ^ Isselbacher EM, Cigarroa JE, Eagle KA (Nov 1994). "Cardiac tamponade complicating proximal (retrograde) aortic dissection. Is pericardiocentesis harmful?". Circulation. 90 (5): 2375–8. doi:10.1161/01.CIR.90.5.2375. PMID 7955196. 13. ^ a b c Longmore, J. M.; Murray Longmore; Wilkinson, Ian; Supraj R. Rajagopalan (2004). Oxford handbook of clinical medicine (6th ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-852558-5. 14. ^ Carmona, Paula; Mateo, Eva; Casanovas, Irene; Peña, Juan J.; Llagunes, Jose; Aguar, Federico; De Andrés, Jose; Errando, Carlos (2012). "Management of Cardiac Tamponade After Cardiac Surgery". Journal of Cardiothoracic and Vascular Anesthesia. Elsevier BV. 26 (2): 302–311. doi:10.1053/j.jvca.2011.06.007. ISSN 1053-0770. PMID 21868250. 15. ^ Vistarini, Nicola; Gabrysz-Forget, Fanny; Beaulieu, Yanick; Perrault, Louis P. (2016). "Tamponade Relief by Active Clearance of Chest Tubes". The Annals of Thoracic Surgery. Elsevier BV. 101 (3): 1159–1163. doi:10.1016/j.athoracsur.2015.10.098. ISSN 0003-4975. PMID 26897195. 16. ^ Patton KT, Thibodeau GA (2003). Anatomy & physiology (5th ed.). St. Louis: Mosby. ISBN 978-0-323-01628-5. 17. ^ Standl, Thomas; Annecke, Thorsten; Cascorbi, Ingolf; Heller, Axel R.; Sabashnikov, Anton; Teske, Wolfram (2019-02-03). "The Nomenclature, Definition and Distinction of Types of Shock". Deutsches Ärzteblatt International. 115 (45): 757–768. doi:10.3238/arztebl.2018.0757. PMC 6323133. PMID 30573009. 18. ^ a b c Smith, Ben (27 February 2017). "UOTW #78 - Ultrasound of the Week". Ultrasound of the Week. Archived from the original on 13 March 2017. Retrieved 13 March 2017. 19. ^ a b Holt L, Dolan B (2000). Accident and emergency: theory into practice. London: Baillière Tindall. ISBN 978-0-7020-2239-5. 20. ^ Chahine, Johnny; Alvey, Heidi (2019), "Left Ventricular Failure", StatPearls, StatPearls Publishing, PMID 30725783, retrieved 2019-08-02 21. ^ American College of Surgeons Committee on Trauma (2007). Advanced Trauma Life Support for Doctors, 7th Edition. Chicago: American College of Surgeons 22. ^ Shlamovitz, Gil (4 August 2011). "Pericardiocentesis". Medscape. Archived from the original on 23 August 2011. Retrieved 16 August 2011. 23. ^ Yarlagadda, Chakri (11 August 2011). "Cardiac Tamponade Treatment & Management". Medscape. Archived from the original on 16 August 2011. Retrieved 16 August 2011. 24. ^ Synovitz C.K., Brown E.J. (2011). Chapter 37. Pericardiocentesis. In Tintinalli J.E., Stapczynski J, Ma O, Cline D.M., Cydulka R.K., Meckler G.D., T (Eds), Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e. Retrieved September 19, 2014 from "Chapter 37. Pericardiocentesis". Archived copy. The McGraw-Hill Companies. 2011. Archived from the original on 2016-03-04. Retrieved 2014-09-20.CS1 maint: archived copy as title (link). 25. ^ Marx, John; Walls, Ron; Hockberger, Robert (2013). Rosen's Emergency Medicine - Concepts and Clinical Practice. Elsevier Health Sciences. p. 448. ISBN 978-1455749874. Archived from the original on 2016-10-02. ## External links[edit] Classification D * ICD-10: I31.9 * ICD-10-CM: I31.4 * ICD-9-CM: 423.3 * MeSH: D002305 External resources * MedlinePlus: 000194 * eMedicine: med/283 emerg/412 * Patient UK: Cardiac tamponade * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * t * e Chest injury, excluding fractures Cardiac and circulatory system injuries * vascular: Traumatic aortic rupture * Thoracic aorta injury * heart: Myocardial contusion/Commotio cordis * Cardiac tamponade * Hemopericardium * Myocardial rupture Lung and lower respiratory tract injuries * Pneumothorax * Hemothorax * Hemopneumothorax * Pulmonary contusion * Pulmonary laceration * Tracheobronchial injury * Diaphragmatic rupture * 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 [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	Cardiac tamponade	c0007177	5,986	wikipedia	https://en.wikipedia.org/wiki/Cardiac_tamponade	2021-01-18T19:03:43	{"mesh": ["D002305"], "umls": ["C0007177"], "wikidata": ["Q929313"]}
A number sign (#) is used with this entry because Diamond-Blackfan anemia-6 (DBA6) is caused by heterozygous mutation in the gene encoding ribosomal protein L5 (RPL5; 603634) on chromosome 1p22. Description Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents in the first year of life. The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Patients show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. The majority of patients have increased mean corpuscular volume, elevated erythrocyte adenosine deaminase activity, and persistence of hemoglobin F. However, some DBA patients do not exhibit these findings, and even in the same family, symptoms can vary between affected family members (summary by Landowski et al., 2013). For a discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650). Clinical Features Aase and Smith (1969) observed 2 brothers with congenital anemia and triphalangeal thumbs. Ventricular septal defect was thought to be present in 1 brother. Alter (1978), Gorlin et al. (1990), and Hurst et al. (1991) considered the syndrome reported by Aase and Smith (1969) to be the same as Blackfan-Diamond syndrome. Alter (1978) and Gorlin et al. (1990) referred to it as Aase-Smith syndrome II. Gazda et al. (2008) reviewed available medical records for 20 of the 24 RPL5 mutation-positive DBA patients and found that 14 of 20 had physical malformations, including craniofacial, thumb, and heart anomalies, and 11 of them had multiple, severe abnormalities. Thumb abnormalities were seen in 8 patients; cleft lip and/or palate or cleft soft palate was seen in 9 patients, isolated or in combination with other facial malformations, such as micrognathia, hypertelorism, or mandibular hypoplasia with retrognathia, and/or with other physical abnormalities of the heart or thumb. One patient had melanoma. Gerrard et al. (2013) reported 5 patients, including a mother and daughter, with DBA6. A 4-year-old Caucasian boy was diagnosed at age 7 weeks. He had growth retardation, cleft palate, esophageal strictures, eosinophilic esophagitis, triphalangeal thumbs, and hepatic iron overload. He was transfusion-dependent. A 39-year-old mother was diagnosed at 5 years of age. She had growth retardation, osteoporosis, thumb abnormalities, and hepatic iron overload. Her 10-year-old daughter had intrauterine growth retardation and fetal distress, and was diagnosed at birth. She had Cathie facies, cleft palate, ventricular septal defect, vitamin D deficiency, and iron overload. Both had increased erythrocyte adenosine deaminase (ADA; 608958). The mother's disorder was steroid-responsive, whereas the daughter developed secondary steroid resistance. The 2 other patients also had cleft palate; one was more severely affected