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## Description
This progressive neurodegenerative disorder is characterized by early childhood onset of spastic ataxia with mental retardation, cerebellar signs, and variable optic atrophy (Hogan and Bauman, 1977).
Clinical Features
Hogan and Bauman (1977) reported 4 unrelated patients with early childhood onset of a progressive neurologic disorder characterized by delayed psychomotor development, spastic ataxia affecting the upper and lower limbs, and later onset of nystagmus and dysarthria. All had a wide-based gait and signs of cerebellar dysfunction, including tremor, dysmetria, and poor coordination of rapid alternating movements and fine finger movements. Hyperreflexia and ankle clonus were commonly present. Three patients had optic atrophy, 2 also with sensorineural hearing loss. Three patients had abnormal EEG findings during sleep, although overt seizures were not reported. Two patients also had evidence of a peripheral neuropathy. Three patients had abnormal EEG findings during sleep, although overt seizures were not reported. Two patients had sibs who were less severely affected. It is difficult to know whether this was distinct from other recessive cerebellar disorders, and Hogan and Bauman (1977) noted overlap with Behr syndrome (210000).
Senanayake (1992) described an 11-year-old girl who had developed spasticity, ataxia, internuclear ophthalmoplegia, dementia, and startle myoclonus at the age of 5 years. The deep tendon reflexes were exaggerated. Computed tomography showed generalized cerebellar atrophy. Her asymptomatic younger brother had early bilateral optic atrophy. The proband was the eldest of 3 children whose parents were first cousins. The cases of Senanayake (1992) were similar to those described by Van Bogaert and Martin (1974); see 271250. There were similarities to a partial hexosaminidase A deficiency (272800), 3-methylglutaconic aciduria III (258501), and adult Leigh disease (161700). However, no biochemical data were presented.
Inheritance
Consanguinity in 1 family and affected sibs in another family reported by Hogan and Bauman (1977) suggested autosomal recessive inheritance of this form of spastic ataxia.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural (variable) Eyes \- Nystagmus \- Optic atrophy \- Decreased visual acuity SKELETAL Spine \- Scoliosis NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Spasticity \- Ataxia \- Wide-based gait \- Upper limbs affected \- Tremor \- Spastic ataxia \- Hyperreflexia \- Mental retardation \- Dysarthria \- Extensor plantar responses \- Ankle clonus \- Cerebellar signs \- Dysmetria \- Poor coordination \- Clumsiness \- Abnormal EEG activity during sleep Peripheral Nervous System \- Peripheral neuropathy (variable) \- Poor vibratory sense MISCELLANEOUS \- Early childhood onset \- Progressive disorder \- Five patients have been reported (as of April 2011) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ATAXIA, SPASTIC, CHILDHOOD-ONSET, AUTOSOMAL RECESSIVE, WITH OPTIC ATROPHY AND MENTAL RETARDATION | c3151619 | 4,200 | omim | https://www.omim.org/entry/270500 | 2019-09-22T16:22:15 | {"omim": ["270500"]} |
A number sign (#) is used with this entry because of evidence that Bethlem myopathy-1 (BTHLM1) is caused by heterozygous mutation in the COL6A1 gene (120220), the COL6A2 gene (120240), or the COL6A3 gene (120250).
See also Ullrich congenital muscular dystrophy-1 (UCMD1; 254090), an allelic disorder that shows autosomal recessive inheritance and a more severe phenotype.
### Genetic Heterogeneity of Bethlem Myopathy
BTHLM2 (616471) is cased by mutation in the COL12A1 gene (120320) on chromosome 6q.
Nomenclature
At the 229th ENMC international workshop, Straub et al. (2018) classified autosomal dominant Bethlem myopathy caused by mutation in one of the collagen VI genes as a form of limb-girdle muscular dystrophy (LGMDD5).
Clinical Features
Bethlem and van Wijngaarden (1976) described 3 Dutch families in which 28 patients suffered from benign myopathy with autosomal dominant inheritance. The onset was in early infancy, progression was slow, and many patients reached an advanced age. The patients had moderate weakness and atrophy of the muscles of the trunk and limbs, the proximal muscles being more involved than the distal muscles, and the extensors more than the flexors. Early flexion contractures of the elbow and interphalangeal joints of the last 4 fingers, and plantar flexion contractures of the ankles were constant findings. In contrast to Emery-Dreifuss muscular dystrophy (310300), contractures of the neck and spine were rarely seen (Mohire et al., 1988). Moreover, 4 of the 28 patients had congenital torticollis. The serum creatine phosphokinase activity was usually not elevated, and histopathologic findings were nonspecific. Genealogic investigations showed no relationship between these 3 families which had lived in the Netherlands from at least the beginning of the 18th century. Arts et al. (1978) described another family of Polish descent in which 6 members in 4 generations suffered from what appeared to be the same disorder. Congenital torticollis was a feature in 1 patient.
Schmalbruch et al. (1987) described a family in which members of both sexes in 3 generations had a benign form of congenital muscular dystrophy. Onset of symptoms was in early childhood and progression, if any, was slow. The proximal limb muscles, the sternocleidomastoid, and anterior tibial muscles were affected. One patient had torticollis and all had heel-cord shortening. There was no cardiomyopathy. Creatine kinase was elevated, and a histologic study showed necrotizing myopathy with pronounced regeneration and formation of aberrant myofibrils (ringbinden) and fibrosis. Leyten et al. (1986) described father and daughter with congenital muscular dystrophy. Mitochondrial abnormalities were found on muscle biopsy.
Merlini et al. (1994) described 2 families with early-onset, benign, autosomal dominant myopathy with contractures and reviewed 6 previously reported families with Bethlem myopathy. In both families, there were several instances of male-to-male transmission. Fifteen of the 21 examined members proved to have myopathy with contractures, although several of them were so mildly affected that they considered themselves asymptomatic. Electromyography demonstrated a myopathic pattern, and nerve conduction tests were normal. CT scan demonstrated unexpectedly severe fatty replacement of paravertebral muscles and relatively preserved gluteal muscles. Merlini et al. (1994) suggested that the hallmark of Bethlem myopathy was contractures of the last 4 fingers. Elbow contractures were also present in more than half the subjects, but the severity was not as great as that seen in Emery muscular dystrophy. There was no cardiac or respiratory involvement.
Tohyama et al. (1994) described an affected mother and daughter with contractures and mild proximal weakness. Muscle biopsy showed dystrophic features with evidence of fiber necrosis and regeneration. CT scanning demonstrated decreased volume of paravertebral muscles and low densities in various proximal muscles with essentially normal distal musculature. Tohyama et al. (1994) distinguished their cases from Bethlem myopathy because of dystrophic changes seen in muscle biopsy. However, the clinical presentation of both the Bethlem cases and these reported were similar.
Bethlem myopathy shows a distribution of proximal muscle weakness similar to that observed in autosomal dominant limb-girdle muscular dystrophy (see, e.g., LGMDD1, 603511). However, Bethlem myopathy differs from most LGMDs in 2 ways: first, Bethlem myopathy presents with joint contractures, most commonly observed at the elbows, ankles, and neck; second, onset in Bethlem myopathy is in early childhood, whereas most dominant LGMDs show adult onset. It is now evident that Bethlem myopathy is a progressive disorder in adulthood (Jobsis et al., 1999). Many patients with Bethlem myopathy need a wheelchair after the age of 50 years, and some die of respiratory failure caused by diaphragmatic paralysis (Haq et al., 1999).
Lampe and Bushby (2005) provided a review of collagen VI-related muscle disorders. The development of contractures is a hallmark of Bethlem myopathy. The contractures may appear and disappear in various joints during childhood, but nearly all patients eventually show flexion contractures of the fingers, wrists, elbows, and ankles, and these, in addition to weakness, contribute to disability. Lampe and Bushby (2005) pictured unusual skin features that may be present in some Bethlem myopathy patients, including follicular hyperkeratosis, keloid formation, and 'cigarette paper' scarring over the knees.
Inheritance
Bethlem myopathy is classically inherited in an autosomal dominant pattern; however, Gualandi et al. (2009) reported 2 unrelated patients with Bethlem myopathy who were each compound heterozygous for a truncating mutation and a missense mutation in the COL6A2 gene (Q819X, 120240.0011 and R830Q/R843W, 120240.0017; R366X, 120240.0018 and D871N, 120240.0019, respectively). Both patients remained ambulatory as adults, and muscle biopsies and studies of fibroblasts showed variable degrees of aberrant collagen VI microfilament formation. Gualandi et al. (2009) noted that autosomal recessive inheritance had not been reported in Bethlem myopathy and suggested that collagen VI-related myopathies comprise a spectrum of conditions with variable severity. In addition, the findings in these patients did not support pure haploinsufficiency as a causative mechanism for Bethlem myopathy, and suggested that some previously reported patients may harbor a second missed mutation. The genotype findings in these patients had important implications for genetic counseling.
Mapping
Speer et al. (1995) studied linkage in the family with Bethlem myopathy originally reported by Mohire et al. (1988). Sixteen affected members with 10 unaffected relatives and 4 spouses were subjected to linkage analysis. Linkage to the 7-cM LGMD1A interval on chromosome 5 could be excluded.
### Genetic Heterogeneity
In 6 Dutch families, Jobsis et al. (1996) demonstrated linkage to highly polymorphic microsatellite markers on chromosome 21q22.3. A maximum 2-point lod score of 6.86 was observed for marker PFKL with a sex averaged recombination fraction of 0.05. One recombination event was thought to exclude the collagen VI alpha-1 gene (120220) as a candidate.
Speer et al. (1996) reported results of linkage analysis in a large family of French-Canadian descent in whom 19 of 36 members were affected with Bethlem myopathy. The diagnostic criteria included proximal greater than distal extremity weakness, joint contractures, and childhood onset of symptoms at approximately 2 to 5 years of age. Since collagen genes were postulated as the candidate genes for Bethlem myopathy mapping to chromosome 21, Speer et al. (1996) analyzed the COL6A3 gene (120250) region on chromosome 2q. Lod scores of 8.13 and 7.03 were observed between Bethlem myopathy and the markers D2S345 and D2S338. Analysis of chromosome 2 markers permitted localization of the disease gene to a 17-cM interval spanned by D2S336 and D2S395. Fluorescence in situ hybridization studies revealed that the COL6A3 gene was localized between D2S336 and D2S395. Speer et al. (1996) reported that this finding was consistent with the hypothesis that in the Dutch families described by Jobsis et al. (1996) and in the family reported by them, Bethlem myopathy is caused by mutations in different subunits of type VI collagen. Nine kindreds showed genetic linkage to the COL6A1-COL6A2 cluster on 21q22.3, whereas one family showed linkage to markers on 2q37 close to COL6A3.
Diagnosis
Hicks et al. (2008) found that immunofluorescence labeling of collagen VI in skin biopsy-derived fibroblast cultures from patients suspected of having Bethlem myopathy was highly predictive of a COL6A mutation compared to immunofluorescence for collagen VI and basal lamina-located perlecan (HSPG2; 142461) in muscle samples. Abnormalities in the fibroblast labeling pattern of collagen VI were detected in more than 78% of genetically confirmed patients. Among 19 patients with an unknown genotype, the fibroblast technique providing a 75% positive predictive value, 100% sensitivity and negative predictive values, and specificity of 63%.
Clinical Management
Merlini et al. (2008) found that treatment of a patient with Bethlem myopathy and 4 UCMD patients with 2 divided doses of orally administered cyclosporin A resulted in decreased mitochondrial dysfunction and apoptosis in skeletal muscle biopsies 1 month later. Cellular signs of muscle regeneration were also observed. Clinical response could not be assessed because of the limited time frame, but the study provided a proof of principle and indicated that mitochondrial dysfunction plays a critical role in the pathogenesis of the disorder.
Molecular Genetics
In affected members of a kindred with Bethlem myopathy, Jobsis et al. (1996) demonstrated a mutation in the COL6A1 gene (120220.0001). In affected members from 2 other kindreds, Jobsis et al. (1996) identified a mutation in the COL6A2 gene (120240.0001). Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha-2-subunit of laminin, these observations suggested to Jobsis et al. (1996) a similar mechanism in Bethlem myopathy.
In affected members of an Italian family with Bethlem myopathy previously reported by Merlini et al. (1994), Vanegas et al. (2002) identified a heterozygous splice site mutation in the COL6A1 gene (120220.0008).
Lampe et al. (2005) sequenced all 3 COL6 genes from genomic DNA in 79 patients with Ullrich congenital muscular dystrophy (UCMD; 254090) or Bethlem myopathy, and found putative mutations in 1 of the COL6 genes in 62% of patients. Some patients showed changes in more than one of the COL6 genes, and some UCMD patients appeared to have dominant rather than recessive disease. Lampe et al. (2005) concluded that these findings may explain some or all of the cases of UCMD that are unlinked to the COL6 gene under a recessive model and noted that the large number of SNPs generated in this study may be of importance in determining the major phenotypic variability seen in this group of disorders.
Lucioli et al. (2005) identified 8 different mutations in the COL6A1 gene in 16 of 30 unrelated probands with a clinical diagnosis of Bethlem myopathy; 2 of the 30 probands had a mutation in the COL6A2 gene and the COL6A3 gene, respectively. The most common COL6A1 mutation was a splice site mutation (120220.0006).
In 2 unrelated patients with Bethlem myopathy, Baker et al. (2007) identified 2 different heterozygous mutations in the COL6A2 gene (120240.0009; 120240.0010). In vitro studies indicated defective collagen VI synthesis and secretion.
In 2 unrelated patients with Bethlem myopathy, Baker et al. (2007) identified 2 different heterozygous mutations in the COL6A3 gene (120250.0005; 120250.0006).
Genotype/Phenotype Correlations
Brinas et al. (2010) classified 49 patients with muscular dystrophy due to mutations in 1 of the 3 COL6A genes into 3 clinical groups: 9 (18%) had a severe phenotype with contractures and never achieved ambulation, 26 (53%) had a moderate phenotype and were initially able to walk but tended to lose ambulation later in childhood, and 14 (29%) had a milder course and remained ambulatory at a mean age of 20 years. All patient fibroblasts showed absent or reduced COL6A secretion, with frequent intracellular retention, and the decreased levels correlated with increased disease severity. Genetic analysis showed equal distribution of mutations across the cohort: 17 (30%) in COL6A1, 26 (46%) in COL6A2, and 13 (23%) in COL6A3. Thirty patients (61%) had dominant de novo mutations, and 18 had recessive mutations. Fourteen patients (28.5%) had truncating mutations. Homozygous truncating mutations before or within the triple helix (TH) domain were associated with the most severe phenotypes. The moderate phenotype was associated with heterozygous mutations resulting in the skipping of part of the TH domains or affecting the glycine residue of the Gly-X-Y domain. RT-PCR analysis was helpful in defining the effect of splice site mutations.
