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For a general phenotypic description and a discussion of primary congenital glaucoma (PCG), see GLC3A (231300). Mapping In a 5-generation consanguineous Turkish family with PCG unlinked to both congenital glaucoma loci GLC3A and GLC3B (600975), Stoilov and Sarfarazi (2002) used genomewide screening, saturation mapping, and haplotype analysis including markers D14S61 and D14S1000 to identify a region of homozygosity defined by markers D14S42, D14S983, D14S1020 and D14S74 in all affected individuals. All markers segregated perfectly with the disease phenotype. The data suggested that a PCG locus (GLC3C) is located on chromosome 14q24.3 within a region of 2.9 cM that is flanked by markers D14S61 and D14S1000. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	GLAUCOMA 3, PRIMARY CONGENITAL, C	c0020302	2,700	omim	https://www.omim.org/entry/613085	2019-09-22T15:59:50	{"doid": ["0050593"], "mesh": ["D006871"], "omim": ["613085"], "orphanet": ["98976"], "genereviews": ["NBK1135"]}
Wikipedia does not currently have an article on bathophobia, but our sister project Wiktionary does: Read the Wiktionary entry on bathophobia You can also: * Search for Bathophobia in Wikipedia to check for alternative titles or spellings. * Start the Bathophobia article, using the Article Wizard if you wish, or add a request for it; but please remember Wikipedia is not a dictionary. wiktionary:Special:Search/bathophobia From a cross-project redirect: This is a redirect that is used as a connection to other Wikimedia projects. A Wikidata element is linked to this page: Bathophobia (Q6898244). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Bathophobia	c1389284	2,701	wikipedia	https://en.wikipedia.org/wiki/Bathophobia	2021-01-18T18:48:01	{"wikidata": ["Q6898244"]}
A number sign (#) is used with this entry because of evidence that stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is caused by homozygous mutation in the ADPRHL2 gene (610624) on chromosome 1p34. Description Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. Patient have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy (summary by Ghosh et al., 2018). Clinical Features Ghosh et al. (2018) reported 6 unrelated families, 5 of which were determined to be consanguineous and 1 with parents who originated from the same small village in Sicily, with a neurodegenerative disorder apparent in childhood after normal early development with some speech and motor acquisition. In most cases, the neurodegeneration was associated with a physiologic stress, such as infection or seizures. The most severely affected family (family 1) included 9 children from the United Arab Emirates, 7 of whom died between 2 and 15 years of age. All patients in this family presented with seizures between 1 and 2 years of age, followed by developmental stagnation and loss of milestones. A detailed history of one of the patients noted that he had cyclic episodes of depressed consciousness and hypoventilation with further loss of milestones. Additional features in this patient included type II fiber atrophy on muscle biopsy, axonal loss on nerve biopsy, and cerebral and cerebellar atrophy. He ultimately required a ventilator and feeding tube and died of respiratory failure at age 9 years. Several other affected children in this family died suddenly during normal activities, such as eating, playing, or sleeping. Seven additional patients from 5 families were subsequently identified. These patients ranged from 2 to 16 years of age; 1 had died in his sleep at age 6. Three of these patients developed generalized multifocal seizures in the first years of life, but 4 patients did not have seizures. Notably, in 1 family (family 4), 1 sib had seizures and the other sib did not. These patients had cerebellar signs with ataxia, dysarthria, dysmetria, tremor, and abnormal eye movements such as strabismus, nystagmus, hypometric saccades, and external ophthalmoplegia, suggesting brainstem dysfunction. Less common features included type II fiber atrophy and fiber type variation on skeletal muscle biopsy, extensor plantar responses, muscle weakness, tongue fasciculations, hearing loss, and axonal or demyelinating sensorimotor polyneuropathy. Most patient had mild global developmental delay with mildly delayed intellectual development, although 1 had patient had normal cognition at age 15. Most patients had cerebellar atrophy on brain imaging; some had spinal cord atrophy and nonspecific white matter abnormalities. Danhauser et al. (2018) reported 12 patients from 8 unrelated families, 4 of which were consanguineous, with CONDSIAS. The patients ranged from 22 months to 32 years of age, and 7 had died between 1 and 30 years of age. Following early normal development, most patients presented in the first years of life with developmental delay or speech delay, although a few patients presented late in the first decade. The patients had episodic infection- or stress-associated neurologic deterioration affecting motor and cognitive function. Features included gait disturbances, ataxia, dystonic posturing, muscle weakness, hypotonia, facial grimacing, and respiratory insufficiency sometimes requiring mechanical ventilation. Many showed developmental regression and loss of ambulation, as well as variable cognitive decline and dysarthria. Five patients had ophthalmologic abnormalities, such as visual impairment, nystagmus, or strabismus, 1 had sensorineural hearing loss, 6 had seizures, and 8 had cerebellar atrophy on brain imaging. Electrophysiologic testing showed an axonal polyneuropathy in 6 patients. Other more variable features included acquired microcephaly and short stature. Inheritance The transmission pattern of CONDSIAS in the families reported by Ghosh et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In affected individuals from 6 unrelated mostly consanguineous families with CONDSIAS, Ghosh et al. (2018) identified homozygous mutations in the ADPRHL2 gene (610624.0001-610624.0006). There were 2 nonsense mutations, 1 frameshift mutation, and 3 missense mutations affecting highly conserved residues in the ADP-ribosyl-glycohydrolase domain. The mutations, which were found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Expression of one of the nonsense mutations (Q334X; 610624.0001) in E. coli resulted in no detectable protein, and analysis of patient cells showed absence of the protein, consistent with a complete loss of function. Expression of one of the missense mutations (T79P; 610624.0003) in E. coli showed that it caused protein destabilization, suggesting that the missense mutations can have a loss-of-function effect. Further functional studies of the variants and studies of patient cells were not performed. Ghosh et al. (2018) suggested that accumulation of poly-ADP ribose (PAR) or failure of reversal of PAR modification could trigger a cell-death response cascade, resulting in progressive neurodegeneration. In patients from 8 unrelated families with CONDSIAS, Danhauser et al. (2018) identified 5 different homozygous mutations in the ADPRHL2 gene (see, e.g., 610624.0007 and 610624.0008). There was 1 missense mutation (V335G; 610624.0007), 1 nonsense, 2 frameshift, and a splice site mutation. The mutations, which were found by exome sequencing, segregated with the disorder in the families. Fibroblasts derived from 2 unrelated patients showed undetectable ADPRHL2 protein as well as impaired cellular removal of ADP-ribose, accumulation of PAR, and reduced viability compared to wildtype when stressed with hydrogen peroxide. The reduced viability and PAR accumulation could be rescued with wildtype ADPRHL2 and with a PARP1 (173870) inhibitor. These findings were consistent with the mutations causing a loss of function and implicated disturbed posttranslational protein ADP-ribosylation as a pathogenetic mechanism. Animal Model Ghosh et al. (2018) demonstrated that knockdown of the Drosophila ADPRHL2 paralog, Parg, resulted in decreased fly survival under oxidative conditions with a similar detrimental effect on neuronal survival when expressed in neurons. Flies with a partially inactivated Parg could survive, but showed progressive neurodegeneration, reduced locomotion, and a reduced lifespan. Expression of wildtype Parg and wildtype human ADPRHL2 rescued the phenotype. Treatment of mutant flies with minocycline, which inhibits PARP (PARP1; 173870) activity, resulted in a dose-dependent rescue of the phenotype. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss (in some patients) Eyes \- Nystagmus \- Abnormal saccades \- Ophthalmoplegia \- Strabismus \- Ptosis Mouth \- Tongue fasciculations MUSCLE, SOFT TISSUES \- Muscle weakness \- Type II fiber atrophy \- Fiber size variation NEUROLOGIC Central Nervous System \- Neurodegeneration after normal early development \- Developmental regression \- Loss of acquired motor milestones \- Ataxia \- Balance problems \- Poor speech \- Dysarthria \- Dysmetria \- Tremor \- Impaired intellectual development \- Seizures (in some patients) \- Extensor plantar responses \- Cerebellar atrophy \- Spinal cord atrophy \- Cerebral atrophy \- Nonspecific white matter abnormalities Peripheral Nervous System \- Sensorimotor axonal or demyelination neuropathy \- Axonal loss Behavioral Psychiatric Manifestations \- Autistic features MISCELLANEOUS \- Onset in first years of life after normal early development \- Episodic deterioration associated with stress or fever \- Sudden death in childhood may occur \- Highly variable severity and features MOLECULAR BASIS \- Caused by mutation in the ADP-ribosylhydrolase-like 2 gene (ADPRHL2, 610624.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	NEURODEGENERATION, CHILDHOOD-ONSET, STRESS-INDUCED, WITH VARIABLE ATAXIA AND SEIZURES	None	2,702	omim	https://www.omim.org/entry/618170	2019-09-22T15:43:18	{"omim": ["618170"]}
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-27 (RP27) is caused by heterozygous mutation in the neural retina leucine zipper gene (NRL; 162080) on chromosome 14q11. One family with a clinical diagnosis of clumped pigment-type retinal degeneration has been reported with compound heterozygous mutation in the NPL gene. For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Clinical Features In a large 3-generation British family (RP251) segregating autosomal dominant retinitis pigmentosa, Bessant et al. (1999) excluded previously identified autosomal dominant loci and identified a heterozygous mutation in the NRL gene (S50T; 162080.0001) in affected members. Bessant et al. (2000) identified 3 other British RP families who carried the same mutation and determined that all 4 families were descended from a common founder. In all 4 families the phenotype was fully penetrant and exhibited only limited variability. Early severe loss of rod function with preserved cone function and a very high incidence of macular edema were the characteristic features. To further define the phenotype associated with the NRL S50T mutation, Bessant et al. (2003) performed detailed clinical, electrophysiologic, and psychophysical studies of 25 members of the original family (14 affected members, 7 unaffected, and 4 spouses). They also obtained information from clinical records for 8 individuals from the 3 families identified by Bessant et al. (2000). Bessant et al. (2003) identified 7 characteristic features of the phenotype that in combination would suggest an underlying NRL mutation. The S50T mutation causes a severe progressive retinal dystrophy affecting first the rod and subsequently the cone photoreceptors. While rod function is profoundly impaired in the first 2 decades of life, cone function remains relatively well preserved at this stage. Significant loss of cone function occurs as the disorder progresses, and in older individuals, all components of the electroretinogram are nondetectable. Patients almost invariably develop macular thickening, frequently with a mild reduction in visual acuity, between ages 15 and 30 years. As the disease progresses, a substantial loss of visual acuity is usually observed, typically in association with the development of a bull's-eye pattern of macular atrophy. Peripheral intraretinal pigment formation is sparse, even in the later stages of the disease. Distinctive peripapillary chorioretinal atrophy develops as the dystrophy progresses. ### Clinical Variability Nishiguchi et al. (2004) reported 2 sibs with a clinical diagnosis of autosomal recessive retinal degeneration of the clumped pigment type who carried compound heterozygous mutations in the NRL gene (see MOLECULAR GENETICS). Both sibs had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium. Mapping Using linkage analysis, Bessant et al. (1999) mapped the retinitis pigmentosa phenotype in their family RP251 to chromosome 14q11, with a maximum lod score of 5.72 (theta = 0.0) at marker D14S64. Molecular Genetics In a 3-generation British family with autosomal dominant retinitis pigmentosa, Bessant et al. (1999) identified a heterozygous missense mutation in the NRL gene (S50T; 162080.0001). Bessant et al. (2000) identified the S50T mutation in 3 additional families and showed that all 4 families carrying the mutation were descended from a common founder. In 2 sibs with a clinical diagnosis of retinal degeneration of the clumped pigment type, Nishiguchi et al. (2004) identified compound heterozygous mutations in the NRL gene (224insC, 162080.0002) and (L160P, 162080.0003). Nishiguchi et al. (2004) noted that no humans with an NRL -/- genotype had previously been reported; only dominant NRL mutations that were unlikely to be null alleles had been reported. All of the published dominant NRL mutations were missense changes affecting 1 of 3 residues: ser50, pro51, or gly122. Patients with recessive NRL mutations had features resembling those caused by mutation in the NR2E3 gene (604485), the only previously known cause of enhanced S-cone syndrome (ESCS; 268100) in humans. In addition to the preservation of S-cone function, patients with recessive NR2E3 or NRL mutations have a similar pattern of intraretinal pigmentation of the fundus. This so-called clumped pigmentary retinal degeneration is found in approximately 0.5% of RP cases. Approximately half of all patients with clumped pigmentary retinal degeneration have mutations in the NR2E3 gene and are considered to have enhanced S-cone syndrome. Nishiguchi et al. (2004) concluded that mutations in NRL are a much less common cause of clumped pigmentary retinal degeneration than mutations in NR2E3. Hernan et al. (2012) screened the NRL gene in 50 Spanish autosomal dominant RP probands and identified a heterozygous missense mutation in 1 (M96T; 162080.0004). The proband's mother and a maternal aunt were also heterozygous for the mutation; all 3 developed night blindness in the second or third decade of life, a later onset of disease than previously reported with mutations in the NRL gene. In vitro functional analysis showed that the M96T mutant increased transactivation to a lesser degree than the S50T or P51L (see Martinez-Gimeno et al., 2001) mutant proteins. In addition, the proband's sister and a cousin carried the mutation but remained asymptomatic at ages 37 and 45 years, respectively. Hernan et al. (2012) suggested that the NRL mutation might not be the sole cause of RP in this family; however, analysis of 550 retinal candidate genes by DNA capturing and massive next-generation sequencing did not reveal any other genomic variation that cosegregated with RP in the family. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Night blindness, with onset in first and second decades of life \- Loss of peripheral vision in third and fourth decades of life \- Decreased visual acuity in fourth decade of life \- Pigmentation in retinal periphery \- Optic disc pallor in fourth decade of life \- Macular edema (in some patients) \- Macular atrophy, bull's eye pattern, in fourth decade of life \- Cataract, posterior subcapsular (in some patients) \- Peripapillary chorioretinal atrophy, progressive \- Nondetectable scotopic electroretinogram with relative preservation of photopic and pattern elements in younger patients \- Photopic visual field defects, asymptomatic, demonstrated by static perimetry in second decade of life \- Nondetectable electroretinogram, all components, in older individuals MISCELLANEOUS \- Some patients have milder phenotype with later onset of symptoms, in second to third decades of life MOLECULAR BASIS \- Caused by mutation in the neural retina leucine zipper gene (NRL, 162080.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	RETINITIS PIGMENTOSA 27	c0035334	2,703	omim	https://www.omim.org/entry/613750	2019-09-22T15:57:46	{"doid": ["0110397"], "mesh": ["D012174"], "omim": ["613750"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-18 (CORD18) is caused by homozygous mutation in the RAB28 gene (612994) on chromosome 4p15. For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy (CORD), see 120970. Clinical Features Roosing et al. (2013) studied a German family in which 3 sibs were diagnosed with cone-rod dystrophy in the second decade of life, with rapidly deteriorating visual acuities and high myopia. Funduscopy showed hyperpigmentation of the fovea, and autofluorescence revealed a slightly hyperfluorescent fovea. Optical coherence tomography (OCT) showed altered photoreceptors in the fovea but intact peripheral photoreceptors. Color-vision tests revealed defects in all axes, and visual field testing showed a central scotoma. On electroretinography (ERG), photopic responses were nondetectable and scotopic responses reduced in all 3 sibs. Roosing et al. (2013) also studied a consanguineous family of Moroccan Jewish origin in which a brother and sister with CORD had a presentation similar to that of the sibs from the German family. The brother presented with low vision from early childhood, with progressive deterioration of visual acuity and high myopia. The retinal pigment epithelium showed foveal atrophy; hypofluorescence was observed in the fovea and a hyperfluorescent ring was noted around the fovea. OCT imaging confirmed absence of photoreceptors in the central fovea, whereas the photoreceptor layer further out appeared largely intact. Color-vision defects were noted in both sibs. Photopic ERG responses were nondetectable, and scotopic responses were moderately reduced. Riveiro-Alvarez et al. (2015) reported 2 unrelated patients of Spanish descent with childhood onset of CORD. Both patients had markedly reduced visual acuity, bull's eye maculopathy, foveal hyperpigmentation, peripapillary atrophy, dyschromatopsia, extinguished photopic ERG responses, and reduced scotopic ERG responses. One patient had high myopia and diplopia. Molecular Genetics In 2 of 3 affected sibs from a German family with CORD, Roosing et al. (2013) performed exome sequencing but found no pathogenic variants in known autosomal recessive CORD-associated genes among the shared variants; there was only a single homozygous shared variant, a nonsense mutation in the RAB28 gene (E189X; 612994.0001), located within the largest shared homozygous region in the family. Sanger sequencing confirmed homozygosity for the mutation in the 3 affected sibs, and it was not found in 176 ethnically matched controls or in the Exome Variant Server database (ESP6500). Sequencing of RAB28 in 468 CORD probands and 149 probands with cone dystrophy revealed no mutations. Analysis of SNP data from more than 400 probands in the European Retinal Disease Consortium, including patients with autosomal recessive CORD, Leber congenital amaurosis (see 204000), and retinitis pigmentosa (see 268000), identified 7 families with large homozygous regions spanning RAB28; Sanger sequencing of RAB28 in those families revealed a homozygous nonsense mutation (R137X; 612994.0002) in affected sibs from a consanguineous family of Moroccan Jewish ancestry with CORD. By whole-exome sequencing in 2 unrelated patients of Spanish ancestry with CORD who did not have mutations in the ABCA4 gene (601691), Riveiro-Alvarez et al. (2015) identified homozygosity for a splice site (615374.0003) and a missense (615374.0004) mutation in the RAB28 gene, respectively. The mutations segregated with the disorder in the families. Neither mutation was found in the 1000 Genomes Project or Exome Variant Server databases or in an internal control database of 6,250 exomes. Sanger sequencing of RAB28 in 107 additional patients of Spanish descent with CORD revealed no mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- High myopia \- Decreased visual acuity, rapidly progressive \- Foveal hyperpigmentation \- Foveal hyperfluorescence \- Foveal atrophy (in some patients) \- Defects in all axes of color vision \- Central scotoma \- Lack of photoreceptors in fovea by optical coherence tomography \- Nondetectable photopic responses on electroretinography \- Reduced scotopic responses on electroretinography MISCELLANEOUS \- Onset of symptoms in the second decade of life MOLECULAR BASIS \- Caused by mutation in the RAS-associated protein-28 gene (RAB28, 612994.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CONE-ROD DYSTROPHY 18	c3809299	2,704	omim	https://www.omim.org/entry/615374	2019-09-22T15:52:25	{"doid": ["0111024"], "omim": ["615374", "120970"], "orphanet": ["1872"], "synonyms": []}
A rare, sex chromosome disorder of sex development characterized by the two different haploid sets of maternal and paternal chromosomes and variable phenotype - from normal male or female genitalia, to different degrees of ambiguous genitalia, and often infertility. Also, in the cases of monochorionic dizygotic twins, it can be confined to blood of both twins. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Tetragametic chimerism	None	2,705	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199310	2021-01-23T19:09:09	{"icd-10": ["Q99.0"], "synonyms": ["46,XX/46,XY chimerism"]}
A very rare genetic disorder characterised by the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate, and severe joint contractures. ## Epidemiology Less than 20 cases have been reported in the literature. ## Clinical description The fingers are thin with absent knuckles and reduced creases over the joints, and patients show an inability to make a full fist. Additional findings may include deformed ears, ptosis, an inability to open the mouth fully, heart defects, and clubfoot. ## Etiology The aetiology remains unknown. There are currently no human genes associated with this disease. ## Diagnostic methods The features of the hand are especially important for the diagnosis. ## Differential diagnosis Clinical overlap between Aase-Smith syndrome I and Gordon syndrome (see this term) has been suggested, due to the presence of distal arthrogryposis and cleft palate in both syndromes. ## Genetic counseling Autosomal dominant inheritance is suggested. ## Management and treatment In the absence of a specific treatment, supportive care and surgical correction should be offered. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Aase-Smith syndrome	c0220686	2,706	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=916	2021-01-23T19:00:12	{"gard": ["5642"], "mesh": ["C535332"], "omim": ["147800"], "umls": ["C0220686"], "icd-10": ["Q87.8"], "synonyms": ["Aase-Smith I syndrome", "Hydrocephalus-cleft palate-joint contractures syndrome"]}
Mast cell sarcoma SpecialtyOncology Mast cell sarcoma is an extremely aggressive[1] form of sarcoma made up of neoplastic mast cells. A sarcoma is a tumor made of cells from connective tissue. Mast cell sarcoma is an extremely rare tumor. Only 3 cases are reported so far. Prognosis is extremely poor. People with a mast cell sarcoma have no skin lesions, and pathology examination of the tumor shows it to be very malignant with an aggressive growth pattern.[2] Mast cell sarcoma should not be confused with extracutaneous mastocytoma, a rare benign mast cell tumor without destructive growth. In the cases observed, mast cell sarcoma terminated quickly as mast cell leukemia; one of the most aggressive human cancers.[3] ## See also[edit] * Mastocytosis ## References[edit] 1. ^ Chott A, Guenther P, Huebner A, Selzer E, Parwaresch R, Horny H, Valent P (2003). "Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma". Am J Surg Pathol. 27 (7): 1013–9. doi:10.1097/00000478-200307000-00019. PMID 12826896. 2. ^ Nancy Gould, "Diagnosis and Classification of Mastocytosis Archived 2004-10-27 at the Wayback Machine", The Mastocytosis Society. 3. ^ Ansell SM, ed. (2008). Rare Hematological Malignancies. Cancer Treatment & Research. Springer. ## External links[edit] Classification D * ICD-10: C96.2 * ICD-10-CM: C96.22 * ICD-9-CM: 202.6 * ICD-O: M9740/3 * MeSH: D012515 * SNOMED CT: 13583002 External resources * Orphanet: 66661 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Mast cell sarcoma	c0036221	2,707	wikipedia	https://en.wikipedia.org/wiki/Mast_cell_sarcoma	2021-01-18T18:33:02	{"mesh": ["D012515"], "umls": ["C0036221"], "orphanet": ["66661"], "wikidata": ["Q17119512"]}
Bulge in the wall of a blood vessel For other uses, see Aneurysm (disambiguation). Not to be confused with ebullism or embolism. aneurysm Other namesAneurism Angiography of an aneurysm in a brain artery. The aneurysm is the large bulge in the center of the image. SpecialtyVascular surgery An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall.[1] Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus (starting point) for clot formation (thrombosis) and embolization. The word is from Greek: ἀνεύρυσμα, aneurysma, "dilation", from ἀνευρύνειν, aneurynein, "to dilate". As an aneurysm increases in size, the risk of rupture increases,[2] leading to uncontrolled bleeding. Although they may occur in any blood vessel, particularly lethal examples include aneurysms of the Circle of Willis in the brain, aortic aneurysms affecting the thoracic aorta, and abdominal aortic aneurysms. Aneurysms can arise in the heart itself following a heart attack, including both ventricular and atrial septal aneurysms. There are congenital atrial septal aneurysms, a rare heart defect. ## Contents * 1 Classification * 1.1 True and false aneurysms * 1.2 Morphology * 1.3 Location * 1.4 Size * 2 Signs and symptoms * 2.1 Cerebral aneurysm * 2.2 Abdominal aneurysm * 2.3 Renal (kidney) aneurysm * 3 Risk factors * 4 Pathophysiology * 5 Mechanics * 6 Diagnosis * 7 Treatment * 7.1 Intracranial * 7.2 Aortic and peripheral * 7.3 Renal * 8 Epidemiology * 8.1 Pediatric aneurysms * 8.2 Risk factors * 8.3 Modeling * 9 Notable cases * 10 References * 11 External links ## Classification[edit] Aneurysms are classified by type, morphology, or location. ### True and false aneurysms[edit] A true aneurysm is one that involves all three layers of the wall of an artery (intima, media and adventitia). True aneurysms include atherosclerotic, syphilitic, and congenital aneurysms, as well as ventricular aneurysms that follow transmural myocardial infarctions (aneurysms that involve all layers of the attenuated wall of the heart are also considered true aneurysms).[3] A false aneurysm, or pseudoaneurysm, is a collection of blood leaking completely out of an artery or vein, but confined next to the vessel by the surrounding tissue. This blood-filled cavity will eventually either thrombose (clot) enough to seal the leak, or rupture out of the surrounding tissue.[3]:357 Pseudoaneurysms can be caused by trauma that punctures the artery, such as knife and bullet wounds,[4] as a result of percutaneous surgical procedures such as coronary angiography or arterial grafting,[5] or use of an artery for injection.[6] ### Morphology[edit] Cross-section of an arterial aneurysm, showing most of the area consisting of organized mural thrombus (tan-brown area) Aneurysms can also be classified by their macroscopic shapes and sizes and are described as either saccular or fusiform. The shape of an aneurysm is not specific for a specific disease.[3]:357 The size of the base or neck is useful in determining the chance of for example endovascular coiling.[7] Saccular aneurysms, or "berry" aneurysms, are spherical in shape and involve only a portion of the vessel wall; they usually range from 5 to 20 cm (2.0 to 7.9 in) in diameter, and are often filled, either partially or fully, by a thrombus.[3]:357Saccular aneurysms have a "neck” that connects the aneurysm to its main ("parent") artery, a larger, rounded area, called the dome. Fusiform aneurysms ("spindle-shaped" aneurysms) are variable in both their diameter and length; their diameters can extend up to 20 cm (7.9 in). They often involve large portions of the ascending and transverse aortic arch, the abdominal aorta, or, less frequently, the iliac arteries.[3]:357 ### Location[edit] Aneurysms can also be classified by their location: Ultrasonography of an aneurysm of the great saphenous vein due to venous valve insufficiency. * Arterial and venous, with arterial being more common.[8] * The heart, including coronary artery aneurysms, ventricular aneurysms, aneurysm of sinus of Valsalva, and aneurysms following cardiac surgery. * The aorta, namely aortic aneurysms including thoracic aortic aneurysms and abdominal aortic aneurysms.[9] * The brain, including cerebral aneurysms, berry aneurysms, and Charcot–Bouchard aneurysms. * The legs, including the popliteal arteries.[citation needed] * The kidney, including renal artery aneurysm and intraparechymal aneurysms.[10] * Capillaries, specifically capillary aneurysms. Cerebral aneurysms, also known as intracranial or brain aneurysms, occur most commonly in the anterior cerebral artery, which is part of the circle of Willis. This can cause severe strokes leading to death. The next most common sites of cerebral aneurysm occurrence are in the internal carotid artery.[11] ### Size[edit] Abdominal aorta size classification Ectatic or mild dilatation >2.0 cm and <3.0 cm[12] Moderate 3.0 - 5.0 cm[12] Large or severe >5.0[12] or 5.5[13] cm Abdominal aortic aneurysms are commonly divided according to their size and symptomatology. An aneurysm is usually defined as an outer aortic diameter over 3 cm (normal diameter of the aorta is around 2 cm),[14] or more than 50% of normal diameter that of a healthy individual of the same sex and age.[9][15] If the outer diameter exceeds 5.5 cm, the aneurysm is considered to be large.[13] The common iliac artery is classified as:[16] Normal Diameter ≤12 mm Ectatic Diameter 12 to 18 mm Aneurysm Diameter ≥18 mm ## Signs and symptoms[edit] Aneurysm presentation may range from life-threatening complications of hypovolemic shock to being found incidentally on X-ray.[17] Symptoms will differ by the site of the aneurysm and can include: ### Cerebral aneurysm[edit] Main article: Cerebral aneurysm Symptoms can occur when the aneurysm pushes on a structure in the brain. Symptoms will depend on whether an aneurysm has ruptured or not. There may be no symptoms present at all until the aneurysm ruptures.[18] For an aneurysm that has not ruptured the following symptoms can occur: * Fatigue * Loss of perception * Loss of balance * Speech problems * Double vision For a ruptured aneurysm, symptoms of a subarachnoid hemorrhage may present: * Severe headaches * Loss of vision * Double vision * Neck pain or stiffness * Pain above or behind the eyes ### Abdominal aneurysm[edit] Illustration depicting location of abdominal aneurysm 3D model of Aortic aneurism Main article: Abdominal aneurysm § Signs and symptoms Abdominal aortic aneurysm involves a regional dilation of the aorta and is diagnosed using ultrasonography, computed tomography, or magnetic resonance imaging. A segment of the aorta that is found to be greater than 50% larger than that of a healthy individual of the same sex and age is considered aneurysmal.[9] Abdominal aneurysms are usually asymptomatic but in rare cases can cause lower back pain or lower limb ischemia. ### Renal (kidney) aneurysm[edit] * Flank pain and tenderness * Hypertension * Haematuria * Signs of hypovolemic shock ## Risk factors[edit] Risk factors for an aneurysm include diabetes, obesity, hypertension, tobacco use, alcoholism, high cholesterol, copper deficiency, increasing age, and tertiary syphilis infection.[17]:602 Connective tissue disorders such as Loeys-Dietz syndrome, Marfan syndrome, and certain forms of Ehlers-Danlos syndrome are also associated with aneurysms. Aneurysms, dissections, and ruptures in individuals under 40 years of age are a major diagnostic criteria of the vascular form of Ehlers-Danlos syndrome (vEDS). [19] Specific infective causes associated with aneurysm include: * Advanced syphilis infection resulting in syphilitic aortitis and an aortic aneurysm * Tuberculosis, causing Rasmussen's aneurysms * Brain infections, causing infectious intracranial aneurysms A minority of aneurysms are associated with genetic factors. Examples include: * Berry aneurysms of the anterior communicating artery of the circle of Willis, associated with autosomal dominant polycystic kidney disease[20] * Familial thoracic aortic aneurysms * Cirsoid aneurysms, secondary to congenital arteriovenous malformations ## Pathophysiology[edit] Aneurysms form for a variety of interacting reasons. Multiple factors, including factors affecting a blood vessel wall and the blood through the vessel, contribute. The pressure of blood within the expanding aneurysm may also injure the blood vessels supplying the artery itself, further weakening the vessel wall. Without treatment, these aneurysms will ultimately progress and rupture.[21] Infection. A mycotic aneurysm is an aneurysm that results from an infectious process that involves the arterial wall.[22] A person with a mycotic aneurysm has a bacterial infection in the wall of an artery, resulting in the formation of an aneurysm. The most common locations include arteries in the abdomen, thigh, neck, and arm. A mycotic aneurysm can result in sepsis, or life-threatening bleeding if the aneurysm ruptures. Less than 3% of abdominal aortic aneurysms are mycotic aneurysms.[23] Syphilis. The third stage of syphilis also manifests as aneurysm of the aorta, which is due to loss of the vasa vasorum in the tunica adventitia.[24] Copper deficiency. A minority of aneurysms are caused by copper deficiency, which results in a decreased activity of the lysyl oxidase enzyme, affecting elastin, a key component in vessel walls.[25][26][27] Copper deficiency results in vessel wall thinning,[28] and thus has been noted as a cause of death in copper-deficient humans,[29] chickens and turkeys[30] ## Mechanics[edit] Aneurysmal blood vessels are prone to rupture under normal blood pressure and flow due to their special mechanical properties that make them weaker. To better understand this phenomenon, we can first look at healthy arterial vessels which exhibit a J-shaped stress-strain curve with high strength and high toughness (for a biomaterial in vivo).[31] Unlike crystalline materials whose linear elastic region follows Hooke's Law under uniaxial loading, many biomaterials exhibit a J-shaped stress-strain curve which is non-linear and concave up.[31] The blood vessel can be under large strain, or the amount of stretch the blood vessel can undergo, for a range of low applied stress before fracture, as shown by the lower part of the curve. The area under the curve up to a given strain is much lower than that for the equivalent Hookean curve, which is correlated to toughness. Toughness is defined as the amount of energy per unit volume a material can absorb before rupturing. Because the amount of energy release is proportional to the amount of crack propagation, the blood vessel wall can withstand pressure and is “tough.” Thus, healthy blood vessels with the mechanical properties of the J-shaped stress-strain curve have greater stability against aneurysms than materials with linear elasticity. Blood vessels with aneurysms, on the other hand, are under the influence of an S-shaped stress-strain curve. As a visual aid, aneurysms can be understood as a long, cylindrical balloon. Because it's a tight balloon under pressure, it can pop at any time a stress beyond a certain force threshold is applied. In the same vein, an unhealthy blood vessel has elastic instabilities that lead to rupture.[31] Initially, for a given radius and pressure, stiffness of the material increases linearly. At a certain point, the stiffness of the arterial wall starts to decrease with increasing load. At higher strain values, the area under the curve increases, thus increasing the impact on the material that would promote crack propagation. The differences in the mechanical properties of the aneurysmal blood vessels and the healthy blood vessels stem from the compositional differences of the vessels. Compared to normal aortas, aneurysmal aortas have a much higher volume fraction of collagen and ground substance (54.8% vs. 95.6%) and a much lower volume fraction of elastin (22.7% vs. 2.4%) and smooth muscles (22.6% vs. 2.2%), which contribute to higher initial stiffness.[32] It was also found that the ultimate tensile strength, or the strength to withstand rupture, of aneurysmal vessel wall is 50% lower than that of normal aortas.[33] The wall strength of ruptured aneurysmal aortic wall was also found to be 54.2 N/cm2, which is much lower than that of a repaired aorta wall, 82.3 N/cm2.[33] Due to the change in composition of the arterial wall, aneurysms overall have much lower strength to resist rupture. Predicting the risk of rupture is difficult due to the regional anisotropy the hardened blood vessels exhibit, meaning that the stress and strength values vary depending on the region and the direction of the vessel they are measured along.[34] ## Diagnosis[edit] Ruptured 7mm left vertebral artery aneurysm resulting in a subarachnoid hemorrhage as seen on a CT scan with contrast Diagnosis of a ruptured cerebral aneurysm is commonly made by finding signs of subarachnoid hemorrhage on a computed tomography (CT) scan. If the CT scan is negative but a ruptured aneurysm is still suspected based on clinical findings, a lumbar puncture can be performed to detect blood in the cerebrospinal fluid. Computed tomography angiography (CTA) is an alternative to traditional angiography and can be performed without the need for arterial catheterization. This test combines a regular CT scan with a contrast dye injected into a vein. Once the dye is injected into a vein, it travels to the cerebral arteries, and images are created using a CT scan. These images show exactly how blood flows into the brain arteries.[citation needed] ## Treatment[edit] Historically, the treatment of arterial aneurysms has been limited to either surgical intervention, or watchful waiting in combination with control of blood pressure. At least, in case of abdominal aortic aneurysm (AAA) the decision does not come without a significant risk and cost, hence, there is a great interest in identifying more advanced decision making approaches that are not solely based on the AAA diameter, but involve other geometrical and mechanical nuances such as local thickness and wall stress.[9] In recent years,[when?] endovascular or minimally invasive techniques have been developed for many types of aneurysms. Aneurysm clips are used for surgical procedure i.e. clipping of aneurysms.[35] ### Intracranial[edit] Main article: Cerebral aneurysm treatment There are currently two treatment options for brain aneurysms: surgical clipping or endovascular coiling. There is currently debate in the medical literature about which treatment is most appropriate given particular situations.[36] Surgical clipping was introduced by Walter Dandy of the Johns Hopkins Hospital in 1937. It consists of a craniotomy to expose the aneurysm and closing the base or neck of the aneurysm with a clip. The surgical technique has been modified and improved over the years. Endovascular coiling was introduced by Italian neurosurgeon Guido Guglielmi at UCLA in 1989. It consists of passing a catheter into the femoral artery in the groin, through the aorta, into the brain arteries, and finally into the aneurysm itself. Platinum coils initiate a clotting reaction within the aneurysm that, if successful, fills the aneurysm dome and prevents its rupture.[37] A flow diverter can be used, but risks complications.[38] ### Aortic and peripheral[edit] Endovascular stent and endovascular coil For aneurysms in the aorta, arms, legs, or head, the weakened section of the vessel may be replaced by a bypass graft that is sutured at the vascular stumps. Instead of sewing, the graft tube ends, made rigid and expandable by nitinol wireframe, can be easily inserted in its reduced diameter into the vascular stumps and then expanded up to the most appropriate diameter and permanently fixed there by external ligature.[39][40] New devices were recently developed to substitute the external ligature by expandable ring allowing use in acute ascending aorta dissection, providing airtight (i.e. not dependent on the coagulation integrity), easy and quick anastomosis extended to the arch concavity[41][42][43] Less invasive endovascular techniques allow covered metallic stent grafts to be inserted through the arteries of the leg and deployed across the aneurysm. ### Renal[edit] Renal aneurysms are very rare consisting of only 0.1–0.09%[44] while rupture is even more rare.[44][45] Conservative treatment with control of concomitant hypertension being the primary option with aneurysms smaller than 3 cm. If symptoms occur, or enlargement of the aneurysm, then endovascular or open repair should be considered.[46] Pregnant women (due to high rupture risk of up to 80%) should be treated surgically.[47] ## Epidemiology[edit] Incidence rates of cranial aneurysms are estimated at between 0.4% and 3.6%. Those without risk factors have expected prevalence of 2–3%.[11]:181 In adults, females are more likely to have aneurysms. They are most prevalent in people ages 35 – 60, but can occur in children as well. Aneurysms are rare in children with a reported prevalence of .5% to 4.6%. The most common incidence are among 50-year-olds, and there are typically no warning signs. Most aneurysms develop after the age of 40.[citation needed] ### Pediatric aneurysms[edit] Pediatric aneurysms have different incidences and features than adult aneurysms.[48] Intracranial aneurysms are rare in childhood, with over 95% of all aneurysms occurring in adults.[11]:235 ### Risk factors[edit] Incidence rates are two to three times higher in males, while there are more large and giant aneurysms and fewer multiple aneurysms.[11]:235 Intracranial hemorrhages are 1.6 times more likely to be due to aneurysms than cerebral arteriovenous malformations in whites, but four times less in certain Asian populations.[11]:235 Most patients, particularly infants, present with subarachnoid hemorrhage and corresponding headaches or neurological deficits. The mortality rate for pediatric aneurysms is lower than in adults.[11]:235 ### Modeling[edit] Vortex formation inside an aneurysm. 1- Blood flow inlet. 2- Vortex formation inside aneurysm. Velocity at center is near zero. 3- Blood flow exit Modeling of aneurysms consists of creating a 3D model that mimics a particular aneurysm. Using patient data for the blood velocity, and blood pressure, along with the geometry of the aneurysm, researchers can apply computational fluid dynamics (CFD) to predict whether an aneurysm is benign or if it is at risk of complication. One risk is rupture. Analyzing the velocity and pressure profiles of the blood flow leads to obtaining the resulting wall shear stress on the vessel and aneurysm wall. The neck of the aneurysm is the most at risk due to the combination of a small wall thickness and high wall shear stress. When the wall shear stress reaches its limit, the aneurysm ruptures, leading to intracranial hemorrhage. Conversely, another risk of aneurysms is the creation of clots. Aneurysms create a pocket which diverts blood flow. This diverted blood flow creates a vortex inside of the aneurysm. This vortex can lead to areas inside of the aneurysm where the blood flow is stagnant, which promotes formations of clots. Blood clots can dislodge from the aneurysm, which can then lead to an embolism when the clot gets stuck and disrupts blood flow. Model analysis allows these risky aneurysms to be identified and treated.[49][50][51][52] In the past, aneurysms were modeled as rigid spheres with linear inlets and outlets. As technology advances, the ability to detect and analyze aneurysms becomes easier. Researchers are able to CT scan a patient's body to create a 3D computer model that possesses the correct geometry. Aneurysms can now be modeled with their distinctive "balloon" shape. Nowadays researchers are optimizing the parameters required to accurately model a patient's aneurysm that will lead to a successful intervention. Current modeling is not able to take into account all variables though. For example, blood is considered to be a non-Newtonian fluid. Some researchers treat blood as a Newtonian fluid instead, as it sometimes has negligible effects to the analysis in large vessels. When analyzing small vessels though, such as those present in intracranial aneurysms. Similarly, sometimes it is difficult to model the varying wall thickness in small vessels, so researchers treat wall thickness as constant. Researchers make these assumptions to reduce computational time. Nonetheless, making erroneous assumptions could lead to a misdiagnosis that could put a patient's life at risk.[49][53][54][55] ## Notable cases[edit] * Lucille Ball, who died from an aortic rupture in the abdominal area days after having undergone apparently successful heart surgery for a dissecting aortic aneurysm[56][57][58] * Laura Branigan, who died of a cerebral aneurysm * David Cone, who suffered from an aneurysm and missed most of the 1996 baseball season * John Olerud, suffered an aneurysm in 1989 and forced to wear batting helmet on field all of his career since then * Albert Einstein, who died from a repaired aortic aneurysm[59] * Thomas Mikal Ford, who died from a ruptured aneurysm in his abdomen. He was 52. * Charles de Gaulle, who died from an aneurysm within his neck[60] * Richard Holbrooke, who died from a thoracic aortic aneurysm[61] * Édith Piaf, who died from an aneurysm due to liver failure * Stuart Sutcliffe, who died from an aneurysm in his brain's right hemisphere[62] * John Ritter, died September 11, 2003 of a misdiagnosed thoracic aortic dissection (aortic aneurysm).[63][64] * Isabel Granada, who died of a cerebral aneurysm[65][66] * Geoffrey Thompson, who died of a brain aneurysm at his daughter's wedding, hosted at his theme park, Blackpool Pleasure Beach. * Edwin Rosario died of an aneurysm in 1997. * Joni Mitchell suffered a brain aneurysm in 2015, but survived. * Grant Imahara died from brain aneurysm in July, 2020. ## References[edit] 1. ^ "Aneurysms". Society of NeuroInterventional Surgery. Retrieved 2018-02-23. 2. ^ Cronenwett JL, Murphy TF, Zelenock GB, Whitehouse WM, Lindenauer SM, Graham LM, Quint LE, Silver TM, Stanley JC (September 1985). 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The New England Journal of Medicine. 371 (22): 2101–8. doi:10.1056/NEJMcp1401430. PMID 25427112. 16. ^ Melissa L Kirkwood. "Iliac artery aneurysm". Retrieved 2018-02-23. Last updated: Mar 27, 2017. 17. ^ a b Walker BR, Colledge NR, Ralston SH (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. p. 604. ISBN 978-0-7020-3085-7. 18. ^ Manasco, Hunter. "The Aphasias". Introduction to Neurogenic Communication Disorders. p. 93. 19. ^ Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK1494/ 20. ^ Schueler SJ, Beckett JH, Gettings DS (August 18, 2010). "Berry Aneurysm in the Brain". freemd. Archived from the original on March 12, 2016. Retrieved November 13, 2011. 21. ^ Juvela S, Porras M, Poussa K (May 2008). "Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture". Journal of Neurosurgery. 108 (5): 1052–60. doi:10.3171/JNS/2008/108/5/1052. PMID 18447733. 22. ^ emedicine – Cerebral Aneurysm Author: Jonathan L Brisman. Coauthors: Emad Soliman, Abraham Kader, Norvin Perez. Updated: Sep 23, 2010 23. ^ Schueler SJ, Beckett JH, Gettings S (November 13, 2011). "Mycotic Aneurysm". Archived from the original on March 12, 2016. Retrieved November 13, 2012. 24. ^ Paulo N, Cascarejo J, Vouga L (February 2012). "Syphilitic aneurysm of the ascending aorta". Interactive Cardiovascular and Thoracic Surgery. 14 (2): 223–5. doi:10.1093/icvts/ivr067. PMC 3279976. PMID 22159251. 25. ^ Mäki J (2002). Lysyl oxidases : cloning and characterization of the fourth and the fifth human lysyl oxidase isoenzymes, and the consequences of a targeted inactivaton of the first described lysyl oxidase isoenzyme in mice (PDF). Oulu: Oulun yliopisto. ISBN 951-42-6739-7. 26. ^ Rucker RB, Kosonen T, Clegg MS, Mitchell AE, Rucker BR, Uriu-Hare JY, Keen CL (May 1998). "Copper, lysyl oxidase, and extracellular matrix protein cross-linking". The American Journal of Clinical Nutrition. 67 (5 Suppl): 996S–1002S. doi:10.1093/ajcn/67.5.996S. PMID 9587142. 27. ^ Smith-Mungo LI, Kagan HM (February 1998). "Lysyl oxidase: properties, regulation and multiple functions in biology". Matrix Biology. 16 (7): 387–98. doi:10.1016/s0945-053x(98)90012-9. PMID 9524359. 28. ^ Senapati A, Carlsson LK, Fletcher CD, Browse NL, Thompson RP (May 1985). "Is tissue copper deficiency associated with aortic aneurysms?". The British Journal of Surgery. 72 (5): 352–3. doi:10.1002/bjs.1800720507. PMID 3995240. S2CID 24990404. 29. ^ Tilson MD (September 1982). "Decreased hepatic copper levels. A possible chemical marker for the pathogenesis of aortic aneurysms in man". Archives of Surgery. 117 (9): 1212–3. doi:10.1001/archsurg.1982.01380330070017. PMID 7202350. 30. ^ Guenthner E, Carlson CW, Emerick RJ (September 1978). "Copper salts for growth stimulation and alleviation of aortic rupture losses in turkeys". Poultry Science. 57 (5): 1313–24. doi:10.3382/ps.0571313. PMID 724600. 31. ^ a b c "DoITPoMS - TLP Library Elasticity in Biological Materials". www.doitpoms.ac.uk. Retrieved 2019-05-24. 32. ^ He, Chang M.; Roach, Margot R. (July 1994). "The composition and mechanical properties of abdominal aortic aneurysms". Journal of Vascular Surgery. 20 (1): 6–13. doi:10.1016/0741-5214(94)90169-4. PMID 8028090. 33. ^ a b Vorp, David A.; Geest, Jonathan P. Vande (August 2005). "Biomechanical Determinants of Abdominal Aortic Aneurysm Rupture". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (8): 1558–1566. doi:10.1161/01.ATV.0000174129.77391.55. ISSN 1079-5642. PMID 16055757. 34. ^ Thubrikar MJ, Labrosse M, Robicsek F, Al-Soudi J, Fowler B (2001). "Mechanical properties of abdominal aortic aneurysm wall". J Med Eng Technol. 25 (4): 133–42. doi:10.1080/03091900110057806. ISSN 0309-1902. PMID 11601439. 35. ^ "Aneurysm Clip". Surgical Units. 36. ^ Raja PV, Huang J, Germanwala AV, Gailloud P, Murphy KP, Tamargo RJ (June 2008). "Microsurgical clipping and endovascular coiling of intracranial aneurysms: a critical review of the literature". Neurosurgery. 62 (6): 1187–202, discussion 1202–3. doi:10.1227/01.neu.0000333291.67362.0b. PMID 18824986. 37. ^ Guglielmi G (September 2007). "History of endovascular endosaccular occlusion of brain aneurysms: 1965-1990". Interventional Neuroradiology. 13 (3): 217–24. doi:10.1177/159101990701300301. PMC 3345485. PMID 20566113. 38. ^ Lv X, Yang H, Liu P, Li Y (February 2016). "Flow-diverter devices in the treatment of intracranial aneurysms: A meta-analysis and systematic review". The Neuroradiology Journal. 29 (1): 66–71. doi:10.1177/1971400915621321. PMC 4978339. PMID 26838174. 39. ^ Nazari, S. (2010). "sp.html". Interactive Cardiovascular and Thoracic Surgery. Fondazionecarrel.org. 10 (2): 161–4. doi:10.1510/icvts.2009.216291. PMID 19933306. Retrieved 2014-05-30. 40. ^ Aluffi A, Berti A, Buniva P, Rescigno G, Nazari S (2002). "Improved device for sutureless aortic anastomosis applied in a case of cancer". Texas Heart Institute Journal. 29 (1): 56–9. PMC 101273. PMID 11995854. 41. ^ Nazari S (February 2010). "Expandable device type III for easy and reliable approximation of dissection layers in sutureless aortic anastomosis. Ex vivo experimental study". Interactive Cardiovascular and Thoracic Surgery. 10 (2): 161–4. doi:10.1510/icvts.2009.216291. PMID 19933306. 42. ^ Stefano Nazari. "Expandable device type III for easy and reliable approximation of dissection layers in sutureless aortic anastomosis. Ex vivo experimental study". Icvts.ctsnetjournals.org. Archived from the original on 2011-09-30. Retrieved 2014-05-30. 43. ^ Nazari, S. (2010). "ndicvts.html". Interactive Cardiovascular and Thoracic Surgery. Fondazionecarrel.org. 10 (2): 161–4. doi:10.1510/icvts.2009.216291. PMID 19933306. Retrieved 2014-05-30. 44. ^ a b Schorn B, Falk V, Dalichau H, et al. (1997). "Kidney salvage in a case of ruptured renal artery aneurysm: case report and literature review". Cardiovasc Surg. 5 (1): 134–136. doi:10.1016/s0967-2109(95)00041-0. PMID 9158136. 45. ^ Tham G, Ekelund L, Herrlin K, Lindstedt EL, Olin T, Bergentz SE (March 1983). "Renal artery aneurysms. Natural history and prognosis". Annals of Surgery. 197 (3): 348–52. doi:10.1097/00000658-198303000-00016. PMC 1352740. PMID 6830341. 46. ^ Uflacker R. Interventional management of visceral artery aneurysms. In: Strandness DE, ed. Vascular Diseases: Surgical & Interventional Therapy. New York, NY: Churchill Livingstone; 1994:823–844. 47. ^ Lumsden AB, Salam TA, Walton KG (1996). "Renal artery an?eurysm: a report of 28 cases". Cardiovasc Surg. 4 (2): 185–189. doi:10.1016/0967-2109(96)82312-X. PMID 8861434. 48. ^ "Brain Aneurysm Basics \| The Brain Aneurysm Foundation". Bafound.org. Archived from the original on 2014-05-30. Retrieved 2014-05-30. 49. ^ a b Nabong, Jennica Rica; David, Guido (October 2017). "Finite element model of size, shape and blood pressure on rupture of intracranial saccular aneurysms". Journal of Physics: Conference Series. 893 (1): 012054. Bibcode:2017JPhCS.893a2054R. doi:10.1088/1742-6596/893/1/012054. ISSN 1742-6596. 50. ^ Algabri, Y. A.; Rookkapan, S.; Chatpun, S. (September 2017). "Three-dimensional finite volume modelling of blood flow in simulated angular neck abdominal aortic aneurysm". IOP Conference Series: Materials Science and Engineering. 243 (1): 012003. Bibcode:2017MS&E..243a2003A. doi:10.1088/1757-899X/243/1/012003. ISSN 1757-899X. 51. ^ Sarrami-Foroushani, Ali; Lassila, Toni; Hejazi, Seyed Mostafa; Nagaraja, Sanjoy; Bacon, Andrew; Frangi, Alejandro F. (2019-06-25). "A computational model for prediction of clot platelet content in flow-diverted intracranial aneurysms". Journal of Biomechanics. 91: 7–13. doi:10.1016/j.jbiomech.2019.04.045. ISSN 0021-9290. PMID 31104921. 52. ^ Zhong, Liang; Zhang, Jun-Mei; Su, Boyang; Tan, Ru San; Allen, John C.; Kassab, Ghassan S. (2018-06-26). "Application of Patient-Specific Computational Fluid Dynamics in Coronary and Intra-Cardiac Flow Simulations: Challenges and Opportunities". Frontiers in Physiology. 9: 742. doi:10.3389/fphys.2018.00742. ISSN 1664-042X. PMC 6028770. PMID 29997520. 53. ^ Liepsch, D.; Sindeev, S.; Frolov, S. (August 2018). "An impact of non-Newtonian blood viscosity on hemodynamics in a patient-specific model of a cerebral aneurysm". Journal of Physics: Conference Series. 1084 (1): 012001. Bibcode:2018JPhCS1084a2001L. doi:10.1088/1742-6596/1084/1/012001. ISSN 1742-6596. 54. ^ Thenier-Villa, José Luis; Riveiro Rodríguez, Antonio; Martínez-Rolán, Rosa María; Gelabert-González, Miguel; González-Vargas, Pedro Miguel; Galarraga Campoverde, Raúl Alejandro; Díaz Molina, Jorge; De La Lama Zaragoza, Adolfo; Martínez-Cueto, Pedro; Pou, Juan; Conde Alonso, Cesáreo (2018-10-01). "Hemodynamic Changes in the Treatment of Multiple Intracranial Aneurysms: A Computational Fluid Dynamics Study". World Neurosurgery. 118: e631–e638. doi:10.1016/j.wneu.2018.07.009. ISSN 1878-8750. PMID 30017759. 55. ^ Sforza, Daniel M.; Putman, Christopher M.; Cebral, Juan R. (June 2012). "Computational fluid dynamics in brain aneurysms". International Journal for Numerical Methods in Biomedical Engineering. 28 (6–7): 801–808. doi:10.1002/cnm.1481. ISSN 2040-7939. PMC 4221804. PMID 25364852. 56. ^ Ball L (April 27, 1989). "Lucy dies". Chicago Tribune. Retrieved May 12, 2013. 57. ^ "Article: Lucille Ball, Pioneer of Television Comedy, Dies at 77". 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Retrieved 5 November 2017. ## External links[edit] Wikimedia Commons has media related to Aneurysms. Look up aneurysm in Wiktionary, the free dictionary. * @neurIST – Integrated Biomedical Informatics for the Management of Cerebral Aneurysms * Brain aneurysm and percent packing calculator Classification D * ICD-10: I72 * ICD-9-CM: 442 * MeSH: D000783 * DiseasesDB: 15088 External resources * MedlinePlus: 001122 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis Authority control * BNE: XX555959 * BNF: cb11981676n (data) * GND: 4131419-0 * LCCN: sh85004986 * NDL: 00561683 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Aneurysm	c0002940	2,708	wikipedia	https://en.wikipedia.org/wiki/Aneurysm	2021-01-18T18:53:15	{"mesh": ["D000783"], "icd-9": ["442"], "icd-10": ["I72"], "wikidata": ["Q189389"]}
1: Total loss of attachment (clinical attachment loss, CAL) is the sum of 2: Gingival recession, and 3: Probing depth Gingival recession, also known as receding gums, is the exposure in the roots of the teeth caused by a loss of gum tissue and/or retraction of the gingival margin from the crown of the teeth.[1] Gum recession is a common problem in adults over the age of 40, but it may also occur starting from the age of a teenager, or around the age of 10. It may exist with or without concomitant decrease in crown-to-root ratio (recession of alveolar bone). ## Contents * 1 Classification * 2 Causes * 3 Symptoms * 4 Gingival grafting * 4.1 Growth-factor techniques * 5 References * 6 External links ## Classification[edit] Various classifications have been proposed to classify gingival recession, Miller’s classification system[2] being the one that is most widely followed. Many cases which are encountered in daily clinical practice cannot be classified according to the criteria of the present classification systems. Kumar & Masamatti's classification system gives a comprehensive depiction of recession defect that can be used to include cases that cannot be classified according to present classifications. A separate classification system for palatal recessions (PR) has been given. A new comprehensive classification system classifies recession on the basis of the position of interdental papilla and buccal/lingual/palatal recessions. Kumar & Masamatti's classification system tries to overcome the limitations of Miller's classification.[3] ## Causes[edit] There are many possible causes for gingival recession: * By far the most common cause is gum disease (periodontal disease).[1][failed verification] * Overaggressive brushing is also cited to cause gum recession.[1] One systemic review of the literature concluded that "The data to support or refute the association between tooth brushing and gingival recession are inconclusive," although aggressive or forceful brushing was not specifically addressed.[4] A subsequent study found horizontal tooth brushing technique (versus Bass technique or circular methods), medium-hardness toothbrush use and brushing only once daily were associated with gingival recession.[5] * Improper flossing (i.e., flossing too roughly or aggressively) which may cut into the gums.[6] * Hereditary thin, fragile or insufficient gingival tissue predisposes to gingival recession.[1] * Dipping tobacco, which affects the mucous membrane lining in the mouth and will cause receding gums over time * Self-inflicted trauma, such as habits like digging a fingernail or pencil into the gum. This type of recession more commonly associated with children and persons with psychiatric disorders. * Scurvy (lack of dietary vitamin C) * Acute necrotizing ulcerative gingivitis * Abnormal tooth position, such as tooth crowding, giving inadequate cover of one or more teeth by the jaw bone.[1] * Piercings in the lip or tongue that wear away the gum by rubbing against it. * Intentional gingival retraction. For example, the adult tooth may not grow out of the gum, and to remedy this, a procedure called an exposure is done. It involves the gum tissue being cut open to allow the adult tooth to grow out. This is a less common cause of gum recession. ## Symptoms[edit] Gum recession is generally not an acute condition. In most cases, receding of gums is a progressive condition that occurs gradually over the years. This is one reason that it is common over the age of 40. Because the changes in the condition of the gums from one day to another are minimal, patients get used to the gums' appearance and tend not to notice the recession visually. Receding gums may remain unnoticed until the condition starts to cause symptoms. Advanced gingival recession. Note particularly severe recession on leftmost incisor. The following signs and symptoms may indicate gum recession: * Tooth mobility * Dentin hypersensitivity (over-sensitive teeth) - short, sharp pain is triggered by hot, cold, sweet, sour, or spicy food and drink. If the cementum covering the root is not protected anymore by the gums, it is easily abraded exposing the dentin tubules to external stimuli. * Teeth may also appear longer than normal (a larger part of the crown is visible if gums are receding) * The roots of the tooth are exposed and visible * The tooth feels notched at the gum line * Change in the tooth’s color (due to the color difference between enamel and cementum) * Spaces between teeth seem to grow (the space is the same, but it seems larger because the gums do not fill it any more) * Cavities below the gum line If the gum recession is caused by gingivitis, the following symptoms may also be present: * Puffy, red, or swollen (inflamed) gums * Gum bleeding while brushing or flossing * Bad breath (halitosis) In some cases, it is the treatment of gingivitis that reveals a gum recession problem, that was previously masked by the gums swelling. ## Gingival grafting[edit] Main article: gum graft Depending on the shape of the gum recession and the levels of bone around the teeth, areas of gum recession can be regenerated with new gum tissue using a variety of gum grafting "periodontal plastic surgery" procedures performed by a specialist in periodontics (a periodontist). These procedures are typically completed under local anesthesia with or without conscious sedation, as the patient prefers. This may involve repositioning of adjacent gum tissue to cover the recession (called a pedicle graft) or use of a free graft of gingival or connective tissue from the roof of the mouth (called a free gingival graft or a Subepithelial connective tissue graft). Alternatively, a material called acellular dermal matrix (processed donated human skin allograft) may be used instead of tissue from the patient's own palate. ### Growth-factor techniques[edit] Recent advances have seen the introduction of platelet-derived growth factor (PDGF) infused bone graft material. This material is usually combined with the cellular matrix to form a soft bone paste that is then covered by the allograft. The development of this type of bone and tissue cellular matrix (also known as ortho filler) results in greater osseointegration with the patient's healthy bone and soft tissue. Healing from such procedures requires 2–4 weeks. After a few months the results can be evaluated and in some cases the new tissue needs to be reshaped in a very minor procedure to get an optimal result. In cases where recession is not accompanied by periodontal bone loss, complete or near complete coverage of the recession area is achievable[citation needed]. ## References[edit] 1. ^ a b c d e Gingival Recession - Causes and treatment Archived 2010-09-17 at the Wayback Machine JADA, Vol 138. http://jada.ada.org. Oct 2007. American Dental Association 2. ^ Miller PD Jr. A classification of marginal tissue recession. Int J Periodontics Restorative Dent 1985;5:8-13. 3. ^ Kumar A, Masamatti SS. A new classification system for gingival and palatal recession. J Indian Soc Periodontol 2013;17:175-81. 4. ^ Rajapakse, P. Sunethra; McCracken, Giles I.; Gwynnett, Erika; Steen, Nick D.; Guentsch, Arndt; Heasman, Peter A. (December 2007). "Does tooth brushing influence the development and progression of non-inflammatory gingival recession? A systematic review". Journal of Clinical Periodontology. 34 (12): 1046–1061. doi:10.1111/j.1600-051X.2007.01149.x. PMID 17953693. 5. ^ Chrysanthakopoulos, Nikolaos Andreas (2011). "Aetiology and Severity of Gingival Recession in an Adult Population Sample in Greece". Dental Research Journal. 8 (2): 64–70. ISSN 1735-3327. PMC 3177396. PMID 22013465. 6. ^ Pradeep, Koppolu; Rajababu, Palaparthy; Satyanarayana, Durvasula; Sagar, Vidya (2012). "Gingival Recession: Review and Strategies in Treatment of Recession". Case Reports in Dentistry. 2012: 563421. doi:10.1155/2012/563421. ISSN 2090-6447. PMC 3467775. PMID 23082256. ## External links[edit] * An academic presentation on gingival recession * Highly informative overview article from the NYTimes. * v * t * e Dentistry involving supporting structures of teeth (Periodontology) Anatomy * Periodontium * Alveolar bone * Biologic width * Bundle bone * Cementum * Free gingival margin * Gingiva * Gingival fibers * Gingival sulcus * Junctional epithelium * Mucogingival junction * Periodontal ligament * Sulcular epithelium * Stippling Disease Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Periodontosis * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Infection * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola * Red complex * Entamoeba gingivalis (amoebic) * Trichomonas tenax Other * Calculus * Clinical attachment loss * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingival recession * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Vertical bony defect Treatment and prevention * Periodontal examination * Ante's law * Brushing * Bleeding on probing * Chlorhexidine gluconate * Flossing * Hydrogen peroxide * Mouthwash * Oral hygiene * Tetracycline * Triclosan * Host modulatory therapy Treatment Conventional therapy * Debridement * Scaling and root planing * Full mouth disinfection * Full mouth ultrasonic debridement Surgery * Apically positioned flap * Bone graft * Coronally positioned flap * Crown lengthening * Free gingival graft * Gingival grafting * Gingivectomy * Guided bone regeneration * Guided tissue regeneration * Enamel matrix derivative * Implant placement * Lateral pedicle graft * Open flap debridement * Pocket reduction surgery * Socket preservation * Sinus lift * Subepithelial connective tissue graft * Tools * Curette * Membrane * Probe * Scaler Important personalities * Tomas Albrektsson * Frank Beube * Per-Ingvar Brånemark * Robert Gottsegen * Gary Greenstein * Jan Lindhe * Brian Mealey * Preston D. Miller * Willoughby D. Miller * Carl E. Misch * John Mankey Riggs * Jay Seibert * Jørgen Slots * Paul Roscoe Stillman * Dennis P. Tarnow * Hom-Lay Wang * James Leon Williams * W. J. Younger Other specialties * Endodontology * Orthodontology * Prosthodontology [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Gingival recession	c0266916	2,709	wikipedia	https://en.wikipedia.org/wiki/Gingival_recession	2021-01-18T18:40:05	{"mesh": ["D005889"], "umls": ["C0266916", "C0017572"], "wikidata": ["Q964920"]}
Midline cervical cleft SpecialtyDermatology Midline cervical clefts are a rare congenital anomaly resulting from incomplete fusion during embryogenesis of the first and second branchial arches in the ventral midline of the neck. The condition presents as a midline cutaneous defect of the anterior neck with a skin projection or sinus, or as a subcutaneous erythematous fibrous cord. Surgical excision is the preferred treatment.[1][2] ## See also[edit] * Accessory tragus * 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. 2. ^ Remukaswamy, G.M.; Soma, M.A.; Hartley, B.E. (2009). "Midline cervical cleft: a rare congenital anomaly". Ann Otol Rhinol Laryngol. 118 (11): 786–90. doi:10.1177/000348940911801107. PMID 19999364. 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Midline cervical cleft	c1274890	2,710	wikipedia	https://en.wikipedia.org/wiki/Midline_cervical_cleft	2021-01-18T18:36:30	{"umls": ["C1274890"], "orphanet": ["141288"], "wikidata": ["Q6842567"]}