with autism spectrum disorder, growth retardation, and neutropenia. Molecular Genetics Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia for mutations in 25 genes encoding ribosomal proteins and identified 15 different mutations in the RPL5 gene in 18 probands and 6 additional family members (see, e.g., 603634.0001-603634.0006); 3 of the mutation-positive patients were from the family with DBA originally described by Aase and Smith (1969) (see 603634.0005). The mutations segregated with disease in multiplex families and were not found in at least 150 controls. Functional studies demonstrated defects in the maturation of ribosomal RNAs associated with mutation in the RPL5 gene. Gazda et al. (2008) stated that RPL5 was the first ribosomal protein gene to be associated with cleft lip and/or cleft palate abnormalities in DBA patients, and that mutations in RPL5 appeared to cause a more severe phenotype than mutations in RPL11 (604175) or RPS19 (603474). Gerrard et al. (2013) identified 4 different heterozygous truncating mutations in the RPL5 gene (see, e.g., 603634.0007 and 603634.0008) in 5 of 19 patients with DBA who were screened for mutations in 80 ribosomal protein genes. INHERITANCE \- Autosomal dominant GROWTH Other \- Failure to thrive \- Growth retardation HEAD & NECK Eyes \- Hypertelorism Mouth \- Cleft lip \- Cleft palate \- Micrognathia \- Mandibular hypoplasia with retrognathia \- Bifid uvula CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect \- Tetralogy of Fallot \- Ventricular hypertrophy \- Patent ductus arteriosus \- Mitral regurgitation, mild \- Mitral valve prolapse, mild RESPIRATORY Airways \- Tracheomalacia (some patients) SKELETAL Hands \- Triphalangeal thumbs \- Hypoplastic thumbs \- Small extra thumbs \- Long proximal thumb phalanges HEMATOLOGY \- Anemia, normochromic macrocytic \- Increased fetal hemoglobin LABORATORY ABNORMALITIES \- Elevated erythrocyte adenosine deaminase (eADA) \- Iron overload (in some patients) MISCELLANEOUS \- Age at diagnosis is usually in the first year of life \- Most patients are steroid responsive MOLECULAR BASIS \- Caused by mutation in ribosomal protein L5 (RPL5, 603634.0001 ) ▲ 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	DIAMOND-BLACKFAN ANEMIA 6	c1260899	5,987	omim	https://www.omim.org/entry/612561	2019-09-22T16:01:12	{"doid": ["1339"], "mesh": ["D029503"], "omim": ["612561"], "orphanet": ["124"], "synonyms": ["Alternative titles", "AASE-SMITH SYNDROME II"], "genereviews": ["NBK7047"]}
A rare congenital skin disease defined as an abnormality of the structure of the scalp hair and characterized by extreme kinkiness of the hair. ## Epidemiology Prevalence of woolly hair is unknown. ## Clinical description Woolly hair can either be present at birth or appear in the first months of life. The curls, with an average diameter of 0.5 cm, lie closely together and usually make the hair difficult to comb; in addition, the hair may be more fragile than usual. The hair growth rate is usually normal but the anagen phase may be truncated, with the result that the hair does not grow to be long. Woolly hair either shows a generalized distribution affecting the entire scalp or a localized circumscribed distribution in the form of a woolly hair nevus. A diffuse partial form, manifesting during adolescence and adulthood, have also been described. In many cases, woolly hair is associated with hypotrichosis. Whilst wooly hair may occur as an isolated finding, it is important to exclude manifestations that occur in syndromic forms such as dilated cardiomyopathy and palmoplantar keratoderma (Carvajal syndrome), arrhythmogenic right ventricular cardiomyopathy and palmoplantar keratoderma (Naxos disease), or with growth failure and neurological symptoms (Menkes disease). ## Etiology Isolated forms are mostly due to homozygous or sometimes compound heterozygous mutations in the genes lipase H (LIPH, 3q27.2) and lysophosphatidic acid receptor 6 (LPAR6, 13q14.2), that act along a common pathway which plays an important role in the control of hair growth as well as hair texture. In only very few patients, heterozygous mutations have been reported in two keratin genes, namely KRT74 (12q13.13) and KRT71 (12q13.13). Mutations have also been reported in KRT25 (17q21.2 ). Recently, a new gene locus was reported for woolly hair on chromosome 4q35.1-q35.2 with a potential disease gene with one affected family only. The etiology of diffuse partial woolly hair and of sporadically occurring woolly hair nevi is unknown. ## Diagnostic methods A thorough dermatological examination with an evaluation of the entire integument should be performed and may also identify any associated manifestations. The examination of the hair shafts by light and electron microscopy reveals an elliptical cross section, variations in caliber, axis rotation and kinked formation, as well as non-homogeneous keratinization. In some cases trichorrexis nodosa is evident. If necessary, the anagen/catagen ratio can be determined using a trichogram. In cases of diffuse partial woolly hair, an increase in intermediate follicles can be detected histopathologically. ## Differential diagnosis Differential diagnosis includes acquired progressive curling of the hair, allotrichia circumscripta symmetrica, acquired partial kinky hair and drug-induced kinky hair. Syndromes with woolly hair should also be excluded, such as Naxos disease, Carvajal syndrome, Woolly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, woolly-hair-palmoplantar keratoderma syndrome, and skin fragility-woolly hair-palmoplantar keratoderma syndrome. ## Genetic counseling Generalized forms due to KRT74 and KRT71 mutations are autosomal dominant, and forms due to LIPH and LPAR6 mutations are autosomal recessive. Sporadic forms may also occur. Follicular mosaicism is likely, while an autosomal dominant transmission has also been discussed for diffuse partial woolly hair. ## Management and treatment No treatment is currently available. Depending on their size and location, woolly hair nevi can be excised. Harsh physical and chemical cosmetic treatments should be avoided. If the presence of a syndrome is suspected, an extensive internal investigation, with a detailed cardiological diagnostic examination, is necessary. ## Prognosis Woolly hair is most pronounced during childhood; the manifestations often become less severe in adulthood. [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	Woolly hair	c0345427	5,988	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=170	2021-01-23T18:39:21	{"gard": ["5597"], "mesh": ["C536745"], "omim": ["194300", "278150", "604379", "615896", "616760"], "umls": ["C0343073", "C0345427"], "icd-10": ["Q84.1"], "synonyms": ["Familial woolly hair syndrome", "Familial wooly hair syndrome", "Hereditary woolly hair syndrome", "Hereditary wooly hair syndrome", "Wooly hair"]}