Substitutions in the conserved Gly-X-Y motif in the triple helix (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies, accounting for almost one-third of all pathogenic mutations. Butterfield et al. (2013) analyzed genotype/phenotype correlations of 194 individuals with glycine substitutions in the TH domain of the COL6A1, COL6A2, or COL6A3 genes. The cohort included 97 newly reported cases and 97 published cases. In all 3 genes, 89% of the mutations clustered in the N-terminal regions before the 17th Gly-X-Y triplet (TH17). This important landmark is delineated by cysteine residues in the COL6A3 chain, which form disulfide bonds stabilizing tetramers. Patients with mutations inside the critical region of Gly-X-Y triplets 10-15 tended to have a more severe phenotype than those with mutations outside this critical region. However, identical glycine substitutions were associated with both severe and mild phenotypes. The most commonly observed mutation was G284R in the COL6A1 gene (120220.0012), found in 28 cases with variable phenotypes. Glycine substitutions in the TH domain were dominantly acting in 96% of cases, and recessive mutations tended to occur in the C-terminal end of the TH domain. Butterfield et al. (2013) concluded that the clustering of glycine substitutions in this region is not based on features of the primary sequence, but rather reflects a functional importance of this domain.
Animal Model
Menazza et al. (2010) investigated whether reactive oxygen species (ROS) produced in mitochondria by monoamine oxidase (MAO) contribute to muscular dystrophy pathogenesis. Pargyline, an MAO inhibitor, reduced ROS accumulation along with a beneficial effect on the dystrophic phenotype of Col6a1 -/- mice, a model of Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD; 254090), and mdx mice, a model of Duchenne muscular dystrophy (310200). Oxidation of myofibrillar proteins, as probed by formation of disulfide crossbridges in tropomyosin (see 191010), was detected in both Col6a1 -/- and mdx muscles. Notably, pargyline significantly reduced myofiber apoptosis and ameliorated muscle strength in Col6a1 -/- mice. Menazza et al. (2010) concluded that there is a novel and determinant role of MAO in muscular dystrophies, adding evidence of the pivotal role of mitochondria and suggesting a therapeutic potential for MAO inhibition.
INHERITANCE \- Autosomal dominant \- Autosomal recessive HEAD & NECK Neck \- Torticollis, congenital CARDIOVASCULAR Heart \- No cardiac involvement RESPIRATORY \- Respiratory failure due to muscle weakness may occur in late stages SKELETAL \- Contractures Limbs \- Contractures of the elbows \- Contractures of the ankles Hands \- Long finger flexion contractures of the last four fingers MUSCLE, SOFT TISSUES \- Delayed motor milestones \- Muscle weakness, limb-girdle \- Proximal muscle weakness more severe than distal muscle weakness \- Extensor muscle weakness more severe than flexor muscle weakness \- Muscle atrophy, mild, more proximal than distal \- Hypotonia, in neonatal onset \- Muscle biopsy shows nonspecific myopathic changes PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements may occur LABORATORY ABNORMALITIES \- Normal or increased serum creatine kinase MISCELLANEOUS \- Variable severity \- Onset usually in early childhood, although ranges from birth to adulthood \- Slow progression \- Approximately half of patients need ambulatory support after the fifth decade \- Ullrich congenital muscular dystrophy ( 254090 ) is an allelic disorder with autosomal recessive inheritance and a more severe phenotype MOLECULAR BASIS \- Caused by mutation in the collagen VI, alpha-1 polypeptide gene (COL6A1, 120220.0001 ) \- Caused by mutation in the collagen VI, alpha-2 polypeptide gene (COL6A2, 120240.0001 ) \- Caused by mutation in the collagen VI, alpha-3 polypeptide gene (COL6A3, 120250.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| BETHLEM MYOPATHY 1 | c1834674 | 4,201 | omim | https://www.omim.org/entry/158810 | 2019-09-22T16:37:56 | {"doid": ["0050663"], "mesh": ["C535436"], "omim": ["158810"], "orphanet": ["610"], "synonyms": ["Alternative titles", "BETHLEM MYOPATHY", "MYOPATHY, BENIGN CONGENITAL, WITH CONTRACTURES", "MUSCULAR DYSTROPHY, BENIGN CONGENITAL", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 5"], "genereviews": ["NBK1503"]} |
An inherited coagulation disorder characterized by recurrent venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein S.
## Epidemiology
Prevalence of partial protein S deficiency (heterozygous individuals) is estimated at 0.16-0.21% in the general population. Prevalence of severe protein S deficiency (homozygous or compound heterozygous individuals) is unknown but is probably comparable to that of severe protein C deficiency which is estimated at 1/500,000. Men and women are equally affected.
## Clinical description
In severe protein S deficiency, the disease manifests several hours to days after birth, with purpura fulminans (see this term) or massive venous thrombosis. Purpura fulminans is a life-threatening condition involving severe clotting throughout the body and causing necrosis of tissues. Severe retinopathy of prematurity (ROP) (see this term) may also occur. Heterozygous patients are usually asymptomatic until adulthood. Thrombotic episodes are mainly provoked by other risk factors such as surgery, pregnancy or immobilization. Deep vein thrombosis of the lower limbs with or without pulmonary embolism is the most common manifestation of the disease. Arterial thrombosis may also occur.
## Etiology
Protein S deficiency is caused by mutations in the PROS1 gene (3q11-q11.2).
## Diagnostic methods
Diagnosis is based on the measurement of protein S antigen levels (total protein S or free protein S) and anticoagulant activity. There are three biological forms. Type I and type III are quantitative deficiencies with low free antigen levels (with normal total protein S levels in type III and decreased total protein S levels in type I deficiency). Type II is a qualitative deficiency with normal total and free protein S levels. Molecular testing is available, but is unnecessary for diagnosis.
## Differential diagnosis
Differential diagnoses include other inherited thrombophilias including antithrombin and protein C deficiencies (see these terms).
## Antenatal diagnosis
Antenatal diagnosis is feasible for families with affected children and is based on the identification of the causal mutation on DNA obtained by chorionic villus sampling.
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
Administration of fresh frozen plasma may be required for the initial treatment of neonatal purpura fulminans. Surgical procedures may be required for excision of thrombotic lesions. Patients with thromboses are treated with anticoagulant therapy (heparin, wafarin). Attention should be paid to the risk of coumarin-induced skin necrosis. Preventive treatment is indicated in cases with strong positive family history of thrombotic diseases, during the peripartum period or perioperatively.
## Prognosis
Prognosis is severe in homozygous or compound heterozygous patients. Prognosis is good for heterozygous patients. With adequate treatment and monitoring, the risk of thromboembolic disease is markedly reduced. Mortality may result from pulmonary embolism.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Severe hereditary thrombophilia due to congenital protein S deficiency | c3278211 | 4,202 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=743 | 2021-01-23T17:10:03 | {"omim": ["612336", "614514"], "icd-10": ["D68.5"], "synonyms": ["Autosomal recessive thrombophilia due to congenital protein S deficiency"]} |
Faye-Petersen et al. (1991) described a female infant, born at term to normal unrelated parents, who showed this combination of abnormalities. The osteochondrodysplasia was of a nonlethal rhizomelic type. Radiologic and light microscopic findings suggested that this was a distinct form of osteochondrodysplasia.
Endocrine \- Hypertension Skel \- Rhizomelic osteochondrodysplasia Inheritance \- Autosomal dominant Neuro \- Callosal agenesis \- Hydrocephalus Heme \- Thrombocytopenia ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| OSTEOCHONDRODYSPLASIA, RHIZOMELIC, WITH CALLOSAL AGENESIS, THROMBOCYTOPENIA, HYDROCEPHALUS, AND HYPERTENSION | c1833688 | 4,203 | omim | https://www.omim.org/entry/166990 | 2019-09-22T16:36:49 | {"mesh": ["C563478"], "omim": ["166990"]} |
## Clinical Features
Edwards et al. (1988) described a family with orofaciodigital manifestations including hypertelorism or telecanthus, broad, bifid nasal tip, median cleft lip, tongue lobulation and/or hamartomas, oral frenula, high-arched or cleft palate, bilateral polydactyly, and duplicated halluces. Males in the family also had abnormal tibia, short stature, and recurrent aspiration pneumonia. The male proband also was noted to have almost complete hypoplasia of the epiglottis and arytenoid cartilages. X-linked recessive inheritance was suggested.
In a review of orofaciodigital syndromes, Toriello (1993) listed the male patient of Goodship et al. (1991), who had classified him as a case of OFDS type I (311200), as a probable case of OFDS VIII. The phenotype included hydrocephalus, absent corpus callosum, hypertelorism, pseudocleft upper lip, lobed tongue, oral frenula, cleft soft palate, atrioventricular septal defect, bifid halluces, and postaxial polydactyly of hands. Toriello (1993) stated that OFDS types I and VIII may be allelic, with male survival occurring in type VIII but not in type I.
INHERITANCE \- X-linked recessive GROWTH Height \- Short stature HEAD & NECK Eyes \- Hypertelorism \- Telecanthus \- Strabismus Nose \- Broad nasal tip \- Bifid nasal tip Mouth \- Median cleft lip \- Tongue lobulation \- Tongue hamartoma \- Oral frenula \- High-arched palate \- Cleft palate Teeth \- Absent teeth RESPIRATORY Larynx \- Hypoplastic epiglottis Lung \- Recurrent aspiration pneumonia SKELETAL Limbs \- Short tibiae Hands \- Polydactyly \- syndactyly Feet \- Bifid halluces \- Forked metatarsal \- Syndactyly SKIN, NAILS, & HAIR Skin \- Milia NEUROLOGIC Central Nervous System \- Developmental delay MISCELLANEOUS \- Mild manifestations in carrier females (cleft lip, cleft tongue) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| OROFACIODIGITAL SYNDROME VIII | c0796101 | 4,204 | omim | https://www.omim.org/entry/300484 | 2019-09-22T16:20:20 | {"doid": ["0060378"], "mesh": ["C557820"], "omim": ["300484"], "orphanet": ["2755"], "synonyms": ["Alternative titles", "OFDS VIII", "ORAL-FACIAL-DIGITAL SYNDROME, TYPE VIII", "ORAL-FACIAL-DIGITAL SYNDROME WITH HYPOPLASTIC EPIGLOTTIS", "EDWARDS SYNDROME"]} |
-spermia,
Further information: Testicular infertility factors
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* talk
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Aspermia —lack of semen; anejaculation
Asthenozoospermia —sperm motility below lower reference limit
Azoospermia —absence of sperm in the ejaculate
Hyperspermia —semen volume above higher reference limit
Hypospermia —semen volume below lower reference limit
Oligozoospermia —total sperm count below lower reference limit
Necrozoospermia—absence of living sperm in the ejaculate
Teratozoospermia —percent normal forms below lower reference limit
In medicine, hyperspermia is a condition in which a male has an abnormally large ejaculate (or semen) volume,[1] and is generally defined in humans when the ejaculate is above 5.5 ml.[2] Males with hyperspermia usually have higher sex drives than males that do not. It is the opposite of hypospermia.
## References[edit]
1. ^ Cooke, S.; Tyler, J. P. P.; Driscoll, G. L. (1995). "Andrology: Hyperspermia: the forgotten condition?". Hum. Reprod. 10 (2): 367–368. doi:10.1093/oxfordjournals.humrep.a135944. PMID 7769063.
2. ^ Padubidri; Daftary (2011). Shaw's Textbook of Gynaecology, 15e. p. 204. ISBN 9788131225486
* v
* t
* e
Male diseases of the pelvis and genitals
Internal
Testicular
* Orchitis
* Hydrocele testis
* Testicular cancer
* Testicular torsion
* Male infertility
* Aspermia
* Asthenozoospermia
* Azoospermia
* Hyperspermia
* Hypospermia
* Oligospermia
* Necrospermia
* Teratospermia
Epididymis
* Epididymitis
* Spermatocele
* Hematocele
Prostate
* Prostatitis
* Acute prostatitis
* Chronic bacterial prostatitis
* Chronic prostatitis/chronic pelvic pain syndrome
* Asymptomatic inflammatory prostatitis
* Benign prostatic hyperplasia
* Prostate cancer
Seminal vesicle
* Seminal vesiculitis
External
Penis
* Balanoposthitis / Balanitis
* Balanitis plasmacellularis
* Pseudoepitheliomatous keratotic and micaceous balanitis
* Phimosis
* Paraphimosis
* Priapism
* Sexual dysfunction
* Erectile dysfunction
* Peyronie's disease
* Penile cancer
* Penile fracture
* Balanitis xerotica obliterans
Other
* Hematospermia
* Retrograde ejaculation
* Postorgasmic illness syndrome
This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it.
* v
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*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hyperspermia | None | 4,205 | wikipedia | https://en.wikipedia.org/wiki/Hyperspermia | 2021-01-18T19:05:45 | {"wikidata": ["Q16989722"]} |
A number sign (#) is used with this entry because CFHR5 deficiency is caused by heterozygous mutation in the CFHR5 gene (608593) on chromosome 1q32.
Clinical Features
Gale et al. (2010) reported 2 unrelated families with an autosomal dominant form of glomerulonephritis resulting in renal failure. Both families had ancestors from the Troodos mountains of Cyprus. Additional patients of Cypriot origin with a similar disorder were subsequently identified. In all, there were 26 patients from 11 families. All had microscopic hematuria, and many developed macroscopic hematuria following upper respiratory tract infections. Renal biopsies showed glomerulonephritis with C3 (120700) deposits in the subendothelium and mesangium. There was also mesangial matrix expansion, increased glomerular cellularity, and segmental capillary wall thickening. The initial pathologic diagnosis in these patients was membranoproliferative glomerulonephritis type I, which was later refined to C3 glomerulonephritis. The risk of progression appeared to be greater in men than in women with the disease. None of the patients had evidence of retinal disease.