Autosomal dominant cerebellar ataxia Other namesAutosomal dominant spinocerebellar ataxia[1] Autosomal dominant is the manner in which this condition is inherited SymptomsMulti system involvement[2] TypesADCS type1, ADCA type 2, ADCA type 3[2] Diagnostic methodMRI, CT scan[3] TreatmentAnticonvulsants may be used[2] Autosomal dominant cerebellar ataxia (ADCA) is a form of spinocerebellar ataxia inherited in an autosomal dominant manner. ADCA is a genetically inherited condition that causes deterioration of the nervous system leading to disorder and a decrease or loss of function to regions of the body.[2] Degeneration occurs at the cellular level and in certain subtypes results in cellular death. Cellular death or dysfunction causes a break or faulty signal in the line of communication from the central nervous system to target muscles in the body. When there is impaired communication or a lack of communication entirely, the muscles in the body do not function correctly. Muscle control complications can be observed in multiple balance, speech, and motor or movement impairment symptoms. ADCA is divided into three types and further subdivided into subtypes known as SCAs (spinocerebellar ataxias).[4] ## Contents * 1 Symptoms and signs * 2 Genetics * 3 Diagnosis * 3.1 ADCA types * 3.1.1 Type 1 * 3.1.2 Type 2/3 * 4 Treatments * 5 Epidemiology * 6 References * 7 Further reading * 8 External links ## Symptoms and signs[edit] Cerebellum Symptoms typically are onset in the adult years, although, childhood cases have also been observed. Common symptoms include a loss of coordination which is often seen in walking, and slurred speech. ADCA primarily affects the cerebellum, as well as, the spinal cord.[5] Some signs and symptoms are:[2] * Episodes of altered level of consciousness * Neurological regression * Multi-system involvement * Movement disorders. * Cerebellar dysfunction ## Genetics[edit] In terms of the genetics of autosomal dominant cerebellar ataxia 11 of 18 known genes are caused by repeated expansions in corresponding proteins, sharing the same mutational mechanism. SCAs can be caused by conventional mutations or large rearrangements in genes that make glutamate and calcium signaling, channel function, tau regulation and mitochondrial activity or RNA alteration.[6] The mechanism of Type I is not completely known, however, Whaley, et al. suggest the polyglutamine product is toxic to the cell at a protein level, this effect may be done by transcriptional dysregulation and disruption of calcium homeostasis which causes apoptosis to occur earlier.[4] ## Diagnosis[edit] In diagnosing autosomal dominant cerebellar ataxia the individuals clinical history or their past health examinations, a current physical examination to check for any physical abnormalities, and a genetic screening of the patients genes and the genealogy of the family are done.[7] The large category of cerebellar ataxia is caused by a deterioration of neurons in the cerebellum, therefore magnetic resonance imaging (MRI) is used to detect any structural abnormality such as lesions which are the primary cause of the ataxia. Computed tomography (CT) scans can also be used to view neuronal deterioration, but the MRI provides a more accurate and detailed picture.[8] ### ADCA types[edit] Currently there are 27 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12- SCA14, SCA15/SCA16, SCA17- SCA23, SCA25, SCA27, SCA28, SCA32, SCA34- SCA37, autosomal dominant cerebellar ataxia and dentatorubral pallidoluysian atrophy .[3] #### Type 1[edit] Type I ADCA is characterized by different symptoms of ataxia as well as other conditions that are dependent on the subtype. Type 1 ADCA is divided into 3 subclasses based on pathogenesis of the subtypes each contain.[4][3][9] L-Glutamin * Subtype 1 -subtypes in the first subclass are caused by CAG nucleotide repeats in the DNA, which code for the amino acid glutamine. This glutamine is toxic to the cell on the level of proteins and has degenerative effects. Within the first subclass of Type 1 are SCA1, SCA2, SCA3, SCA17, and DRPLA. This first subclass is the most common of Type 1 ADCAs with SCA3 being the most common subtype of all of Type 1. SCA3, Machado-Joseph disease, is the most common because the mutation repeats more than 56 times while the regular length is around 13 to 31.[4] * Subtype 2 -the second subclass of Type 1 ADCA is also caused by the same nucleotide repeats but instead in RNA and in a region that does not code for proteins. Gene expression is affected instead of proteins in subtype two SCAs because of this. Subtype 2 contains SCA8, SCA10, and SCA12.[4] * Subtype 3 -the third subclass of Type 1 ADCA is caused by different mutations and deletions in genes. It comprises SCA13, SCA14, SCA15, SCA16, SCA27, and SCA28.[4] #### Type 2/3[edit] Type II ADCA is composed of SCA7 and syndromes associated with pigmentary maculopathies.[4] SCA7 is a disease that specifically displays retinal degeneration, along with the common degeneration of the cerebellum. Moving further into SCA7's pathology, a similar genetic process is described, while the function of ATXN7 (an ataxin gene) is much like a component of the SAGA complex. The SAGA complex uses two histone-modifying techniques to regulate transcription. These activities are the Gcn5 histone acetyltransferase and the Usp22 deubiquitinase. Mutant ATXN7 in HAT activity causes an increase in activity, which was reported from an in-vivo analysis in the retina. There are also studies that show a loss in activity when human ATXN7 in yeast was used. The SCA7 autosomal-dominant inheritance pattern is similar to a mutant ATXN5-induced gain in Gcn5 HAT.[10] Spinocerebellar ataxia type 15 has been classified as an ADCA Type III as it has been noted to have postural and action tremor in addition to cerebellar ataxia.[4] Additionally, spinocerebellar ataxia type 20 (SCA20) is organized in ADCA III that often exhibits disease-like symptoms at an earlier age, sometime starting at fourteen years old.[4][11][12] ## Treatments[edit] In terms of a cure there is currently none available, however for the disease to manifest itself, it requires mutant gene expression.[10] Manipulating the use of protein homeostasis regulators can be therapeutic agents, or a treatment to try and correct an altered function that makes up the pathology is one current idea put forth by Bushart, et al.[10][13] There is some evidence that for SCA1 and two other polyQ disorders that the pathology can be reversed after the disease is underway.[10] There is no effective treatments that could alter the progression of this disease, therefore care is given, like occupational and physical therapy for gait dysfunction and speech therapy.[medical citation needed] ## Epidemiology[edit] In terms of frequency, it is estimated at 2 per 100,000, it has identified in different regions of the world. Some clusters of certain types of autosomal dominant cerebellar ataxia reach a prevalence of 5 per 100,000.[2] ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Autosomal dominant cerebellar ataxia". www.orpha.net. Retrieved 8 August 2019. 2. ^ a b c d e f "Autosomal Dominant Cerebellar Ataxia information page. Patient \| Patient". Patient. Retrieved 2016-03-25. 3. ^ a b c RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Autosomal dominant cerebellar ataxia type 1". www.orpha.net. Retrieved 2016-03-25. 4. ^ a b c d e f g h i Whaley, Nathaniel; Fujioka, Shinsuke; Wszolek, Zbigniew K (1 January 2011). "Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics". Orphanet Journal of Rare Diseases. 6 (1): 33. doi:10.1186/1750-1172-6-33. PMC 3123548. PMID 21619691. 5. ^ Bird, Thomas D. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Hereditary Ataxia Overview. Seattle (WA): University of Washington, Seattle. PMID 20301317.Last Revision: March 3, 2016. 6. ^ Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Durr A. doi:10.1016/S1474-4422(10)70183-6 – via ScienceDirect (Subscription may be required or content may be available in libraries.) 7. ^ Brusse E, Maat-Kievit JA, van Swieten JC (2007). "Diagnosis and management of early- and late-onset cerebellar ataxia". Clin. Genet. 71 (1): 12–24. doi:10.1111/j.1399-0004.2006.00722.x. PMID 17204042. 8. ^ Ludger, Schols (2003). "Autosomal Dominant Cerebellar Ataxia" (PDF). Orphanet. Orphanet. Retrieved 25 March 2016. 9. ^ "SCA1". Genetics Home Reference. 2016-03-21. Retrieved 2016-03-25. 10. ^ a b c d Orr, H. T. (16 April 2012). "The cell biology of disease: Cell biology of spinocerebellar ataxia". The Journal of Cell Biology. 197 (2): 167–177. doi:10.1083/jcb.201105092. PMC 3328388. PMID 22508507. 11. ^ Pulst, Stefan M. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Spinocerebellar Ataxia Type 2. Seattle (WA): University of Washington, Seattle. PMID 20301452.Revised 2015 12. ^ Fujioka, Shinsuke; Sundal, Christina; Wszolek, Zbigniew K (2013-01-18). "Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics". Orphanet Journal of Rare Diseases. 8 (1): 14. doi:10.1186/1750-1172-8-14. PMC 3558377. PMID 23331413. 13. ^ Bushart, David D.; Murphy, Geoffrey G.; Shakkottai, Vikram G. (2016-01-01). "Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease". Annals of Translational Medicine. 4 (2): 25. doi:10.3978/j.issn.2305-5839.2016.01.06. ISSN 2305-5839. PMC 4731605. PMID 26889478. ## Further reading[edit] * Burk, K (1996). "Autosomal dominant cerebellar ataxia type I Clinical features and MRI in families with SCA1, SCA2 and SCA" (PDF). Brain. 119 (5): 1497–1505. doi:10.1093/brain/119.5.1497. PMID 8931575. Retrieved 25 March 2016. * Louis, Elan D.; Mayer, Stephan A.; Rowland, Lewis P. (2015-08-31). Merritt's Neurology. Lippincott Williams & Wilkins. ISBN 9781496321077. * LeDoux, Mark S. (2005-01-25). Movement Disorders: Genetics and Models. Academic Press. ISBN 9780080470566. ## External links[edit] Classification D * ICD-10: G11.1 External resources * Patient UK: Autosomal dominant cerebellar ataxia * Orphanet: 99 Scholia has a topic profile for Autosomal dominant cerebellar ataxia. * 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 * 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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 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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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Autosomal dominant cerebellar ataxia	c4087347	2,711	wikipedia	https://en.wikipedia.org/wiki/Autosomal_dominant_cerebellar_ataxia	2021-01-18T18:52:42	{"gard": ["4346"], "orphanet": ["99"], "synonyms": ["ADCA", "Autosomal dominant spinocerebellar ataxia"], "wikidata": ["Q622925"]}
Silica granuloma SpecialtyDermatology Silica granulomas are a skin condition which may be caused by automobile and other types of accidents which produces tattooing of dirt (silicon dioxide) into the skin that then induces the granuloma formation.[1]:46 ## See also[edit] * Granuloma * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. ## External links[edit] Classification D * ICD-10: L92.8 (ILDS L92.874) * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Silica granuloma	c0263621	2,712	wikipedia	https://en.wikipedia.org/wiki/Silica_granuloma	2021-01-18T18:58:18	{"umls": ["C0263621"], "icd-10": ["L92.8"], "wikidata": ["Q7514911"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia with axonal neuropathy-3 (SCAN3) is caused by homozygous or compound heterozygous mutation in the COA7 gene (615623) on chromosome 1p32. Description Spinocerebellar ataxia with axonal neuropathy-3 (SCAN3) is an autosomal recessive neuromuscular disorder characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy and distal sensory impairment due to an axonal peripheral neuropathy. Affected individuals have gait disturbances and sometimes manual dexterity difficulties, as well as cerebellar ataxia associated with cerebellar atrophy on brain imaging. Additional features usually include dysarthria, hyporeflexia, and increased serum creatine kinase. Some patients may have impaired intellectual development (summary by Higuchi et al., 2018). For a discussion of genetic heterogeneity of SCAN, see SCAN1 (607250). Clinical Features Martinez Lyons et al. (2016) reported a 19-year-old woman with a slowly progressive neurodegenerative disorder presenting as delayed psychomotor development around 1 year of age. This was followed by difficulty walking with frequent falls and poor balance, leukoencephalopathy on brain imaging, and a mixed axonal demyelinating sensorimotor neuropathy. Additional neurologic features included mild cognitive impairment, dysmetria, ataxic gait, tremor, limb weakness, and hyporeflexia with muscle wasting. Higuchi et al. (2018) reported 4 unrelated Japanese patients with SCAN3. Three patients were in their twenties, whereas 1 was 63 years of age. Three patients presented before age 5 years with foot deformities, gait disturbance, and poor manual dexterity; the fourth patient presented at age 15 years with walking difficulties. The disorder was slowly progressive, and common features included ataxia, dysarthria, steppage gait, foot drop, Romberg sign, and distal weakness and muscle atrophy of all 4 limbs. All patients also had distal sensory impairment with hyporeflexia. Most remained ambulatory, although 1 patient required a wheelchair at age 9 years; this patient also had cognitive impairment (IQ of 68). Brain imaging showed cerebellar atrophy in all patients. Nerve conduction studies were consistent with a peripheral axonal neuropathy, and sural nerve biopsy showed chronic axonal degeneration with a marked loss of large and medium myelinated fibers. Laboratory studies showed mildly increased serum creatine kinase in all patients, as well as increased serum lactate and pyruvate in blood or cerebrospinal fluid. Skeletal muscle biopsy from 1 patient showed a few ragged-red fibers and some COX-negative fibers, suggesting a subclinical mitochondrial myopathy. Cultured patient fibroblasts and skeletal muscle tissue showed variably decreased levels and activity of mitochondrial respiratory complexes I and IV. Higuchi et al. (2018) concluded that the ataxia resulted from a combination of peripheral sensory neuropathy and cerebellar ataxia. Inheritance The transmission pattern of SCAN3 in the families reported by Higuchi et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In a 19-year-old woman with SCAN3, Martinez Lyons et al. (2016) identified compound heterozygous mutations in the COA7 gene (615623.0001 and 615623.0002). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed no detectable COA7 protein, decreased amounts of COX structural subunits MTCO2 (516040) and MTCO3 (516050), and decreased levels of fully assembled complex IV. These defects could be rescued by expression of wildtype COA7. In 4 unrelated Japanese patients with SCAN3, Higuchi et al. (2018) identified homozygous or compound heterozygous mutations in the COA7 gene (see, e.g., 615623.0003-615623.0005). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Expression of some of the variants in HeLa cells showed that they localized normally to the mitochondria. The mutations were postulated to result in a loss of function with a neurodegenerative effect. The patients were ascertained from 1,396 Japanese patients with peripheral neuropathy who underwent genetic analysis. Animal Model Higuchi et al. (2018) found that knockdown of the Drosophila Coa7 gene caused morphologically aberrant rough eyes with fusion of ommatidia and lack of bristles compared to controls. Mutant flies also showed a shorter life span and locomotor defects, which were associated with abnormalities in the formation of motor neurons at presynaptic terminals at the neuromuscular junction. INHERITANCE \- Autosomal recessive SKELETAL Feet \- Pes cavus \- Hammertoes MUSCLE, SOFT TISSUES \- Distal muscle weakness \- Distal muscle atrophy \- Ragged red fibers seen on muscle biopsy \- COX-negative fibers NEUROLOGIC Central Nervous System \- Cerebellar ataxia \- Ataxic gait \- Limb and trunk ataxia \- Poor fine motor skills \- Poor manual dexterity \- Dysarthria \- Dysmetria \- Tremor \- Impaired intellectual development (in some patients) \- Cerebellar atrophy \- Leukoencephalopathy (in some patients) \- Spinal cord atrophy (in some patients) Peripheral Nervous System \- Foot drop \- Steppage gait \- Hyporeflexia \- Distal sensory impairment \- Axonal peripheral neuropathy \- Loss of myelinated fibers seen on sural nerve biopsy LABORATORY ABNORMALITIES \- Increased serum creatine kinase, mild \- Increased serum and CSF lactate \- Variably decreased activities of mitochondrial complexes I and IV MISCELLANEOUS \- Onset in first decade \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the cytochrome C oxidase assembly factor 7 gene (COA7, 615623.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE, WITH AXONAL NEUROPATHY 3	None	2,713	omim	https://www.omim.org/entry/618387	2019-09-22T15:42:12	{"omim": ["618387"]}
A number sign (#) is used with this entry because a mutation in the PMP22 gene (601097) on chromosome 17 was identified in a single family with the acute (AIDP) and chronic (CIDP) forms of inflammatory demyelinating polyneuropathy. Description Guillain-Barre syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy characterized most commonly by symmetric limb weakness and loss of tendon reflexes. It is a putative autoimmune disorder presenting after an infectious illness, most commonly Campylobacter jejuni, a gram-negative bacterium that causes acute enteritis (Yuki and Tsujino, 1995; Koga et al., 2005). Approximately 1 in 1,000 individuals develops GBS after C. jejuni infection (Nachamkin, 2001). Although rare familial cases have been reported, GBS is considered to be a complex multifactorial disorder with both genetic and environmental factors rather than a disorder following simple mendelian inheritance (Geleijns et al., 2004). Clinical Features Davidson et al. (1992) reported the disorder in a father and son. The father's illness was at the age of 58 years. He recovered completely after a 2-month hospitalization during which he was treated with plasmapheresis. The son was hospitalized 9 years later at the age of 43 years; he also was treated with plasmapheresis, with complete recovery in 3 months. Davidson et al. (1992) commented on remarkably similar HLA typing results in the father and son. Yuki and Tsujino (1995) reported 2 Japanese sisters who developed GBS following C. jejuni enteritis. The 19-month-old sister first developed flaccid tetraplegia and areflexia without sensory impairment and later showed esotropia, dysphagia, dysarthria, and nuchal weakness. All symptoms began to improve after about 2 weeks, and she was able to walk without support at day 117. Her 3.5-year-old sister developed similar clinical features, as well as respiratory failure and absence of corneal reflexes. She became comatose at day 7. She regained consciousness on day 22 and slowly recovered muscle function and the ability to walk without support at day 166. Both children met the clinical criteria for GBS following culture-confirmed C. jejuni enteritis. Geleijns et al. (2004) reported 12 Dutch families in which at least 2 members had GBS. Clinical features were variable, even within families. The most common manifestations were motor deficits, including limb weakness, ataxia, ophthalmoplegia, bulbar weakness, dysphagia, and ptosis, although many patients also had sensory deficits. Almost all had a prodromal infectious illness. Among sibs, the observed incidence was increased 2.6-fold compared to the expected incidence. There was also a trend toward decreased age at onset in younger generations. Inheritance Saunders and Rake (1965) reported a brother and sister in whom muscle weakness developed 4 years apart. MacGregor (1965) reported a father with GBS whose daughter had an acute febrile illness with painful sensory neuropathy. Although these early reports suggested familial occurrence, Yuki and Tsujino (1995) noted that some of the patients reported by Saunders and Rake (1965) and MacGregor (1965) would not have fulfilled the accepted diagnostic criteria for GBS. Bar-Joseph et al. (1991) reported 3 children, born of consanguineous parents in Israel, who all developed GBS before age 3 years. Based on the observation of 12 Dutch families with at least 2 affected members, Geleijns et al. (2004) concluded that there may be a genetic component to increased susceptibility to GBS. Molecular Genetics Guillain-Barre syndrome has been associated with antecedent C. jejuni infections. Ma et al. (1998) found a higher frequency of a rare polymorphism in the TNFA gene (-308G-A; 191160.0004) in 43 Japanese patients with GBS who had had antecedent infection with C. jejuni compared to 85 community controls. Despite the association of Guillain-Barre syndrome with antecedent C. jejuni infection, only a minority of infected individuals develop the disease, implying a role for genetic factors in conferring susceptibility. Pandey and Vedeler (2003) genotyped 83 patients and 196 healthy controls in Norway for immunoglobulin KM genes (genetic markers of the constant region of kappa immunoglobulin chains; 147200) by PCR-RFLP. The frequency of KM3 homozygotes was significantly increased in the patients compared with controls. Conversely, the frequency of KM1/KM3 heterozygotes was significantly decreased in patients compared with controls. The results suggested that KM genes may be relevant to the etiology of Guillain-Barre syndrome. Korn-Lubetzki et al. (2002) described a family of Jewish Kurdish origin in which the father and 2 daughters were diagnosed with inflammatory demyelinating polyneuropathy within 10 years of each other. In the 2 patients tested, the father with the chronic form and a daughter with the acute form, a deletion in the PMP22 gene (601097.0004) typical of hereditary neuropathy with liability to pressure palsies (HNPP; 162500) was identified. The authors suggested that screening for the HNPP deletion in patients with atypical, recurrent, or familial inflammatory demyelinating polyneuropathy may be warranted. Pathogenesis The C. jejuni cst-II gene, which is involved in the biosynthesis of ganglioside-like lipooligosaccharides (LOS), has an asn51-to-thr (N51T) polymorphism that encodes a bifunctional alpha-2,3- and alpha-2,8-sialyltransferase and a monofunctional alpha-2,3-sialyltransferase, respectively. This polymorphism is assumed to affect autoantibody responses in the host through changes in the ganglioside epitope on the outer core of the organism. In a comparison of C. jejuni isolates from 105 patients with GBS, including 25 patients with similar neurologic variants, with 65 patients with uncomplicated enteritis, Koga et al. (2005) found that the neuropathic strains more frequently had the cst-II gene (85%), in particular the cst-II thr51 variant, compared to enteric strains (52%). C. jejuni strains with asn51 regularly expressed the GQ1b epitope (83%), those with thr51 had the GM1 (92%) and GD1a (91%) epitopes, and the presence of these strains in neuropathy patients corresponded to specific autoantibody reactivity. Koga et al. (2005) concluded that the genetic polymorphism of C. jejuni may determine autoantibody reactivity as well as clinical presentation of GBS, possibly through modification of host-mimicking molecules. Hu et al. (2006) detected the IL23p19 protein (IL23A; 605580) in cerebrospinal fluid isolated from 5 patients with GBS. Sural nerve biopsies from these patients showed IL23p19 immunostaining in endoneurial macrophages. IL23A RNA was upregulated in sciatic nerve samples from 5 rats with experimental autoimmune neuritis (EAN), an animal model of GBS. Peak expression of IL23A RNA in the diseased animals occurred 2 days prior to peak clinical disease severity and then decreased to undetectable levels with clinical improvement. Hu et al. (2006) concluded that IL23 may play a role in the early effector phase of immune-mediated demyelination of the peripheral nerve. Misc \- Usually sporadic Neuro \- Acute demyelinating polyneuropathy Inheritance \- ? Autosomal dominant form ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	GUILLAIN-BARRE SYNDROME, FAMILIAL	c0393819	2,714	omim	https://www.omim.org/entry/139393	2019-09-22T16:40:28	{"doid": ["12842"], "mesh": ["D020277"], "omim": ["139393"], "icd-9": ["357.81"], "icd-10": ["G61.81"], "orphanet": ["98916"], "synonyms": ["AIDP", "POLYNEUROPATHY, INFLAMMATORY DEMYELINATING, ACUTE", "Acute inflammatory polyneuropathy", "GBS, acute inflammatory demyelinating polyradiculoneuropathic form", "Acute idiopathic demyelinating polyneuropathy", "Guillain-Barré syndrome, acute inflammatory demyelinating polyradiculoneuropathic form", "Alternative titles"]}
Disease in rabbits caused by Myxoma virus This article is about the disease in rabbits. For the Radiohead song, see Hail to the Thief. Myxoma virus Myxoma virus (transmission electron microscope) Virus classification (unranked): Virus Realm: Varidnaviria Kingdom: Bamfordvirae Phylum: Nucleocytoviricota Class: Pokkesviricetes Order: Chitovirales Family: Poxviridae Genus: Leporipoxvirus Species: Myxoma virus Myxomatosis is a disease caused by Myxoma virus, a poxvirus in the genus Leporipoxvirus. The natural hosts are tapeti (Sylvilagus brasiliensis) in South and Central America, and brush rabbits (Sylvilagus bachmani) in North America. The myxoma virus causes only a mild disease in these species, but causes a severe and usually fatal disease in European rabbits (Oryctolagus cuniculus). Myxomatosis is an excellent example of what occurs when a virus jumps from a species adapted to it to a naive host, and has been extensively studied for this reason. The virus was intentionally introduced in Australia, France, and Chile in the 1950s to control wild European rabbit populations. ## Contents * 1 Cause * 2 Transmission * 3 Pathophysiology * 4 Clinical presentation in European rabbits * 5 Diagnosis * 6 Treatment * 7 Prevention * 7.1 Vaccination * 7.2 Other preventive measures * 8 Use as a population control agent * 8.1 Australia * 8.2 Europe * 8.3 South America * 9 Use as an evolutionary model * 10 In fiction * 11 References * 12 Further reading * 13 External links ## Cause[edit] Myxoma virus is in the genus Leporipoxvirus (family Poxviridae; subfamily Chordopoxvirinae). Like other poxviruses, myxoma viruses are large DNA viruses with linear double-stranded DNA. Virus replication occurs in the cytoplasm of the cell. The natural hosts are tapeti (Sylvilagus brasiliensis) in South and Central America, and brush rabbits (Sylvilagus bachmani) in North America. The myxoma virus causes only a mild disease in these species, with symptoms limited to the formation of skin nodules.[1] Myxomatosis is the name of the severe and often fatal disease in European rabbits caused by the myxoma virus. Different strains exist which vary in their virulence. The Californian strain, which is endemic to the west coast of the United States and Baja in Mexico, is the most virulent, with reported case fatality rates of 100%. The South American strain, present in South America and Central America, is slightly less virulent, with reported case fatality rates of 99.8%. Strains present in Europe and Australia have become attenuated, with reported case fatality rates of 50%-95%. While wild rabbits in Europe and Australia have developed some immunity to the virus, this is not generally true of pet rabbits.[2] ## Transmission[edit] Myxomatosis is transmitted primarily by insects. Disease transmission commonly occurs via mosquito or flea bites, but can also occur via the bites of mites, flies, and lice. The myxoma virus does not replicate in these insect hosts, but is physically carried by biting insects from one rabbit to another. Seasonality is driven by the availability of insect vectors and the proximity of infected wild rabbits.[3] The myxoma virus can also be transmitted by direct contact. Infected rabbits shed the virus in ocular and nasal secretions and from areas of eroded skin. The virus may also be present in semen and genital secretions. Poxviruses are fairly stable in the environment and can be spread by contaminated objects such as water bottles, feeders, caging, or people's hands.[3] They are resistant to drying but are sensitive to some disinfectants.[4] ## Pathophysiology[edit] A laboratory study in which European rabbits received intradermal injections of a South American strain of the myxoma virus demonstrated the following progression of disease. Initially the virus multiplied in the skin at the site of inoculation. Approximately 2 days following inoculation the virus was found in nearby lymph nodes, and at 3 days it was found in the bloodstream and abdominal organs. At approximately 4 days the virus was isolated from non-inoculated skin as well as from the testes. Slight thickening of the eyelids and the presence of virus in conjunctival fluid was detectable on day 5. Testicular engorgement was noticed on day 6.[5] ## Clinical presentation in European rabbits[edit] European rabbit with Lausanne strain of myxomatosis (West Yorkshire, UK) European rabbit with Californian strain of myxomatosis, indicated by swollen eyelids and genitals (Santa Cruz, California) The clinical signs of myxomatosis depend on the strain of virus, the route of inoculation, and the immune status of the host. Symptoms of the classic nodular form of the disease include a subcutaneous mass at the site of inoculation, swelling and edema of the eyelids and genitals, a milky or purulent ocular discharge, fever, lethargy, depression, and anorexia.[citation needed] According to Meredith (2013), the typical time course of the disease is as follows: Days after infection Clinical signs 2-4 Swelling at site of infection 4 Fever 6 Swelling of eyelids, face, base of ears, and anogenital area 6 Secondary skin lesions, including red pinpoint lesions on eyelids and raised masses on body 6-8 Clear ocular and nasal discharge that becomes mucopurulent and crusting 7-8 Respiratory distress 8-9 Hypothermia 10 Complete closure of eyelids due to swelling 10-12 Death In peracute disease with a highly virulent strain, death may occur within 5 to 6 days of infection with minimal clinical signs other than the conjunctivitis. Death usually occurs between days 10 and 12. Highly virulent strains, such as those present in North and South America, have essentially 100% case fatality rates. In rabbits infected with attenuated, less virulent strains of the virus, the lesions seen are more variable and generally milder, and the time course is delayed and prolonged. Many rabbits will survive and the cutaneous lesions gradually scab and fall off, leaving scarring. A milder form of the disease is also seen in previously vaccinated domestic rabbits that have partial immunity. Vaccinated rabbits often present with localized scabbed lesions, frequently on the bridge of the nose and around the eyes, or multiple cutaneous masses over the body. They are often still bright and alert, and survive with nursing care.[1] Respiratory symptoms are a common finding in rabbits that survive the first stages of myxomatosis. Mucopurulent nasal discharge occurs, leading to gasping and stertorous respiration with extension of the head and neck. Secondary bacterial pneumonia occurs in many cases. Chronic respiratory disease, such as nasal discharge, is common in surviving rabbits. Even in apparently recovered rabbits, it is not unusual to find lung lobes filled with fluid rather than air at necropsy.[3] Since the 1970s an "amyxomatous" form of the disease has been reported in Europe which lacks the cutaneous nodules typical of myxomatosis. This form is clinically milder and generally nonlethal. Respiratory signs, including clear or purulent nasal discharge, predominate. Perineal edema, swollen eyelids, and purulent blepharoconjunctivitis are generally still present. This form has been observed in wild rabbits, but is significant mainly in farmed rabbits.[1] ## Diagnosis[edit] Diagnosis of myxomatosis in European rabbits is often made on the basis of the characteristic clinical appearance. If a rabbit dies without exhibiting the classic symptoms of myxomatosis, or if further confirmation is desired, a number of laboratory tests are available. Historically these have included histopathology, electron microscopy, and virus isolation. Histopathologic examination of affected skin typically shows undifferentiated mesenchymal cells within a matrix of mucin, inflammatory cells, and edema. Intracytoplasmic inclusions may be seen in the epidermis and in conjunctival epithelium.[6] Negative-stain electron microscopic examination can also be used for diagnosis due to the large size and distinctive structure of poxviruses. This method allows rapid visualization of poxviruses, but does not allow specific verification of virus species or variants.[7] Virus isolation remains the "gold standard" against which other methods of virus detection are compared. Theoretically at least, a single viable virus present in a specimen can be grown in cultured cells, thus expanding it to produce enough material to permit further detailed characterization.[8] The more recent development of molecular methods such as polymerase chain reaction (PCR) and real-time polymerase chain reaction assays has created faster and more accurate methods of myxoma virus identification.[7] Real time PCR simplifies the diagnosis of myxomatosis by allowing nasal, ocular, or genital swabs to be quickly tested. It can also be used on paraffin-embedded tissue samples to confirm the presence of Myxoma virus and identify the viral strain.[9] ## Treatment[edit] At present, no specific treatment exists for myxomatosis. If the decision is made to attempt treatment, careful monitoring is necessary to avoid prolonging suffering. Previously vaccinated rabbits or those infected with an attenuated strain may recover given supportive care with fluids, food, and broad spectrum antivirals. Cessation of food and water intake, ongoing severe weight loss, or rectal temperatures below 37 C (98.6 F) are reasons to consider euthanasia.[3] ## Prevention[edit] ### Vaccination[edit] Vaccines against myxomatosis are available in some countries. All are modified live vaccines based either on attenuated myxoma virus strains or on the closely related Shope fibroma virus, which provides cross-immunity. It is recommended that all rabbits in areas of the world where myxomatosis is endemic be routinely vaccinated, even if kept indoors, because of the ability of the virus to be carried inside by vectors or fomites. In group situations where rabbits are not routinely vaccinated, vaccination in the face of an outbreak is beneficial in limiting morbidity and mortality.[1] The vaccine does not provide 100% protection,[3] so it is still important to prevent contact with wild rabbits and insect vectors. Myxomatosis vaccines must be boostered regularly to remain effective, and annual vaccinations are usually recommended.[1] In Europe and the United Kingdom a bivalent vectored vaccine called Nobivac Myxo-RHD[10] is available that protects against both myxomatosis and rabbit haemorrhagic disease. This vaccine is licensed for immunization of rabbits 5 weeks of age or older, with onset of immunity taking approximately 3 weeks. Protection against myxomatosis and rabbit hemorrhagic disease has a duration of immunity for 12 months, and annual vaccination is recommended to ensure continued protection.The vaccine has been shown to reduce mortality and clinical signs of myxomatosis.[11] Vaccination against myxomatosis is currently prohibited in Australia due to concerns that the vaccine virus could spread to wild rabbits and increase their immunity to myxomatosis. As feral rabbits in Australia already cause a great deal of environmental damage, this concern is taken seriously by the government.[12] Many pet rabbits in Australia continue to die from myxomatosis due to their lack of immunity.[13] There is at least one campaign to allow the vaccine for domestic pets.[14] The Australian Veterinary Association supports the introduction of a safe and effective myxomatosis vaccine for pet rabbits,[15] and the RSPCA of Australia has repeatedly called for a review of available myxoma virus vaccines and a scientific assessment of their likely impacts in the Australian setting.[16] Although myxomatosis is endemic in parts of Mexico and the United States, there is no commercially available vaccine in either of these countries. Information on recently reported cases in the United States is available from the House Rabbit Society.[17] In the United States the importation of vaccines is overseen by the Animal and Plant Health Inspection Service, part of the Department of Agriculture.[18] ### Other preventive measures[edit] In locations where myxomatosis is endemic but no vaccine is available, preventing exposure to the myxoma virus is of vital importance. Even vaccinated rabbits need protection, as the vaccines are not 100% effective. The risk of a pet's contracting myxomatosis can be reduced by preventing contact with wild rabbits, keeping rabbits indoors (preferred) or behind screens to prevent mosquito exposure, and using rabbit-safe medications to treat and prevent fleas, lice, and mites. Any new rabbit that may have been exposed should be quarantined, and rabbits suspected of having myxomatosis should be immediately isolated until the diagnosis is ruled out. If the disease is confirmed all contaminated cages, dishes, or other objects should be disinfected with 10% bleach, 10% sodium hydroxide, or 1%–1.4% formalin.[19] ## Use as a population control agent[edit] Rabbit and myxomatosis introductions around the world with dates Myxoma virus was the first virus intentionally introduced into the wild with the purpose of eradicating a vertebrate pest, namely the European rabbit in Australia and Europe. The long-term failure of this strategy has been due to natural selective pressures on both the rabbit and virus populations, which resulted in the emergence of myxomatosis-resistant animals and attenuated virus variants. The process is regarded as a classical example of host-pathogen coevolution following cross-species transmission of a pathogen.[20] ### Australia[edit] Rabbits around a waterhole in the myxomatosis trial site on Wardang Island, Australia in 1938 Releasing the Myxoma virus in Australia European rabbits were brought to Australia in 1788 by early English settlers (see Rabbits in Australia). Initially used as a food source, they later became feral and their numbers soared. In November 1937, the Australian Council for Scientific and Industrial Research used Wardang Island to conduct its first field trials of myxomatosis, which established the methodology for the successful release of the myxoma virus throughout the country.[21] In 1950, the SLS strain of myxoma virus from the South American tapeti (Sylvilagus brasiliensis) was released in Australia as a biological control agent against feral rabbits. The virus was at first highly lethal, with an estimated case fatality rate of close to 99.8%. Within a few years, however, this strain was replaced by less virulent ones, which permitted longer survival of infected rabbits and enhanced disease transmission. The virus created strong selection pressure for the evolution of rabbits resistant to myxomatosis. As rabbits became more resistant the viral strains responded by becoming less virulent.[2] Rabbit hemorrhagic disease virus has also been used to control wild rabbit populations in Australia since 1995.[22] ### Europe[edit] In June 1952, Dr. Paul-Félix Armand-Delille, the owner of an estate in northwestern France, inoculated two wild rabbits with the Lausanne strain of myxoma virus.[23] His intention was to only eradicate rabbits on his property, but the disease quickly spread to Western Europe, Ireland and the United Kingdom.[24] Some dissemination of the virus was clearly deliberate, such as the introduction into Britain in 1953 and the introduction into Ireland in 1954.[25] Unlike in Australia, however, strenuous efforts were made to stop the spread in Europe. These efforts were in vain. It was estimated that the wild rabbit population in the United Kingdom fell by 99%, in France by 90% to 95%, and in Spain by 95%. This in turn drove specialized rabbit predators, such as the Iberian lynx and the Spanish imperial eagle, to the brink of extinction.[26][27] As well as decreasing the wild rabbit population and the population of its natural predators, myxomatosis had significant impacts on the large rabbit farming industry, which produced domestic rabbits for meat and fur.[28] The Lausanne strain of the myxoma virus creates the formation of large purple skin nodules, a symptom not seen in other strains. As happened in Australia, the virus has generally become less virulent and the wild rabbit populations more resistant since then.[24] ### South America[edit] Two pairs of European rabbits set free in 1936 at Punta Santa Maria resulted in an infestation that spread over the northern half of Tierra del Fuego. More rabbits were introduced in 1950 near Ushuaia by the Argentinian Navy and a private rabbit farmer. The rabbits quickly became pests, riddling the ground with holes and leaving it bare of grass. By 1953 the rabbit population numbered about 30 million. In 1954 Chilean authorities introduced a Brazilian strain of myxoma virus to Tierra del Fuego, which succeeded in bringing rabbits to very low population levels.[29] ## Use as an evolutionary model[edit] Evolutionary history of the Myxoma virus in Europe and Australia Given the importance of viral evolution to disease emergence, pathogenesis, drug resistance, and vaccine efficacy, it has been well studied by theoreticians and experimentalists. The introductions of myxoma virus into European rabbit populations in Australia and France created natural experiments in virulence evolution.[30] While initial viral strains were highly virulent, attenuated strains were soon recovered from the field. These attenuated strains, which allowed rabbits to survive longer, came to dominate because they were more readily transmitted. As the complete genome sequences of multiple myxoma strains have been published, scientists have been able to pinpoint exactly which genes are responsible for the changes in the myxoma virus's virulence and behavior.[31] ## In fiction[edit] Myxomatosis is referred to as "the white blindness" by the rabbit characters of the novel Watership Down by Richard Adams, and in the story a rabbit chief had driven out all rabbits who seemed to be afflicted. In one of the novel's folk tales about the rabbit hero El-ahrairah, the transmission of the disease is explained to him by the lord of the rabbit underworld, the Black Rabbit of Inle ("it is carried by the fleas in rabbits' ears; they pass from the ears of a sick rabbit to those of his companions").[32] ## References[edit] 1. ^ a b c d e Meredith, A (2013). "Viral skin diseases of the rabbit". Veterinary Clinics of North America: Exotic Animal Practice. 16 (3): 705–714. doi:10.1016/j.cvex.2013.05.010. PMID 24018033. 2. ^ a b Kerr, P (2017). "Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia". PLOS Pathogens. 13 (3): e1006252. doi:10.1371/journal.ppat.1006252. PMC 5349684. PMID 28253375. 3. ^ a b c d e Kerr, P (2013). "Viral Infections of Rabbits". Veterinary Clinics of North America: Exotic Animal Practice. 16 (2): 437–468. doi:10.1016/j.cvex.2013.02.002. PMC 7110462. PMID 23642871. 4. ^ "Disinfection". The Center for Food Security and Public Health. Retrieved 21 July 2019. 5. ^ Fenner, F; Woodroofe, GM (1953). "The pathogenesis of infectious myxomatosis: the mechanism of infection and the immunological response in the European rabbit (Oryctolagus cuniculus)". The British Journal of Experimental Pathology. 34 (4): 400–411. PMID 13093911. 6. ^ Quesenberry, K (2012). Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (Third ed.). Elsevier Saunders. p. 240. ISBN 978-1-4160-6621-7. 7. ^ a b MacLachlan, J (2017). Fenner's Veterinary Virology, 5th Edition. Elsevier. p. 158. ISBN 978-0-12-800946-8. 8. ^ MacLachlan, J (2017). Fenner's Veterinary Virology, 5th Edition. Elsevier. p. 112. ISBN 978-0-12-800946-8. 9. ^ Albini, S; Sigrist, B; Güttinger, R; et al. (6 December 2011). "Development and validation of a real-time polymerase chain reaction assay" (PDF). Journal of Veterinary Diagnostic Investigation. 24 (1): 135–137. doi:10.1177/1040638711425946. PMID 22362943. S2CID 32171325. 10. ^ "Nobivac Myxo RHD". MSD Animal Health. Retrieved 20 July 2019. 11. ^ "Nobivac Myxo RHD Data Sheet". European Medicine Agency. Retrieved 20 July 2019. 12. ^ "A Statement from the Chief Veterinary Officer (Australia) on myxomatosis vaccine availability in Australia". Australian Government Department of Agriculture. Retrieved 20 July 2019. 13. ^ "The Rabbit Sanctuary Myxomatosis Hotline". Myxomatosis. Retrieved 20 July 2019. 14. ^ "Myxo Campaign". Myxomatosis. Retrieved 20 July 2019. 15. ^ "Myxomatosis vaccination of pet rabbits". Australian Veterinary Association. Retrieved 20 July 2019. 16. ^ "Why can't I vaccinate my rabbit against Myxomatosis?". Royal Society for the Prevention of Cruelty to Animals. Retrieved 20 July 2019. 17. ^ "Myxomatosis in the US". House Rabbit Society. Retrieved 23 August 2019. 18. ^ "Veterinary Biologics". United States Department of Agriculture, Animal and Plant Health Inspection Service. Retrieved 23 July 2019. 19. ^ Oglesbee, B (2011). Blackwell's Five-Minute Veterinary Consult: Small Mammal (Second ed.). West Sussex, UK: Wiley-Blackwell. p. 455. ISBN 978-0-8138-2018-7. 20. ^ MacLachlan, J (2017). Fenner's Veterinary Virology, 5th Edition. Elsevier. p. 168. ISBN 978-0-12-800946-8. 21. ^ "Rabbits around a waterhole at the enclosed trial site at Wardang Island, 1938". National Archives of Australia. Retrieved 28 July 2019. 22. ^ Mahar JE, Read AJ, Gu X, Urakova N, Mourant R, Piper M, Haboury S, Holmes EC, Strive T, Hall RN (January 2018). "Detection and Circulation of a Novel Rabbit Hemorrhagic Disease Virus in Australia". Emerg Infect Dis. 24 (1): 22–31. doi:10.3201/eid2401.170412. PMC 5749467. PMID 29260677. 23. ^ Davis, J. "Darwin's rabbit is revealing how the animals became immune to myxomatosis". Natural History Museum. Retrieved 14 August 2019. 24. ^ a b Kerr, P; Liu, J; Cattadori, I; et al. (6 March 2015). "Myxoma Virus and the Leporipoxviruses: An Evolutionary Paradigm". Viruses. 7 (3): 1020–1061. doi:10.3390/v7031020. PMC 4379559. PMID 25757062. 25. ^ Bartrip, P (2008). Myxomatosis: A History of Pest Control and the Rabbit. London, UK: Tauris Academic Studies. ISBN 978-1845115722. 26. ^ Gil-Sánchez, JM; McCain, EB (14 October 2011). "Former range and decline of the Iberian lynx (Lynx pardinus) reconstructed using verified records". Journal of Mammalogy. 92 (5): 1081–1090. doi:10.1644/10-MAMM-A-381.1. 27. ^ Sánchez, B. "Action plan for the Spanish imperial eagle (Aquila adalberti) in the European Union" (PDF). European Commission. Retrieved 14 August 2019. 28. ^ Cadogan, S (23 March 2017). "How a thriving food industry faded away to nothing in the 1960s". The Irish Examiner. Cork. Retrieved 15 October 2017. 29. ^ Jaksic, F (1983). "Rabbit and Fox Introductions in Tierra del Fuego: History and Assessment of the Attempts at Biological Control of the Rabbit Infestation". Biological Conservation. 26 (4): 369–370. doi:10.1016/0006-3207(83)90097-6. 30. ^ Bull, JJ; Lauring, AS; Condit, RC (2014). "Theory and Empiricism in Virulence Evolution". PLOS Pathogens. 10 (10): e1004387. doi:10.1371/journal.ppat.1004387. PMC 4207818. PMID 25340792. 31. ^ Burgess, HM; Mohr, I (2016). "Evolutionary clash between myxoma virus and rabbit PKR in Australia". Proceedings of the National Academy of Sciences. 113 (15): 3912–3914. Bibcode:2016PNAS..113.3912B. doi:10.1073/pnas.1602063113. PMC 4839419. PMID 27035991. 32. ^ Cassidy, A (2019). Vermin, Victims and Disease: British Debates Over Bovine Tuberculosis and Badgers. Springer Nature. p. 178. ISBN 9783030191863. ## Further reading[edit] * Deane, C.D. 1955. Note on myxomatosis in hares. Bulletin of the Mammal Society of the British Isles. 3: 20. * Fenner, Frank. 1965. Myxomatosis. Cambridge University Press. ISBN 978-0521049917. ## External links[edit] Wikimedia Commons has media related to Myxomatosis. * An interview with Frank Fenner * A Statement from the Chief Veterinary Officer (Australia) on myxomatosis vaccine availability in Australia * v * t * e Flea-borne diseases Bacterial infection (all G-) * Murine typhus * Lyme disease * Rocky Mountain spotted fever * Ehrlichiosis * Relapsing fever * Tularemia Viral infection * Tick-borne meningoencephalitis * Colorado tick fever * Crimean-Congo hemorrhagic fever * Myxomatosis Protozoan infection * Babesiosis * Cytauxzoonosis Helminth * Hymenolepiasis tapeworm Vectors [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Myxomatosis	c0027152	2,715	wikipedia	https://en.wikipedia.org/wiki/Myxomatosis	2021-01-18T19:00:21	{"mesh": ["D009234"], "wikidata": ["Q1342455"]}
A rare pulmonary condition characterized by accumulation of pus in the pleural cavity, most commonly as a consequence of pneumonia, but also trauma and surgical procedures. Clinical signs and symptoms depend on host factors, as well as the nature of the causative microorganism, among others, and include cough, chest pain, dyspnea, and fever. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pleural empyema	c0014013	2,716	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=449266	2021-01-23T17:05:59	{"mesh": ["D016724"], "umls": ["C0014013"]}
## Description Thiemann disease is a rare disorder that is considered to be a form of avascular necrosis of the proximal interphalangeal joints of the fingers and toes. The clinical symptoms usually appear in adolescence (Kotevoglu-Senerdem et al., 2003). Clinical Features Familial osteoarthropathy of fingers was first described by Thiemann (1909). Allison and Blumberg (1958) described 2 unrelated families in which many members (23 in 1 family and 20 in the other) had painless deformity at the proximal interphalangeal joints beginning in childhood or adolescence. The proposita in 1 family showed nodular enlargement of the proximal and distal interphalangeal joints of all digits. Those of the terminal joints resembled Heberden nodes. The terminal phalanges of the fingers were shortened. There was slight restriction of flexion at both wrists, but this was not accompanied by a deformity. The feet showed hallux valgus. Radiographs of the feet showed changes like those in the fingers. Trippel (1950) and Fournier et al. (1969) each described 1 family with Thiemann disease. Boehme (1963) reported 2 brothers with Thiemann epiphyseal disease involving the proximal interphalangeal joints of the fingers. The metaphyses and epiphyses were broad and short. Onset was at 13 and 17 years. The parents were not related and they and other family members were not affected. Gewanter and Baum (1985) reported 2 unrelated children with no other known affected individuals in their families. Both children had a history of swollen, tender proximal interphalangeal joints with radiographic evidence of irregularities of the epiphyses leading to premature fusion and subsequent shortening of the middle phalanges. Schantz and Rasmussen (1986) reexamined 7 patients (4 males, 3 females) with Thiemann disease. Two patients had had pain in the affected digits for several years. In 4 patients, radiographs after closure of the growth plates showed normal phalangeal dimensions without arthrosis. The authors concluded that different degrees of severity of epiphyseal disturbance occur in this disorder. Population Genetics Giedion (1976) classified Thiemann disease with acrodysplasias and stated: 'We have never seen a typical case of this condition, which by now may be extinct.' Although Thiemann disease is considered to be a rare disorder, Gewanter and Baum (1985) and Kotevoglu-Senerdem et al. (2003) suggested that greater recognition of its features may lead to its more frequent diagnosis. Diagnosis ### Differential Diagnosis Allison and Blumberg (1958) stated that this disorder can be distinguished from osteoarthritis, rheumatoid arthritis, and gout by its early age of onset, equal sex incidence, benign course, absence of symptoms, characteristic joint distribution, and lack of abnormal laboratory findings. Kotevoglu-Senerdem et al. (2003) reported 2 Turkish brothers, aged 14 and 17 years, with Thiemann disease. The 17-year-old proband had been misdiagnosed 3 years earlier as having rheumatoid arthritis. The authors stated that the characteristic symmetrical, firm, relatively painless deformity and x-ray findings of the epiphyseal irregularities should suggest the diagnosis of Thiemann disease. Inheritance Allison and Blumberg (1958) stated that the pattern of transmission in the families they reported resembled that of previously reported families, i.e., autosomal dominant inheritance. However, in 1 of their families, 2 children of first-cousin affected parents were much more severely affected than their sibs. The authors suggested that the 2 children may have been homozygotes. Rubinstein (1975) suggested autosomal dominant transmission of Thiemann disease. Limbs \- Proximal interphalangeal joint osteoarthropathy Radiology \- Avascular necrosis of phalangeal epiphyses \- Broad and short phalangeal metaphyses and epiphyses Misc \- Onset in second decade 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	THIEMANN DISEASE	c0264081	2,717	omim	https://www.omim.org/entry/165700	2019-09-22T16:37:02	{"mesh": ["C537144"], "omim": ["165700"], "orphanet": ["3314"], "synonyms": ["THIEMANN EPIPHYSEAL DISEASE", "Osteochondrosis of phalangeal epiphyses", "Alternative titles", "OSTEOARTHROPATHY OF FINGERS, FAMILIAL", "Aseptic necrosis of phalangeal epiphyses", "Osteochondritis of phalangeal epiphyses"]}
Anterior segment dysgenesis (ASD) refers to a spectrum of disorders that affect the development of the front of the eye (the anterior segment), which includes the cornea, iris, ciliary body, and lens. The specific eye abnormalities (alone or in combination) vary depending on the subtype of ASD and genetic cause, and some types may also be associated with neurological abnormalities. Glaucoma develops in approximately 60% of people with ASD, during infancy or much later. Specific eye signs and symptoms of ASD may include: * Underdevelopment of the iris (iris hypoplasia). * An enlarged or reduced cornea diameter. * Growth of new blood vessels (vascularization) and opacity in the cornea. * Posterior embryotoxon (a thickened and displaced Schwalbe's line). * Corectopia (displacement of the pupil). * Polycoria (more than one pupillary opening). * An abnormal iridocorneal angle (the angle formed by the iris and cornea). * Ectopia lentis (displacement of the lens). * Aphakia (absent lens). * Cataracts. * Anterior synechiae (when the iris adheres to the cornea). * Posterior keratoconus (thinning of the cornea). Individual disorders within the ASD spectrum include Axenfeld-Rieger syndrome (which includes disorders formerly known as Axenfeld anomaly, Axenfeld syndrome, Rieger anomaly, Rieger syndrome, and iridogoniodysgenesis) and Peters anomaly. ASD may be caused by mutations in any of several genes and inheritance can be autosomal dominant or autosomal recessive, depending on the responsible gene. Treatment of signs and symptoms depends on the specific features in each person with ASD and may involve medications, eye surgery, or corrective lenses for poor vision. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Anterior segment dysgenesis	c1862839	2,718	gard	https://rarediseases.info.nih.gov/diseases/10025/anterior-segment-dysgenesis	2021-01-18T18:02:05	{"mesh": ["C537775"], "omim": ["107250"], "orphanet": ["88632"], "synonyms": ["FOXE3-related ocular disorder", "Familial ocular anterior segment mesenchymal dysgenesis", "ASMD", "Anterior segment dysgenesis", "Anterior segment developmental anomaly", "ASOD", "Anterior segment mesenchymal dysgenesis", "Anterior segment ocular dysgenesis"]}
A rare common cystic lymphatic malformation characterized by a benign cystic lesion composed of dilated lymphatic channels. Microcystic lesions consist of cysts smaller than 1 cm in diameter. They usually present at birth or during the first years of life and most often occur in the head and neck region but may affect any site. Symptoms depend on the location and extent of the lesion. Infection, trauma, or intracystic hemorrhage can lead to lesional expansion. Malignant transformation does not 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Microcystic lymphatic malformation	c0334543	2,719	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79490	2021-01-23T18:56:20	{"icd-10": ["D18.1"], "synonyms": ["Capillary lymphangioma", "Capillary lymphatic malformation", "Cutaneous lymphangioma circumscriptum", "Microcystic infiltrating lymphatic malformation", "Microcystic lymphangioma", "Superficial lymphangioma", "Superficial lymphatic malformation"]}
Thrombotic thrombocytopenic purpura (TTP), acquired is a blood disorder characterized by low platelets (i.e., thrombocytopenia), small areas of bleeding under the skin (i.e., purpura), low red blood cell count, and hemolytic anemia. TTP causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and decrease or stop blood flow to organs such as the brain, kidneys, and heart. Complications may include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems. Hemolytic anemia can lead to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Acquired TTP usually begins in adulthood, but can affect children. An episode of TTP usually occurs suddenly and lasts for days or weeks, but it may continue for months. Relapses (or flareups) can occur in up to 60 percent of people who have the acquired TTP. Acquired TTP is caused when a person's body mistakingly makes antibodies that block the activity of the ADAMTS13 enzyme. THe ADAMTS13 enzyme normally helps control the activity of certain blood clotting factors. Treatment includes plasma exchange and in some cases may also include corticosteroid therapy or rituximab. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Thrombotic thrombocytopenic purpura, acquired	c2584778	2,720	gard	https://rarediseases.info.nih.gov/diseases/4607/thrombotic-thrombocytopenic-purpura-acquired	2021-01-18T17:57:22	{"mesh": ["C536901"], "synonyms": ["Purpura, thrombotic thrombocytopenic", "TTP", "Moschowitz syndrome", "Idiopathic thrombotic thrombocytopenic purpura"]}
Idiopathic pulmonary hemosiderosis is a respiratory disease due to repeated episodes of diffuse alveolar hemorrhage without any underlying apparent cause, most often in children. Anemia, cough, and pulmonary infiltrates on chest radiographs are found in majority of the patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Idiopathic pulmonary hemosiderosis	c0020807	2,721	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99931	2021-01-23T18:15:38	{"gard": ["6763"], "mesh": ["C536281"], "omim": ["178550", "235500"], "umls": ["C0020807"], "icd-10": ["E83.1+", "J99.8*"]}
Hypoinsulinemic hypoglycemia and body hemihypertrophy is a rare, genetic, endocrine disease characterized by neonatal macrosomia, asymmetrical overgrowth (typically manifesting as left-sided hemihypertrophy) and recurrent, severe hypoinsulinemic (or hypoketotic hypo-fatty-acidemic) hypoglycemia in infancy, which results in episodes of reduced consciousness and seizures. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hypoinsulinemic hypoglycemia and body hemihypertrophy	c3278384	2,722	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=293964	2021-01-23T17:14:35	{"omim": ["240900"]}
A number sign (#) is used with this entry because of evidence that trigonocephaly-2 (TRIGNO2) is caused by heterozygous mutation in the FREM1 gene (608944) on chromosome 9p22. Description Trigonocephaly occurs predominantly as a nonsyndromic craniosynostosis and has an estimated prevalence of between 1:15,000 and 1:68,000 live births (summary by Vissers et al., 2011). For a discussion of genetic heterogeneity of isolated trigonocephaly, see TRIGNO1 (190440). A syndromic form of trigonocephaly is associated with monosomy for an 8-Mb interval of chromosome 9p22.3 (see 158170). Cytogenetics Using high-density chromosome 9-specific arrays, Vissers et al. (2011) reanalyzed the deletion breakpoints of 4 patients with syndromic metopic craniosynostosis and de novo copy number variation involving chromosome 9p22.3 (see 158170), 3 of whom were previously studied by Swinkels et al. (2008). Two of the patients' rearrangements contained deletion breakpoints within the FREM1 gene (608944), deleting exons 7 to 37 and 10 to 37, respectively; in the remaining 2 patients, the FREM1 gene was entirely deleted. Vissers et al. (2011) concluded that the CNV data were consistent with a model in which haploinsufficiency of FREM1 is associated with trigonocephaly. Molecular Genetics Vissers et al. (2011) analyzed the FREM1 gene in 104 patients with nonsyndromic metopic craniosynostosis and identified heterozygous missense mutations in 3 patients (608944.0008 and 608944.0009) that were not found in control chromosomes. Incomplete penetrance was demonstrated in 2 of the families, in which family members who also carried the mutation in heterozygosity displayed minimal or no craniofacial abnormalities. Animal Model Vissers et al. (2011) studied C57BL/6J mice carrying the ENU-generated Frem1(bat) mutation, which is thought to represent a hypomorphic allele rather than a null allele. Morphometric analysis of skulls from homozygous and heterozygous mutant mice demonstrated craniofacial malformations consistent with the craniofacial features seen in the 9p22 deletion syndrome (158170), in particular metopic craniosynostosis and midface asymmetry and/or hypoplasia. The penetrance of the phenotypes in mice correlated to mutant gene dosage. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Trigonocephaly \- Microcephaly (in some patients) Eyes \- Hypertelorism (in some patients) SKELETAL Skull \- Metopic craniosynostosis MOLECULAR BASIS \- Caused by mutation in the FRAS1-related extracellular matrix protein-1 gene (FREM1, 608944.0008 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	TRIGONOCEPHALY 2	c0265535	2,723	omim	https://www.omim.org/entry/614485	2019-09-22T15:55:07	{"mesh": ["D003398"], "omim": ["614485"], "orphanet": ["3366"], "synonyms": ["Alternative titles", "CRANIOSYNOSTOSIS, METOPIC"]}
Psychosexual disorder SpecialtyPsychiatry, psychology Psychosexual disorder is a sexual problem that is psychological, rather than physiological in origin. "Psychosexual disorder" was a term used in Freudian psychology. The term of psychosexual disorder (Turkish: Psikoseksüel bozukluk) used by the TAF for homosexuality as a reason to ban the LGBT people from military service. ## Contents * 1 Paraphilias * 1.1 Fetishism and transvestic fetishism * 1.2 Sexual sadism and sexual masochism * 1.3 Voyeurism, exhibitionism and frotteurism * 2 Diagnosis * 3 Treatment * 4 History * 4.1 Sigmund Freud * 4.2 Richard Freiherr von Kraft-Ebing * 4.3 Havelock Ellis * 5 See also * 6 References * 7 External links ## Paraphilias[edit] Paraphilias are generally defined as psychosexual disorders in which significant distress or an impairment in a domain of functioning results from recurrent intense sexual urges, fantasies or behaviors generally involving an unusual object, activity, or situation.[1] An alternative definition is given by the DSM-5 which labels them as sexual; attractions to objects, situations or people that deviate from the desires and sexual behaviors that are considered to be socially acceptable. Examples of these paraphilias would include fetishism, sexual masochism and sadism and more.[2] ### Fetishism and transvestic fetishism[edit] Fetishism is a disorder that is characterized by a sexual fixation, fantasies or behaviors toward an inanimate object, these objects frequently are articles of clothing. It is only through this object which the individual can achieve sexual gratification. It is not rare that an individual will rub or smell the object. This disorder is more common in males and it is not understood why.[3] Transvestic fetishism also commonly known as transvestism.[citation needed] ### Sexual sadism and sexual masochism[edit] The disorders known as sexual sadism and sexual masochism are oftentimes confused or hard to separate when their definitions are compared but diagnostic criteria differ slightly between the two and allows for more easy classification.[4] Sexual sadism disorder and sexual masochism are defined as receiving sexual arousal from the humiliation, pain and or suffering of an individual and are thought to overlap with multiple other conditions due to its description along with diagnostic criteria.[4] ### Voyeurism, exhibitionism and frotteurism[edit] Voyeurism is self-reported sexual arousal from spying on others or the observation of others who are engaged in sexual interaction.[5] Exhibitionism a public act of exposing parts of one's body that are not socially acceptable to be exposed.[5] Exhibitionistic acts are among the most common of the potentially law-breaking sexual behaviors.[5] Examples of this would include "streaking" during a professional sporting event or protesting a political event in the nude.[citation needed] Frotteurism is considered a rare paraphilia that revolves around an individual's sexual satisfaction being derived from rubbing upon another non-consenting individual.[6] The term frotteurism itself can be broken down and derived from the French verb frotter which means rubbing.[5] ## Diagnosis[edit] In the DSM-5 all paraphilia disorders can be diagnosed by two main criteria that are referred to criteria A and criteria B respectively. The A and B criteria include a duration in which the behavior must be present for (typically six months) and specific details of actions or thoughts that are correlated specifically with the respective disorder being diagnosed.[7] ## Treatment[edit] Psychosexual disorders can vary greatly in severity and treatability. Medical professionals and licensed therapists are necessary in diagnosis and treatment plans. Treatment can vary from therapy to prescription medication. Sex therapy, behavioral therapy, and group therapy may be helpful to those suffering distress from sexual dysfunction. More serious sexual perversions may be treated with androgen blockers or selective serotonin reuptake inhibitors (SSRIs) to help restore hormonal and neurochemical balances.[8] ## History[edit] ### Sigmund Freud[edit] Sigmund Freud has contributed to the idea of psychosexual disorders and furthered research of the topic through his ideas of psychosexual development and his psychoanalytic sex drive theory. According to Freud's ideas of psychosexual development, as a child, one will progress through five stages of development. These stages being the oral stage (1 -1 1/2 yrs), the anal stage(1 1/2- 3yrs) phallic stage (3-5 yrs), the latency stage (5-12 yrs) and the genital stage (from puberty on). A psychosexual disorder could arise in an individual if the individual does not progress through these stages properly. Proper progression through these stages requires the correct amounts of stimulation and gratification at each stage. If there is too little stimulation at a certain stage fixation occurs and becoming overly fixated could lead to a psychosexual disorder. In contrast, too much stimulation at a certain stage of development could lead to regression when that individual is in distress, also possibly leading to a psychosexual disorder.[9][10] ### Richard Freiherr von Kraft-Ebing[edit] Richard Krafft-Ebing was a German psychiatrist who sought to revolutionize sexuality in the late nineteenth century. Working in a time of sexual modesty, Krafft-Ebing brought light to sexuality as an innate human nature verses deviancy. His most notable work, Psychopathia Sexualis, was a collection of case studies highlighting sexual practices of the general public.[11] The textbook was the first of its kind recognizing the variation within human sexuality, such as: nymphomania, fetishism, and homosexuality.[12] Psychiatrists were now able to diagnose psychosexual disorders in place of perversions. Psychopathia Sexualis was used as reference in psychological, medical, and judicial settings. Krafft-Ebing is considered the founder of medical sexology; he is the predecessor of both Sigmund Freud and Havelock Ellis.[citation needed] ### Havelock Ellis[edit] Havelock Ellis was an English physician and writer born in the eighteen hundreds who studied human sexuality, and is referred to as one of the earliest sexologists. Ellis's work was geared towards human sexual behavior. His major work was a seven-volume publication called Studies in the Psychology of Sex, which related sex to society. Published in 1921, Studies in the Psychology of Sex covered the evolution of modesty, sexual periodicity, auto-erotism, sexual inversion, sexual impulse, sexual selection, and erotic symbolism.[13] Ellis also conceived the term eonism, which references a man dressing as a woman. He elaborated on this term in his publication of Eonism and Other Supplementary Studies.[14] He wrote Sexual Inversion as well in hopes to address any ignorance people have on the topic.[15] ## See also[edit] * LGBT rights in Turkey * Psychoanalysis * Sigmund Freud * Psychosexual development ## References[edit] 1. ^ Balon., R. (2013). Commentary: Controversies in the Diagnosis and Treatment of Paraphilias. Journal of Sex & Marital Therapy. 39(7), 20. DOI: 10.1080/0092623X.2012.709219 2. ^ Kamens, S. R. (2011). On the Proposed Seual and Gender Identity Diagnoses for DSM-5. The Humanistic Psychologist. 39,37-59. DOI: 10.1080/08873267.2011.539935 3. ^ Wise, T. N. (1985). Fetishism: Etiology and treatment: A review from multiple perspectives. Comprehensive Psychiatry. 26(3): 249-257. doi:10.1016/0010-440X(85)90070-7 4. ^ a b Berner, W., Berger, P., Hill, A. (2003). Sexual Sadism. International Journal of Offender Therapy and Comparative Criminology. 47(4): 383-395. DOI:10.1080/13552600108413321 5. ^ a b c d Langstrom, N. (2010). The Dem Diagnostic Criteria for Exhibitionism, Voyeurism and Frotteurism. Arch Sex Behavior. 39: 317-324. DOI 10.1007/s10508-009-9577-4 6. ^ Horley, J. (2001). Frotteurism: A term in search of an underlying disorder? Journal of Sexual Aggression: An international interdisciplinary forum for research, theory and practice. 7(1): 51-55. DOI:10.1080/13552600108413321 7. ^ American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing 8. ^ Psychosexual Disorders. (n.d.). Retrieved March 20, 2016, from http://www.mdguidelines.com/psychosexual-disorders 9. ^ Fancher, Raymond E.; Rutherford, Alexandra (2012). Pioneers of psychology : a history (4th ed.). New York: W.W. Norton. ISBN 978-0-393-93530-1. 10. ^ Freud, S. (1940). The development of the sexual function. Standard edition, 23, 152-156. 11. ^ Oosterhuis, Harry (2012-04-01). "Sexual Modernity in the Works of Richard von Krafft-Ebing and Albert Moll". Medical History. 56 (Special Issue 02): 133–155. doi:10.1017/mdh.2011.30. ISSN 2048-8343. PMC 3381524. PMID 23002290. 12. ^ "Full text of "Psychopathia Sexualis, with especial reference to the antipathic sexual instinct, a medico-forensic study;"". archive.org. Retrieved 2016-04-18. 13. ^ Ellis, H. (1921). Studies in the Psychology of Sex. Volume 6, 2. 14. ^ Crozier, I. (2000). Havelock Ellis, eonism and the patient's discourse; or, writing a book about sex. Volume 11, 125-154. 15. ^ Ellis, H. (1925). Sexual inversion. 3rd edition, 9-10. ## External links[edit] Classification D * ICD-10: F66.8-F66.9 * ICD-9-CM: 302.7 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Psychosexual disorder	c0033951	2,724	wikipedia	https://en.wikipedia.org/wiki/Psychosexual_disorder	2021-01-18T18:39:01	{"umls": ["C0033951"], "icd-10": ["F66.8", "F66.9"], "wikidata": ["Q7256482"]}