A rare multiple congenital anomaly syndrome characterized by dysmorphic facial features, congenital diaphragmatic hernia, pulmonary hypoplasia, and distal limb hypoplasia, in addition to variable expression of additional malformations. ## Epidemiology The birth prevalence of Fryns syndrome (FS) has been estimated at 1/14,000 births. ## Clinical description Polyhydramnios is often noted during pregnancy and neonates present with a spectrum of various malformations at birth. The classical features of FS include CDH (unilateral in 75% of cases), dysmorphic craniofacial features (coarse facies, ocular hypertelorism, microphthalmia, low-set, poorly formed ears, a broad and flat nasal bridge, thick nasal tip with anteverted nares, long philtrum, tented upper lip, macrostomia and microretrognathia), and limb malformations (mainly distal limb hypoplasia that includes short and broad hands, short digits, short terminal phalanges, hypoplastic or absent nails, and clinodactyly). Thorax is small with widely spaced nipples. Brain (ventricular dilation, hydrocephalus) and cardiac malformations (atrial and ventricular septal defects, aortic abnormalities) are reported frequently in affected individuals. Additional anomalies include orofacial clefting as well as pulmonary (lung hypoplasia), gastrointestinal (malrotation, anal atresia, omphalocele (see this term)), uro-genital (renal cysts, ureteral dilation, cryptorchidism), and musculo-skeletal (talipes, broad clavicles) malformations. In those that survive the neonatal period, severe developmental delay and intellectual disability is common. Death is mainly due to complications of CDH and pulmonary hypoplasia. ## Etiology The etiology is not clear. Several chromosomal aberrations including microdeletions involving chromosome bands 15q26.2 and 8p23.1 have been reported in probands with FS but the causal genes are yet to be identified. ## Diagnostic methods Diagnosis is based purely on clinical findings (CDH with brachytelephalangy, nail hypoplasia, craniofacial dysmorphism, pulmonary hypoplasia and/or polyhydramnios) as the causal gene has not yet been identified. Array comparative genomic hybridization (array CGH) can be useful in differentiating FS from other chromosomal conditions with CDH, as FS is associated with a normal karyotype. Radiographs, ultrasounds, echocardiograms, and magnetic resonance imaging (MRI) may be necessary to identify all anomalies present. ## Differential diagnosis Differential diagnosis includes Donnai-Barrow syndrome, Matthew-Wood syndrome, Simpson-Golabi-Behmel syndrome, Cornelia de Lange syndrome, tetrasomy 12p, distal monosomy 15q (see these terms) and other chromosome aberrations. ## Antenatal diagnosis Prenatal diagnosis is possible, in couples with a previously affected child, by 3D ultrasonography and fetal MRI revealing the characteristic malformations. Exclusion of chromosomal abnormalities and gene mutations is needed prior to diagnosis. ## Genetic counseling FS is thought to be inherited as an autosomal recessive trait and genetic counseling is possible in those with a family history of the disease. ## Management and treatment Management of FS is multidisciplinary and may necessitate pediatric specialists in neurology, cardiology, gastroenterology, and nephrology as well as clinical geneticists, developmental pediatricians and regular follow-up in a specialized centre. Supportive treatments are directed at the management of the diaphragmatic hernia and include extra-corporeal membrane oxygenation and nitric oxide and surfactant as therapies for persistent pulmonary hypertension of the newborn. Other malformations are managed with standard treatment procedures. ## Prognosis Prognosis depends on malformations present, but is usually poor with survival beyond the neonatal period being rare. Patients without diaphragmatic defects have a better prognosis. [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	Fryns syndrome	c0220730	5,989	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2059	2021-01-23T18:41:18	{"gard": ["3699"], "mesh": ["C538070"], "omim": ["229850"], "umls": ["C0220730"], "icd-10": ["Q87.8"], "synonyms": ["Diaphragmatic hernia-abnormal face-distal limb anomalies syndrome"]}
A number sign (#) is used with this entry because of evidence that transient infantile hypertriglyceridemia (HTGTI) is caused by homozygous or compound heterozygous mutation in the GPD1 gene (138420) on chromosome 12q13. Description Transient infantile hypertriglyceridemia is an autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. The long-term outcome of affected individuals is unclear (summary by Basel-Vanagaite et al., 2012). Clinical Features Basel-Vanagaite et al. (2012) reported 10 patients from 4 consanguineous Israeli-Arab families with transient infantile hypertriglyceridemia and fatty liver. All presented with similar laboratory features between 1 and 9 months of age. Six were asymptomatic, 3 had vomiting, and 1 had poor weight gain. Initial examination showed severely enlarged livers, mild to severe fasting hypertriglyceridemia, and abnormally increased liver enzymes. Bilirubin and synthetic hepatic function were normal. Three patients also had splenomegaly. Ten patients had sonographic evidence of fatty liver, including diffuse hyperechogenicity with a fine granular pattern, and loss of portal spaces in some. Most other laboratory findings were normal, except in a pair of twins in 1 family who had additional medical problems, and 3 patients who had abnormal lipoprotein levels. Five of 9 patients tested showed mildly elevated fasting urinary dicarboxylic acids, which decreased with age. Triglyceride levels decreased in 8 individuals later in infancy or childhood, but still remained elevated in 7 patients. Two patients had liver biopsies at ages 4.5 and 2.5 years, respectively, which showed steatosis with fibrosis and septal formation. The oldest patient, who was 23 years old, was asymptomatic, with short stature, elevated liver enzymes, fatty liver, and no evidence of cardiovascular disease or pancreatitis. None of the patients were obese and none had cutaneous xanthomas. Heterozygous parents did not have increased triglyceride levels or biochemical evidence of hepatic dysfunction. Because most affected individuals were young, no conclusions could be drawn about the influence of severe childhood hypertriglyceridemia on the risk for coronary heart disease later in life. Joshi et al. (2014) reported a Caucasian female infant with hepatomegaly and hypertriglyceridemia. She presented in early infancy with failure to thrive, vomiting, and an enlarged