In a comment on the report of Gale et al. (2010), Karumanchi and Thadhani (2010) noted the clinical similarity of this disorder, which they termed 'CFHR5 nephropathy,' to IgA nephropathy (161950).
Vernon et al. (2012) reported a girl who developed chronic glomerulonephritis with C3 deposits following a streptococcal infection. The patient presented at age 7 years with dark-colored proteinuria after a 10-day history of fever and sore throat. After treatment for the infection, she had persistent hematuria and proteinuria. Nine months later, kidney biopsy showed mesangial hypercellularity, segmental endocapillary hypercellularity, and segmental capillary wall double contours. There was mesangial and capillary deposition of C3, C9 (120940), and CFHR5. Electron microscopy showed thickening of the glomerular basement membranes, intramembranous electron-dense deposits, and subendothelial and subepithelial deposits. Twenty months after presentation, a second kidney biopsy showed persistent membranoproliferative glomerulonephritis with tubulointerstitial scarring. Serum CFHR5 was decreased to 37.3% of control values. Treatment with an angiotensin receptor (see 106165) blocker resulted in improved kidney function.
Inheritance
The transmission pattern of CFHR5 deficiency in the Cypriot families reported by Gale et al. (2010) was consistent with autosomal dominant inheritance.
Molecular Genetics
By linkage analysis followed by candidate gene analysis in 2 families with CFHR5 deficiency and glomerulonephritis with family origins in Cyprus, Gale et al. (2010) identified a heterozygous duplication of exons 2 and 3 of the CFHR5 gene (608593.0001). The internal duplication was not seen in a set of 102 controls, but was found in 1 of 1,015 Cypriot controls. Screening of this gene in additional patients of Cypriot origin identified several more with the same duplication. In total, 26 patients from 11 ostensibly unrelated families with renal disease carried the mutation. Haplotype analysis performed in 5 families indicated a founder effect. In vitro functional expression studies showed that the mutant protein bound less well to surface-bound complement compared to wildtype. However, the mutant protein circulated and showed enhanced cofactor activity with complement factor I (CFI; 217030) compared to wildtype CFHR5. Although the precise pathomechanism, was unclear, the findings of abnormal complement deposition in patient renal biopsies indicated a defect in the regulation of C3.
In a girl with CFHR5 deficiency resulting in glomerulonephritis and persistent renal disease following a streptococcal infection, Vernon et al. (2012) identified a heterozygous truncating mutation in the CFHR5 gene (608693.0005). The mutation was also present in her unaffected mother and sister, suggesting that presence of the mutation is not sufficient to cause disease, but likely acts as a susceptibility factor for the development of glomerulonephritis.
INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Glomerulonephritis \- Hematuria \- Renal failure \- End-stage renal disease \- Glomerular C3 deposits, subendothelial and mesangial \- Mesangial matrix expansion \- Increased glomerular cellularity \- Segmental capillary wall thickening MISCELLANEOUS \- Hematuria may become apparent after respiratory infections (synpharyngitic) \- Progressive disorder \- Progression more frequent in men than women \- First identified in individuals of Cypriot origin MOLECULAR BASIS \- Caused by mutation in the complement factor H-related 5 gene (CFHR5, 608593.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CFHR5 DEFICIENCY | c0017662 | 4,206 | omim | https://www.omim.org/entry/614809 | 2019-09-22T15:54:15 | {"mesh": ["D015432"], "omim": ["614809"], "orphanet": ["329931", "329918", "54370"], "synonyms": ["Non-Ig-mediated membranoproliferative glomerulonephritis", "Non-Ig-mediated MPGN", "Non-immunoglobulin-mediated MPGN", "C3 glomerulopathy"]} |
Sara et al. (1981) developed a radioreceptor assay utilizing human fetal brain plasma membrane as matrix and somatomedin A as receptor. The concentration of the somatomedin thus assayed was about 4-fold higher in fetal blood than in adult blood. At birth, values fell in the adult range. Hitherto, 2 somatomedins (multitargetal growth-promoting polypeptides) had been purified from adult human plasma: somatomedin A (IGF2; 147470) and somatomedin C (IGF1; 147440)
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SOMATOMEDIN, EMBRYONIC | c1866879 | 4,207 | omim | https://www.omim.org/entry/182400 | 2019-09-22T16:34:45 | {"omim": ["182400"]} |
Tullio phenomenon, sound-induced vertigo, dizziness, nausea or eye movement (nystagmus) was first described in 1929 by the Italian biologist Prof. Pietro Tullio. (1881–1941)[1][2] During his experiments on pigeons, Tullio discovered that by drilling tiny holes in the semicircular canals of his subjects, he could subsequently cause them balance problems when exposed to sound.
The cause is usually a fistula in the middle or inner ear, allowing abnormal sound-synchronized pressure changes in the balance organs.[3] Such an opening may be caused by a barotrauma (e.g. incurred when diving or flying), or may be a side effect of fenestration surgery, syphilis or Lyme disease. Patients with this disorder may also experience vertigo, imbalance and eye movement set off by changes in pressure, e.g. when nose-blowing, swallowing or when lifting heavy objects.
Tullio phenomenon is also one of the common symptoms of superior canal dehiscence syndrome (SCDS), first diagnosed in 1998 by Dr. Lloyd B. Minor, The Johns Hopkins University, Baltimore, United States.[4]
## References[edit]
1. ^ Tullio, Pietro: Das Ohr und die Entstehung der Sprache und Schrift. Berlin, Germany: Urban & Schwarzenberg; 1929.
2. ^ Tullio, Pietro: Some experiments and considerations on experimental otology and phonetics: A lecture delivered at the meeting of the "Società dei cultori delle scienze ... e naturali" of Cagliari on 1st, July 1929: L. Cappelli 1929 ASIN: B0008B2T6Y
3. ^ Watson, R.D; et al. (2000-02-08). "Vestibular Hypersensitivity to sound". Neurology. Neurology.org. 54 (3): 722–8. doi:10.1212/WNL.54.3.722. PMID 10680810.
4. ^ Basura GJ, Cronin SJ, Heidenreich KD (2014). "Tullio phenomenon in superior semicircular canal dehiscence syndrome". Neurology. 82 (11): 1010. doi:10.1212/WNL.0000000000000217. PMID 24638216.
## External links[edit]
* Encyclopædia Britannica - Tullio Phenomenon
* Dr. Timothy C. Hain - Tullio's phenomenon
* University of Rochester
* Brain - Otolith Tullio Phenomenon
* American Hearing Research Foundation - Perilymph Fistula - Tullio Phenomenon
* Vestibular Disorders Association - SCDS
* Hopkins Medical News - The Clue in the Old Bones
* Hopkins Gazette - Old Bone Collection Reveals Basis for Some Dizziness
* Delaware Biotechnology Institute - SCDS with Tullio
* Delaware Biotechnology Institute - SCDS with Tullio - animation
* "Doctor, I can hear my eyes" \- W Albuquerque, A M Bronstein
* v
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* e
Physiology of balance and hearing
Hearing
General
* Auditory system
* Bone conduction
* Otoacoustic emission
* Tullio phenomenon
Pathway
* inner ear: Hair cells → Spiral ganglion → Cochlear nerve VIII →
* pons: Cochlear nucleus (Anterior, Dorsal) → Trapezoid body → Superior olivary nuclei →
* midbrain: Lateral lemniscus → Inferior colliculi →
* thalamus: Medial geniculate nuclei →
* cerebrum: Acoustic radiation → Primary auditory cortex
Balance
General
* Vestibular system
Pathway
* inner ear: Vestibular nerve VIII →
* pons: Vestibular nuclei (Medial vestibular nucleus, Lateral vestibular nucleus)
* cerebellum: Flocculonodular lobe
* spinal cord: Vestibulospinal tract (Medial vestibulospinal tract, Lateral vestibulospinal tract)
* thalamus: Ventral posterolateral nucleus
* cerebrum: Vestibular cortex
* Vestibulo-oculomotor fibers
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Tullio phenomenon | c0349686 | 4,208 | wikipedia | https://en.wikipedia.org/wiki/Tullio_phenomenon | 2021-01-18T18:35:01 | {"umls": ["C0349686"], "wikidata": ["Q684277"]} |
A number sign (#) is used with this entry because of evidence that complex cortical dysplasia with other brain malformations-3 (CDCBM3) is caused by heterozygous mutation in the KIF2A gene (602591) on chromosome 5q12.
For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
Clinical Features
Poirier et al. (2013) reported 2 unrelated children with microcephaly (-4 SD and -2.5 SD, respectively), early-onset epilepsy, and various malformations of cortical development, including agyria, posterior or frontal pachygyria, subcortical band heterotopia, and thin corpus callosum. One patient had dysmorphic basal ganglia. Brainstem and cerebellum were normal in both patients. Both had severe developmental delay and were bedridden with spastic paraplegia at ages 1 and 4 years, respectively.
Molecular Genetics
In 2 unrelated patients with complex cortical dysplasia and microcephaly, Poirier et al. (2013) identified different de novo heterozygous mutations in the KIF2A gene (H321D, 602591.0001 and S317N, 602591.0002). The first mutation was found by whole-exome sequencing and was not present in several genomic databases, including dbSNP, 1000 Genomes, the Exome Variant Server, and a local Paris Descartes Bioinformatics platform database. The second mutation was found by screening 162 individuals with various malformations of cortical development for variants in kinesin genes. In vitro functional expression studies showed that both mutations caused abnormal protein folding, resulting in abnormal cellular localization and a loss of protein function. Because KIF2A functions as a dimer, Poirier et al. (2013) postulated a dominant-negative effect. The findings extended the association between microtubule-based cellular processes and proper cortical development.
INHERITANCE \- Autosomal dominant GROWTH Other \- Intrauterine growth retardation (1 patient) HEAD & NECK Head \- Microcephaly Eyes \- Nystagmus (1 patient) NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Seizures \- Spastic tetraplegia \- Malformations of cortical development \- Thick cortex \- Subcortical band heterotopia \- Pachygyria \- Agyria \- Thin corpus callosum \- Dysmorphic basal ganglia (1 patient) MISCELLANEOUS \- Two unrelated patients have been reported (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the kinesin heavy chain member 2A (KIF2A, 602591.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 3 | c3809414 | 4,209 | omim | https://www.omim.org/entry/615411 | 2019-09-22T15:52:14 | {"omim": ["615411"]} |
A number sign (#) is used with this entry because autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA (mtDNA) deletions-4 (PEOA4) is caused by heterozygous mutation in the nuclear-encoded DNA polymerase gamma-2 gene (POLG2; 604983) on chromosome 17q.
Description
Progressive external ophthalmoplegia-4 is an autosomal dominant form of mitochondrial disease that variably affects skeletal muscle, the nervous system, the liver, and the gastrointestinal tract. Age at onset ranges from infancy to adulthood. The phenotype ranges from relatively mild, with adult-onset skeletal muscle weakness and weakness of the external eye muscles, to severe, with a multisystem disorder characterized by delayed psychomotor development, lactic acidosis, constipation, and liver involvement (summary by Young et al., 2011).
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Clinical Features
Longley et al. (2006) described a female patient with late-onset progressive external ophthalmoplegia (PEO) caused by heterozygous mutation in the gene encoding the catalytic subunit of DNA polymerase gamma (POLG2; 604983). The patient, aged 60 years, developed exercise intolerance and muscle pain by age 40, followed by ptosis, progressive external ophthalmoplegia, and mild weakness of the facial and limb muscles. She had impaired glucose tolerance, evidence of a cardiac conduction defect (left bundle branch block and intermittent bigeminy), and elevated serum creatine kinase. Her similarly affected mother was deceased; 2 sisters were unaffected. Skeletal muscle histochemistry revealed a mosaic cytochrome c oxidase (COX; see 123864) defect with 6% COX-negative fibers. Biochemical analysis of a skeletal muscle homogenate revealed normal respiratory chain complex activity. Southern blot analysis and long-range PCR of skeletal muscle mitochondrial DNA (mtDNA) revealed multiple mtDNA deletions. Real-time PCR of single muscle fibers detected high percentage levels of deleted mtDNA in the majority of COX-defective muscle fibers, typical of a multiple mtDNA deletion disorder. Longley et al. (2006) remarked that the patient had no specific clinical features that were different from 100 other PEO patients who were screened for mutations in POLG2 but had no mutation in the gene.
Young et al. (2011) reported 3 unrelated patients with PEOA4. There was large variability in clinical features and in severity. A 6-month-old boy was irritable and showed failure to thrive, lethargy, hypotonia, liver disease, and refractory seizures. A 19-year-old woman had progressive external ophthalmoplegia, exercise intolerance, easy fatigability, gastroesophageal reflux, delayed gastric emptying, respiratory insufficiency, lactic acidosis, and a history of failure to thrive. Muscle biopsy showed abnormal mitochondria. The third patient was an 8-year-old boy with neonatal hypotonia, developmental delay, seizures, constipation, abnormal liver enzymes, ketosis, cortical blindness, and cerebellar atrophy.
Molecular Genetics
Longley et al. (2006) screened for mutation in the POLG2 gene (604983) in 101 patients with PEO and multiple mtDNA deletions in skeletal muscle in whom no mutations in genes known to be associated with autosomal dominant PEO were found. They identified a heterozygous POLG2 mutation, G451E (604983.0001), in 1 patient. The smaller 55-kD accessory subunit (p55) of DNA polymerase gamma, encoded by the POLG2 gene, confers high processivity on the DNA polymerase gamma protein complex by increasing its affinity to DNA. Although G451E p55 retained a wildtype ability to bind DNA, it failed to enhance DNA-binding strength of the DNA polymerase gamma protein complex. The disorder was thought most likely to have arisen through haploinsufficiency or heterodimerization of the mutated and wildtype proteins, which promote mtDNA deletions by stalling the DNA replication fork. The progressive accumulation of mtDNA deletions causes cytochrome c oxidase (COX) deficiency in muscle fibers and results in the clinical phenotype.
Young et al. (2011) sequenced the POLG2 gene in 112 samples from patients suspected of having a defect in mtDNA replication, but who did not have mutations in the POLG gene (174763). Eight heterozygous POLG2 variants were identified in 8 patients and in 1 unaffected control. Detailed in vitro functional expression studies indicated that only 3 of the 7 novel variants, P205R (604983.0003), R369G (604983.0004), and a 2-bp deletion (1423delTT; 604983.0005), were functionally pathogenic. These mutant proteins showed variable defects in DNA binding, binding to the p140 catalytic component of mtDNA polymerase, and ability to stimulate p140-induced primer extension, indicating an impairment in processivity. The other variants identified, G103S, L153V, D386E, and S423Y, were believed to be polymorphisms because they showed activity similar to the wildtype protein in functional assays. The study emphasized the need to characterize biochemical consequences of variants quantitatively before classifying them as pathogenic.