Shared psychosis, a psychiatric syndrome in which symptoms of a delusional belief are transmitted from one individual to another For other uses, see Folie à deux (disambiguation). This article's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (July 2020) (Learn how and when to remove this template message) Induced delusional disorder Other namesLasègue-Falret syndrome, induced delusional disorder, shared psychotic disorder Pronunciation * UK: /ˌfɒli æ ˈdɜː, -i ɑː-/, US: /foʊˌliː ə ˈdʌ/,[1] French: [fɔli a dø] SpecialtyPsychiatry Folie à deux ('madness for two'), also known as shared psychosis[2] or shared delusional disorder (SDD), is a psychiatric syndrome in which symptoms of a delusional belief, and sometimes hallucinations,[3][4] are transmitted from one individual to another.[5] The same syndrome shared by more than two people may be called folie à... trois ('three') or quatre ('four'); and further, folie en famille ('family madness') or even folie à plusieurs ('madness of several'). The disorder was first conceptualized in 19th-century French psychiatry by Charles Lasègue and Jean-Pierre Falret and is also known as Lasègue-Falret syndrome.[3][6] Recent psychiatric classifications refer to the syndrome as shared psychotic disorder (DSM-4 – 297.3) and induced delusional disorder (ICD-10 – F24), although the research literature largely uses the original name. This disorder is not in the current DSM (DSM-5), which considers the criteria to be insufficient or inadequate. DSM-5 does not consider Shared Psychotic Disorder (Folie à Deux) as a separate entity, but rather, the physician should classify it as “Delusional Disorder” or in the “Other Specified Schizophrenia Spectrum and Other Psychotic Disorder”. ## Contents * 1 Signs and symptoms * 1.1 Type of delusions * 1.2 Biopsychosocial effects * 2 Causes * 3 Diagnosis * 3.1 Related phenomena * 3.2 Prevalence * 4 Treatment * 4.1 Medication * 4.2 Therapy * 5 Notable cases * 6 In popular culture * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] This syndrome is most commonly diagnosed when the two or more individuals of concern live in proximity, may be socially or physically isolated, and have little interaction with other people. Various sub-classifications of folie à deux have been proposed to describe how the delusional belief comes to be held by more than one person:[7] * Folie imposée is where a dominant person (known as the 'primary', 'inducer' or 'principal') initially forms a delusional belief during a psychotic episode and imposes it on another person or persons (the 'secondary', 'acceptor', or 'associate') with the assumption that the secondary person might not have become deluded if left to his or her own devices. If the parties are admitted to hospital separately, then the delusions in the person with the induced beliefs usually resolve without the need of medication. * Folie simultanée describes either the situation where two people considered to suffer independently from psychosis influence the content of each other's delusions so they become identical or strikingly similar, or one in which two people "morbidly predisposed" to delusional psychosis mutually trigger symptoms in each other. Folie à deux and its more populous derivatives are in many ways a psychiatric curiosity. The current Diagnostic and Statistical Manual of Mental Disorders states that a person cannot be diagnosed as being delusional if the belief in question is one "ordinarily accepted by other members of the person's culture or subculture." It is not clear at what point a belief considered to be delusional escapes from the folie à... diagnostic category and becomes legitimate because of the number of people holding it. When a large number of people may come to believe obviously false and potentially distressing things based purely on hearsay, these beliefs are not considered to be clinical delusions by the psychiatric profession and are labelled instead as mass hysteria. As with most psychological disorders, the extent and type of delusion varies, but the non-dominant person's delusional symptoms usually resemble those of the inducer.[8] Prior to therapeutic interventions, the inducer typically does not realize that they are causing harm but instead believe they are helping the second person to become aware of vital or otherwise notable information. ### Type of delusions[edit] Psychology Today magazine defines delusions as "fixed beliefs that do not change, even when a person is presented with conflicting evidence."[9] Types of delusion include:[10][11] * Bizarre delusions are clearly implausible and not understood by peers within the same culture, even those with psychological disorders; for example, if one thought that all of their organs had been taken out and replaced by someone else's while they were asleep without leaving any scar and without their waking up. It would be impossible to survive such a procedure, and even surgery involving transplantation of multiple organs would leave the person with severe pain, visible scars, etc. * Non-bizarre delusions are common among those with personality disorders and are understood by people within the same culture. For example, unsubstantiated or unverifiable claims of being followed by the FBI in unmarked cars and watched via security cameras would be classified as a non-bizarre delusion; while it would be unlikely for the average person to experience such a predicament, it is possible and therefore understood by those around them. * Mood-congruent delusions correspond to a person's emotions within a given timeframe, especially during an episode of mania or depression. For example, someone with this type of delusion may believe with certainty that they will win $1 million at the casino on a specific night despite lacking any way to see the future or influence the probability of such an event. Similarly, someone in a depressive state may feel certain that their mother will get hit by lightning the next day, again in spite of having no means of predicting or controlling future events. * Mood-neutral delusions are not affected by mood, and can be bizarre or non-bizarre; the formal definition provided by Mental Health Daily is "a false belief that isn't directly related to the person's emotional state." An example would be a person who is convinced that somebody has switched bodies with their neighbor, the belief persisting irrespective of changes in emotional status. ### Biopsychosocial effects[edit] As with many psychiatric disorders, shared delusional disorder can negatively impact the psychological and social aspects of a person's wellbeing. Unresolved stress resulting from a delusional disorder will eventually contribute to or increase the risk of other negative health outcomes such as cardiovascular disease, diabetes, obesity, immunological problems, and others.[12] These health risks increase with the severity of the disease, especially if an affected person does not receive or comply with adequate treatment. Persons with a delusional disorder have a significantly high risk of developing psychiatric comorbidities such as depression and anxiety. This may be attributable to a genetic pattern shared by 55% of SDD patients.[13] Shared delusional disorder can have a profoundly negative impact on a person's quality of life.[14] Persons diagnosed with a mental health disorder commonly experience social isolation, which is detrimental to psychological health. This is especially problematic with SDD because social isolation contributes to the onset of the disorder; in particular, relapse is likely if returning to an isolated living situation in which shared delusions can be reinstated. ## Causes[edit] While the exact causes of SDD are unknown, the main two contributors are stress and social isolation.[15] People who are socially isolated together tend to become dependent on those they are with, leading to an inducers influence on those around them. Additionally, people developing shared delusional disorder do not have others reminding them that their delusions are either impossible or unlikely. Because of this, treatment for shared delusional disorder includes those affected be removed from the inducer.[16] Stress is also a factor because it triggers mental illness. The majority of people that develop shared delusional disorder are genetically predisposed to mental illness, but this predisposition is not enough to develop a mental disorder. However, stress can increase the risk of this disorder. When stressed, an individuals adrenal gland releases the "stress hormone" cortisol into the body, increasing the brain's level of dopamine; this change can be linked to the development of a mental illness, such as a shared delusional disorder.[13] ## Diagnosis[edit] Shared delusional disorder is difficult to diagnose because usually, the afflicted person does not seek out treatment because they do not realize that their delusion is abnormal as it comes from someone in a dominant position who they trust. Furthermore, since their delusion comes on gradually and grows in strength over time, their doubt is slowly weakened during this time. Shared delusional disorder is diagnosed using the DSM-5 and according to this the person afflicted must meet three criteria:[8] 1. They must have a delusion that develops in the context of a close relationship with an individual with an already established delusion. 2. The delusion must be very similar or even identical to the one already established one that the primary case has. 3. The delusion cannot be better explained by any other psychological disorder, mood disorder with psychological features, a direct result of physiological effects of substance abuse or any general medical condition. ### Related phenomena[edit] Reports have stated that a phenomenon similar to folie à deux was induced by the military incapacitating agent BZ in the late 1960s.[17][18] ### Prevalence[edit] Shared delusional disorder is most commonly found in women with slightly above-average IQs who are isolated from their family, and are in relationships with a dominant person who has delusions. The majority of secondary cases (people who develop the shared delusion) also meet the criteria for Dependent Personality Disorder which is characterized by a pervasive fear that leads them to need constant reassurance, support and guidance.[19] Additionally, 55% of secondary cases had a relative with a psychological disorder that included delusions and, as a result, the secondary cases are usually susceptible to mental illness. ## Treatment[edit] After a person has been diagnosed, the next step is to determine the proper course of treatment. The first step is to separate the formerly healthy person from the inducer and see if the delusion goes away or lessens over time.[16] If this is not enough to stop the delusions there are two possible courses of action: Medication or therapy which is then broken down into personal therapy and/or family therapy. With treatment, the delusions and therefore the disease will eventually lessen so much so that it will practically disappear in most cases. However left untreated it can become chronic and lead to anxiety, depression, aggressive behavior and further social isolation. Unfortunately there are not many statistics about the prognosis of shared delusional disorder as it is a rare disease and it is expected that the majority of cases go unreported; however, with treatment, the prognosis is very good. ### Medication[edit] If the separation alone is not working, antipsychotics are often prescribed for a short time to prevent the delusions. Antipsychotics are medications that reduce or relieve symptoms of psychosis such as delusions or hallucinations (seeing or hearing something that is not there). Other uses of antipsychotics include stabilizing moods for people with mood swings and mood disorders ( i.e. in bipolar patients), reducing anxiety in anxiety disorders and lessening tics in people with Tourettes. Antipsychotics do not cure psychosis but they do help reduce the symptoms and when paired with therapy, the afflicted person has the best chance of recovering. While antipsychotics are powerful, and often effective, they do have side effects such as inducing involuntary movements and should only be taken if absolutely required and under the supervision of a psychiatrist.[20] ### Therapy[edit] The two most common forms of therapy for people suffering from shared delusional disorder are personal and family therapy.[21][22] Personal therapy is one-on-one counseling that focuses on building a relationship between the counselor and the patient and aims to create a positive environment where the patient feels that they can speak freely and truthfully. This is advantageous because the counselor can usually get more information out of the patient to get a better idea of how to help them if that patient feels safe and trusts them. Additionally if the patient trusts what the counsellor says disproving the delusion will be easier.[21] Family therapy is a technique in which the entire family comes into therapy together to work on their relationships and to find ways to eliminate the delusion within the family dynamic. For example, if someone's sister is the inducer the family will have to get involved to ensure the two stay apart and to sort out how the family dynamic will work around that. The more support a patient has the more likely they are to recover, especially since SDD usually occurs because of social isolation.[22] ## Notable cases[edit] * In May 2008, in the case of twin sisters Ursula and Sabina Eriksson, Ursula ran into the path of an oncoming articulated lorry, sustaining severe injuries.[23] Sabina then immediately duplicated her twin's actions by stepping into the path of an oncoming car; both sisters survived the incident with severe but non-life-threatening injuries. It was later claimed that Sabina Eriksson was a 'secondary' sufferer of folie à deux, influenced by the presence or perceived presence of her twin sister, Ursula—the 'primary'. Sabina later told an officer at the police station, "We say in Sweden that an accident rarely comes alone. Usually at least one more follows—maybe two."[24] However, upon her release from hospital, Sabina behaved erratically before stabbing a man to death.[25][26][27] * The case of Ian Brady and Myra Hindley, Britain's notorious child killers in what became known as the Moors Murders, is another instance where folie à deux was said to occur. Hindley came, through her relationship with Brady to believe his racist philosophy that included a fascination with Hitler and fascism. * Another case involved a married couple by the name of Margaret and Michael, both aged 34 years, who were discovered to be suffering from folie à deux when they were both found to be sharing similar persecutory delusions. They believed that certain persons were entering their house, spreading dust and fluff and "wearing down their shoes." Both had, in addition, other symptoms supporting a diagnosis of emotional contagion, which could be made independently in either case.[28] * Psychiatrist Reginald Medlicott published an article about the Parker-Hulme murder case called “Paranoia of the Exalted Type in a Setting of Folie a Deux - A Study of Two Adolescent Homicides”, arguing that the intense relationship and shared fantasy world of the two teenaged friends reinforced and exacerbated the mental illness that led to the murder: “each acted on the other as a resonator increasing the pitch of their narcissism.”[29] * In 2016, a case involving a family of five from Melbourne, Australia made headlines when they abruptly fled their home and travelled more than 1,600 km (1,000 mi) across the state of Victoria because some of the family had become convinced someone was out to kill and rob them. No such evidence was found by the police, and the symptoms of those involved resolved on their own once the family returned to their home.[30] * The book Bad Blood: Secrets and Lies in a Silicon Valley Startup suggests that this ailment plagued the founder of Theranos, Elizabeth Holmes, and her boyfriend/business partner Ramesh Balwani. * It was suspected a family of eleven members from Burari, India suffered from this condition.[31][32] On 30 June 2018, the family committed suicide due to the shared belief of one of its members.[33] ## In popular culture[edit] * "Folie à Deux" is the title of the nineteenth episode in the fifth season of The X-Files (1998). The episode details a story of a man who believes his boss is an insect monster, a delusion that Fox Mulder begins to share after investigation. * Bug (2006) is a film that depicts a couple with a shared delusion that aphids are living under their skin. * In Season 2, Episode 3 of Criminal Minds, "The Perfect Storm" (2006), Dr. Reid mentions that the rapists had this condition. * In 2008, American rock band Fall Out Boy released their fourth album, Folie à Deux. * The independent film Apart (2011) depicts two lovers affected and diagnosed with induced delusional disorder, trying to uncover a mysterious and tragic past they share. In a 2011 interview, director Aaron Rottinghaus stated the film was based on research from actual case studies.[34][31] * In 2011, in CSI: Miami (Season 9, Episode 15 "Blood Lust"), it was revealed the killer couple had this condition. * In 2012, in Criminal Minds (Season 7, Episode 19 "Heathridge Manor"), it was revealed the killer family had this condition. * In 2017, in Chance (Season 2, Episode 9 "A Madness of Two"), it was revealed the villains are suffering from this condition. * The Vanished (2020) shows a couple who lost a child continuing to hold on to the delusional thought of their existence. ## See also[edit] * Anxiety disorder * Codependency * Delusion * Delusional disorder * Cotard delusion * Capgras delusion * Fregoli delusion * Delusional parasitosis * Emotional contagion * Folie à Deux (album) * Hive mind * Hysterical contagion * Major depressive disorder * Mass hysteria * Mass psychogenic illness * Paraphrenia * Schizophrenia * Slender Man stabbing * Unipathy ## References[edit] 1. ^ Wells, John C. (2008), Longman Pronunciation Dictionary (3rd ed.), Longman, p. 665, ISBN 9781405881180 2. ^ Berrios, G. E., and I. S. Marková. 2015. "Shared Pathologies. Pp. 3–15 in Troublesome disguises: Managing challenging Disorders in Psychiatry (2nd ed.), edited by D. Bhugra and G. Malhi. London: Wiley. 3. ^ a b Arnone D, Patel A, Tan GM (2006). "The nosological significance of Folie à Deux: a review of the literature". Annals of General Psychiatry. 5: 11. doi:10.1186/1744-859X-5-11. PMC 1559622. PMID 16895601. 4. ^ Dantendorfer K, Maierhofer D, Musalek M (1997). "Induced hallucinatory psychosis (folie à deux hallucinatoire): pathogenesis and nosological position". Psychopathology. 30 (6): 309–15. doi:10.1159/000285071. PMID 9444699. 5. ^ "Dr. Nigel Eastman in the BBC documentary 'Madness In The Fast Lane'". Documentarystorm.com. 2010-09-24. Archived from the original on 2010-10-01. Retrieved 2011-05-31. 6. ^ Berrios G E (1998) Folie à deux (by W W Ireland). Classic Text Nº 35. History of Psychiatry 9: 383–395 7. ^ Dewhurst, Kenneth; Todd, John (1956). "The psychosis of association: Folie à deux". Journal of Nervous and Mental Disease. 124 (5): 451–459. doi:10.1097/00005053-195611000-00003. PMID 13463598. 8. ^ a b "Shared Psychotic Disorder Symptoms - Psych Central". Psych Central. 2016-05-17. Retrieved 2018-03-22. 9. ^ "Delusional Disorder \| Psychology Today". Psychology Today. Retrieved 2018-03-22. 10. ^ "Delusion Types". News-Medical.net. 2010-08-15. Retrieved 2018-03-22. 11. ^ "4 Types of Delusions & Extensive List of Themes - Mental Health Daily". Mental Health Daily. 2015-04-29. Retrieved 2018-03-22. 12. ^ "How stress affects your body and behavior". Mayo Clinic. Retrieved 2018-03-22. 13. ^ a b "Stress May Trigger Mental Illness and Depression In Teens". EverydayHealth.com. Retrieved 2018-03-22. 14. ^ "Anxiety: Causes, symptoms, and treatments". Medical News Today. Retrieved 2018-03-22. 15. ^ "Shared Psychotic Disorder - Treatment Options". luxury.rehabs.com. Retrieved 2018-03-22. 16. ^ a b "Symptoms of Shared Psychotic Disorder". www.mentalhelp.net. Retrieved 2018-03-22. 17. ^ "Incapacitating Agents". Brooksidepress.org. Retrieved 2011-05-31. 18. ^ "Medscape Access". Emedicine.com. Retrieved 2011-05-31. 19. ^ "Dependent Personality Disorder Symptoms - Psych Central". Psych Central. 2017-12-17. Retrieved 2018-03-22. 20. ^ "CAMH: Antipsychotic Medication". www.camh.ca. Retrieved 2018-03-22. 21. ^ a b "Benefits of Individual Therapy \| Therapy Groups". www.therapygroups.com. Retrieved 2018-03-22. 22. ^ a b "Teen Treatment Center Blog". Teen Treatment Center. Retrieved 2018-03-22. 23. ^ "TV Review: Madness In The Fast Lane – BBC1". The Sentinel. 11 August 2010. Retrieved 31 August 2010. 24. ^ "TV Preview: Madness In The Fast Lane – BBC1, 10.35 pm". The Sentinel. 10 August 2010. Retrieved 31 August 2010. 25. ^ "Why was Sabina Eriksson free to kill?". The Sentinel. 3 September 2009. Retrieved 31 August 2010. 26. ^ Bamber, J (7 September 2009). "Could M6 film of killer have saved victim?". The Sentinel. Retrieved 31 August 2010. 27. ^ Madness In The Fast Lane Archived 2010-10-01 at the Wayback Machine Retrieved 3 February 2011. 28. ^ This case study is taken from Enoch and Ball's 'Uncommon Psychiatric Syndromes' (2001, p181) 29. ^ McCurdy, Marian Lea (2007). "Women Murder Women: Case Studies in Theatre and Film" (PDF). 30. ^ "Tromp family: The mystery of a tech-free road trip gone wrong - BBC News". BBC News. 2016-09-07. Retrieved 2016-09-07. 31. ^ a b PTI. "Burari deaths: Family may have been suffering from 'shared psychosis'". @businessline. 32. ^ "Burari deaths: Family could have been suffering from 'shared psychotic disorder', says Delhi Police". Hindustan Times. 3 July 2018. 33. ^ "Delhi Family Found Hanging Expected To Be Saved 'When Water Turns Blue'". NDTV.com. 34. ^ Cangialosi, Jason. "SXSW 2011: Interview with Aaron Rottinghaus, Director of 'Apart'". Yahoo!. Archived from the original on 29 April 2014. Retrieved 13 August 2013. ## Further reading[edit] * Enoch, D., and H. Ball. 2001. "Folie à deux (et Folie à plusieurs)." In Uncommon psychiatric syndromes (4th ed.). London: Arnold. ISBN 0340763884 * Halgin, R., and S. Whitbourne. 2002. Abnormal Psychology: Clinical Perspectives on Psychological Disorders. McGraw-Hill. ISBN 0072817216 * Hatfield, Elaine; Caccioppo, John T & Rapson, Richard L. (1994). Emotional contagion (Studies in Emotional and Social Interaction). Cambridge, UK: Cambridge University Press. ISBN 0-521-44948-0. * Ketchum, James S. 2007\. Chemical Warfare: Secrets Almost Forgotten A Personal Story of Medical Testing of Army Volunteers (2nd ed.). Chembook, Inc. ISBN 1424300800; ISBN 978-1424300808. * Metzner, Ralph, ed. (1999-06-02). Ayahuasca: Human Consciousness and the Spirits of Nature. New York, NY: Thunder's Mouth Press. ISBN 1-56025-160-3. * Wehmeier PM, Barth N, Remschmidt H (2003). "Induced delusional disorder. a review of the concept and an unusual case of folie à famille". Psychopathology. 36 (1): 37–45. doi:10.1159/000069657. PMID 12679591. ## External links[edit] * Folie à deux: Two case reports * "Shared Psychotic Manic Syndrome in Monozygotic Twins". * "Genetic of Psychogenic? A case study of "Folie a quarter" including twins" * Shared Delusional Disorder in a Cult Classification D * ICD-10: F24 * ICD-9-CM: 297.3 * MeSH: D012753 * DiseasesDB: 34350 External resources * eMedicine: med/3352 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Folie à deux	c0036939	2,725	wikipedia	https://en.wikipedia.org/wiki/Folie_%C3%A0_deux	2021-01-18T18:56:47	{"mesh": ["D012753"], "icd-9": ["297.3"], "icd-10": ["F24"], "wikidata": ["Q1435409"]}
Serous cystadenoma may refer to: * Ovarian serous cystadenoma, a very common benign tumour of the ovary * Pancreatic serous cystadenoma, also known as serous microcystic adenoma Index of articles associated with the same name This article includes a list of related items that share the same name (or similar names). If an internal link incorrectly led you here, you may wish to change the link to point directly to the intended article. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Serous cystadenoma	c0206709	2,726	wikipedia	https://en.wikipedia.org/wiki/Serous_cystadenoma	2021-01-18T19:09:36	{"mesh": ["D018293"], "umls": ["C0206709"], "wikidata": ["Q7455061"]}
A number sign (#) is used with this entry because of evidence that cone-rod dystrophy and hearing loss-1 (CRDHL1) is caused by homozygous or compound heterozygous mutation in the CEP78 gene (617110) on chromosome 9q21. Description CRDHL1 is characterized by cone-rod dystrophy and sensorineural hearing loss, with relatively late onset of both ocular and hearing impairment. The funduscopic findings are characteristic, showing ring-shaped atrophy along the major vascular arcades that manifests on fundus autofluorescence as a hypoautofluorescent band along the vascular arcades surrounded by hyperautofluorescent borders (Namburi et al., 2016). ### Genetic Heterogeneity of Cone-Rod Dystrophy and Hearing Loss CRDHL2 (618358) is caused by mutation in the CEP250 gene (609689) on chromosome 20q11. Clinical Features Nikopoulos et al. (2016) described a Greek man and a Swedish brother and sister who had cone-rod dystrophy associated with hearing loss. The 59-year-old Greek man had reduced vision in bright light since early adulthood, which progressed to severe central vision loss by age 40 years, with nystagmus, photophobia, and dyschromatopsia. Funduscopy at age 53 revealed macular coalescent hypochromatic lesions in the right eye and minor macular changes in the left eye. Visual field examination showed diffuse suppression bilaterally, with relative conservation of the peripapillary area and superior periphery. Full-field electroretinography (ERG) displayed flat cone responses, but some residual rod-mediated signals in the left eye. The proband also reported minor hearing problems; audiogram confirmed a mild deficit, but more severe than natural age-related hearing loss. The affected Swedish sibs both had visual problems from childhood, including loss of color sensitivity and central vision. Both also had a hearing deficit from a young age, and both used hearing aids; audiogram of the sister showed substantial sensorineural hearing loss, which was nonprogressive over 11 years of follow-up. Funduscopy showed macular degenerative changes in both sibs, with attenuated vessels and some spicular pigment in the midperiphery but fewer changes in the periphery. Progressive deterioration of the visual field was reported and documented as expanding from the center to the periphery; both sibs retained some residual peripheral vision, especially in low-light conditions. Full-field ERGs revealed almost no residual cone activity, but there were some rod-mediated responses even at ages 66 and 69 years. Namburi et al. (2016) reported 6 individuals from 5 Jewish families of Iranian, Iraqi, or Afghan origin who exhibited both cone-rod dystrophy and sensorineural hearing loss (SNHL). All affected individuals presented with similar cone-dominated symptoms with a variable age of onset (10 to 35 years), including photophobia, low visual acuity, impaired color vision, and visual field defects, accompanied by SNHL which also had a variable age of onset (10 to 45 years). ERG testing showed progressive loss of cone photoreceptor function, followed by that of rods, and was in some patients accompanied by a reduced b/a wave ratio in the dark-adapted state (electronegative pattern). Electrooculography (EOG) was performed in 4 patients and showed a reduced Arden ratio, which the authors suggested was due to photoreceptor degeneration. Fundoscopic findings included prominent retinal atrophy along the major vascular arcades surrounding the macula, which expanded at older ages, as well as mild macular retinal pigment epithelium (RPE) changes and subtle peripheral salt-and-pepper changes; no bone spicule-like pigmentation was seen. Characteristic ring-shaped atrophy was evident on fundus autofluorescence (FAF) imaging, manifesting as a hypoautofluorescent band along the vascular arcades, surrounded by hyperautofluorescent borders. Testing performed in 3 patients confirmed severe deficiency of color vision. Audiometry tests revealed bilateral SNHL affecting the middle frequencies, high frequencies, or both. None of the affected individuals reported significant abnormalities of the vestibular system. Namburi et al. (2016) noted that the phenotype observed in these patients did not fall within the standard classification of Usher syndrome (see 276900), in which the retinal disease is typical retinitis pigmentosa with early rod dysfunction. Fu et al. (2017) studied 4 affected sibs from 2 unrelated consanguineous Chinese families with juvenile or adult-onset cone-rod dystrophy and SNHL. In the first family, 2 sisters aged 33 years and 41 years reported several decades of progressive vision loss, with severely reduced visual acuity on examination. Photophobia, color vision loss, and recent progressive hearing loss were also noted. ERG testing showed similar results in both patients, with cone responses reduced more than rod responses. Funduscopy showed grayish retinal pigment mottling along the retinal vessels, with attenuated retinal arteries. FAF showed annular hypofluorescent patches around the posterior pole with an inner hyperfluorescent ring around the macular region, and ocular coherence tomography (OCT) showed reduced thickness of the macular region with loss of the ellipsoid zone. In the second family, a sister and brother were affected. The sister reported night blindness from early childhood, hypochromatopsia and mild hearing loss from age 8 years, and visual field decrease with central vision loss from age 10 years. At age 35, her visual acuities were 20/125 and 20/200, and hypochromatopsia was confirmed by color vision testing. Funduscopy showed attenuated vessels, waxy optic disc, and pigment deposits in the midperiphery, with macular involvement as well. Fundus fluorescein angiography (FFA) revealed aberrant vascular arcades and speckled areas of increased fluorescence in the midperiphery. Attenuation of the outer nucleus layer and RPE as well as loss of the ellipsoid zone were suggested by OCT, and both scotopic and photopic responses were abolished on ERG. Fu et al. (2017) designated the phenotype as an atypical form of Usher syndrome. Mapping In a consanguineous Jewish family with cone-rod dystrophy and sensorineural hearing loss, Namburi et al. (2016) performed homozygosity mapping and identified a 65.6-Mb region on chromosome 9, as well as a 34-Mb region on chromosome 19. Analysis of polymorphic markers in 2 affected sibs showed that they shared only a single homozygous region on chromosome 9, spanning 16 Mb and flanked by SNPs rs369854466 and rs728695. Molecular Genetics In a cohort of 34 probands with cone-rod dystrophy, 29 from Greece and 5 from Sweden, Nikopoulos et al. (2016) performed whole-exome sequencing and identified biallelic mutations in the CEPL78 gene (617110.0001-617110.0003) in a Greek man and a Swedish woman, who both also exhibited hearing loss. The mutations segregated with disease in each family and were not found in 350 controls or in public variant databases. The authors sequenced CEP78 in another cone-rod dystrophy cohort, involving 99 unrelated individuals of Swedish, Swiss, Dutch, and Pakistani origin, but did not find any additional causative variants. In 2 affected brothers from a consanguineous Jewish family with cone-rod dystrophy and sensorineural hearing loss mapping to chromosome 9, Namburi et al. (2016) performed whole-exome sequencing and identified homozygosity for a splice site mutation in the CEP78 gene (617110.0004) that segregated with disease and was not found in an in-house database of 408 Israeli exomes or in public variant databases. The authors screened 4 more Jewish probands with a similar phenotype for the CEP78 splice site mutation and identified homozygosity for the mutation in 1 patient, and compound heterozygosity for the splice site mutation and a 1-bp deletion in CEP78 (617110.0005) in 1 patient. The remaining 2 patients were homozygous for the 1-bp deletion. Analysis of 249 Eastern Jewish probands with inherited retinal diseases did not reveal any additional CEP78 disease-causing mutations. The 5 mutation-carrying families were Jews of Iranian, Iraqi, or Afghan origin, and haplotype analysis revealed a shared and distinct haplotype for each mutation, confirming that these are founder mutations. In 2 sisters from a consanguineous Han Chinese family with cone-rod dystrophy and sensorineural hearing loss, negative for mutation in known retinal disease genes, Fu et al. (2017) performed whole-exome sequencing and identified homozygosity for a splice site mutation in the CEP78 gene (617110.0006) that segregated with disease and was found to be extremely rare in the ExAC population database (1/30,990). In a similarly affected proband from a second consanguineous Chinese family, WES revealed homozygosity for a different splice mutation in CEP78 (617110.0007). The authors also screened 71 unsolved cases of Usher syndrome, but did not find any biallelic CEP78 mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural Eyes \- Photophobia \- Reduced vision in bright light \- Severely reduced central vision \- Nystagmus \- Reduced or absent color vision \- Progressive deterioration of visual fields, from center to periphery \- Macular degeneration \- Attenuated retinal vessels \- Retinal atrophy along vascular arcades surrounding macula \- Macular retinal pigment epithelium (RPE) changes, mild \- Pigment deposition in midperiphery \- Spicular pigment in midperiphery (rare) \- Salt-and-pepper changes in periphery \- Aberrant vascular arcades on fundus fluorescein angiography (FFA) \- Speckled areas of increased fluorescence in midperiphery on FFA \- Hypoautofluorescent bands along vascular arcades, surrounded by hyperautofluorescent borders, on fundus autofluorescence imaging \- Absent or severely reduced cone responses on electroretinography (ERG) \- Presence of residual rod responses on ERG (in most patients) \- Reduced b/a wave ratio in dark-adapted state on ERG (in some patients) \- Reduced Arden ratio on electrooculography \- Reduced thickness of macular region on ocular coherence tomography (OCT) \- Attenuation of outer nuclear layer on OCT \- Attenuation of RPE on OCT \- Loss of ellipsoid zone on OCT MISCELLANEOUS \- Variable age of onset for visual or hearing symptoms, ranging from first to fourth or fifth decades of life MOLECULAR BASIS \- Caused by mutation in the 78-kD centrosomal protein gene (CEP78, 617110.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CONE-ROD DYSTROPHY AND HEARING LOSS 1	c4310657	2,727	omim	https://www.omim.org/entry/617236	2019-09-22T15:46:23	{"omim": ["617236"], "synonyms": ["Alternative titles", "CRDHL"]}
A rare developmental defect during embryogenesis characterized by moderate to severe prenatal and postnatal growth retardation, microcephaly, a distinctive facial appearance, profound psychomotor delay, hip and knee contractures and rockerbottom feet. ## Epidemiology Bowen-Conradi syndrome (BCS) birth prevalence is estimated at 1 per 355 within the Hutterite population living in small farming colonies in the Prairie provinces and Great Plains of North America with a carrier frequency as high as 1/10 in the Hutterite population. Outside this population, BCS is considered very rare and has only been reported clinically in 9 patients worldwide to date. To date, there are no non-Hutterite patients reported with biallelic EMG1 pathogenic variants. ## Clinical description Prenatally BCS is characterized by intrauterine growth retardation and often a breech presentation. BCS patients fail to thrive, experience severe feeding problems and seldom live past infancy. Distinctive malformations of the head and craniofacial region describe microcephaly at birth, micrognathia and a prominent nose with a noticeable lack of glabellar angle. BCS patients have a severe psychomotor delay, stiff joints, campodactyly or clinodactyly of the little finger and rockerbottom feet. Finger, hip and knee flexion contractures are frequently present. Less common BCS features described include cryptorchidism, seizures, cleft lip with or without cleft palate, congenital heart defect, hypospadias, renal, brain, or other malformations. ## Etiology In the Hutterite population, BCS is over-represented secondary to a founder effect, and is due to a missense mutation in the EMG1 gene located to 12p13.3, leading to disturbances in ribosomal biosynthesis. ## Diagnostic methods Diagnosis is typically made postnatally based on clinical manifestations and can then be confirmed with molecular testing. The diagnosis can first be identified on antenatal ultrasound; however the findings (particularly in a non-Hutterite infant) are non-specific and would likely not suggest BCS. In a Hutterite fetus, even in the absence of a positive family history, findings such as microcephaly, contractures, and rocker-bottom feet would be strongly suggestive of BCS. ## Differential diagnosis Differential diagnosis includes trisomy 18, COFS syndrome and fetal akinesia deformation sequence. Other conditions with microcephaly and severe growth and developmental delay such as chromosome breakage disorders, DNA damage repair disorders, microcephalic primordial dwarfisms and certain forms of carbohydrate deficient glycoprotein syndromes may also show some overlap. ## Antenatal diagnosis In cases with a family history, prenatal diagnosis is available and possible by amniocentesis or chorionic villus sampling and DNA analysis. Targeted mutation analysis of the Hutterite mutation is available prenatally (although rarely pursued) and in some instances carrier testing of both Hutterite parents of a presumed affected pregnancy can strengthen the possibility of diagnosis ## Genetic counseling BCS transmission is autosomal recessive. With the discovery of the causative mutation in the Hutterite population, carrier testing is available. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment Treatment is merely symptomatic. Feeding is significantly compromised, and most infants require tube feeding. No curative treatment is presently available. The natural history is similar to aneuploidy syndromes such as trisomy 18 and the discussion of palliative care is appropriate. ## Prognosis Prognosis is extremely poor. Most children die within the first 2 years of life (range 1 day-9 years). Those who survive beyond 1 year of age show extreme growth failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Bowen-Conradi syndrome	c1859405	2,728	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1270	2021-01-23T18:40:21	{"gard": ["5950"], "mesh": ["C537081"], "omim": ["211180"], "umls": ["C1859405"], "icd-10": ["Q87.8"], "synonyms": ["Bowen syndrome, Hutterite type"]}
A rare autosomal recessive cerebellar ataxia (ARCA), characterized by progressive cerebellar ataxia associated with frequent oculomotor apraxia, severe neuropathy and an elevated serum alpha-fetoprotein (AFP) level. ## Epidemiology The prevalence of AOA2 in France is estimated to be 1/900,000. ## Clinical description AOA2 is mostly an adolescent onset disorder (age at onset ranges between 10 and 25 years), with a mean age of 14-15 years, that manifests as progressive cerebellar ataxia associated with peripheral neuropathy (98%), cerebellar atrophy (96%), occasional oculomotor apraxia (OMA; 51%; inability to coordinate eyes ± head movements: when the head turns toward a lateral target; the head reaches the target before the eyes), pyramidal signs (21%), head tremor (14%), dystonia (14%), strabismus (12%), chorea (10%) and saccadic pursuit without OMA (4.5%). ## Etiology AOA2 results from mutations in SETX gene (9q34), encoding senataxin protein, a DNA/RNA helicase localized in nucleus which is implicated in DNA break repair. Some correlations between genotype and phenotype have been established for example deletions and nonsense mutations are correlated to more severe phenotypes than missense mutations. Mutations in the gene PIK3R5 (17p13.1) have also been implicated in the pathogenesis of AOA2. PIK3R5 encodes a regulatory subunit that interacts with class 1B phosphoinositide-3-kinase (key enzymes in various signal transduction pathways that regulate cell survival and growth, metabolism, immune, and cardiac functions). ## Diagnostic methods Diagnosis is based on clinical features, progressive evolution leading to important motor handicap, absence of extra-neurologic findings and family history. Laboratory findings show an elevated AFP serum level (above 7 µg/L). Electromyography findings reveal axonal sensory-motor neuropathy. Oculographic recordings can demonstrate OMA. Cerebral magnetic resonance imagery displays cerebellar atrophy. Diagnosis is confirmed by molecular analysis of the pathogenic gene. ## Differential diagnosis Differential diagnosis includes Friedreich ataxia, ataxia with vitamin E deficiency, AOA1, ataxia-telangiectasia, ataxia-telangiectasia-like disorder, autosomal recessive spastic ataxia of Charlevoix-Saguenay. ## Antenatal diagnosis Carrier testing for at-risk family members and prenatal testing are possible if the disease-causing alleles in a family are known. ## Genetic counseling Transmission of AOA2 is autosomal recessive. Genetic counseling is recommended as each sib of an affected individual has 25% risk of being affected, 50% risk of being an asymptomatic carrier, and 25% risk of being neither affected nor a carrier. ## Management and treatment No specific treatment exists for AOA2 and management is mainly supportive. It includes physical therapy for cerebellar ataxia and disabilities resulting from peripheral neuropathy; educational support for reading and writing difficulties, speech therapy for dysarthria and cognitive impairment. Routine follow-up with a neurologist or a neurogenetician is recommended. ## Prognosis AOA2 is a progressive neurodegenerative disorder and most patients will become wheelchair bound at a mean age of 29.9 years ± 3.84 after a mean disease duration of 15.3 years ± 3.52. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Spinocerebellar ataxia with axonal neuropathy type 2	c1853761	2,729	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=64753	2021-01-23T17:28:13	{"gard": ["12860"], "mesh": ["C537308"], "omim": ["606002", "615217"], "icd-10": ["G60.2"], "synonyms": ["AOA2", "Ataxia-oculomotor apraxia type 2", "SCAN 2", "SCAR1"]}
A number sign (#) is used with this entry because this form of nonobstructive spermatogenic failure, designated Y-linked spermatogenic failure-2 (SPGFY2), is most often caused by interstitial deletions on the Y chromosome. Complete deletion of the AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. In addition, mutations in the USP9Y gene (400005) are associated with nonobstructive azoospermia and hypospermatogenesis. Description About 2 to 3% of human males are infertile because of defects in sperm function, primarily due to oligozoospermia (defined as less than 10-15 million sperm per mL of semen) or azoospermia (Hull et al., 1985). ### Heterogeneity of Spermatogenic Failure For a discussion of Y-linked spermatogenic failure due to Sertoli cell-only syndrome, see 400042. For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). Clinical Features Tiepolo and Zuffardi (1976) observed the involvement of Yq deletions in male infertility when they were analyzing cells from idiopathic infertile males. Molecular studies (Reijo et al., 1995; Vogt et al., 1996; Pryor et al., 1997, Foresta et al., 2001) have since shown that microdeletions at Yq11 may represent the etiologic factor in as many as 10 to 20% of cases with idiopathic azoospermia or severe oligozoospermia. Most of the deletions occur de novo and fall in 3 nonoverlapping regions, designated AZFa, AZFb, and AZFc (see Vogt et al., 1996), of which the distally located AZFc is most frequently deleted (Yen, 1998). Foresta et al. (2001) reviewed published data on more than 4,800 infertile men who had been screened for Y-chromosome microdeletions and found that patients with Y-chromosome deletions frequently have sperm either in the ejaculate or within the testis and are therefore suitable candidates for assisted reproduction techniques. However, the authors noted that while the use of spermatozoa carrying Y-chromosome deletions may produce pregnancies, in such cases the genetic anomaly will invariably be passed on to male offspring. Cytogenetics A role for the human Y chromosome in spermatogenesis was first suggested by the studies of Tiepolo and Zuffardi (1976), who karyotyped 1,170 subfertile men and identified 6 azoospermic individuals with microscopically detectable deletions of distal Yq. In 4 cases in which the father was tested, all were found to carry intact Y chromosomes. On the basis of these de novo deletions in azoospermic men, Tiepolo and Zuffardi (1976) proposed the existence of a spermatogenesis gene, or 'azoospermia factor' (AZF), on Yq. Lange et al. (2009) screened DNA samples from 2,380 patients, including 1,550 men who presented with spermatogenic failure and 830 patients in whom light microscopy revealed a structurally anomalous Y chromosome or sex reversal, and identified 60 unrelated individuals with isodicentric (idic) or isocentromeric (iso) Y chromosomes, 51 of which apparently arose via a palindromic mechanism, yielding an idicYp in 49 cases and an idicYq in 2 cases, whereas the remaining 9 arose via recombination in heterochromatic sequences, yielding an idicYp in 2 cases and an isoYp in 7 cases. Lange et al. (2009) identified idicYp and isoYp chromosomes in 18 otherwise healthy men with greatly diminished or no sperm production, and stated that such chromosomal abnormalities are among the more common genetic causes of severe spermatogenic failure. Mapping By Southern blot analysis and in situ hybridization with Y-specific DNA probes in 3 45,X males, Andersson et al. (1988) localized AZF to interval 6 of the Y chromosome, as defined by Vergnaud et al. (1986). AZF has been divided into 3 regions, designated AZFa, AZFb, and AZFc (see Vogt et al., 1996). By in situ hybridization with 3 different Y-specific DNA probes in a 28-year-old azoospermic male, Chandley et al. (1989) demonstrated a de novo deletion at Yq11 that resulted in loss of all distal heterochromatin. In the screening of DNA from 21 patients with structural abnormalities in Yq, Ma et al. (1992) constructed a detailed map of interval 6. In a panel of 19 chromosomally normal azoospermic men, they screened DNA with the same set of probes and found microdeletions in 2. They suggested that these microdeletions disrupted the AZF locus. By means of a molecular screen specific for microdeletions in interval 6 of the Y chromosome, Vogt et al. (1992) found a de novo microdeletion in 2 of 19 'chromosomally normal' sterile males. They mapped the position of the Y deletion of one patient to the distal part of Yq11.22 or the proximal part of Yq11.23, and the deletion of the other patient to the distal part of Yq11.23. These microdeletions probably did not overlap. Since AZF had been mapped to Y interval 6, Vogt et al. (1992) postulated that the microdeletion affected the functional DNA structure of the putative AZF gene. Typing EBV-immortalized cell lines from azoospermic or severely oligospermic patients for the expression of H-Y antigen, Simpson et al. (1993) found no correlation between spermatogenic failure and the absence of HYA (JARID1D; 426000), thus separating the AZF locus region from HYA. Molecular Genetics Ma et al. (1993) reported the isolation and characterization of a gene family located within interval 6 (subinterval XII-XIV) of Yq11.23, a region of approximately 200 kb that, when deleted, is associated with azoospermia or severe oligospermia (see RBMY1A1; 400006). Analysis of the predicted protein products suggested a possible role in RNA processing or translational control during early spermatogenesis. The expression of the genes appeared to be testis specific, and the genes showed a male-specific conservation of expression in DNA from several other mammals. The Y-chromosome RNA recognition motif (YRRM) family includes a minimum of 3 members. Ma et al. (1993) detected deletions of YRRM sequences in 2 oligospermic patients with no previously detected mutation. Kobayashi et al. (1994) analyzed DNA from 63 Japanese men with either azoospermia or severe oligospermia whose Y chromosomes were cytogenetically normal. They examined 15 loci on the long arm between DYS7E and DYZ1, and the YRRM1 (RBMY1A1) locus. They detected microdeletions in 10 of the men; the YRRM1 gene was involved in only 3 of them. The remaining 7 patients showed deletion between DYS7C and DYS239 in common, indicating the presence of at least 1 additional gene, deletion of which causes azoospermia. Reijo et al. (1995) studied 89 men with nonobstructive azoospermia, 78 of whom had undergone testis biopsy, revealing Sertoli cell-only syndrome (SCO; 400042) in 42 of them and testicular maturation arrest in 36. Deletions of portions of the Y chromosome long arm were found in 12 of the 89 men; all 12 deletions overlapped an approximately 5x10(5)-kb AZF region presumed to contain 1 or more genes for spermatogenesis. The 12 deletions were associated with highly variable testicular defects, ranging from complete absence of germ cells to spermatogenic arrest with occasional production of condensed spermatids. No Y-chromosome deletions were detected in 90 fertile male controls. Using exon trapping within the deleted region, Reijo et al. (1995) identified a single-copy gene, designated DAZ (for 'deleted in azoospermia'; 400003), which is transcribed in the adult testis and appears to encode an RNA-binding protein. ### Azoospermia Factor Regions Vogt et al. (1996) analyzed 370 men with idiopathic azoospermia or severe oligozoospermia for deletions of 76 loci in Yq11 and detected different microdeletions in 13 patients. Three patients showed a microdeletion in proximal Yq11, 3 had a microdeletion in interval D13-D16, and 7 had a microdeletion in D20-D22; among patients within each group, the extension of deleted intervals was the same. Vogt et al. (1996) analyzed testis biopsies from patients with deletions in different regions of Yq11. A patient with a deletion in proximal Yq11 had SCO (only Sertoli cells but no germ cells were visible in all tubules of the testis sections). In 3 patients with a microdeletion in middle Yq11, testicular histology revealed spermatogenic arrest at the spermatocyte stage: populations of spermatogonia and spermatocytes were normal in tubules and no post-meiotic germ cells could be detected, which indicated that disruption of spermatogenesis occurred before or during meiosis at the spermatocyte stage. Results of studies in 5 patients with microdeletions in distal Yq11 suggested a post-meiotic spermatid or sperm maturation defect. Because microdeletions were found in 3 different Yq11 subregions that led to spermatogenesis disruption at different phases of the process, Vogt et al. (1996) proposed the presence of 3 spermatogenesis loci in Yq11, which they designated AZFa, AZFb, and AZFc. They proposed in addition that each locus is active during a different phase of male germ cell development. Pryor et al. (1997) evaluated the Y chromosomes of 200 consecutive infertile men and 200 normal men and identified microdeletions in 14 infertile men (7%) and 4 normal men (2%). The size and location of the deletions varied and did not correlate with the severity of spermatogenic failure or testicular pathology: for example, of 2 patients with SCO type I, 1 had a deletion in AZFa whereas the other had an intact AZFa region but a deletion of AZFb and AZFc; and another patient with a deletion in AZFc had spermatogenic arrest. Brandell et al. (1998) detected partial Y-chromosome deletions in 9 of 80 men (11%) undergoing testicular sperm extraction (TESE) due to azoospermia or cryptozoospermia. Two patients had isolated AZFc deletions with hypospermatogenesis on testicular biopsy and spermatozoa extracted by TESE. One patient with deletion of all 3 AZF regions had SCO on biopsy and TESE failed. The remaining 6 patients had deletions involving AZFb alone or AZFb and AZFc; 5 underwent testicular biopsies of which 4 revealed spermatocytic arrest and 1 hypospermatogenesis. None of the latter patients had spermatozoa extracted by TESE. Brandell et al. (1998) suggested that the presence of an AZFb deletion is a significantly adverse prognostic finding for TESE. In a blind study, Krausz et al. (1999) screened DNA from 131 infertile males (46 idiopathic and 85 nonidiopathic) for Y-chromosome microdeletions. Of males with idiopathic infertility and an apparently normal 46,XY chromosome complement, 19% had microdeletions of either the AZFa, AZFb, or AZFc region. There was no strict correlation between the extent or location of the deletion and the phenotype. The AZFb deletions did not include the active RBM gene. Significantly, a high frequency of microdeletions (7%) was found in patients with known causes of infertility and a 46,XY chromosome complement. These included deletions of the AZFb and AZFc regions, with no significant difference in the location or extent of the deletion compared with the former group. Testicular histology was available in 6 patients, 5 of whom had large deletions in the AZFc region. On histology, 1 patient had SCO syndrome, 1 had hypospermatogenesis, 2 had premeiotic arrest, and 1 had meiotic arrest. The sixth patient had an AZFb microdeletion, with spermatogenic arrest at the spermatocyte II phase. Foresta et al. (2001) reviewed the literature on Y-chromosome microdeletions, including published data on more than 4,800 infertile men who had been screened for Y microdeletions. Overall, the prevalence of Y-chromosome microdeletions was 4% in oligozoospermic patients, 14% in idiopathic severely oligozoospermic men, 11% in azoospermic men, and 18% in idiopathic azoospermic subjects. The authors noted that patient selection criteria appeared to substantially influence the prevalence of microdeletions. There was no clear correlation between the size and localization of the deletions and the testicular phenotype, but larger deletions were associated with the most severe testicular damage. Madgar et al. (2002) screened 61 infertile Israeli men, 15 with severe oligospermia and 46 with azoospermia, for microdeletions of the Y chromosome involving the AZF region and for the (CAG)n repeat length of the androgen receptor (AR; 313700). Fifty fertile Israeli men were similarly analyzed. Five azoospermic men, representing 8.2% of the entire sample and 10.8% of the azoospermic subjects, displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 compared with 16.6 in fertile men, a statistically significant difference (p = 0.003). Foresta et al. (2005) hypothesized that infertile men may be more likely than fertile men to have genetic abnormalities. They studied 750 severely oligozoospermic men who were candidates for intracytoplasmic sperm injection and 303 fertile men. They analyzed the peripheral blood karyotype, the Y-chromosome long arm for detection of microdeletions in the azoospermia factors, and the cystic fibrosis (CFTR; 602421) and AR genes for mutations. A total of 104 genetic abnormalities were detected, corresponding to a frequency of 13.9%. Chromosomal aberrations were present in 5.6% of infertile men and 0.3% of controls, and they were in most cases alterations of the sex chromosomes. Y-chromosome long-arm microdeletions were detected in 6.0% of infertile men and most frequently included the azoospermia factor c (AZFc) region, whereas no cases were found in controls. Mutations in the CFTR gene were diagnosed in 1.2% of infertile men and 1.0% of controls, and mutations in the AR gene were found in 1.1% of infertile men and none of the 188 controls. Over a 10-year period, Ferlin et al. (2007) studied 3,073 consecutive infertile Italian men, of which 625 had nonobstructive azoospermia and 1,372 had severe oligospermia, and identified microdeletions in 99 individuals. The prevalence of microdeletions was 3.2% in unselected infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with severe oligozoospermia. Most deletions were of the AZFc-b2/b4 subtype and were associated with a variable spermatogenic phenotype, with sperm present in 72% of cases. Complete AZFa and AZFb (P5/proximal P1) deletions were associated with Sertoli cell-only syndrome and alterations in spermatocyte maturation, respectively, whereas partial deletions in these regions were associated with a milder phenotype and frequent presence of sperm. No Yq microdeletions were found in men with more than 5 million sperm/mL or in 310 controls. ### AZFa Region Sargent et al. (1999) refined the deletion breakpoints in 4 patients with AZFa male infertility. All patients had DFFRY (USP9Y; 400005) and an anonymous EST, AZFaT1, deleted in their entirety, and 3 patients also had DBY (400010) deleted. The 3 patients with AZFaT1, DFFRY, and DBY deleted showed a severe Sertoli cell-only syndrome type 1 phenotype, whereas the patient that had retained DBY showed a milder oligozoospermic phenotype. RT-PCR analysis of mouse testis RNA showed that Dby is expressed primarily in somatic cells, whereas Dffry is expressed specifically in testis in a germ cell-dependent fashion. Sun et al. (1999) were the first to trace spermatogenic failure to a point mutation in a Y-linked gene or to a deletion of a single Y-linked gene. They sequenced the AZFa region of the Y chromosome and identified 2 previously described functional genes: USP9Y and DBY. Screening of the 2 genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appeared to be heritable and of little functional consequence. In a man with nonobstructive azoospermia, they identified a de novo mutation in USP9Y (400005.0001); the mutation was not present in his fertile brother. A testicular biopsy of the patient revealed premeiotic and meiotic germ cells in most seminiferous tubules, with small numbers of postmeiotic cells (spermatids) in a few tubules, suggesting a diagnosis of hypospermatogenesis with spermatogenic arrest. Sun et al. (1999) also identified a single gene deletion associated with spermatogenic failure, again involving USP9Y (400005.0002), by reanalyzing patient 'SAYER' reported by Brown et al. (1998); see 400042. Foresta et al. (2000) reported a complete sequence map of the AZFa region, the genomic structure of AZFa genes, and their deletion analysis in 173 infertile men with well-defined spermatogenic alterations. Deletions were found in 9 patients: DBY alone was deleted in 6, USP9Y only in 1, and 1 each with USP9Y-DBY or DBY-UTY missing. No patients solely lacked UTY (400009). There was no clear correlation between the size and the location of the deletions and the testicular phenotype; patients lacking DBY exhibited either Sertoli cell-only syndrome or severe hypospermatogenesis. Expression analysis of AZFa genes and their X homologs revealed ubiquitous expression for all of them except DBY; a shorter DBY transcript was expressed only in testis. The authors suggested that DBY plays a key role in the spermatogenic process. Sun et al. (2000) defined deletion breakpoints in 2 unrelated azoospermic men with AZFa deletions. In the proximal breakpoint region, they identified a 10-kb provirus of the HERV15 class of endogenous retroviruses. In the distal breakpoint region, they found a second HERV15 provirus, 94% identical in DNA sequence to the first and in the same orientation. The AZFa deletions in the 2 men differed slightly, but all breakpoints fell within the HERV15 proviruses. The authors suggested that recombination between these 2 HERV15 proviruses could account for most AZFa deletions. Bosch and Jobling (2003) detected Y-chromosomal short tandem repeat (Y-STR) allele duplications within the AZFa region and showed that 2 chromosomes carrying these duplicated alleles contained a third junction-specific endogenous retroviral elements (HERV) sequence. Sequence analysis of these cases, which most likely represent independent duplication events, showed that breakpoints lie in the same region of inter-HERV sequence identity as do deletion breakpoints, suggesting that the mechanism of duplication is the reciprocal of the mechanism resulting in deletion. Noting the accumulated Y-STR allele diversity between duplicated copies of the AZFa region, the authors determined that one of the duplication chromosomes has been in the population for at least 17 generations, and therefore must be compatible with male fertility. In a 42-year-old man who underwent spermatologic and genetic analysis as part of an infertility analysis after his partner had a miscarriage, Luddi et al. (2009) identified a 513,594-bp deletion in the AZFa region of the Y chromosome, with breakpoints located approximately 320,521 bp upstream and 33,465 bp downstream of the USP9Y gene (400005.0002). Spermatologic analysis revealed that total progressive motility was slightly reduced (mild asthenozoospermia), but all other sperm characteristics were within the normal range. His father and brother, who did not undergo spermatologic analysis, were also found to carry the deletion. The authors concluded that USP9Y is not essential for normal sperm production and fertility in humans. ### AZFb Region The AZFa, AZFb, and AZFc intervals were defined by interstitial Y-chromosome deletions that impair or extinguish spermatogenesis (Vogt et al., 1996). Repping et al. (2002) studied 11 unrelated azoospermic men who had previously been determined to have interstitial deletions involving AZFb, including 3 characterized as having deletions of AZFb only and 8 with deletions of AZFb plus AZFc. Using high-resolution breakpoint mapping and deletion-junction amplification and sequencing, Repping et al. (2002) found that the deletions previously thought to define the AZFb region actually extended 1.5 Mb into the AZFc region. They concluded that no distinct AZFb interval exists. Using BAC clones, Ferlin et al. (2003) assembled a complete map of AZFb, which was estimated to extend over 3.2 Mb, with repeated sequences representing only 12% of the region. Among 700 infertile men with spermatogenic failure, Ferlin et al. (2003) found that 4 unrelated subjects (2 with a complete absence of germ cells in their testes and 2 with severe hypospermatogenesis) had partial AZFb deletions and apparently identical breakpoints. Another 8 affected men had complete AZFb deletions. Reporting the results of a 'best practice' meeting on guidelines for the molecular diagnosis of Y-chromosome microdeletions, Simoni et al. (2004) stated that no consensus had been reached regarding the existence of a distinct AZFb region versus a model in which the AZFb and AZFc regions are overlapping. ### AZFc Region Deletions of the AZFc region of the Y chromosome are the most common known causes of spermatogenic failure. Kuroda-Kawaguchi et al. (2001) determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping-sequencing process. A complex of 3 palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from 6 distinct families of amplicons, with unit lengths of 115 to 678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. For characterization of naturally occurring deletions in AZFc, Kuroda-Kawaguchi et al. (2001) studied 48 infertile men who were azoospermic or severely oligospermic (less than 5 million sperm per mL) and had interstitial Yq deletions limited to AZFc. The deletions were remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably serve as substrates for homologous recombination. Krausz et al. (2001) performed a double-blind molecular study of Y-chromosome deletions in 138 consecutive Danish patients seeking intracytoplasmic sperm injection treatment, 100 men of known fertility, and 107 young military conscripts from the general Danish population. No microdeletions or gene-specific deletions were detected in normospermic subjects or in subfertile men with a sperm count of more than 1x10(6)/mL. Deletions of the AZFc region were detected in 17% of individuals with idiopathic azoo/cryptozoospermia and in 7% of individuals with nonidiopathic azoo/cryptozoospermia. Krausz et al. (2001) concluded that the composition of the study population is the major factor in determining deletion frequency; Y-chromosome microdeletions are specifically associated with severe spermatogenic failure; and the frequency of Yq microdeletions in the Danish population is similar to that of other countries, suggesting that the involvement of microdeletions in the relatively low sperm count of the Danish population is unlikely. Frydelund-Larsen et al. (2002) analyzed the serum concentrations of reproductive hormones in infertile patients with AZFc microdeletions and compared these to concentrations in a matched group of infertile patients without Yq microdeletions and to those in a group of fertile control individuals. In contrast to the study of Foresta et al. (2001) in which patients with Yq microdeletions had lower FSH (136530) and higher inhibin B (147290) plasma concentrations compared to patients without microdeletions, Frydelund-Larsen et al. (2002) found low serum inhibin B and elevated FSH levels in the majority of 16 patients with AZFc microdeletions compared with fertile control subjects, suggesting that in patients with AZF microdeletions the serum concentration of inhibin B depends upon the functional interaction between Sertoli cells and spermatocytes and/or spermatids. Bilateral testicular biopsies in 10 of the AZFc-deleted patients revealed a variable histologic pattern of severe testiculopathy: 2 patients had bilateral spermatocytic arrest and 1 had bilateral SCO syndrome; the remainder had a combination of both, and some cases showed signs of testicular atrophy. Frydelund-Larsen et al. (2002) suggested that the variable histologic picture might be related to a progressive nature of the testicular defect caused by deletion of the AZFc region. There are rare AZFc-deleted men who have conceived multiple children naturally (Chang et al., 1999; Gatta et al., 2002). All sons of these men are infertile. Repping et al. (2004) identified the b2/b3 deletion, a recurrent 1.8-Mb deletion that removes half of the AZFc region, including 12 members of 8 testis-specific gene families. Deleted genes include RBMY1A1, BPY2 (400013), DAZ, CDY1 (400016), PRY (400019), CSPG4LY (400034), GOLGA2LY (400035), TTTY3 (400036), TTTY4 (400037), TTTY5 (400038), TTTY6 (400039), and TTTY17 (400040). The authors found the deletion primarily in branch N in the Y-chromosome genealogy, in which all chromosomes carried the deletion. Branch N is widely distributed in northern Eurasia, accounts for the majority of Y chromosomes in some populations, and appears to be several thousand years old. The deletion has at most a modest effect on fitness, either because it spares at least 1 near-identical copy of each gene family, or because it has been counterbalanced by another genetic factor. To determine the incidence of various partial AZFc deletions and their effect on fertility, Machev et al. (2004) discriminated 4 types of DAZ-CDY1 partial deletions and performed combined quantitative and qualitative analyses of the AZFc region in 300 infertile men and 399 controls. Only one deletion type, DAZ3/4 (400027, 400048)-CDY1a (400016), was associated with male infertility (p = 0.042), suggesting that most of the partial deletions are neutral variants. A stronger association, however, was found between loss of the CDY1a sequence family variant (SFV) and infertility (p = 0.002). Machev et al. (2004) concluded that loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility. Using AZFc-specific STS markers and DAZ-specific single nucleotide variants, Ferlin et al. (2005) studied 337 infertile men with different impairments of spermatogenesis and 263 normozoospermic fertile men. The authors identified 18 cases of partial AZFc deletions in the infertile group (5.3%) and 1 case in the control group (0.4%); 17 deletions had the so-called gr/gr pattern, 1 had the b2/b3 pattern, and 1 represented a novel deletion with breakpoints in the b3 and b4 amplicons. A father and 5 sons who had apparently identical gr/gr deletions with loss of DAZ3/DAZ4 had very different seminal patterns, ranging from moderate oligospermia to azoospermia, and the normozoospermic man with a partial AZFc deletion also had a gr/gr pattern with loss of DAZ3/DAZ4. Analysis of DAZ gene copy number in this study together with published data led Ferlin et al. (2005) to suggest that only partial AZFc deletions removing DAZ1/DAZ2 (400003, 400026) are associated with spermatogenic impairment, whereas those removing DAZ3/DAZ4 may have little or no effect on fertility. Giachini et al. (2005) analyzed 150 oligo- and azoospermic men and 189 normospermic controls and identified 2 types of partial AZFc deletions, gr/gr and b2/b3. The frequency of gr/gr deletions was significantly higher in the infertile group than controls (5.3% vs 0.5%, p less than 0.012), whereas the frequency of the b2/b3 was not different between the 2 groups. Gene-specific analysis revealed 3 distinct deletion patterns; the authors suggested that combined studies based on gene copy and haplotype analysis might distinguish pathogenic from neutral deletions. In epidemiologic studies, male infertility has shown an association with testicular germ cell tumor (TGCT; 273300). Since the gr/gr deletion is associated with infertility, Nathanson et al. (2005) postulated an association between the gr/gr deletion and TGCT. They analyzed this deletion in a large series of TGCT cases with or without a family history of TGCT. The gr/gr deletion was present in 3% of TGCT cases with a family history, 2% of TGCT cases without a family history, and 1.3% of unaffected males. Presence of the gr/gr deletion was associated with a 2-fold increased risk of TGCT and a 3-fold increased risk of TGCT among patients with a positive family history. The gr/gr deletion was more strongly associated with seminoma TGCT than with nonseminoma TGCT. The data indicated that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT. Arredi et al. (2007) analyzed 8 Y-chromosome haplogroups in 41 unrelated infertile Italian males with the AZFc b2/b4 deletion and 93 Italian men with at least 1 child and no microdeletion. They found that men with microdeletions had a significantly higher frequency of the E haplogroup (29.3% vs 9.7%, p less than 0.01). The authors concluded that Y-chromosome background affects the occurrence of AZFc b2/b4 deletions in this population. Lin et al. (2007) screened 580 Han Chinese in Taiwan for AZFc deletion and duplication and found that 9.5% had AZFc partial deletion, 2.7% had partial deletion followed by duplication, and 1.7% had partial duplication. Rearrangement frequencies varied significantly between different Y-chromosome haplogroups, ranging from 2.9% in O3e to 100% in N and Q. Additional screening in 142 oligospermic men and 107 fertile controls found no significant differences in gr/gr or b2/b3 deletion; however, the frequency of AZFc partial duplication in the infertile group was significantly higher than that in the fertile control group (7.0% vs 0.9%, p = 0.0031). Lin et al. (2007) concluded that AZFc partial deletion and partial duplication are common polymorphisms in Han Chinese, and that AZFc partial duplication, but not AZFc partial deletion, is a risk factor for male infertility in the Taiwanese population. Zhang et al. (2007) typed complete and partial AZFc deletions as well as 19 binary haplogroup markers in 296 Chinese men with spermatogenic impairment and 280 healthy controls. Haplogroup Q1 was found to be gr/gr-deleted, and fixation of the b2/b3 deletion was confirmed in haplogroup N. AZFc partial deletions were not associated with spermatogenic failure in this population, suggesting phenotypic variation of partial AZFc deletions across populations. Giachini et al. (2008) screened 556 infertile Italian men and 487 normozoospermic controls for partial AZFc deletions using sequence-tagged site (STS) analysis followed by CDY1-DAZ gene dosage and copy number analysis, and found that the frequency of gr/gr deletions in patients was significantly different from controls (p less than 0.001; odds ratio, 7.9); however, the authors did not detect a significant effect of b2/b3 deletions or partial AZFc duplications on spermatogenesis in their population. In 160 European men with confirmed gr/gr deletions, including 16 fertile or normospermic men, 26 with azoospermia, 93 with crypto- or oligozoospermia, and 14 with astheno- and/or teratozoospermia, Krausz et al. (2009) analyzed known AZFc structural variants associated with this deletion and Y-SNP-defined haplogroup chromosome background, but found that none of these factors accounted for a significant proportion of the spermatogenic variation associated with gr/gr deletions. The authors concluded that the phenotypic variation of gr/gr deletion carriers in men of European background is largely independent of the Y-chromosomal background. Noordam et al. (2011) analyzed the presence or absence of STS markers in 840 men who were each part of a subfertile couple, unselected for sperm count. Thirty-one men (3.7%) had deletion of 1 or more STS markers: 22 had gr/gr deletions, 4 had b2/b4 deletions, 4 had b2/b3 deletions, and 1 had a b1/b3 deletion. Using real-time quantitative PCR, Noordam et al. (2011) determined actual copy numbers of the DAZ, BPY2, CDY1, CSPG4LY, and GOLGA2LY genes in the 31 men with partial AZFc deletions. For all AZFc genes, they found an association between a reduction in the copy number of each individual AZFc gene and reduced total motile sperm count (TMC). In gr/gr-deleted men, restoration of reduced gene copy numbers via secondary duplication restored their TMC to normal values. Noordam et al. (2011) suggested that the gene content of the AZFc region has been preserved throughout evolution through a dosage effect of the AZFc genes on TMC, safeguarding male fertility. Rozen et al. (2012) screened 20,884 anonymized DNA samples from men of 5 populations (India, Poland, Tunisia, United States, and Vietnam) for 6 recurrent interstitial deletions in the AZFc region, and found that 1 of every 27 men carried 1 of 4 deletions: gr/gr, b2/b3, b1/b3, and b2/b4, in descending order of prevalence. The 1.6-Mb gr/gr deletion, found in 2.4% of the men, almost doubled the risk of severe spermatogenic failure (SSF), defined as a sperm count of less than 5 million per milliliter of semen in the absence of physical obstruction. The gr/gr deletion accounted for approximately 2.2% of SSF, although less than 2% of men with the deletion were affected. The 1.8-Mb b2/b3 deletion, found in 1.1% of men, did not appear to be a risk factor for SSF. The 1.6-Mb b1/b3 deletion, found in 0.1% of men, appeared to increase the risk of SSF by a factor of 2.5, although less than 2% of men with the deletion were affected and it accounted for only 0.15% of SSF. The 3.5-Mb b2/b4 deletion, present in 0.043% of men, was associated with a 145-fold increase in the risk of SSF and accounted for approximately 6% of SSF. Rozen et al. (2012) concluded that a single rare variant of major effect, the b2/b4 deletion, and a single common variant of modest effect, the gr/gr deletion, are largely responsible for the contribution of the ACFc region to severe spermatogenic failure. ### AZFd Region Kent-First et al. (1999) designed a panel of 9 multiplexed reactions, including 48 Y-linked STSs, for the identification of infertility-associated microdeletions of the Y chromosome. They identified a fourth AZF region required for normal spermatogenesis, located between AZFb and AZFc, which they designated AZFd. Reporting the results of a 'best practice' meeting on guidelines for the molecular diagnosis of Y-chromosome microdeletions, Simoni et al. (2004) stated that the sequence of the male-specific portion of the Y chromosome (MSY) and the mechanism underlying the microdeletions have shown definitely that the putative fourth AZFd region postulated by Kent-First et al. (1999) does not exist. ### Y-Chromosome Haplogroups Krausz et al. (2001) typed the Y chromosome in a group of oligo- or azoospermic Danish men who had previously been shown (Krausz et al., 2001) not to harbor microdeletions in the AZFa, b, or c regions and compared the haplotype distribution with that of a group of unselected Danish males. One class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; p less than 0.001) in the group of men with either idiopathic oligozoospermia (defined as less than 20 million sperm/mL) or azoospermia compared to the control Danish male population (4.6%). The authors hypothesized that since this class of Y chromosome may be at risk for infertility among Danish men, active selection against such a haplotype could alter the pattern of Y-chromosome haplotype distribution in the general population. Carvalho et al. (2003) analyzed 84 Japanese oligo- or azoospermic men for Yq microdeletions and also defined their Y haplogroups using a battery of unique event polymorphisms. In the 6 infertile men in whom likely pathologic microdeletions were found, there was no significant association between Y-chromosome haplogroups and the microdeletions. Carvalho et al. (2003) also compared the Y-haplogroup frequencies in a subset sample of 51 patients with idiopathic azoospermia to those in 57 fertile control Japanese males and observed no significant differences. The authors concluded that Y microdeletions and other molecular events associated with male infertility in Japan occur independently of Y-chromosome background. GU \- Nonobstructive oligo- or azoospermia \- Azoospermia factor (AZF) Misc \- Predicted protein products suggest role in RNA processing or translational control during early spermatogenesis \- Testis specific gene expression Inheritance \- Y-linked (Yq11.23) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SPERMATOGENIC FAILURE, Y-LINKED, 2	c1507149	2,730	omim	https://www.omim.org/entry/415000	2019-09-22T16:17:01	{"doid": ["0070187"], "mesh": ["C536297"], "omim": ["415000"], "orphanet": ["1646"], "synonyms": ["Alternative titles", "SPERMATOGENIC FAILURE, NONOBSTRUCTIVE, Y-LINKED", "AZOOSPERMIA, NONOBSTRUCTIVE, Y-LINKED", "OLIGOZOOSPERMIA, NONOBSTRUCTIVE, Y-LINKED", "OLIGOSPERMIA, NONOBSTRUCTIVE, Y-LINKED", "SPERMATOGENIC ARREST, Y-LINKED"], "genereviews": ["NBK1339"]}
An extremely rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by a CMT neuropathy associated with developmental delay, self-abusive behavior, dysmorphic features and vestibular Schwannoma. Motor nerve conduction velocities demonstrate features of both demyelinating and axonal pathology. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Autosomal recessive intermediate Charcot-Marie-Tooth disease type B	c3150897	2,731	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254334	2021-01-23T17:10:52	{"gard": ["12454"], "omim": ["613641"], "icd-10": ["G60.0"], "synonyms": ["RI-CMT type B"]}