abdomen. Laboratory studies showed abnormal liver enzymes, increased plasma triglycerides, and elevated cholesterol. Liver biopsy showed diffuse steatohepatitis. She was successfully managed with a high-calorie, low-fat diet, and she showed normal development at age 1.5 years. Inheritance The transmission pattern of transient infantile hypertriglyceridemia in the families reported by Basel-Vanagaite et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics By homozygosity mapping followed by candidate gene analysis of 4 consanguineous families with transient infantile hypertriglyceridemia, Basel-Vanagaite et al. (2012) identified a homozygous splice site mutation in the GPD1 gene (138420.0001), predicted to result in a truncated protein lacking a functional site responsible for initial substrate recognition. Overexpression of the mutant cDNA in a human hepatocellular carcinoma cell line resulted in a 33% increase in triglyceride secretion compared to wildtype. Basel-Vanagaite et al. (2012) suggested that a defect in this gene may limit the conversion of glycerol-3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP), thus increasing the amount of G3P available for triglyceride synthesis. The transient nature of the hypertriglyceridemia was compatible with the fact that the rates of triglyceride secretion by hepatocytes are higher in neonates than in adults. In a Caucasian female infant with HTGTI, Joshi et al. (2014) found compound heterozygosity for a point mutation in the GPD1 gene (R229Q; 138420.0002) and a deletion of the GPD1 gene. Each genetic defect was inherited from an unaffected parent. Patient liver sample showed a complete absence of isoform 1 of the GPD1 protein. The activities of CPT1 (600528) and CPT2 (600650) were decreased, but no mutations were found in these genes. Additional functional studies were not performed. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Poor growth (in some patients) ABDOMEN Liver \- Hepatomegaly \- Hepatic steatosis \- Hepatic fibrosis \- Septal formation \- Abnormal liver enzymes Spleen \- Splenomegaly (in some patients) LABORATORY ABNORMALITIES \- Hypertriglyceridemia, transient \- Abnormal liver enzymes \- Increased urinary dicarboxylic acid, transient \- Increased serum cholesterol (in 3 of 10 patients) \- Abnormal serum lipoprotein levels (in 3 of 10 patients) MISCELLANEOUS \- Onset in infancy \- Serum triglycerides decrease with age \- Liver enzymes decrease with age MOLECULAR BASIS \- Caused by mutation in the glycerol-3-phosphate dehydrogenase 1 gene (GPD1, 138420.0001 ) ▲ 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	HYPERTRIGLYCERIDEMIA, TRANSIENT INFANTILE	c3280953	5,990	omim	https://www.omim.org/entry/614480	2019-09-22T15:55:08	{"omim": ["614480"], "orphanet": ["300293"], "synonyms": ["Transient infantile hypertriglyceridemia and fatty liver"]}
A rare genetic syndrome with a central nervous system malformation as a major feature, characterized by a triad of high alpha-fetoprotein levels in both maternal serum and amniotic fluid, cerebral ventriculomegaly, and renal macro- and microcysts. Variable findings include congenital nephrotic syndrome, aqueductal stenosis, gray matter heterotopias, and cardiac 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	Ventriculomegaly-cystic kidney disease	c1857423	5,991	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443988	2021-01-23T17:02:32	{"mesh": ["C565657"], "omim": ["219730"], "umls": ["C1857423"], "synonyms": ["Congenital nephrosis-cerebral ventriculomegaly syndrome", "VMCKD"]}
## Clinical Features Van Royen-Kerkhof et al. (1998) reported a nonconsanguineous family of Indonesian and white Dutch ancestry in which 2 brothers had a Joubert (see 213300)-like syndrome, and 1 of the brothers and a sister also had type I Gaucher disease (230800). Joubert syndrome was initially diagnosed in the proband based on the presence of episodic hyperpnea/apnea, agenesis of the cerebellar vermis and corpus callosum, hydrocephalus, and chorioretinal coloboma. Severely delayed psychomotor development and generalized seizures were major clinical features until death at 4 years of age. Postmortem lysosomal enzyme studies unexpectedly showed severe deficiency of glucocerebrosidase activity in cultured skin fibroblasts, and he was found to be compound heterozygous for the most common glucocerebrosidase mutations in the Netherlands, N370S (606463.0003) and L444P (606463.0001). His younger sister, who had mental retardation and autistic behavior with a normal MRI of the brain at 7 years of age, was also found to have Gaucher disease. The proband's younger brother, who 'fulfilled the diagnostic criteria' for Joubert syndrome, died at 8 months of age. Kroes et al. (2005) restudied the family reported by Van Royen-Kerkhof et al. (1998), which then included 2 more sibs, both born after artificial donor insemination: a healthy girl and a third affected boy. The boy had hydrocephalus and a Dandy-Walker malformation on prenatal ultrasound, confirmed by MRI which also showed an abnormally smooth cortical surface; the infant died immediately after delivery. Autopsy showed macrocephaly, slight frontal bossing, and low-set, posteriorly rotated ears. Eyes were not examined. There was aberrant origin of the right subclavian artery, 13 ribs on both sides, and Meckel diverticulum. Examination of the brain showed severe hydrocephalus, absent cerebellar vermis with a cyst-like structure in the posterior fossa, and a wide fourth ventricle. There was no separation of brainstem structures, and the medulla oblongata was abnormally shaped with dorsoventral flattening and absent posterior raphe. Histologic examination showed loss of Purkinje cells in the cerebellar hemispheres and cerebellar cortical dysplasia, with focal disorganization of the upper cortical layers of the cerebral cortex and extensive leptomeningeal heterotopia. Kroes et al. (2005) stated that on the basis of brain anomalies alone, it was not certain that the 3 cases represented the same disorder, although the pedigree was suggestive of X-linked inheritance. The authors concluded that the phenotype was distinct from Joubert syndrome, citing the absence of the molar tooth sign and the presence of additional supratentorial brain malformations, and proposed the designation 'X-linked cerebral-cerebellar-coloboma syndrome.' INHERITANCE \- X-linked recessive HEAD & NECK Head \- Hydrocephalus \- Macrocephaly Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Chorioretinal coloboma CARDIOVASCULAR Vascular \- Aberrant origin of right subclavian artery RESPIRATORY \- Hyperpnea, periodic Apnea, periodic CHEST Ribs Sternum Clavicles & Scapulae \- Thirteen ribs ABDOMEN Gastrointestinal \- Meckel diverticulum NEUROLOGIC Central Nervous System \- Hydrocephalus \- Hypotonia \- Agenesis or severe hypoplasia of cerebellar vermis \- Agenesis of corpus callosum \- Severely delayed psychomotor development \- Seizures \- Enlarged lateral ventricles \- Open Sylvian fissures \- Misshapen posterior fossa MISCELLANEOUS \- One family reported (as of November 2011) ▲ 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	CEREBRAL-CEREBELLAR-COLOBOMA SYNDROME, X-LINKED	c3275487	5,992	omim	https://www.omim.org/entry/300864	2019-09-22T16:19:20	{"omim": ["300864"], "orphanet": ["163961"], "synonyms": ["X-linked intellectual disability, Kroes type"]}
Pyruvate carboxylase deficiency Other namesLeigh necrotizing encephalopathy due to pyruvate carboxylase deficiency[1] SpecialtyEndocrinology Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid to accumulate in the blood.