INHERITANCE \- Autosomal dominant GROWTH Other \- Failure to thrive (in some patients) HEAD & NECK Eyes \- External ophthalmoplegia, progressive (PEO) \- Ptosis \- Cortical blindness (1 patient) CARDIOVASCULAR Heart \- Cardiac conduction defects ABDOMEN Liver \- Liver disease (in some patients) Gastrointestinal \- Constipation (in some patients) \- Delayed gastric emptying (in some patients) \- Gastroesophageal reflux (in some patients) MUSCLE, SOFT TISSUES \- Exercise intolerance \- Muscle weakness, progressive \- Muscle pain \- Facial muscle weakness \- Limb muscle weakness \- Muscle biopsy shows multiple mitochondrial DNA (mtDNA) deletions \- Muscle biopsy shows decreased activity of cytochrome c oxidase NEUROLOGIC Central Nervous System \- Developmental delay (in some patients) \- Seizures (in some patients) \- Hypotonia (in some patients) \- Cerebellar atrophy (1 patient) ENDOCRINE FEATURES \- Impaired glucose tolerance LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased serum creatine kinase \- Abnormal liver enzymes (in some patients) MISCELLANEOUS \- Variable age at onset (range infancy to adult) \- Progressive disorder \- Variable severity MOLECULAR BASIS \- Caused by mutation in the DNA polymerase gamma-2 gene (POLG2, 604983.0001 ) ▲ 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 4 | c1864668 | 4,210 | omim | https://www.omim.org/entry/610131 | 2019-09-22T16:05:04 | {"mesh": ["C566437"], "omim": ["610131", "157640"], "orphanet": ["254892"], "synonyms": ["adPEO", "Alternative titles", "PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL DOMINANT 4"], "genereviews": ["NBK487393"]} |
Myeloproliferative neoplasm
Other namesMyeloproliferative diseases (MPDs)
Myelogram of someone with a myeloproliferative disorder.
SpecialtyHematology and oncology
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.
The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers.
In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia.[1]
## Contents
* 1 Classification
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Incidence
* 6 History
* 7 References
* 8 External links
## Classification[edit]
MPNs are classified as blood cancers by most institutions and organizations.[2] In MPNs, the neoplasm (abnormal growth) starts out as benign and can later become malignant.
As of 2016, the World Health Organization lists the following subcategories of MPNs:[3]
* Chronic myeloid leukemia (CML)
* Chronic neutrophilic leukemia (CNL)
* Polycythemia vera (PV)
* Primary myelofibrosis (PMF)
* PMF, Prefibrotic Stage
* PMF, Overt Fibrotic Stage
* Essential thrombocythemia (ET)
* Chronic eosinophilic leukemia (not otherwise specified)
* MPN, unclassifiable (MPN-U)
## Causes[edit]
MPNs arise when precursor cells (blast cells) of the myeloid lineages in the bone marrow develop somatic mutations which cause them to grow abnormally. There is a similar category of disease for the lymphoid lineage, the lymphoproliferative disorders acute lymphoblastic leukemia, lymphomas, chronic lymphocytic leukemia and multiple myeloma.[citation needed]
## Diagnosis[edit]
People with MPNs might not have symptoms when their disease is first detected via blood tests.[4] Depending on the nature of the myeloproliferative neoplasm, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B12 (or B12 binding capacity), serum urate[5] or direct sequencing of the patient's DNA.[6] According to WHO diagnostic criteria published in 2016, myeloproliferative neoplasms are diagnosed as follows:[7]
* Chronic myeloid leukemia
Chronic myeloid leukemia (CML) has a presence of the hallmark Philadelphia Chromosome (BCR-ABL1) mutation.
* Chronic neutrophilic leukemia
Chronic neutrophilic leukemia (CNL) is characterized by a mutation in the CSF3R gene and an exclusion of other causes of neutrophilia.
* Essential thrombocythemia
Essential thrombocythemia (ET) is diagnosed with a platelet count greater than 450 × 109/L and is associated with the JAK2 V617F mutation in up to 55% of cases[8] and with an MPL (thrombopoietin receptor) mutation in up to 5% of cases:.[9] There should be no increase in reticulin fibers and the patient should not meet the criteria for other MPNs, in particular Pre-PMF.
* Polycythemia vera
Polycythemia vera (PV) is associated most often with the JAK2 V617F mutation in greater than 95% of cases, whereas the remainder have a JAK2 exon 12 mutation. High hemoglobin or hematocrit counts are required, as is a bone marrow examination showing "prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes."
* Prefibrotic/early primary myelofibrosis
Prefibrotic primary myelofibrosis (Pre-PMF) is typically associated with JAK2, CALR, or MPL mutations and shows a reticulin fibrosis no greater than grade 1. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.
* Overtly fibrotic myelofibrosis
Like pre-PMF, overt primary myelofibrosis is associated with JAK2, CALR, or MPL mutations. However, a bone marrow biopsy will show reticulin and/or collagen fibrosis with a grade 2 or 3. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.
* MPN-U
Patients with otherwise unexplained thrombosis and with neoplasms that can't be classified in one of the other categories.
## Treatment[edit]
No curative drug treatment exists for MPNs.[10] Hematopoietic stem cell transplantation can be a curative treatment for a small group of patients, however MPN treatment is typically focused on symptom control and myelosuppressive drugs to help control the production of blood cells.
The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications. The goal of treatment for MF is amelioration of anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET. Tyrosine kinase inhibitors like imatinib have improved the prognosis of CML patients to near-normal life expectancy.[11]
Recently, a JAK2 inhibitor, namely ruxolitinib, has been approved for use in primary myelofibrosis.[12] Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms.
## Incidence[edit]
Although considered rare diseases, incidence rates of MPNs are increasing, in some cases tripling. It is hypothesized that the increase may be related to improved diagnostic abilities from the identification of the JAK2 and other gene markers, as well as continued refinement of the WHO guidelines.[13]
There is wide variation in reported MPN incidence and prevalence worldwide, with a publication bias suspected for essential thrombocythemia and primary myelofibrosis.[14]
## History[edit]
The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek.[15] The discovery of the association of MPNs with the JAK2 gene marker in 2005 and the CALR marker in 2013 improved the ability to classify MPNs.[16]
MPNs were classified as blood cancers by the World Health Organization in 2008.[17] Previously, they were known as myeloproliferative diseases (MPD).
In 2016, Mastocytosis was no longer classified as an MPN.[18]
## References[edit]
1. ^ "Preventing Myelofibrosis from Progressing to Acute Myeloid Leukemia". Cure Today. Retrieved 2020-07-09.
2. ^ "Are Myeloproliferative Neoplasms (MPNs) Cancer?". #MPNresearchFoundation. Retrieved 2020-07-10.
3. ^ Arber, Daniel A.; Orazi, Attilio; Hasserjian, Robert; Thiele, Jürgen; Borowitz, Michael J.; Le Beau, Michelle M.; Bloomfield, Clara D.; Cazzola, Mario; Vardiman, James W. (2016-05-19). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 0006-4971. PMID 27069254.
4. ^ "Symptoms, Diagnosis, & Risk Factors | Seattle Cancer Care Alliance". www.seattlecca.org. Retrieved 2020-07-10.
5. ^ Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates (2001). Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN 0-443-06377-X.
6. ^ Magor GW, Tallack MR, Klose NM, Taylor D, Korbie D, Mollee P, Trau M, Perkins AC (September 2016). "Rapid Molecular Profiling of Myeloproliferative Neoplasms Using Targeted Exon Resequencing of 86 Genes Involved in JAK-STAT Signaling and Epigenetic Regulation". The Journal of Molecular Diagnostics. 18 (5): 707–718. doi:10.1016/j.jmoldx.2016.05.006. PMID 27449473.
7. ^ Barbui, Tiziano; Thiele, Jürgen; Gisslinger, Heinz; Kvasnicka, Hans Michael; Vannucchi, Alessandro M.; Guglielmelli, Paola; Orazi, Attilio; Tefferi, Ayalew (2018-02-09). "The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion". Blood Cancer Journal. 8 (2): 15. doi:10.1038/s41408-018-0054-y. ISSN 2044-5385. PMC 5807384. PMID 29426921.
8. ^ Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, et al. (December 2005). "Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study". Lancet. 366 (9501): 1945–53. doi:10.1016/S0140-6736(05)67785-9. PMID 16325696. S2CID 36419846.
9. ^ Beer PA, Campbell PJ, Scott LM, Bench AJ, Erber WN, Bareford D, et al. (July 2008). "MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort". Blood. 112 (1): 141–9. doi:10.1182/blood-2008-01-131664. PMID 18451306.
10. ^ "MPN summary".
11. ^ Tefferi, Ayalew; Vainchenker, William (2011-01-10). "Myeloproliferative Neoplasms: Molecular Pathophysiology, Essential Clinical Understanding, and Treatment Strategies". Journal of Clinical Oncology. 29 (5): 573–582. doi:10.1200/JCO.2010.29.8711. ISSN 0732-183X. PMID 21220604.
12. ^ Tibes R, Bogenberger JM, Benson KL, Mesa RA (October 2012). "Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms". Molecular Diagnosis & Therapy. 16 (5): 269–83. doi:10.1007/s40291-012-0006-3. PMID 23023734. S2CID 16010648.
13. ^ Roaldsnes, Christina; Holst, René; Frederiksen, Henrik; Ghanima, Waleed (2017). "Myeloproliferative neoplasms: trends in incidence, prevalence and survival in Norway". European Journal of Haematology. 98 (1): 85–93. doi:10.1111/ejh.12788. ISSN 1600-0609. PMID 27500783. S2CID 19156436.
14. ^ Titmarsh, Glen J.; Duncombe, Andrew S.; McMullin, Mary Frances; O'Rorke, Michael; Mesa, Ruben; De Vocht, Frank; Horan, Sarah; Fritschi, Lin; Clarke, Mike; Anderson, Lesley A. (June 2014). "How common are myeloproliferative neoplasms? A systematic review and meta-analysis". American Journal of Hematology. 89 (6): 581–587. doi:10.1002/ajh.23690. ISSN 1096-8652. PMID 24971434.
15. ^ Dameshek W (April 1951). "Some speculations on the myeloproliferative syndromes". Blood. 6 (4): 372–5. doi:10.1182/blood.V6.4.372.372. PMID 14820991.
16. ^ "Understanding MPNs- Overview | MPNRF". #MPNresearchFoundation. Retrieved 2020-07-10.
17. ^ "What are Myeloproliferative Neoplasms (MPNs)?".
18. ^ Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. (February 2018). "The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion". Blood Cancer Journal. 8 (2): 15. doi:10.1038/s41408-018-0054-y. PMC 5807384. PMID 29426921.
## External links[edit]
* Myeloproliferative+Disorders at the US National Library of Medicine Medical Subject Headings (MeSH)
* MPN Info via Cancer.gov
Classification
D
* ICD-10: D47.1
* ICD-9-CM: 205.1, 238.4, 289.89, 289.9
* ICD-O: 9950/0-9964/3
* MeSH: D009196
External resources
* Orphanet: 98274
* 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]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Myeloproliferative neoplasm | c0282609 | 4,211 | wikipedia | https://en.wikipedia.org/wiki/Myeloproliferative_neoplasm | 2021-01-18T18:35:02 | {"mesh": ["D009196", "D019046"], "umls": ["C0282609"], "icd-9": ["289.9", "238.4", "205.1", "289.89"], "wikidata": ["Q1898104"]} |
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (March 2011) (Learn how and when to remove this template message)
Isobutyryl-coenzyme A dehydrogenase deficiency
Other namesIBD deficiency
Valine
Isobutyryl-coenzyme A dehydrogenase deficiency, is a rare metabolic disorder in which the body is unable to process certain amino acids properly.
People with this disorder have inadequate levels of an enzyme that helps break down the amino acid valine, resulting in a buildup of valine in the urine, a symptom called valinuria.
## Contents
* 1 Genetics
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Genetics[edit]
Isobutyryl-coenzyme A dehydrogenase deficiency has an autosomal recessive pattern of inheritance.
Defects in the ACAD8 gene cause isobutyryl-coenzyme A dehydrogenase deficiency. The ACAD8 gene provides instructions for making an enzyme that plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for processing valine, an amino acid that is part of many proteins. If a mutation in the ACAD8 gene reduces or eliminates the activity of this enzyme, the body is unable to break down valine properly. As a result, poor growth and reduced energy production may occur.
This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are needed to be born with the disorder. The parents of an individual with an autosomal recessive disorder are carriers of one copy of the defective gene, but do not show signs and symptoms of the disorder.
## Diagnosis[edit]
Babies with this disorder are usually healthy at birth. The signs and symptoms may not appear until later in infancy or childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia). Another feature of this disorder may be very low blood levels of carnitine (a natural substance that helps convert certain foods into energy).
Isobutyryl-CoA dehydrogenase deficiency may be worsened by long periods without food (fasting) or infections that increase the body's demand for energy. Some individuals with gene mutations that can cause isobutyryl-CoA dehydrogenase deficiency may never experience any signs and symptoms of the disorder.
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2017)
## See also[edit]
* Isobutyryl-coenzyme A
## References[edit]
## External links[edit]
Classification
D
* OMIM: 604773
* MeSH: C535541
* DiseasesDB: 34225
* Isobutyryl-coenzyme A dehydrogenase deficiency at NLM Genetics Home Reference
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Isobutyryl-coenzyme A dehydrogenase deficiency | c1969809 | 4,212 | wikipedia | https://en.wikipedia.org/wiki/Isobutyryl-coenzyme_A_dehydrogenase_deficiency | 2021-01-18T19:10:45 | {"gard": ["10223"], "mesh": ["C535541"], "umls": ["C1969809"], "orphanet": ["79159"], "wikidata": ["Q6085391"]} |
Intertrigo
Axillary intertrigo (bacterial)
Pronunciation
* /ˌɪntərˈtraɪɡoʊ/
SpecialtyDermatology
Intertrigo refers to a type of inflammatory rash (dermatitis) of the superficial skin that occurs within a person's body folds.[1] These areas are more susceptible to irritation and subsequent infection due to factors that promote skin breakdown such as moisture, friction, and exposure to bodily secretions such as sweat, urine or feces.[1] Areas of the body which are more likely to be affected by intertrigo include the inframammary fold, intergluteal cleft, armpits, and spaces between the fingers or toes. Skin affected by intertrigo is more prone to infection than intact skin.[1]
The term "intertrigo" commonly refers to a secondary infection with bacteria (such as Corynebacterium minutissimum), fungi (such as Candida albicans), or viruses. A frequent manifestation is candidal intertrigo.