A number sign (#) is used with this entry because 20 to 60% of cases of Silver-Russell syndrome (SRS) are caused by the epigenetic changes of DNA hypomethylation at the H19/IGF2-imprinting control region (ICR1; 616186) on chromosome 11p15.5. ICR1 regulates the imprinted expression of H19 (103280) and IGF2 (147470). About 10% of SRS cases are due to maternal uniparental disomy of chromosome 7 (summary by Penaherrera et al., 2010). Description Silver-Russell syndrome is a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. Hypomethylation at distal chromosome 11p15 (ICR1) represents a major cause of the disorder. Opposite epimutations, namely hypermethylation at the same region on 11p15, are observed in about 5 to 10% of patients with Beckwith-Wiedemann syndrome (BWS; 130650), an overgrowth syndrome (Bartholdi et al., 2009). Clinical Features Silver-Russell syndrome (SRS) was reported independently by Silver et al. (1953) and Russell (1954). Silver et al. (1953) described 2 unrelated children with congenital hemihypertrophy, low birth weight, short stature, and elevated urinary gonadotropins. Russell (1954) described 5 unrelated children with intrauterine growth retardation and characteristic facial features, including triangular shaped face with a broad forehead and pointed, small chin with a wide, thin mouth. Two children had body asymmetry. Although each of these authors emphasized different phenotypic features, the whole picture was later identified as the 'Russell-Silver syndrome' (Patton, 1988). Chitayat et al. (1988) described hepatocellular carcinoma in a 4-year-old boy with Russell-Silver syndrome. His brother had low birth weight and bilateral clinodactyly of the fifth fingers and grew slowly. Neither brother showed asymmetry. Donnai et al. (1989) described unusually severe Silver-Russell syndrome in 3 children with pre- and postnatal growth deficiency. Price et al. (1999) reevaluated 57 patients in whom the diagnosis of SRS had been considered definite or likely. In 50 patients the clinical findings complied with a very broad definition of SRS. Notable additional findings included generalized camptodactyly in 11 individuals, many with distal arthrogryposis. Thirteen of the 25 males studied required genital surgery for conditions including hypospadias and inguinal hernia. Severe feeding problems were reported by 56% of parents, and sweating and pallor were described by 52% of parents in the early weeks of life. Fourteen of the 38 individuals of school age had been considered for special education; 4 attended special school. Molecular analysis in 42 subjects identified uniparental disomy (UPD) of chromosome 7 in 4 subjects. The phenotype in these 4 cases was generally milder than that in the non-UPD cases, with only 2 having the classic facial dysmorphism. Anderson et al. (2002) conducted a study of gastrointestinal complications of SRS by questionnaire distributed by MAGIC, a support group for individuals with SRS. One-hundred thirty-five completed surveys were returned, of which 65 related to children with clear-cut SRS. Of these, 50 (77%) had gastrointestinal symptoms: gastroesophageal reflux disease (34%), esophagitis (25%), food aversion (32%), and failure to thrive (63%). Gronlund et al. (2011) identified ophthalmologic abnormalities in 17 of 18 children with Silver-Russell syndrome. Best corrected visual acuity of the better eye was less than 0.1 log of the minimal angle of resolution (less than 20/200; legal blindness) in 11 children, and 11 children had refractive errors. Anisometropia (greater than 1 diopter) was noted in 3 children. Subnormal stereo acuity and near point of convergence were found in 2 of 16 children. The total axial length in both eyes was shorter compared with that of controls. Of 16 children, 3 had small optic discs, 3 had large cup:disc ratio, and 4 had increased tortuosity of retinal vessels. Gronlund et al. (2011) recommended ophthalmologic examination for children with SRS. Inheritance Rimoin (1969) described monozygotic male twins concordant for Silver dwarfism. However, Nyhan and Sakati (1976) and Samn et al. (1990) described monozygotic twins discordant for RSS. Bailey et al. (1995) described triplets, one of whom had RSS. The evidence was strong that he and his triplet brother were monozygotic; the brother was unaffected. The clinical characteristics consistent with RSS were a birth weight of less than 3 SD below the mean for gestational age and lower than either of his same-gestation sibs. The affected child had a small head circumference and a short birth length. Fuleihan et al. (1971) observed 3 affected sibs among the 6 offspring of consanguineous Lebanese parents. Craniofacial disproportion and other minor anomalies were present. The mother was very short. Another possible familial occurrence was observed by Silver (cited by Gareis et al., 1971), who found that the mother of one of his cases was only 59 inches tall and had triangular facies and incurved fifth fingers. Tanner et al. (1975) reported on a longitudinal study of 39 cases. None of 61 sibs was affected. The authors found no distinction between Silver and Russell syndromes. Escobar et al. (1978) reported affected half brother and sister and reviewed reported familial cases. Duncan et al. (1990) reported 7 affected persons in two 3-generation families. Three members of each family had an undergrowth of the left side of the body when compared with the normal right side. The authors noted that the clinical features were milder than those reported in sporadic cases. Duncan et al. (1990) found that in 17 reported families, multiple maternal relatives had complete or partial expression of Silver-Russell syndrome. Of 197 probands analyzed, 19% had one or more affected relatives. Two families with affected twins were consistent with new dominant mutation; possible autosomal recessive inheritance was found in 4 families. Because no male-to-male transmission was documented in 21 families in the literature or in the 2 families reported by Duncan et al. (1990), they suggested that X-linked dominant inheritance is a possibility. Al-Fifi et al. (1996) reported 2 families with apparent autosomal dominant transmission of RSS. In 1 family, the mother (height 140 cm) and a son and daughter of hers were affected. The mother's father was remarkably short and thin until his late teens, but was later of normal height (25th centile) with triangular face, mild asymmetry, and prominent ears. In the second family, the mother's height and weight were below the third percentile for age before puberty. After puberty, her height reached the 25th percentile but she remained thin. A son and daughter were thought to be affected. Ounap et al. (2004) described 2 sisters who met the criteria for SRS proposed by Price et al. (1999). The parents had normal facial features, normal height, and normal postnatal growth. Ounap et al. (2004) stated that this was the second well-documented case of familial recurrence of SRS suggesting autosomal recessive inheritance, the other being that of 6 sibs (5 males and 1 female) of normal first-cousin Arab parents (Teebi, 1992). In the family reported by Ounap et al. (2004), Bartholdi et al. (2009) identified hypomethylation at chromosome 11p15. Bartholdi et al. (2009) also reported another family in which 2 sibs had SRS associated with hypomethylation at 11p15. The authors postulated germ cell mosaicism of an incorrect methylation mark at the ICR1 during spermatogenesis in the fathers. Bartholdi et al. (2009) reported a father and daughter with SRS who both had partial hypomethylation at chromosome 11p15, suggesting vertical transmission. Although the mechanism was difficult to explain, the authors postulated that the missing methylation mark in the father was not reset or corrected (setting of a methylation mark) during spermatogenesis. The findings had implications for genetic counseling. Diagnosis On the basis of radiographs of 15 patients, Herman et al. (1987) concluded that no single finding is pathognomonic; however, between the ages of 2 and 10 years, delayed maturation, clinodactyly, fifth middle or distal phalangeal hypoplasia, ivory epiphyses, and a second metacarpal pseudoepiphysis are suggestive. Price et al. (1999) proposed diagnostic criteria for SRS: (1) birth weight below or equal to -2 SD from the mean; (2) poor postnatal growth below or equal to -2 SD from the mean at diagnosis; (3) preservation of occipitofrontal head circumference (OFC); (4) classic facial phenotype; and (5) asymmetry. Price et al. (1999) noted that some cases associated with uniparental disomy (UDP) (see below) might remain undiagnosed if strict criteria are applied, and suggested that the presence of feeding difficulties may be particularly helpful in making a diagnosis in these cases. Cytogenetics ### Chromosome 17 Ramirez-Duenas et al. (1992) observed severe Russell-Silver syndrome in a girl with translocation t(17;20)(q25;q13). No evidence of imbalance was found. The father exhibited the same balanced translocation. Ramirez-Duenas et al. (1992) questioned whether the RSS locus is located on either chromosome 17 or 20 and whether the patient's phenotype resulted from either unmasking of heterozygosity or genomic imprinting via paternal disomy. Midro et al. (1993) found the identical chromosome 17 breakpoint (17q25) in an 8-year-old boy with a de novo t(1;17)(q31;q25) and Silver-Russell syndrome. In a child with RSS, Eggermann et al. (1998) reported a heterozygous paternally inherited deletion of the gene encoding chorionic somatomammotropin hormone (CSH1; 150200), which maps to 17q22-q24. The authors noted that deletions of CSH1 with no phenotypic consequences have been reported; however, a role for the heterozygous deletion in this case was considered possible. Dorr et al. (2001) prepared a physical and transcript map of the critical region for the RSS translocation breakpoint on 17q23-q24. ### Chromosome 7 Eggerding et al. (1994) noted that 3 cases of maternal uniparental disomy for chromosome 7 (mUPD7) had been reported in patients with intrauterine and postnatal growth retardation. Two patients were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous (see 219700). One patient was found because he was homozygous for a rare COL1A2 mutation (120160.0030). Eggerding et al. (1994) reported a female child with growth retardation in whom the normal chromosome 7 homologs were replaced by isochromosomes of 7p and 7q. Molecular studies showed that the child had paternal 7p isodisomy and maternal 7q isodisomy. Phenotypically, she had triangular facies, mild clinodactyly, and limb asymmetry. The authors suggested that imprinting may play a role. Kotzot et al. (1995) investigated 35 patients with either Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for UPD7. Maternal disomy was found in 4 of the 35 patients, including 3 with isodisomy and 1 with heterodisomy. The data confirmed the localization of 1 or more maternally imprinted genes on chromosome 7. In a prospective study of 33 patients with sporadic Russell-Silver syndrome, Preece et al. (1997) studied the parent of origin of chromosome 7 using variable number tandem repeat (VNTR) or microsatellite repeat markers and identified 2 patients with maternal UPD of chromosome 7. The probands' condition was clinically mild and symmetrical, and showed no gross clinical differences from that of the 30 patients with chromosome 7 derived from both parents. Eggermann et al. (1997) studied 37 patients with Silver-Russell syndrome using short tandem repeat markers from chromosomes 2, 7, 9, 14, and 16. Uniparental disomy for chromosome 7 was detected in 3 SRS patients. In all 3 cases, it was maternal in origin. In 1 of the 3 families, complete isodisomy was found, and in the other 2 families, the allelic patterns were consistent with partial and complete heterodisomy, respectively. Short tandem repeat typing for uniparental disomy for chromosomes 2, 9, 14, and 16 was unrevealing. All 3 cases with maternal UPD7 had typical clinical features of SRS, with 2 of them classified as moderately severe. One was treated with human growth hormone with good results. Dupont et al. (2002) reported a case of SRS in a child with an apparently balanced, maternally-inherited reciprocal translocation, t(7;16)(q21;q24), and maternal heterodisomy for chromosome 7. Microsatellite analysis showed a normal biparental inheritance of chromosome 16 but confirmed maternal heterodisomy of chromosome 7. The child presented with growth retardation and minor facial dysmorphism without mental retardation. Monk et al. (2002) estimated that approximately 10% of SRS cases showed maternal uniparental disomy for chromosome 7. They suggested that the phenotype in these cases may be due to disruption of imprinted gene expression, as opposed to the unmasking of a mutant recessive allele. Monk et al. (2002) described 2 SRS patients and 4 probands with pre- and postnatal growth restriction with a range of cytogenetic disruptions of chromosome 7p, including duplications, pericentric inversions, and a translocation. In these 6 novel cases, and 3 previously described probands with duplications, Monk et al. (2002) mapped the breakpoints using FISH probes from a contig of PACs and BACs constructed from the centromere to 7p14. They identified a common breakpoint region within 7p11.2 in all 9 cases, pinpointing this specific interval. They also studied the imprinting status of genes within the 7p14-p11.1 region flanked by the most extreme breakpoints. By examining 77 families with SRS, Nakabayashi et al. (2002) identified 2 patients with de novo chromosomal rearrangements involving the short arm of chromosome 7. One patient had a partial duplication and was cytogenetically characterized 46,XX,dup(7)(p12p14), and the other patient had a paracentric inversion and was characterized 46,XY,inv(7)(p14p21). The duplication breakpoint interrupted the C7ORF10 gene (609187), and the inversion breakpoint mapped to the 5-prime end of the C7ORF10 gene, possibly just within intron 1. However, Nakabayashi et al. (2002) suggested that the inversion breakpoint may affect both C7ORF10 and C7ORF11, since the 2 genes are separated by less than 100 bp. Guettard et al. (2008) reported a 35-year-old man with myoclonus-dystonia (159900) and Silver-Russell syndrome. He developed symptoms of myoclonus-dystonia at age 17. Features of SRS included intrauterine growth retardation, short stature, and facial dysmorphism. He did not have mental retardation. Cytogenetic analysis identified mosaicism for a small supernumerary ring chromosome 7, which was considered unlikely to contribute to the phenotype. Microsatellite analysis indicated loss of the paternal allele and maternal UPD7 with maternally imprinted loss of SGCE gene (604149) expression. The findings indicated UPD7 resulted in repression of both alleles of the maternally imprinted SGCE gene, suggesting loss of function of SGCE as the disease mechanism in myoclonus-dystonia. Guettard et al. (2008) suggested that some patients with SRS and similar cytogenetic abnormalities may develop symptoms of myoclonus-dystonia. Penaherrera et al. (2010) found that 3 of 35 blood samples from patients with SRS had maternal UPD7. All were highly methylated at the SGCE promoter. ### Chromosome 1 Van Haelst et al. (2002) reported a patient with phenotypic features of Silver-Russell syndrome who had trisomy 1q32.1-q42.1. ### Chromosome X Li et al. (2004) reported a female infant with a karyotype of 45,X on prenatal amniocytes. After delivery she was noted to have features consistent with Russell-Silver syndrome, including a triangular face with prominent forehead, large eyes, a thin nose, malar hypoplasia, thin upper lip with downturned corner of the mouth, and a pointed chin. Marked body asymmetry was evident at birth, with the left side significantly smaller than the right side. She also had a diphalangeal left fifth finger. Skin fibroblast culture and analysis showed a karyotype of 45,X on the right side and 45,X/46,XX on the left side. The case is another illustration of the genetic heterogeneity of the Russell-Silver phenotype. ### Chromosome 11 Chiesa et al. (2012) described 2 maternal 11p15.5 microduplications with contrasting phenotypes. In the first case, a 1.2-Mb inverted duplication of chromosome 11p15 derived from the maternal allele resulted in Silver-Russell syndrome. The duplication encompassed the entire 11p15.5 imprinted gene cluster, and hypermethylation of CpGs throughout the ICR2 region was observed. These findings were consistent with the maintenance of genomic imprinting, with a double dosage of maternal imprinting and resulting in a lack of KCNQ1OT1 (604115) transcription. In the second case, a maternally inherited 160-kb inverted duplication that included only ICR2 and the most 5-prime 20 kb of KCNQ1OT1 resulted in a BWS (130650) phenotype in 5 individuals in 2 generations. This duplication was associated with hypomethylation of ICR2 resulting from partial loss of the imprinted methylation of the maternal allele, expression of a truncated KCNQ1OT1 transcript, and silencing of CDKN1C (600856). Chromatin RNA immunopurification studies suggested that the KCNQ1OT1 RNA interacts with chromatin through its most 5-prime 20-kb sequence, providing a mechanism for the silencing activity of this noncoding RNA. The finding of similar duplications of ICR2 resulting in different methylation imprints suggested that the ICR2 sequence is not sufficient for establishing DNA methylation on the maternal chromosome, and that some other property, possibly orientation-dependent, is needed. Molecular Genetics Abu-Amero et al. (2008) provided a review of the complex genetic etiology of Silver-Russell syndrome, which primarily involves chromosomes 7 and 11. ### Genes on Chromosome 7 In the mouse, and presumably the human as well, the gene encoding growth factor receptor-bound protein-10 (GRB10; 601523) is imprinted. GRB10 protein binds to the insulin receptor (INSR; 147670) and IGF1R via its Src homology 2 domain and inhibits the associated tyrosine kinase activity that is involved in the growth-promoting activities of insulin (INS; 176730) and insulin-like growth factors I (IGF1; 147440) and II (IGF2; 147470). The mouse Grb10 gene is located on proximal chromosome 11. Miyoshi et al. (1998) suggested that, in the mouse, Grb10 is responsible for the imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies, respectively. Based on the location of the human GRB10 gene on 7p12-p11.2 and reports that maternal uniparental disomy 7 may be responsible for Russell-Silver syndrome, Miyoshi et al. (1998) identified GRB10 as a candidate gene for the disorder. Joyce et al. (1999) estimated that approximately 10% of cases of SRS are associated with maternal uniparental disomy of chromosome 7, suggesting that at least one imprinted gene on chromosome 7 is involved in the pathogenesis of the disease. They reported a proximal 7p interstitial inverted duplication in a mother and daughter, both of whom had features of SRS, including markedly short stature, low birth weight, facial asymmetry, and fifth finger clinodactyly. Fluorescence in situ hybridization with YAC probes enabled delineation of the duplicated region as 7p13-p12.1. This region of proximal 7p is known to be homologous to an imprinted region in mouse chromosome 11 and contains the growth-related genes GRB10, epidermal growth factor receptor (EGFR; 131550), and insulin-like growth factor-binding protein-1 (IGFBP1; 146730), all of which had been suggested as candidate genes for SRS. Molecular analysis in the case of Joyce et al. (1999) showed that the duplication in both mother and daughter spanned a distance of approximately 10 cM and included GRB10 and IGFBP1 but not EGFR. The de novo duplication in the mother was shown to be of paternal origin. To test the hypothesis that submicroscopic duplications of 7p, whether maternal or paternal in origin, are responsible for at least some cases of SRS, they screened a further 8 patients and found duplications of either GRB10 or IGFBP1. The results were thought to suggest that imprinted genes may not underlie the SRS phenotype. Joyce et al. (1999) proposed an alternative hypothesis to explain the occurrence of maternal UPD7 in some cases of SRS. They suggested that SRS may be caused by the inheritance of an additional copy of chromosome 7 material, either as a result of small duplications or undetected trisomy. They pointed out that 6 cases of maternal UPD7 had been shown to have arisen by trisomy rescue. They considered it possible that all cases of maternal UPD7 arise in this way and that an additional copy of the SRS gene(s) in an undetected trisomic cell line is responsible for the phenotype. Somatic mosaicism might help account for the asymmetric growth patterns often seen in SRS, a mechanism implicated in the hemihypertrophy observed in Beckwith-Wiedemann syndrome (130650). In a study of genetic and phenotypic similarities among patients exhibiting developmental verbal dyspraxia (DVD; 602081), Feuk et al. (2006) studied 7 cases of Russell-Silver syndrome with maternal UPD7. All showed absence of a paternal copy of FOXP2 (605317). All had marked speech delay and difficulties in speech output, particularly articulation. Feuk et al. (2006) considered it noteworthy that while SRS is clinically and genetically heterogeneous, mainly only patients with complete maternal UPD7 (approximately 10%) exhibit DVD. These and other observations suggested that absence of paternal FOXP2 is the cause of DVD in SRS. Wakeling et al. (2000) studied the imprinting status of IGFBP1 and IGFBP3 (146732) in normal fetuses and in patients with SRS. Biallelic expression of both genes was found in normal fetal tissue and in 2 SRS patients with UPD7 and 4 SRS patients without UPD7. Wakeling et al. (2000) concluded that IGFBP1 and IGFBP3 were unlikely to be involved in SRS. Monk et al. (2000) identified a de novo duplication of 7p13-p11.2 in a 5-year-old girl with features characteristic of SRS. FISH confirmed the presence of a tandem duplication encompassing the GRB10, IGFBP1, and IGFBP3 genes, but not the EGFR gene. Microsatellite markers showed that the duplication was of maternal origin. These findings provided the first evidence that SRS may result from overexpression of a maternally expressed imprinted gene, rather than from absent expression of a paternally expressed gene. The GRB10 gene lies within the duplicated region and was considered to be a strong candidate, since it is a known growth repressor. Monk et al. (2000) demonstrated that the GRB10 genomic interval replicates asynchronously in human lymphocytes, suggestive of imprinting. An additional 36 SRS probands were investigated for duplication of GRB10, but none was found. However, it remained possible that GRB10 and/or other genes within 7p13-p11.2 are responsible for some cases of SRS. Yoshihashi et al. (2000) performed mutation analysis of the GRB10 gene in 58 unrelated patients with SRS and identified a pro95-to-ser substitution within the N-terminal domain in 2 of the patients. However, Hannula et al. (2001), Hitchins et al. (2001), and McCann et al. (2001) presented evidence creating uncertainty about the role of the GRB10 gene in Russell-Silver syndrome. Among 11 patients with RSS, Martinez et al. (2001) found no molecular evidence for duplication of chromosomal segment 7p11.2-p13. Hannula et al. (2001) studied 4 patients with maternal UPD7 and argued that they might compose a distinct phenotypic entity among Silver-Russell syndrome patients with a mild phenotype. In a systematic screening with microsatellite markers for maternal UPD of chromosome 7 in patients with SRS, Hannula et al. (2001) identified a patient with a small segment of matUPD7 (7q31-qter) and biparental inheritance of the remainder of the chromosome. The pattern was thought to be explained by somatic recombination in the zygote. The matUPD7 segment extended for 35 Mb and included the imprinted gene cluster of PEG1/MEST (601029) and COPG2 (604355) at 7q32. GRB10 at 7p12-p11.2 was located within the region of biparental inheritance in this case. Hitchins et al. (2001) used expressed polymorphisms to determine the imprinting status of the GRB10 gene in multiple human fetal tissues. Expression from the paternal allele was exclusive in the spinal cord and predominant in fetal brain, whereas expression from both parental alleles was detected in a wide range of other organs and peripheral tissues. The role GRB10 might play in the etiology of RSS involving chromosome 7 was difficult to predict in view of the imprinting profile of the gene. Further doubt about the role of GRB10 in RSS was cast by the absence of mutations detected by sequencing in 18 classic RSS patients, where major structural chromosomal abnormalities and matUPD7 had previously been excluded. McCann et al. (2001) likewise cast doubt on the role of GRB10 in Silver-Russell syndrome. Using RT-PCR, they confirmed that GRB10 imprinting in brain and muscle is isoform specific, and they demonstrated absence of imprinting in growth plate cartilage, the tissue most directly involved in linear growth. Thus, they considered it unlikely that GRB10 is the gene responsible for SRS. ### Genes on Chromosome 11 Given the crucial role of the 11p15 imprinted region in the control of fetal growth, Gicquel et al. (2005) hypothesized that dysregulation of genes at 11p15 might be involved in syndromic intrauterine growth retardation. In the telomeric imprinting center region ICR1 of the 11p15 region in several individuals with clinically typical Silver-Russell syndrome, they identified an epimutation (demethylation). The epigenetic defect was associated with, and probably responsible for, relaxation of imprinting and biallelic expression of H19 (103280) and downregulation of IGF2 (147470). These findings provided new insight into the pathogenesis of SRS and strongly suggested that the 11p15 imprinted region, in addition to the imprinted region of 7p13-p11.2 and 7q31-qter, is involved in SRS. The loss of paternal methylation in individuals with SRS may have resulted from a deficient acquisition of methylation during spermatogenesis or from a lack of maintenance of methylation after fertilization. The 5 individuals with SRS that carried the epimutation had only a partial loss of methylation, and 4 of them had body asymmetry. These data suggested that the loss of methylation occurred after fertilization and resulted in a mosaic distribution of the epimutation. The epimutation described in individuals with SRS by Gicquel et al. (2005) is the exact opposite of one of the molecular defects responsible for Beckwith-Wiedemann syndrome (BWS; 130650): approximately 10% of individuals with BWS have hypermethylation of the H19 promoter. The most common epimutation in individuals with BWS involves the centromeric 11p15 subdomain and consists of loss of methylation of the maternal KCNQ1OT1 (604115) allele. Paternal inheritance of a null KCNQ1OT1 allele results in fetal growth retardation by 20 to 25% but does not affect expression of H19 or IGF2. One of the 5 individuals with the epimutation was a monozygotic twin, and her twin had no clinical features of SRS. Both twins had a loss of methylation in the telomeric 11p15 domain in their leukocyte DNA and biallelic expression of H19 in their blood cells. However, in skin fibroblasts, only the affected twin showed abnormal methylation. This observation was consistent with results obtained from BWS-discordant monozygotic twins and suggested that the presence of the epigenetic defect of blood cells of both twins results from shared fetal circulation. The H19 differentially methylated region (DMR) controls the allele-specific expression of both the imprinted H19 tumor suppressor gene and the IGF2 growth factor. Hypermethylation of this DMR--and subsequently of the H19 promoter region--is a major cause of the clinical features of gigantism and/or asymmetry seen in Beckwith-Wiedemann syndrome or in isolated hemihypertrophy. Bliek et al. (2006) reported a series of patients with hypomethylation of the H19 locus. The main clinical features of asymmetry and growth retardation were the opposite of those seen in patients with hypermethylation of this region. In addition, they found that complete hypomethylation of the H19 promoter was associated in 2 of 3 patients with the full clinical spectrum of Silver-Russell syndrome. Following up on the work of Gicquel et al. (2005) on epigenetic mutations in the etiology of SRS, Eggermann et al. (2006) screened a cohort of 51 SRS patients for epimutations in ICR1 (the telomeric imprinting center region of 11p15) and KCNQ1OT1 (604115) by methylation-sensitive Southern blot analyses. ICR1 demethylation was observed in 16 of the 51 SRS patients, corresponding to a frequency of approximately 31%. Changes in methylation at the KCNQ1OT1 locus were not detected. Combining these data with those on maternal duplications in 11p15, nearly 35% of SRS cases are associated with detectable (epi)genetic disturbances in 11p15. Eggermann et al. (2006) suggested that a general involvement of 11p15 changes in growth-retarded patients with only minor or without further dysmorphic features must be considered. SRS and BWS may be regarded as 2 diseases caused by opposite (epi)genetic disturbances of the same chromosomal region displaying opposite clinical pictures. Schonherr et al. (2007) stated that methylation defects in the imprinted region of 11p15 can be detected in about 30% of patients with SRS. They reported the first patient with SRS with a cryptic duplication restricted to the centromeric imprinting center ICR2 in 11p15. The maternally inherited duplication in this patient included a region of 0.76 to 1.0 Mbp and affected the genes regulated by the ICR2, among them CDKN1C (600856) and LIT1 (604115). Netchine et al. (2007) screened for 11p15 epimutation and mUPD7 in SRS and non-SRS small-for-gestational-age (SGA) patients to identify epigenetic-phenotypic correlations. Of the 127 SGA patients studied, 58 were diagnosed with SRS; 37 of these (63.8%) displayed partial loss of methylation (LOM) of the 11p15 ICR1 domain, and 3 (5.2%) had mUPD7. No molecular abnormalities were found in the non-SRS SGA group. Birth weight, birth length, and postnatal body mass index (BMI) were lower in the abnormal 11p15 SRS group (ab-ICR1-SRS) than in the normal 11p15 SRS group (-3.4 vs -2.6 SD score (SDS), -4.4 vs -3.4 SDS, and -2.5 vs -1.6 SDS, respectively; p less than 0.05). Among SRS patients, prominent forehead, relative macrocephaly, body asymmetry, and low BMI were significantly associated with ICR1 LOM. All ab-ICR1-SRS patients had at least 4 of 5 criteria of the scoring system. Netchine et al. (2007) concluded that the 11p15 ICR1 epimutation is a major, specific cause of SRS exhibiting failure to thrive. They proposed a clinical scoring system (including a BMI of less than -2 SDS), highly predictive of 11p15 ICR1 LOM, for the diagnosis of SRS. Bullman et al. (2008) reported a patient with SRS who had mosaic maternal uniparental disomy of chromosome 11 with abnormal methylation of ICR2. MLPA analysis showed 12 informative loci between chromosome 11p15.5 to 11q23.3. The isodisomy was the reciprocal of the mosaic paternal isodisomy seen in patients with BWS. Azzi et al. (2009) studied the methylation status of 5 maternally and 2 paternally methylated loci in a series of 167 patients with 11p15-related fetal growth disorders. Seven of 74 (9.5%) Russell-Silver (RSS) patients and 16 of 68 (24%) Beckwith-Wiedemann (BWS; 130650) patients showed multilocus loss of methylation (LOM) at regions other than ICR1 and ICR2 11p15, respectively. Moreover, over two-thirds of multilocus LOM RSS patients also had LOM at a second paternally methylated locus, DLK1/GTL2 IG-DMR. No additional clinical features due to LOM of other loci were found, suggesting an (epi)dominant effect of the 11p15 LOM on the clinical phenotype for this series of patients. Surprisingly, 4 patients displayed LOM at both ICR1 and ICR2 11p15; 3 of them had a RSS and 1 patient had a BWS phenotype. The authors concluded that multilocus LOM can also concern RSS patients, and that LOM can involve both paternally and maternally methylated loci in the same patient. Using PCR-based methylation analysis, Penaherrera et al. (2010) found that 13 (37%) of 35 blood samples from patients with SRS showed methylation levels at H19/IGF2 ICR1 that were more than 2 SD below the mean for controls. Clinically, SRS patients had a lower birth weight (at least 2 SD below the mean), relative macrocephaly, and a higher frequency of body asymmetry compared to SRS patients without these epigenetic changes. One patient had a mediastinal neuroblastoma. Controls had considerable variability in methylation (30 to 47%) at ICR1, which Penaherrera et al. (2010) noted can cause some ambiguity in establishing clear cutoffs for diagnosis. ### Other Genes Penaherrera et al. (2010) found no changes in methylation of the KVDMR1 (see KCNQ1; 607542), PLAGL1 (603044), or PEG10 (609810) genes in blood samples of 35 patients with SRS. Whole genome methylation analysis of a subset of 22 SRS patients, including 10 who had hypomethylation at ICR1, showed no global disruption in methylation in these patients compared to controls. ### Exclusion Studies Previous studies had shown that individuals with a deletion of 15q26.1-qter, which includes the insulin-like growth factor I receptor gene (IGF1R; 147370), may exhibit some phenotypic characteristics resembling those of Russell-Silver syndrome. Abu-Amero et al. (1997) investigated 33 RSS probands, with normal karyotypes, and their parents for the presence of both copies of IGF1R by gene dosage analysis of Southern blot hybridization. All 33 probands had both copies of the gene. Two important functional regions of IGF1R were also investigated for DNA mutations using SSCP analysis; no mutations were found. The patients were from the series of cases studied by Preece et al. (1997). Genotype/Phenotype Correlations Binder et al. (2008) compared the genotype in 44 patients with SRS with the endocrine phenotype. Epimutations at 11p15 were found in 19 of the 44, UPD7 in 5, and small structural aberrations of the short arm of chromosome 11 in 2. Of the 44 cases, 18 were negative for any genetic defect known (41%). The most severe phenotype was found in children with 11p15 SRS. Children with UPD7 SRS had a significantly higher birth length than the 11p15 SRS subjects (P less than 0.004) but lost height SD score postpartum, whereas children with 11p15 SRS showed no change in height SD score. There was a trend toward more height gain in children with UPD7 than in those with 11p15 epimutation under GH therapy (+2.5 vs +1.9 height SD score after 3 years) (P = 0.08). Binder et al. (2008) concluded that children with SRS and an 11p15 epimutation have IGFBP3 (146732) excess and show endocrine characteristics suggesting IGF1 (147440) insensitivity, whereas children with SRS and UPD7 were not different with respect to endocrine characteristics from nonsyndromic short children born SGA. This phenotype-genotype correlation implicated divergent endocrine mechanisms of growth failure in SRS. Bartholdi et al. (2009) found that 106 (53%) of 201 patients with suspected SRS actually fulfilled clinical criteria for the disorder. Hypomethylation at the ICR1 on chromosome 11p15 was observed in 41 (38.5%) of the 106 patients. The majority of patients showed hypomethylation of both H19 and IGF2, but 10 showed selective hypomethylation of H19 and 2 showed selective hypomethylation of IGF2. However, the authors noted that the IGF2-specific probe showed a broader variation in controls as compared to the H19 probe. Seven (6.6%) of the 106 patients had uniparental disomy of chromosome 7. Patients carrying epimutations had higher disease scores than those with maternal uniparental disomy of chromosome 7 or those with no identified defects, indicating that hypomethylation at 11p15 was associated with a more severe phenotype, particularly body asymmetry. No genetic anomaly was detected in 54.7% of patients. History Tanner and Ham (1969) suggested that the designation 'Silver dwarf' be reserved for children of short stature and low birth weight who have asymmetry of arms, legs, body or head, and incurved fifth fingers. They suggested that the designation 'Russell dwarf' be reserved for the similar situation when asymmetry is lacking. Patton (1988) noted that this distinction had not been generally accepted. INHERITANCE \- Autosomal dominant (loss of paternal allele) GROWTH Height \- Average adult male height, 149.5 cm \- Average female adult height, 138 cm Weight \- Small for gestational age infant Other \- Lateral asymmetry \- Partial or total asymmetry \- Intrauterine growth retardation HEAD & NECK Head \- Pseudohydrocephalic appearance \- Normal head circumference Face \- Small, triangular face \- Micrognathia \- Frontal bossing Eyes \- Blue sclera in infancy Mouth \- Downturned corners of mouth CARDIOVASCULAR Heart \- Cardiac defects GENITOURINARY Ureters \- Posterior urethral valves \- Hypospadias SKELETAL \- Skeletal maturation retardation Skull \- Craniofacial disproportion \- Delayed fontanel closure Limbs \- Asymmetry of arms and/or legs Hands \- Fifth finger clinodactyly \- Fifth digit middle or distal phalangeal hypoplasia Feet \- Syndactyly of 2nd-3rd toes SKIN, NAILS, & HAIR Skin \- Cafe-au-lait spots NEUROLOGIC Central Nervous System \- Developmental delay ENDOCRINE FEATURES \- Fasting hypoglycemia \- Growth hormone deficiency in some individuals NEOPLASIA \- Craniopharyngioma \- Testicular seminoma \- Wilms tumor \- Hepatocellular carcinoma MISCELLANEOUS \- Imprinted disorder \- Marked heterogeneity \- Majority cases are sporadic \- Chromosome rearrangements have been reported \- Maternal uniparental disomy (UPD)7 reported in some cases MOLECULAR BASIS \- Contiguous gene syndrome caused by deletion of paternal allele on chromosome 7 \- Caused by epigenetic changes of DNA hypomethylation at the H19/IGF2-imprinting control region (ICR1, 616186 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SILVER-RUSSELL SYNDROME	c0175693	2,732	omim	https://www.omim.org/entry/180860	2019-09-22T16:35:06	{"doid": ["14681"], "mesh": ["D056730"], "omim": ["180860"], "icd-10": ["Q87.1"], "orphanet": ["813"], "synonyms": ["Alternative titles", "RUSSELL-SILVER SYNDROME", "SILVER-RUSSELL DWARFISM"], "genereviews": ["NBK1324"]}
Depression characterized by improved mood in response to positive events Main article: Major depressive disorder Atypical depression Other namesDepression with atypical features Depression subtypes SpecialtyPsychiatry SymptomsLow mood, mood reactivity, hyperphagia, hypersomnia, leaden paralysis, interpersonal rejection sensitivity ComplicationsSuicide Usual onsetTypically adolescence[1] TypesPrimary anxious, primarily vegetative[1] Risk factorsBipolar disorder, anxiety disorder, female sex[2] Differential diagnosisMelancholic depression, anxiety disorder, bipolar disorder Frequency15-29% of depressed patients[3] Atypical depression as it has been known in the DSM IV, is depression that shares many of the typical symptoms of the psychiatric syndromes of major depression or dysthymia but is characterized by improved mood in response to positive events. In contrast to atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.[4] Despite its name, "atypical" depression does not mean it is uncommon or unusual.[5] The reason for its name is twofold: it was identified with its "unique" symptoms subsequent to the identification of melancholic depression and its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e., MAOIs had clinically significant benefits for atypical depression, while tricyclics did not).[6] Atypical depression is four times more common in females than in males.[7] Individuals with atypical features tend to report an earlier age of onset (e.g. while in high school) of their depressive episodes, which also tend to be more chronic[8] and only have partial remission between episodes. Younger individuals may be more likely to have atypical features, whereas older individuals may more often have episodes with melancholic features.[4] Atypical depression has high comorbidity of anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits.[8] Atypical depression is more common in individuals with bipolar I,[8] bipolar II,[8][9] cyclothymia[8] and seasonal affective disorder.[4] Depressive episodes in bipolar disorder tend to have atypical features,[8] as does depression with seasonal patterns.[10] ## Contents * 1 Pathophysiology * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 Research * 6 See also * 7 References * 8 External links ## Pathophysiology[edit] Significant overlap between atypical and other forms of depression have been observed, though studies suggest there are differentiating factors within the various pathophysiological models of depression. In the endocrine model, evidence suggests the HPA axis is hyperactive in melancholic depression, and hypoactive in atypical depression. Atypical depression can be differentiated from melancholic depression via verbal fluency tests and psychomotor speed tests. Although both show impairment in several areas such as visuospatial memory and verbal fluency, melancholic patients tend to show more impairment than atypical depressed patients.[11] Furthermore, regarding the inflammatory theory of depression, inflammatory blood markers (cytokines) appear to be more elevated in atypical depression when compared to non-atypical depression.[12] ## Diagnosis[edit] The diagnosis of atypical depression is based on the criteria stated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The DSM-5 defines atypical depression as a subtype of major depressive disorder that presents with "atypical features", characterized by: * Mood reactivity (i.e., mood brightens in response to actual or potential positive events) * At least two of the following: * Significant weight gain or increase in appetite (hyperphagia); * Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression); * Leaden paralysis (i.e., heavy feeling resulting in difficulty moving the arms or legs); * Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment. Criteria are not met for With Melancholic Features or With Catatonic Features during the same episode. ## Treatment[edit] Due to the differences in clinical presentation between atypical depression and melancholic depression, studies were conducted in the 1980s and 1990s to assess the therapeutic responsiveness of the available antidepressant pharmacotherapy in this subset of patients.[13] Currently, antidepressants such as SSRIs, SNRIs, NRIs, and mirtazapine are considered the best medications to treat atypical depression due to efficacy and fewer side effects than previous treatments.[14] Bupropion, a norepinephrine reuptake inhibitor, may be uniquely suited to treat the atypical depression symptoms of lethargy and increased appetite in adults.[14] Before the year 2000, monoamine oxidase inhibitors (MAOIs) were shown to be of superior efficacy compared to other antidepressants for the treatment of atypical depression, and were used as first-line treatment for atypical depression. Regardless of the demonstrated superiority, treatment with MAOIs requires avoidance of tyramine-containing foods (aged cheese, wine, fava beans) and have many undesirable adverse effects such as hypertensive crisis.[13] Hypertensive crisis is a state of extremely high blood pressure and present with symptoms such as sweating, palpitations, chest pain, shortness of breath.[15] For these reasons, MAOIs are rarely used as the preferred agent in the setting of atypical depression. There is also a newer, selective and reversible MAOI Moclobemide, which doesn't require tyramine diet and has less side effects. Tricyclic antidepressants (TCAs) were also used prior to the year 2000 for atypical depression, but were not as efficacious as MAOIs, and have fallen out of favor with prescribers due to the less tolerable side effects of TCAs and more adequate therapies being available.[13] Some evidence supports that psychotherapy such as cognitive behavioral therapy (CBT) has equal efficacy to MAOI.[16] These are talk therapy sessions with psychiatrists to help the individual identify troubling thoughts or experiences that may have affected their mental state, and corresponding develop coping mechanisms for each identified issue.[17] No robust guidelines for the treatment of atypical depression currently exist.[18] ## Epidemiology[edit] True prevalence of atypical depression is difficult to determine. Several studies conducted in patients diagnosed with a depressive disorder show that about 40% exhibit atypical symptoms, with four times more instances found in female patients.[19] Research also supports that atypical depression tends to have an earlier onset, with teenagers and young adults more likely to exhibit atypical depression than older patients.[20] Patients with atypical depression have shown to have higher rates of neglect and abuse in their childhood as well as alcohol and drug disorders in their family.[11] Overall, rejection sensitivity is the most common symptom, and due to some studies forgoing this criterion, there is concern for underestimation of prevalence.[21] ## Research[edit] In general, atypical depression tends to cause greater functional impairment than other forms of depression. Atypical depression is a chronic syndrome that tends to begin earlier in life than other forms of depression—usually beginning in the teenage years. Similarly, patients with atypical depression are more likely to suffer from personality disorders and anxiety disorders such as borderline personality disorder, avoidant personality disorder, generalized anxiety disorder, obsessive-compulsive disorder, and bipolar disorder.[4] Recent research suggests that young people are more likely to suffer from hypersomnia while older people are more likely to suffer from polyphagia.[22] Medication response differs between chronic atypical depression and acute melancholic depression. Some studies suggest that the older class of antidepressants, monoamine oxidase inhibitors (MAOIs), may be more effective at treating atypical depression.[23] While the more modern SSRIs and SNRIs are usually quite effective in this illness, the tricyclic antidepressants typically are not.[4] The wakefulness-promoting agent modafinil has shown considerable effect in combating atypical depression, maintaining this effect even after discontinuation of treatment.[24] Antidepressant response can often be enhanced with supplemental medications, such as buspirone, bupropion, or aripiprazole. Psychotherapy, whether alone or in combination with medication, is also an effective treatment.[citation needed] ## See also[edit] * Psychiatry portal * Masked depression * Treatment-resistant depression ## References[edit] 1. ^ a b Davidson JR; Miller RD; Turnbull CD; Sullivan JL (1982). "Atypical depression". Arch Gen Psychiatry. 39 (5): 527–34. doi:10.1001/archpsyc.1982.04290050015005. PMID 7092486. 2. ^ Singh T, Williams K (2006). "Atypical depression". Psychiatry (Edgmont). 3 (4): 33–9. PMC 2990566. PMID 21103169. 3. ^ Thase ME (2007). "Recognition and diagnosis of atypical depression". J Clin Psychiatry. 68 Suppl 8: 11–6. PMID 17640153. 4. ^ a b c d e American Psychiatric Association. (2000). Mood Disorders. In Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) Washington, DC: Author.[page needed] 5. ^ "Atypical depression". Mayo Clinic. Retrieved 2013-06-23. 6. ^ Cristancho, Mario (2012-11-20). "Atypical Depression in the 21st Century: Diagnostic and Treatment Issues". Psychiatric Times. Retrieved 23 November 2013. 7. ^ Dorota Łojko, et. al (2017). "Atypical depression: current perspectives, Neuropsychiatric Disease and Treatment 8. ^ a b c d e f Singh T, Williams K (2006). "Atypical depression". Psychiatry. 3 (4): 33–9. PMC 2990566. PMID 21103169. 9. ^ Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Bemi E (1998). "The high prevalence of 'soft' bipolar (II) features in atypical depression". Comprehensive Psychiatry. 39 (2): 63–71. doi:10.1016/S0010-440X(98)90080-3. PMID 9515190. 10. ^ Juruena MF, Cleare AJ (2007). "Superposição entre depressão atípica, doença afetiva sazonal e síndrome da fadiga crônica" [Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome]. Revista Brasileira de Psiquiatria (in Portuguese). 29 Suppl 1: S19–26. doi:10.1590/S1516-44462007000500005. PMID 17546343. 11. ^ a b Bosaipo, Nayanne Beckmann; Foss, Maria Paula; Young, Allan H.; Juruena, Mario Francisco (2017-02-01). "Neuropsychological changes in melancholic and atypical depression: A systematic review". Neuroscience & Biobehavioral Reviews. 73: 309–325. doi:10.1016/j.neubiorev.2016.12.014. ISSN 0149-7634. PMID 28027956. 12. ^ Łojko D, Rybakowski JK (2017). "Atypical depression: current perspectives". Neuropsychiatr Dis Treat. 13: 2447–2456. doi:10.2147/NDT.S147317. PMC 5614762. PMID 29033570. 13. ^ a b c Stewart, Jonathan W.; Thase, Michael E. (2007-04-15). "Treating DSM-IV Depression With Atypical Features". The Journal of Clinical Psychiatry. 68 (4): e10. doi:10.4088/jcp.0407e10. ISSN 0160-6689. PMID 17474800. 14. ^ a b "Clinical Practice Review for Major Depressive Disorder \| Anxiety and Depression Association of America, ADAA". adaa.org. Retrieved 2019-11-22. 15. ^ "mao_pharmacology [TUSOM \| Pharmwiki]". tmedweb.tulane.edu. Retrieved 2019-11-20. 16. ^ Mercier, MA (1992). "A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression". The Journal of Clinical Psychiatry. 53 (5): 166–70. PMID 1592844. 17. ^ "What is Psychotherapy?". www.psychiatry.org. Retrieved 2019-11-21. 18. ^ Łojko, Dorota (2017). "Atypical depression: current perspectives". Neuropsychiatric Disease and Treatment. 13: 2447–2456. doi:10.2147/NDT.S147317. PMC 5614762. PMID 29033570. 19. ^ Dorota Łojko, et. al (2017). "Atypical depression: current perspectives, Neuropsychiatric Disease and Treatment 20. ^ Tanvir Singh et. al (2006). "Atypical depression, Psychiatry (Edgmont). 21. ^ Quitkin FM (2002). "Depression With Atypical Features: Diagnostic Validity, Prevalence, and Treatment". Prim Care Companion J Clin Psychiatry. 4 (3): 94–99. doi:10.4088/pcc.v04n0302. PMC 181236. PMID 15014736. 22. ^ Posternak MA, Zimmerman M (2001). "Symptoms of atypical depression". Psychiatry Research. 104 (2): 175–81. doi:10.1016/S0165-1781(01)00301-8. PMID 11711170. 23. ^ "Atypical depression - Symptoms and Causes". Mayo Clinic. Retrieved 18 March 2020. 24. ^ Vaishnavi S, Gadde K, Alamy S, Zhang W, Connor K, Davidson JR (2006). "Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment". Journal of Clinical Psychopharmacology. 26 (4): 373–8. doi:10.1097/01.jcp.0000227700.263.75.39. PMID 16855454. ## External links[edit] 1. Stewart JW, Quitkin FM, McGrath PJ, Klein DF (2005). "Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions". Journal of Affective Disorders. 86 (2–3): 161–7. doi:10.1016/j.jad.2005.01.009. PMID 15935235. 2. Atypical Depression - Depression Central Mood Disorders & Treatment, Satish Reddy, MD., Editor (Formerly Dr. Ivan Goldberg's Depression Central) Classification D * ICD-10: F32.8 * ICD-9-CM: 296.2x * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Atypical depression	c0154437	2,733	wikipedia	https://en.wikipedia.org/wiki/Atypical_depression	2021-01-18T18:34:14	{"umls": ["C0154437"], "wikidata": ["Q2657784"]}
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 25 (MC1DN25) is caused by homozygous or compound heterozygous mutation in the NDUFB3 gene (603839) on chromosome 2q33. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Calvo et al. (2012) reported a female infant, born of unrelated parents of British and Dutch descent, with severe lethal mitochondrial complex I deficiency. The pregnancy was complicated by intrauterine growth retardation and premature birth at 31 weeks' gestation; respiratory insufficiency required extensive artificial ventilation in the neonatal period. After discharge home, she showed hypotonia with poor feeding and significant lactic acidosis and died unexpectedly at age 4 months. Skeletal muscle biopsy showed variation in the shape and size of muscle fibers, and atrophic fibers containing nemaline rods. Biochemical analysis showed complex I deficiency with borderline low complex III deficiency, the latter of which may have been an artifact. Haack et al. (2012) reported a patient with complex I deficiency who had encephalopathy, myopathy, hypotonia, developmental delay, and lactic acidosis. Molecular Genetics In a female infant, born of unrelated parents of British and Dutch descent, with severe lethal mitochondrial complex I deficiency, Calvo et al. (2012) identified a homozygous missense mutation in the NDUFB3 gene (W22R; 603839.0001). The unaffected mother was a carrier; DNA from the father was not available. In a patient with complex I deficiency, Haack et al. (2012) identified compound heterozygosity for 2 mutations in the NDUFB3 gene: the previously described W22R mutation and G70X (603839.0002). The mutations were identified by exome sequencing. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Failure to thrive ABDOMEN Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia \- Myopathy \- Variation in fiber size and shape seen on skeletal muscle biopsy \- Nemaline rods NEUROLOGIC Central Nervous System \- Global developmental delay \- Encephalopathy METABOLIC FEATURES \- Lactic acidosis PRENATAL MANIFESTATIONS Delivery \- Premature delivery LABORATORY ABNORMALITIES \- Mitochondrial complex I deficiency in various tissues MISCELLANEOUS \- Onset in utero or infancy \- Early death may occur \- Two unrelated patients have been reported (last curated January 2019) MOLECULAR BASIS \- Caused by mutation in the NADH-ubiquinone oxidoreductase subunit B3 gene (NDUFB3, 603839.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 25	c2936907	2,734	omim	https://www.omim.org/entry/618246	2019-09-22T15:43:00	{"mesh": ["C537475"], "omim": ["618246"], "orphanet": ["2609"]}
A number sign (#) is used with this entry because Treacher Collins syndrome-3 (TCS3) is caused by compound heterozygous mutation in the POLR1C gene (610060) on chromosome 6p21. Description Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss (Dauwerse et al., 2011). For additional phenotypic information and a discussion of genetic heterogeneity of Treacher Collins syndrome, see TCS1 (154500). Clinical Features Richieri-Costa et al. (1993) and Splendore et al. (2000) both reported sibs with Treacher Collins syndrome who were born to normal parents. The possibility of either nonpenetrance or germline mosaicism in one of the parents could not be discarded. Inheritance Treacher Collins syndrome-3 is an autosomal recessive disorder (Dauwerse et al., 2011). Molecular Genetics Dauwerse et al. (2011) analyzed the POLR1C gene in 252 individuals with Treacher Collins syndrome and identified 3 patients, including 1 from a family previously studied by Splendore et al. (2000), with compound heterozygous mutations (610060.0001-610060.0005, respectively). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Zygomatic complex hypoplasia \- Mandibular hypoplasia Ears \- Microtia \- Hearing loss, conductive Eyes \- Downslanting palpebral fissures \- Coloboma, lower eyelid Mouth \- Cleft palate MOLECULAR BASIS \- Caused by mutation in the polymerase I, RNA, subunit C gene (POLR1C, 610060.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	TREACHER COLLINS SYNDROME 3	c0242387	2,735	omim	https://www.omim.org/entry/248390	2019-09-22T16:25:36	{"doid": ["2908"], "mesh": ["D008342"], "omim": ["248390"], "orphanet": ["861"], "synonyms": ["Alternative titles", "MANDIBULOFACIAL DYSOSTOSIS, TREACHER COLLINS TYPE, AUTOSOMAL RECESSIVE"], "genereviews": ["NBK1532"]}
PELVIS syndrome SpecialtyDermatology PELVIS syndrome is a congenital condition characterized by perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag.[1] ## See also[edit] * SACRAL syndrome * List of cutaneous conditions ## References[edit] 1. ^ Girard C., Bigorre M., Guillot B., Bessis D. (2006). "PELVIS Syndrome". Archives of Dermatology. 142 (7): 884–888. doi:10.1001/archderm.142.7.884. PMID 16847205.CS1 maint: uses authors parameter (link) * 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 chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	PELVIS syndrome	c4510867	2,736	wikipedia	https://en.wikipedia.org/wiki/PELVIS_syndrome	2021-01-18T18:46:17	{"orphanet": ["83628"], "synonyms": ["Lower body hemangioma-urogenital anomalies-myelopathy-bony deformities-anorectal and arterial malformations-renal anomalies syndrome", "PELVIS syndrome", "Perineal hemangioma-external genitalia malformations-lipomyelomeningocele-vesicorenal abnormalities-imperforate anus-skin tag syndrome", "SACRAL syndrome"], "wikidata": ["Q7118941"]}
Form of cataract due to an occupational exposure Glassblower's cataracts are a form of cataract due to an occupational exposure. They are formed by many years or decades of exposure to infrared radiation while working in the occupation of glass blowing, or working close to hot or molten metals such with metal foundry workers[1] or blacksmiths. Glassblower's cataracts are due to chronic exposure to infrared radiation emitted due to the extreme heating of glass or molten metal. The infrared radiation is absorbed by the iris and lens of the eye. This causes cataracts after decades of exposure. [2] This condition may be prevented by wearing protective glasses while practicing these occupations. A person glassblowing. Comparison between a healthy eye versus one with a Cataract. ## Contents * 1 Mechanism * 2 Prevention * 3 Symptoms * 4 Diagnosis * 5 Treatment * 6 References ## Mechanism[edit] Glassblowers tend to work with very high-temperature objects and equipment, which emit a great deal of infrared radiation through black-body radiation. The ocular lens, like all matter, has the capacity to store incident photon energy by resonance absorption. Absorption of infrared photons increases vibration of molecules, which is observed as increased temperature. Large important biomolecules such as proteins tend to lose their space structure when vibrating, known as denaturation. The rate of protein denaturation is temperature dependent as described by the Arrhenius equation. Damage to biological tissue owing to the high rate of vibration damage is called thermal damage.[3] Prior to recent research, it was theorized that one possible mechanism was the large intake of fluid due to excessive sweating on the job. Within this theory, it was suggested that the evaporation of the sweat within the cornea "could lead to increased concentration of the aqueous humour," this increase could therefore induce the cataract. [4] This however has not been proven to be true and instead it is generally accepted that the infrared photons as mentioned above are the primary cause of glassblower's cataracts. ## Prevention[edit] Unfortunately, there is not one clear cut way to prevent cataracts. As this specific type of cataract is associated with occupational exposures to infrared radiation, wearing protective eye equipment while on the job or taking frequent breaks can lessen the strain on the eyes. Some modifiable common risk factors unrelated to occupation are smoking, excessive alcohol consumption, deficiency in vitamin E, B1, and B2, and increased exposure of sunlight to the eyes. Risk factors that are not modifiable include previous eye injury, family history, diabetes, the use of corticosteroids, and previous eye surgery. To lessen the risk of developing cataracts it is best to limit alcohol consumption, not use or stop the use of tobacco, get adequate amounts of vitamins E, B1, and B2, and wear sunglasses and/or a wide brim hat while outside. Even if you are taking all of these steps it is still recommended that patients have eye exams every other year, or every year if over 60.[5] ## Symptoms[edit] As with cataracts not associated with glassblowing, symptoms typically have a gradual onset. Initially, people generally are unaware they have cataracts. Blurry vision is one of the first symptoms to appear which gradually worsens as the cataracts develop further. Colors may eventually become more and more faded, eyes will become more sensitive to light, and sometimes people will have trouble seeing at nighttime. Double vision can occur and the need to change prescriptions often are also common symptoms. Over time, vision loss can occur in people who have well developed, untreated cataracts.[6] ## Diagnosis[edit] Pictured here is a slit lamp. When used with a binocular microscope, the ophthalmologist can examine the eye with a small beam (slit) of light. The slit of light can accentuate features of the eye when directed at an angle. The microscope used in combination with the slit lamp allows for greater magnification (10 - 25 times) than typical handheld devices. Like symptoms, glassblowers cataracts can also be diagnosed the same way as cataracts not associated with glassblowing. To diagnose cataracts, a comprehensive eye exam must be done. This exam will include dilation to measure the response of the pupils. A slit lamp examination will also be conducted to examine the cornea, iris, and other areas closer to the front of the eye. A slit lamp is used because it makes it easier for ophthalmologists to spot abnormalities. When the eye is dilated, the pupils widen so that the ophthalmologist can see the back of the eye more clearly. This is where he or she will look for signs of cataracts, glaucoma, and will examine the retina and optic nerve. During this comprehensive eye exam, a refraction and visual acuity test will also be performed. These tests assess the clarity and sharpness of a person's vision and each eye is tested individually. After combining all the data collected in this eye exam, an ophthalmologist can accurately diagnose cataracts if certain conditions are met. [7] A posterior chamber intraocular lens prior to insertion. This is inserted during cataract surgery after the cloudy eye's natural lens is removed. ## Treatment[edit] The treatment for this condition depends on how developed the cataracts are. Early on getting a new prescription and wearing sunglasses may be all a doctor suggests. If the cataracts begin to interfere with every day life, an ophthalmologist will most likely will suggest surgery. During this surgery the clouded lens will be removed and replaced with a new, artificial lens. This lens is called an intraocular lens or IOL. The surgery itself is very safe and 9 out of 10 people who undergo this surgery can see clearer post-op. [7] ## References[edit] 1. ^ Roberts, B. H. (1921). "A Series of Cases of "glassblowers' Cataract" Occurring in Chainmakers". The British Journal of Ophthalmology. 5 (5): 210–212. doi:10.1136/bjo.5.5.210. PMC 512590. PMID 18168103. 2. ^ Geddes, LA; Roeder, RA (2006). Handbook of Electrical Hazards and Accidents (2nd ed.). Lawyers & Judges Publishing Company. p. 465. ISBN 978-0913875445. 3. ^ Söderberg, P G; Talebizadeh, N; Yu, Z; Galichanin, K (2016-01-15). "Does infrared or ultraviolet light damage the lens?". Eye. 30 (2): 241–246. doi:10.1038/eye.2015.266. PMC 4763141. PMID 26768915. 4. ^ "Glassblowers' ocular health and safety: optical radiation hazards and eye protection assessment". Ophthalmic and Physiological Optics. 17 (3): 216–224. 1997. doi:10.1111/j.1475-1313.1997.0_877.x. ISSN 0275-5408. PMID 9196663. 5. ^ Publishing, Harvard Health. "By the way, doctor: What can I do to prevent cataracts?". Harvard Health. Retrieved 2020-04-07. 6. ^ "Cataracts". National Eye Institute. August 3, 2019. 7. ^ a b "Cataract Diagnosis and Treatment". American Academy of Ophthalmology. 2019-10-01. Retrieved 2020-04-07. * v * t * e Occupational safety and health Occupational diseases and injuries * Acrodynia * Asbestosis * Asthma * Barotrauma * Berylliosis * Brucellosis * Byssinosis ("brown lung") * Chalicosis * Chimney sweeps' carcinoma * Chronic solvent-induced encephalopathy * Coalworker's pneumoconiosis ("black lung") * Concussions in sport * Decompression sickness * De Quervain syndrome * Erethism * Exposure to human nail dust * Farmer's lung * Fiddler's neck * Flock worker's lung * Glassblower's cataract * Golfer's elbow * Hearing loss * Hospital-acquired infection * Indium lung * Laboratory animal allergy * Lead poisoning * Mesothelioma * Metal fume fever * Mule spinners' cancer * Noise-induced hearing loss * Phossy jaw * Pneumoconiosis * Radium jaw * Repetitive strain injury * Silicosis * Silo-filler's disease * Sports injury * Surfer's ear * Tennis elbow * Tinnitus * Writer's cramp Occupational hygiene * Occupational hazard * Biological hazard * Chemical hazard * Physical hazard * Psychosocial hazard * Hierarchy of hazard controls * Prevention through design * Exposure assessment * Occupational exposure limit * Occupational epidemiology * Workplace health surveillance Professions * Environmental health * Industrial engineering * Occupational health nursing * Occupational health psychology * Occupational medicine * Occupational therapist * Safety engineering Agencies and organizations * Canadian Centre for Occupational Health and Safety * European Agency for Safety and Health at Work * UK Health and Safety Executive * International Labour Organization * US National Institute for Occupational Safety and Health * US Occupational Safety and Health Administration * National Institute for Safety and Health at Work (Spain) * World Health Organization Standards * Bangladesh Accord * ISO 45001 * Occupational Safety and Health Convention, 1981 * Worker Protection Standard (US) * Working Environment Convention, 1977 Safety * Checklist * Code of practice * Contingency plan * Diving safety * Emergency procedure * Emergency evacuation * Hazard * Hierarchy of hazard controls * Hazard elimination * Administrative controls * Engineering controls * Hazard substitution * Personal protective equipment * Job safety analysis * Lockout-tagout * Permit To Work * Operations manual * Redundancy (engineering) * Risk assessment * Safety culture * Standard operating procedure Legislation * Diving regulations * Occupational Safety and Health Act (United States) See also * Environment, health and safety * Environmental toxicology * Ergonomics * Health physics * Indoor air quality * International Chemical Safety Card * National Day of Mourning (Canadian observance) * Process safety management * Public health * Risk management * Safety data sheet * Toxic tort * Workers' compensation * Category * Occupational diseases * Journals * Organizations * Commons * Glossary [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Glassblower's cataract	c1398738	2,737	wikipedia	https://en.wikipedia.org/wiki/Glassblower%27s_cataract	2021-01-18T18:53:44	{"wikidata": ["Q16964175"]}
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: "Diastrophic dysplasia" – news · newspapers · books · scholar · JSTOR (July 2008) (Learn how and when to remove this template message) Diastrophic dysplasia Other namesDTD SpecialtyMedical genetics Diastrophic dysplasia is an autosomal recessive[1] dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting.)[2] Diastrophic dysplasia is due to mutations in the SLC26A2 gene. Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility. ## Contents * 1 Signs and symptoms * 2 Genetic * 3 Prevalence * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] This condition is also characterized by an unusual clubfoot with twisting of the metatarsals, inward- and upward-turning foot, tarsus varus and inversion adducted appearances. Furthermore, they classically present with scoliosis (progressive curvature of the spine) and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a cleft palate. Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears. The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis, type 2; however diastrophic dysplasia tends to be less severe. ## Genetic[edit] Diastrophic dysplasia has an autosomal recessive pattern of inheritance. It is one of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. The protein encoded by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia. This condition is an autosomal recessive disorder, meaning that the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder. ## Prevalence[edit] Diastrophic dysplasia affects about one in 100,000 births. ## See also[edit] * Achondrogenesis type 1B ## References[edit] 1. ^ Hästbacka J, Sistonen P, Kaitila I, Weiffenbach B, Kidd KK, De La Chapelle A (December 1991). "A linkage map spanning the locus for diastrophic dysplasia (DTD)". Genomics. 11 (4): 968–973. doi:10.1016/0888-7543(91)90021-6. PMID 1783404. 2. ^ "diastrophic - Definition from the Merriam-Webster Online Dictionary". Retrieved 2009-03-12. This article incorporates some public domain text from The U.S. National Library of Medicine ## External links[edit] Classification D * ICD-10: Q77.5 * OMIM: 222600 * MeSH: C536170 C536170, C536170 * DiseasesDB: 30759 External resources * eMedicine: orthoped/632 * Orphanet: 628 * GeneReviews/NCBI/NIH/UW entry on Diastrophic Dysplasia * 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 * v * t * e Genetic disorder, membrane: Solute carrier disorders 1-10 * SLC1A3 * Episodic ataxia 6 * SLC2A1 * De Vivo disease * SLC2A5 * Fructose malabsorption * SLC2A10 * Arterial tortuosity syndrome * SLC3A1 * Cystinuria * SLC4A1 * Hereditary spherocytosis 4/Hereditary elliptocytosis 4 * SLC4A11 * Congenital endothelial dystrophy type 2 * Fuchs' dystrophy 4 * SLC5A1 * Glucose-galactose malabsorption * SLC5A2 * Renal glycosuria * SLC5A5 * Thyroid dyshormonogenesis type 1 * SLC6A19 * Hartnup disease * SLC7A7 * Lysinuric protein intolerance * SLC7A9 * Cystinuria 11-20 * SLC11A1 * Crohn's disease * SLC12A3 * Gitelman syndrome * SLC16A1 * HHF7 * SLC16A2 * Allan–Herndon–Dudley syndrome * SLC17A5 * Salla disease * SLC17A8 * DFNA25 21-40 * SLC26A2 * Multiple epiphyseal dysplasia 4 * Achondrogenesis type 1B * Recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia * SLC26A4 * Pendred syndrome * SLC35C1 * CDOG 2C * SLC39A4 * Acrodermatitis enteropathica * SLC40A1 * African iron overload see also solute carrier 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Diastrophic dysplasia	c1857255	2,738	wikipedia	https://en.wikipedia.org/wiki/Diastrophic_dysplasia	2021-01-18T18:46:39	{"gard": ["6275"], "mesh": ["C565626", "C536170"], "umls": ["C1857255"], "orphanet": ["628"], "wikidata": ["Q3335666"]}
After-death paleness that occurs in those with light/white skin Stages of death 1. Pallor mortis 2. Algor mortis 3. Rigor mortis 4. Livor mortis 5. Putrefaction 6. Decomposition 7. Skeletonization 8. Fossilization * v * t * e Pallor mortis (Latin: pallor "paleness", mortis "of death"), the first stage of death, is an after-death paleness that occurs in those with light/white skin.[1] An opto-electronical colour measurement device is used to measure pallor mortis on bodies.[2] ## Timing and applicability[edit] Pallor mortis occurs almost immediately, generally within 15–25 minutes, after death. Paleness develops so rapidly after death that it has little to no use in determining the time of death, aside from saying that it either happened less than 30 minutes ago or more, which could help if the body were found very soon after death.[3] ## Cause[edit] Pallor mortis results from the collapse of capillary circulation throughout the body.[2] Gravity then causes the blood to sink down into the lower parts of the body, creating livor mortis.[4] ## Similar paleness in living persons[edit] A living person can look deathly pale. This can happen when blood escapes from the surface of the skin, in a matter of deep shock. Also heart failure (insufficientia cordis) can make the face look paled; the person then might have blue lips. Skin can also look deathly pale as a result of vasoconstriction as part of the body's homeostatic systems in cold conditions, or if the skin is deficient in vitamin D, as seen in people who spend most of the time indoors, away from sunlight.[5] ## References[edit] 1. ^ Schäfer, AT (2000). "Colour measurements of pallor mortis". International Journal of Legal Medicine. 113 (2): 81–3. doi:10.1007/pl00007713. PMID 10741481. 2. ^ a b Schäfer, A.Th. (2000-02-01). "Colour measurements of pallor mortis". International Journal of Legal Medicine. 113 (2): 81–83. doi:10.1007/PL00007713. ISSN 1437-1596. PMID 10741481. 3. ^ "Every corpse has a story: How experts find clues in the dead". NewsComAu. 2018-12-13. Retrieved 2019-10-02. 4. ^ Hill, Kyle. "The Coroner Report: Weekend at Bernie s". Scientific American Blog Network. Retrieved 2019-10-02. 5. ^ "Causes of skin paleness in dark and light skin". Medical News Today. Retrieved 2019-10-02. * v * t * e Death In medicine Cell death * Necrosis * Avascular necrosis * Coagulative necrosis * Liquefactive necrosis * Gangrenous necrosis * Caseous necrosis * Fat necrosis * Fibrinoid necrosis * Temporal lobe necrosis * Programmed cell death * AICD * Anoikis * Apoptosis * Autophagy * Intrinsic apoptosis * Necroptosis * Paraptosis * Parthanatos * Phenoptosis * Pseudoapoptosis * Pyroptosis * Autolysis * Autoschizis * Eschar * Immunogenic cell death * Ischemic cell death * Pyknosis * Karyorrhexis * Karyolysis * Mitotic catastrophe * Suicide gene * Abortion * Accidental death * Autopsy * Brain death * Brainstem death * Clinical death * DOA * Death by natural causes * Death rattle * Dysthanasia * End-of-life care * Euthanasia * Lazarus sign * Lazarus syndrome * Medical definition of death * Organ donation * Terminal illness * Unnatural death Lists * Causes of death by rate * Expressions related to death * Natural disasters * People by cause of death * Premature obituaries * Preventable causes of death * Notable deaths by year * Unusual deaths Mortality * Birthday effect * Child mortality * Gompertz–Makeham law of mortality * Infant mortality * Karoshi * Maternal death * Maternal mortality in fiction * Memento mori * Micromort * Mortality displacement * Mortality rate * RAMR * Mortality salience * Perinatal mortality After death Body Stages * Pallor mortis * Algor mortis * Rigor mortis * Livor mortis * Putrefaction * Decomposition * Skeletonization * Fossilization Preservation * Cryopreservation * Cryonics * Neuropreservation * Embalming * Maceration * Mummification * Plastination * Prosection * Taxidermy Disposal * Burial * Natural burial * Cremation * Dismemberment * Excarnation * Promession * Resomation * Beating heart cadaver * Body donation * Cadaveric spasm * Coffin birth * Death erection * Dissection * Gibbeting * Postmortem caloricity * Post-mortem interval Other aspects * Afterlife * Cemetery * Consciousness * Customs * Crematorium * Examination * Funeral * Grief * Intermediate state * Internet * Mourning * Online mourning * Obituary * Vigil Paranormal * Ghosts * Near-death experience * Near-death studies * Necromancy * Out-of-body experience * Reincarnation research * Séance Legal * Abortion law * Administration * Capital punishment * Cause of death * Civil death * Coroner * Death-qualified jury * Death certificate * Declared death in absentia * Death row * Dying declaration * Inquest * Legal death * Murder * Necropolitics * Prohibition of death * Right to die * Suspicious death * Trust law * Will Fields * Forensic pathology * Funeral director * Mortuary science * Necrobiology * Post-mortem chemistry * Post-mortem photography * Taphonomy * Biostratinomy * Thanatology Other * Apparent death * Dark tourism * Darwin Awards * Death and culture * Death anniversary * Death anxiety * Death deity * Personification of death * Dying-and-rising god * Psychopomp * Death camp * Death drive * Death education * Death from laughter * Death hoax * Death knell * Death march * Death messenger * Death notification * Death panel * Death poem * Death pose * Death-positive movement * Death squad * Death threat * Death trajectory * Dignified death * Extinction * Fan death * Festival of the Dead * Fascination with death * Hierarchy of death * Homicide * Last rites * Martyr * Megadeath * Museum of Death * Necronym * Necrophilia * Necrophobia * The Order of the Good Death * Predation * Sacrifice * human * Suicide * Assisted suicide * Thanatosensitivity * The Goodbye Family * Category * Outline This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e This article related to pathology is a stub. You can help Wikipedia by expanding it. * v * t * e This article related to Latin words and phrases 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pallor mortis	None	2,739	wikipedia	https://en.wikipedia.org/wiki/Pallor_mortis	2021-01-18T18:33:32	{"wikidata": ["Q3493484"]}