[2] High levels of these substances can damage the body's organs and tissues, particularly in the nervous system. Pyruvate carboxylase deficiency is a rare condition, with an estimated incidence of 1 in 250,000 births worldwide. Type A of the disease appears to be much more common in some Algonkian Indian tribes in eastern Canada, while the type B disease is more present in European populations.[3] ## Contents * 1 Genetics * 2 Diagnosis * 2.1 Classification * 2.1.1 Type A * 2.1.2 Type B * 2.1.3 Type C * 3 Treatment * 4 References * 5 External links ## Genetics[edit] Pyruvate carboxylase deficiency has an autosomal recessive pattern of inheritance. Mutations in the PC gene cause pyruvate carboxylase deficiency. The PC gene provides instructions for making an enzyme called pyruvate carboxylase. This enzyme is active in mitochondria, which are the energy-producing centers within cells. It is involved in several important cellular functions including the generation of glucose, a simple sugar that is the body's main energy source. Pyruvate carboxylase also plays a role in the formation of the protective sheath that surrounds certain nerve cells (myelin) and the production of brain chemicals called neurotransmitters. Mutations in the PC gene reduce the amount of pyruvate carboxylase in cells or disrupt the enzyme's activity. The missing or altered enzyme cannot carry out its essential role in generating glucose, which impairs the body's ability to make energy in mitochondria. Additionally, a loss of pyruvate carboxylase allows potentially toxic compounds such as lactic acid and ammonia to build up and damage organs and tissues. Researchers suggest that the loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, also contributes to the neurologic features of pyruvate carboxylase deficiency. This condition is inherited in an autosomal recessive pattern, which means two copies of the gene must be inherited for the disorder to be present. The parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene, but do not show signs and symptoms of the disorder. ## Diagnosis[edit] ### Classification[edit] Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms. #### Type A[edit] Type A, which has been identified mostly in people from North America, has moderately severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food. Children with pyruvate carboxylase deficiency type A typically survive only into early childhood. #### Type B[edit] Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth. #### Type C[edit] This type is characterised by its late onset and is associated with isolated mild intellectual delay. ## Treatment[edit] Pyruvate carboxylase deficiency treatment typically consists of providing the body with alternate sources of energy (anaplerotic therapy), such as a diet rich in proteins and carbohydrates but not lipids. ## References[edit] 1. ^ "Pyruvate carboxylase deficiency \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 April 2019. 2. ^ "Pyruvate carboxylase deficiency". MedlinePlus. NIH - U.S. National Library of Medicine. Retrieved 29 November 2020. 3. ^ "Pyruvate Carboxylase Deficiency". ## External links[edit] Classification D * ICD-10: E74.4 * ICD-9-CM: 271.8 * OMIM: 266150 * MeSH: D015324 * DiseasesDB: 7378 External resources * eMedicine: med/1979 ped/1967 * GeneReview/NCBI/NIH/UW entry on Pyruvate Carboxylase Deficiency * Pyruvate carboxylase deficiency at NLM Genetics Home Reference This article incorporates text from this source, which is in the public domain. * v * t * e Mitochondrial diseases Carbohydrate metabolism * PCD * PDHA Primarily nervous system * Leigh disease * LHON * NARP Myopathies * KSS * Mitochondrial encephalomyopathy * MELAS * MERRF * PEO No primary system * DAD * MNGIE * Pearson syndrome Chromosomal * OPA1 * Kjer's optic neuropathy * SARS2 * HUPRA syndrome * TIMM8A * Mohr–Tranebjærg syndrome see also mitochondrial proteins * v * t * e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders Including glycogen storage diseases (GSD) Sucrose, transport (extracellular) Disaccharide catabolism * Congenital alactasia * Sucrose intolerance Monosaccharide transport * Glucose-galactose malabsorption * Inborn errors of renal tubular transport (Renal glycosuria) * Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose: * Essential fructosuria * Fructose intolerance Galactose / galactosemia: * GALK deficiency * GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis * GSD type 0 (glycogen synthase deficiency) * GSD type IV (Andersen's disease, branching enzyme deficiency) * Adult polyglucosan body disease (APBD) Glycogenolysis Extralysosomal: * GSD type III (Cori's disease, debranching enzyme deficiency) * GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency) * GSD type V (McArdle's disease, myophosphorylase deficiency) * GSD type IX (phosphorylase kinase deficiency) Lysosomal (LSD): * GSD type II (Pompe's disease, glucosidase deficiency) Glucose ⇄ CAC Glycolysis * MODY 2/HHF3 * GSD type VII (Tarui's disease, phosphofructokinase deficiency) * Triosephosphate isomerase deficiency * Pyruvate kinase deficiency Gluconeogenesis * PCD * Fructose bisphosphatase deficiency * GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency) Pentose phosphate pathway * Glucose-6-phosphate dehydrogenase deficiency * Transaldolase deficiency * 6-phosphogluconate dehydrogenase deficiency Other * Hyperoxaluria * Primary hyperoxaluria * Pentosuria * Aldolase A 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	Pyruvate carboxylase deficiency	c2931141	5,993	wikipedia	https://en.wikipedia.org/wiki/Pyruvate_carboxylase_deficiency	2021-01-18T18:35:52	{"gard": ["7512"], "mesh": ["C536255", "D015324"], "umls": ["C2931141"], "icd-9": ["271.8"], "orphanet": ["3008"], "wikidata": ["Q7263794"]}