Intertrigo occurs more often in warm and humid conditions. Generally, intertrigo is more common in people with a weakened immune system including children, the elderly, and immunocompromised people.[1] The condition is also more common in people who experience urinary incontinence and decreased ability to move.[1]
## Contents
* 1 Cause
* 1.1 Bacterial
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Cause[edit]
An intertrigo usually develops from the chafing of warm, moist skin in the areas of the inner thighs and genitalia, the armpits, under the breasts, the underside of the belly, behind the ears, and the web spaces between the toes and fingers. An intertrigo usually appears red and raw-looking, and may also itch, ooze, and be sore. Intertrigos occur more often among overweight individuals, those with diabetes, those restricted to bed rest or diaper use, and those who use medical devices, like artificial limbs, that trap moisture against the skin. Also, there are several skin diseases that can cause an intertrigo to develop, such as dermatitis or inverse psoriasis.
### Bacterial[edit]
Bacterial intertrigo can be caused by Streptococci and Corynebacterium minutissimum.[1][2]
## Diagnosis[edit]
Intertrigo can be diagnosed clinically by a medical professional after taking a thorough history and performing a detailed physical examination. Many other skin conditions can mimic intertrigo's appearance including erythrasma, inverse psoriasis, scabies, pyoderma, atopic dermatitis, candidiasis, seborrheic dermatitis, and fungal infections of the superficial skin caused by Tinea versicolor or Tinea corporis.[1]
## Treatment[edit]
Intertrigo is treated by addressing associated infections, by removing moisture from the site, and by using substances at the site to help maintain skin integrity. If the individual is overweight, losing weight may also help. Relapses of intertrigo are common.
Keeping the area of the intertrigo dry and exposed to the air can help prevent recurrences, as can removing moisture from the area using absorbent fabrics or body powders, including plain cornstarch and judiciously used antiperspirants.
Greases, oils, and barrier ointments, may help by protecting skin from moisture and from friction. Antifungal powders, most commonly clotrimazole 1%, may also be used in conjunction with a barrier ointment. Diaper rash ointment can also help.
Fungal infections associated with intertrigo may be treated with prescription antifungals applied directly to the skin (in most cases) or systemic antifungals, including fluconazole, nystatin, and griseofulvin.
Intertrigo is also a known symptom of vitamin B6 deficiency.[3]
## See also[edit]
* Diaper rash
* List of skin diseases
## References[edit]
1. ^ a b c d e f g Kalra, MG; Higgins, KE; Kinney, BS (April 2014). "Intertrigo and secondary skin infections". American Family Physician. 89 (7): 569–73. PMID 24695603.
2. ^ Tüzün, Y; Wolf, R; Engin, B; Keçici, AS; Kutlubay, Z (July–August 2015). "Bacterial infections of the folds (intertriginous areas)". Clinics in Dermatology (Review). 33 (4): 420–8. doi:10.1016/j.clindermatol.2015.04.003. PMID 26051056.
3. ^ Tong, Y (2014). "Seizures caused by pyridoxine (vitamin B6) deficiency in adults: A case report and literature review". Intractable Rare Dis Res. 3 (2): 52–6. doi:10.5582/irdr.2014.01005. PMC 4204538. PMID 25343127.
## External links[edit]
Classification
D
* ICD-10: L30.4 (ILDS L30.490))
* ICD-9-CM: 695.89
* MeSH: D007402
* DiseasesDB: 29852
External resources
* MedlinePlus: 003223
* eMedicine: article/1087691
* A.O.C.D.: Intertrigo
* eMedicine: Intertrigo (by Samuel Selden, M.D.)
* DERMAdoctor: Intertrigo (by Audrey Kunin, M.D.)
* 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]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Intertrigo | c0021807 | 4,213 | wikipedia | https://en.wikipedia.org/wiki/Intertrigo | 2021-01-18T18:31:00 | {"mesh": ["D007402"], "icd-9": ["695.89"], "icd-10": ["L30.4"], "wikidata": ["Q796150"]} |
Distal trisomy 2q is a rare chromosomal anomaly, resulting from the partial duplication of the long arm of chromosome 2, characterized by moderate psychomotor delay, mild intellectual disability, facial dysmorphism (high hairline, prominent forehead, hypertelorism, upslanting palpebral fissures, large, low-set and/or posteriorly rotated ears, depressed/broad nasal bridge, prominent nasal tip, thin upper lip vermillion), clino-/camptodactyly and normal or increased body measurements. On occasion genital anomalies (hypospadias, cryptorchidism, shawl scrotum) and short stature may be observed.
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Distal trisomy 2q | c4706361 | 4,214 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96094 | 2021-01-23T18:15:12 | {"icd-10": ["Q92.3"], "synonyms": ["Distal duplication 2q", "Telomeric duplication 2q", "Trisomy 2qter"]} |
A number sign (#) is used with this entry because of evidence that immunodeficiency-44 (IMD44) is caused by homozygous mutation in the STAT2 gene (600556) on chromosome 12q13.
Description
Immunodeficiency-44 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to viral infections and adverse multisystemic reaction to vaccination in some patients. Affected individuals appear to have defects in mitochondrial fission and fusion (summary by Shahni et al., 2015).
Clinical Features
Hambleton et al. (2013) reported a 5-year-old boy, born of consanguineous parents, with a history of disseminated vaccine-strain measles that developed 6 days after routine measles/mumps/rubella (MMR) vaccination at age 18 months. An infant sib later died suddenly in the context of a 2-day febrile illness with features of overwhelming viral infection on postmortem examination. Analysis of the extended kindred identified 3 other patients with variable manifestations of a similar immunodeficiency: 2 children had a history of severe viral illnesses, including 1 who developed encephalitis after MMR vaccination, but the recent infection history of their homozygous mother was unremarkable. However, other viral illnesses in these patients were generally mild: 3 of the 5 had unremarkable varicella and 1 had a primary herpes simplex viral infection manifest as gingivostomatitis, but not encephalitis. In addition, the proband showed evidence of normal adaptive immunity in positive antibody titers against live and killed vaccines, including MMR, and naturally encountered viral pathogens. None of the patients had a predisposition to bacterial infections. Laboratory studies of the proband did not suggest a B- or T-cell immunodeficiency, and patient fibroblasts showed increased selective susceptibility to viral infection compared to controls, resulting from a failure of the type 1 interferon response to alpha-interferon (IFNA1; 147660). Immunoblotting of selected interferon-stimulated genes in proband fibroblasts suggested a block in signaling with ISGF3 (see 147574). The overall findings suggested that type 1 interferon signaling through ISGF3 is not essential for host defense against the majority of common childhood viral infections.
Shahni et al. (2015) reported 2 sibs, born of unrelated Albanian parents, who developed a febrile illness soon after MMR vaccination at about 1 year of age. The patients had an appropriate immunologic response to vaccination, but showed ongoing multisystem deterioration. One child developed opsoclonus/myoclonus 1 month after the vaccination and was successfully treated with intravenous acyclovir and steroids. He remained well until age 2.5 years, when he presented with systemic infection and seizures suggestive of meningoencephalitis. He developed significant neurologic impairment including intractable seizures, spasticity, chorea, and severe cortical visual impairment. The other child showed persistent malaise and fever and developed septic shock with metabolic acidosis. She made a slow recovery without neurologic deficits. Both patients also had evidence of mild renal tubulopathy. Because there was laboratory evidence suggestive of mitochondrial dysfunction, muscle biopsy was performed, which showed abnormally long mitochondria with normal respiratory chain enzyme activities.
Inheritance
The transmission pattern of IMD44 in the family reported by Hambleton et al. (2013) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 5 affected members of a consanguineous kindred with IMD44, Hambleton et al. (2013) identified a homozygous splice site mutation in the STAT2 gene (600556.0001). Patient fibroblasts showed no detectable STAT2 protein. In vitro studies of patient fibroblasts showed increased susceptibility to infection with viruses and a complete failure of the type I interferon response; this defect was rescued after transduction with wildtype STAT2.
In 2 sibs with IMD44, Shahni et al. (2015) identified a homozygous nonsense mutation in the STAT2 gene (C612X; 600556.0002). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Patient skeletal muscle and fibroblasts showed dense elongated mitochondria which were restored by transduction of wildtype STAT2, and knockdown of STAT2 in control cells resulted in a 4-fold increase in mitochondrial length. Mitochondria from the patient reported by Hambleton et al. (2013) showed similar abnormalities. Patient fibroblasts showed undetectable STAT2 protein levels and increased levels of several outer and inner mitochondrial membrane fusion proteins, such as MFN1 (608506), MFN2 (608507), and OPA1 (605290), consistent with an increase in mitochondrial mass. Patient cells also showed abnormal phosphorylation of DNM1L (603850), resulting in DNM1L inactivity, impaired mitochondrial fission, and relative hyperfusion. Phosphorylation of STAT1 (600555) was also disrupted, confirming a disturbance in the alpha-interferon pathway. STAT2-deficient patient cells showed impaired apoptosis in response to alpha-interferon compared to controls. The report suggested a link between innate immunity and mitochondrial dysfunction.
INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Abnormally long mitochondria seen on muscle biopsy NEUROLOGIC Central Nervous System \- Encephalopathy (in some patients) \- Neurologic decompensation, infection-associated (in some patients) IMMUNOLOGY \- Increased susceptibility to certain viral infections \- Normal serologic immunoglobulin production to vaccination \- Impaired antiviral response to alpha-interferon signaling LABORATORY ABNORMALITIES \- Increased plasma lactate (in some patients) MISCELLANEOUS \- Two unrelated families have been reported (last curated November 2015) \- Variable severity \- Multisystem decompensation in response to viral infection MOLECULAR BASIS \- Caused by mutation in the signal transducer and activator of transcription 2 (STAT2, 600556.0001 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| IMMUNODEFICIENCY 44 | c4225260 | 4,215 | omim | https://www.omim.org/entry/616636 | 2019-09-22T15:48:23 | {"omim": ["616636", "616669"], "orphanet": ["431166"], "synonyms": ["Primary immunodeficiency with post-MMR vaccine viral infection"]} |
## Clinical Features
Megarbane et al. (1999) described a Lebanese family in which 12 persons had secundum atrial defect and various cardiac and noncardiac anomalies. Cardiac anomalies were left axis deviation of the electrocardiographic QRS, right bundle branch block, atrial fibrillation, Wolff-Parkinson-White syndrome, nodal atrioventricular rhythm, aortic stenosis, pulmonic valve stenosis, mitral stenosis (Lutembacher syndrome), and low implantation of the tricuspid valve (Ebstein disease). Noncardiac abnormalities consisted of hypertelorism, cleft lip, and pectus excavatum. The authors suggested that this combination constitutes a hitherto undescribed autosomal dominant midline disorder of the heart and upper half of the body with almost full penetrance and variable expressivity. The disorder occurred in 4 generations and by implication in a fifth because the first generation had 2 affected sibs. There were several instances of male-to-male transmission.
Mapping
### Exclusion Studies
Megarbane et al. (1999) stated that genotyping with polymorphic markers covering the 5q34 region, the site of the CSX gene (600584) which is mutant in atrial septal defect with atrioventricular conduction defects (108900), and 19q13, where progressive familial heart block (113900) has been mapped, yielded negative results. Megarbane (1999) also tested for linkage to HLA, which has been claimed for secundum type atrial septal defect (108800). HLA haplotype was determined for 8 persons, 6 affected and 2 unaffected. No linkage was found, as none of the affected persons had the same haplotype. The lack of linkage, as well as the associated defects, indicates that the family suffered from a different disorder than HLA-linked ASD.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ATRIAL SEPTAL DEFECT, SECUNDUM, WITH VARIOUS CARDIAC AND NONCARDIAC DEFECTS | c1863648 | 4,216 | omim | https://www.omim.org/entry/603642 | 2019-09-22T16:12:48 | {"mesh": ["C566351"], "omim": ["603642"]} |
Anterior ischemic optic neuropathy (AION) is an eye disease characterized by infarction of the optic disk leading to vision loss. It can be nonarteritic (nonarteritic anterior ischemic optic neuropathy or NAION) or arteritic, the latter being associated with giant cell arteritis (GCA; often termed temporal arteritis). Vision loss with both varieties is typically rapid (over minutes, hours, or days) and painless. Symptoms such as a general feeling of being unwell (malaise), muscle aches and pains, headaches over the temple, pain when combing hair, pain in the jaw after chewing, and tenderness over the temporal artery (one of the major arteries of the head) may be present with giant cell arteritis. At exam, visual acuity is reduced and the optic disc is swollen. In both subtypes, visual field examination is often reduced in the inferior and central visual fields. The visual loss is usually permanent, with some recovery possibly occurring within the first weeks or months. The arteritic variety is treated with corticosteroids. Treatment of the nonarteritic variety with aspirin or corticosteroids has not been helpful.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Anterior ischemic optic neuropathy | c0751711 | 4,217 | gard | https://rarediseases.info.nih.gov/diseases/9790/anterior-ischemic-optic-neuropathy | 2021-01-18T18:02:05 | {"mesh": ["D018917"], "synonyms": ["AION", "Ischemic optic neuropathy"]} |
Congenital analbuminemia (CAA) is a rare disorder characterized by the absence or very low levels of human serum albumin (HSA). Although albumin is the most abundant plasma protein and has many functions, patients with CAA present with only a few mild clinical signs, such as fatigue, low blood pressure, and swelling (edema). However, CAA patients may loss fat tissue (lipodystrophy) and present with high cholesterol, which may result in early atherosclerosis and heart problems. Rarely, CAA may be complicated by hypercoagulability (when the blood tends to clot too much), osteoporosis (which causes bones to become weak and brittle) and respiratory tract infections. It is more severe in the fetus or during early infancy.[1134] CAA is caused by mutations in the ALB gene. Inheritance is autosomal recessive. Treatment aims to prevent heart and vascular problems and may include statins and periodic albumin infusions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital analbuminemia | c0878666 | 4,218 | gard | https://rarediseases.info.nih.gov/diseases/13056/congenital-analbuminemia | 2021-01-18T18:01:11 | {"omim": ["616000"], "orphanet": ["86816"], "synonyms": ["Analbuminemia", "ANALBA"]} |
Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. Asymptomatic cases are also reported. DPD deficiency increases the risk of 5-FU toxicity.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Dihydropyrimidinuria | c0342803 | 4,219 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=38874 | 2021-01-23T18:35:22 | {"gard": ["12347"], "mesh": ["C562815"], "omim": ["222748"], "umls": ["C0342803", "C3495551"], "icd-10": ["E79.8"], "synonyms": ["Dihydropyrimidinase deficiency"]} |
HDN due to anti-Kell alloimmunization
SpecialtyObstetrics, maternal–fetal medicine, neonatology
Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease.[1] Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective.