In a 13-year-old Turkish girl and her 11-year-old brother, Kilic et al. (1998) described a syndrome of camptodactyly, fibrosis of the medial rectus muscle of the eye, severe myopia, facial anomalies, joint contractures, and mild scoliosis. The girl also had ptosis. The children were intellectually normal. The parents were normal but consanguineous. The syndrome characterized by camptodactyly and joint contractures associated with multiple eye anomalies including ptosis, exophthalmos, and strabismus had been described in a 16-year-old Jewish girl by Rozin et al. (1984). She also had short stature and scoliosis, and her facial features were similar to those reported by Kilic et al. (1998). Parental consanguinity was found in that family also. Differences from other camptodactyly syndromes were reviewed. Garcia-Ortiz et al. (2006) reported a 25-year-old Mexican man with a facial gestalt and other features similar to those of the patients previously described by Rozin et al. (1984) and Kilic et al. (1998), including ptosis, camptodactyly, flexion contractures, and scoliosis. The patient also had mental retardation, possibly a consequence of neonatal hypoxia, and had additional skeletal features including segmentation anomalies of the spine and carpal synostosis. Garcia-Ortiz et al. (2006) suggested that the skeletal changes might represent the natural history of this disorder; or, together with the mental retardation, might indicate a microdeletion syndrome. The patient died suddenly during sleep at age 25; no autopsy was done. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CAMPTODACTYLY, MYOPIA, AND FIBROSIS OF THE MEDIAL RECTUS MUSCLE OF EYE	c2931051	2,740	omim	https://www.omim.org/entry/602612	2019-09-22T16:13:33	{"mesh": ["C535876"], "omim": ["602612"], "orphanet": ["1323"]}
For a general phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease, see 104300. Mapping In a genome screen of individuals from an isolated population from the southwestern area of the Netherlands, ascertained as part of the Genetic Research in Isolated Populations (GRIP) program, Liu et al. (2007) found the strongest evidence of linkage for chromosome 1q21 (AD13; 611152). Approximately 30 cM upstream of this locus, at 1q25, another peak (AD14) was found (hlod = 4.0 at marker D1S218). Liu et al. (2007) noted that these 2 loci were in a linkage region spanning 1q21-q31 identified by Zubenko et al. (1998), Hiltunen et al. (2001), Myers et al. (2002), and Blacker et al. (2003). Haplotype analysis showed that the 2 linkage peaks on chromosome 1q21 and 1q25 are explained by different haplotypes, of 15 cM and 21 cM, respectively, segregating in different families. The 1q25 region was confirmed when testing for association with cognitive function as an endophenotype of AD in 197 distantly related subjects. The study indicated that potential disease-causing genes at 1q25 are RGSL2 (611013), RALGPS2 (617819), and C1ORF49. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ALZHEIMER DISEASE 14	c0276496	2,741	omim	https://www.omim.org/entry/611154	2019-09-22T16:03:37	{"doid": ["0110047"], "mesh": ["D000544"], "omim": ["611154"], "orphanet": ["1020"]}
Checkpoint inhibitor induced colitis SpecialtyGastroenterology SymptomsDiarrhea, abdominal pain, rectal bleeding ComplicationsPerforation, toxic megacolon Usual onset~6-7 weeks after starting checkpoint inhibitor[1] CausesCancer immunotherapy treatment Risk factorsCaucasian, NSAID use, anti-CTLA4 treatment, melanoma, history of prior checkpoint inhibitor induced colitis, Faecalibacterium in fecal microbiota Diagnostic methodColonoscopy, stool tests for infection Differential diagnosisInfectious colitis, gastrointestinal metastases (rare) PreventionNone TreatmentCorticosteroids, infliximab, vedolizumab PrognosisAssociated with improved overall survival Frequency0.7 – 1.6% (anti-PD1) 5.7 – 9.1% (anti-CTLA-4) 13.6% (combination therapy) Checkpoint inhibitor induced colitis is an inflammatory condition affecting the colon (colitis), which is caused by cancer immunotherapy (checkpoint inhibitor therapy). Symptoms typically consist of diarrhea, abdominal pain and rectal bleeding. Less commonly, nausea and vomiting may occur, which may suggest the present of gastroenteritis. The severity of diarrhea and colitis are graded based on the frequency of bowel movements and symptoms of colitis, respectively. The gold standard for the diagnosis of checkpoint inhibitor induced colitis is colonoscopy with evaluation of the terminal ileum. However, in most cases, a flexible sigmoidoscopy is sufficient. Infection should be ruled out with stool studies, including Clostridioides difficile, bacterial culture, ova and parasites. Symptoms of upper abdominal pain, nausea or vomiting warrant evaluation with upper endoscopy. Treatment of immune checkpoint inhibitor colitis is based on severity, as defined by the grade of diarrhea and colitis. Mild cases by managed with temporary interruption of immune checkpoint inhibitor therapy, dietary modification (low residue), and/or loperamide. More severe cases require immune suppression with corticosteroid therapy. If steroids are ineffective, infliximab may be considered. If colitis fails to improve with infliximab, then vedolizumab may be effective. ## Contents * 1 Epidemiology * 2 Pathophysiology * 3 Signs and symptoms * 3.1 Grading colitis and diarrhea * 4 Diagnosis * 5 Treatment * 6 Complications * 7 See also * 8 References ## Epidemiology[edit] The prevalence of checkpoint inhibitor induced colitis varies depending on the regimen of immunotherapy. The incidence is 0.7 – 1.6% for anti-programmed cell death protein 1 (PD1) agents, 5.7 – 9.1% for anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and about 13.6% for combination therapy.[2] The risk associated with ipilimumab is dose dependent, such that higher doses are associated with higher rates of colitis.[3] However, other agents (nivolumab and pembrolizumab) are not associated with a dose dependent effect on the risk of immune mediated colitis.[3] Risk factors for immune mediated colitis include Caucasian race, treatment with an anti-CTLA4 based regimen, melanoma as cancer type,[4] nonsteroidal anti-inflammatory drug (NSAID) use,[5] and a prior history of checkpoint inhibitor induced colitis. ## Pathophysiology[edit] Immune checkpoints are important for the normal development of T regulatory cells (Tregs) in the intestine. Mice with the CTLA-4 gene removed (eg CTLA-4 knockout) develop severe autoimmune disease, with diffuse infiltration of T cells in multiple organs and fatal enterocolitis.[2] Immune checkpoint inhibitor colitis is typically characterized by either diffuse mucosal inflammation or focal active colitis with patchy crypt abscesses.[6] Common findings of acute colitis include: intraepithelial neutrophilic infiltrates, crypt abscesses, and increased apoptotic cells within crypts. However, the histologic appearance varies, and evidence of chronic inflammation is seen in some cases, including intraepithelial lymphocytes or basal lymphocytes and crypt architecture distortion.[6] Histologic inflammation may occur as early as 1-2 weeks after immune checkpoint inhibitor therapy, well before the onset of symptoms.[6] Anti-PD-1 induced colitis may lead to more CD8+ T cell inflammation, whereas Anti-CTLA4 induced colitis may involve more CD4+ T cell infiltration and higher mucosal levels of the inflammatory molecule TNF alpha. Amongst people treated with immune checkpoint inhibitors, those with Faecalibacterium genus and other Firmicutes present in the colonic flora have longer progression-free survival and overall survival. In addition, a higher rate of checkpoint inhibitor induced colitis is associated with the presence of Faecalibacterium in the fecal microbiota.[7] ## Signs and symptoms[edit] The most common symptom is diarrhea, which occurs in 92 percent of cases, followed by abdominal pain (82%) and rectal bleeding (64%).[2] About 46% of cases include fever and 36% involve nausea and vomiting.[2] Less often, nausea and vomiting may be present. Weight loss has been reported.[1] Onset of diarrhea generally occurs about 6–7 weeks after starting immune checkpoint inhibitor therapy.[1] ### Grading colitis and diarrhea[edit] The extent of diarrhea is graded based on severity, from 1 to 5. Grade 1 diarrhea is defined by an increase in the number of stools below four per day (compared with baseline). Grade 2 diarrhea is defined by an increase of 4–6 bowel movements per day. Grade 3 diarrhea is defined by an increase by 7 or more bowel movements per day. Grade 4 diarrhea involves life-threatening consequences, such as shock, whereas grade 5 results in death. The extent of colitis is also graded based on severity, from 1 to 5. Grade 1 colitis does not result in any symptoms, while grade 2 colitis leads to abdominal pain, mucous and blood in the stools. Grade 3 colitis is defined by severe pain, peritoneal signs and ileus. Grade 4 colitis is defined by life-threatening consequences, including perforation, ischemia, necrosis, bleeding, or toxic megacolon. Grade 5 colitis results in death. ## Diagnosis[edit] Colonoscopy with evaluation of the terminal ileum is the gold standard in the diagnosis of checkpoint inhibitor induced colitis.[6][2] However, in most cases, a limited evaluation of the distal colon with flexible sigmoidoscopy is sufficient.[6][2][8] Endoscopic findings may include loss of vascular pattern, erythema, edema, erosions, ulcers, exudates, granularity, and bleeding.[1][9] Biopsies should be taken even in endoscopic findings are normal, as inflammation may not be immediately apparent and may only be seen on histology (microscopic colitis).[6] Symptoms of nausea, vomiting and epigastric pain may suggest involvement of the upper gastrointestinal tract. If present, evaluation with upper endoscopy is warranted.[6] There are no stool tests or blood tests specific for checkpoint inhibitor induced colitis.[1] However, diagnostic evaluation should include ruling out infectious causes for diarrhea and colitis.[6] Stool studies should include: Clostridioides difficile toxin, bacterial culture, ova and parasites. Testing for CMV infection should be considered.[6] Fecal calprotectin may be helpful, and is very sensitive and specific for inflammation in the intestines.[6] Elevations in fecal calprotectin correlate with the extent of intestinal inflammation.[2] Computed tomography (CT) imaging may show evidence of colitis, though the sensitivity is relatively low (50%).[1] Free air in the peritoneum indicates bowel perforation.[1] Abdominal imaging may be necessary to rule out toxic megacolon or perforation.[1] Though rare, gastrointestinal metastases (rare) should be considered as a cause of symptoms.[6] ## Treatment[edit] Treatment varies depending on the severity of disease. For mild disease, supportive care may be sufficient, including loperamide and a low residue or bland diet. For more severe disease, the immune checkpoint inhibitor should be discontinued. Corticosteroid therapy is used to decrease inflammation, at a dose of roughly prednisone 1–2 mg per kg of body weight per day. In cases that do not respond to corticosteroid therapy, infliximab may be used. For cases that fail to respond to infliximab, or where infliximab is contraindicated, vedolizumab may be used.[5] Overall, response rates from treatment are 59% for corticosteroids, 81% for infliximab, and 85% for vedolizumab.[10] Surgery with resection of the colon (colectomy) is necessary in some instances,[11] particularly if severe complications occur, such as perforation[1] or toxic megacolon. Fecal calprotectin, a stool test and marker of inflammation, may be used to follow improvement in colitis.[5] ## Complications[edit] High grade colitis may lead to severe complications, including perforation, toxic megacolon and death. Bleeding may occur due to colitis. Treatment with corticosteroids may lead to infectious complications, including: urinary tract infections, C. difficile infection, and pneumonia.[4] ## See also[edit] * Immunotherapy ## References[edit] 1. ^ a b c d e f g h i Tian, Y; Abu-Sbeih, H; Wang, Y (2018). "Immune Checkpoint Inhibitors-Induced Colitis". Advances in Experimental Medicine and Biology. 995: 151–157. doi:10.1007/978-3-030-02505-2_7. ISBN 978-3-030-02504-5. PMID 30539510. 2. ^ a b c d e f g Bellaguarda, Emanuelle; Hanauer, Stephen (February 2020). "Checkpoint Inhibitor–Induced Colitis". The American Journal of Gastroenterology. 115 (2): 202–210. doi:10.14309/ajg.0000000000000497. PMID 31922959. 3. ^ a b Kumar, V; Chaudhary, N; Garg, M; Floudas, CS; Soni, P; Chandra, AB (2017). "Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy". Frontiers in Pharmacology. 8: 49. doi:10.3389/fphar.2017.00049. PMC 5296331. PMID 28228726. 4. ^ a b Wang, Yinghong; Abu-Sbeih, Hamzah; Mao, Emily; Ali, Noman; Ali, Faisal Shaukat; Qiao, Wei; Lum, Phillip; Raju, Gottumukkala; Shuttlesworth, Gladis; Stroehlein, John; Diab, Adi (11 May 2018). "Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson". Journal for ImmunoTherapy of Cancer. 6 (1): 37. doi:10.1186/s40425-018-0346-6. PMC 5946546. PMID 29747688. 5. ^ a b c Brahmer, Julie R.; Lacchetti, Christina; Schneider, Bryan J.; Atkins, Michael B.; Brassil, Kelly J.; Caterino, Jeffrey M.; Chau, Ian; Ernstoff, Marc S.; Gardner, Jennifer M.; Ginex, Pamela; Hallmeyer, Sigrun; Holter Chakrabarty, Jennifer; Leighl, Natasha B.; Mammen, Jennifer S.; McDermott, David F.; Naing, Aung; Nastoupil, Loretta J.; Phillips, Tanyanika; Porter, Laura D.; Puzanov, Igor; Reichner, Cristina A.; Santomasso, Bianca D.; Seigel, Carole; Spira, Alexander; Suarez-Almazor, Maria E.; Wang, Yinghong; Weber, Jeffrey S.; Wolchok, Jedd D.; Thompson, John A. (10 June 2018). "Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline". Journal of Clinical Oncology. 36 (17): 1714–1768. doi:10.1200/JCO.2017.77.6385. PMC 6481621. PMID 29442540. 6. ^ a b c d e f g h i j k Som, Aniruddh; Mandaliya, Rohan; Alsaadi, Dana; Farshidpour, Maham; Charabaty, Aline; Malhotra, Nidhi; Mattar, Mark C (26 February 2019). "Immune checkpoint inhibitor-induced colitis: A comprehensive review". World Journal of Clinical Cases. 7 (4): 405–418. doi:10.12998/wjcc.v7.i4.405. PMC 6397821. PMID 30842952. 7. ^ Chaput, N.; Lepage, P.; Coutzac, C.; Soularue, E.; Le Roux, K.; Monot, C.; Boselli, L.; Routier, E.; Cassard, L.; Collins, M.; Vaysse, T.; Marthey, L.; Eggermont, A.; Asvatourian, V.; Lanoy, E.; Mateus, C.; Robert, C.; Carbonnel, F. (June 2017). "Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab". Annals of Oncology. 28 (6): 1368–1379. doi:10.1093/annonc/mdx108. PMID 28368458. 8. ^ Wright, AP; Piper, MS; Bishu, S; Stidham, RW (June 2019). "Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor-induced colitis". Alimentary Pharmacology & Therapeutics. 49 (12): 1474–1483. doi:10.1111/apt.15263. PMC 6637018. PMID 31035308. 9. ^ Nishida, T; Iijima, H; Adachi, S (10 September 2019). "Immune checkpoint inhibitor-induced diarrhea/colitis: Endoscopic and pathologic findings". World Journal of Gastrointestinal Pathophysiology. 10 (2): 17–28. doi:10.4291/wjgp.v10.i2.17. PMC 6751508. PMID 31559106. 10. ^ Ibraheim, Hajir (2020). "Systematic review with meta‐analysis: effectiveness of anti‐inflammatory therapy in immune checkpoint inhibitor‐induced enterocolitis". Alimentary Pharmacology & Therapeutics. 52 (9): 1432–1452. doi:10.1111/apt.15998 (inactive 2021-01-18). PMID 32920854.CS1 maint: DOI inactive as of January 2021 (link) 11. ^ Spain, L; Diem, S; Larkin, J (March 2016). "Management of toxicities of immune checkpoint inhibitors". Cancer Treatment Reviews. 44: 51–60. doi:10.1016/j.ctrv.2016.02.001. PMID 26874776. * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Checkpoint inhibitor induced colitis	None	2,742	wikipedia	https://en.wikipedia.org/wiki/Checkpoint_inhibitor_induced_colitis	2021-01-18T19:10:31	{"wikidata": ["Q96374841"]}
A group of rare arthrogryposis syndromes characterized by congenital contractures of two or more areas of the body, primarily involving the hands and feet, while the proximal joints are largely spared, in the absence of primary neurologic and/or muscle disease affecting limb function. Diagnostic features include camptodactyly or pseudocamptodactyly, hypoplastic or absent flexion creases, overriding fingers, ulnar deviation at the wrist, talipes equinovarus, calcaneovalgus deformities, vertical talus, and/or metatarsus varus. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Distal arthrogryposis	c0265213	2,743	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97120	2021-01-23T18:19:47	{"umls": ["C0265213"], "icd-10": ["Q68.8"]}
## Clinical Features Williams et al. (1978) described 3 sisters and a brother with microcephaly, mental retardation, and early onset of symptoms of achalasia. The brother, who died in Mexico at age 4.5 years, had recurrent vomiting (Dumars et al., 1980). The parents denied consanguinity but came from the same small village in Mexico. Hernandez et al. (1989) stated that 2 of the affected sibs in this family had initially been reported by Polonsky and Guth (1970) as having familial achalasia (200400). Khalifa (1988) reported 2 Libyan brothers, aged 7 and 9 years, with achalasia of the cardia, microcephaly, and mental retardation. Their parents were first cousins and were unaffected. Two other male sibs and a female twin of one of the affected brothers were also unaffected. Hernandez et al. (1989) reported an affected boy born to second-cousin Mexican parents who came from the same area of northwest Mexico as the patients reported by Dumars et al. (1980). Wafik and Kini (2017) reported a 6-year-old girl, born to second-cousin Pakistani parents, with achalasia cardia, microcephaly, and intellectual disability. She was noted to have partial synophrys, a hirsute back, and unilateral convergent squint. Inheritance Consanguinity in the families reported by Khalifa (1988), Hernandez et al. (1989), and Wafik and Kini (2017) suggests autosomal recessive inheritance. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Eyes \- Esotropia (1 patient) \- Synophrys, partial (1 patient) ABDOMEN Gastrointestinal \- Achalasia SKIN, NAILS, & HAIR Hair \- Hirsutism (1 patient) NEUROLOGIC Central Nervous System \- Intellectual disability ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ACHALASIA-MICROCEPHALY SYNDROME	c1860212	2,744	omim	https://www.omim.org/entry/200450	2019-09-22T16:31:40	{"doid": ["0050796"], "mesh": ["C536010"], "omim": ["200450"], "orphanet": ["929"]}
Human disease Precocious puberty Other namesEarly puberty SpecialtyGynecology, endocrinology Precocious puberty is the early development of phenotypical sex organs before the age of 8 in girls and 9 in boys. In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of children with precocious puberty, the early development is triggered by a disease such as a tumor or injury of the brain.[1] Even when there is no disease, unusually early puberty can have adverse effects on social behavior and psychological development, can reduce adult height potential, and may shift some lifelong health risks. Central precocious puberty can be treated by suppressing the pituitary hormones that induce sex steroid production. The opposite condition is delayed puberty. The term is used with several slightly different meanings that are usually apparent from the context. In its broadest sense, and often simplified as early puberty, "precocious puberty" sometimes refers to any physical sex hormone effect, due to any cause, occurring earlier than the usual age, especially when it is being considered as a medical problem. Stricter definitions of "precocity" may refer only to central puberty starting before a statistically specified age based on percentile in the population (e.g., 2.5 standard deviations below the population mean),[2] on expert recommendations of ages at which there is more than a negligible chance of discovering an abnormal cause, or based on opinion as to the age at which early puberty may have adverse effects. A common definition for medical purposes is onset before 8 years in girls or 9 years in boys.[3] ## Contents * 1 Causes * 1.1 Central * 1.2 Peripheral * 1.3 Isosexual and heterosexual * 1.4 Effects of precocious puberty * 1.5 Research * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 See also * 6 References * 7 External links ## Causes[edit] Pubertas praecox is the Latin term used by physicians in the 19th century. Early pubic hair, breast, or genital development may result from natural early maturation or from several other conditions.[citation needed] ### Central[edit] If the cause can be traced to the hypothalamus or pituitary, the cause is considered central. Other names for this type are complete or true precocious puberty.[4] Causes of central precocious puberty can include: * damage to the inhibitory system of the brain (due to infection, trauma, or irradiation) * hypothalamic hamartoma produces pulsatile gonadotropin-releasing hormone (GnRH) * Langerhans cell histiocytosis * McCune–Albright syndrome Central precocious puberty can also be caused by brain tumors, infection (most commonly tuberculous meningitis, especially in developing countries), trauma, hydrocephalus, and Angelman syndrome.[5] Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses, thus resulting in reduced final height and short stature.[6] Adrenocortical oncocytomas are rare with mostly benign and nonfunctioning tumors. There have been only three cases of functioning adrenocortical oncocytoma that have been reported up until 2013. Children with adrenocortical oncocytomas will present with "premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone" which are some of the presentations associated with precocious puberty.[7][8] Precocious puberty in girls begins before the age of 8. The youngest mother on record is Lina Medina, who gave birth at the age of either 5 years, 7 months and 17 days[9] or 6 years 5 months as mentioned in another report.[10] "Central precocious puberty (CPP) was reported in some patients with suprasellar arachnoid cysts (SAC), and SCFE (slipped capital femoral epiphysis) occurs in patients with CPP because of rapid growth and changes of growth hormone secretion."[11] If no cause can be identified, it is considered idiopathic or constitutional. ### Peripheral[edit] Secondary sexual development induced by sex steroids from other abnormal sources is referred to as peripheral precocious puberty or precocious pseudopuberty. It typically presents as a severe form of disease with children. Symptoms are usually as a sequelae from adrenal insufficiency (because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency, the former being more common), which includes but is not limited to hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. Blood tests will typically reveal high level of androgens with low levels of cortisol. Causes can include: * Endogenous sources * Gonadal tumors (such as arrhenoblastoma) * Adrenal tumors * Germ cell tumor[12][13] * Congenital adrenal hyperplasia * McCune–Albright syndrome * Familial male-limited precocious puberty (testotoxicosis) * Exogenous hormones * Environmental exogenous hormones * As treatment for another condition ### Isosexual and heterosexual[edit] Generally, patients with precocious puberty develop phenotypically appropriate secondary sexual characteristics. This is called isosexual precocity.[14] In some cases, a patient may develop characteristics of the opposite sex. For example, a male may develop breasts and other feminine characteristics, while a female may develop a deepened voice and facial hair. This is called heterosexual or contrasexual precocity. It is very rare in comparison to isosexual precocity and is usually the result of unusual circumstances. As an example, children with a very rare genetic condition called aromatase excess syndrome- in which exceptionally high circulating levels of estrogen are present- usually develop precocious puberty. Males and females are hyper-feminized by the syndrome.[14] The "opposite" case would be the hyper-masculinisation of both male and female patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, in which there is an excess of androgens. Thus, in the aromatase excess syndrome the precocious puberty is isosexual in females and heterosexual in males, whilst in the CAH it's isosexual in males and heterosexual in females.[citation needed] ### Effects of precocious puberty[edit] ### Research[edit] Although the causes of early puberty are still somewhat unclear, girls who have a high-fat diet and are not physically active or are obese are more likely to physically mature earlier.[15][16][17] "Obese girls, defined as at least 10 kilograms (22 pounds) overweight, had an 80 percent chance of developing breasts before their ninth birthday and starting menstruation before age 12 – the western average for menstruation is about 12.7 years."[17] In addition to diet and exercise habits, exposure to chemicals that mimic estrogen (known as xenoestrogens) is another possible cause of early puberty in girls. Bisphenol A, a xenoestrogen found in hard plastics, has been shown to affect sexual development.[18] "Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls."[16] While more girls are increasingly entering puberty at younger ages, new research indicates that some boys are actually starting later (delayed puberty).[19][20] "Increasing rates of obese and overweight children in the United States may be contributing to a later onset of puberty in boys, say researchers at the University of Michigan Health System."[20] High levels of beta-hCG in serum and cerebrospinal fluid observed in a 9-year-old boy suggest a pineal gland tumor. The tumor is called a chorionic gonadotropin secreting pineal tumor. Radiotherapy and chemotherapy reduced tumor and beta-hCG levels normalized.[21] In a study using neonatal melatonin on rats, results suggest that elevated melatonin could be responsible for some cases of early puberty.[22] Familial cases of idiopathic central precocious puberty (ICPP) have been reported, leading researchers to believe there are specific genetic modulators of ICPP. Mutations in genes such as LIN28,[23][24] and LEP and LEPR, which encode leptin and the leptin receptor,[25] have been associated with precocious puberty. The association between LIN28 and puberty timing was validated experimentally in vivo, when it was found that mice with ectopic over-expression of LIN28 show an extended period of pre-pubertal growth and a significant delay in puberty onset.[26] Mutations in the kisspeptin (KISS1) and its receptor, KISS1R (also known as GPR54), involved in GnRH secretion and puberty onset, are also thought to be the cause for ICPP[27][28] However, this is still a controversial area of research, and some investigators found no association of mutations in the LIN28 and KISS1/KISS1R genes to be the common cause underlying ICPP.[29] The gene MKRN3, which is a maternally imprinted gene, was first cloned by Jong et al. in 1999. MKRN3 was originally named Zinc finger protein 127. It is located on human chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and has since been identified as a cause of premature sexual development or CPP.[30] The identification of mutations in MKRN3 leading to sporadic cases of CPP has been a significant contribution to better understanding the mechanism of puberty.[31] MKRN3 appears to act as a "brake" on the central hypothalamic-pituitary access. Thus, loss of function mutations of the protein allow early activation of the GnRH pathway and cause phenotypic CPP. Patients with a MKRN3 mutation all display the classic signs of CCP including early breast and testes development, increased bone aging and elevated hormone levels of GnRH and LH.[32] ## Diagnosis[edit] Studies indicate that breast development in girls and the appearance of pubic hair in both girls and boys are starting earlier than in previous generations.[16][33][34] As a result, "early puberty" in children as young as 9 and 10 is no longer considered abnormal, particularly with girls. Although it is not considered as abnormal, it may be upsetting to parents[19][35] and can be harmful to children who mature physically at a time when they are immature mentally.[36] No age reliably separates normal from abnormal processes in children, but the following age thresholds for evaluation are thought to minimize the risk of missing a significant medical problem: * Breast development in boys before appearance of pubic hair or testicular enlargement * Pubic hair or genital enlargement (gonadarche) in boys with onset before 9.5 years * Pubic hair (pubarche) before 8 or breast development (thelarche) in girls with onset before 7 years * Menstruation (menarche) in girls before 10 years Medical evaluation is sometimes necessary to recognize the few children with serious conditions from the majority who have entered puberty early but are still medically normal. Early sexual development warrants evaluation because it may: * induce early bone maturation and reduce eventual adult height * indicate the presence of a tumour or other serious problem * cause the child, particularly a girl, to become an object of adult sexual interest.[17][37][38] ## Treatment[edit] One possible treatment is with anastrozole. Histrelin, triptorelin, or leuprorelin, any GnRH agonists, may be used. Non-continuous usage of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH).[39] However, when used regularly, GnRH agonists cause a decreased release of FSH and LH. Prolonged use has a risk of causing osteoporosis. After stopping GnRH agonists, pubertal changes resume within 3 to 12 months.[citation needed] ## Prognosis[edit] Early puberty is posited to put girls at higher risk of sexual abuse;[17][38] however, a causal relationship is, as yet, inconclusive.[38] Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults.[17][37][40] Helping children control their weight is suggested to help delay puberty. Early puberty additionally puts girls at a "far greater" risk for breast cancer later in life[citation needed]. Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair; these "biological milestones" typically occurred only at 13 or older in the past. African-American girls are especially prone to early puberty.[16] There are theories debating the trend of early puberty, but the exact causes are not known.[citation needed] Though boys face fewer problems upon early puberty than girls, early puberty is not always positive for boys; early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of hormones that affect them.[41] Because they appear older than their peers, pubescent boys may face increased social pressure to conform to adult norms; society may view them as more emotionally advanced, although their cognitive and social development may lag behind their appearance.[41] Studies have shown that early maturing boys are more likely to be sexually active and are more likely to participate in risky behaviors.[42] ## See also[edit] * Delayed puberty * List of youngest birth mothers * List of youngest birth fathers * Premature menopause and premature ovarian failure ## References[edit] 1. ^ "Precocious Puberty". KidsHealth. Retrieved 2013-09-09. 2. ^ precocious+puberty at the US National Library of Medicine Medical Subject Headings (MeSH) 3. ^ "precocious puberty" at Dorland's Medical Dictionary[dead link] 4. ^ David Gardner, Dolores Shoback. Basic And Clinical Endocrinology. McGraw-Hill Medical; 2011. 9th Edition. Pg. 550 5. ^ Dickerman, R. D.; Stevens, Q. E.; Steide, J. A.; Schneider, S. J. (2004). "Precocious puberty associated with a pineal cyst: is it disinhibition of the hypothalamic-pituitary axis?". Neuro Endocrinology Letters. 25 (3): 173–175. PMID 15349080. 6. ^ Kumar, Manoj; Mukhopadhyay, Satinath; Dutta, Deep (2015-01-15). "Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: An Indian perspective". Indian Journal of Endocrinology and Metabolism. 19 (2): 228–235. doi:10.4103/2230-8210.149316. PMC 4319262. PMID 25729684. 7. ^ Subbiah, Sridhar; Nahar, Uma; Samujh, Ram; Bhansali, Anil (May 2013). "Heterosexual precocity: rare manifestation of virilizing adrenocortical oncocytoma". Annals of Saudi Medicine. 33 (3): 294–297. doi:10.5144/0256-4947.2013.294. ISSN 0256-4947. PMC 6078526. PMID 23793435. "So far, in the pediatric age group, only three cases of functioning adrenocortical oncocytoma have been reported. We report a case of functioning adrenocortical oncocytoma in a 3 1/2-year-old female child who presented with premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone. She was managed successfully with right adrenalectomy, and the tumor histology was consistent with adrenal oncocytoma." 8. ^ Santos-Silva, Rita; Bonito-Vítor, Artur; Campos, Miguel; Fontoura, Manuel (2014). "Gonadotropin-Dependent Precocious Puberty in an 8-Year-Old Boy with Leydig Cell Testicular Tumor". Hormone Research in Paediatrics. 82 (2): 133–137. doi:10.1159/000358084. ISSN 1663-2818. PMID 24862970. S2CID 9961260. 9. ^ "Six decades later, world's youngest mother awaits aid". The Telegraph. August 27, 2002. Archived from the original on July 22, 2009. Retrieved April 13, 2016. 10. ^ "Little Mother". Time. December 16, 1957. Archived from the original on April 22, 2009. Retrieved January 9, 2008. 11. ^ Yamato, Fumiko; Takaya, Junji; Higashino, Hirohiko; Yamanouchi, Yasuo; Suehara, Hiroshi; Kobayashi, Yohnosuke (March 2005). "Slipped capital femoral epiphysis during the treatment of precocious puberty with a gonadotropin-releasing hormone-agonist: aetiological considerations". European Journal of Pediatrics. 164 (3): 173–174. doi:10.1007/s00431-004-1578-7. PMID 15592875. S2CID 27162486. 12. ^ Masse, R. J.; Shaw, P. J.; Burgess, M. (2008). "Intracranial choriocarcinoma causing precocious puberty and cured with combined modality therapy". Journal of Paediatrics and Child Health. 29 (6): 464–467. doi:10.1111/j.1440-1754.1993.tb03022.x. PMID 8286166. 13. ^ Antoniazzi, F.; Zamboni, G. (2004). "Central precocious puberty: current treatment options". Paediatric Drugs. 6 (4): 211–231. doi:10.2165/00148581-200406040-00002. PMID 15339200. S2CID 21330464. 14. ^ a b Jarzabek-Bielecka, G; Warchoł-Biedermann, K; Sowińska, E; Wachowiak-Ochmańska, K (April 2011). "[Precocious puberty]". Ginekologia Polska. 82 (4): 281–6. PMID 21735696. 15. ^ (Tanner, 1990). 16. ^ a b c d Kaplowitz, P. B.; Slora, E. J.; Wasserman, R. C.; Pedlow, S. E.; Herman-Giddens, M. E. (2001). "Earlier onset of puberty in girls: relation to increased body mass index and race". Pediatrics. 108 (2): 347–353. doi:10.1542/peds.108.2.347. PMID 11483799. 17. ^ a b c d e McKenna, Phil (2007-03-05). "Childhood obesity brings early puberty for girls". New Scientist. Archived from the original on 2008-04-19. Retrieved 2010-05-22. 18. ^ Libertun, C.; Lux-Lantos, V.; Bianchi, M.; Fernández, M. (2009). "Neonatal Exposure to Bisphenol a Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats". Environmental Health Perspectives. 117 (5): 757–762. doi:10.1289/ehp.0800267. PMC 2685838. PMID 19479018. 19. ^ a b Cooney, Elizabeth (2010-02-11). "Puberty gap: Obesity splits boys, girls. Adolescent males at top of the BMI chart may be delayed". NBC News. Retrieved 2010-05-22. 20. ^ a b "Childhood Obesity May Contribute to Later Onset of Puberty for Boys". Science Daily. February 2010. Retrieved 2010-05-22. 21. ^ Kuo, H. C.; Sheen, J. M.; Wu, K. S.; Wei, H. H.; Hsiao, C. C. (2006). "Precocious puberty due to human chorionic gonadotropin-secreting pineal tumor". Chang Gung Medical Journal. 29 (2): 198–202. PMID 16767969. 22. ^ Esouifino, A. I.; Villanúa, M. A.; Agrasal, C. (1987). "Effect of neonatal melatonin administration on sexual development in the rat". Journal of Steroid Biochemistry. 27 (4–6): 1089–1093. doi:10.1016/0022-4731(87)90194-4. PMID 3121932. 23. ^ Park, Sung Won; Lee, Seung-Tae; Sohn, Young Bae; Cho, Sung Yoon; Kim, Se-Hwa; Kim, Su Jin; Kim, Chi Hwa; Ko, Ah-Ra; Paik, Kyung-Hoon; Kim, Jong-Won; Jin, Dong-Kyu (1 January 2012). "polymorphisms are associated with central precocious puberty and early puberty in girls". Korean Journal of Pediatrics. 55 (10): 388–92. doi:10.3345/kjp.2012.55.10.388. PMC 3488615. PMID 23133486. 24. ^ Ong, Ken K; Elks, Cathy E; Li, Shengxu; Zhao, Jing Hua; Luan, Jian'an; Andersen, Lars B; Bingham, Sheila A; Brage, Soren; Smith, George Davey; Ekelund, Ulf; Gillson, Christopher J; Glaser, Beate; Golding, Jean; Hardy, Rebecca; Khaw, Kay-Tee; Kuh, Diana; Luben, Robert; Marcus, Michele; McGeehin, Michael A; Ness, Andrew R; Northstone, Kate; Ring, Susan M; Rubin, Carol; Sims, Matthew A; Song, Kijoung; Strachan, David P; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Wong, Andrew; Deloukas, Panagiotis; Barroso, Inês; Mooser, Vincent; Loos, Ruth J; Wareham, Nicholas J (16 May 2009). "Genetic variation in LIN28B is associated with the timing of puberty". Nature Genetics. 41 (6): 729–733. doi:10.1038/ng.382. PMC 3000552. PMID 19448623. 25. ^ Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh (15 February 2012). "Study of leptin levels and gene polymorphisms in patients with central precocious puberty". Pediatric Research. 71 (4–1): 361–367. doi:10.1038/pr.2011.69. PMID 22391636. 26. ^ Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, Takeuchi A, Grasemann C, Rinn JL, Lopez MF, Hirschhorn JN, Palmert MR, Daley GQ (July 2010). "Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies". Nat Genet. 42 (7): 626–30. doi:10.1038/ng.593. PMC 3069638. PMID 20512147. 27. ^ Teles, Milena Gurgel; Silveira, Leticia Ferreira Gontijo; Tusset, Cintia; Latronico, Ana Claudia (1 October 2011). "New genetic factors implicated in human GnRH-dependent precocious puberty: The role of kisspeptin system". Molecular and Cellular Endocrinology. 346 (1–2): 84–90. doi:10.1016/j.mce.2011.05.019. PMID 21664234. S2CID 27207961. 28. ^ Silveira, LG; Noel, SD; Silveira-Neto, AP; Abreu, AP; Brito, VN; Santos, MG; Bianco, SD; Kuohung, W; Xu, S; Gryngarten, M; Escobar, ME; Arnhold, IJ; Mendonca, BB; Kaiser, UB; Latronico, AC (May 2010). "Mutations of the KISS1 gene in disorders of puberty". The Journal of Clinical Endocrinology and Metabolism. 95 (5): 2276–80. doi:10.1210/jc.2009-2421. PMC 2869552. PMID 20237166. 29. ^ Tommiska, Johanna; Sørensen, Kaspar; Aksglaede, Lise; Koivu, Rosanna; Puhakka, Lea; Juul, Anders; Raivio, Taneli (1 January 2011). "LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty". BMC Research Notes. 4 (1): 363. doi:10.1186/1756-0500-4-363. PMC 3184284. PMID 21939553. 30. ^ Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi PC, et al. (2013). "Central precocious puberty caused by mutations in the imprinted gene MKRN3". N Engl J Med. 368 (26): 2467–2475. doi:10.1056/nejmoa1302160. PMC 3808195. PMID 23738509. 31. ^ Macedo DB, Abreu AP, Reis AC, Montenegro LR, Dauber A, Beneduzzi D, Cukier P, Silveira LF, Teles MG, Carroll RS, et al. (2014). "Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3". J Clin Endocrinol Metab. 99 (6): E1097–1103. doi:10.1210/jc.2013-3126. PMC 4037732. PMID 24628548. 32. ^ Abreu AP, Macedo DB, Brito VN, et al. (2015). "A new pathway in the control of the initiation of puberty: the MKRN3 gene". Journal of Molecular Endocrinology. 54 (3): R131–R139. doi:10.1530/jme-14-0315. PMC 4573396. PMID 25957321. 33. ^ Zukauskaite, S.; Lasiene, D.; Lasas, L.; Urbonaite, B.; Hindmarsh, P. (2005). "Onset of breast and pubic hair development in 1231 preadolescent Lithuanian schoolgirls". Archives of Disease in Childhood. 90 (9): 932–936. doi:10.1136/adc.2004.057612. PMC 1720558. PMID 15855182. 34. ^ Roberts, Michelle (2005-05-15). "Why puberty now begins at seven". BBC News. Retrieved 2010-05-22. 35. ^ Ritter, Jim (2000-08-02). "Parents worried by girls' earlier start of puberty". Chicago Sun-Times. 36. ^ Diana Zuckerman (2001). "Early Puberty in Girls". The Ribbon. Cornell University Program on Breast Cancer and Environmental Risk Factors. Retrieved 18 February 2018. 37. ^ a b (Stattin & Magnussion, 1990) 38. ^ a b c Mendle J, Leve L, Van Ryzin M, Natsuaki M (August 2013). "Linking Childhood Maltreatment With Girls' Internalizing Symptoms: Early Puberty as a Tipping Point". Journal of Research on Adolescence. 24 (3): 626–30. doi:10.1111/jora.12075. PMC 4236856. PMID 25419091. 39. ^ Florence Comite; Cutler, Gordon B.; Rivier, Jean; Vale, Wylie W.; Loriaux, D. Lynn; Crowley, William F. (24 December 1981). "Short-Term Treatment of Idiopathic Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone". New England Journal of Medicine. 305 (26): 1546–1550. doi:10.1056/NEJM198112243052602. PMID 6458765. 40. ^ (Caspi et al.1993: Lanza and Collins, 2002) 41. ^ a b Garn, SM. Physical growth and development. In: Friedman SB, Fisher M, Schonberg SK, editors. Comprehensive Adolescent Health Care. St Louis: Quality Medical Publishing; 1992. Retrieved on 2009-02-20 42. ^ Susman, EJ; Dorn, LD; Schiefelbein, VL. Puberty, sexuality, and health. In: Lerner MA, Easterbrooks MA, Mistry J., editors. Comprehensive Handbook of Psychology. New York: Wiley; 2003. Retrieved on 2009-02-20 ## External links[edit] Classification D * ICD-10: E30.1, E22.8 * ICD-9-CM: 259.1 * OMIM: 176400 * MeSH: D011629 * DiseasesDB: 10519 External resources * MedlinePlus: 001168 * eMedicine: ped/1882 * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Precocious puberty	c0034013	2,745	wikipedia	https://en.wikipedia.org/wiki/Precocious_puberty	2021-01-18T19:02:00	{"gard": ["7446"], "mesh": ["D011629"], "umls": ["C0034013"], "icd-9": ["259.1"], "icd-10": ["E22.8", "E30.1"], "orphanet": ["95708"], "wikidata": ["Q224513"]}
Not to be confused with nephrosis. Inflammation of the kidneys Nephritis Enlarged kidney(anatomy) SpecialtyNephrology TypesGlomerulonephritis[1] and Interstitial nephritis[2] Diagnostic methodUltrasound, X-ray[3] TreatmentDepends on type(See type) Nephritis is inflammation of the kidneys and may involve the glomeruli, tubules, or interstitial tissue surrounding the glomeruli and tubules.[4] ## Contents * 1 Types * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 5.1 Prevalence * 6 See also * 7 References * 8 External links ## Types[edit] * Glomerulonephritis is inflammation of the glomeruli. Glomerulonephritis is often implied when using the term "nephritis" without qualification.[1] * Interstitial nephritis (or tubulo-interstitial nephritis) is inflammation of the spaces between renal tubules.[2] ## Causes[edit] Nephritis is often caused by infections, and toxins, but is most commonly caused by autoimmune disorders that affect the major organs like kidneys.[5] * Pyelonephritis is inflammation that results from a urinary tract infection that reaches the renal pelvis of the kidney.[6] * Lupus nephritis is inflammation of the kidney caused by systemic lupus erythematosus (SLE), a disease of the immune system.[7] * Athletic nephritis is nephritis resulting from strenuous exercise.[8] Bloody urine after strenuous exercise may also result from march hemoglobinuria, which is caused by trauma to red blood cells, causing their rupture, which leads to the release of hemoglobin into the urine.[9] ## Mechanism[edit] Renin–angiotensin system Nephritis can produce glomerular injury, by disturbing the glomerular structure with inflammatory cell proliferation.[10] This can lead to reduced glomerular blood flow, leading to reduced urine output (oliguria)[11] and retention of waste products (uremia).[12] As a result, red blood cells may leak out of damaged glomeruli, causing blood to appear in the urine (hematuria).[13] Low renal blood flow activates the renin–angiotensin–aldosterone system (RAAS), causing fluid retention and mild hypertension.[14] As the kidneys inflame, they begin to excrete needed protein from the affected individual's body into the urine stream. This condition is called proteinuria.[15] Loss of necessary protein due to nephritis can result in several life-threatening symptoms. The most serious complication of nephritis can occur if there is significant loss of the proteins that keep blood from clotting excessively. Loss of these proteins can result in blood clots, causing sudden stroke.[16] ## Diagnosis[edit] The diagnosis depends on the cause of the nephritis, in the case of lupus nephritis, blood tests, X-rays and an ultrasound can help ascertain if the individual has the condition.[3] ## Treatment[edit] Disease burden of nephritis/nephrosis worldwide in 2004.[17] no data less than 40 40–120 120–200 200–280 280–360 360–440 440–520 520–600 600–680 680–760 Treatment (or management) of nephritis depends on what has provoked the inflammation of the kidney(s). In the case of lupus nephritis, hydroxychloroquine could be used.[18] ### Prevalence[edit] Nephritis represents the ninth most common cause of death among all women in the US (and the fifth leading cause among non-Hispanic black women).[19] Worldwide the highest rates[clarification needed] of nephritis are 50-55% for African or Asian descent, then Hispanic at 43% and Caucasian at 17%.[20] The average age of this inflammation (lupus nephritis in this case) is about 28.4 years old for an individual who has been diagnosed with the condition[21] ## See also[edit] * Nephrotic syndrome * Bright's Disease * Goodpasture syndrome * Lupus nephritis ## References[edit] 1. ^ a b "Glomerulonephritis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-06-14. 2. ^ a b "Interstitial nephritis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-06-14. 3. ^ a b "American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. \| National Guideline Clearinghouse". www.guideline.gov. Archived from the original on 15 September 2016. Retrieved 23 July 2016. 4. ^ Keto Acids – Advances in Research and Application 2013 Edition p.220e 5. ^ "Acute Nephritis; Nephrosis; Nephritic syndrome information. Patient \| Patient". Patient. Retrieved 23 July 2016. 6. ^ "Pyelonephritis: Kidney Infection". www.niddk.nih.gov. Retrieved 2015-06-14. 7. ^ "Lupus Nephritis". www.niddk.nih.gov. Retrieved 2015-06-14. 8. ^ "Nephritis Symptoms". esagil.org. 9. ^ Shinton, N. K. (2007). Desk Reference for Hematology. CRC Press. ISBN 9781420005127. Retrieved 2019-02-14. 10. ^ "Glomerular Diseases". www.niddk.nih.gov. Retrieved 2015-06-15. 11. ^ "Oliguria: Background, Etiology, Epidemiology". Medscape. eMedicine. Retrieved 23 July 2016. 12. ^ "uremia \| accumulation in the blood of constituents normally eliminated in the urine that produces a severe toxic condition and usually occurs in severe kidney disease". www.merriam-webster.com. Retrieved 2015-06-14. 13. ^ "Hematuria (Blood in the Urine)". www.niddk.nih.gov. Retrieved 2015-06-14. 14. ^ Ashar, Bimal; Miller, Redonda; Sisson, Stephen; Hospital, Johns Hopkins (2012-02-20). Johns Hopkins Internal Medicine Board Review: Certification and Recertification. Elsevier Health Sciences. ISBN 978-0323087988. 15. ^ "Proteinuria". www.niddk.nih.gov. Retrieved 2015-06-14. 16. ^ Jr, Donald E. Thomas (2014-05-22). The Lupus Encyclopedia: A Comprehensive Guide for Patients and Families. JHU Press. ISBN 9781421409849. 17. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov 11, 2009. 18. ^ "Hydroxychloroquine: MedlinePlus Drug Information". medlineplus.gov. Retrieved 23 July 2016. 19. ^ "Leading Causes of Death - Women's Health USA 2010". mchb.hrsa.gov. Retrieved 2015-06-14. 20. ^ Lerma, Edgar; Rosner, Mitchell (2012-10-28). Clinical Decisions in Nephrology, Hypertension and Kidney Transplantation. Springer Science & Business Media. ISBN 9781461444541. 21. ^ "Lupus Nephritis: Practice Essentials, Background, Pathophysiology". 2018-04-22. Cite journal requires `\|journal=` (help) ## External links[edit] Classification D * MeSH: D009393 * SNOMED CT: 52845002 Scholia has a topic profile for Nephritis. * v * t * e Kidney disease Glomerular disease * See Template:Glomerular disease Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremia Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Nephritis	c0027697	2,746	wikipedia	https://en.wikipedia.org/wiki/Nephritis	2021-01-18T19:08:43	{"mesh": ["D009393"], "umls": ["C0027697"], "wikidata": ["Q401402"]}
orthopedic injury This article is about acute hip dislocation. For developmental hip dysplasia, see Hip dysplasia. Dislocation of hip X-ray showing a joint dislocation of the left hip. SpecialtyOrthopedics SymptomsHip pain, trouble moving the hip[1] ComplicationsAvascular necrosis of the hip, arthritis[1] TypesAnterior, posterior[1] CausesTrauma[1] Diagnostic methodConfirmed by X-rays[2] Differential diagnosisHip fracture, hip dysplasia[3] PreventionSeat-belts[1] TreatmentReduction of the hip carried out under procedural sedation[1] PrognosisVariable[4] FrequencyUncommon[5] A hip dislocation is a disruption of the joint between the femur and pelvis.[1] Specifically it is when the ball–shaped head of the femur comes out of the cup–shaped acetabulum of the pelvis.[1] Symptoms typically include pain and an inability to move the hip.[1] Complications may include avascular necrosis of the hip, injury to the sciatic nerve, or arthritis.[1] Dislocations are typically due to significant trauma such as a motor vehicle collision or fall from height.[1] Often there are also other associated injuries.[2][6] Diagnosis is generally confirmed by plain X-rays.[2] Hip dislocations can also occur following a hip replacement or from a developmental abnormality known as hip dysplasia.[7] Efforts to prevent the condition include wearing a seat-belt.[1] Emergency treatment generally follows advanced trauma life support.[2] This is generally followed by reduction of the hip carried out under procedural sedation.[1] A CT scan is recommended following reduction to rule out complications.[8] Surgery is required if the joint cannot be reduced otherwise.[2] Often a few months are required for healing to occur.[1] [9] Hip dislocations are uncommon.[5] Males are affected more often than females.[3] Traumatic dislocations occurs most commonly in those 16 to 40 years old.[4] The condition was first described in the medical press in the early 1800s.[2] ## Contents * 1 Signs and symptoms * 1.1 Posterior dislocation * 1.2 Anterior dislocation * 2 Cause * 3 Mechanism * 4 Diagnosis * 4.1 Classification * 4.1.1 Posterior dislocation * 4.1.2 Anterior dislocation * 4.1.3 Central dislocation * 4.1.4 Hip dysplasia * 5 Management * 5.1 Uncomplicated * 5.2 Complicated * 6 Rehabilitation * 6.1 Exercises * 7 Epidemiology * 8 Other animals * 9 References * 10 External links ## Signs and symptoms[edit] The affected leg is virtually immovable by the person, and is usually extremely painful.[10] Dislocations are categorized as either posterior or anterior, based on the location of the head of the femur (see classification above).[11] ### Posterior dislocation[edit] Nine out of ten hip dislocations are posterior.[12] The affected limb will be in a position of flexion, adduction, and internally rotated in this case.[12] The knee and the foot will be in towards the middle of the body.[10] A sciatic nerve palsy is present in 8%-20% of cases.[12] ### Anterior dislocation[edit] In an anterior dislocation the limb is held by the person in externally rotated, extension and abduction.[13] Femoral nerve palsies can be present, but are uncommon.[12] ## Cause[edit] Dislocations of the hip typically take a high degree of force.[2] About 65% of cases are related to motor vehicle collisions, with falls and sports injuries being the cause of many of the rest.[2] ## Mechanism[edit] The hip joint includes the articulation of the femoral head (of femur) and the acetabulum of the pelvis. In hip dislocation, the femoral head is dislodged from this socket. Posterior dislocation is the most prevalent, in which the femoral head lies posterior and superior to the acetabulum. This is most common when the femur is adducted and internally rotated. The opposite is true for the shoulder, where the most common dislocation occurs in the anterior and inferior directions.[14] Motor vehicle traffic collisions are responsible for almost all posterior hip dislocations.[4] The posterior side of the hip exhibits primarily hip extension, dealing with the muscles: gluteus maximus, hamstring muscles (biceps femoris, semitendinosus, semimembranosus), and the six deep external rotators (piriformis, obturator externus, obturator internus, gemellus superior, gemellus inferior, and quadrates femoris).[15] To actually dislocate a healthy hip, a great amount of force needs to be applied. Falls from a height, such as a ladder, can also generate enough force to dislocate a hip. In older individuals, even a slight fall could cause this type of injury. Wear and tear that the body undergoes throughout the years leads to increased incidents of hip dislocation in the older population.[16] Several other injuries are also associated with hip dislocation. Fractures in the pelvis and legs, and minor back or head injuries can also occur, along with a hip dislocation, that is caused by a fall or athletic injury.[citation needed] ## Diagnosis[edit] Reimer's migration index can be used to indicate hip dislocation. The migration index (MI) is normally less than 33%.[17] Anterior-posterior (AP) X-rays of the pelvis, AP and lateral views of the femur (knee included) are ordered for diagnosis.[12] The size of the head of the femur is then compared across both sides of the pelvis. The affected femoral head will appear larger if the dislocation is anterior, and smaller if posterior.[13] A CT scan may also be ordered to clarify the fracture pattern.[citation needed] ### Classification[edit] #### Posterior dislocation[edit] Posterior dislocations with an associated fracture are categorised by the Thompson and Epstein classification system, the Stewart and Milford classification system, and the Pipkin system (when associated with femoral head fractures).[18][13] #### Anterior dislocation[edit] There is also a Thompson and Epstein classification system for anterior hip dislocations.[18][13] #### Central dislocation[edit] Central dislocation is an outdated term for medial displacement of the femoral head into a displaced acetabular fracture.[13] It is no longer used. #### Hip dysplasia[edit] Dislocation of the left hip, secondary to developmental hip dysplasia. Closed arrow marks the acetabulum, open arrow the femoral head. Further information: X-ray of hip dysplasia Hip dysplasia is a condition in which a child is born with a hip problem. Hip dysplasia is when the formation of the hip joint is abnormal. The ball at the top of the thighbone which is known as the femoral head is not stable within the socket (which is also known as the acetabulum).[citation needed] Hip dysplasia is the preferred term because it provides a more accurate description of the spectrum of abnormalities that affect the immature hip.[19] The term "congenital" dislocation is no longer recommended, except for very rare conditions, in which there is a ("teratologic") fixed dislocation location present at birth.[12] ## Management[edit] ### Uncomplicated[edit] The hip should be reduced as quickly as possible to reduce the risk of osteonecrosis of the femoral head.[4] This is done via inline manual traction with general anesthesia and muscle relaxation, or conscious sedation.[13] Fractures of the femoral head and other loose bodies should be determined prior to reduction. Common closed reduction methods include the Allis method and Stimson method.[20] Once reduction is completed management becomes less urgent and appropriate workup including CT scanning can be completed.[13] Post-reduction, people may begin early crutch-assisted ambulation with weight bearing as tolerated.[citation needed] ### Complicated[edit] If the dislocated hip cannot be reduced by manipulation alone, an immediate open (surgical) reduction is necessary. A CT scan or Judet views should be obtained prior to transfer to the surgical suite.[13] ## Rehabilitation[edit] Hip dislocation rehabilitation can take anywhere from two to three months, depending on the person. Complications to nearby nerves and blood vessels can sometimes cause loss of blood supply to the bone, also known as osteonecrosis. The protective cartilage on the bone can also be disturbed from this type of injury. For this reason, it is important for people to contact a physician and get treatment immediately following injury.[16] * The first step to recovering from a hip dislocation is reduction. This refers to putting the bones back into their intended positions. Normally, this is done by a physician while the person is under a sedative. Other times, a surgical procedure is required to reduce the hip bones back into their natural state.[21] * Next, rest, ice, and take anti-inflammatory medication to reduce swelling at the hip.[21] * Weight bearing is allowed for the type one posterior dislocation, but should only be done as pain allows and person is comfortable.[21] * Within 5–7 days of the injury occurrence, people may perform passive range of motion exercises to increase flexibility.[21] * A walking aid should be used until the person is comfortable with both weight bearing and range of motion.[21] ### Exercises[edit] A set of ankle weights. Modified side plank. Individuals suffering from hip dislocation should participate in physical therapy and receive professional prescriptive exercises based on their individual abilities, progress, and overall range of motion. The following are some typical recommended exercises used as rehabilitation for hip dislocation. It is important to understand that each individual has different capabilities that can best be assessed by a physical therapist or medical professional, and that these are simply recommendations.[21] * Bridge- Lie flat on back. Place arms with palms down beside body. Keep feet hip distance apart and bend knees. Slowly lift hips upward. Hold position for three to five seconds. This helps strengthen the glutes and increase stability of the hip joint.[21] * Supine leg abduction\- Lie flat on back. Slowly slide leg away from body and then back in, keeping the knees straight. This exercises the gluteus medius and helps to maintain stability in the hip while walking.[21] * Side Lying Leg abduction\- Lie on one side with one leg on top of the other. Slowly lift the top leg towards the ceiling and then lower it back down slowly.[21] * Standing Hip abduction- Standing up and holding on to a nearby surface, slowly lift one leg away from the midline of the body and then lower it back to starting position. This is simply a more advanced way to do any of the lying hip abduction exercises, and should be done as the person progresses in rehab.[21] * Knee raises- While standing and holding onto a chair, slowly lift one leg off the ground and bring it closer to the body while bending the knee. Then lower the leg back down slowly. This helps to strengthen the hip flexor muscles and retain stability in the hip.[21] * Hip flexion and extensions\- Standing, hold on to a nearby chair or surface. Swing one leg forwards away from you, and hold the position for three to five seconds. Then swing the leg slowly backwards and behind your body. Hold for three to five seconds. This exercise helps to increase range of motion, as well as strengthening the hip flexor and hip extensor muscles that control much of the hip joint.[21] * Adding ankle weights to any exercises can be done as progress is made in rehabilitation.[21] ## Epidemiology[edit] 16-40 year-old males are responsible for the majority of hip dislocations. These hip dislocations are typically posterior, and a direct result of motor vehicle traffic collisions.[4] ## Other animals[edit] Main article: Dislocation of hip in animals ## References[edit] 1. ^ a b c d e f g h i j k l m n "Hip Dislocation". AAOS. June 2014. Retrieved 7 June 2018. 2. ^ a b c d e f g h Beebe MJ, Bauer JM, Mir HR (July 2016). "Treatment of Hip Dislocations and Associated Injuries: Current State of Care". The Orthopedic Clinics of North America. 47 (3): 527–49. doi:10.1016/j.ocl.2016.02.002. PMID 27241377. 3. ^ a b Blankenbaker DG, Davis KW (2016). Diagnostic Imaging: Musculoskeletal Trauma E-Book. Elsevier Health Sciences. p. 495. ISBN 9780323442954. 4. ^ a b c d e Egol KA (2015). Handbook of fractures (5th ed.). Philadelphia: Wolters Kluwer Health. p. Chapter 27. ISBN 9781451193626. OCLC 960851324. 5. ^ a b "Hip Dislocation". www.orthobullets.com. Retrieved 7 June 2018. 6. ^ Clegg TE, Roberts CS, Greene JW, Prather BA (April 2010). "Hip dislocations--epidemiology, treatment, and outcomes". Injury. 41 (4): 329–34. doi:10.1016/j.injury.2009.08.007. PMID 19796765. 7. ^ Callaghan JJ, Rosenberg AG, Rubash HE (2007). The Adult Hip. Lippincott Williams & Wilkins. p. 1032. ISBN 9780781750929. 8. ^ "Hip Dislocations". Merck Manuals Professional Edition. August 2017. Retrieved 7 June 2018. 9. ^ Clarke S, Santy-Tomlinson J (2014). Orthopaedic and Trauma Nursing: An Evidence-based Approach to Musculoskeletal Care. John Wiley & Sons. p. 292. ISBN 9781118438848. 10. ^ a b "Hip Dislocation-OrthoInfo - AAOS". orthoinfo.aaos.org. Retrieved 1 October 2017. 11. ^ Goddard NJ (August 2000). "Classification of traumatic hip dislocation". Clinical Orthopaedics and Related Research. 377 (377): 11–4. doi:10.1097/00003086-200008000-00004. PMID 10943180. 12. ^ a b c d e f Essentials of musculoskeletal care. Sarwark, John F. Rosemont, Ill.: American Academy of Orthopaedic Surgeons. 2010. ISBN 9780892035793. OCLC 706805938.CS1 maint: others (link) 13. ^ a b c d e f g h Browner BD, Jupiter JB, Krettek C, Anderson PA (9 December 2014). Skeletal trauma : basic science, management, and reconstruction (Fifth ed.). Philadelphia, PA. ISBN 9781455776283. OCLC 898159499. 14. ^ Hip Dislocation in Emergency Medicine at eMedicine 15. ^ Floyd, R.T. (2009). Manual of structural kinesiology. New York, NY: McGraw-Hill[page needed] 16. ^ a b "Hip Dislocation-OrthoInfo - AAOS". Orthoinfo.aaos.org. 1 June 2014. Retrieved 1 March 2015. 17. ^ Persiani P, Molayem I, Calistri A, Rosi S, Bove M, Villani C (October 2008). "Hip subluxation and dislocation in cerebral palsy: outcome of bone surgery in 21 hips" (PDF). Acta Orthopaedica Belgica. 74 (5): 609–14. PMID 19058693. 18. ^ a b Thompson, Vernon P.; Epstein, Herman C. (1951). "Traumatic Dislocation of the Hip". The Journal of Bone & Joint Surgery. 33 (3): 746–792. doi:10.2106/00004623-195133030-00023. 19. ^ Jackson JC, Runge MM, Nye NS (December 2014). "Common questions about developmental dysplasia of the hip". American Family Physician. 90 (12): 843–50. PMID 25591184. 20. ^ Stimson LA (1883). A treatise on fractures. The Library of Congress. Philadelphia, H.C. Lea's son & co. 21. ^ a b c d e f g h i j k l m Hip Dislocation Treatment & Management at eMedicine ## External links[edit] Classification D * ICD-10: S73.0, Q65.0-Q65.2 * ICD-9-CM: 835 * OMIM: 142700 * MeSH: D006618 * DiseasesDB: 3056 External resources * eMedicine: emerg/144 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum * v * t * e Dislocations/subluxations, sprains and strains Joints and ligaments Head and neck * Dislocation of jaw * Whiplash Shoulder and upper arm * GH (Dislocated shoulder) * AC (Separated shoulder) * ALPSA lesion * SLAP tear * Bankart lesion Elbow and forearm * Pulled elbow * Gamekeeper's thumb Hip and thigh * Hip dislocation Knee and leg * Tear of meniscus * Anterior cruciate ligament injury * Unhappy triad * Patellar dislocation * Knee dislocation Ankle and foot * Sprained ankle (High ankle sprain) * Turf toe Muscles and tendons Shoulder and upper arm * Rotator cuff tear Hip and thigh * Pulled hamstring Knee and leg * Patellar tendon rupture * Achilles tendon rupture * Shin splints [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hip dislocation	c0019554	2,747	wikipedia	https://en.wikipedia.org/wiki/Hip_dislocation	2021-01-18T18:54:57	{"gard": ["2691"], "mesh": ["D006617"], "umls": ["C0019554"], "icd-9": ["835"], "icd-10": ["Q65.2", "S73.0", "Q65.0"], "wikidata": ["Q634638"]}
## Clinical Features Shashi et al. (1996) described a newborn infant with first-cousin parents who had a complex congenital heart defect and minor anomalies suggestive of trisomy 18. Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period from postoperative complications. On interphase fluorescence in situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal controlled liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal. Shashi et al. (1996) concluded that the apparent mosaicism for trisomy 18 in the liver may have been spurious, and that the pattern of anomalies, together with the parental consanguinity, may indicate a new autosomal recessive malformation syndrome. The illustrated appearance of the patient was unusual with broad nasal root, narrow palpebral fissures, telecanthus, deficient alae nasi, apparently low-set ears which were malformed, preauricular tags, and micrognathia. Eyes \- Narrow palpebral fissures \- Telecanthus Inheritance \- Autosomal recessive Lab \- ? mosaicism for trisomy 18 in the liver Mouth \- Micrognathia Nose \- Broad nasal root \- Deficient alae nasi Cardiac \- Complex congenital heart defect Ears \- Low-set ears \- Malformed ears \- Preauricular tags ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	TRISOMY 18-LIKE SYNDROME	c1832677	2,748	omim	https://www.omim.org/entry/601161	2019-09-22T16:15:16	{"mesh": ["C563382"], "omim": ["601161"]}
Generalized arterial calcification of infancy (GACI) is a disorder affecting the circulatory system that becomes apparent before birth or within the first few months of life. It is characterized by abnormal accumulation of the mineral calcium (calcification) in the walls of the blood vessels that carry blood from the heart to the rest of the body (the arteries). This calcification often occurs along with thickening of the lining of the arterial walls (the intima). These changes lead to narrowing (stenosis) and stiffness of the arteries, which forces the heart to work harder to pump blood. As a result, heart failure may develop in affected individuals, with signs and symptoms including difficulty breathing, accumulation of fluid (edema) in the extremities, a bluish appearance of the skin or lips (cyanosis), severe high blood pressure (hypertension), and an enlarged heart (cardiomegaly). People with GACI may also have calcification in other organs and tissues, particularly around the joints. In addition, they may have hearing loss or softening and weakening of the bones (rickets). Some individuals with GACI also develop features similar to those of another disorder called pseudoxanthoma elasticum (PXE). PXE is characterized by the accumulation of calcium and other minerals (mineralization) in elastic fibers, which are a component of connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Features characteristic of PXE that also occur in GACI include yellowish bumps called papules on the underarms and other areas of skin that touch when a joint bends (flexor areas); and abnormalities called angioid streaks affecting tissue at the back of the eye, which can be detected during an eye examination. As a result of the cardiovascular problems associated with GACI, individuals with this condition often do not survive past infancy, with death typically caused by a heart attack or stroke. However, affected individuals who survive their first six months, known as the critical period, can live into adolescence or early adulthood. ## Frequency The prevalence of GACI has been estimated to be about 1 in 391,000. At least 200 affected individuals have been described in the medical literature. ## Causes In about two-thirds of cases, GACI is caused by mutations in the ENPP1 gene. This gene provides instructions for making a protein that helps break down a molecule called adenosine triphosphate (ATP), specifically when it is found outside the cell (extracellular). Extracellular ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate is important in controlling calcification and other mineralization in the body. Mutations in the ENPP1 gene are thought to result in reduced availability of pyrophosphate, leading to excessive calcification in the body and causing the signs and symptoms of GACI. GACI can also be caused by mutations in the ABCC6 gene. This gene provides instructions for making a protein called MRP6, also known as the ABCC6 protein. This protein is found primarily in the liver and kidneys, with small amounts in other tissues such as the skin, stomach, blood vessels, and eyes. MRP6 is thought to transport certain substances across the cell membrane; however, the substances have not been identified. Some studies suggest that the MRP6 protein stimulates the release of ATP from cells through an unknown mechanism, allowing it to be broken down into AMP and pyrophosphate and helping to control deposition of calcium and other minerals in the body as described above. Other studies suggest that a substance transported by MRP6 is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues. Mutations in the ABCC6 gene lead to an absent or nonfunctional MRP6 protein. It is unclear how a lack of properly functioning MRP6 protein leads to GACI. This shortage may impair the release of ATP from cells. As a result, little pyrophosphate is produced, and calcium accumulates in the blood vessels and other tissues affected by GACI. Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium characteristic of GACI. Some people with GACI do not have mutations in the ENPP1 or ABCC6 gene. In these affected individuals, the cause of the disorder is unknown. ### Learn more about the genes associated with Generalized arterial calcification of infancy * ABCC6 * ENPP1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Generalized arterial calcification of infancy	c1859728	2,749	medlineplus	https://medlineplus.gov/genetics/condition/generalized-arterial-calcification-of-infancy/	2021-01-27T08:25:50	{"gard": ["8380"], "mesh": ["C565944"], "omim": ["208000", "614473"], "synonyms": []}
Marfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression. Because connective tissue is found throughout the body, Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening. Many people with Marfan syndrome have additional heart problems including a leak in the valve that connects two of the four chambers of the heart (mitral valve prolapse) or the valve that regulates blood flow from the heart into the aorta (aortic valve regurgitation). Leaks in these valves can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations). Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), loose joints, and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), stretch marks (striae) not related to weight gain or loss, and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head. Most individuals with Marfan syndrome have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition. The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan syndrome can be fatal early in life; however, with proper treatment, many affected individuals have normal lifespans. ## Frequency The incidence of Marfan syndrome is approximately 1 in 5,000 worldwide. ## Causes Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils bind to molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, microfibrils cannot bind to growth factors, so excess growth factors are available and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues in Marfan syndrome. ### Learn more about the gene associated with Marfan syndrome * FBN1 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Marfan syndrome	c0024796	2,750	medlineplus	https://medlineplus.gov/genetics/condition/marfan-syndrome/	2021-01-27T08:24:57	{"gard": ["6975"], "mesh": ["D008382"], "omim": ["154700"], "synonyms": []}