Nematode dermatitis SpecialtyDermatology Nematode dermatitis is a cutaneous condition characterized by widespread folliculitis caused by Ancylostoma caninum.[1]:435 ## See also[edit] * 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. This infection-related 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	Nematode dermatitis	None	5,994	wikipedia	https://en.wikipedia.org/wiki/Nematode_dermatitis	2021-01-18T18:57:09	{"wikidata": ["Q6991009"]}
A partial deletion of the long arm of chromosome 4 characterized by complex behavioral difficulties, developmental and delay/ intellectual disability, and minor dysmorphic features, including subtle facial asymmetry (most prominent in the mandible), mild hypotelorism, long nasal bridge, small low-set ears, narrow mouth, and mild hand deformities, such as bilateral short 5th metacarpals, and short hands. [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	4q25 proximal deletion syndrome	None	5,995	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=502437	2021-01-23T19:07:56	{"synonyms": ["Proximal del(4)(q25)", "Proximal monosomy 4q25"]}
Primary angiitis of the central nervous system is a rare form of vasculitis (inflammation of blood vessels) affecting the blood vessels that nourish the brain, spinal cord and peripheral nerves. This condition can lead to narrowing and blockage of the blood vessels of the central nervous system which can eventually cause aneurysms, ischemia and/or hemmorrhage. The cause of this condition is unknown. Signs and symptoms of this condition may begin suddenly or develop over time. Some of the symptoms may incude headaches that do not go away, fever, rapid weight loss, confusion or forgetfulness, and general malaise. Treatment for this condition involves a course of immunosuppresive steroids. [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	Primary angiitis of the central nervous system	c2930862	5,996	gard	https://rarediseases.info.nih.gov/diseases/8703/primary-angiitis-of-the-central-nervous-system	2021-01-18T17:58:12	{"mesh": ["C535276"], "orphanet": ["140989"], "synonyms": ["PACNS", "Primary central nervous system vasculitis", "Primary CNS vasculitis", "Granulomatous angiitis of the central nervous system"]}
For the 1970s rock band Piblokto!, see Pete Brown. Piblokto, also known as pibloktoq and Arctic hysteria, is a condition most commonly appearing in Inughuit (Greenlandic Inuit) societies living within the Arctic Circle. Piblokto is a culture-specific hysterical reaction in Inuit, especially women, who may perform irrational or dangerous acts, followed by amnesia for the event. Piblokto may be linked to repression of the personality of Inuit women.[1] The condition appears most commonly in winter.[2] It is considered to be a form of a culture-bound syndrome, although more recent studies (see Skepticism section) question whether it exists at all. Piblokto is also part of the glossary of cultural bound syndromes found in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).[3] ## Contents * 1 History * 2 Origin * 3 Symptoms * 4 Causes * 5 Skepticism * 6 See also * 7 Notes * 8 References * 9 Further reading ## History[edit] Piblokto was first documented in 1892 and reports by European explorers describe the phenomenon as common to all Arctic regions. Explorers were the first to record piblokto in writing. Among these, Admiral Robert Peary provided a detailed look into the disorder during an expedition to Greenland. The acts Peary and his men witnessed among the Inuit women provided entertainment,[citation needed] and, having sent the women's male counterparts out on missions, Peary's men reaped the sexual benefits of being the only males present.[citation needed][4] Piblokto is not limited to the indigenous people; reports of stranded sailors during the 1800s exhibiting the same symptoms have been found. The disorder is said to have existed before Western contact and still occurs today.[5] However, as discussed below, many scholars now hold that culture bound disorders may often be an artifact of colonial encounters, and contemporary discussions of piblokto in medical anthropology and cross-cultural psychiatry consider it to be an example of the suspect nature of culture bound syndromes.[6] ## Origin[edit] Piblokto is most often found in but not confined to the Inughuit culture in the polar regions of northern Greenland. Similar symptoms have been reported in European sailors stranded in Arctic regions in the 1800s. Among the Inughuit, the attacks are not considered out of the ordinary. No native theory of the disorder is currently reported. This condition is most often seen in Inughuit women.[7] Piblokto is most common during long Arctic nights.[8] ## Symptoms[edit] Piblokto is an abrupt dissociative episode with four phases: social withdrawal, excitement, convulsions and stupor, and recovery.[9] In his book Handbook of Cultural Psychiatry, Wen-Shing Tseng provides the following example adapted from Foulks:[10] > Mrs. A is a 30-year-old woman who has had periodic episodes of "strange experiences" in the past 3 years (since her mother's death). Three years ago, in the winter, during her first episode, she was acutely assaultive and tried to harm herself. The attack lasted about 15 min and she remembered nothing about it afterward. Two years ago, she had her second attack, which lasted about half an hour, during which time she ran from her home into the snow, tearing off her clothing. ## Causes[edit] Although there is no known cause for piblokto, Western scientists have attributed the disorder to the lack of sun, the extreme cold, and the desolate state of most villages in the region. A reason for this disorder present in this culture may be due to the isolation of their cultural group.[11] This culture-bound syndrome is possibly linked to vitamin A toxicity (hypervitaminosis A).[12][13] The native Inughuit diet or Eskimo nutrition provides rich sources of vitamin A through the ingestion of livers, kidneys, and fat of arctic fish and mammals and is possibly the cause or a causative factor. This causative factor is through the disturbance that has been reported for males, females, adults, children, and dogs.[14] The ingestion of organ meats, particularly the livers of some Arctic mammals, such as the polar bear and bearded seal, where the vitamin is stored in toxic quantities, can be fatal to most people. Inughuit tradition states that it is caused by evil spirits possessing the living. Shamanism and animism are dominant themes in Inughuit traditional beliefs with the angakkuq (healer) acting as a mediator with the supernatural forces. Angakkuit use trance states to communicate with spirits and carry out faith healing. There is a view among the Inughuit that individuals entering trance states should be treated with respect given the possibility of a new "revelation" emerging as a result. Treatment in piblokto cases usually involves allowing the episode to run its course without interference. While piblokto can often be confused with other conditions, (including epilepsy) in which failure to intervene can lead to the victim coming to harm, most cases tend to be more typical. ## Skepticism[edit] Although piblokto has a place in the historical record and official medical canons, a number of Arctic researchers and Arctic residents doubt its existence. The phenomenon, they suggest, may be more rooted in the experience and behavior of the early European explorers than the Inuit themselves.