Hemolytic disease of the newborn (anti-Kell1) is caused by a mismatch between the Kell antigens of the mother and fetus. About 91% of the population are Kell1 negative and about 9% are Kell1 positive. A fraction of a percentage are homozygous for Kell1. Therefore, about 4.5% of babies born to a Kell1 negative mother are Kell1 positive.[citation needed]
The disease results when maternal antibodies to Kell1 are transferred to the fetus across the placental barrier, breaching immune privilege. These antibodies can cause severe anemia by interfering with the early proliferation of red blood cells as well as causing alloimmune hemolysis. Very severe disease can occur as early as 20 weeks gestation. Hydrops fetalis can also occur early. The finding of anti-Kell antibodies in an antenatal screening blood test (indirect Coombs test) is an indication for early referral to a specialist service for assessment, management and treatment.[citation needed]
## Contents
* 1 Presentation
* 1.1 Complications
* 2 Cause
* 3 Mechanism
* 3.1 Antibody specific
* 4 Testing
* 4.1 Mother
* 4.2 Father
* 4.3 Fetus
* 4.4 MCA scans
* 5 Intervention
* 5.1 Early pregnancy
* 5.2 Mid to late pregnancy
* 6 After Birth
* 6.1 Testing
* 7 Prevention
* 8 Treatment
* 9 Transfusion Reactions
* 10 See also
* 11 References
* 12 Further reading
* 13 External links
## Presentation[edit]
### Complications[edit]
* High at birth or rapidly rising bilirubin[2]
* Prolonged hyperbilirubinemia[2]
* Bilirubin Induced Neuorlogical Dysfunction[3]
* Cerebral Palsy[4]
* Kernicterus[5]
* Neutropenia[6][7]
* Thrombocytopenia[6]
* Hemolytic Anemia - MUST NOT be treated with iron[8]
* Late onset anemia - Must NOT be treated with iron. Can persist up to 12 weeks after birth.[9][10][11]
## Cause[edit]
Mothers who are negative for the Kell1 antigen develop antibodies after being exposed to red blood cells that are positive for Kell1. Over half of the cases of hemolytic disease of the newborn owing the anti-Kell antibodies are caused by multiple blood transfusions, with the remainder due to a previous pregnancy with a Kell1 positive baby.[citation needed]
## Mechanism[edit]
Hemolytic disease of the fetus and newborn (HDN) is a condition where the passage of maternal antibodies results in the hemolysis of fetal/neonatal red cells. The antibodies can be naturally occurring such as anti-A, and anti-B, or immune antibodies developed following a sensitizing event.[12] Isoimmunization occurs when the maternal immune system is sensitized to red blood cell surface antigens. The most common causes of isoimmunization are blood transfusion, and fetal-maternal hemorrhage.[13] The hemolytic process can result in anemia, hyperbilirubinemia, neonatal thrombocytopenia, and neonatal neutropenia.[6] With the use of RhD Immunoprophylaxis, (commonly called Rhogam), the incidence of anti-D has decreased dramatically and other alloantibodies are now a major cause of HDN.[12]
### Antibody specific[edit]
Anti-Kell can cause severe anemia regardless of titer.[14] Anti-Kell suppresses the bone marrow,[15] by inhibiting the erythroid progenitor cells.[16][17]
anti-Kell2, anti-Kell3 and anti-Kell4 antibodies
Hemolytic disease of the newborn can also be caused by anti-Kell2, anti-Kell3 and anti-Kell4 IgG antibodies. These are rarer and generally the disease is milder.[citation needed]
## Testing[edit]
Testing for HDN involves blood work from both mother and father, and may also include assessment with amniocentesis and Middle Cerebral Artery scans.[citation needed]
### Mother[edit]
Blood testing for the mother is called an Indirect Coombs Test (ICT) or an Indirect Agglutination Test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Critical titers are associated with significant risk of fetal anemia and hydrops.[18] Titers of 1:8 or higher is considered critical for Kell. Titers of 1:16 or higher are considered critical for all other antibodies. After critical titer is reached, care is based on MCA scans. If antibodies are low and have a sudden jump later in pregnancy, an MCA scan is warranted. If the titer undergoes a 4 fold increase, it should be considered significant regardless of if the critical value has been reached. Maternal titers are not useful in predicting fetal anemia after the first affected gestation and should not be used for the basis of care.[19] Titers are tested monthly until 24 weeks, after which they are done every 2 weeks.[13]
In only 2 situations are patients not monitored identically to patients who are Rh sensitized. The first is that of alloimmunization to the c, E, or, C antigens. Some concern exists that hemolysis may occur in these patients with a lower than 1:16 titer. Thus, if the initial titer is 1:4 and stable but increases at 26 weeks' gestation to 1:8, assessment with MCA Doppler velocity at that point is reasonable. However, if the patient presents in the first trimester with a 1:8 titer that remains stable at 1:8 throughout the second trimester, continued serial antibody titers are appropriate. The second situation in which patients should not be treated identically to patients who are Rh D sensitized is that of Kell isoimmunization because several cases of severe fetal hemolysis with anti-Kell antibodies have occurred in the setting of low titers.[18]
In the case of a positive ICT, the woman must carry a medical alert card or bracelet for life because of the risk of a transfusion reaction.[citation needed]
### Father[edit]
Blood is generally drawn from the father to help determine fetal antigen status.[20] If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen.[21] This test can help with knowledge for the current baby, as well as aid in the decision about future pregnancies. With RhD, the test is called the RhD genotype. With RhCE, and Kell antigen it is called an antigen phenotype.[22]
### Fetus[edit]
There are 3 possible ways to test the fetal antigen status. Cell-free DNA, Amniocentesis, and Chorionic Villus Sampling (CVS). Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.[citation needed]
* Cell-free DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol.[23] Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.[citation needed]
* Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.[13]
* CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.[13]
### MCA scans[edit]
Middle cerebral artery - peak systolic velocity is changing the way sensitized pregnancies are managed.[24] This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with intrauterine transfusion (IUT).[25][24]
## Intervention[edit]
There are several intervention options available in early, mid and late pregnancies.
### Early pregnancy[edit]
* IVIG - IVIG stands for Intravenous Immunoglobulin. It is used in cases of previous loss, high maternal titers, known aggressive antibodies, and in cases where religion prevents blood transfusion. Ivig can be more effective than IUT alone.[26] Fetal mortality was reduced by 36% in the IVIG and IUT group than in the IUT alone group. IVIG and plasmapheresis together can reduce or eliminate the need for an IUT.[27]
* Plasmapheresis - Plasmapheresis aims to decrease the maternal titer by direct plasma replacement.[28] Plasmapheresis and IVIG together can even be used on women with previously hydropic fetuses and losses.[29][30]
### Mid to late pregnancy[edit]
* IUT - Intrauterine Transfusion (IUT) is done either by intraperitoneal transfusion (IPT) or intravenous transfusion (IVT).[31] IVT is preferred over IPT.[18] IUTs are only done until 35 weeks. After that, the risk of an IUT is greater than the risk from post birth transfusion.[32]
* Steroids - Steroids are sometimes given to the mother before IUTs and early delivery to mature the fetal lungs.[32][19]
* Phenobarbital - Phenobarbital is sometimes given to the mother to help mature the fetal liver and reduce hyperbilirubinemia.[19][33]
* Early Delivery - Delivery can occur anytime after the age of viability.[18] Emergency delivery due to failed IUT is possible, along with induction of labor at 35–38 weeks.[32][34]
## After Birth[edit]
### Testing[edit]
* Coombs - after birth baby will have a direct coombs test run to confirm antibodies attached to the infant's red blood cells. This test is run from cord blood.[2]
In some cases, the direct coombs will be negative but severe, even fatal HDN can occur.[35] An indirect coombs needs to be run in cases of anti-C,[36] anti-c,[36] and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN.[28]
* Hgb - the infant's hemoglobin should be tested from cord blood.[2]
* Reticulocyte count - Reticulocytes are elevated when the infant is producing more blood to combat anemia.[2] A rise in the retic count can mean that an infant may not need additional transfusions.[37] Low retic is observed in infants treated with IUT and in those with HDN from anti-Kell[36]
* Neutrophils - as Neutropenia is one of the complications of HDN, the neutrophil count should be checked.[6][7]
* Thrombocytes - as thrombocytopenia is one of the complications of HDN, the thrombocyte count should be checked.[6]
* Bilirubin should be tested from cord blood.[2]
* Ferritin - because most infants affected by HDN have iron overload, a ferritin must be run before giving the infant any additional iron.[8]
* Newborn Screening Tests - Transfusion with donor blood during pregnancy or shortly after birth can affect the results of the Newborn Screening Tests. It is recommended to wait and retest 10–12 months after last transfusion. In some cases, DNA testing from saliva can be used to rule out certain conditions.[citation needed]
## Prevention[edit]
Suggestions have been made that women of child-bearing age or young girls should not be given a transfusion with Kell1 positive blood. Donated blood is not currently screened (in the U.S.A.) for the Kell blood group antigens as it is not considered cost effective at this time.[citation needed]
It has been hypothesized[by whom?] that IgG anti-Kell1 antibody injections would prevent sensitization to RBC surface Kell1 antigens in a similar way that IgG anti-D antibodies (Rho(D) Immune Globulin) are used to prevent Rh disease, but the methods for IgG anti-Kell 1 antibodies have not been developed at the present time.[citation needed]
## Treatment[edit]
* Phototherapy - Phototherapy is used for cord bilirubin of 3 or higher. Some doctors use it at lower levels while awaiting lab results.[38]
* IVIG - IVIG has been used to successfully treat many cases of HDN. It has been used not only on anti-D, but on anti-E as well.[39] IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy.[40] The AAP recommends "In isoimmune hemolytic disease, administration of intravenousγ-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 μmol/L) of the exchange level . If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ-globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."[38]
* Exchange transfusion - Exchange transfusion is used when bilirubin reaches either the high or medium risk lines on the nonogram provided by the American Academy of Pediatrics (Figure 4).[38] Cord bilirubin >4 is also indicative of the need for exchange transfusion.[41]
## Transfusion Reactions[edit]
Once a woman has antibodies, she is at high risk for a transfusion reaction.[42] For this reason, she must carry a medical alert card at all times and inform all doctors of her antibody status.
"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A,B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures"[43]
Summary of transfusion reactions in the US[44]
## See also[edit]
* Coombs test
* Hematology
* Hemolytic anemia
* Kell antigen system
* Hemolytic disease of the newborn
## References[edit]
1. ^ De Haas, M.; Thurik, F. F.; Koelewijn, J.M.; Van Der Schoot, C.E. (2015). "Haemolytic disease of the fetus and newborn". Vox Sanguinis. 109 (2): 99–113. doi:10.1111/vox.12265. PMID 25899660.
2. ^ a b c d e f Murray, N. A; Roberts, I. A G (2007). "Haemolytic disease of the newborn". Archives of Disease in Childhood: Fetal and Neonatal Edition. 92 (2): F83–8. doi:10.1136/adc.2005.076794. PMC 2675453. PMID 17337672.
3. ^ Shapiro, Steven M (2004). "Definition of the Clinical Spectrum of Kernicterus and Bilirubin-Induced Neurologic Dysfunction (BIND)". Journal of Perinatology. 25 (1): 54–9. doi:10.1038/sj.jp.7211157. PMID 15578034. S2CID 19663259.
4. ^ Blair, Eve; Watson, Linda (2006). "Epidemiology of cerebral palsy". Seminars in Fetal and Neonatal Medicine. 11 (2): 117–25. doi:10.1016/j.siny.2005.10.010. PMID 16338186.
5. ^ Lande, Lottie (1948). "Clinical signs and development of survivors of kernicterus due to Rh sensitization". The Journal of Pediatrics. 32 (6): 693–705. doi:10.1016/S0022-3476(48)80225-8. PMID 18866937.
6. ^ a b c d e Koenig, J. M.; Christensen, R. D. (1989). "Neutropenia and thrombocytopenia in infants with Rh hemolytic disease". The Journal of Pediatrics. 114 (4 Pt 1): 625–31. doi:10.1016/s0022-3476(89)80709-7. PMID 2494315.
7. ^ a b Lalezari, P; Nussbaum, M; Gelman, S; Spaet, T. H. (1960). "Neonatal neutropenia due to maternal isoimmunization". Blood. 15 (2): 236–43. doi:10.1182/blood.V15.2.236.236. PMID 14413526.[permanent dead link]
8. ^ a b Rath, M. E. A.; Smits-Wintjens, V. E. H. J.; Oepkes, D.; Walther, F. J.; Lopriore, E. (2013). "Iron status in infants with alloimmune haemolytic disease in the first three months of life". Vox Sanguinis. 105 (4): 328–33. doi:10.1111/vox.12061. PMID 23802744.
9. ^ Mitchell, S; James, A (1999). "Severe late anemia of hemolytic disease of the newborn". Paediatrics & Child Health. 4 (3): 201–3. doi:10.1093/pch/4.3.201. PMC 2828194. PMID 20212966.
10. ^ Al-Alaiyan, S.; Al Omran, A. (1999). "Late hyporegenerative anemia in neonates with rhesus hemolytic disease". Journal of Perinatal Medicine. 27 (2): 112–5. doi:10.1515/JPM.1999.014. PMID 10379500. S2CID 32155893.