Anterior horn disease Anterior horn(#1above) is affected in this condition SpecialtyNeurology Anterior horn disease is one of a number of medical disorders affecting the anterior horn of the spinal cord.[1][2] Anterior horn diseases include spinal muscular atrophy, poliomyelitis and amyotrophic lateral sclerosis. ## References[edit] 1. ^ Brazis, Paul W.; Masdeu, Joseph C.; Biller, José (2012). Localization in Clinical Neurology. Lippincott Williams & Wilkins. p. 109. ISBN 9781451153583. Retrieved 27 October 2017. 2. ^ Garrison, Susan J. (2003). Handbook of Physical Medicine and Rehabilitation: The Basics. Lippincott Williams & Wilkins. p. 180. ISBN 9780781744348. Retrieved 27 October 2017. This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Anterior horn disease	c0154681	2,751	wikipedia	https://en.wikipedia.org/wiki/Anterior_horn_disease	2021-01-18T19:07:38	{"mesh": ["D016472"], "umls": ["C0154681"], "wikidata": ["Q4771350"]}
Syringofibroadenoma Other namesAcrosyringeal nevus of Weedon and Lewis SpecialtyDermatology Syringofibroadenoma is a cutaneous condition characterized by a hyperkeratotic nodule or plaque involving the extremities.[1]:668 It is considered of eccrine origin.[2] ## See also[edit] * Syringadenoma papilliferum * 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. 2. ^ "Syringofibroadenoma pathology - DermNet New Zealand". www.dermnet.org.nz. ## External links[edit] Classification D * ICD-10: D23(ILDS D23.L32) * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Syringofibroadenoma	c1266060	2,752	wikipedia	https://en.wikipedia.org/wiki/Syringofibroadenoma	2021-01-18T18:39:33	{"mesh": ["D057091"], "umls": ["C1266060"], "icd-10": ["D23"], "wikidata": ["Q7663357"]}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-64 (EIEE64) is caused by heterozygous mutation in the RHOBTB2 gene (607352) on chromosome 8p21. Description Early infantile epileptic encephalopathy-64 is a neurodevelopmental disorder characterized by onset of seizures usually in the first year of life and associated with intellectual disability, poor motor development, and poor or absent speech. Additional features include hypotonia, abnormal movements, and nonspecific dysmorphic features. The severity is variable: some patients are unable to speak, walk, or interact with others as late as the teenage years, whereas others may have some comprehension (summary by Straub et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features Straub et al. (2018) reported 10 unrelated patients, ranging in age from 2 to 17 years, with early-onset seizures and moderate to profound intellectual disability with poor or absent speech. Nine of the patients developed variable types of seizures in the first year of life; 1 patient (individual 8) had onset of focal seizures at age 3 years. Seizure types were variable and included focal dyscognitive, complex partial, and generalized tonic-clonic seizures. Five individuals had status epilepticus, but 1 mildly affected individual (patient 10) had only febrile seizures that ceased spontaneously. Most patients responded to antiepileptic treatment. Five patients had developmental regression corresponding to onset or worsening of epilepsy. All patients had severely impaired neurodevelopment, and most were unable to walk or could walk only with support. Individuals 8 and 10, who showed a relatively late onset of epilepsy (age 3 years) and had only febrile seizures, respectively, had the mildest cognitive impairment and good comprehension compared to the other patients. Many patients had poor overall postnatal growth, and 5 had microcephaly (-3 to -4.5 SD). Additional common features included hypotonia and abnormal movements, such as dystonia, limb hypertonia, or paroxysmal chorea-like movements. Four patients had hemiparesis, often associated with seizures. Some patients had stereotypic movements or behavioral abnormalities. Four patients had nonspecific abnormalities on brain imaging, including delayed myelination, thin corpus callosum, enlarged ventricles, cortical atrophy, and cerebellar hypoplasia. Some patients had minor nonspecific dysmorphic features, such as epicanthal folds, micrognathia, depressed nasal root or bridge, smooth philtrum, large ears, and thin upper lip. Molecular Genetics In 10 unrelated patients with EIEE64, Straub et al. (2018) identified 5 different de novo heterozygous missense mutations in the RHOBTB2 gene (607352.0001-607352.0005). The mutations were found by trio-based exome sequencing and the patients were ascertained through matchmaking platforms and international collaborative efforts. All of the mutations affected either the first or second BTB domains, at positions important for stabilizing interactions within the domain or for dimer formation. Overexpression of 3 of the mutations (R483H, R511Q, and A474G) in HEK293 cells resulted in increased levels of the mutant protein compared to wildtype, most likely because of impaired degradation in the proteasome. These mutations did not impair binding to CUL3 (603136), and immunofluorescence studies did not show obvious mislocalization or abnormal protein aggregation compared to controls. Material from affected individuals was not available. Straub et al. (2018) concluded that the mutations resulted in altered protein function rather than haploinsufficiency or a loss of function. Animal Model Straub et al. (2018) found that neuronal overexpression of the single RhoBTB ortholog in Drosophila resulted in increased seizure susceptibility, as measured by the 'bang sensitivity' test, as well as severe locomotor defects in the negative geotaxis assay. Pan-neuronal knockdown did not result in increased seizure susceptibility, but did cause locomotor defects. Learning and memory did not appear to be affected by knockdown or overexpression of the gene. Decreased dosage of RhoBTB was associated with impaired dendrite development with reduced numbers of dendritic branches and reduced total size and length of dendritic branches, whereas overexpression did not result in significant dendritic changes. The findings suggested a role for RhoBTB in neurologic function and possibly dendrite development. INHERITANCE \- Autosomal dominant GROWTH Other \- Poor postnatal growth HEAD & NECK Head \- Microcephaly (in some patients) Face \- Dysmorphic facial features, variable, nonspecific \- Micrognathia \- Smooth philtrum Ears \- Large ears Eyes \- Epicanthal folds Nose \- Depressed nasal bridge Mouth \- Thin upper lip MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability, moderate to profound \- Poor or absent speech \- Inability to walk \- Walking with support \- Seizures, variable \- Status epilepticus \- Developmental regression \- Abnormal movements \- Dystonia \- Limb hypertonia \- Paroxysmal chorea-like movements \- Hemiparesis \- Nonspecific abnormalities on brain imaging (in some patients) \- Delayed myelination \- Thin corpus callosum \- Enlarged ventricles \- Cortical atrophy \- Cerebellar hypoplasia Behavioral Psychiatric Manifestations \- Stereotypic movements \- Behavioral abnormalities MISCELLANEOUS \- Onset in the first year of life \- Variable severity \- Seizures tend to respond to medical treatment \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the Rho-related BTB domain-containing protein 2 gene (RHOBTB2, 607352.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 64	c4693899	2,753	omim	https://www.omim.org/entry/618004	2019-09-22T15:44:06	{"omim": ["618004"]}
Part of a series on Psychology * Outline * History * Subfields Basic types * Abnormal * Behavioral genetics * Biological * Cognitive/Cognitivism * Comparative * Cross-cultural * Cultural * Differential * Developmental * Evolutionary * Experimental * Mathematical * Neuropsychology * Personality * Positive * Quantitative * Social Applied psychology * Applied behavior analysis * Clinical * Community * Consumer * Counseling * Critical * Educational * Environmental * Ergonomics * Forensic * Health * Humanistic * Industrial and organizational * Legal * Medical * Military * Music * Occupational health * Political * Religion * School * Sport * Traffic Lists * Disciplines * Organizations * Psychologists * Psychotherapies * Publications * Research methods * Theories * Timeline * Topics * Psychology portal * v * t * e The Truman Show delusion, informally known as Truman syndrome, is a type of delusion in which the person believes that their lives are staged reality shows, or that they are being watched on cameras. The term was coined in 2008 by brothers Joel Gold and Ian Gold, a psychiatrist and a neurophilosopher, respectively, after the film The Truman Show. The Truman Show delusion is not officially recognized nor listed in the Diagnostic and Statistical Manual of the American Psychiatric Association.[1] ## Contents * 1 Background * 2 Delusions * 2.1 Cultural impact * 3 Reported cases * 3.1 Truman Syndrome * 4 Medical relevance * 5 Filmmaker's reaction * 6 See also * 7 References ## Background[edit] Main article: The Truman Show Rapid expansion of technology raises questions about which delusions are possible and which ones are bizarre. Dolores Malaspina, DSM-5 editor[2] The Truman Show is a 1998 comedy drama film directed by Peter Weir and written by Andrew Niccol. Actor Jim Carrey plays Truman Burbank, a man who discovers he is living in a constructed reality televised globally around the clock. Since he was in the womb his entire life has been televised, and all the people in his life have been paid actors. As he discovers the truth about his existence, Burbank fights to find an escape from those who have controlled him his entire life.[3] The concept predates this particular film, which was inspired by a 1989 episode of The Twilight Zone in its 1980s incarnation, titled "Special Service", which begins with the protagonist discovering a camera in his bathroom mirror. This man soon learns that his life is being broadcast 24/7 to TV watchers worldwide.[4] Author Philip K. Dick wrote a novel, Time Out of Joint (1959), in which the protagonist lives in a created world in which his "family" and "friends" are all paid to maintain the illusion. Later science fiction novels repeat the theme. While these books do not share the reality-show aspects of The Truman Show, they do have in common the concept of a world that has been constructed by others, around one's personal aspects. ## Delusions[edit] Main article: Delusion Delusions – fixed, fallacious beliefs – are symptoms that, in the absence of organic disease, indicate psychiatric disease. The content of delusions varies considerably (limited by the imagination of the delusional person), but certain themes have been identified; for example, persecution. These themes have diagnostic importance in that they point to certain diagnoses. Persecutory delusions are, for instance, classically linked to psychosis. ### Cultural impact[edit] The content of delusions are invariably tied to a person's life experience, and contemporary culture seems to play an important role.[5] A retrospective study conducted in 2008[6] showed how delusional content has evolved over time from religious/magical, to political and eventually to technically themed. The authors concluded that: > sociopolitical changes and scientific and technical developments have a marked influence on the delusional content in schizophrenia. Psychiatrist Joseph Weiner commented that: > ...in the 1940s, psychotic patients would express delusions about their brains being controlled by radio waves; now delusional patients commonly complain about implanted computer chips.[7] The Truman Show Delusion could represent a further evolution in the content of persecutory delusions in reaction to a changing pop culture. > Because reality shows are so visible, it is an area that a patient can easily incorporate into a delusional system. Such a person would believe they are constantly being videotaped, watched, and commented upon by a large TV audience.[7] ## Reported cases[edit] While the prevalence of the disorder is not known, there have been several hundred cases reported. There have been recorded instances of people suffering from the Truman Show Delusion from around the world. Joel Gold, a psychiatrist at Bellevue Hospital Center in New York City, and Clinical Associate Professor of psychiatry at New York University, and his brother Ian, who holds a research chair in Philosophy and Psychiatry at Montreal's McGill University,[3] are the foremost researchers on the subject. They have communicated, since 2002, with over a hundred individuals suffering from the delusion. They have reported that one patient traveled to New York City after 9/11 to make sure that the terrorist attacks were not a plot twist in his personal Truman Show, while another traveled to a Lower Manhattan federal building to seek asylum from his show.[3] Another patient had worked as an intern on a reality TV program, and believed that he was secretly being tracked by cameras, even at the polls on Election Day in 2004. He shouted that then-President George W. Bush was a "Judas," which brought him to Bellevue Hospital and Gold's attention.[8] One of Gold's patients, an upper-middle class Army veteran who wanted to climb the Statue of Liberty in the belief that doing so would release him from the "show",[8][9] described his condition this way: > I realized that I was and am the center, the focus of attention by millions and millions of people ... My family and everyone I knew were and are actors in a script, a charade whose entire purpose is to make me the focus of the world's attention.[8] The choice of the name "Truman Show Delusion" by the Golds was influenced by the fact that three of the five patients Joel Gold initially treated for the syndrome explicitly linked their perceived experiences to the film.[8] ### Truman Syndrome[edit] In the United Kingdom, psychiatrists Paolo Fusar-Poli, Oliver Howes, Lucia Valmaggia and Philip McGuire of the Institute of Psychiatry in London described in the British Journal of Psychiatry what they referred to as the "Truman Syndrome": > [A] preoccupying belief that the world had changed in some way that other people were aware of, which he interpreted as indicating he was the subject of a film and living in a film set (a ‘fabricated world’). This cluster of symptoms ... is a common presenting complaint in individuals ... who may be in the prodromal phase of schizophrenia.[10] The authors suggest that the "Truman explanation" is a result of the patients' search for meaning in their perception that the ordinary world has changed in some significant but inexplicable way. ## Medical relevance[edit] The Truman Show delusion is not officially recognized and is not a part of the Diagnostic and Statistical Manual of the American Psychiatric Association.[1] The Golds do not say that it is a new diagnosis but refer to it as "a variance on known persecutory and grandiose delusions."[7] ## Filmmaker's reaction[edit] After hearing about the condition, Andrew Niccol, writer of The Truman Show, said, "You know you've made it when you have a disease named after you."[11] ## See also[edit] * Dream argument * Five minute hypothesis * Frank Chu * Solipsism * Matrix hypothesis * Problem of other minds ## References[edit] Notes 1. ^ a b Grohol, John M. "DSM-VI: Reality TV Disorder" on PsychCentral 2. ^ Marantz, Andrew (September 16, 2013). "Unreality Star: The paranoid used to fear the C.I.A. Now their delusions mirror "The Truman Show"". The New Yorker: 32–37. 3. ^ a b c Kershaw, Sarah "Look Closely, Doctor: See the Camera?" The New York Times (August 27, 2008) 4. ^ "Movies That Stole Their Plots from 'The Twilight Zone'" Flavorwire. N.p., 13 Aug. 2012. Web. 10 Aug. 2014. 5. ^ Rokeach, Milton (2011). The Three Christs of Ypsilanti. NY, NY: New York Review Books. pp. 125, 127. ISBN 978-1-59017-384-8. "[September 15] [T]he [three] men [who have schizophrenia] had read about the Yeti in a magazine article on the Abominable Snowman; the introduction of this material marked a brand-new tack, about which we were to hear much more in the months to come...[October 30] I ask Leon if he is married. He replies that he is betrothed…to the Virgin Mary. He adds [a new belief] that his uncle said he could get a wife from the Yeti if he wanted to." 6. ^ Skodlar B, Dernovsek MZ, Kocmur M (2008). "Psychopathology of schizophrenia in Ljubljana (Slovenia) from 1881 to 2000: changes in the content of delusions in schizophrenia patients related to various sociopolitical, technical and scientific changes". The International Journal of Social Psychiatry. 54 (2): 101–11. doi:10.1177/0020764007083875. PMID 18488404. S2CID 41662275. 7. ^ a b c Wright, Suzanne "The Truman Delusion" on WebMD 8. ^ a b c d "Reality Bites" Archived 2015-09-24 at the Wayback Machine National Post (July 21, 2008) 9. ^ Ellison, Jesse "When Life is Like a TV Show" Newsweek (August 2, 2008) 10. ^ Fusar-Poli, Paolo; Howes, O.; Valmaggia, L.; McGuire, P. (2008). "'Truman' signs and vulnerability to psychosis". British Journal of Psychiatry. 193 (2): 168. doi:10.1192/bjp.193.2.168. PMID 18670010. 11. ^ "NZ filmmaker adds to medical lexicon". 3 News NZ. March 20, 2013. Archived from the original on 2013-07-29. Retrieved 2017-10-25. Further reading * Deuze, Mark (2012). Media Life. Cambridge, UK: Polity. ISBN 978-0-7456-6203-9. * Duncan, Erica (2015). "Suspicious Minds: How Culture Shapes Madness". American Journal of Psychiatry. 172 (1): 98–99. doi:10.1176/appi.ajp.2014.14091092. * Gold, Joel; Gold, Ian (November 2012). "The "Truman Show" delusion: Psychosis in the global village". Cognitive Neuropsychiatry. 17 (6): 455–472. doi:10.1080/13546805.2012.666113. PMID 22640240. S2CID 35017035. * Gold, Joel; Gold, Ian (2014). Suspicious Minds: How Culture Shapes Madness. New York: Simon and Schuster. ISBN 9781439181577. * Mishara, Aaron L. & Fusar-Poli, Paolo (2013). "The Phenomenology and Neurobiology of Delusion Formation During Psychosis Onset: Jaspers, Truman Symptoms, and Aberrant Salience". Schizophrenia Bulletin. 39 (2): 278–286. doi:10.1093/schbul/sbs155. PMC 3576172. PMID 23354468. * Varga, ÉJ; Herold, R; Tényi, T. (2016). "Effect of culture to delusions: Introduction of the Truman Show delusion". Psychiatria Hungarica (in Hungarian). 31 (4): 359–363. * v * t * e Psychiatry Subspecialties * Addiction psychiatry * Biological psychiatry * Child and adolescent psychiatry * Cognitive neuropsychiatry * Cross-cultural psychiatry * Developmental disability * Descriptive psychiatry * Eating disorder * Emergency psychiatry * Forensic psychiatry * Geriatric psychiatry * Immuno-psychiatry * Liaison psychiatry * Military psychiatry * Narcology * Neuropsychiatry * Palliative medicine * Pain medicine * Psychotherapy * Sleep medicine Organizations * American Academy of Child and Adolescent Psychiatry * American Board of Psychiatry and Neurology * American Neuropsychiatric Association * American Psychiatric Association * Campaign Against Psychiatric Abuse * Chinese Society of Psychiatry * Democratic Psychiatry * European Psychiatric Association * Global Initiative on Psychiatry * Hong Kong College of Psychiatrists * Independent Psychiatric Association of Russia * Indian Psychiatric Society * National Institute of Mental Health * Philadelphia Association * Royal Australian and New Zealand College of Psychiatrists * Royal College of Psychiatrists * Working Commission to Investigate the Use of Psychiatry for Political Purposes * World Psychiatric Association * Taiwanese Society of Child and Adolescent Psychiatry Related topics * Anti-psychiatry * Behavioral medicine * Clinical neuroscience * Imaging genetics * Neuroimaging * Neurophysiology * Philosophy of psychiatry * Political abuse of psychiatry * Insulin shock therapy * Electroconvulsive therapy * Pentylenetetrazol * Biopsychiatry controversy * Controversies about psychiatry * Psychiatrist * Psychiatric epidemiology * Psychiatric genetics * Psychiatric hospital * Psychiatric survivors movement * Psychosomatic medicine * Psycho-oncology * Psychopharmacology * Psychosurgery * Psychoanalysis Lists * Outline of the psychiatric survivors movement * Psychiatrists * Neurological conditions and disorders * Counseling topics * Psychotherapies * Psychiatric medications * by condition treated * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	The Truman Show delusion	None	2,754	wikipedia	https://en.wikipedia.org/wiki/The_Truman_Show_delusion	2021-01-18T18:28:14	{"wikidata": ["Q633567"]}
Goudsmit et al. (1971) reported a family in which 2 sisters and 3 brothers had Dohle bodies. Two of these 5 died of acute myeloblastic leukemia and 2 others had iron-resistant anemia. The parents and another sib did not have Dohle bodies. No statement concerning parental consanguinity was made. Dohle bodies of polymorphonuclear leukocytes are also seen in the May-Hegglin anomaly (155100). Inheritance \- Autosomal recessive Heme \- Dohle bodies \- Acute myeloblastic leukemia \- Iron-resistant anemia ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	DOHLE BODIES AND LEUKEMIA	c1857225	2,755	omim	https://www.omim.org/entry/223350	2019-09-22T16:28:38	{"mesh": ["C565617"], "omim": ["223350"]}
Ruminal tympany, also known as bloat, is a disease of ruminant animals, characterized by an excessive volume of gas in the rumen. Ruminal tympany may be primary, known as frothy bloat, or secondary, known as free-gas bloat.[1] In the rumen, food eaten by the ruminant is fermented by microbes. This fermentation process continually produces gas, the majority of which is expelled from the rumen by eructation (burping).[2] Ruminal tympany occurs when this gas becomes trapped in the rumen. In frothy bloat (primary ruminal tympany), the gas produced by fermentation is trapped within the fermenting material in the rumen, causing a build up of foam which cannot be released by burping.[3] In cattle, the disease may be triggered after an animal eats a large amount of easily fermenting plants, such as legumes, alfalfa, red clover, or white clover.[1] Some legumes, such as sainfoin, birdsfoot trefoil and cicer milkvetch are not associated with causing bloat in cattle.[4] In feedlot cattle, a diet containing a high proportion of cereal grain can lead to primary ruminal tympany.[5] The main signs of bloat in cattle are distension of the left side of the abdomen, dyspnea (difficulty breathing) and severe distress. If gas continues to accumulate, the right side of the abdomen may also become distended, with death occurring in cattle within 3–4 hours after symptoms begin.[1] In free-gas bloat (secondary ruminal tympany), gas builds up in the rumen and cannot escape, due to blockage of the esophagus.[1] ## Treatment[edit] 1. Removal of gases through trocar or cannula 2. Use stomach tube and remove the ruminal digesta 3. Medi oral (antifoaming agent) 10ml+250ml warm water and drench to the animal. If antifoaming agent not available, vegetable oil can be used, 400–500ml per large animal 4. Sodium bicarbonate 5. Nux vomica 6. Antihistamine is used to avoid lameness. One particular sign in acidosis is lameness. Because lactic acid accumulates in the coronary band, it causes irritation; histamine is released which causes lameness, so antihistamine is used to avoid it.[citation needed] ## Cultural depictions[edit] * Thomas Hardy's novel Far from the Madding Crowd depicts a flock of sheep suffering from bloat, which are treated by Gabriel Oak with a trocar to release the gas. * In the second chapter of James Herriot's book All Creatures Great and Small), an anxious James waits to meet his new boss, and is haunted by an urban legend of a new vet who ruined his career when he blew up a farmer's shed by lighting a match while gas was being released from a bloated cow. This same accident was portrayed in the TV Series of the same name, but with Farmer Skerry striking a match to light his cigarette as James' colleague Tristan releases the gas. Here, the scene was played for humor instead of as a disaster.[6] ## References[edit] 1. ^ a b c d Constable, PD; Hinchcliff, KW; Done, SH; Gruenberg, W (2016). "Chapter 8: Diseases of the alimentary tract - ruminants. Ruminal tympany (bloat)". Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats (11 ed.). Elsevier Health Sciences. pp. 473–482. ISBN 9780702070587. 2. ^ Reese, William O (2013). "Chapter 12: Digestion and absorption". Functional anatomy and physiology of domestic animals (4th ed.). Wiley. pp. 359–420. ISBN 9781118685891. 3. ^ Boden, Edward (2001). "Bloat". Black's veterinary dictionary (20th ed.). London: A & C Black. pp. 68–69. ISBN 9780713650624. 4. ^ Majak, W; Hall, JW; McCaughey, WP (May 1995). "Pasture management strategies for reducing the risk of legume bloat in cattle". Journal of Animal Science. 73 (5): 1493–8. doi:10.2527/1995.7351493x. PMID 7665381. 5. ^ Cheng, KJ; McAllister, TA; Popp, JD; Hristov, AN; Mir, Z; Shin, HT (January 1998). "A review of bloat in feedlot cattle". Journal of Animal Science. 76 (1): 299–308. doi:10.2527/1998.761299x. PMID 9464911. 6. ^ https://www.imdb.com/title/tt0509030/ This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Ruminal tympany	c0267225	2,756	wikipedia	https://en.wikipedia.org/wiki/Ruminal_tympany	2021-01-18T18:30:27	{"wikidata": ["Q3333918"]}
Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the body’s tissue. White blood cells fight off infections that enter the body. Bone marrow also contains platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs. [1] ## Contents * 1 History * 2 Causes * 3 Epidemiology * 4 Signs and symptoms * 5 Treatment * 6 References ## History[edit] Bone marrow failure is associated with three types of diseases, Fanconi anemia (FA), dyskeratosis congenita, and aplastic anemia. Fanconi anemia is an inherited blood disorder due to abnormal breakages in DNA genes. It is linked to hyperpigmentation, which is the darkening of an area of skin or nails caused by increased melanin. According to Histopathology, “However, in about 30% of FA patients no physical abnormalities are found”.[2] Dyskeratosis congenita often affects multiple parts of the body. Individuals with this disorder usually show changes in skin pigmentations, unusual fingernail growth, and mucosa leukoplakia; the inner part of the mouth is encased with white patches that may never resolve.[2] Aplastic anemia happens when bone marrow doesn’t produce enough new blood cells throughout the body. Aplastic anemia is an acquired autoimmune disease, which occurs when the immune system mistakenly attacks and destroys healthy body tissue.[3] ## Causes[edit] Bone marrow failure in both children and adults can be either inherited or acquired. Inherited bone marrow failure is often the cause in young children, while older children and adults may acquire the disease later in life.[4] A maturation defect in genes is a common cause of inherited bone marrow failure.[5] The most common cause of acquired bone marrow failure is aplastic anemia.[5] Working with chemicals such as benzene could be a factor in causing the illness. Other factors include radiation or chemotherapy treatments, and immune system problems. ## Epidemiology[edit] For those with severe bone marrow failure, the cumulative incidence of resulting stem cell transplantation or death was greater than 70% by individuals 60 years of age.[6] The incidence of bone marrow failure is triphasic: one peak at two to five years during childhood (due to inherited causes), and two peaks in adulthood, between 20 to 25 years old and after 60 years old (from acquired causes).[7] One in ten individuals with bone marrow failure have unsuspected Fanconi anemia (FA).[7] FA is the most common inherited bone marrow failure with an incidence of one to five episodes per million individuals.[7] The carrier frequency for FA is 1 in 200 to 300, however this differs by ethnicity.[7] In Europe and North America, the incidence of acquired aplastic anemia is rare with two episodes per million people each year, yet in Asia rises with 3.9 to 7.4 episodes per million people each year.[8] While acquired aplastic anemia with an unknown cause is rare, it is commonly permanent and life threatening as half of those with this condition die within the first six months.[9] The prevalence of bone marrow failure is over three times higher in Japan and East Asia than in the United States and Europe.[9] When one's body fails to produce blood cell lines, the morbidity and mortality rate increases.[9] Myelodysplastic syndromes (MDS) is a form of blood cancer found within the bone marrow in which the body no longer produces enough healthy, normal blood cells.[10] MDS are a frequently unrecognized and rare group of bone marrow failure disorders, yet the incidence rate has rose from 143 reported cases in 1973 to approximately 15,000 cases in the United States each year. Although MDS is often under-diagnosed, leading the believed actual incidence rate to be estimated at 35,000 to 55,000 new cases annually.[9] One in three people with MDS progress to acute myeloid leukemia.[10] For lower risk patients, those who do not undergo a bone marrow transplant have an average survival rate of up to six years.[10] However, high-risk patients have a survival rate of approximately five months.[10] ## Signs and symptoms[edit] The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and tend to last longer than normal. Children have a bigger chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent colds can also be symptoms of bone marrow failure.[11] ## Treatment[edit] The type of treatment depends on the severity of the patient’s bone marrow failure disease. Blood transfusion is one treatment. Blood is collected from volunteer donors who agree to let doctors draw blood stem cells from their blood or bone marrow for transplantation.[12] Blood that is taken straight from collected blood stem cells is known as peripheral blood stem cell donation. A peripheral stem cell donor must have the same blood type as the patient receiving the blood cells. Once the stem cells are in the patient’s body through an IV, the cells mature and become blood cells. Before donation, a drug is injected into the donor, which increases the number of stem cells into their body. Feeling cold and lightheaded, having numbness around the mouth and cramping in the hands are common symptoms during the donation process. After the donation, the amount of time for recovery varies for every donor, “But most stem cell donors are able to return to their usual activities within a few days to a week after donation”.[12] ## References[edit] 1. ^ "Bone Marrow Failure In Children - What You Need to Know". www.drugs.com. Retrieved 2017-01-31. 2. ^ a b Leguit, Roos J; Jan G. van den Tweel (2010). "The Pathology Of Bone Marrow Failure" (PDF). The Pathology of Bone Marrow Failure. 57 (5): 655–670. doi:10.1111/j.1365-2559.2010.03612.x. PMID 20727024. S2CID 1807526. 3. ^ "Aplastic Anemia". Health and Wellness Magazine. 12 December 2010. 4. ^ "Bone Marrow Failure In Children". Thomson Reuters (2011): 1-5. Retrieved 7 Nov 2011. 5. ^ a b Besa, Emmanuel C. "Bone Marrow Failure". Medscape Reference: Drugs, Diseases & Procedures. WebMD, LLC, (2011): 1-5. Missing or empty `\|url=` (help) 6. ^ Blanche, Alter (January 2018). "Cancer in the National Cancer Institute Inherited Bone Marrow Failure Syndrome Cohort After Fifteen Years of Follow-Up". Hemaematologica - Via MEDLINE (EBSCO). 7. ^ a b c d Moore, Christine (January 2019). "Bone Marrow Failure". StatPearls. 8. ^ Ashraf, Malouf (May 2018). "Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders (Review)". Cochrane Database of Systematic Reviews. 9. ^ a b c d Nagalla, Srikanth. "Bone Marrow Failure". Medscape. 10. ^ a b c d MDS Foundation. "What is MDS?". Myelodysplastic Syndromes Foundation, Inc. 11. ^ Kitchen, Rose. "Signs & Symptoms of Bone Marrow Failure". eHow Health. Demand Media, Inc (2011): 1-4. Missing or empty `\|url=` (help) 12. ^ a b "Blood and bone marrow donation definition". Mayo Clinic. Retrieved 6 December 2011. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Bone marrow failure	c0030312	2,757	wikipedia	https://en.wikipedia.org/wiki/Bone_marrow_failure	2021-01-18T19:02:29	{"mesh": ["D000080983", "D010198"], "umls": ["CL406855"], "wikidata": ["Q7882181"]}
A rare hereditary ataxia characterized by an early onset symptomatic generalized epilepsy, progressive cerebellar ataxia resulting in significant difficulties to walk or wheelchair dependency, and intellectual disability. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency	c4310780	2,758	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=404493	2021-01-23T17:25:04	{"omim": ["616949"], "icd-10": ["G11.1"], "synonyms": ["SCAR23", "Spinocerebellar ataxia autosomal recessive type 23"]}
Primary pulmonary histoplasmosis SpecialtyInfectious disease Primary pulmonary histoplasmosis is caused by inhalation of Histoplasma capsulatum spores, and approximately 10% of people with this acute infection develop erythema nodosum.[1]:316 ## See also[edit] * Histoplasmosis ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Primary pulmonary histoplasmosis	None	2,759	wikipedia	https://en.wikipedia.org/wiki/Primary_pulmonary_histoplasmosis	2021-01-18T18:58:42	{"icd-9": ["115.95"], "wikidata": ["Q7243160"]}
Spinocerebellar ataxia 15 (SCA15) is a neurological condition characterized by slowly progressive gait and limb ataxia, often in combination with eye movement abnormalities and balance, speech and swallowing difficulties. The onset of symptoms typically occurs between ages 7 and 66 years. The ability to walk independently is often maintained for many years following onset of symptoms. SCA15 is caused by mutations in the ITPR1 gene. It is inherited in an autosomal dominant manner. Diagnosis is based on clinical history, physical examination, molecular genetic testing, and exclusion of other similar diseases. There is no effective treatment known to modify disease progression. Patients may benefit from occupational and physical therapy for gait dysfunction and speech therapy for dysarthria. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Spinocerebellar ataxia 15	c1847725	2,760	gard	https://rarediseases.info.nih.gov/diseases/10477/spinocerebellar-ataxia-15	2021-01-18T17:57:36	{"mesh": ["C564685"], "omim": ["606658"], "orphanet": ["98769"], "synonyms": ["Spinocerebellar ataxia 16 (formerly)", "Spinocerebellar ataxia type 15", "SCA16 (formerly)", "SCA15/16", "SCA15"]}
Disease where stones form in the gallbladder Gallstone Other namesGallstone disease, cholelith, cholecystolithiasis (gallstone in the gallbladder), choledocholithiasis (gallstone in a bile duct)[1] Gallstones typically form in the gallbladder and may result in symptoms if they block the biliary system. Pronunciation * Cholelith /ˈkoʊləlɪθ/, cholelithiasis /ˌkoʊləlɪˈθaɪəsɪs/ SpecialtyGeneral surgery SymptomsNone, crampy pain in the right upper abdomen[2][3][4] ComplicationsInflammation of the gallbladder, inflammation of the pancreas, liver inflammation[2][4] Usual onsetAfter 40 years old[2] Risk factorsBirth control pills, pregnancy, family history, obesity, diabetes, liver disease, rapid weight loss[2] Diagnostic methodBased on symptoms, confirmed by ultrasound[2][4] PreventionHealthy weight, diet high in fiber, diet low in simple carbohydrates[2] TreatmentAsymptomatic: none[2] Pain: surgery[2] PrognosisGood after surgery[2] Frequency10–15% of adults (developed world)[4] A gallstone is a stone formed within the gallbladder out of precipitated bile components.[2] The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones,[5] and choledocholithiasis refers to presence of migrated gallstones within bile ducts. Most people with gallstones (about 80%) are asymptomatic.[2][3] However, when a gallstone obstructs the bile duct and causes acute cholestasis, a reflexive smooth muscle spasm often occurs, resulting in an intense cramp-like visceral pain in the right upper part of the abdomen known as a biliary colic (or "gallbladder attack").[4] This happens in 1–4% of those with gallstones each year.[4] Complications of gallstones may include inflammation of the gallbladder (cholecystitis), inflammation of the pancreas (pancreatitis), obstructive jaundice, and infection in bile ducts (cholangitis).[4][6] Symptoms of these complications may include pain of more than five hours duration, fever, yellowish skin, vomiting, dark urine, and pale stools.[2] Risk factors for gallstones include birth control pills, pregnancy, a family history of gallstones, obesity, diabetes, liver disease, or rapid weight loss.[2] The bile components that form gallstones include cholesterol, bile salts, and bilirubin.[2] Gallstones formed mainly from cholesterol are termed cholesterol stones, and those mainly from bilirubin are termed pigment stones.[2][3] Gallstones may be suspected based on symptoms.[4] Diagnosis is then typically confirmed by ultrasound.[2] Complications may be detected on blood tests.[2] The risk of gallstones may be decreased by maintaining a healthy weight with exercise and a healthy diet.[2] If there are no symptoms, treatment is usually not needed.[2] In those who are having gallbladder attacks, surgery to remove the gallbladder is typically recommended.[2] This can be carried out either through several small incisions or through a single larger incision, usually under general anesthesia.[2] In rare cases when surgery is not possible, medication can be used to dissolve the stones or lithotripsy to break them down.[7] In developed countries, 10–15% of adults have gallstones.[4] Rates in many parts of Africa, however, are as low as 3%.[8] Gallbladder and biliary related diseases occurred in about 104 million people (1.6% of people) in 2013 and they resulted in 106,000 deaths.[9][10] Women more commonly have stones than men and they occur more commonly after the age of 40.[2] Certain ethnic groups have gallstones more often than others.[2] For example, 48% of Native Americans have gallstones.[2] Once the gallbladder is removed, outcomes are generally good.[2] ## Contents * 1 Definitions * 2 Signs and symptoms * 2.1 Other complications * 3 Risk factors * 4 Pathophysiology * 4.1 Composition * 4.1.1 Cholesterol stones * 4.1.2 Pigment stones * 4.1.3 Mixed stones * 5 Diagnosis * 6 Prevention * 7 Treatment * 7.1 Surgical * 7.2 Medical * 8 Traditional medicine * 9 See also * 10 References * 11 External links ## Definitions[edit] Gallstone disease refers to the condition where gallstones are either in the gallbladder or common bile duct.[5] The presence of stones in the gallbladder is referred to as cholelithiasis, from the Greek chol\- (bile) + lith\- (stone) + -iasis (process).[1] Presence of gallstones in the common bile duct is called choledocholithiasis, from the Greek chol\- (bile) + docho\- (duct) + lith\- (stone) + iasis\- (process).[1] Choledocholithiasis is frequently associated with obstruction of the bile ducts, which in turn can lead to cholangitis, from the Greek: chol\- (bile) + ang\- (vessel) + itis\- (inflammation), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas, which in turn can result in pancreatitis. ## Signs and symptoms[edit] Gallstones, regardless of size or number,[11] may be asymptomatic, even for years. Such "silent stones" do not require treatment.[12][13] A characteristic symptom of a gallstone attack is the presence of colicky pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting. The pain steadily increases for approximately 30 minutes to several hours. A person may also experience referred pain between the shoulder blades or below the right shoulder. Often, attacks occur after a particularly fatty meal and almost always happen at night, and after drinking. In addition to pain, nausea, and vomiting, a person may experience a fever. If the stones block the duct and cause bilirubin to leak into the bloodstream and surrounding tissue, there may also be jaundice and itching. If this is the case, the liver enzymes are likely to be raised.[14] ### Other complications[edit] Rarely, gallstones in cases of severe inflammation may erode through the gallbladder into adherent bowel potentially causing an obstruction termed gallstone ileus.[15] Other complications include ascending cholangitis if there is a bacterial infection which can cause purulent inflammation in the biliary tree and liver, and acute pancreatitis as blockage of the bile ducts can prevent active enzymes being secreted into the bowel, instead damaging the pancreas.[14] Rarely gallbladder cancer may occur as a complication.[6] ## Risk factors[edit] Gallstone risk increases for females (especially before menopause) and for people near or above 40 years;[16] the condition is more prevalent among both North and South Americans[clarification needed] and people of European descent than among other ethnicities. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder.[17] Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and low-calorie diet.[citation needed] The absence of such risk factors does not, however, preclude the formation of gallstones. Nutritional factors that may increase risk of gallstones include constipation; eating fewer meals per day; low intake of the nutrients folate, magnesium, calcium, and vitamin C;[18] low fluid consumption;[19] and, at least for men, a high intake of carbohydrate, a high glycemic load, and high glycemic index diet.[20] Wine and whole-grained bread may decrease the risk of gallstones.[21] Rapid weight loss increases risk of gallstones.[22] The weight loss drug orlistat is known to increase the risk of gallstones.[23] Cholecystokinin deficiency caused by celiac disease increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed.[24] Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as from sickle-cell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections.[25] People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones.[26][27] Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.[28] Cholesterol modifying medications can affect gallstone formation. Statins inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones.[29][30] Fibrates increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones.[30] Bile acid malabsorption may also be a risk. ## Pathophysiology[edit] Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct.[31] The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. In addition, increased levels of the hormone estrogen, as a result of pregnancy or hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation. ### Composition[edit] From left to right: cholesterol stone, mixed stone, pigment stone. The composition of gallstones is affected by age, diet and ethnicity.[32] On the basis of their composition, gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones.[3] An ideal classification system is yet to be defined.[33] #### Cholesterol stones[edit] Cholesterol stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese–classification system).[33] Between 35% and 90% of stones are cholesterol stones.[3] #### Pigment stones[edit] Bilirubin ("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and calcium (calcium phosphate) salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese-classification system).[33] Between 2% and 30% of stones are bilirubin stones.[3] #### Mixed stones[edit] Mixed (brown pigment stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese- classification system).[33] Other common constituents are calcium carbonate, palmitate phosphate, bilirubin and other bile pigments (calcium bilirubinate, calcium palmitate and calcium stearate). Because of their calcium content, they are often radiographically visible. They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured hepatocytes and bacteria) which hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed.[3] Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball.[34] The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick secretions that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. * Gallbladder opened to show small cholesterol gallstones * X-ray microtomograph of a gallstone * The large, yellow stone is largely cholesterol, while the green-to-brown stones are mostly composed of bile pigments * Play media CT images of gallstones * Large gallstone * Numerous small gallstones made up largely of cholesterol ## Diagnosis[edit] Diagnosis is typically confirmed by abdominal ultrasound. Other imaging techniques used are ERCP and MRCP. Gallstone complications may be detected on blood tests.[2] A positive Murphy's sign is a common finding on physical examination during a gallbladder attack. * A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on ultrasound. There is 4 mm gall bladder wall thickening. * Biliary sludge and gallstones. There is borderline thickening of the gallbladder wall. * Gallstones as seen on plain X-ray * Large gallstone as seen on CT * Play media A normal gallbladder on ultrasound with bowel peristalsis creating the false appearance of stones ## Prevention[edit] Maintaining a healthy weight by getting sufficient exercise and eating a healthy diet that is high in fiber may help prevent gallstone formation.[2] The medication ursodeoxycholic acid (UDCA) appears to prevent formation of gallstones during weight loss.[35] A high fat diet during weight loss also appears to prevent gallstones.[35] ## Treatment[edit] ### Surgical[edit] Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population—between 10 and 15%—who develop a condition called postcholecystectomy syndrome[36] which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain.[37] There are two surgical options for cholecystectomy: * Open cholecystectomy is performed via an abdominal incision (laparotomy) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release.[12] * Laparoscopic cholecystectomy, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one-night hospital stay, followed by a few days of home rest and pain medication.[12] Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP).[38] ### Medical[edit] Cholesterol gallstones can sometimes be dissolved with ursodeoxycholic acid taken by mouth, but it may be necessary for the person to take this medication for years.[38] ## Traditional medicine[edit] Gallstones can be a valued by-product of animals butchered for meat because of their use as an antipyretic and antidote in the traditional medicine of some cultures, particularly, in traditional Chinese medicine. The most highly prized gallstones tend to be sourced from old dairy cows, termed calculus bovis or niu-huang (yellow thing of cattle) in Chinese. Some slaughterhouses carefully scrutinize workers for gallstone theft.[39] ## See also[edit] * Porcelain gallbladder * Mirizzi's syndrome ## References[edit] 1. ^ a b c Quick, Clive R. G.; Reed, Joanna B.; Harper, Simon J. F.; Saeb-Parsy, Kourosh; Deakin, Philip J. (2013). Essential Surgery E-Book: Problems, Diagnosis and Management: With STUDENT CONSULT Online Access. Elsevier Health Sciences. p. 281. ISBN 9780702054839. 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 "Gallstones". NIDDK. November 2013. Archived from the original on 28 July 2016. Retrieved 27 July 2016. 3. ^ a b c d e f g Lee, JY; Keane, MG; Pereira, S (June 2015). "Diagnosis and treatment of gallstone disease". The Practitioner. 259 (1783): 15–9, 2. PMID 26455113. 4. ^ a b c d e f g h i Ansaloni, L (2016). "2016 WSES guidelines on acute calculous cholecystitis". World Journal of Emergency Surgery : WJES. 11: 25. doi:10.1186/s13017-016-0082-5. PMC 4908702. PMID 27307785. 5. ^ a b Internal Clinical Guidelines Team (October 2014). "Gallstone Disease: Diagnosis and Management of Cholelithiasis, Cholecystitis and Choledocholithiasis. Clinical Guideline 188": 101. PMID 25473723. Cite journal requires `\|journal=` (help) 6. ^ a b "Complications". nhs.uk. Retrieved 13 May 2018. 7. ^ "Treatment for Gallstones". National Institute of Diabetes and Digestive and Kidney Diseases. November 2017. 8. ^ editors, Ronnie A. Rosenthal, Michael E. Zenilman, Mark R. Katlic (2011). Principles and practice of geriatric surgery (2nd ed.). Berlin: Springer. p. 944. ISBN 9781441969996. Archived from the original on 2016-08-15.CS1 maint: extra text: authors list (link) 9. ^ Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509. PMID 26063472. 10. ^ GBD 2013 Mortality and Causes of Death, Collaborators (10 January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/s0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 11. ^ Acalovschi, Monica; Blendea, Dan; Feier, Cristina; Letia, Alfred I.; Raitu, Nadia; Dumitrascu, Dan L.; Veres, Adina (2003). "Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study". The American Journal of Gastroenterology. 98 (8): 1856–1860. PMID 12907344. 12. ^ a b c National Institute of Diabetes and Digestive and Kidney Diseases (2007). "Gallstones" (PDF). Bethesda, Maryland: National Digestive Diseases Information Clearinghouse, National Institutes of Health, United States Department of Health and Human Services. Archived from the original (PDF) on 2010-12-05. Retrieved 2010-11-06. 13. ^ Heuman DM, Mihas AA, Allen J (2010). "Cholelithiasis". Omaha, Nebraska: Medscape (WebMD). Archived from the original on 2010-11-20. Retrieved 2010-11-06. 14. ^ a b "Gallstones (Cholelithiasis) Clinical Presentation: History, Physical Examination". emedicine.medscape.com. Archived from the original on 2016-11-14. Retrieved 2016-11-14. 15. ^ Fitzgerald JE, Fitzgerald LA, Maxwell-Armstrong CA, Brooks AJ (2009). "Recurrent gallstone ileus: time to change our surgery?". Journal of Digestive Diseases. 10 (2): 149–151. doi:10.1111/j.1751-2980.2009.00378.x. PMID 19426399. S2CID 43696188. 16. ^ Roizen MF and Oz MC, Gut Feelings: Your Digestive System, pp. 175–206 in Roizen and Oz (2005) 17. ^ Koppisetti, Sreedevi; Jenigiri, Bharat; Terron, M. Pilar; Tengattini, Sandra; Tamura, Hiroshi; Flores, Luis J.; Tan, Dun-Xian; Reiter, Russel J. (2008). "Reactive Oxygen Species and the Hypomotility of the Gall Bladder as Targets for the Treatment of Gallstones with Melatonin: A Review". Digestive Diseases and Sciences. 53 (10): 2592–603. doi:10.1007/s10620-007-0195-5. PMID 18338264. S2CID 22785223. 18. ^ Ortega RM, Fernández-Azuela M, Encinas-Sotillos A, Andrés P, López-Sobaler AM (1997). "Differences in diet and food habits between patients with gallstones and controls". Journal of the American College of Nutrition. 16 (1): 88–95. doi:10.1080/07315724.1997.10718655. PMID 9013440. Archived from the original on 2008-07-20. Retrieved 2010-11-06. 19. ^ Medicine, Institute of; Board, Food Nutrition; Intakes, Standing Committee on the Scientific Evaluation of Dietary Reference; Water, Panel on Dietary Reference Intakes for Electrolytes and (2005). 4 Water \| Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate \| The National Academies Press. p. 124. doi:10.17226/10925. ISBN 978-0-309-09169-5. 20. ^ Tsai, C.-J.; Leitzmann, M. F.; Willett, W. C.; Giovannucci, E. L. (2005-06-01). "Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men". Gut. 54 (6): 823–828. doi:10.1136/gut.2003.031435. ISSN 1468-3288. PMC 1774557. PMID 15888792. 21. ^ Misciagna, Giovanni; Leoci, Claudio; Guerra, Vito; Chiloiro, Marisa; Elba, Silvana; Petruzzi, José; Mossa, Ascanio; Noviello, Maria R.; Coviello, Angelo; Minutolo, Marino Capece; Mangini, Vito; Messa, Caterina; Cavallini, Aldo; Michele, Giampiero De; Giorgio, Italo (1996). "Epidemiology of cholelithiasis in southern Italy. Part II". European Journal of Gastroenterology & Hepatology. 8 (6): 585–93. doi:10.1097/00042737-199606000-00017. PMID 8823575. S2CID 11355563. 22. ^ Choices, NHS. "Should you lose weight fast? - Live Well—NHS Choices". www.nhs.uk. Archived from the original on 2016-02-16. Retrieved 2016-02-16. 23. ^ Commissioner, Office of the. "Safety Information—Xenical (orlistat) capsules". www.fda.gov. Archived from the original on 2016-06-11. Retrieved 2016-06-18. 24. ^ Wang HH, Liu M, Li X, Portincasa P, Wang DQ (2017). "Impaired intestinal cholecystokinin secretion, a fascinating but overlooked link between celiac disease and cholesterol gallstone disease". Eur J Clin Invest (Review). 47 (4): 328–333. doi:10.1111/eci.12734. PMID 28186337. 25. ^ Trotman, Bruce W.; Bernstein, Seldon E.; Bove, Kevin E.; Wirt, Gary D. (1980). "Studies on the Pathogenesis of Pigment Gallstones in Hemolytic Anemia". Journal of Clinical Investigation. 65 (6): 1301–8. doi:10.1172/JCI109793. PMC 371467. PMID 7410545. 26. ^ Endocrine and Metabolic Disorders: Cutaneous Porphyrias, pp. 63–220 in Beers, Porter and Jones (2006) 27. ^ Thunell S (2008). "Endocrine and Metabolic Disorders: Cutaneous Porphyrias". Whitehouse Station, New Jersey: Merck Sharp & Dohme Corporation. Retrieved 2010-11-07. 28. ^ M. A. Cahan, M. A.; L. Balduf; K. Colton; B. Palacioz; W. McCartney; T. M. Farrell (2006). "Proton pump inhibitors reduce gallbladder function". Surgical Endoscopy. 20 (9): 1364–1367. doi:10.1007/s00464-005-0247-x. PMID 16858534. S2CID 20833380. 29. ^ Kan, He-Ping; Guo, Wen-Bin; Tan, Yong-Fa; Zhou, Jie; Liu, Cun-Dong; Huang, Yu-Qi (2014-10-09). "Statin use and risk of gallstone disease: A meta-analysis". Hepatology Research. 45 (9): 942–948. doi:10.1111/hepr.12433. ISSN 1386-6346. PMID 25297889. S2CID 25636425. 30. ^ a b Preiss, David; Tikkanen, Matti J.; Welsh, Paul; Ford, Ian; Lovato, Laura C.; Elam, Marshall B.; LaRosa, John C.; DeMicco, David A.; Colhoun, Helen M. (2012-08-22). "Lipid-modifying therapies and risk of pancreatitis: a meta-analysis". JAMA. 308 (8): 804–811. doi:10.1001/jama.2012.8439. ISSN 1538-3598. PMID 22910758. 31. ^ Experimental investigation of the flow of bile in patient specific cystic duct models M Al-Atabi, SB Chin…, Journal of biomechanical engineering, 2010 32. ^ Channa, Naseem A.; Khand, Fateh D.; Khand, Tayab U.; Leghari, Mhhammad H.; Memon, Allah N. (2007). "Analysis of human gallstones by Fourier Transform Infrared (FTIR)". Pakistan Journal of Medical Sciences. 23 (4): 546–50. ISSN 1682-024X. Archived from the original on 2011-08-24. Retrieved 2010-11-06. 33. ^ a b c d Kim IS, Myung SJ, Lee SS, Lee SK, Kim MH (2003). "Classification and nomenclature of gallstones revisited" (PDF). Yonsei Medical Journal. 44 (4): 561–70. doi:10.3349/ymj.2003.44.4.561. ISSN 0513-5796. PMID 12950109. Retrieved 2010-11-06. 34. ^ Gallstones—Cholelithiasis; Gallbladder attack; Biliary colic; Gallstone attack; Bile calculus; Biliary calculus Archived 2011-02-07 at the Wayback Machine Last reviewed: July 6, 2009. Reviewed by: George F. Longstreth. Also reviewed by David Zieve 35. ^ a b Stokes, Caroline S.; Gluud, Lise Lotte; Casper, Markus; Lammert, Frank (2014-07-01). "Ursodeoxycholic Acid and Diets Higher in Fat Prevent Gallbladder Stones During Weight Loss: A Meta-analysis of Randomized Controlled Trials". Clinical Gastroenterology and Hepatology. 12 (7): 1090–1100.e2. doi:10.1016/j.cgh.2013.11.031. ISSN 1542-3565. PMID 24321208. 36. ^ Jensen (2010). "Postcholecystectomy syndrome". Omaha, Nebraska: Medscape (WebMD). Archived from the original on 2010-12-23. Retrieved 2011-01-20. 37. ^ Zackria, R; Waheed, A (January 2019). "Postcholecystectomy Syndrome". StatPearls. PMID 30969724. 38. ^ a b National Health Service (2010). "Gallstones — Treatment". NHS Choices: Health A-Z—Conditions and treatments. London: National Health Service. Archived from the original on 2010-11-14. Retrieved 2010-11-06. 39. ^ "Interview with Darren Wise. Transcrip". Omaha, Nebraska: Medscape (WebMD). Archived from the original on 2010-11-21. Retrieved 2010-11-06. ## External links[edit] Wikimedia Commons has media related to Gallstones. * "Gallstones". MedlinePlus. U.S. National Library of Medicine. Classification D * ICD-10: K80 * ICD-9-CM: 574 * OMIM: 600803 * MeSH: D042882 * DiseasesDB: 2533 * SNOMED CT: 235919008 External resources * MedlinePlus: 000273 * eMedicine: emerg/97 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum Authority control * GND: 4137688-2 * NDL: 00572683 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Gallstone	c0008350	2,761	wikipedia	https://en.wikipedia.org/wiki/Gallstone	2021-01-18T18:39:31	{"mesh": ["D042882", "D002769"], "umls": ["C0267869", "CL386104"], "icd-9": ["574", "574.9"], "icd-10": ["K80"], "wikidata": ["Q272714"]}
Hematidrosis Other namesBlood sweat, haematidrosis, hematohidrosis, hemidrosis Red-tinted sweat (or "blood sweat") caused by hematohidrosis SpecialtyDermatology Hematidrosis, also called blood sweat, is a very rare condition in which a human sweats blood.[1] The term is from Ancient Greek haîma/haímatos (αἷμα/αἵματος), meaning blood, and hīdrṓs (ἱδρώς), meaning sweat. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Instances * 6 See also * 7 References ## Signs and symptoms[edit] Blood usually oozes from the forehead, nails, umbilicus, and other skin surfaces. In addition, oozing from mucocutaneous surfaces causing nosebleeds, bloodstained tears, and vicarious menstruation are common.[2] The episodes may be preceded by intense headache and abdominal pain and are usually self-limiting. In some conditions, the secreted fluid is more dilute and appears to be blood-tinged, while others may have darker bright red secretions resembling blood.[3] While the extent of blood loss generally is minimal, hematidrosis also results in the skin becoming extremely tender and fragile. ## Causes[edit] Hematidrosis is a condition in which capillary blood vessels that feed the sweat glands rupture, causing them to exude blood, occurring under conditions of extreme physical or emotional stress.[4] Severe mental anxiety activates the sympathetic nervous system to invoke the stress- Fight-or-flight response to such a degree as to cause hemorrhage of the vessels supplying the sweat glands.[5] It has been suggested that acute fear and extreme stress can cause hematidrosis.[6] ## Diagnosis[edit] Investigation such as platelets count, platelet aggregation test, coagulation profile and skin biopsy reveal no abnormalities and direct light microscopy of fluid demonstrates presence of normal red blood cells. Investigations also failed to show any vasculitis or skin appendages (i.e. sweat glands, sebaceous glands and hair follicles) abnormalities.[3][7] A 2015 case study investigated hematidrosis with a patient who has epilepsy.[8] ## Treatment[edit] Effect on the body is weakness and mild to moderate dehydration from the severe anxiety and both blood and sweat loss.[9] The condition is very rare but there are reports in medical literature of successful treatment with beta blockers (propranolol 10 mg)[10][11] with significant reduction in the frequency of spontaneous blood oozing. The successful use of beta blockers supports the theory that the condition is induced by stress and anxiety yet this etiology is not established yet as the high prevalence of stress and anxiety in the modern era did not change the incidence of this extremely rare disease, suggesting that other co-abnormality also play a key role in this disease.[7] Atropine sulfate transdermal patches have also been used successfully.[3] Favorable results with psychiatric counselling to reduce stress highlight the relationship between psychogenic causes and hematohidrosis.[5] Jesus on the Mount of Olives ## Instances[edit] Dermatological research notes the presence of hematidrosis in people awaiting execution.[5] It has also been proposed as a possible explanation for Jesus' agony in the garden of Gethsemane (Luke 22:44)[12] and for claims associated with stigmata.[13][14] Leonardo da Vinci described a soldier who sweated blood before battle. The phenomenon has also been observed in individuals in fear for their lives; a case occurred during the London blitz, and a case of fear of a storm while sailing, etc.[13] ## See also[edit] * Haemolacria – blood in tears * Hyperhidrosis ## References[edit] 1. ^ Tshifularo, M. (2014). "Blood otorrhea: blood stained sweaty ear discharges: hematohidrosis; four case series (2001-2013)" (PDF). American Journal of Otolaryngology. 35 (2): 271–3. doi:10.1016/j.amjoto.2013.09.006. PMID 24315735. 2. ^ Holoubek, J. E.; Holoubek, A. B. (1996). "Blood, sweat and fear. "A classification of hematidrosis"". Journal of Medicine. 27 (3–4): 115–33. PMID 8982961. 3. ^ a b c Biswas, S.; Surana, T.; De, A.; Nag, F. (2013). "A curious case of sweating blood". Indian Journal of Dermatology. 58 (6): 478–80. doi:10.4103/0019-5154.119964. PMC 3827523. PMID 24249903. 4. ^ Freddrick Z., Dr "Hematidrosis" 5. ^ a b c Jerajani, H. R.; Jaju, Bhagyashri; Phiske, M. M.; Lade, Nitin (2009). "Hematohidrosis – A rare clinical phenomenon". Indian Journal of Dermatology. 54 (3): 290–2. doi:10.4103/0019-5154.55645. PMC 2810702. PMID 20161867. 6. ^ Holoubek JE; Holoubek AB (1996). "Blood, Sweat and Fear: A Classification of Hematidrosis". Journal of Medicine. 27 (3–4): 115–133. PMID 8982961. 7. ^ a b Mora, E; Lucas, J (2013). "Hematidrosis: Blood sweat". Blood. 121 (9): 1493. doi:10.1182/blood-2012-09-450031. PMID 23570065. 8. ^ Shen H., Wang Z., Wu T., Wang J., Ren C., Chen H., Yu Z., Don W. (2015). "Haematidrosis associated with epilepsy in a girl successfully Treated with oxcarbazepine: Case report". Journal of International Medical. 43 (2): 263–69. doi:10.1177/0300060514562488.CS1 maint: multiple names: authors list (link) 9. ^ Zhang FK, Zheng YL, Liu JH, Chen HS, Liu SH, Xu MQ; et al. (2004). "Clinical and laboratory study of a case of hematidrosis". Zhonghua Xue Ye Xue Za Zhi. 25: 147–50.CS1 maint: multiple names: authors list (link) 10. ^ Wang, Z.; Yu, Z.; Su, J.; Cao, L.; Zhao, X.; Bai, X.; Zhan, S.; Wu, T.; Jin, L.; Zhou, P.; Ruan, C. (2010). "A Case of Hematidrosis Successfully Treated with Propranolol". American Journal of Clinical Dermatology. 11 (6): 440–43. doi:10.2165/11531690-000000000-00000. PMID 20666570. 11. ^ Khalid, S. R.; Maqbool, S; Raza, N; Mukhtar, T; Ikram, A; Qureshi, S (2013). "Ghost spell or hematohidrosis". Journal of the College of Physicians and Surgeons (JCPSP). 23 (4): 293–94. PMID 23552544. 12. ^ William D. Edwards; Wesley J. Gabel; Floyd E. Hosmer (March 21, 1986). "On the Physical Death of Jesus Christ" (PDF). JAMA. 255 (11): 1455–1463. CiteSeerX 10.1.1.621.365. doi:10.1001/jama.1986.03370110077025. PMID 3512867.CS1 maint: uses authors parameter (link) 13. ^ a b Manonukul J, Wisuthsarewong W, Chantorn R, Vongirad A, Omeapinyan P. (2008). Hematidrosis: A pathologic process or stigmata. A case report with comprehensive histopathologic and immunoperoxidase studies. Am J Dermatopathol 30: 135-139. 14. ^ Kluger, N; Cribier, B. (2013). Stigmata: From Saint-Francis of Assisi to Idiopathic Haematidrosis. Ann Dermatol Venereol 140: 771-777. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hematidrosis	c1536022	2,762	wikipedia	https://en.wikipedia.org/wiki/Hematidrosis	2021-01-18T19:01:27	{"gard": ["13131"], "umls": ["C1536022"], "wikidata": ["Q1642094"]}
## Cloning and Expression In a search for genes able to cause dedifferentiated rat hepatoma cells to recover normal liver-specific functions, Ng et al. (1992) isolated a novel human DNA sequence, which they termed HALF1 for 'human activator of liver function-1.' Boccaccio et al. (1994) cloned genomic DNA containing HALF1. They analyzed a 6.6-kb genomic fragment (GenBank X63773) containing HALF1 and its flanking sequences. More than half of the fragment was composed of interspersed repeated sequences. The repeats included 10 SINEs, 1 LINE, and a processed pseudogene of the ribosomal L21 gene (RPL21P1), all retroposons. No other types of repeats were present. Mapping Using FISH, Boccaccio et al. (1994) mapped the HALF1 genomic sequence and its flanking regions, including the RPL21P1 pseudogene, to chromosome 12q24.2-q24.3. This location was indistinguishable by FISH from the map location of the liver-specific transcription factor HNF1 (142410). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	RIBOSOMAL PROTEIN L21 PSEUDOGENE 1	c1863884	2,763	omim	https://www.omim.org/entry/603416	2019-09-22T16:13:04	{"omim": ["603416"]}
A number sign (#) is used with this entry because of evidence that progressive myoclonic epilepsy-6 (EPM6) is caused by homozygous or compound heterozygous mutation in the GOSR2 gene (604027) gene on chromosome 17q21. Description Progressive myoclonic epilepsy-6 is an autosomal recessive neurologic disorder characterized by onset of ataxia in the first years of life, followed by action myoclonus and seizures later in childhood, and loss of independent ambulation in the second decade. Cognition is not usually affected, although mild memory difficulties may occur in the third decade (summary by Corbett et al., 2011). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). Clinical Features Corbett et al. (2011) reported 6 patients, including 2 sibs, with early childhood onset of progressive myoclonic epilepsy. One child was born of consanguineous Australian parents, and the others were of German or Dutch descent. The phenotype was homogeneous: patients developed progressive ataxia between ages 1 and 3 years, followed by action myoclonus between ages 6 to 10 years. Most became wheelchair-bound with areflexia in their mid-teens, although 1 patient became wheelchair-bound at age 24. A few patients had tremor and fine motor problems. All had seizures of some sort, either drop attacks, absence seizures, or tonic-clonic seizures. EEG showed active generalized spike and wave and polyspike patterns, as well as photosensitivity. All patients developed scoliosis, 2 had syndactyly, and most had increased serum creatine kinase. Cognition was normal in all, although 2 patients showed subtle memory difficulties in the third decade. Van Egmond et al. (2014) reported 5 additional Dutch patients with EPM6 confirmed by genetic analysis. The patients ranged in age from 7 to 26 years. All patients had symptom onset between 2 and 3 years of age, mainly gait disorder and clumsiness consistent with ataxia, although 1 patient had febrile seizures. All patients developed progressive ataxia and myoclonus, and myoclonus was exacerbated by stress or stimuli. The myoclonus was disabling, resulting in dysarthria and disruption of fine motor function. One patient became wheelchair-bound at age 8 years. Four patients developed seizures in the first decade, mainly tonic-clonic seizures. Three patients had scoliosis. Electrophysiologic studies showed cortical reflex myoclonus; additional studies showed that the areflexia was due to both a sensory neuropathy and chronic anterior horn cell involvement, suggesting peripheral nerve involvement and central neuronal cell loss in the spinal cord. Laboratory studies showed increased serum creatine kinase in only 1 patient. Brain imaging was normal, and cognition remained stable. Praschberger et al. (2015) reported a 61-year-old woman with EPM6. She presented with mild gait ataxia at age 2 years, and had transient episodes of motor deterioration triggered by infection and fever. She developed generalized action myoclonus and epilepsy around age 14. The disorder was progressive, and she became wheelchair-bound in her thirties. Cognitive dysfunction was not a prominent feature. Brain imaging showed generalized cerebral and cerebellar atrophy. Additional features included scoliosis and areflexia. She lived in a residential facility and was dependent for activities of daily living. Praschberger et al. (2015) noted that the phenotype in this patient was somewhat milder than that in previously reported patients. Inheritance Progressive myoclonic epilepsy-6 shows an autosomal recessive pattern of inheritance (Corbett et al., 2011). Molecular Genetics In 5 unrelated patients with progressive myoclonic epilepsy-6, Corbett et al. (2011) identified a homozygous loss-of-function mutation in the GOSR2 gene (G144W; 604027.0001). Haplotype analysis indicated a founder effect, most likely of European origin, approximately 3,600 years earlier. Van Egmond et al. (2014) reported 5 additional Dutch patients with EPM6, all of whom were homozygous for the G144W mutation. In a 61-year-old woman with EPM6, Praschberger et al. (2015) identified compound heterozygous mutations in the GOSR2 gene: G144W and a novel in-frame deletion (604027.0002). The patient's brother, who had cervical dystonia, was heterozygous for the G144W mutation. Functional studies of the mutations were not performed. The patient was 1 of 43 patients with a similar disorder who were screened for defects in the GOSR2 gene. INHERITANCE \- Autosomal recessive SKELETAL Spine \- Scoliosis NEUROLOGIC Central Nervous System \- Ataxia \- Difficulty walking \- Action myoclonus \- Seizures \- Tonic-clonic seizures \- Absence seizures \- Drop attacks \- Dysarthria \- Areflexia \- Tremor, variable \- Active generalized spike and wave and polyspike pattern seen on EEG \- Photosensitivity seen on EEG \- Mild cognitive impairment (in 2 patients) LABORATORY ABNORMALITIES \- Increased serum creatine kinase (in some patients) MISCELLANEOUS \- Onset of ataxia between 1 and 3 years of age \- Onset of myoclonus later in childhood \- Progressive disorder \- Some patients become wheelchair-bound in second decade MOLECULAR BASIS \- Caused by mutation in the Golgi SNAP receptor complex member 2 gene (GOSR2, 604027.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	EPILEPSY, PROGRESSIVE MYOCLONIC, 6	c3279627	2,764	omim	https://www.omim.org/entry/614018	2019-09-22T15:56:47	{"doid": ["891"], "omim": ["614018"], "orphanet": ["280620"], "synonyms": ["EPM6", "GOSR2-related progressive myoclonus ataxia", "North Sea progressive myoclonus epilepsy", "PME type 6", "Progressive myoclonus epilepsy type 6"]}
Collection of cerebrospinal fluid (CSF), without blood, located under the dural membrane This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (July 2010) (Learn how and when to remove this template message) 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: "Subdural hygroma" – news · newspapers · books · scholar · JSTOR (January 2009) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Subdural hygroma Subdural hygroma, frontal and temporal. Man of 80 years old. SpecialtyNeurology A subdural hygroma (SDG) is a collection of cerebrospinal fluid (CSF), without blood, located under the dural membrane of the brain. Most subdural hygromas are believed to be derived from chronic subdural hematomas. They are commonly seen in elderly people after minor trauma but can also be seen in children following infection or trauma. One of the common causes of subdural hygroma is a sudden decrease in pressure as a result of placing a ventricular shunt. This can lead to leakage of CSF into the subdural space especially in cases with moderate to severe brain atrophy. In these cases the symptoms such as mild fever, headache, drowsiness and confusion can be seen, which are relieved by draining this subdural fluid. ## Contents * 1 Etiology and Pathophysiology * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Etiology and Pathophysiology[edit] Subdural hygromas require two conditions in order to occur. First, there must be a separation in the cell layers of the dural membrane of the brain. Second, the resulting subdural space that occurs from the separation of layers must remain uncompressed in order for CSF to accumulate in the subdural space resulting in the hygroma.[1] Subdural hygromas most commonly occur when events such as head trauma, infections, or cranial surgeries happen in tandem with brain atrophy, severe dehydration, prolonged spinal drainage, or any other event that causes a decrease in intracranial pressure.[1] This provides the basis for why subdural hygromas more commonly occur in infants and elderly; infants have compressible brains while elderly patients have a greater amount of space for fluid to accumulate due to brain atrophy from age.[1] ## Signs and symptoms[edit] Most subdural hygromas are small and clinically insignificant. Majoriy of patient with SDG will not experience symptoms. However, some commonly reported, but nonspecific, symptoms of SDG that have been reported include headache and nausea. Focal neurologic deficits and seizures have also been reported but are nonspecific to SDG.[1] Larger hygromas may cause secondary localized mass effects on the adjacent brain parenchyma, enough to cause a neurologic deficit or other symptoms. Acute subdural hygromas can be a potential neurosurgical emergency, requiring decompression. Acute hygromas are typically a result of head trauma—they are a relatively common posttraumatic lesion—but can also develop following neurosurgical procedures, and have also been associated with a variety of conditions, including dehydration in the elderly, lymphoma and connective tissue diseases. ## Diagnosis[edit] In the majority of cases, if there has not been any acute trauma or severe neurologic symptoms, a small subdural hygroma on the head CT scan will be an incidental finding. If there is an associated localized mass effect that may explain the clinical symptoms, or concern for a potential chronic SDH that could rebleed, then an MRI, with or without neurologic consultation, may be useful. It is not uncommon for chronic subdural hematomas (SDHs) on CT reports for scans of the head to be misinterpreted as subdural hygromas, and vice versa. Magnetic resonance imaging (MRI) should be done to differentiate a chronic SDH from a subdural hygroma, when clinically warranted. Elderly patients with marked cerebral atrophy, and secondary widened subarachnoid CSF spaces, can also cause confusion on CT. To distinguish chronic subdural hygromas from simple brain atrophy and CSF space expansion, a gadolinium-enhanced MRI can be performed. Visualization of cortical veins traversing the collection favors a widened subarachnoid space as seen in brain atrophy, whereas subdural hygromas will displace the cortex and cortical veins. ## Treatment[edit] Most subdural hygromas that are asymptomatic do not require any treatment. Some might opt to perform a simple burr-holes to alleviate intracranial pressure (ICP). Occasionally a temporary drain is placed for 24-48 hours post op. In recurrent cases a craniotomy may be performed to attempt to locate the location of the CSF Leak. In certain cases a shunt can be placed for additional drainage. Great caution is used when choosing to look for the CSF leak due to them generally being difficult to spot. ## References[edit] 1. ^ a b c d LEE, K. S. (1998-01-01). "The pathogenesis and clinical significance of traumatic subdural hygroma". Brain Injury. 12 (7): 595–603. doi:10.1080/026990598122359. ISSN 0269-9052. * Taveras, Juan M. et al., eds. Radiology: Diagnosis, Imaging, Intervention. 1994- ISBN 0-397-57115-1; ch. 37: 9-13. * Brain Inj 1998 Jul;12(7):595-603. * McCluney KW, Yeakley JW, Fenstermacher MJ, et al. «Subdural hygroma versus atrophy on MR brain scans: "the cortical vein sign"». AJNR Am J Neuroradiol 1992;13: 1335–39. ## External links[edit] * https://thejns.org/focus/view/journals/neurosurg-focus/26/6/article-pE8.xml Classification D * ICD-10: D18.1 * ICD-9-CM: 674.0 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Subdural hygroma	c0751533	2,765	wikipedia	https://en.wikipedia.org/wiki/Subdural_hygroma	2021-01-18T18:52:44	{"mesh": ["D013353"], "umls": ["C0751533"], "icd-9": ["432.1"], "icd-10": ["D18.1"], "wikidata": ["Q3792460"]}