[11] In 1988 Parks Canada historian Lyle Dick began a substantial challenge to the concept that piblokto exists at all. Dick examined the original records of the European Arctic explorers, and ethnographic and linguistic reports on Inughuit societies, and discovered that not only is the majority of academic speculation into piblokto based on reports of only eight cases, but the word "piblokto" / "pibloktoq" does not exist within Inuktun (the Inughuit language); possibly, Dick concluded, this may have been the result of errors in phonetic transcription. In a 1995 paper published in the journal Arctic Anthropology,[15] and in his 2001 book Muskox land: Ellesmere Island in the Age of Contact, Dick suggests that piblokto is a "phantom phenomenon", arising more from the Inuhuit reaction to European explorers in their midst.[11] Similarly, Hughes and Simons have described piblokto as a "catch-all rubric under which explorers lumped various Inuhuit anxiety reactions, expressions of resistance to patriarchy or sexual coercion, and shamanistic practice".[16] Simply put, rather than understanding piblokto as a strange cultural phenomenon, some critical scholars now understand it to be an expression of trauma of colonial violence, including rape. For example, transcultural psychiatry scholar Laurence Kirmayer writes: > Most comprehensive psychiatric texts mention pibloktoq as a culture-bound syndrome characterized by sudden wild and erratic behaviour. Recently, the historian Lyle Dick collected all the published accounts of pibloktoq, of which there are only about 25. It seems that psychiatric case description transformed a situation of sexual exploitation of Inuit women by explorers into a discrete disorder worthy of a new diagnostic label. With hindsight, we can see how insensitivity to the impact of exploration on other peoples distorted the picture when vital information on social context was not included. The legacy of these colonialist blinkers is still with us ...[17] ## See also[edit] * Wendigo * Cabin fever * Kayak angst * Prairie madness * Menerik (ru) (sometimes meryachenie[Note 1]) – a condition similar to piblokto found in Siberia among Yakuts, Yukagirs, and Evenks. Sidorov and Davydov draw a distinction between piblokto-like menerik and latah-like meryachenie.[18] Others use meryachenie as an umbrella term for both piblokto-like and latah-like states. * Culture-bound syndrome ## Notes[edit] 1. ^ Also spelled as meriachenie, meryacheniye, meryachenye, meriachen'e, meryachen'e, meriachenye, as well as emiryachenie, emiryachenye, emiriachen'e, emeryachenye, emeriachen'e, emiryachen'e, emiriachenie, emeryachenie. ## References[edit] 1. ^ Segen's Medical Dictionary. (2012). Farlex, Inc. Pibloktoq 2. ^ Taylor, S., Shelor, N., & Abdelnour, M. (1972). Nutritional ecology: a new perspective. 3. ^ Mezzich JE (2002). "International surveys on the use of ICD-10 and related diagnostic systems". Psychopathology. 35: 72–5. doi:10.1159/000065122. PMID 12145487.. 4. ^ Wallace, Anthony F. C.; Ackerman, Robert E. (1960). "An Interdisciplinary Approach to Mental Disorder among the Polar Eskimos of Northwest Greenland". Anthropologica. 2 (2): 249–260. doi:10.2307/25604472. 5. ^ Lister, J. "Two Perspectives on the Etiology of Pibloktoq". Archived from the original on 2015-02-20. 6. ^ Nakamura, Karen (2013). A Disability of the Soul: An Ethnography of Disability and Mental Illness in Contemporary Japan. Cornell University Press. p. 98. ISBN 978-0-8014-5192-8. 7. ^ Ruiz, P. (2007). "Focusing on Culture and Ethnicity in America" (PDF). Archived from the original (PDF) on 2012-03-26. 8. ^ Brill, A. (1913). "Piblokto or Hysteria Among Peary's Eskimos". Journal of Nervous and Mental Disease. 40 (8): 514–520. 9. ^ Fulk, M. (2012) Pibloktoq. 10. ^ Tseng, Wen-Shing (2001-06-06). Handbook of Cultural Psychiatry. Academic Press. p. 244. ISBN 9780127016320. 11. ^ a b c Ephron, Sarah. (July/August 2003) Arctic Hysteria, from Up Here Magazine; archived at SarahEfron.com 12. ^ Kontaxakis V., Skourides D., Ferentinos P., Havaki-Kontaxaki B., Papadimitriou G. (2009). "Isotretinoid and Psychopathology: A Review". Annals of General Psychiatry. 8: 2. doi:10.1186/1744-859X-8-2. PMC 2637283. PMID 19154613.CS1 maint: multiple names: authors list (link) 13. ^ Smith, S. (2012, December 6). What is Piblokto? wiseGEEK: clear answers for common questions. Retrieved March 29, 2013. 14. ^ Landy D (1985). "Pibloktoq (hysteria) and Inuit nutrition: possible implication of hypervitaminosis A". Soc Sci Med. 21: 173–85. doi:10.1016/0277-9536(85)90087-5. PMID 4049004. 15. ^ Dick, L (February 1995). "'Pibloktoq' (Arctic Hysteria): A construction of European-Inuit relations". Arctic Anthropology. 32 (2): 2. JSTOR 40316385. 16. ^ Simons, R. C.; Hughes, C. C. (1985). The culture-bound syndromes: folk illnesses of psychiatric and anthropological interest. Holland: D. Reidel. pp. 275, 289. ISBN 90-277-1858-X. 17. ^ Kirmayer, L. J. (2007). "Cultural psychiatry in historical perspective". Textbook of cultural psychiatry. Cambridge University Press. pp. 3–19. ISBN 978-0-521-85653-9. 18. ^ Sidorov, P. I.; Davydov, A. N. (1992). "Ethnopsychiatric research in the national minorities of Northern Russia and Siberia". Bekhterev Review of Psychiatry and Medical Psychology. Washington. ISBN 0-88048-667-8. ISSN 1064-6930. ## Further reading[edit] * Landy D (1985). "Pibloktoq (hysteria) and Inuit nutrition: possible implication of hypervitaminosis A". Soc Sci Med. 21 (2): 173–85. doi:10.1016/0277-9536(85)90087-5. PMID 4049004. * Parker, S (1962). "Eskimo psychopathology in the context of Eskimo personality and culture". American Anthropologist. 64: 76–96. doi:10.1525/aa.1962.64.1.02a00080. * Higgs, Rachel D. (2011) "Pibloktoq - A study of a culture-bound syndrome in the circumpolar region," The Macalester Review: Vol. 1: Iss. 1, Article 3. [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	Piblokto	c0270604	5,997	wikipedia	https://en.wikipedia.org/wiki/Piblokto	2021-01-18T18:56:34	{"icd-10": ["F44.88", "F44.7"], "wikidata": ["Q1779438"]}