11. ^ Jadala, Hareesh; V., Pooja; K., Raghavendra; M., Prithvish; B., Srinivas (2016). "Late onset severe anemia due to rhesus isoimmunization". International Journal of Contemporary Pediatrics: 1472–3. doi:10.18203/2349-3291.ijcp20163704.
12. ^ a b Basu, Sabita; Kaur, Ravneet; Kaur, Gagandeep (2011). "Hemolytic disease of the fetus and newborn: Current trends and perspectives". Asian Journal of Transfusion Science. 5 (1): 3–7. doi:10.4103/0973-6247.75963. PMC 3082712. PMID 21572705.
13. ^ a b c d Cacciatore, A; Rapiti, S; Carrara, S; Cavaliere, A; Ermito, S; Dinatale, A; Imbruglia, L; Recupero, S; La Galia, T; Pappalardo, E. M.; Accardi, M. C. (2009). "Obstetric management in Rh alloimmunizated pregnancy". Journal of Prenatal Medicine. 3 (2): 25–7. PMC 3279102. PMID 22439037.
14. ^ Van Wamelen, D J.; Klumper, F J.; De Haas, M; Meerman, R H.; Van Kamp, I L.; Oepkes, D (2007). "Obstetric History and Antibody Titer in Estimating Severity of Kell Alloimmunization in Pregnancy". Obstetrics & Gynecology. 109 (5): 1093–8. doi:10.1097/01.AOG.0000260957.77090.4e. PMID 17470588. S2CID 24848319.
15. ^ Gowri, Vaidyanathan; Al-Dughaishi, Tamima; Al-Rubkhi, Ikhlasss; Al-Duhli, Maymoona; Al-Harrasi, Yusra (2015). "Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome". Asian Journal of Transfusion Science. 9 (2): 150–4. doi:10.4103/0973-6247.162710. PMC 4562135. PMID 26420934.
16. ^ Vaughan, Janet I.; Manning, Monica; Warwick, Ruth M.; Letsky, Elizabeth A.; Murray, Neil A.; Roberts, Irene A.G. (1998). "Inhibition of Erythroid Progenitor Cells by Anti-Kell Antibodies in Fetal Alloimmune Anemia". New England Journal of Medicine. 338 (12): 798–803. doi:10.1056/NEJM199803193381204. PMID 9504940.
17. ^ http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/news/clinical/obstetrics-gynecology-womens-health/kell-sensitization-can-cause-fe?page=full[full citation needed]
18. ^ a b c d Erythrocyte Alloimmunization and Pregnancy at eMedicine
19. ^ a b c Hemolytic Disease of Newborn~treatment at eMedicine
20. ^ Scheffer, PG; Van Der Schoot, CE; Page-Christiaens, Gcml; De Haas, M (2011). "Noninvasive fetal blood group genotyping of rhesus D, c, E and of K in alloimmunised pregnant women: Evaluation of a 7-year clinical experience". BJOG. 118 (11): 1340–8. doi:10.1111/j.1471-0528.2011.03028.x. PMID 21668766.
21. ^ Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects ISBN 978-0-12-397788-5[page needed][full citation needed]
22. ^ https://www.aacc.org/publications/cln/articles/2015/march/molecular-typing-for-red-blood-cell-antigens[full citation needed]
23. ^ Finning, Kirstin; Martin, Peter; Summers, Joanna; Daniels, Geoff (2007). "Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma". Transfusion. 47 (11): 2126–33. doi:10.1111/j.1537-2995.2007.01437.x. PMID 17958542.
24. ^ a b Mari, Giancarlo; Deter, Russell L.; Carpenter, Robert L.; Rahman, Feryal; Zimmerman, Roland; Moise, Kenneth J.; Dorman, Karen F.; Ludomirsky, Avi; Gonzalez, Rogelio; Gomez, Ricardo; Oz, Utku; Detti, Laura; Copel, Joshua A.; Bahado-Singh, Ray; Berry, Stanley; Martinez-Poyer, Juan; Blackwell, Sean C. (2000). "Noninvasive Diagnosis by Doppler Ultrasonography of Fetal Anemia Due to Maternal Red-Cell Alloimmunization". New England Journal of Medicine. 342 (1): 9–14. doi:10.1056/NEJM200001063420102. PMID 10620643.
25. ^ Mari, G. (2005). "Middle cerebral artery peak systolic velocity for the diagnosis of fetal anemia: The untold story". Ultrasound in Obstetrics and Gynecology. 25 (4): 323–30. doi:10.1002/uog.1882. PMID 15789353.
26. ^ Voto, L. S.; Mathet, E. R.; Zapaterio, J. L.; Orti, J; Lede, R. L.; Margulies, M (1997). "High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): A new alternative for the treatment of severe fetal hemolytic disease". Journal of Perinatal Medicine. 25 (1): 85–8. doi:10.1515/jpme.1997.25.1.85. PMID 9085208. S2CID 22822621.
27. ^ Novak, Deborah J.; Tyler, Lisa N.; Reddy, Ramakrishna L.; Barsoom, Michael J. (2008). "Plasmapheresis and intravenous immune globulin for the treatment of D alloimmunization in pregnancy". Journal of Clinical Apheresis. 23 (6): 183–5. doi:10.1002/jca.20180. PMID 19003884.
28. ^ a b Arora, Satyam; Doda, Veena; Maria, Arti; Kotwal, Urvershi; Goyal, Saurabh (2015). "Maternal anti-M induced hemolytic disease of newborn followed by prolonged anemia in newborn twins". Asian Journal of Transfusion Science. 9 (1): 98–101. doi:10.4103/0973-6247.150968. PMC 4339947. PMID 25722586.
29. ^ Palfi, Miodrag; Hildén, Jan-Olof; Matthiesen, Leif; Selbing, Anders; Berlin, Gösta (2006). "A case of severe Rh (D) alloimmunization treated by intensive plasma exchange and high-dose intravenous immunoglobulin". Transfusion and Apheresis Science. 35 (2): 131–6. doi:10.1016/j.transci.2006.07.002. PMID 17045529.
30. ^ Ruma, Michael S.; Moise, Kenneth J.; Kim, Eunhee; Murtha, Amy P.; Prutsman, Wendy J.; Hassan, Sonia S.; Lubarsky, Suzanne L. (2007). "Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization". American Journal of Obstetrics and Gynecology. 196 (2): 138.e1–6. doi:10.1016/j.ajog.2006.10.890. PMID 17306655.
31. ^ Deka, Dipika (2016). "Intrauterine Transfusion". Journal of Fetal Medicine. 27 (3): 13–17. doi:10.1007/s40556-016-0072-4. PMID 26811110. S2CID 42005756.
32. ^ a b c http://www.uptodate.com/contents/intrauterine-fetal-transfusion-of-red-cells[full citation needed]
33. ^ https://www.mombaby.org/wp-content/uploads/2016/03/UNC-Isoimmunization-Detection-Prevention.pdf[full citation needed][permanent dead link]
34. ^ Rimon, E.; Peltz, R.; Gamzu, R.; Yagel, S.; Feldman, B.; Chayen, B.; Achiron, R.; Lipitz, S. (2006). "Management of Kell isoimmunization — evaluation of a Doppler-guided approach". Ultrasound in Obstetrics and Gynecology. 28 (6): 814–20. doi:10.1002/uog.2837. PMID 16941575.
35. ^ Heddle, N. M.; Wentworth, P.; Anderson, D. R.; Emmerson, D.; Kelton, J. G.; Blajchman, M. A. (1995). "Three examples of Rh haemolytic disease of the newborn with a negative direct antiglobulin test". Transfusion Medicine. 5 (2): 113–6. doi:10.1111/j.1365-3148.1995.tb00197.x. PMID 7655573.
36. ^ a b c Hemolytic Disease of Newborn~workup at eMedicine
37. ^ https://www.ucsfbenioffchildrens.org/pdf/manuals/42_Hemol.pdf[full citation needed]
38. ^ a b c American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. (2004). "Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation". Pediatrics. 114 (1): 297–316. doi:10.1542/peds.114.1.297. PMID 15231951.
39. ^ Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero (2010). "Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn". The Journal of Maternal-Fetal & Neonatal Medicine. 23 (9): 1059–61. doi:10.3109/14767050903544751. PMID 20092394. S2CID 25144401.
40. ^ Gottstein, R (2003). "Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn". Archives of Disease in Childhood: Fetal and Neonatal Edition. 88 (1): F6–10. doi:10.1136/fn.88.1.F6. PMC 1755998. PMID 12496219.
41. ^ Hemolytic Disease of Newborn~followup at eMedicine
42. ^ Strobel, Erwin (2008). "Hemolytic Transfusion Reactions". Transfusion Medicine and Hemotherapy. 35 (5): 346–353. doi:10.1159/000154811. PMC 3076326. PMID 21512623.
43. ^ Transfusion Reactions at eMedicine
44. ^ https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/ucm302847.htm[full citation needed]
## Further reading[edit]
* Geifmanholtzman, O; Wojtowycz, M; Kosmas, E; Artal, R (1997). "Female alloimmunization with antibodies known to cause hemolytic disease". Obstetrics & Gynecology. 89 (2): 272–5. doi:10.1016/S0029-7844(96)00434-6. PMID 9015034. S2CID 36953155.
* Weiner, Carl P.; Widness, John A. (1996). "Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia". American Journal of Obstetrics and Gynecology. 174 (2): 547–51. doi:10.1016/S0002-9378(96)70425-8. PMID 8623782.
## External links[edit]
Classification
D
* ICD-10: P55.8
* ICD-9-CM: 773.2
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hemolytic disease of the newborn (anti-Kell) | None | 4,220 | wikipedia | https://en.wikipedia.org/wiki/Hemolytic_disease_of_the_newborn_(anti-Kell) | 2021-01-18T18:53:16 | {"icd-9": ["773.2"], "icd-10": ["P55.8"], "orphanet": ["275944"], "synonyms": ["Anti-K HDN", "Maternal anti-Kell alloimmunization"], "wikidata": ["Q5712506"]} |
A number sign (#) is used with this entry because of evidence that mitochondrial DNA depletion syndrome-4B (MTDPS4B), which manifests as a neurogastrointestinal encephalopathy (MNGIE), is caused by compound heterozygous mutation in the POLG gene (174763) on chromosome 15q26.
See also MTDPS1 (603041) for a more common form of MNGIE caused by recessive mutation in the thymidine phosphorylase gene (TYMP; 131222).
Description
Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003).
For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).
Clinical Features
Vissing et al. (2002) reported 2 sisters who presented at age 15 years with unsteady gait and gastrointestinal malabsorption. Other features included neurogenic changes on EMG, peripheral neuropathy, ophthalmoplegia, and diffuse muscle weakness. The disorder was indistinguishable from that known as mitochondrial gastrointestinal encephalopathy (MNGIE) due to mutation in the TYMP gene (131222), except for absence of leukoencephalopathy on MRI and mildly reduced thymidine phosphorylase activity (42% of control). In addition, no mutation in the TYMP or the DNT2 (605292) gene was found in 1 of the patients. Vissing et al. (2002) suggested that the condition may be due to a nuclear gene mutation causing a defect in intergenomic signaling.
Van Goethem et al. (2003) provided a follow-up of the patients reported by Vissing et al. (2002). Features included chronic gastrointestinal pseudoobstruction, PEO, axonal sensory ataxic neuropathy, muscle weakness, and cachexia. Brain MRI was normal. Muscle biopsy demonstrated few ragged-red fibers, cytochrome c oxidase negative fibers, decreased enzymatic activities of respiratory chain complexes I and IV, depletion of mtDNA, and multiple mtDNA deletions.
Giordano et al. (2009) reported a newborn boy with congenital myopathy and gastrointestinal pseudoobstruction due to compound heterozygous mutations in the POLG gene (174763.0006 and 174763.0021). He presented with severe hypotonia and generalized muscle weakness, requiring ventilatory assistance and total parenteral nutrition. Hearing loss was detected by auditory evoked potentials, and brain MRI showed mildly enlarged ventricles, but leukoencephalopathy was not noted. He also developed severe abdominal distention with a hypoactive bowel. MRI revealed marked intestinal dilation without mechanical obstruction. Other features included low-set ears, hearing loss, and bilateral clubfoot. Laboratory studies showed hypoglycemia, hypomagnesemia, and hypokalemia; lactate was normal, and liver enzymes were unremarkable. Skeletal muscle biopsy showed scattered, hypertrophic COX-deficient fibers, and there was marked mtDNA depletion in muscle (93% decrease compared to controls). The patient died at age 20 days from respiratory failure. There was no liver damage aside from that resulting from parenteral nutrition. Analysis of the bowel showed that mtDNA depletion was confined mainly to the external layer of the muscularis propria.
Kurt et al. (2010) reported 2 unrelated patients, a girl and a boy, with mtDNA depletion associated with features of MNGIE and of Alpers syndrome with hepatic involvement (MTDPS4A; 203700). Both had compound heterozygous mutations in the POLG gene (P1073L (174763.0022) in both, and A467T (174763.0002) and G848S (174763.0006), respectively). Both patients showed developmental delay. The girl was hypotonic at birth, and later had short stature, neurosensory hearing loss, celiac disease, liver dysfunction with hepatic fibrosis, and gastrointestinal pseudoobstruction with dysmotility. Brain MRI showed signal abnormalities in the basal ganglia and thalami. She died at age 9 years. RT-PCR showed severe mtDNA depletion in liver tissue (72.1% depletion compared to controls). The boy had poor growth, hypotonia, seizures, and intestinal hypomotility, and died at age 10 months. Muscle tissue showed mtDNA depletion (64%). Kurt et al. (2010) emphasized the phenotypic variability associated with recessive POLG mutations, and noted that various signs and symptoms can occur.