A rare soft tissue tumor characterized by a compressive mass located in the mediastinum and/or pleura and lung, including prominent lymph node involvement, histologically poorly differentiated and frequently showing rhabdoid features. Loss of SMARCA4 is typically accompanied by SMARCA2-deficiency. Presenting symptoms include dyspnea, cough, chest pain, or dysphagia, among others. The tumors are aggressive with limited response to chemotherapies, rapid local progression, high recurrence rate after surgical resection, and short median survival times. There is a strong association with smoking. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SMARCA4-deficient sarcoma of thorax	None	2,766	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=466962	2021-01-23T17:05:00	{"synonyms": ["SMARCA4-deficient thoracic sarcoma"]}
Pyridoxal 5'-phosphate-dependent epilepsy is a rare genetic metabolic disorder. Babies born with this disorder are not able to make enough Vitamin B6 and this causes the baby to start having seizures soon after they are born (also called early onset or neonatal onset seizures). The normal drugs to treat seizures (anti-seizure medications or anti-convulsants) do not work for these babies, however seizures can be controlled by pyridoxal 5'-phosphate (the active form of Vitamin B6). Published studies in 2015 have shown that some babies with pyridoxal 5'-phosphate-dependent epilepsy also respond well to pyridoxene (a different form of Vitamin B6). Pyridoxal 5'-phosphate-dependent epilepsy is caused by changes or mutations in the PNPO gene and is inherited in an autosomal recessive manner. Diagnosis is suspected by early onset of seizures which are not controlled by normal anti-seizure medications. Genetic testing is used to confirm the diagnosis. The disorder is fatal without treatment. Early treatment is important to decrease the chance of long term developmental delays. Some babies with early treatment have developed normally without any intellectual disabilities. There are less than 50 known cases of pyridoxal 5'-phosphate-dependent epilepsy as of 2015. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pyridoxal 5'-phosphate-dependent epilepsy	c1864723	2,767	gard	https://rarediseases.info.nih.gov/diseases/10730/pyridoxal-5-phosphate-dependent-epilepsy	2021-01-18T17:58:01	{"mesh": ["C566449"], "omim": ["610090"], "umls": ["C1864723"], "orphanet": ["79096"], "synonyms": ["Pyridoxine-5'-phosphate oxidase deficiency", "PNPO Deficiency", "Pyridoxamine 5-prime-phosphate oxidase deficiency", "PNPO-related neonatal epileptic encephalopathy"]}
Malignant dysgerminomatous germ cell tumor of ovary is the most common form of malignant germ cell tumor of ovary (see this term), arising from germ cells in the ovary, usually presenting during adolescence with pelvic mass, fever, vaginal bleeding, and acute abdomen and is characterized by bilaterality (around 10% of cases), association with dysgenetic gonads (5 to 10% of cases), elevated serum lactate dehydrogenase (LDH) and human chorionic gonadotrophin (hCG) (in the presence of syncitiotrophoblasts). Malignant dysgerminomatous germ cell tumor of ovary responds well to chemotherapy, potentially sparing patients from infertility and early mortality. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Malignant dysgerminomatous germ cell tumor of the ovary	None	2,768	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99912	2021-01-23T18:18:03	{"icd-10": ["C56"], "synonyms": ["Dysgerminomatous germ cell cancer of the ovary", "Malignant ovarian dysgerminoma"]}
No Sex (Anti-HIV/AIDS ― Signage) in Ghana: These Signages from the Ghana AIDS Commission are everywhere in Ghana. Like other countries worldwide, HIV/AIDS is present in Ghana. As of 2014, an estimated 150,000 people infected with the virus. HIV prevalence is at 1.37 percent in 2014 and is highest in the Eastern Region of Ghana and lowest in the northern regions of the country. In response to the epidemic, the government has established the Ghana AIDS Commission which coordinates efforts amongst NGO's, international organizations and other parties to support the education about and treatment of aids throughout Ghana and alleviating HIV/AIDS issues in Ghana. ## Contents * 1 Prevalence * 2 National response * 3 See also * 4 References ## Prevalence[edit] Health informatics of Ghana's population satisfaction with health care in Ghana and health care provider information The HIV/AIDS elimination in Ghana seems to be progressing rapidly. The Government of Ghana and Ghana AIDS Commission estimated the number of adults and children living with HIV as of 2014 at 150,000 and prevalence at 1.37% in 2014. The Joint United Nations Program on HIV/AIDS (UNAIDS) estimated the HIV prevalence in adults to be 0.9% at the end of 2012, with an estimated 200,000 people living with HIV/AIDS."Health Profile: Ghana". Ghana's system of HIV surveillance for women attending antenatal clinics has functioned well since its establishment in 1994. Sentinel surveys of 21 antenatal clinic sites in 2002 reported a range from 3.1% to 9.1% in prevalence among pregnant women. In 2002, the median HIV prevalence at four of these sites in Accra was 4.1%; elsewhere in Ghana, prevalence in antenatal clinics ranged from 3.2% to 3.4% in 2002. HIV prevalence is highest in the Eastern Region of Ghana and lowest in the northern regions of the country. Prevalence is generally higher in urban areas, in mining and border towns, and along main transportation routes. HIV-1 accounts for 92% of HIV cases in Ghana; another 7.4% of reported HIV cases are dual infections with HIV-1 and HIV-2. Only 0.5% of HIV cases were exclusively HIV-2. Heterosexual intercourse is the mode of transmission for about 80% of HIV cases, with mother-to-child transmission accounting for another 15%. According to the 2003 Demographic and Health Survey, HIV prevalence is very low among most younger age groups, as relatively few are infected during their youth (with the exceptions of infants infected through their mothers). The infection peaks late, compared to other countries, at 35–39 years for women and 40–45 years for men. The infection levels are highest in middle income and middle educational groups, with the poor and unemployed less affected. With 1.47% being Ghana's adult prevalence rate it is the 34th country with the highest rate out of 196 countries in the world with Swaziland having the highest rate. That means that Ghana has a pretty good chance of not getting rid of HIV/AIDS from the whole country. Maybe they would be able to get rid of HIV/AIDS but at least not all of it because it does not tell us the children's prevalence rate.[1] Though evidence is still being gathered for making program decisions, some populations thought to be at risk include sex workers, transport workers, prisoners, sexual partners of people living with HIV/AIDS, and men who have sex with men and their female sexual partners. HIV prevalence among uniformed services is not fully established. Approximately 9,600 children under age 15 are living with HIV/AIDS, and at the end of 2003, nearly 170,000 children under age 17 had lost one or both parents to AIDS. At that time only a few thousand of these children had received assistance such as food aid, health care, protection services, or educational or psychosocial support. There is widespread knowledge of HIV and modes of transmission—with awareness of AIDS estimated at greater than 95%—although fear and stigmatization of HIV-positive people remain high. The populace are at risk of further HIV spread for a variety of reasons, including engaging in transactional sex, marriage and gender relations that disadvantage women and make them vulnerable to HIV, inaccurate perceptions of personal risk, and stigma and discrimination toward people living with HIV/AIDS. ## National response[edit] The Ghana AIDS Commission is the coordinating body for all HIV/AIDS-related activities in the country; it oversees an expanded response to the epidemic and is responsible for carrying out the National Strategic Framework on HIV/AIDS for the 2001–2005 period. The Ghana AIDS Commission is currently reviewing the National Strategic Framework II, covering 2006–2010, with stakeholders, and bilateral and multilateral partners. The frameworks set targets for reducing new HIV infections, address service delivery issues and individual and societal vulnerability, and promote the establishment of a multisectoral, multidisciplinary approach to HIV/AIDS programs.[2] Ghana's goal is to prevent new HIV infections as well as to mitigate the socioeconomic and psychological effects of HIV/AIDS on individuals, communities, and the nation. The first national strategic plan focused on five themes: prevention of new infections; care and support for people living with HIV/AIDS; creation of an enabling environment for a national response; decentralization of implementation of HIV/AIDS activities through institutional arrangements; research; and monitoring and evaluation of programs. The second national strategic plan, currently in process, focuses on: policy, advocacy, and enabling environment; coordination and management of the decentralized response; mitigating the economic, sociocultural, and legal impacts; prevention and Behavior Change Communication; treatment, care, and support; research and surveillance; and monitoring and evaluation.[2] Multilateral and bilateral partners, nongovernmental organizations (NGOs), and civil society organizations actively participate in the national response, with more than 2,500 community-based organizations and NGOs reportedly implementing HIV/AIDS activities in Ghana. Substantial funding for HIV/AIDS activities is received from the Ghana AIDS Commission. Activities include the five-country, World-Bank-led HIV/AIDS Abidjan-Lagos Transport Corridor project; the World Bank-funded Treatment Acceleration Program for public-private partnership in HIV/AIDS management; the World Health Organization (WHO) 3X5 initiative; the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM).[2] Following the Declaration of Commitment of the United Nations General Assembly Special Session on HIV/AIDS in 2001, the Government of Ghana earmarked 15% of its health budget for HIV/AIDS activities, and all ministries were asked to create an HIV/AIDS budget line. Available funding to support Ghana's response to the HIV/AIDS epidemic includes about $6.7 million from GFATM; about $12 million from multilateral partners, including the World Bank; and about $8 million from bilateral donors. Based on the level of funding already committed by the national government and its donors, WHO estimates a $5 to $12.8 million funding gap for HIV/AIDS activities in Ghana for the period 2004–2005.[2] ## See also[edit] * Health care in Ghana ## References[edit] 1. ^ Field Listing :: Adult prevalence rate.cia.gov. Retrieved 7 May 2016. 2. ^ a b c d "Health Profile: Ghana" Archived 2008-08-16 at the Wayback Machine. USAID. This article incorporates text from this source, which is in the public domain. * v * t * e Healthcare in Ghana Health Insurance Universal Health Care Health Care * National Health Insurance Scheme * List of hospitals Eye care * Eye care in Ghana Eye conditions * Glaucoma * Acute haemorrhagic conjunctivitis Optometry * Optometry in Ghana * Ghana Optometric Association * Dept of Optometry, KNUST * Dept of Optometry, UCC Government * Ministry of Health * Ghana Health Service Epidemics and Diseases * Water supply and sanitation * Water privatization * HIV/AIDS * Ghana AIDS Commission * 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 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* 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	HIV/AIDS in Ghana	None	2,769	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Ghana	2021-01-18T19:03:11	{"wikidata": ["Q5629834"]}
VIPoma is an extremely rare type of pancreatic neuroendocrine tumor (see this term) that secretes vasoactive intestinal polypeptide (VIP) leading to the manifestations of watery diarrhea, hypokalemia and achlorhydia or hypochhlorhydia (known as WDHA syndrome). ## Epidemiology The incidence of VIPoma in the general population is of less than 1/10,000,000 individuals per year. There is a slight female predominance. ## Clinical description The median age of diagnosis is the fifth decade of life but VIPoma can occur at any age. The most common presentation includes chronic watery diarrhea (described as >3L/day, odorless, blood and mucus free and unaffected by fasting), hypokalemia (manifesting with muscle weakness, abdominal muscle cramps, or respiratory depression), and various dietary deficiencies (iron and B12 deficiency) caused by achlorhydia/hypochlorhydia. Other less common manifestations include nausea, vomiting, weight loss, bloating, indigestion, skin rash and facial flushing, backache and lethargy. In 60-80% of cases, metastasis has occurred at the time of diagnosis as symptoms usually only occur once a tumor has reached a certain size. The most common site of metastasis is liver but lung, lymph node and kidney involvement have also been reported. If untreated, prolonged dehydration can lead to renal failure and cardiac arrest. In rare cases, VIPomas are non-functional. ## Etiology Most cases are sporadic but VIPomas can also occur in association with multiple endocrine neoplasia type 1 (MEN1; see this term). VIPomas are, in 90% of cases, located in the pancreas (mainly in the body and tail) and are usually solitary with a diameter ranging from 1-7cm. The remainder (10%) originate from non-pancreatic tissue such as the colon, liver and neural crest-derived tissues (mainly pediatric cases). These tumors secrete VIP, which stimulates cyclic adenosine monophosphate (cAMP) production in the intestine, causing increased water and electrolyte secretion into the lumen. VIP also has an inhibitory effect on gastric mucosa parietal cells leading to decreased gastric acid production. ## Diagnostic methods Diagnosis is based on clinical, laboratory and imaging findings. Typical blood laboratory findings include elevated VIP levels (>200pg/mL is diagnostic), hypokalemia, hypochlorhydia or achlorhydia, hyperglycemia, hypercalcemia and non-anion gap metabolic acidosis. Computed tomography (CT) and octreotide scans, magnetic resonance imaging (MRI) and endoscopic ultrasound can be used to localize neoplasms, confirming diagnosis. Immunohistochemically, VIPomas stain positively for VIP, synaptophysin, chromagranin A, somatostatin, neuron specific enolase and cytokeratin. ## Differential diagnosis Differential diagnoses include all other causes of chronic diarrhea such as malabsorption syndrome, Crohn disease, ulcerative colitis, microscopic colitis (see these terms), and gastrointestinal infections. ## Management and treatment Initial treatment focuses on replacing the massive loss of fluids, restoring electrolyte levels and reversing acidosis. Some patients may require intravenous fluid and potassium replacement in a hospital setting. Octreotide (a somatostatin analogue) is successful in controlling diarrhea and reducing VIP hormone levels. Loperamide may also be used. Surgical resection is the standard treatment in those with primary or metastatic VIPoma. Unresectable metastatic disease has been treated with chemotherapy (docorubicin/streptozocin regimen) in some cases. ## Prognosis Prognosis is highly variable and is dependent on many factors. In those with benign, surgically resectable tumors, the reported 5-year survival rate is almost 95%. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	VIPoma	c0011993	2,770	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97282	2021-01-23T18:39:09	{"gard": ["3787", "5493"], "mesh": ["D003969"], "umls": ["C0011993", "C0086768"], "icd-10": ["E16.8"], "synonyms": ["Diarrheogenic islet cell tumor", "Pancreatic cholera", "VIP-secreting tumor", "Verner-Morrison syndrome", "WDHA syndrome", "Watery diarrhea-hypokalemia-achlorhydria syndrome"]}
Scimitar syndrome is characterized by a combination of cardiopulmonary anomalies including partial anomalous pulmonary venous return connection of the right lung to the inferior caval vein leading to the creation of a left-to-right shunt. ## Epidemiology The prevalence is estimated at between 1/100,000 and 1/33,333 live births. Females seem to be more frequently affected than males. ## Clinical description In the majority of cases, the disease manifests in the first months of life. In the neonatal period, the disease presents with congestive cardiac failure, most commonly due to pulmonary hypertension and respiratory distress. The right lung is most frequently involved. Variable degrees of hypoplasia and malformations of the pulmonary arteries are found in the affected lung, as well as arterial supply from the aorta, which can also arise above or below the diaphragm. The heart itself is usually right-sided. Rarely, the disease may manifest with a small shunt, a cardiac murmur, and recurrent respiratory infections in children and adults. About one-fourth of affected patients have associated congenital heart disease (aortic coarctation, tetralogy of Fallot, patent arterial duct or ventricular septal defect; see these terms). Other reported associated anomalies include bronchogenic cysts, horseshoe lung, accessory diaphragm and hernias. ## Etiology The etiology is not completely understood. In several patients with total anomalous pulmonary venous return, the gene locus has been mapped to chromosome 4q12. ## Diagnostic methods The diagnosis is based on clinical presentation and transthoracic or transesophageal echocardiography, angiography, computed tomography and magnetic resonance angiography. The characteristic feature on chest radiographs, giving the condition its name, is a lesion in the shape of a scimitar (a type of curved Turkish sword). ## Differential diagnosis Scimitarsyndrome must be differentiated from pseudoscimitar syndrome (abnormal descending vein draining into the left atrium) and from Kartagener syndrome (see this term). ## Antenatal diagnosis Prenatal diagnosis is feasible by fetal echocardiography. Rarely, Scimitar syndrome is diagnosed incidentally in older children and adults who undergo chest radiography for diverse reasons. ## Management and treatment Management depends on the hemodynamic state. No therapy is required if the amount of blood flowing to the inferior caval vein is small. In case of significant left-to-right shunt and pulmonary hypertension, surgical correction is warranted, and can include repair of the anomalous venous return, ligation of collateral arteries, and right pneumonectomy. ## Prognosis When diagnosed in infancy, the syndrome is associated with significant mortality due to severe respiratory insufficiency, cardiac failure, and pulmonary infections. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Scimitar syndrome	c0036400	2,771	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=185	2021-01-23T18:44:16	{"mesh": ["D012587"], "umls": ["C0036400"], "icd-10": ["Q26.8"], "synonyms": ["Congenital pulmonary venolobar syndrome", "Epibronchial right pulmonary vein syndrome", "Halasz syndrome", "Hypogenetic lung syndrome"]}
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly, infantile-onset epileptic encephalopathy, and profound developmental delay. Additional reported features include cortical visual impairment, sensorineural hearing loss, increased muscle tone, limb contractures, scoliosis, and dysmorphic features like midface hypoplasia, narrow forehead, short nose, narrowed nasal bridge, and small chin. Brain imaging may show thin corpus callosum and delayed myelination. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	RNF13-related severe early-onset epileptic encephalopathy	None	2,772	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=544503	2021-01-23T17:07:54	{"omim": ["618379"], "icd-10": ["G40.4"], "synonyms": ["RNF13-related severe EOEE"]}
Amorphosynthesis, also called a hemi-sensory deficit, is a neuropsychological condition in which a patient experiences unilateral inattention to sensory input.[1] This phenomenon is frequently associated with damage to the right cerebral hemisphere resulting in severe sensory deficits that are observed on the contralesional (left) side of the body. A right-sided deficit is less commonly observed and the effects are reported to be temporary and minor.[2] Evidence suggests that the right cerebral hemisphere has a dominant role in attention and awareness to somatic sensations through ipsilateral and contralateral stimulation.[3][4][5] In contrast, the left cerebral hemisphere is activated only by contralateral stimuli.[6][7][8] Thus, the left and right cerebral hemispheres exhibit redundant processing to the right-side of the body and a lesion to the left cerebral hemisphere can be compensated by the ipsiversive processes of the right cerebral hemisphere.[9] For this reason, right-sided amorphosynthesis is less often observed and is generally associated with bilateral lesions.[10] ## Contents * 1 Anatomy * 2 Causes * 3 Types * 4 Treatment * 5 Signs and Symptoms * 5.1 Left Parietal Lobe Lesion * 5.2 Right Parietal Lobe Lesion * 6 Primary Research * 6.1 Denny-Brown and Banker * 6.2 Fazlullah * 6.3 Cherington and Yarnell * 7 Case Studies * 7.1 Denny-Brown: Amorphosynthesis From Left Parietal Lesion * 7.2 Fazlullah:Tactile Perception Rivalry And Tactile-Amorphosynthesis In The Localization Of Cerebral Lesions * 7.3 Cherington: Amorphosynthesis on the Chess Board * 8 History * 9 References ## Anatomy[edit] Brain areas in the parietal lobes play an integral role in processing and interpreting somatic sensations from the body or environment.[11] The right parietal lobe is associated with sensory integration and perception whereas the left parietal lobe is believed to function at a more conceptual level involving speech, reading and writing.[10] The central sulcus divides the frontal lobe from the parietal lobe which is located superior to the occipital lobe and posterior to the frontal lobe. The primary somatosensory cortex- the main processing center for tactile sensations- is positioned posterior to the central sulcus, on the post-central gyrus. The somatosensory system is also associated with the perception of temperature, taste, vision, proprioception and kinesthesia.[12] Sensory receptors that are spread throughout the body [skin, organs, muscles, etc.] send sensory input signals to the cortex via sensory afferent neurons.[13] The parietal lobes then act as a main determinant for the summation of stimuli and spatial awareness.[14] In research by Denny-Brown and Banker,[15] a disturbance in the physiological process of perceiving somatic sensations was termed amorphosynthesis. This concept was associated with lesions of the parietal lobe leading to the ineffectual processing of sensory stimulus on the opposite side of the lesion.[15] ## Causes[edit] Amorphosynthesis is most closely related to damage of the right parietal lobe but instances of left parietal and bilateral damage have also been reported.[16] The inattention to or suppression of somatic sensations on the contralesional side of the body can manifest in the cerebral processing centers that produce the sensory modalities for touch, taste, vision, smell, and proprioception.[17] This phenomenon is frequently associated with other unilateral conditions such as hemispatial neglect, metamorphognosia, hemiplegia, hemisomatognosia, kinesthetic hallucination, anosognosia, balint optic ataxia, anaesthoagnosia and apraxia.[18] The causes of cerebral brain damage to either hemisphere can include traumatic brain injury, stroke, infection, surgery or a tumor.[19] Causes of Amorphosynthesis are: * Cerebrovascular accidents that have affected cerebral hemispheres, such as occlusion of the right middle cerebral artery.[20] * Diffused brain lesion and lesions on other parts of the central nervous system (CNS).[21] ## Types[edit] The amorphosynthesis of sensory stimuli is associated with different perceptual and conceptual effects relative to the severity of damage to the parietal lobe. The degree of sensory suppression has been explored with bilateral and ipsilateral double stimulation methods in patients with either extensive or superficial parietal lesions.[22][23][24][25][26] Complete extinction is commonly observed in which patients with extensive right parietal damage show complete and constant inattention to tactile stimuli on the contralesional side of the body.[23] Incomplete extinction is frequently associated with lesions that are less extensive or superficial in nature. This phenomenon is supported by studies showing that if two stimuli are simultaneously applied to both sides of the body, the patient [with their eyes closed] will ignore the stimulus that is applied to the affected side and report a tactile sensation from the unaffected side alone.[24][25] If each side of the body is separately stimulated, then each stimulus is correctly reported without delay. Incomplete sensory suppression has also been observed using ipsilateral double stimulation to one side of the body.[26] Results indicate that stimulation to a proximal and distal segment [for example, the face and hand] on one side of the body will result in a distal [hand] stimulus suppression, to which the patient will report feeling only the proximal [face] stimulation.[22] Further evidence suggests that the parietal lobe gives rise to the processing of attention and awareness that is necessary for sensory perception. In studies of double stimulation in which the patient has their eyes open, incomplete extinction is eliminated when attention is directed to the application of stimulus on the affected side. This phenomenon is not observed in patients with complete extinction in which there is extensive damage to the parietal lobe, suggesting that the subsequent sensory suppression is not affected by expectant attention[22][26] Subtypes of amorphosynthesis, depending on the type of deficit, have been referred to as tactile amorphosynthesis, visual amorphosynthesis, and amorphosynthetic apraxia of speech or writing[18][22] ## Treatment[edit] Treatment of amorphosynthesis is often carried out by a variety of clinicians, neuropsychologists, physical therapists, occupational therapists, caretakers, speech-language pathologists and optometrists, depending on the severity and type of sensory suppression.[27] Rehabilitation consists of developing an individualized treatment plan that is designed to help the person address the deficits that are affecting them. Trained professions can help to improve communication and are primarily advised to direct attention to the contralesional [affected] side of the body. Although not all deficits have seen improvements after therapy, evidence suggests that many patients are able to live independently following treatment implementation[28][29] ## Signs and Symptoms[edit] S. Fazlullah, in his article Tactile Perceptual and Tactile-Amorphosynthesis in the Localization of Cerebral Lesions (1956), provides a detailed explanation of the specific signs and symptoms in amorphosynthesis caused by left and right parietal lobe lesions. ### Left Parietal Lobe Lesion[edit] Gerstmann syndrome: * A patient is unable to recognize his/her finger. * A patient is unable to differentiate right from left. * A patient makes mistakes while writing. * A patient is unable to name things. Parietal apraxia: * A patient is unable to understand or execute actions. Constructional apraxia: * A patient has trouble drawing. ### Right Parietal Lobe Lesion[edit] Anosognosia * A patient cannot perceive a defective function such as hemiplegia, or paralysis of one side of the body. Hemiasomatognosia * A patient cannot focus attention on the left side of the body and believes that this side of the body feels “strange.” Metamorphognosia * A patient perceives part of the body as too heavy or thick. Corporeal agnosia * A patient loses sensation in the left side of the body and mistakenly believes that an extremity has been lost. Phantom Sensations * A patient believes that a part of the body has doubled. Transposition of Parts of the Body * A patient neglects the left side of the body, always performing actions with her right and searching for her left extremities in places other than the hospital bed, such as a locker. Constructional apraxia * When asked to arrange, draw, or copy a simple model of one- to three-dimensional figures, a patient consistently neglects important details on the model's left side. For example, when asked to draw a figure of a few matchsticks, the patient would only draw the matchsticks on the figure's right side. Disorientation of space: * A patient is unable recognize depth of space. Agnosia of left portion of space: * A patient is unable to perceive sensation on the left of her body. * A patient is unable to see from the left eye. Anaesthoagnosia: * A patient has loss sensation on the left side of his/her body. Balint optic ataxia: * A patient is unable to see two things at once. * A patient is unable to coordinate ocular movement. * A patient is unable to see objects on the left peripheral field.[30] ## Primary Research[edit] ### Denny-Brown and Banker[edit] According to Denny-Brown's 1954 article[31] lesions of the parieto-occipital region cause disturbance of recognition in a patient – left-sided lesions usually cause agnosia, while right-sided lesions usually cause lack of recognition of the person's left side and extrapersonal space. Denny-Brown defines agnosia as a disorder in formation or use of symbolic concepts, such as recognizing body parts; in naming objects; in understanding numbers; or in understanding geographic and/or spatial location. It applies to both sides of a person, even though a lesion in only one side of the parietal lobe – the dominant one – causes it. He argues that amorphosynthesis, on the other hand, is usually caused by a lesion in the non-dominant parieto-occipital lobe and results in lack of awareness on the opposite side of the body. Before Denny-Brown, researchers such as Lange,[32] Dide,[33] Lenz,[34] and McFie and associates[35] proposed that the brain's right hemisphere controls a specific function in spatial perception, explaining why damage to the parieto-occipital lobe of the right hemisphere results in the loss of spatial perception. In his article, Denny-Brown alternately proposes that lesions of the parieto-occipital lobe cause errors in spatial summation, not spatial perception. By using a case study, he argues that amorphosynthesis actually may result from lesions of either side of the parietal lobe, depending on the patient's dominant hemisphere. He further argues that lesions in the dominant lobe cause both amorphosynthesis and agnosia – the agnosia just obscures the amorphosynthesis. ### Fazlullah[edit] According to Fazlullah's article[30] bilateral simultaneous and ipsilateral double stimuli in testing cutaneous (skin) sensations can help study the sensory suppression phenomenon called Tactile-Amorphosynthesis. ### Cherington and Yarnell[edit] According to Cherington and Yarnell's article[21] The game of chess can be used as a tool to study the visual perception of subjects who have a dominant hemisphere infarction, for that reason, it is useful to the understanding of the evolution of amorphosynthesis. ## Case Studies[edit] ### Denny-Brown: Amorphosynthesis From Left Parietal Lesion[edit] A 36 yr. old white married boilermaker named W.F. was admitted to the Boston City Hospital on March 23, 1953, after a week of general weakness and malaise. Three days before his admission, he developed a throbbing bilateral headache, and on the day of admission, he was unable to walk or support himself due to right-sided weakness. On the first day, his symptoms were severe – while he could perform simple movements of his right limbs, he did not feel pain, temperature, or touch on his right side and refused to acknowledge that his right limbs were his. In fact, he repeatedly threw his right arm from the hospital bed, believing that the arm did not belong to him. On the second day, W.F. was transferred to a neurological division for further examination. Even though he had been right handed his entire life, he ate, wrote, and held a cigarette in his left hand. When asked to extend his arms or grab an object with his right hand, he repeatedly hyperextended the fingers on his right hand without being conscious of doing so. He also shaved with his left hand and only on the left half of his face, not realizing there was anything wrong with his actions. When stimulated with pain, temperature, touch, and vibration, W.F. reported feeling these sensations on his right side but described them as “not as clear” as on the left. When both sides of his body were simultaneously stimulated, he was unable to distinguish sensation on his right side. Denny-Brown terms this phenomenon extinction, and for the first week, the patient's left side remained dominant over his right side. In addition, when stimulated by two points simultaneously on his right side, W.F. could not distinguish between them – the right side of his face was dominant over his right arm and leg, and his right leg over his right arm, throughout the first week. Importantly, W.F. gave no evidence of agnosia. He expressed himself clearly, named objects well, had no trouble finding his way about the hospital, and could even draw maps of Boston, Massachusetts, and the USA fairly well. He was able to identify all the parts of his body and distinguish right from left on his own body, and his initial belief that his right arm belonged to somebody else ceased after the second day of hospitalization. But he still had difficulty perceiving the right side of his body – even on the 12th day, he would properly put his left hand into the sleeve of his shirt when dressing but simply drape the shirt around his right side, not realizing he had done so. Even though left-sided lesions of the parieto-occipital lobe usually cause agnosia, W.F. appeared to have a left-sided lesion causing amorphosynthesis. Electroencephalograms, obtained on admission and a week later, showed focal slow waves in the left parietal and occipital leads, and the clinical diagnosis was a left anterior parietal lesion, most likely caused by a small hemorrhage in the brain. In analyzing W.F., Denny-Brown raises the question of why the patient's left-sided lesion caused amorphosynthesis rather than agnosia. In general, as Denny-Brown explains in his introduction, left-sided lesions cause agnosia while right-sided lesions cause amorphosynthesis. He gives two possible explanations – first, that the right hemisphere might be dominant in the patient, not the left. This would suggest that just as right-handed and left-handedness differ among the population, so too does the dominance of the parieto-occipital lobe. While Denny-Brown notes that he cannot refute this explanation, he sees it as more likely that the patient's lesion simply did not extend posteriorly to produce agnosia. Therefore, he argues that the difference between causes of amorphosynthesis and agnosia is directly related to the size and extension of the parieto-occipital lesion. As a whole, he concludes that amorphosynthesis of the opposite side of the body from a parieto-occipital lesion can occur on as a result of either left or right-sided lesion, even though amorphosynthesis from right parietal lesion is more commonly observed.[31] ### Fazlullah:Tactile Perception Rivalry And Tactile-Amorphosynthesis In The Localization Of Cerebral Lesions[edit] At the time of Fazlullah's writing, neurologists were interested in the clinical value of using bilateral simultaneous and ipsilateral double stimuli in testing sensations of the skin. This testing is applied simultaneously on two sides of the body. In such studies, patients are required to announce whether or not they can feel any type of sensation on either side of their body. Such procedures are meant to study the sensory suppression phenomenon present in tactile-amorphosynthesis. In Fazlullah's study, patients with parietal lesions were blindfolded and tested for tactile-amorphosynthesis by applying simultaneous stimulation on both sides of the body. Patients were then asked to report on the size, shape and nature of the presented object. Results determined that patients with a right parietal lobe lesions presented symptoms such as anosognosia, hemiasomatognosia, metamorphognosia, corporeal agnosia, phantom sensations, transposition of parts of the body, constructional apraxia, disorientation of space, agnosia of the left portion of space, anaesthoagnosia, and Balint optic ataxia, while patients with left parietal lobe lesions presented symptoms such as Gerstmann syndrome, parietal apraxia and construction apraxia. Other patients with symptoms of Tactile-Amorphosynthesis showed signs of lobe lesions in the sensory tract and the spinal cord glioma. For this reason, such studies as Fazlullah's suggest that patients with lesions in other regions of the brain or spinal cord can also develop tactile-amorphosynthesis.[30] ### Cherington: Amorphosynthesis on the Chess Board[edit] A 23-year-old college student who collapsed the day after a party due to the consumption of heroin showed signs of arterial branch disease in the interior, middle and left parietal veins through bilateral carotid angiography. Further testing, radio isotope scintigraphy, revealed the spread of a left parietal occipital tumor a week after. Once fully conscious, the patient showed signs of hemiparesis and deficit in right visual field. However, the patient was still able to speak with no sign of disturbance in language. By the 11th day, double simultaneous stimulation showed rare mistakes being made on the right side of his visual field as well as unawareness of the right side of his body. These symptoms caused a diagnosis of Amorphosynthesis. Although the patient made rare mistakes on the right side of his visual field, he also showed improvement when playing chess by correctly using his pieces, making more passive moves and blunts on the right side on the chessboard. Double simultaneous testing revealed a fully intact right visual field as well as movement. Stereognosis determined that the patient was capable of localizing touch on his right hand. In general, games can become useful when evaluating spatial perception problems such as those found in patients with amorphosynthesis. The improvements recorded from this patient are in relation with Denny-Brown and Welman's observations of patients with disordered visual spatial summations with dominant hemisphere lesions.[21] ## History[edit] * Oppenheim (1885, 1911) described the stimulation applied on individuals with hemiplegia on both sides of the body as “double stimulation”. * Head and Holmes (1911) observed Tactile-Amorphosynthesis on individuals with cortical disorders. * Bender (1945) observed Tactile-Amorphosynthesis in patients with parietal lobe lesions and termed it as “extinction”. * Critchley (1949) after reviewing the phenomenon suggested a more explanatory term, “Tactile inattention”. * Brain (1955) termed this suppression in sensory as “Perceptual rivalry”. * Present day, there is no agreement of the nature and terminology of Tactile-Amorphosynthesis and further research is not currently being pursued.[21] ## References[edit] 1. ^ Unsworth, C. A. [2007]. Cognitive and Perceptual Dysfunction. Philadelphia: Davis Company. 2. ^ Weintraub, S., Ahern, G. L., Daffner, K.R. & Price, B.H. [1992]. Right-sided hemispatial neglect. Neurology, 42[3]: 223. 3. ^ Mesulam, M-M. [1981]. A cortical network for directed attention and unilateral neglect. Ann Neurol, 10: 309-325. 4. ^ Mesulam, M-M. [1990]. Large-scale neurocognitive networks and distributed processing for attention, language and memory. Ann Neurol, 28: 597-613. 5. ^ Heilman, K. M. & Valenstein, E. [1979]. Neglect and related disorders. New York: Oxford University Press. 6. ^ Heilman, K. M. & Van Den Abell, T. [1980]. Right hemispheric dominance for attention: the mechanism underlying hemispheric asymmetries of inattention. Neurology, 30: 327-330. 7. ^ Gitelman, D. R., Alpert, N., Kosslyn, S., Daffner, K., Scinto, L., Thompson, W. & Mesulam, M-M. [1994]. Functional imaging of exploratory attentional movements. Neurology, 44: 328. 8. ^ Reivich, M., Gur, R. & Alavi, A. [1983]. Positron emission tomographic studies of sensory stimuli, cognitive processes and anxiety. Hum Neurobiol, 2: 25-33. 9. ^ Iachini, T., Ruggiero, G., Conson, M. & Trojano, L. [2009]. Lateralization of egocentric and allocentric spatial processing after parietal brain lesions. Brain and Cognition, 69[3]: 512-520. 10. ^ a b Weintraub, S., Daffner, K. R, Ahern, G. L., Price, B. H., & Mesulam, M-M. [1996]. Right-sided hemispatial neglect and bilateral cerebral lesions. J Neurol Neurosurg Psychiatry, 60: 342-344. 11. ^ 11\. Blakemore, S. & Frith, U. [2005]. The Learning Brain. Oxford: Blackwell Publishing. 12. ^ Penfield, W., & Rasmussen, T. [1950]. The cerebral cortex of a man: A clinical study of localization of function. New York: Macmillan. 13. ^ Saladin, K.S. [2004]. Anatomy and Physiology. New York: McGraw-Hill. 14. ^ Fogassi, L. & Luppino, G. [2005]. Motor functions of the parietal lobe. Current Opinion in Neurobiology, 15: 626-631. 15. ^ a b Denny-Brown, D. & Banker, B. Q [1954]. Amorphosynthesis from left parietal lesion. AMA Arch Neurol Psychiatry, 71[3]: 302-313. 16. ^ Kim, M., Na, D.L., Kim, G.M., Adair, J.C., Lee, K.H. & Heilman, K.M. [1999]. Ipsilateral neglect: behavioural and anatomical features. J Neurol Neurosurg Psychiatry, 67: 35-38. 17. ^ Association for Research in Nervous and Mental Disease [1958]. The brain and human behaviour. Ulster Med J., 27[2]: 173-174. 18. ^ a b Hinterbuchnes, L. [1974]. Aphasia. N Y Acad Med., 50[5]: 589-601. 19. ^ Karnath, H. [1997]. Spatial orientation and the representation of space with parietal lobe lesions. Philos Trans R Soc Lond B Biol Sci., 352[1360]: 1411-9. 20. ^ Adam and Victor's Principles of Neurology 21. ^ a b c d Cherington, Michael, and Philip Yarnell. "Amorphosynthesis on the Chess Board." Scandinavian Journal of Rehabilitation Medecine 7, no. 4 (February 1975): 176-78. . 22. ^ a b c d Fazlullah, M. [1956]. Tactile perceptual rivalry and tactile-amorphosynthesis in the localization of cerebral lesions. Postgrad Medical Journal, 32[369]: 338-346. 23. ^ a b Brozzoli, C., Dematte, M. L., Pavani, F., Frassinetti, F. & Farne, A. [2006]. Neglect and extinction: within and between sensory modalities. Restor Neurol Neurosci, 24[4]: 217–232. 24. ^ a b Haan, B., Karnath, H. O. & Driver, J. [2012]. Mechanisms and anatomy of unilateral extinction after brain injury. Neuropsychologia, 50[6]: 1045–53. 25. ^ a b Kim, M., Na, D. L., Kim, G. M., Adair, J. C., Lee, K. H. & Heilman, K. M. [1999]. Ipsilesional neglect: behavioural and anatomical features. Journal of Neurology, Neurosurgery & Psychiatry, 67: 35–38. 26. ^ a b c Vaishnavi, S., Calhoun, J., Southwood, M. H. & Chatterjee, A. [2000]. Sensory and response interference by ipsilesional stimuli in tactile extinction. Cortex, 36[1]: 81–92. 27. ^ Pierce S. R. & Buxbaum L. J. [2002]. Treatments of unilateral neglect: A review. Archives of Physical Medicine and Rehabilitation, 83[2]: 256–268. 28. ^ Hellweg, S. & Johannes, S. [2008]. Physiotherapy after traumatic brain injury: A systematic review of the literature. Brain Injury, 22[5]: 365–373. 27. 29. ^ Watson, M. [2001]. Do patients with severe traumatic brain injury benefit from physiotherapy? A review of the evidence. Physical therapy Reviews, 6: 233-249. 30. ^ a b c Fazlullah, S. "Tactile Perceptual Rivalry and Tactile-Amorphosynthesis in the Localization of Cerebral Lesions." Postgraduate Medical Journal 32, no. 369 (July 1956): 338-52. 31. ^ a b Denny-Brown, D., and Betty Q. Banker. "Amorphosynthesis from Left Parietal Lesion." A.M.A. Archives of Neurology and Psychiatry 71, no. 3 (March 1954): 302-13. 32. ^ Lange, J.: Agnosien und Apraxien, in Bumke, O., und Foerster, O.: Handbuch der Neurologie, 1936, Vol. 6, pp. 807-960. 33. ^ Dide, M.: Diagnostic anatomo-clinique de desorientations temporo-spatiales, Rev. neurol. 69:720-725, 1938. 34. ^ Lenz, H.: Raumsinnstorung bei Hirnverletzungen, Deutsche Ztschr. Nervenh. 157:22-64, 1944. 35. ^ McFie, J.; Piercy, M. F., and Zangwill, O. L.: Visuo-Spatial Agnosia Associated with Lesions of the Right Cerebral Hemisphere, Brain 75:433-471, 1952 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Amorphosynthesis	c0278179	2,773	wikipedia	https://en.wikipedia.org/wiki/Amorphosynthesis	2021-01-18T19:01:33	{"umls": ["C0278179"], "wikidata": ["Q4747782"]}
Diffuse infantile fibromatosis is a condition affecting infants during the first 3 years of life. It is usually confined to the muscles of the arms, neck, and shoulder area.[1]:607 There is a multicentric infiltration of muscle fibers with fibroblasts resembling those seen in aponeurotic fibromas.[1]:607 ## See also[edit] * Skin lesion ## References[edit] 1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. This Dermal and subcutaneous growths 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Diffuse infantile fibromatosis	c0406580	2,774	wikipedia	https://en.wikipedia.org/wiki/Diffuse_infantile_fibromatosis	2021-01-18T18:30:52	{"wikidata": ["Q5275414"]}
A rare neoplastic disease characterized by a localized, unifocal, low-grade tumor composed of mature mast cells, without evidence of systemic mastocytosis or skin lesions. The tumor most commonly arises in the lung and shows a non-destructive growth pattern. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Extracutaneous mastocytoma	c0272202	2,775	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66662	2021-01-23T18:33:40	{"mesh": ["D034801"], "umls": ["C0272202"], "icd-10": ["C96.2"]}
## Description Partial dorsal agenesis, or congenital short pancreas, is characterized by the presence of the accessory papilla, the terminal end of the main dorsal duct of Santorini, or the pancreatic body. All of these structures are missing in complete dorsal agenesis of the pancreas (Wildling et al., 1993). Clinical Features Wildling et al. (1993) reported complete agenesis of the dorsal pancreas in a woman who developed insulin-dependent diabetes mellitus at the age of 39 years. The diagnosis was suspected by abdominal ultrasound and confirmed by abdominal computed tomography (CT), magnetic resonance imaging, and endoscopic retrograde pancreatography. Her exocrine pancreatic function was essentially normal. Both of her sons, each by a different father, likewise had agenesis of the dorsal pancreas by CT but no evidence of diabetes mellitus. A daughter was unaffected. Inheritance Wildling et al. (1993) suggested that the transmission pattern in the family they reported with agenesis of the dorsal pancreas was consistent with autosomal dominant or X-linked dominant inheritance. INHERITANCE \- Autosomal dominant ABDOMEN Pancreas \- Enlarged pancreatic head \- Absent corpus, tail and uncinate process ENDOCRINE FEATURES \- Diabetes mellitus, susceptibility to ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	PANCREAS, DORSAL, AGENESIS OF	c1850096	2,776	omim	https://www.omim.org/entry/167755	2019-09-22T16:36:43	{"mesh": ["C564908"], "omim": ["167755"], "orphanet": ["2805"]}
Juvenile plantar dermatosis Other namesAtopic winter feet,[1] Dermatitis plantaris sicca,[1] Forefoot dermatitis,[1] Moon-boot foot syndrome,[1] and Sweaty sock dermatitis[1] SpecialtyDermatology Juvenile plantar dermatosis is a condition usually seen in children between the ages of 3 and 14, and involves the cracking and peeling of weight bearing areas of the soles of the feet.[1] One of the earliest descriptions was made by British dermatologist Darrell Wilkinson.[2] ## See also[edit] * Sulzberger–Garbe syndrome * List of cutaneous conditions ## References[edit] 1. ^ a b c d e f Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ "Munks Roll Details for Peter Edward Darrell Sheldon Wilkinson". munksroll.rcplondon.ac.uk. Retrieved 2017-11-10. ## External links[edit] Classification D * ICD-10: L30.1 (ILDS L30.170) * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji * 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 chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Juvenile plantar dermatosis	c0406302	2,777	wikipedia	https://en.wikipedia.org/wiki/Juvenile_plantar_dermatosis	2021-01-18T18:40:46	{"umls": ["C0406302"], "icd-10": ["L30.1"], "wikidata": ["Q6318967"]}
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 23 (MC1DN23) is caused by homozygous mutation in the NDUFA12 gene (614530) on chromosome 12q22. One such patient has been reported. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Ostergaard et al. (2011) reported a 10-year-old girl, born of consanguineous Pakistani parents, with mitochondrial complex I deficiency manifesting as Leigh syndrome (see 256000). The patient had delayed motor development, with walking at age 20 months. From age 2 years, she showed progressive loss of motor abilities and developed scoliosis and dystonia. At age 10 years, she had poor growth, used a wheelchair, and had severe muscular atrophy and hypotonia. Hypertrichosis was noted. Vision and hearing were normal, and she attended a special school where she had learned to read and write. Molecular Genetics In a 10-year-old girl, born of consanguineous Pakistani parents, with complex I deficiency manifesting as Leigh syndrome, Ostergaard et al. (2011) identified a homozygous nonsense mutation in the NDUFA12 gene (614530.0001). The mutation was identified by homozygosity mapping followed by candidate gene sequencing. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor overall growth SKELETAL Spine \- Scoliosis SKIN, NAILS, & HAIR Hair \- Hypertrichosis MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle atrophy NEUROLOGIC Central Nervous System \- Delayed motor development \- Delayed walking \- Progressive loss of motor abilities \- Dystonia \- Learning difficulties \- White matter abnormalities consistent with Leigh syndrome LABORATORY ABNORMALITIES \- Mitochondrial complex I deficiency in various tissues MISCELLANEOUS \- Onset in early childhood \- Progressive disorder \- One patient, born of consanguineous Pakistani parents, has been reported (last curated January 2019) MOLECULAR BASIS \- Caused by mutation in the NADH-ubiquinone oxidoreductase subunit A12 gene (NDUFA12, 614530.0001 ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 23	None	2,778	omim	https://www.omim.org/entry/618244	2019-09-22T15:42:58	{"omim": ["618244"], "orphanet": ["255241"], "synonyms": ["Infantile subacute necrotizing encephalopathy with leukodystrophy", "Leigh disease with leukodystrophy"]}
Phosphoserine aminotransferase deficiency is an extremely rare form of serine deficiency syndrome (see this term) characterized clinically in the two reported cases to date by acquired microcephaly, psychomotor retardation, intractable seizures and hypertonia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Phosphoserine aminotransferase deficiency, infantile/juvenile form	c1970253	2,779	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284417	2021-01-23T17:10:12	{"mesh": ["C567032"], "omim": ["610992"], "umls": ["C1970253"], "icd-10": ["E72.8"], "synonyms": ["PSAT deficiency, infantile/juvenile form"]}
## Summary ### Clinical characteristics. NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of NTRK1-CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common. ### Diagnosis/testing. The diagnosis of NTRK1-CIPA is established in a proband with suggestive clinical findings and biallelic pathogenic variants in NTRK1 identified by molecular genetic testing. ### Management. Treatment of manifestations: Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology. For anhidrosis: Monitoring body temperature helps to institute timely measures to prevent/manage hyperthermia or hypothermia. For insensitivity to pain: Modify as much as reasonable a child’s activities to prevent injuries. Inability to provide proper immobilization as a treatment for orthopedic injuries often delays healing; additionally, bracing and invasive orthopedic procedures increase the risk for infection. Methods used to prevent injuries to the lips, buccal mucosa, tongue, and teeth include tooth extraction, and/or filing (smoothing) of the sharp incisal edges of teeth, and/or use of a mouth guard. Skin care with moisturizers can help prevent palmar and plantar hyperkeratosis and cracking and secondary risk of infection; neurotrophic keratitis is best treated with routine care for eyes, prevention of corneal infection, and daily observation of the ocular surface. Interventions for behavioral, developmental, and motor delays as well as educational and social support for school-age children and adolescents are recommended. Surveillance: Daily evaluation by parents and caregivers for early signs of otherwise unrecognized injury. Regular examinations by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology to help prevent serious injuries and initiate early treatment. Annual follow up at a center that provides comprehensive care and communication between the various subspecialties that are needed for optimal care. Agents/circumstances to avoid: Hot or cold environments; hot or cold foods; hot showers or baths; jumping or high-impact activities and sports. Evaluation of relatives at risk: If the NTRK1 pathogenic variants in a family are known, molecular genetic testing can clarify the genetic status of at-risk infants, so that those who are affected can be monitored to avoid hyperpyrexia and its potential complications and oral injuries when the primary teeth erupt. ### Genetic counseling. NTRK1-CIPA results from the presence of two NTRK1 pathogenic variants. Typically one pathogenic variant is inherited from each parent (autosomal recessive inheritance); however, in some instances both pathogenic variants are from one parent (uniparental isodisomy). * Autosomal recessive (AR) inheritance. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. * Uniparental isodisomy. The risk to sibs of an affected individual is not increased over that of the general population. For AR inheritance, once the NTRK1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. For uniparental isodisomy, once the NTRK1 pathogenic variant has been identified in an affected family member, carrier testing for at-risk family members is possible. ## Diagnosis ### Suggestive Findings NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) should be suspected in individuals with the following clinical findings and family history. Clinical findings * Impaired perception of pain: * In infants. Biting of the tongue, lips, or fingers after the first teeth erupt * In older individuals. Repeated traumatic injuries including bruising, bone fractures, and painless joint dislocations often associated with neurogenic arthropathy (Charcot joint) of the knees and ankles. * A history of failure to recognize burns and other injuries * Failure of painful stimuli fail to evoke either withdrawal or emotional change. For example, no tenderness or pain sensation is elicited even when apparently injured joints or broken bones are moved passively or actively. * Impaired visceral pain perception * Impaired temperature perception, confirmed when: * Consistent errors are made in distinguishing between hot and cold moist substances; * Extreme cold or heat fails to elicit the usual withdrawal response. * Anhidrosis (absence of sweating), manifesting as recurrent febrile episodes beginning in early infancy * Impairment of the autonomic nervous system, which may be evident by the presence of Horner syndrome and the cold pressor test * Intellectual disability Family history consistent with autosomal recessive inheritance, including affected sibs in a single generation, simplex cases (i.e., a single affected family member), and/or parental consanguinity ### Establishing the Diagnosis The diagnosis of NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is established in a proband with biallelic pathogenic variants in NTRK1 identified by molecular genetic testing (see Table 1). Note: Identification of biallelic NTRK1 variants of uncertain significance (or identification of one known NTRK1 pathogenic variant and one NTRK1 variant of uncertain significance) does not establish or rule out a diagnosis of this disorder. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of NTRK1-CIPA has not been considered – perhaps because they are too young to manifest the full spectrum of clinical findings – are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 Single-gene testing. Sequence analysis of NTRK1 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. Note: Targeted analysis for pathogenic variants can be performed first in individuals of the following ancestry (see Table 5): * Israeli Bedouins. Variant p.Pro621SerfsTer12 accounts for 89% of pathogenic variants [Shatzky et al 2000]. * Japanese. Variant p.Arg554GlyfsTer104 accounts for more than 50% of pathogenic variants, c.851-33T>A for 13%, and p.Asp674Tyr for 10% [Indo 2001]. Note: Homozygosity for an NTRK1 pathogenic variant in an individual with NTRK1-CIPA may be the result of uniparental isodisomy for chromosome 1 (i.e., two copies of the chromosome 1 with the NTRK1 pathogenic variant are inherited from one parent and no copy of chromosome 1 is inherited from the other parent). Therefore, accurate recurrence risk counseling relies on testing both parents to determine if each is heterozygous for that NTRK1 variant (see Genetic Counseling). A multigene panel that includes NTRK1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in NTRK1 Congenital Insensitivity to Pain with Anhidrosis View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method NTRK1Sequence analysis 3>97% 4, 5 Gene-targeted deletion/duplication analysis 6<3% 7, 8 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Miura et al [2000b], Indo [2001], Geng et al [2018], Li et al [2019], and data derived from the subscription-based professional view of Human Gene Mutation Databas [Stenson et al 2017] 5\. While two variants common in Asian populations, c.851-33T>A and c.[851_798C>T;851_794C>G], are detectable by sequence analysis, they are outside the range normally analyzed [Indo 2001, Geng et al 2018, Li et al 2019]. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 7\. Huehne et al [2008], Geng et al [2018], Xue et al [2018], Li et al [2019] 8\. Detection rate varies by population. An intragenic deletion was observed in multiple Chinese families [Geng et al 2018]. ## Clinical Characteristics ### Clinical Description NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by profound sensory loss affecting pain and temperature perception, absence of sweating (anhidrosis), and intellectual disability. Anhidrosis. Because sweating plays an important role in maintaining normal body temperature, anhidrosis (the failure to sweat) disturbs thermoregulation in hot environmental conditions and increases susceptibility to recurrent febrile episodes [Indo 2002, Indo 2018]. Recurrent episodic fevers, usually the first clinical sign of NTRK1-CIPA, can begin in infancy or early childhood depending on environmental temperature. Recurrent febrile convulsions are also observed in some affected infants. Occasionally, hypothermia is observed in cold environments. Anhidrosis is present on the trunk and upper extremities in 100% of cases and more variable in other areas of the body [Ismail et al 1998, Axelrod 2002]. Although with warming the intertriginous areas of the neck, axillae, and groin can become slightly moist, no definite sweating is noted. This moisture is probably due to delayed insensible water loss. Insensitivity to pain. While impaired pain perception may not be apparent in early infancy, parents may recall that their infant with NTRK1-CIPA did not cry during venipuncture or immunizations [Indo 2002, Indo 2018]. Tongue ulcers and fingertip biting, the characteristic self-mutilation signs observed in infants with NTRK1-CIPA, begin when the primary incisors erupt, and can result in a bifid or absent tongue. Although taste buds are normal, traumatic injuries of the tongue, such as a partial loss of papillae and scar formation, may cause secondary hypogeusia or decreased taste sensation [Amano et al 1998]. Biting of the fingers and ulcerated fingertips is common. Bruises, cuts, and burns do not elicit normal reactions and are often unrecognized at the time that they occur. Accidental injuries such as falls or burns lead to multiple scars and can lead to cellulitis in the skin. Orthopedic problems are one of the most characteristic and serious complications of NTRK1-CIPA [Bar-On et al 2002, Kim et al 2013]. Frequent orthopedic complications: * Multiple fractures often with hyperplastic new bone formation, avascular necrosis, and osteomyelitis * Auto-amputation, self-mutilation (including self-inflicted soft tissue injuries) * Leg length discrepancy * Joint subluxation and dislocation resulting in Charcot neuroarthropathy of the feet, ankles, knees, and hips * Septic arthritis * Progressive scoliosis Amputations of fingers or limbs are common as a result of these complications. Decreased pain perception does not spare any area, affecting even cranial nerves and visceral sensation [Yagev et al 1999, Shorer et al 2001]. Neurotrophic keratitis (degenerative disease of the corneal epithelium resulting from impaired corneal sensation) manifests initially as superficial punctate keratopathy which later can result in corneal ulceration and even perforation [Yagev et al 1999, Amano et al 2006, Mimura et al 2008]. Of note, tearing (both overflow or emotional) is normal. Intellectual disability. Most individuals with NTRK1-CIPA have varying degrees of intellectual disability and show characteristic behaviors [Indo 2002, Indo 2018]. Affected individuals show defects in conceptual thinking, abstract reasoning, and social behavior, as well as moderate to severe emotional disturbance. Some may exhibit rage. Assessments of cognitive and adaptive behavior suggest that many children with NTRK1-CIPA have intellectual disability (or learning disabilities) and severe attention-deficit/hyperactivity disorder [Levy Erez et al 2010]. Irritability, hyperactivity, impulsivity, and acting-out behaviors typically improve with age. The prognosis for independent functioning varies. Other * Often the skin is dry with lichenification; the nails are dystrophic. Palmoplantar hyperkeratosis (thickening of the soles and the palms) appears in late infancy, often with scars and abrasions [Bonkowsky et al 2003]. Significant fissuring of the plantar skin is common. Some affected individuals develop deep heel ulcers that are slow to heal [Mardy et al 1999]. * Hypotonia is seen frequently in the early years, but strength and tone normalize as the individual gets older; tendon reflexes are normal [Axelrod 2002]. * Gastrointestinal dysmotility is mild or absent. * Vomiting is not a feature, but can be observed in some affected individuals. * Speech is usually clear. Normal findings * Touch, vibration, and position senses * Motor functions (unless repeated trauma has caused secondary dysfunction of motor neurons or limbs) * Deep tendon reflexes and superficial abdominal and cremasteric reflexes Neurophysiology of NTRK1-CIPA See Indo [2018] (full text) for information on the neurophysiology of NTRK1-CIPA. ### Genotype-Phenotype Correlations Clinical phenotype varies widely even among individuals with the same two NTRK1 pathogenic variants [Shatzky et al 2000]. ### Nomenclature Terms previously used to describe NTRK1-CIPA include: * Familial dysautonomia type II * Congenital sensory neuropathy with anhidrosis ### Prevalence While NTRK1-CIPA (or HSAN IV) has been reported worldwide, it is extremely rare in most populations except the Japanese and Israeli Bedouins. Of note, the number of Japanese with NTRK1-CIPA was estimated between 130 and 210 [Haga et al 2015]. Relatively common founder pathogenic variants have been reported in the Japanese and Israeli Bedouin populations [Miura et al 2000b, Shatzky et al 2000, Indo 2001] (see Table 5): * Three variants – c.851-33T>A, p.Arg554GlyfsTer104, and p.Asp674Tyr – account for roughly 70% of pathogenic NTRK1 variants among Japanese. * One variant – p.Pro621SerfsTer21 – accounts for 89% of pathogenic NTRK1 variants among Israeli Bedouins [Shatzky et al 2000, Indo 2001]. Half of reported affected individuals are offspring of consanguineous parents [Axelrod 2002]. Specific carrier frequencies are not available. ## Differential Diagnosis The differential diagnosis of NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) includes other genes associated with congenital insensitivity to pain (see Congenital Insensitivity to Pain Overview) as well as other hereditary disorders (see Table 2) and acquired conditions (see Table 3) with clinical manifestations similar to those of NTRK1-CIPA. ### Table 2. Hereditary Disorders in the Differential Diagnosis of NTRK1-CIPA View in own window Gene(s)DisorderMOIClinical Features of Differential Disorder Overlapping w/NTRK1-CIPADistinguishing from NTRK1-CIPA COL1A1 COL1A2COL1A1/2-related osteogenesis imperfectaADMultiple fractures * Fractures cause pain & occur w/minimal or no trauma. * Assoc w/other features incl blue sclera, short stature, joint hypermobility, deafness EDA EDAR EDARADDHypohidrotic ectodermal dysplasiaXL AR AD * Hypohidrosis * Risk of hyperthermia Insensitivity to pain not a feature ELP1 (IKBKAP)Familial dysautonomia (HSAN III)AR↓ pain from birthGI dysfunction, vomiting crises, recurrent pneumonia, cardiovascular & temperature instability HPRT1Lesch-Nyhan syndromeXLProgressive self-injurious behavior (biting fingers, hands, lips, cheeks; banging the head or limbs) * Hyperuricemia * Progressive, severe DD/ID * Abnormal involuntary movements MPV17MPV17-related hepatocerebral mitochondrial DNA depletion syndromeAR * Absent pain responses from birth * DD * Infantile-onset liver dysfunction typically → liver failure; failure to thrive, lactic acidosis, & hypoglycemia * More severe neurologic involvement; may incl white matter abnormalities on MRI & seizures NGFNGF-CIPA 1 (HSAN V)ARInsensitivity to pain, anhidrosis, & ID 1, 2NGF-CIPA & NTRK1-CIPA cannot reliably be differentiated on a clinical basis. 2 AD = autosomal dominant; AR = autosomal recessive; CIPA = congenital insensitivity to pain with anhidrosis; DD = developmental delay; GI = gastrointestinal; HSAN = hereditary sensory and autonomic neuropathy; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. Carvalho et al [2011] 2\. Indo [2012] ### Table 3. Acquired Conditions in the Differential Diagnosis of NTRK1-CIPA View in own window DisorderOverlapping Clinical FeaturesClinical Features of the Disorder Distinguishing from NTRK1-CIPA Leprosy 1 * Insensitivity to pain * Painless injuries * Skin lesions (hypopigmented macules, nodules, plaques, or diffuse skin infiltration) * Enlargement of peripheral nerves * Localized (not universal) insensitivity to pain * Absence of anhidrosis Non-accidental /abusive injuryMultiple unexplained injuries * Normal response to pain (although caregivers may deny this) * Different pattern of injuries (proportionate to size & development) * Absence of anhidrosis 1\. Daneshjou et al [2012], Iftikhar & Javed [2013] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with NTRK1 Congenital Insensitivity to Pain Disorders View in own window System/ConcernEvaluationComment AnhidrosisPhysical exam of the skinAssess for dry skin & palmoplantar hyperkeratosis (often assoc w/cracking); determine if individual is using skin moisturizer daily. Regulation of body temperatureInquire about history of hyperthermia or hypothermia. Insensitivity to painMultiple unintentional injuriesPhysical exam of whole bodyAssess for bruises, cuts, & burns, as well as fingertip biting. Orthopedic injuriesExam of bones & joints by an orthopedistAssess for fractures, avascular necrosis, septic arthritis/osteomyelitis, self-mutilation, joint subluxation, Charcot neuroarthropathy, leg length discrepancy, & scoliosis. Dental risks for injuryExam for oral lesionsAssess for traumatic lingual injuries, burns, self-biting, auto-extraction of teeth, & overall dental health. Neuropathic keratitisOphthalmologic examAssess for superficial punctate keratopathy & corneal ulceration/perforation/infection. Developmental delayNeurologic exam & standardized tests for developmental milestonesAssess for DD & ID, incl defects in conceptual thinking & abstract reasoning. Behavioral problemsFormal eval of cognitive & adaptive functionsAssess for social behaviors & emotional disturbances; ADHD. Genetic counselingBy genetics professionals 1To inform affected persons & families re nature, MOI, & implications of NTRK1-CIPA in order to facilitate medical & personal decision making Family support/ResourcesAssess: * Use of community or online resources incl Parent to Parent; * Need for social work involvement for parental support. ADHD = attention-deficit/hyperactivity disorder; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance 1\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Treatment of Manifestations Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology at a center that provides comprehensive care and communication between the various subspecialties that are needed for optimal care. It is important to provide assistance and encourage therapies for behavioral, developmental, and motor delays that are appreciated during infancy and early childhood as well as to provide educational and social support for school-age children and adolescents. For details see Table 3, Congenital Insensitivity to Pain Overview. ### Prevention of Primary Manifestations For details see Table 4, Congenital Insensitivity to Pain Overview. ### Prevention of Secondary Complications For details see Table 5, Congenital Insensitivity to Pain Overview. ### Surveillance In addition to daily evaluation by parents and caregivers for early signs of otherwise unrecognized injury, regular examinations by a pediatrician, orthopedist, dentist, dermatologist, and ophthalmologist are recommended to assess and advise on various physical, mental, and behavioral problems. For details, see Table 6, Congenital Insensitivity to Pain Overview. ### Agents/Circumstances to Avoid Avoid the following: * Hot or cold environments; hot or cold foods; hot showers or baths * Jumping or high-impact activities and sports ### Evaluation of Relatives at Risk If the NTRK1 pathogenic variants in a family are known, molecular genetic testing may be used to clarify the genetic status of at-risk infants so that those who are affected can be monitored to avoid: * Hyperpyrexia and its potential complications, including febrile seizures; * Injuries to the tongue, lips, and teeth when the primary teeth erupt. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Women with CIP are able to become pregnant and bear children normally; however, reports regarding pregnancy in women with NTRK1-CIPA are rare. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	NTRK1 Congenital Insensitivity to Pain with Anhidrosis	None	2,780	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1769/	2021-01-18T21:08:57	{"synonyms": ["Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV)"]}
A number sign (#) is used with this entry because of evidence that septooptic dysplasia can be caused by mutation in the homeobox gene HESX1 (601802) on chromosome 3p14. Mutation in the HESX1 gene can also cause combined pituitary hormone deficiency-5 (CPHD5), without associated optic nerve hypoplasia or defects of midline brain structures. For a discussion of phenotypic and genetic heterogeneity of CPHD, see CPHD1 (613038). Growth hormone deficiency with pituitary anomalies can also be caused by mutation in the HESX1 gene. Description Septooptic dysplasia is a clinically heterogeneous disorder loosely defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum (Dattani et al., 1998). The diagnosis of this rare congenital anomaly is made when 2 or more features of the classic triad are present. Approximately 30% of patients have complete manifestations, 62% display hypopituitarism, and 60% have an absent septum pellucidum. The disorder is equally prevalent in males and females and is more common in infants born to younger mothers, with a reported incidence of 1 in 10,000 live births (summary by Webb and Dattani, 2010). Also see 516020.0012 for a form of septooptic dysplasia associated with cardiomyopathy and exercise intolerance. Clinical Features According to Rush and Bajandas (1978), the term 'septooptic dysplasia' was coined in 1956 by de Morsier, who pointed out the association of optic nerve hypoplasia and absence of the septum pellucidum. Hoyt et al. (1970) reported the association of pituitary dwarfism. Brook et al. (1972) described 4 unrelated children with hypoplastic optic nerves, absent septum pellucidum, and endocrinologic abnormalities. Harris and Haas (1972) noted that septooptic dysplasia is characterized by hypoplastic optic discs with characteristic double margin, an absent septum pellucidum, and growth hormone (GH; 139250) deficiency. Harris and Haas (1972) stated that there was no evidence for a mendelian basis for septooptic dysplasia syndrome. Benner et al. (1990) reported one of the few familial occurrences: a brother and sister had features of septooptic dysplasia including bilateral optic nerve hypoplasia, absent septum pellucidum, and partial pituitary insufficiency. Additionally, midline central nervous system abnormalities of the corpus callosum and cerebellum were demonstrated. The posterior fossa changes suggested a variant of the Dandy-Walker syndrome (220200). Willnow et al. (1996) reported studies on 18 patients with septooptic dysplasia. CCT or MRI yielded the following results: 4 patients had cavum septum pellucidum, 3 patients had hypoplasia of the cerebellum, 1 had aplasia of the corpus callosum, and 1 had aplasia of the fornix. An empty sella with or without an ectopic pituitary was seen in 4 cases. Severe psychomotor retardation was present in 14 of the 18 patients. All patients had short stature. Head circumference and weight were within normal limits. A high prevalence of pituitary dysfunction was revealed, most commonly GH deficiency and failure of the pituitary to respond to thyrotropin releasing hormone (TSH; 613879). Wales and Quarrell (1996) described a sister and brother from a consanguineous mating in whom septooptic dysplasia was present, suggesting mendelian inheritance. The female was born with dislocation of the hip and talipes equinovarus. Hypoglycemia developed at 7 hours, at which time blood tests revealed undetectable levels of GH, adrenocorticotropic hormone (ACTH), luteinizing hormone (LH; 152780), and follicle-stimulating hormone (FSH; 136530). Anterior pituitary hormone replacement therapy was begun at 7 days and she remained well subsequently. CT scan of the brain demonstrated absent septum pellucidum and corpus callosum. Vision and optic disc examination were normal at 18 months. At birth, the male was found to have micropenis and cryptorchidism, and hypoglycemia was detected at 4 hours of age. There were no other congenital abnormalities. Because of low hormone levels, full anterior pituitary hormone replacement was started on the first day. He subsequently developed profound but transient hypocalcemia which responded to calcium and vitamin D supplements. Repeat CT scanning showed absence of the septum pellucidum and corpus callosum. A double second-cousin had nesidioblastosis (256450), a probably unrelated disorder (see also craniotelencephalic dysplasia, 218670). Brain imaging of the affected sibs by Brickman et al. (2001) showed undescended or ectopic posterior pituitary. Brodsky et al. (1997) described sudden and unexpected death in 5 children with septooptic dysplasia. All children had corticotropin deficiency, all had thermoregulatory disturbances, and 4 children had diabetes insipidus. In at least 4 children, clinical deterioration was caused by fever and dehydration from a presumed viral illness, which appeared to precipitate adrenal crisis. Thomas et al. (2001) noted that the septooptic dysplasia phenotype is highly variable, with 62% of affected individuals having associated hypopituitarism and 30% displaying all 3 manifestations, including optic nerve hypoplasia and agenesis of midline structures. In a study group comprising 55 optic nerve hypoplasia patients, Birkebaek et al. (2003) reported that 49% had an abnormal septum pellucidum on MRI, and 64% had a hypothalamic-pituitary axis abnormality. Twenty-seven patients (49%) had endocrine dysfunction, and 23 of these had hypothalamic-pituitary axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal septum pellucidum (56%) than a normal septum pellucidum (39%). Patients were divided into 4 groups based on septum pellucidum and hypothalamic-pituitary axis appearance: (1) both normal; (2) abnormal septum pellucidum and normal hypothalamic-pituitary axis; (3) normal septum pellucidum and abnormal hypothalamic-pituitary axis; and (4) both abnormal. The frequency of multiple pituitary hormone deficiency was highest (56%) in group 4, lower (35%) in group 3, and even lower (22%) in group 2. Precocious puberty was most common in group 2. None of the patients in group 1 had endocrine dysfunction. The authors concluded that septum pellucidum and hypothalamic-pituitary axis appearances on MRI can be used to predict the likely spectrum of endocrinopathy. Stevens and Dobyns (2004) reported a boy with optic nerve hypoplasia, pituitary dysfunction, and MRI findings consistent with septooptic dysplasia, who also had multiple limb defects suggestive of amniotic bands. The authors reviewed 5 similar cases from the literature and concluded that there is evidence for a vascular pathogenesis of septooptic dysplasia in some patients. Harrison et al. (2004) reported another male infant with septooptic dysplasia and limb malformations, including syndactyly of several fingers and toes, hypoplastic digits, and ring constriction of at least 1 finger. He had bilateral hypoplastic optic nerves, absence of the septum pellucidum, and colpocephaly with a normal pituitary-hypothalamic axis. McNay et al. (2007) studied 210 patients with septooptic dysplasia for whom detailed clinical information was available and stated that 60 (29%) of the patients displayed the full spectrum (optic nerve hypoplasia (ONH), midline forebrain defects, and hypopituitarism), whereas 2 of the 3 features were present in 150 (71%) of the patients: 38 (18%) had ONH and midline defects, 83 (39%) had ONH and hypopituitarism, and 29 (14%) had hypopituitarism and midline defects. Webb and Dattani (2010) reviewed septooptic dysplasia, noting that there is a wide variation in the severity of the clinical features found and in their association with other diagnoses, which follows no clear pattern. The main reported clinical findings are hypopituitarism (62% to 80%), with growth hormone deficiency being the commonest endocrine abnormality; visual impairment, which is severe in 23% of patients; and developmental delay, which is more common in children with bilateral (57%) than unilateral (32%) optic nerve hypoplasia. Seizures, developmental delay, and cerebral palsy are the most frequent neurologic associations. Molecular Genetics In 2 sibs with septooptic dysplasia reported by Wales and Quarrell (1996), Dattani et al. (1998) demonstrated homozygosity for a missense mutation in the HESX1 gene (601802.0001). Genetic analysis of the HESX1 gene in 18 patients with sporadic septooptic dysplasia revealed no abnormalities, suggesting that mutations in the HESX1 gene are not a frequent occurrence in sporadic disease. Thomas et al. (2001) scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to septooptic dysplasia with panhypopituitarism. The authors identified heterozygosity for 3 different missense mutations, respectively, in 2 brothers with GH deficiency, 1 of whom also had optic nerve hypoplasia (601802.0002), an unrelated girl with GH deficiency and pituitary anomalies (601802.0003), and a boy with combined pituitary hormone deficiency (CPHD) involving GH, thyrotropin (TSH; 188540), LH, and FSH, without optic nerve hypoplasia or midline brain defects (601802.0010). All 3 mutations had been inherited from an unaffected parent, and in 1 pedigree, an unaffected sib also carried the mutation, indicating incomplete penetrance; the mutations were not found in 100 control chromosomes. Thomas et al. (2001) hypothesized that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutations in the HESX1 gene. In a Japanese patient with sporadic pituitary and optic nerve hypoplasia, Tajima et al. (2003) identified a heterozygous insertion mutation in the HESX1 gene (601802.0004). In a patient with combined pituitary hormone deficiency, but without optic nerve hypoplasia, Carvalho et al. (2003) identified a homozygous mutation in the HESX1 gene (601802.0005). Sobrier et al. (2006) reported 2 unrelated Italian patients with panhypopituitarism who, at birth, presented with hypoglycemic seizures and respiratory distress complicated by shock, in a familial context of neonatal death in 1 family. MRI exam showed anterior pituitary aplasia in a flat sella turcica and a normally located posterior pituitary without optic nerve hypoplasia in both patients. Sequencing of HESX1 exons and their flanking intronic regions revealed homozygosity for a frameshift mutation (601802.0007) and a splice defect (601802.0008), respectively. Heterogeneity McNay et al. (2007) determined the contribution of HESX1 genetic defects to the etiology of hypopituitarism. Nonfamilial patients (724) with either septooptic dysplasia (314 patients) or isolated pituitary dysfunction, optic nerve hypoplasia, or midline neurologic abnormalities (410 patients) originally screened by SSCP were rescreened by heteroduplex detection for mutations in the coding and regulatory regions of HESX1. In addition, direct sequencing of HESX1 was performed in 126 patients with familial hypopituitarism from 66 unrelated families and in 11 patients born to consanguineous parents. All patients studied had at least 1 of the 3 classic features associated with septooptic dysplasia (optic nerve hypoplasia, hypopituitarism, and midline forebrain defects). The overall incidence of coding region mutations within the cohort was less than 1%. McNay et al. (2007) concluded that mutations within HESX1 are a rare cause of septooptic dysplasia and hypopituitarism, and that the large number of familial patients with septooptic dysplasia in whom no mutations were identified is suggestive of an etiological role for other genetic factors. INHERITANCE \- Autosomal dominant \- Autosomal recessive GROWTH Height \- Short stature (if untreated) HEAD & NECK Eyes \- Optic nerve hypoplasia \- Hypoplastic optic discs SKELETAL Hands \- Supernumerary digits \- Hypoplastic digits NEUROLOGIC Central Nervous System \- Absent septum pellucidum \- Absent corpus callosum \- Midline forebrain defects \- Psychomotor retardation METABOLIC FEATURES \- Hypoglycemia, neonatal (in some patients) ENDOCRINE FEATURES \- Hypoplasia of anterior pituitary \- Ectopic or absent posterior pituitary \- Diabetes insipidus LABORATORY ABNORMALITIES \- Low or absent growth hormone (GH) \- Low or absent thyrotropin (TSH) \- Low or absent follicle-stimulating hormone (FSH) \- Low or absent luteinizing hormone (LH) \- Low or absent adrenocorticotropic hormone (ACTH) MISCELLANEOUS \- Variable phenotype \- Diagnosis made when at least 2/3 features present (optic nerve hypoplasia, hypopituitarism with pituitary hypoplasia, midline forebrain defects) MOLECULAR BASIS \- Caused by mutation in the homeo box gene expressed in ES cells (HESX1, 601802.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SEPTOOPTIC DYSPLASIA	c0338503	2,781	omim	https://www.omim.org/entry/182230	2019-09-22T16:34:49	{"doid": ["0060857"], "mesh": ["D025962"], "omim": ["182230"], "orphanet": ["3157", "95494"], "synonyms": ["Alternative titles", "DE MORSIER SYNDROME"], "genereviews": ["NBK1378"]}
Quebec platelet disorder Other namesFactor V Quebec Autosomal dominant is the manner of inheritance of this condition Quebec platelet disorder (QPD) is a rare autosomal dominant bleeding disorder first described in a family from the province of Quebec in Canada.[1][2] The disorder is characterized by large amounts of the fibrinolytic enzyme urokinase-type plasminogen activator (uPA) in platelets.[3] This causes accelerated fibrinolysis (blood clot breakdown) which can result in bleeding.[4] ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Presentation[edit] Individuals with QPD are at risk for experiencing a number of bleeding symptoms, including joint bleeds, hematuria, and large bruising.[5] In 2010, the genetic cause of QPD was determined as a mutation involving an extra copy of the gene encoding uPA.[6] The mutation causes overproduction of uPA, an enzyme that accelerates blood clot breakdown.[4] ## Pathophysiology[edit] The disorder is characterized by large amounts of uPA in platelets.[3] Consequently, stored platelet plasminogen is converted to plasmin, which is thought to play a role in degrading a number of proteins stored in platelet α-granules.[7] These proteins include platelet factor V, von Willebrand factor, fibrinogen, thrombospondin-1, and osteonectin.[3] There is also a quantitative deficiency in the platelet protein multimerin 1 (MMRN1). Furthermore, upon QPD platelet activation, uPA can be released into forming clots and accelerate clot lysis, resulting in delayed-onset bleeding (12-24hrs after injury).[8] ## Diagnosis[edit] Genetic testing is the only way to definitively diagnose QPD, as most other tests cannot confirm this diagnosis.[9] Methods include polymerase chain reaction or Southern blotting for the genetic sequence, or assays for platelet uPA levels or platelet granules.[9] ## Treatment[edit] Bleeding episodes are treated using antifibrinolytic medication, particularly tranexamic acid, to prevent fibrinolysis.[9] ## History[edit] The discovery was made by a team of doctors at McMaster University led by Dr. Catherine Hayward, a hematologist.[10] ## References[edit] 1. ^ Hayward CP, Rivard GE, Kane WH, Drouin J, Zheng S, Moore JC, Kelton JG (1996). "An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect". Blood. 87 (12): 4967–78. doi:10.1182/blood.V87.12.4967.bloodjournal87124967. PMID 8652809. 2. ^ Diamandis M, Veljkovic DK, Maurer-Spurej E, Rivard GE, Hayward CPM (2008). "Quebec platelet disorder: features, pathogenesis and treatment". Blood Coagulation and Fibrinolysis. 19 (2): 109–119. doi:10.1097/mbc.0b013e3282f41e3e. PMID 18277131. 3. ^ a b c Kahr, 2001 4. ^ a b Diamandis, Maria; Veljkovic, D Kika; Maurer-Spurej, Elisabeth; Rivard, Georges E; Hayward, Catherine PM (March 2008). "Quebec platelet disorder: features, pathogenesis and treatment:". Blood Coagulation & Fibrinolysis. 19 (2): 109–119. doi:10.1097/MBC.0b013e3282f41e3e. ISSN 0957-5235. 5. ^ McKay & Haq, 2004 6. ^ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP (Feb 2010). "Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene". Blood. 115 (6): 1264–6. doi:10.1182/blood-2009-07-233965. PMID 20007542. 7. ^ Sheth, 2003 8. ^ Diamandis & Adam, 2006 9. ^ a b c Blavignac, Jessica; Bunimov, Natalia; Rivard, Georges; Hayward, Catherine P.M. (September 2011). "Quebec Platelet Disorder: Update on Pathogenesis, Diagnosis, and Treatment". Seminars in Thrombosis and Hemostasis. 37 (06): 713–720. doi:10.1055/s-0031-1291382. ISSN 0094-6176. 10. ^ "Gene that causes rare bleeding disorder identified". CTV.ca. Archived from the original on 2010-03-06. Retrieved 2010-03-04. ## External links[edit] Classification D * ICD-10: D69.1 * OMIM: 601709 * MeSH: C536260 External resources * Orphanet: 220436 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Quebec platelet disorder	c1866423	2,782	wikipedia	https://en.wikipedia.org/wiki/Quebec_platelet_disorder	2021-01-18T18:47:56	{"gard": ["8345"], "mesh": ["C536260"], "umls": ["C1866423"], "orphanet": ["220436"], "wikidata": ["Q7269853"]}
A clinico-serological subtype of mixed cryoglobulinemia syndrome, is an immune complex disorder, characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins containing both polyclonal IgGs and polyclonal IgMs. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Mixed cryoglobulinemia type III	None	2,783	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93555	2021-01-23T17:52:18	{"icd-10": ["D89.1"], "synonyms": ["MC type III"]}
An epithelioid trophoblastic tumor is an extremely rare gestational trophoblastic tumor (GTT; see this term) which generally occurs several years after pregnancy. ## Epidemiology Annual incidence and prevalence are not known. ## Clinical description Indicative signs are irregular metrorrhagia and moderate increases in chorionic gonadotropin levels. Histologically, the myometrium and cervix uteri are invaded by regular epithelioid cells of intermediate trophoblasts, clustered in a hyaline stroma. Total hysterectomy is the basic treatment option. ## Etiology Etiology is not known. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Epithelioid trophoblastic tumor	c1266159	2,784	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254698	2021-01-23T18:41:01	{"umls": ["C1266159"], "icd-10": ["D39.2"]}
Xerophthalmia In xerophthalmia, bitot's spots occur after conjuncival xerosis. Pronunciation * /ˌzɪərɒfˈθælmiə/ (listen) SpecialtyOphthalmology SymptomsNight blindness ComplicationsBlindness due to corneal opacity CausesVitamin A deficiency (main) Xerophthalmia (from Ancient Greek "xērós" (ξηρός) meaning "dry" and "ophthalmos" (οφθαλμός) meaning "eye") is a medical condition in which the eye fails to produce tears. It may be caused by vitamin A deficiency, which is sometimes used to describe that condition, although there may be other causes. Xerophthalmia caused by a severe vitamin A deficiency is described by pathologic dryness of the conjunctiva and cornea. The conjunctiva becomes dry, thick and wrinkled. If untreated, it can lead to corneal ulceration and ultimately to blindness as a result of corneal damage. Xerophthalmia usually implies a destructive dryness of the conjunctival epithelium due to dietary vitamin A deficiency—a rare condition in developed countries, but still causing much damage in developing countries. Other forms of dry eye are associated with aging, poor lid closure, scarring from a previous injury, or autoimmune diseases such as rheumatoid arthritis and Sjögren's syndrome, and these can all cause chronic conjunctivitis. Radioiodine therapy can also induce xerophthalmia, often transiently, although in some patients late onset or persistent xerophthalmia has been observed.[1] The damage to the cornea in vitamin A associated xerophthalmia is quite different from damage to the retina at the back of the globe, a type of damage which can also be due to lack of vitamin A, but which is caused by lack of other forms of vitamin A which work in the visual system. Xerophthalmia from hypovitaminosis A is specifically due to lack of the hormone-like vitamin A metabolite retinoic acid, since (along with certain growth-stunting effects) the condition can be reversed in vitamin A deficient rats by retinoic acid supplementation (however the retinal damage continues). Since retinoic acid cannot be reduced to retinal or retinol, these effects on the cornea must be specific to retinoic acid. This is in keeping with retinoic acid's known requirement for good health in epithelial cells, such as those in the cornea. ## Contents * 1 Cause * 2 Classification * 3 Prevention * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 Further reading * 9 External links ## Cause[edit] The condition is not congenital and develops over the course of a few months as the lacrimal glands fail to produce tears. Other conditions involved in the progression already stated include the appearance of Bitot's spots, which are clumps of keratin debris that build up inside the conjunctiva and night blindness, which precedes corneal ulceration and total blindness. ## Classification[edit] World Health Organization classified xerophthalmia into following stages:[2] * XN-Night blindness * X1A-Conjunctival xerosis * X1B-Bitot spots * X2-Corneal xerosis * X3A-Corneal ulceration/keratomalacia, involving less than one-third of the cornea * X3B-Corneal ulceration/keratomalacia, involving more than one-third of the cornea * XS-Corneal scar due to xerophthalmia * XF-Xerophthalmic fundus ## Prevention[edit] Prophylaxis consists of periodic administration of Vitamin A supplements. WHO recommended schedule, which is universally recommended is as follows: * Infants 6–12 months old and any older children weighing less than 8 kg – 100,000 IU orally every 3–6 months * Children over 1 year and under 6 years of age – 200,000 IU orally every 6 months * Infants less than 6 months old, who are not being breastfed – 50,000 IU orally should be given before they attain the age of 6 months ## Treatment[edit] Treatment can occur in two ways: treating symptoms and treating the deficiency. Treatment of symptoms usually includes the use of artificial tears in the form of eye drops, increasing the humidity of the environment with humidifiers, and wearing wraparound glasses when outdoors. Treatment of the deficiency can be accomplished with a Vitamin A or multivitamin supplement or by eating foods rich in Vitamin A. Treatment with supplements and/or diet can be successful until the disease progresses as far as corneal ulceration, at which point only an extreme surgery can offer a chance of returning sight. ## Epidemiology[edit] Xerophthalmia usually affects children under nine years old and "accounts for 20,000–100,000 new cases of childhood blindness each year in the developing countries." The disease is largely found in developing countries like many of those in Africa and Southern Asia. ## See also[edit] * Keratoconjunctivitis * Keratoconjunctivitis sicca * Keratomalacia, also caused by vitamin A deficiency. ## References[edit] 1. ^ Solans, R.; Bosch, J.A.; Galofre, P.; others (2001), "Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy.", Journal of Nuclear Medicine, 42 (5): 738–43, PMID 11337569 2. ^ John F., Salmon (2020). "Cornea". Kanski's clinical ophthalmology : a systematic approach (9th ed.). Edinburgh: Elsevier. p. 247. ISBN 978-0-7020-7713-5. OCLC 1131846767. ## Further reading[edit] * Medicine.Net. "Definition of Xerophthalmia." 26 May 2003. * Jellife DB. "Xerophthalmia: A World-wide Drive for Prevention." Journal of Tropical Pediatrics 1980; 26: ii-iii. 4 November 2009. ## External links[edit] Classification D * ICD-10: E50.6-E50.7 * ICD-9-CM: 264.6-264.7 * MeSH: D014985 * DiseasesDB: 34035 External resources * MedlinePlus: 000426 * Patient UK: Xerophthalmia * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Xerophthalmia	c0043349	2,785	wikipedia	https://en.wikipedia.org/wiki/Xerophthalmia	2021-01-18T18:48:39	{"mesh": ["D014985"], "umls": ["C0043349"], "wikidata": ["Q1054713"]}
Svejcar et al. (1976) described 2 brothers with only the fifth digit on each limb. There were no other abnormalities and no consanguinity was known. This may have been an instance of gonadal mosaicism because Sommer and Hines (1992) described a clear instance of autosomal dominant inheritance; indeed, in that family, 3 persons were affected in the first generation, suggesting germinal mosaicism. Two instances of 2-generation tetramelic monodactyly were referenced by Sommer and Hines (1992). This trait may be intimately related or perhaps identical to split-hand/foot malformation (ectrodactyly; 183600), which is notorious for the phenomenon of presumed or possible germinal mosaicism (David, 1972). Limbs \- Ectrodactyly \- Monodactyly \- Isolated fifth digit of each limb 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	TETRAMELIC MONODACTYLY	c1861233	2,786	omim	https://www.omim.org/entry/187510	2019-09-22T16:32:44	{"mesh": ["C566066"], "omim": ["187510"], "orphanet": ["2564"]}
Frydman et al. (1993) described a male infant, born of first-cousin parents, with omphalocele, prune belly, thoracolumbar scoliosis, anal atresia, urethral obstruction with hypertrophic urinary bladder, dilated ureters, and dysplastic and hypoplastic kidneys. The proband's mother and all 3 of his sisters had cervical ribs. One sister had chronic immune thrombocytopenia (CIT), Sprengel deformity, and a clubfoot. Another sister had preaxial polydactyly and CIT. Frydman et al. (1993) proposed that all of these abnormalities were different manifestations of the same syndrome with varying expressivity in males and females (or in homo- and heterozygotes). GU \- Urethral obstruction \- Hypertrophic urinary bladder \- Dilated ureters \- Dysplastic kidneys \- Hypoplastic kidneys Thorax \- Cervical ribs \- Sprengel anomaly Inheritance \- Autosomal recessive Spine \- Thoracolumbar scoliosis Limbs \- Clubfoot \- Preaxial polydactyly Abdomen \- Omphalocele \- Prune belly GI \- Anal atresia Heme \- Chronic immune thrombocytopenia (CIT) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CERVICAL RIBS, SPRENGEL ANOMALY, ANAL ATRESIA, AND URETHRAL OBSTRUCTION	c1832391	2,787	omim	https://www.omim.org/entry/601389	2019-09-22T16:14:53	{"mesh": ["C538072"], "omim": ["601389"]}
A number sign (#) is used with this entry because frontonasal dysplasia-1 (FND1), also designated frontorhiny, is caused by homozygous mutation in the aristaless-like homeobox-3 gene (ALX3; 606014) on chromosome 1p13. Description The term frontonasal dysplasia was coined by Sedano et al. (1970) to describe a constellation of findings limited to the face and head. The disorder is defined as 2 or more of the following: (1) true ocular hypertelorism; (2) broadening of the nasal root; (3) median facial cleft affecting the nose and/or upper lip and palate; (4) unilateral or bilateral clefting of the alae nasi; (5) lack of formation of the nasal tip; (6) anterior cranium bifidum occultum (see 168500); and (7) a V-shaped or widow's peak frontal hairline (Sedano and Gorlin, 1988). Most reported cases are sporadic, but a few familial cases have been reported. Twigg et al. (2009) characterized frontonasal malformation (FNM) as a 'very heterogeneous group of disorders' and summarized clinical features. Also see acromelic frontonasal dysplasia (AFND; 603671), frontofacionasal dysplasia (FFND; 229400), oculoauriculofrontonasal syndrome (OAFNS; 601452), the acrofrontofacionasal dysostosis syndromes (201180, 239710), and craniofrontonasal syndrome (304110). ### Genetic Heterogeneity of Frontonasal Dysplasia Frontonasal dysplasia-2 (FND2; 613451) is caused by mutation in the ALX4 gene (605420) on chromosome 11p11. Frontonasal dysplasia-3 (FND3; 613456) is caused by mutation in the ALX1 gene (601527) on chromosome 12q21. Clinical Features Twigg et al. (2009) described a particular form of frontonasal dysplasia, which they called frontorhiny, characterized by distinctive facial appearance with hypertelorism, wide nasal bridge, short nasal ridge, splayed nasal bones with bifid nasal tip, broad columella that attaches to the face above the alae, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. Additional recurrent features present in a minority of individuals included upper eyelid ptosis and midline dermoid cysts of craniofacial structures. Twigg et al. (2009) extended their analysis to the sibs reported by Lees et al. (2007), a brother and sister, offspring of consanguineous parents, with ptosis, hypertelorism, long eyelashes, bifid nose, upturned nares, very broad columella, histologically proven intranasal dermoid, and soft tissue swelling of the philtrum. One sib also had a midline cleft lip and lipomas on the forehead, and an MRI showed a lipoma of the posterior corpus callosum. The other sib had narrowing of the posterior choanae and conductive hearing loss. Although neither sib had an abnormal skull shape, Lees et al. (2007) had suggested that the sibs had craniorhiny (123050). Twigg et al. (2009) disagreed with this classification, citing differences in facial morphology, absence of craniosynostosis, and autosomal recessive inheritance. Twigg et al. (2009) also suggested that the proband in the report by Toriello et al. (1985) (see 164000) may have had frontorhiny. ### General Craniofacial Features of FND The craniofacial features of frontonasal dysplasia include anterior cranium bifidum, ocular hypertelorism, orofacial clefting, and notching or clefting of the alae nasi (Sedano et al., 1970). Moreno Fuenmayor (1980) reported a consanguineous Venezuelan family in which 3 members had frontonasal dysplasia. Fifteen other members of the pedigree had hypertelorism and/or bifid nose. Fryburg et al. (1993) observed a black family from the Bahamas in which the mother, 2 of her sons, and her brother had variable manifestations of frontonasal dysplasia. The mother had very mild expression but her brother and 2 sons were more severely affected. The affected brother and 4 other members of the mother's sibship, 2 female and 2 male, had postaxial polydactyly. The authors considered postaxial polydactyly to be a separate autosomal dominant trait segregating in this family because the trait is a frequent isolated finding and is often seen in relatives of patients without FND. In addition, none of the affected family members had any malformations involving other parts of their bodies. The mother had only slight increase in interpupillary distance, wide nose with a broad nasal tip, and diastasis of the central incisors. She had had extra digits removed bilaterally. The mother's brother had a bifid nasal tip with a short columella. One of the sons was mildly affected, the other very severely affected. ### Associated Features of FND De Moor et al. (1987) reported 3 unrelated children with frontonasal dysplasia associated with tetralogy of Fallot. All had true hypertelorism and a median nasal groove, with absence of the nasal tip. None had mental deficiency. Multifactorial inheritance was proposed. Meinecke and Blunck (1989) described a single case of frontonasal dysplasia associated with congenital heart defect and pointed to similarities to the patients reported by De Moor et al. (1987). Lees et al. (1998) described 3 males and 3 females with hypertelorism, midline facial cleft, sphenoethmoidal encephalocele, agenesis of the corpus callosum, optic disc anomalies (peripapillary staphyloma, hypoplastic optic discs, absent optic chiasm, and morning glory disc anomaly), and pituitary dysfunction (growth hormone deficiency, hypothyroidism, diabetes insipidus, and hypoadrenalism). One of the males had previously been described by Leitch and Winter (1996). Lees et al. (1998) suggested that these patients represent a distinct entity, which lies within the spectrum of the frontonasal dysplasia syndrome. Nevin et al. (1999) described a 2-year-old girl with anterior cranium bifidum occultum, lipoma of the genu and anterior part of the corpus callosum, and hypertelorism. The mother had a history of a 'nasal drip' at birth caused by a defect in the cribriform plate. This required surgery at the age of 5.5 years. At the age of 31 years, the only clinical signs in the mother were a widow's peak, mild hypertelorism, and a left nostril slightly smaller than the right. Lopes et al. (2004) described a 15-month-old girl with frontonasal dysplasia, frontal and nasal hemangiomas, optic disc anomalies (salt-and-pepper retina, megalopapillae, and iris synechiae), hearing loss, lymphedema of upper and lower limbs, neuronal migration error, and mild neuropsychomotor delay. Lopes et al. (2004) suggested that this child had a previously unrecognized syndrome. Guion-Almeida and Richieri-Costa (2009) described 10 Brazilian male patients with frontonasal dysplasia, cleft lip/palate, mental retardation, lack of language acquisition, and midline central nervous system anomalies, mainly agenesis of the corpus callosum, large interhemispheric cysts, gyral anomalies, and occasional neuronal heterotopias. Guion-Almeida and Richieri-Costa (2009) suggested that these patients represent a newly recognized recurrent-pattern syndrome of unknown cause previously subsumed under frontonasal dysplasia. ### Reviews Wu et al. (2007) reviewed 104 cases of FND, grouped FND patients into 7 different phenotypic subtypes in addition to isolated FND, and provided references for the cases in each category. Inheritance The patients with FND1 reported by Twigg et al. (2009) exhibited autosomal recessive inheritance. Gonzales-Ramos (1981) reviewed a considerable number of cases, all sporadic. He described the case of a woman with severe frontonasal dysplasia, all of whose 7 children were normal. He concluded that reports of dominant inheritance (e.g., Friede, 1954) may have represented Greig syndrome (145400). Autosomal recessive inheritance was suggested by the inbred kindred reported by Moreno Fuenmayor (1980). The findings in the family reported by Fryburg et al. (1993) are consistent with autosomal or X-linked dominant inheritance. Mohammed et al. (2004) reported 5 sets of same-sex twins in which only a single twin was affected with frontonasal dysplasia. Zygosity testing established monozygosity in all 5 sets of twins with a probability of greater than 99:1. Mohammed et al. (2004) concluded that the observed malformations were nongenetic in origin and, by extrapolation, proposed that most singleton cases of frontonasal dysplasia also arise from true errors of early development and that occult monozygotic twinning may be a predisposing factor. Cytogenetics Stevens and Qumsiyeh (1995) described a 4-year-old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, with a total of 4 breakpoints. The child had a widow's peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2-4 vertebrae, and structural brain abnormalities on MRI. Stevens and Qumsiyeh (1995) proposed that search for a gene underlying this disorder should focus on 4 chromosome bands: 3q23, 3q27, 7q21, and 11q21. Pathogenesis Brugmann et al. (2010) showed that excessive Hedgehog activity, caused by truncating the primary cilia on cranial neural crest cells, caused hypertelorism and frontonasal dysplasia. Elimination of the intraflagellar transport protein Kif3a (604683) led to excessive Hedgehog responsiveness in facial mesenchyme, which was accompanied by broader expression domains of Gli1 (165220), Ptch1 (601309), and Shh (600725), and reduced expression domains of Gli3 (165240). Broader domains of Gli1 expression corresponded to areas of enhanced neural crest cell proliferation in the facial prominences of Kif3a conditional knockouts. Avian Talpid embryos that lack primary cilia exhibited similar molecular changes and similar facial phenotypes. Brugmann et al. (2010) hypothesized that a severe narrowing of the facial midline and excessive expansion of the facial midline may both be attributable to disruptions in Hedgehog pathway activity. Molecular Genetics Assuming recessive inheritance, Twigg et al. (2009) mapped the locus in 3 families with frontorhiny to chromosome 1 and identified mutations in the ALX3 gene (606014) on chromosome 1p13.3. Twigg et al. (2009) identified a total of 7 different homozygous pathogenic mutations in 7 families. One of these families had been reported by Lees et al. (2007). These mutations comprised missense substitutions at critical positions within the conserved homeodomain as well as nonsense, frameshift, and splice site mutations, all predicting severe or complete loss of function. Twigg et al. (2009) confirmed that there were no mutations in the ALX1 (601527) or ALX4 (605420) genes in these patients. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Cranium bifidum occultum (defect in midline frontal bone) Face \- Widow's peak Ears \- Preauricular tag \- Low-set ear \- Conductive hearing loss Eyes \- Hypertelorism \- Lateral displacement of inner canthi \- Microphthalmia \- Epicanthal folds \- Ptosis \- Coloboma \- Cataract Nose \- Broad nasal root \- Variable bifid nose \- Broad notched nasal tip \- Accessory nasal tag \- Notched alae nasi Mouth \- Median cleft lip \- Median cleft palate CARDIOVASCULAR Heart \- Tetralogy of Fallot CHEST External Features \- Pectoral muscle hypoplasia/aplasia (Poland syndrome) SKELETAL Skull \- Cranium bifidum occultum \- Maxillary hypoplasia \- Hypoplastic frontal sinuses Hands \- Brachydactyly \- Clinodactyly \- Camptodactyly SKIN, NAILS, & HAIR Skin \- Frontal cutaneous lipoma Hair \- Widow's peak NEUROLOGIC Central Nervous System \- Mental retardation \- Lipoma of corpus callosum \- Agenesis of corpus callosum \- Anterior basal encephalocele MISCELLANEOUS \- Majority of patients have normal intelligence MOLECULAR BASIS \- Caused by mutation in the aristaless-like homeobox 3 gene (ALX3, 606014.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	FRONTONASAL DYSPLASIA 1	c1876203	2,788	omim	https://www.omim.org/entry/136760	2019-09-22T16:40:58	{"mesh": ["C538065"], "omim": ["136760"], "orphanet": ["391474"], "synonyms": ["Alternative titles", "FRONTONASAL MALFORMATION", "ALX3-related frontonasal dysplasia", "Isolated median cleft face syndrome", "Frontonasal dysplasia type 1", "FRONTONASAL DYSPLASIA", "MEDIAN FACIAL CLEFT SYNDROME", "FRONTORHINY"]}
Hunan hand syndrome Other namesChili burn SpecialtyDermatology CausesExposure to capsaicin from improper handling of chili peppers, higher risk from high concentrations of capsaicin PreventionWearing rubber gloves when preparing or handling chili peppers, especially for superhot chilis Hunan hand syndrome (also known as "Chili burn"[1]) is a temporary, but very painful, cutaneous condition that commonly afflicts those who handle, prepare, or cook with fresh or roasted chili peppers.[1] It was first described in an eponymous case report in the New England Journal of Medicine in 1981.[2] It occurs when the phytochemical capsaisin, which can be present in very high concentrations in certain varieties of chili peppers, (especially with superhot peppers such as ghost peppers or carolina reapers) contacts cutaneous free nerve endings which are present in high density in the finger tips of its victims. This triggers the release of substance P, which in turn causes a sensation of intense burning pain. Various treatments for Hunan Hand have been described, including soaking the affected fingers in lidocaine;[2] milk or vinegar;[3] or the use of local nerve blocks, gabapentin, or topical corticosteroids.[4] Hunan hand can be prevented by the simple expedient of wearing rubber gloves when handling chili peppers. ## See also[edit] * Kang cancer * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 2. ^ a b Weinberg RB (October 1981). "Hunan Hand". New England Journal of Medicine. 305 (17): 1020. PMID 7278919. 3. ^ Vogl TP (January 1982). "Treatment of Hunan Hand". New England Journal of Medicine. 306 (3): 178. doi:10.1056/nejm198201213060321. PMID 7054672. 4. ^ Saxena AK; Mandhyan R (March 2013). "Multimodal approach for the management of Hunan hand syndrome". Pain Practice. 13 (3): 227–2300. doi:10.1111/j.1533-2500.2012.00567.x. PMID 22681338. * v * t * e Chili peppers Capsicum annuum cultivars * Aleppo * Banana * Bell * Bird's eye * Black Pearl * Cascabel * Cayenne * Cheongyang * Chiltepin * Cubanelle * Chile de árbol * Dundicut * Espelette * Facing Heaven * Fish * Florina * Friggitello * Guajillo * Guntur Sannam * Hungarian wax * Jalapeño * Korean * Medusa * New Mexico * Big Jim * Chimayo * Fresno * Sandia * Santa Fe Grande * Padrón * Pasilla * Peperoncino * Pequin * Peter * Pimiento * Piquillo * Poblano * Serrano * Shishito * Siling haba * Urfa biber Capsicum baccatum cultivars * Bishop's crown * Lemon drop * Peppadew Capsicum chinense cultivars * Adjuma * Ají caballero * Ají dulce * Bhut jolokia * Carolina Reaper * Datil * Dragon's Breath * Ellachipur Sanman * Fatalii * Habanero * Hainan yellow lantern * Infinity * Komodo Dragon * Madame Jeanette * Nagabon * Naga Morich * Naga Viper * Pepper X * Red Savina * Scotch bonnet * Trinidad Moruga scorpion * Trinidad Scorpion Butch T Capsicum frutescens cultivars * African Birdseye * Kambuzi * Malagueta * Siling labuyo * Tabasco pepper Culinary uses * Adobada * Chili con carne * Chili dog * Chili pepper paste * Chili pepper water * Chili powder * Chili thread * Ema datshi * Filfel chuma * Gochujang * Harissa * Nam phrik * Peppersoup * Piperade Condiments and sauces * Biber salçası * Chili oil * Chili sauce * Hot sauce * Pepper jelly * Pickapeppa Sauce * Sriracha sauce * Sweet chili sauce * Tabasco sauce * XO sauce See also * Capsaicin * Chile Pepper Institute * Chilympiad * Elephant Pepper Development Trust * Hot pepper challenge * Hunan hand syndrome * Pepper spray * Ristra * Scoville scale * Category 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hunan hand syndrome	None	2,789	wikipedia	https://en.wikipedia.org/wiki/Hunan_hand_syndrome	2021-01-18T19:05:18	{"wikidata": ["Q16914162"]}
A rare partial autosomal trisomy/tetrasomy characterized by global developmental delay, intellectual disability, autistic behavior, muscular hypotonia, macrocephaly and facial dysmorphism (frontal bossing, short palpebral fissures, low set, dysplastic ears, short or shallow philtrum, high arched or narrow palate, micrognathia). Other associated clinical features include sleep disturbances, seizures, aplasia/hypoplasia of the corpus callosum, skeletal abnormalities (large hands and feet, long fingers and toes, talipes). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	5p13 microduplication syndrome	c2750805	2,790	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329802	2021-01-23T19:07:51	{"mesh": ["C567717"], "omim": ["613174"], "umls": ["C2750805"], "icd-10": ["Q92.3"], "synonyms": ["Dup(5)(p13)", "Trisomy 5p13"]}
## Description Oculopharyngodistal myopathy (OPDM) is characterized by adult-onset of eye and facial muscle weakness, distal muscle weakness and atrophy, and pharyngeal involvement, resulting in dysphagia and dysarthria. There are variable manifestations of the disorder regarding muscle involvement and severity. Both autosomal recessive and autosomal dominant inheritance have been reported. OPDM is considered distinct from oculopharyngeal muscular dystrophy (OPMD; 164300), which is caused by mutation in the PABPN1 gene (602279) (summary by Durmus et al., 2011). Clinical Features Satoyoshi and Kinoshita (1977) described 4 families with a form of oculopharyngeal myopathy characterized by adult-onset of slowly progressive ptosis and extraocular palsy, weakness of the masseter, facial, and bulbar muscles, and distal weakness of the limbs. In 1 autopsy case, no remarkable changes were found in the central and peripheral nervous system. Muscle biopsy specimens in 1 patient from each family showed myopathic patterns. Uyama et al. (1998) reported 2 Japanese brothers, born of consanguineous parents, with oculopharyngodistal myopathy. Each had weakness of the tibialis anterior muscles, which began after ages 40 and 35 years, respectively. Soon after, they developed distal upper limb weakness, foot drop, ptosis, external ophthalmoplegia, weakness of facial muscles, nasal voice, and dysphagia. Further studies showed areflexia, moderately increased serum creatine kinase, myogenic EMG changes without myotonia. The clinical phenotype was similar to that reported by Satoyoshi and Kinoshita (1977). Skeletal muscle biopsies showed small angulated fibers and rimmed vacuoles with a frequency of 3% in 1 and 6% in the other, autophagic vacuoles, and 15- to 18-nm cytoplasmic inclusions. A comparison of the phenotype with 4 patients with distal myopathy with rimmed vacuoles (DMRV; 605820) and 36 with OPMD indicated that the disorder in the Japanese brothers was distinct. Patients with DMRV did not have oculopharyngeal muscle involvement, and those with OPMD did not have prominent distal muscle involvement. In histologic comparison, the Japanese brothers did not have OPMD-specific intranuclear inclusions on biopsy, but there were some similar ultrastructural characteristics to DMRV, namely the presence of rimmed vacuoles and 15- to 18-nm cytoplasmic inclusions. Uyama et al. (1998) concluded that OPDM is a distinct disorder. Van der Sluijs et al. (2004) reported 25-year follow-up of 2 Dutch sibs with OPDM. The sister developed distal lower limb weakness, ptosis, and dysphagia at age 25 years, whereas the brother developed ptosis in his late teens. Both had slow progression of the disorder, which ultimately included ptosis, external ophthalmoplegia, facial muscle weakness resulting in myopathic facies, and distal muscle weakness and atrophy of the legs and arms. By age 46, the sister used a wheelchair outdoors and had decreased respiratory flow. The brother developed pneumonia and died at age 55. At that time, he was wheelchair-bound with hypotonic paralysis of both legs, had paresis of both arms, and complete external ophthalmoplegia. Van der Sluijs et al. (2004) concluded that OPDM is a different disorder from OPMD. Durmus et al. (2011) reported 47 patients from 9 unrelated Turkish families with OPDM. The mean age at onset was 22.1 years (range, 7 to 50 years), and most presented with ptosis and variable degrees of ophthalmoparesis. Those with a disease duration of more than 5 years tended to develop facial muscle wasting, particularly of the orbicularis oris, malar, and zygomatic muscles. There was more variable involvement of other muscles. Thirty-four patients with disease duration of more than 5 years showed slowly progressive weakness initially affecting the distal muscles. However, 4 patients examined early in the disease had clear proximal muscle weakness, especially in the lower extremities. Nine patients had no skeletal muscle weakness; 3 were wheelchair-bound at 15, 21, and 27 years after onset. Most had major swallowing difficulties, resulting in weight loss, and dysarthria. Other common features included tongue weakness, high palate, and bowing of the vocal cords. Two patients had sensorineural hearing loss, and 3 had impaired hearing. Thirteen patients had some evidence of respiratory involvement, even at early stages of the disease. Sternocleidomastoid muscle weakness was not seen until late stages of the disease. Serum creatine kinase levels were normal or increased, and EMG showed myopathic changes with occasional myotonic discharges. Skeletal muscle biopsies of 12 patients showed myopathic changes with rimmed vacuoles. Three patients examined ultrastructurally showed autophagic vacuoles containing multilamellar structures. Molecular genetic studies excluded the pathologic repeat expansion in the PABPN1 gene (602279), and linkage analysis excluded multiple genes known to be involved in various muscular dystrophy and myopathies. Durmus et al. (2011) suggested the term 'faciooculolaryngopharyngeal myopathy with distal and respiratory involvement,' or FOLP-DR, to better describe the features of this disorder. Inheritance Both autosomal dominant and autosomal recessive inheritance have been reported. Satoyoshi and Kinoshita (1977) reported 4 families with oculopharyngeal myopathy in which the transmission pattern was consistent with autosomal dominant inheritance. One of their families had affected persons spanning 3 generations with male-to-male transmission. Among 9 unrelated Turkish families with OPDM, Durmus et al. (2011) found that transmission pattern was consistent with autosomal dominant inheritance in 5 and autosomal recessive inheritance in 1; the pattern could not be determined in the 3 remaining families. INHERITANCE \- Autosomal dominant \- Autosomal recessive GROWTH Weight \- Weight loss due to dysphagia HEAD & NECK Face \- Facial muscle atrophy \- Facial muscle weakness \- Myopathic face Ears \- Hearing loss, sensorineural (less common) Eyes \- Ptosis \- External ophthalmoplegia Mouth \- High-arched palate \- Tongue weakness RESPIRATORY \- Respiratory insufficiency due to muscle weakness \- Restrictive ventilatory defect \- Recurrent pneumonia due to aspiration Nasopharynx \- Pharyngeal weakness Larynx \- Laryngeal weakness \- Bowing of the vocal cords ABDOMEN Gastrointestinal \- Dysphagia MUSCLE, SOFT TISSUES \- Distal muscle weakness \- Distal muscle atrophy \- Proximal muscle weakness \- Foot drop \- Difficulty walking \- Facial muscle atrophy \- Myogenic changes seen on EMG \- Fiber size variation seen on muscle biopsy \- Angulated fibers \- Rimmed vacuoles \- Autophagic vacuoles with multilamellar structures seen on electron microscopy NEUROLOGIC Peripheral Nervous System \- Areflexia VOICE \- Dysarthria \- Nasal voice LABORATORY ABNORMALITIES \- Serum creatine kinase may be normal or increased MISCELLANEOUS \- Mean age at onset 22 years (range 7 to 50 years) \- Slowly progressive disorder \- Ptosis is usually presenting feature \- Other muscle become involved about 5 years after onset \- Highly variable severity of muscle weakness \- Both autosomal dominant and autosomal recessive inheritance have been described ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	OCULOPHARYNGODISTAL MYOPATHY	c1834014	2,791	omim	https://www.omim.org/entry/164310	2019-09-22T16:37:17	{"mesh": ["C563508"], "omim": ["164310"], "orphanet": ["98897"], "synonyms": ["Alternative titles", "FACIOOCULOLARYNGOPHARYNGEAL MYOPATHY WITH DISTAL AND RESPIRATORY INVOLVEMENT"]}
Moyamoya angiopathy - short stature - facial dysmorphism - hypergonadotropic hypogonadism is a very rare, hereditary, neurological, dysmorphic syndrome characterized by moyamoya disease, short stature of postnatal onset, and stereotyped facial dysmorphism. ## Epidemiology The syndrome is extremely rare and has been reported in three unrelated families to date, with 10 affected individuals in several generations. These families are not from Japan or Asia, whereas in general the incidence of moyamoya disease (see this term) is highest in Japan and other Asian countries, in comparison with other parts of the world. ## Clinical description Affected patients are all male (X-linked inheritance) and have moyamoya angiopathy (progressive stenosis of the terminal portion of the intracranial internal carotid arteries), short stature, hypergonadotropic hypogonadism, and other variable manifestations including stroke, hypertension, dilated cardiomyopathy (see this term), premature coronary heart disease, premature hair graying, azoospermia, and early bilateral acquired cataract. Moyamoya angiopathy causes cerebral infarcts or hemorrhage and acute neurological symptoms. Facial dysmorphism is characterized by hypertelorism, flared nares, long philtrum, and mild ptosis. Carrier females are not affected. ## Etiology The genetic cause appears to involve Xq28 deletions removing MTCP1/CMC4and BRCC3 (Xq28) .The specific pathophysiological mechanisms underlying this disorder remain obscure, but appear to involve alteration in DNA repair. ## Genetic counseling Reported cases are suggestive of a hereditary syndrome with an X-linked recessive pattern of 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome	c3151857	2,792	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280679	2021-01-23T17:07:08	{"omim": ["300845"], "synonyms": ["Moyamoya disease-short stature-facial dysmorphism-hypergonadotropic hypogonadism"]}
Maculopapular cutaneous mastocytosis (MCM) is a form of cutaneous mastocytosis (CM; see this term) characterized by the presence of multiple hyperpigmented macules, papules or nodules associated with abnormal accumulation of mast cells in the skin. ## Epidemiology MCM is the most common form of CM (accounting for up to 90% of cases) but the prevalence in the general population is unknown. Incidence has been estimated at between 1/1000 and 1/125 births. This entity is most commonly reported among the Caucasian population and affects both sexes, although a slight male predominance (1.7-1.8:1) has been reported in cases with early onset. ## Clinical description The majority of patients present in infancy or childhood but onset may also occur in adulthood. As lesions vary in aspect, several subvariants have been described in the past (plaque form, typical form, telangiectatic form, and nodular form) but are all now grouped under the same entity. The plaque or papular form presents with orange/yellow papules or plaques often appearing during the first few months of life. Typical or classic forms have a more widespread, symmetrical distribution of round or oval red/brown macules. The telangiectatic form (telangiectasia macularis eruptiva perstans; TMEP) is a disputed entity described as a rare variant occurring in adults and characterized by the presence of red/brown telangiectatic macules. The nodular form is rare. In MCM, the size and number of lesions is variable, typically ranging in size from 1 mm to over 1 cm and in number from 10-1000 lesions. MCM may appear on all regions of the body but the trunk and extremities are most frequently involved. The palms and soles are usually spared. Darier's sign, dermographism and pruritus are additional features of MCM. Extensive mechanical manipulation and other factors that trigger mast cell degranulation (non-steroidal anti-inflammatory drugs, physical stimuli, emotional stress, insect venom and certain foods) may lead to systemic symptoms such as flushing, headache, dyspnea, wheezing, rhinorrhea, nausea, vomiting, diarrhea, and syncope. ## Etiology Mutations in the KIT gene (4q11-q12) have been identified in patients with MCM. However, this mutation is rare in the pediatric population and the etiology and pathogenesis of MCM in these cases remains to be determined. MCM generally occurs sporadically but rare familial cases have been reported. ## Diagnostic methods Diagnosis in children is based on the clinical appearance of the lesions and the positive Darier's sign. Occasionally (generally in cases with presentation after 5 years of age), a skin biopsy may be required for confirmation of the diagnosis. In adults, a bone marrow examination should be performed to exclude the diagnosis of SM. ## Differential diagnosis The diagnosis is usually straightforward but misdiagnosis as chronic urticaria or idiopathic anaphylaxis has been reported. ## Management and treatment Trigger factors should be avoided and symptomatic management includes administration of antihistamines, topical steroids and mast cell membrane stabilizers. PUVA or UVA1 therapy may also be used for adolescents or adults who do not respond to other forms of treatment. ## Prognosis The prognosis is good, especially for patients with childhood onset below the age of 5 years, with improvement (around 50% of cases) or complete resolution (30% of cases) of symptoms by adolescence. In contrast, spontaneous resolution is rare in patients with adult-onset forms of the disease and there is a higher risk of systemic involvement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Maculopapular cutaneous mastocytosis	c0042111	2,793	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79457	2021-01-23T18:22:54	{"mesh": ["D014582"], "omim": ["154800"], "umls": ["C0042111"], "icd-10": ["Q82.2"], "synonyms": ["Urticaria pigmentosa"]}
Bruyn and Went (1964) described a degenerative disorder of the central nervous system associated with optic atrophy in at least 18 members of a family. One of these was female but the diagnosis was in some doubt in this case. The neurologic disorder showed features intermediate between those of hereditary spastic paraplegia (Strumpell-Lorrain) and Hallervorden-Spatz disease. The laboratory studies (Went, 1964) showed some peculiarities, e.g., abnormal oral glucose tolerance tests and mild red cell macrocytosis, but have thus far not contributed particularly to an understanding of the disorder. Eyes \- Optic atrophy Inheritance \- X-linked Neuro \- Spastic paraplegia Lab \- Mild red cell macrocytosis Metabolic \- Abnormal oral glucose tolerance ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	OPTIC ATROPHY--SPASTIC PARAPLEGIA SYNDROME	c1839565	2,794	omim	https://www.omim.org/entry/311100	2019-09-22T16:17:29	{"mesh": ["C564084"], "omim": ["311100"]}
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: "Congenital rubella syndrome" – news · newspapers · books · scholar · JSTOR (December 2007) (Learn how and when to remove this template message) Congenital rubella syndrome White pupils due to congenital cataracts in a child with congenital rubella syndrome SpecialtyTeratology Congenital rubella syndrome (CRS) can occur in a developing fetus of a pregnant woman who has contracted rubella, usually in the first trimester. If infection occurs 0–28 days before conception, the infant has a 43% risk of being affected. If the infection occurs 0–12 weeks after conception, the risk increases to 81%. If the infection occurs 13–26 weeks after conception, the risk is 54% of the infant being affected by the disease. Infants are not generally affected if rubella is contracted during the third trimester, or 26–40 weeks after conception. Problems rarely occur when rubella is contracted by the mother after 20 weeks of gestation and continues to disseminate the virus after birth. It was discovered in 1941 by Australian Norman McAlister Gregg.[1] ## Contents * 1 Signs and symptoms * 2 Prevention * 3 References * 4 External links ## Signs and symptoms[edit] Infant with skin lesions from congenital rubella "Salt-and-pepper" retinopathy is characteristic of congenital rubella.[2] Congenital rubella serology time-line The classic triad for congenital rubella syndrome is:[3] * Sensorineural deafness (58% of patients) * Eye abnormalities—especially retinopathy, cataract, glaucoma, and microphthalmia (43% of patients) * Congenital heart disease—especially pulmonary artery stenosis and patent ductus arteriosus (50% of patients)[4] Other manifestations of CRS may include: * Spleen, liver, or bone marrow problems (some of which may disappear shortly after birth) * Intellectual disability * Small head size (microcephaly) * Low birth weight[5] * Thrombocytopenic purpura * Extramedullary hematopoiesis (presents as a characteristic blueberry muffin rash) * Enlarged liver * Small jaw size * Skin lesions [5] Children who have been exposed to rubella in the womb should also be watched closely as they age for any indication of: * Developmental delay[5] * Autism[6] * Schizophrenia[7] * Growth retardation[8] * Learning disabilities * Diabetes mellitus[9] ## Prevention[edit] Vaccinating the majority of the population is effective at preventing congenital rubella syndrome.[10] For women who plan to become pregnant, the MMR (measles mumps, rubella) vaccination is highly recommended, at least 28 days prior to conception.[5] The vaccine should not be given to women who are already pregnant as it contains live viral particles.[5] Other preventative actions can include the screening and vaccinations of high-risk personnel, such as medical and child care professions.[11] ## References[edit] 1. ^ Atkinson, William (2011). Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 301–323. ISBN 9780983263135. Retrieved 30 March 2015. 2. ^ Sudharshan S, Ganesh SK, Biswas J (2010). "Current approach in the diagnosis and management of posterior uveitis". Indian J Ophthalmol. 58 (1): 29–43. doi:10.4103/0301-4738.58470. ISSN 0301-4738. PMC 2841371. PMID 20029144. 3. ^ "Congenital rubella syndrome \| Sense". www.sense.org.uk. Retrieved 2015-07-30. 4. ^ Oster ME, Riehle-Colarusso T, Correa A (January 2010). "An update on cardiovascular malformations in congenital rubella syndrome". Birth Defects Research Part A: Clinical and Molecular Teratology. 88 (1): 1–8. doi:10.1002/bdra.20621. PMID 19697432. 5. ^ a b c d e "Congenital Rubella Symptoms & Causes \| Boston Children's Hospital". www.childrenshospital.org. Retrieved 2019-03-05. 6. ^ Muhle, R; Trentacoste, SV; Rapin, I (May 2004). "The genetics of autism". Pediatrics. 113 (5): e472–86. doi:10.1542/peds.113.5.e472. PMID 15121991. 7. ^ Brown, A. S (9 February 2006). "Prenatal Infection as a Risk Factor for Schizophrenia". Schizophrenia Bulletin. 32 (2): 200–202. doi:10.1093/schbul/sbj052. PMC 2632220. PMID 16469941. 8. ^ Naeye, Richard L. (1965-12-20). "Pathogenesis of congenital rubella". JAMA. 194 (12): 1277–1283. doi:10.1001/jama.1965.03090250011002. ISSN 0098-7484. PMID 5898080. 9. ^ Forrest, Jill M.; Menser, Margaret A.; Burgess, J. A. (1971-08-14). "High Frequency of Diabetes Mellitus in Young Adults with Congenital Rubella". The Lancet. 298 (7720): 332–334. doi:10.1016/S0140-6736(71)90057-2. PMID 4105044. 10. ^ "Rubella vaccines: WHO position paper" (PDF). Wkly Epidemiol Rec. 86 (29): 301–16. 15 July 2011. PMID 21766537. 11. ^ "Congenital Rubella - Pediatrics". Merck Manuals Professional Edition. Retrieved 2019-03-05. ## External links[edit] Classification D * ICD-10: P35.0 * ICD-9-CM: 771.0 * MeSH: D012410 * DiseasesDB: 11729 External resources * MedlinePlus: 001658 * eMedicine: emerg/388 * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti syndrome * 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 * t * e Vertically transmitted infections Gestational * Viruses * Congenital rubella syndrome * Congenital cytomegalovirus infection * Neonatal herpes simplex * Hepatitis B * Congenital varicella syndrome * HIV * Fifth disease * Bacteria * Congenital syphilis * Other * Toxoplasmosis * transplacental * TORCH complex During birth * transcervical * Candidiasis * Gonorrhea * Listeriosis Late pregnancy * Listeriosis * Congenital cytomegalovirus infection By breastfeeding * Breastfeeding * Tuberculosis * HIV [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Congenital rubella syndrome	c0035921	2,795	wikipedia	https://en.wikipedia.org/wiki/Congenital_rubella_syndrome	2021-01-18T18:31:59	{"gard": ["4744"], "mesh": ["D012410"], "umls": ["C0035921"], "icd-9": ["771.0"], "icd-10": ["P35.0"], "orphanet": ["290"], "wikidata": ["Q1724539"]}
A number sign (#) is used with this entry because of evidence that trichomegaly (TCMGLY) is caused by homozygous mutation in the FGF5 gene (165190) on chromosome 4q21. Clinical Features Unusually long eyelashes is a morphologic trait which is observed in multiple relatives and has been reported in association with a variety of medical problems as indicated by Goldstein and Hutt (1972). They found it with cataract in a brother and sister who also had hereditary spherocytosis. Gray (1944), who appears to have coined the term 'trichomegaly,' reported the trait in father and daughter. Harrison and Mullaney (1997) observed an 18-month-old girl with marked elongation of the eyelashes and corneal irritation. Her sibs also had trichomegaly. The parents stated that they regularly trimmed the children's lashes because of marked elongation. The parents and grandparents were first cousins, and all had normal lashes. Photographs of the proposita and her affected brother and sister were provided. Higgins et al. (2014) studied 2 large consanguineous Pakistani families in which 8 and 16 individuals, respectively, had trichomegaly. In both families, hair growth was most striking in the eyelashes; however, examination of plucked forearm hairs showed that those hairs were significantly longer and showed increased variance in length, but no increase in thickness, compared to controls. Affected members of 1 family also showed mild hypertrichosis of the eyebrows as well as on the cheeks and forehead. Analysis of root tip morphology revealed a shift toward anagen morphology in patient hairs (59-65% anagen) compared to ethnically matched controls (17%). Mapping In a large consanguineous Pakistani family segregating autosomal recessive trichomegaly, Higgins et al. (2014) performed homozygosity mapping and identified a single region of homozygosity on chromosome 4q21.21 that was shared among affected individuals and was absent in unaffected family members. Molecular Genetics In 2 large consanguineous Pakistani families segregating autosomal recessive trichomegaly, Higgins et al. (2014) performed exome sequencing and identified homozygosity for a splice site and a frameshift mutation in the FGF5 gene (165190.0001 and 165190.0002, respectively) in affected individuals. The mutations, which segregated with disease in each family, were not found in 50 ethnically matched controls or in public databases. Sequencing FGF5 in unrelated probands from 5 more families with trichomegaly identified a missense mutation (Y174H; 165190.0003) in 1 proband from Pakistan. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Hypertrichosis of cheeks and forehead, mild Eyes \- Unusually long eyelashes \- Hypertrichosis of eyebrows, mild SKIN, NAILS, & HAIR Hair \- Body hair longer than normal \- Increased variability in length of body hair \- Shift in anagen-to-telogen ratio towards anagen \- Unusually long eyelashes MOLECULAR BASIS \- Caused by mutation in the fibroblast growth factor 5 gene (FGF5, 165190.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	TRICHOMEGALY	c0854699	2,796	omim	https://www.omim.org/entry/190330	2019-09-22T16:32:29	{"omim": ["190330"], "orphanet": ["411788"], "synonyms": ["Alternative titles", "EYELASHES, LONG"]}
A number sign (#) is used with this entry because of evidence that microcephaly, seizures, and developmental delay (MCSZ) is caused by homozygous or compound heterozygous mutation in the PNKP gene (605610) on chromosome 19q13. Description Microcephaly, seizures, and developmental delay is an autosomal recessive neurodevelopmental disorder with onset in infancy. There is a range of phenotypic severity: some patients have a disease course consistent with early infantile epileptic encephalopathy (EIEE), whereas others have more well-controlled seizures and a protracted course associated with cerebellar atrophy and peripheral neuropathy (Shen et al., 2010 and Poulton et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features Shen et al. (2010) reported 6 unrelated kindreds, including 3 consanguineous families of Arabic Palestinian origin and 1 each of Arabic, Turkish, and mixed European ancestry, with microcephaly, infantile-onset seizures, and developmental delay, which the authors abbreviated as MCSZ. There were 11 affected individuals ranging in age from 1 month to 21 years. Microcephaly was progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly. However, 5 patients had a slightly simplified gyral pattern, 5 had enlarged ventricles, and 6 had a thin corpus callosum. All patients had microcephaly at birth; some were noted to have microcephaly on prenatal ultrasound. Onset of treatment-resistant seizures occurred before 6 months of age, and most seizures were of the complex partial type. Two patients had surgical resection, and 4 had placement of a vagal stimulator to control seizures. All had severe intellectual disability and delayed motor milestones with absent speech or speech limited to a few words. Most patients had behavioral problems with hyperactivity. A seventh family of mixed European origin with a slightly less severe phenotype was also identified. The patients were aged 8 years and 18 months. The older girl walked at 14 months, spoke at 18 months, and conversed at the level of a 3.5-year-old. She had moderate seizure control. Cells from 1 affected individual showed sensitivity to irradiation in culture, reflecting a deficiency in nonhomologous end-joining of DNA. In addition, patients' cells were significantly impaired in their ability to repair hydrogen-peroxide induced free radical DNA damage, and also showed a delayed ability to repair camptothecin-induced damage compared to controls. Despite the laboratory evidence of damage in DNA repair mechanisms, none of the patients had an apparent immunodeficiency, and none had developed cancer. ### Clinical Variability Poulton et al. (2013) reported 2 brothers, born of consanguineous Dutch parents from an isolated population, with early-childhood onset of a neurodegenerative disorder. Both patients showed microcephaly (-3.25 to -3.5 SD) and global developmental delay from infancy. One patient developed febrile seizures at 2.5 years of age. At age 9 years, he had severe microcephaly (-6 SD), short stature (-4 SD), and ataxic gait. The disorder was progressive: in his teens, he became wheelchair-bound, showed severe cerebellar atrophy on brain imaging, and developed a sensorimotor axonal polyneuropathy characterized by loss of reflexes, hypotonia, and muscular atrophy. The patient's younger brother had similar features, with delayed development, progressive microcephaly (-4.75 SD), loss of independent walking, severe progressive cerebellar atrophy, and signs of a demyelinating polyneuropathy. He developed seizures at age 12 months. The seizure frequency decreased over time in both patients. Poulton et al. (2013) emphasized the neurodegenerative character of the disorder in these patients, and suggested that the phenotype was distinct from that reported by Shen et al. (2010). Inheritance The transmission pattern of MCSZ in the families reported by Shen et al. (2010) was consistent with autosomal recessive inheritance. Molecular Genetics By genomewide linkage analysis followed by candidate gene sequencing of a region on chromosome 19q13 in families with EIEE10, Shen et al. (2010) identified homozygous or compound heterozygous mutations in the PNKP gene (605610.0001-605610.0004), resulting in a loss of protein function. In 2 Dutch brothers, born of consanguineous parents, with a somewhat protracted course of MCSZ, Poulton et al. (2013) identified a homozygous truncating mutation in the PNKP gene (605610.0002). Patient fibroblasts showed increased susceptibility under stress conditions compared to controls. The same mutation had been found by Shen et al. (2010) in patients with a more severe epilepsy phenotype. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly, progressive MUSCLE, SOFT TISSUES \- Hypotonia \- Muscular atrophy NEUROLOGIC Central Nervous System \- Mental retardation, severe \- Delayed motor development \- Seizures, refractory, infantile-onset \- Lack of speech or only a few words \- Cerebellar ataxia (in some patients) \- Loss of independent ambulation \- Simplified gyral pattern \- Thin corpus callosum \- Enlarged ventricles \- Cerebellar atrophy, progressive (in some patients) Peripheral Nervous System \- Sensorimotor polyneuropathy (in some patients) \- Hyporeflexia (in some patients) Behavioral Psychiatric Manifestations \- Hyperactivity LABORATORY ABNORMALITIES \- Patient cells show defective DNA repair in response to irradiation and free radical damage MISCELLANEOUS \- Onset prenatally or at birth \- Some patients may have a more protracted disorder with neurodegeneration MOLECULAR BASIS \- Caused by mutation in the polynucleotide kinase 3-prime phosphatase gene (PNKP, 605610.0001 ) ▲ 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 inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	c0393706	2,797	omim	https://www.omim.org/entry/613402	2019-09-22T15:58:47	{"doid": ["0080457"], "omim": ["613402"], "orphanet": ["1934"], "synonyms": ["Alternative titles", "EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10"]}
Vici syndrome is a multisystem disorder characterized by agenesis (failure to develop) of the corpus callosum, cataracts , hypopigmentation of the eyes and hair, cardiomyopathy, and combined immunodeficiency. Hearing loss, seizures, and delayed motor development have also been reported. Swallowing and feeding difficulties early on may result in a failure to thrive. Recurrent infections of the respiratory, gastrointestinal, and urinary tracts are common. Vici syndrome is caused by mutations in the EPG5 gene and is inherited in an autosomal recessive manner. Treatment is mainly supportive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Vici syndrome	c1855772	2,798	gard	https://rarediseases.info.nih.gov/diseases/448/vici-syndrome	2021-01-18T17:57:11	{"mesh": ["C535566"], "omim": ["242840"], "umls": ["C1855772"], "orphanet": ["1493"], "synonyms": ["Immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum", "Absent corpus callosum cataract immunodeficiency", "Dionisi Vici Sabetta Gambarara syndrome"]}
Pontiac fever (PF) is a mild form of legionellosis (see this term) manifesting with flu-like symptoms such as nausea, myalgia, fever, cough and headache but without pneumonia. ## Epidemiology The incidence is unknown. Due to the disease's mild and non-specific manifestations it is thought to be underreported. PF is characterised by a high attack rate (number of patients affected / number of people exposed) of up to 95%. ## Clinical description Pontiac fever has a short incubation period ranging from 30-90 hours after infection and affects mainly adults but also children. The disease manifests as an influenza-like syndrome with fever, headache, myalgia and fatigue. In some cases, patients may also experience thoracic pain, dyspnea, diarrhea and vomiting, ocular redness with photophobia and arthralgia. These symptoms usually last 2-7 days and patients recover without treatment. ## Etiology PF is caused by an infection with Legionella pneumophila and Legionella non-pneumophila by inhalation of aerosols from contaminated water, most frequently from showers, whirlpools, spas and hot tubs. The bacteria are found in wet soil and water. It is currently unknown why infection with Legionella evolves into LD or PF in any given case, but as PF is usually observed in immunocompetent patients, immune system status could play a role. ## Diagnostic methods Laboratory diagnosis is rarely performed and is usually done retrospectively by detecting seroconversion or high titers of antibody to Legionella in serum samples. The diagnosis can also be made by detection of the L. pneumophila antigen in urine samples. ## Differential diagnosis Influenza closely resembles PF and must therefore be excluded. ## Management and treatment No treatment is needed for PF and recovery without treatment is the rule. ## Prognosis There is no fatality associated with PF. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pontiac fever	c0343528	2,799	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99748	2021-01-23T17:03:10	{"mesh": ["D007877"], "umls": ["C0343528"], "icd-10": ["A48.2"]}

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