## Description Congenital laryngeal (glottic) webs are uncommon, membrane-like structures that extend across the laryngeal lumen near the level of the vocal cords. They are thought to result from incomplete resorption of an epithelial layer that normally obliterates the developing laryngeal opening at about the sixth week of embryologic life. This layer is usually completely eliminated by the tenth week. Most laryngeal webs occur at the glottic level and affect the vocal cords. More than 90% are located anteriorly and extend toward the arytenoids. While affected persons may have onset of manifestations at any age, with hoarse or weak voice and frequent upper respiratory infections, they usually manifest the condition as infants, with respiratory distress, stridor, and an unusual cry (Strakowski et al., 1988; Singh et al., 2009). Clinical Features Cohen (1985) divided laryngeal (glottic) webs into 4 types based on their appearance and an estimation of the degree of airway obstruction. Type 1 glottic webs are uniform in thickness with no subglottic extension; they compromise less than 35% of the airway and there is usually no airway obstruction. Type 2 glottic webs are slightly thicker, with a significantly thicker anterior component. Subglottic involvement is minimal. The web restricts the airway by 35 to 50% and usually causes little airway distress. Type 3 glottic webs are thick; the anterior portion of the web is solid, extends into the subglottis, and the true vocal cords are not well delineated. The web restricts the airway to 50 to 75%, and obstruction is moderately severe. Type 4 glottic webs are uniformly thick and extend into the subglottic area with resulting subglottic stenosis, occluding 75 to 90% of the airway. Respiratory obstruction is severe, and the patient is almost always aphonic (summary by Singh et al., 2009). Howie et al. (1961) described subglottic bar in a grandfather, mother, and 2 daughters (4 persons in 3 generations). Severe dyspnea with respiratory infection in a 6-year-old brought the condition to attention. All 4 had a harsh, quivering, high-pitched, weak voice and 3 had suffered from respiratory distress with inspiratory stridor. Imperfect adduction of the vocal cords was an associated finding. Inheritance Strakowski et al. (1988) found fewer than 10 reported families with laryngeal webs, 6 of which were reported before 1910. Strakowski et al. (1988) described 5 affected individuals in 3 generations of a family and suggested autosomal dominant inheritance. Three of the 5 were males, but there was no instance of male-to-male transmission. Cytogenetics Laryngeal web associated with deletions and microdeletions of 22q11.2, with or without signs of the velocardiofacial syndrome (192430) or DiGeorge syndrome (188400), was noted by Gay et al. (1981), Driscoll et al. (1992), Lindsay et al. (1995), and Fokstuen et al. (1997). Fokstuen et al. (1997) observed type III laryngeal atresia (glottic web) in 3 patients with 22q11.2 microdeletion. One patient showed a 'classic' 22q11.2 deletion phenotype with clinical overlap with DiGeorge syndrome and velocardiofacial syndrome. However, the pattern of congenital anomalies in the 2 others was less specific, heart defects and minor anomalies being the only outstanding clinical manifestations suspicious for monosomy 22q11.2. Fokstuen et al. (1997) suggested that laryngeal atresia represents an additional malformation that should prompt investigation of the 22q11.2 deletion, especially in combination with congenital heart defects. Stoler et al. (1998) reported a laryngeal web in 2 additional children with 22q11 deletions. Marble et al. (1998) evaluated a mother and son, both of whom had congenital subglottic web and 22q11.2 deletion. The son, a neonate, had interrupted aortic arch, small ears, downsloping palpebral fissures, and micrognathia, as well as hypocalcemia. The mother had had a weak cry neonatally and hoarseness of the voice during early childhood. Subglottic web was discovered at the age of 4 years and was excised, leading to significant improvement in her voice but some residual hoarseness. Her serum calcium was normal. Resp \- Congenital anterior laryngeal (glottic) web \- Frequent upper respiratory infections \- Respiratory distress \- Stridor Voice \- Hoarse or weak voice \- Unusual cry 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	LARYNGEAL WEB, FAMILIAL	c1835494	5,998	omim	https://www.omim.org/entry/150360	2019-09-22T16:39:04	{"mesh": ["C563636"], "omim": ["150360"], "orphanet": ["2374"], "synonyms": ["Alternative titles", "GLOTTIC WEB, CONGENITAL ANTERIOR", "SUBGLOTTIC WEB", "SUBGLOTTIC BAR"]}
A number sign (#) is used with this entry because of evidence that cataract-48 (CTRCT48) is caused by homozygous mutation in the DNMBP gene (611282) on chromosome 10q24. Description Cataract-48 (CTRCT48) is characterized by infantile or early-childhood cataracts and visual impairment (Ansar et al., 2018). Clinical Features Ansar et al. (2018) reported 12 patients from 3 unrelated consanguineous Pakistani families with bilateral infantile or early childhood cataracts. Other ocular features included exotropia, bilateral amblyopia, distorted or constricted pupils, divergent squint, and pendular nystagmus. Electroretinography (ERG) performed in 5 patients showed grossly normal responses in 3 of them, but in 1 patient (family F385) photopic responses were reduced and in another (family F372), both photopic and scotopic responses were reduced. Molecular Genetics In 11 affected individuals from 2 unrelated Pakistani families (F385 and F372) with infantile or early-childhood cataracts, Ansar et al. (2018) performed whole-exome sequencing and identified homozygosity for a nonsense mutation (R271X; 611282.0001) and a 2-bp deletion (611282.0002) in the DNMBP gene, respectively. Each mutation segregated with disease in the family, and neither was found in 240 local controls or in the gnomAD database. In a 4-year-old girl with early childhood cataract from a third Pakistani family (F3), who was negative for mutation in 115 known cataract-related genes, they identified homozygosity for a 4-bp deletion in DNMBP (611282.0003). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Reduced vision at birth \- Bilateral cataracts \- Exotropia \- Bilateral amblyopia \- Divergent squint \- Pendular nystagmus \- Distorted pupils \- Constricted pupils \- Reduced scotopic and/or photopic responses on electroretinography (in some patients) MISCELLANEOUS \- Onset of cataracts in infancy or early childhood MOLECULAR BASIS \- Caused by mutation in the dynamin-binding protein gene (DNMBP, 611282.0001 ) ▲ 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	CATARACT 48	None	5,999	omim	https://www.omim.org/entry/618415	2019-09-22T15:42:02	{"omim": ["618415"]}

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