Molecular Genetics
In 2 sisters with features of MNGIE but no leukoencephalopathy in whom no mutations were found in the TYMP gene by Vissing et al. (2002), Van Goethem et al. (2003) identified compound heterozygosity for 3 mutations in the POLG gene: T251I (174763.0007) and P587L (174763.0011), which were in cis on the same allele, and N864S (174763.0012), which was in trans.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Weight loss, progressive Other \- Thin body habitus \- Marked cachexia HEAD & NECK Ears \- Hearing loss (1 patient) Eyes \- External ophthalmoplegia, progressive (PEO) ABDOMEN Liver \- Some patients may have hepatic dysfunction Gastrointestinal \- Gastrointestinal dysmotility \- Malabsorption \- Chronic malnutrition \- Chronic intestinal pseudoobstruction \- Abdominal pain \- Constipation, chronic \- Abdominal distention MUSCLE, SOFT TISSUES \- Mitochondrial myopathy \- Hypotonia \- Muscle weakness, diffuse \- Ragged red fibers seen on muscle biopsy \- mtDNA depletion seen on muscle biopsy \- Multiple mitochondrial DNA (mtDNA) deletions seen on muscle biopsy \- Decreased activity of cytochrome c oxidase seen on muscle biopsy \- Decreased activities of complexes I and IV NEUROLOGIC Central Nervous System \- Developmental delay (in some) \- Seizures (in some) \- Ataxia \- White matter abnormalities (in some) Peripheral Nervous System \- Sensory ataxic neuropathy MISCELLANEOUS \- Onset in infancy or late childhood \- Variable severity \- Some phenotypic overlap with Alpers syndrome (MTDPS4A, 203700 ) \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the DNA polymerase-gamma gene (POLG, 174763.0006 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE) | c0872218 | 4,221 | omim | https://www.omim.org/entry/613662 | 2019-09-22T15:57:58 | {"doid": ["0080123"], "mesh": ["C537477"], "omim": ["613662"], "orphanet": ["298"], "synonyms": ["Alternative titles", "MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, POLG-RELATED", "MNGIE, POLG-RELATED"], "genereviews": ["NBK26471"]} |
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.
Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.
Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.
## Frequency
The incidence of severe congenital neutropenia is estimated to be 1 in 200,000 individuals.
## Causes
Severe congenital neutropenia can result from mutations in one of many different genes. These genes play a role in the maturation and function of neutrophils, which are cells produced by the bone marrow. Neutrophils secrete immune molecules and ingest and break down foreign invaders.
Gene mutations that cause severe congenital neutropenia lead to the production of neutrophils that die off quickly or do not function properly. Some gene mutations result in unstable proteins that build up in neutrophils, leading to cell death. Other gene mutations result in proteins that impair the maturation or function of neutrophils, preventing these cells from responding appropriately to immune signals.
About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene. Another 10 percent are caused by mutations in the HAX1 gene. The other genes each account for only a small percentage of all cases of this condition. In about one-third of people with severe congenital neutropenia, the cause of the disorder is unknown.
### Learn more about the genes associated with Severe congenital neutropenia
* ELANE
* HAX1
* TCIRG1
* WAS
Additional Information from NCBI Gene:
* CSF3R
* G6PC3
* GFI1
* JAGN1
* VPS45
## Inheritance Pattern
Most cases of severe congenital neutropenia are classified as sporadic and occur in people with no apparent history of the disorder in their family. Some of these cases are associated with changes in specific genes; however in some cases the cause of the disorder is unknown.
When severe congenital neutropenia is caused by mutations in the ELANE gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Mutations in a few other genes that cause this condition are also inherited in an autosomal dominant pattern.
When severe congenital neutropenia is caused by mutations in the HAX1 gene, it 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. Many cases of this condition are caused by genetic mutations that are inherited in an autosomal recessive pattern.
In rare cases, severe congenital neutropenia is inherited in an X-linked recessive pattern. In these cases, the gene that causes the condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Severe congenital neutropenia | c1859966 | 4,222 | medlineplus | https://medlineplus.gov/genetics/condition/severe-congenital-neutropenia/ | 2021-01-27T08:25:05 | {"mesh": ["C565969"], "omim": ["202700", "613107", "610738", "612541", "615285", "616022", "617014", "300299"], "synonyms": []} |
## Inheritance
Romanus (1948) described 7 cases of inverted nipples in 5 sibships in 4 generations. Shafir et al. (1979) observed 16 affected persons in 4 generations of a Sephardic family. Females are more frequently affected than males.
INHERITANCE \- Autosomal dominant CHEST Breasts \- Inverted nipples ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| NIPPLES INVERTED | c0269269 | 4,223 | omim | https://www.omim.org/entry/163600 | 2019-09-22T16:37:22 | {"omim": ["163600"], "synonyms": ["Alternative titles", "MAMMILLAE INVERTITAE"]} |
Mollie Fancher, the "Brooklyn Enigma"
A fasting girl was one of a number of young Victorian era girls, usually pre-adolescent, who claimed to be able to survive over indefinitely long periods of time without consuming any food or other nourishment. In addition to refusing food, fasting girls claimed to have special religious or magical powers.
The ability to survive without nourishment was attributed to some saints during the Middle Ages, including Catherine of Siena and Lidwina of Schiedam, and regarded as a miracle and a sign of sanctity. Numerous cases of fasting girls were reported in the late 19th century. Believers regarded such cases as miraculous.[1]
In some cases, the fasting girls also exhibited the appearance of stigmata. Doctors, however, such as William A. Hammond ascribed the phenomenon to fraud and hysteria on the part of the girl.[2] Historian Joan Jacobs Brumberg believes the phenomenon to be an early example of anorexia nervosa.[3][4]
## Contents
* 1 Mollie Fancher
* 2 Sarah Jacob
* 3 Other fasting girls
* 4 See also
* 5 References
* 6 Further reading
## Mollie Fancher[edit]
Mary J. "Mollie" Fancher (August 16, 1848 – February, 1916), otherwise known as the "Brooklyn Enigma", was extremely well known for her claim of not eating or eating very little for extended periods of time. She attended a reputable school and, by all reports, was an excellent student. At age 16, she was diagnosed with dyspepsia. At around the age of 19, reports came out that she had abstained from eating for seven weeks.
It was after two accidents, in 1864 and 1865, that she became famous for her ability to abstain from food. As a result of the accidents, Mollie Fancher lost her ability to see, touch, taste, and smell. She claimed to have powers that involved her being able to predict events as well as to read without the ability of sight.
By the late 1870s, she was claiming to eat little or nothing at all for many months. Her claim to abstinence from food lasted for 14 years. Doctors and people in the public began to question her abilities and wished to perform tests to determine the truthfulness of her claims. The claims to abstinence were never verified and she died in February 1916.[5][6]
## Sarah Jacob[edit]
Sarah Jacob.
A case that led to a death and arrests was that of Sarah Jacob (May 12, 1857 – December 17, 1869), the "Welsh fasting girl", who claimed not to have eaten any food at all after the age of ten.[7] A local vicar, initially skeptical, became convinced that the case was authentic and Jacob enjoyed a long period of publicity, during which she received numerous gifts and donations from people who believed she was miraculous.
Doctors were becoming increasingly skeptical about her claims and eventually proposed that she be monitored in a hospital environment to see whether her claims about fasting were true. In 1869, her parents agreed for a test to be conducted under strict supervision by nurses from Guy's Hospital. The nurses were instructed not to deny Jacob food if she asked for it, but to see that any she received was observed and recorded. After two weeks, she was showing clear signs of starvation.
The vicar told the parents that she was failing and that the nurses ought to be sent away so that she could get food. The parents refused and continued to refuse even when informed that their daughter was dying, insisting that they had frequently seen her like this before and that lack of food had nothing to do with her symptoms. Jacob died of starvation a few days later and it was found that she had actually been consuming very little amounts of food secretly, which she could no longer do under medical supervision.[8][9][10] Her parents were convicted of manslaughter and sentenced to hard labor.[11]
## Other fasting girls[edit]
Another case was that of New Jersey's Lenora Eaton in 1881. Reputable citizens in Eaton's town promoted her as someone who had "lived without eating". During these times, Eaton was marked as a "special person and symbol of faith in the miraculous". When these claims were investigated and doctors were sent to help her, Eaton continued to refuse to eat and died after forty-five days.[12]
In 1889, the Boston Globe ran a story, "Who Took the Cold Potato? Dr. Mary Walker Says the Fasting Girl Bit a Doughnut."[13] Dr. Walker reported that Josephine Marie Bedard, known as the Tingwick girl, was a fraud. The evidence was circumstantial: "At the hotel I searched her clothing and found in one of her pockets a doughnut with a bite taken out of it.... On Fast day I had a lunch served to me... I left a platter with three pieces of fried potato on it. I went there and one of the pieces was gone... when I returned, Josephine had her handkerchief to her mouth." Asked whether that was all the evidence, she said, "after I accused her of it she broke down and cried."
Because fasting girls were such a curiosity in the Victorian era, many companies and individuals rushed to put them on display. In the case of Josephine Marie Bedard, two different Boston-based enterprises, the Nickelodeon and Stone and Shaw's museum, competed in court for the right to "exhibit the girl" publicly. Still, even as she was used for blatant commercial gain, there was also an element of scientific inquiry in regarding Bedard as a medical phenomenon. While a modern institutional review board would not have approved the violation of privacy for these young women for commercial gain, the practice was allowed in the Victorian era as demonstrated in the examples.
## See also[edit]
* Anorexia mirabilis
* Ann Moore (impostor)
* Inedia
## References[edit]
1. ^ "Fasting For Autophagy". Saturday, September 26, 2020
2. ^ Blustein, Bonnie Ellen. (1991). Preserve Your Love for Science: Life of William A Hammond, American Neurologist. Cambridge University Press. p. 197. ISBN 0-521-39262-4
3. ^ Lawson, Carol (December 8, 1985). "Anorexia: It's Not A New Disease". The New York Times. Retrieved May 2, 2010.
4. ^ Brody, Jane E. (May 19, 1988). "HEALTH; Personal Health". The New York Times. Retrieved May 2, 2010.
5. ^ Brumberg, Fasting Girls pp. 78–85
6. ^ Nickell, Joe (2017). "Mystery of Mollie Fancher, 'The Fasting Girl,' and Others Who Lived without Eating". Skeptical Inquirer. 41 (6): 18–21.
7. ^ "The Welsh Fasting Girl - Report of the trial". Welshlegalhistory.org. Retrieved 2014-04-20.
8. ^ A Continuation of the Case of the Welsh Fasting Girl The British Medical Journal. Accessed 2 May 2019.
9. ^ Brumberg, Fasting Girls, pp. 65–69
10. ^ William A. Hammond (1879). Fasting Girls: Their Physiology and Pathology. G. P. Putnam's Sons., page images at Google Books
11. ^ Staff (May 26, 1873). "The Case of Trance at Turville". The Sydney Morning Herald: p. 3. (Reprinted from The Observer).
12. ^ Brumberg, Fasting Girls, p. 92
13. ^ "Who Took the Cold Potato? Dr. Mary Walker Says the Fasting Girl Bit a Doughnut." The Boston Daily Globe, April 9, 1889, p. 8
## Further reading[edit]
* Rudolph M. Bell. Holy Anorexia. (University Of Chicago Press, June 15, 1987)
* Joan Jacobs Brumberg. Fasting Girls: The History of Anorexia Nervosa. (Vintage; Subsequent edition, October 10, 2000)
* Joan Jacobs Brumberg. Fasting Girls: Reflections on Writing the History of Anorexia Nervosa. Monographs of the Society for Research in Child Development. Vol. 50, No. 4/5, History and Research in Child Development (1985), pp. 93–104.
* Caroline Walker Bynum. Holy Feast and Holy Fast: The Religious Significance of Food to Medieval Women. (University of California Press; New Ed. edition, January 7, 1988)
* William A. Hammond. Fasting Girls: Their Physiology and Pathology. (Putnam, 1879)
* Karen Hollis. (2001). Fasting Women: Bodily Claims and Narrative Crises in Eighteenth-Century Science. Eighteenth-Century Studies. Vol. 34, No. 4. pp. 523–538.
* Hyder E. Rollins. (1921). Notes on Some English Accounts of Miraculous Fasts. Journal of American Folklore. Vol. 34, No. 134. pp. 357–376.
* Walter Vandereycken. From Fasting Saints to Anorexic Girls: The History of Self-Starvation. (NYU Press, July 1, 1994)
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fasting girl | None | 4,224 | wikipedia | https://en.wikipedia.org/wiki/Fasting_girl | 2021-01-18T19:01:56 | {"wikidata": ["Q5437105"]} |
## Clinical Features
David (1973) described a family, with the surname Nelson, in which a novel dermatoglyphic syndrome occurred in a mother and 3 of her children. The palmar features were the same as those in ROES (125550), but the only striking feature in the fingerprints was that the loops were rather 'pointed' and came near to being tented arches.
Inheritance
David (1973) suggested that this dermatoglyphic trait is inherited in an autosomal dominant manner.
Mapping
David et al. (1973) performed linkage analysis in the family with Nelson syndrome and found a low positive lod score with the Duffy blood group locus (FY; 110700).
Inheritance \- Autosomal dominant Skin \- Pointed loop fingertip patterns \- Vertical crack in ridges of hypothenar eminence \- Distal t triradius displacement ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DERMAL RIDGES, NELSON SYNDROME | c1852161 | 4,225 | omim | https://www.omim.org/entry/125530 | 2019-09-22T16:42:25 | {"mesh": ["C565110"], "omim": ["125530"]} |
Leukoencephalopathy-dystonia-motor neuropathy syndrome is a peroxisomal neurodegenerative disorder characterized by spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotrophic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leukoencephalopathy-dystonia-motor neuropathy syndrome | c3150990 | 4,226 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163684 | 2021-01-23T17:58:14 | {"gard": ["12471"], "omim": ["613724"], "icd-10": ["E75.2"]} |
## Description
Peripheral arterial occlusive disease (PAOD) results from atherosclerosis of large and medium peripheral arteries, as well as the aorta. Many risk factors contribute to PAOD, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease.
Mapping
Gudmundsson et al. (2002) cross-matched a population-based list of Icelandic patients with PAOD who had undergone angiography and/or revascularization procedures with a genealogy database of the entire nation and defined 116 extended families containing 272 patients. A genomewide scan with microsatellite markers revealed significant linkage to 1p31 with an allele-sharing lod score of 3.93. They designated this locus PAOD1. Subtracting 35 patients with a history of stroke increased the lod score to 4.93. This suggested that, although POAD and other vascular diseases share risk factors, genetic factors specific to some types of vascular disease may exist.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| PERIPHERAL ARTERIAL OCCLUSIVE DISEASE 1 | c1847493 | 4,227 | omim | https://www.omim.org/entry/606787 | 2019-09-22T16:10:00 | {"mesh": ["C564658"], "omim": ["606787"], "synonyms": ["Alternative titles", "PAOD1"]} |
Rupture of the urethra is an uncommon result of penile injury, incorrect catheter insertion, straddle injury, or pelvic girdle fracture. The urethra, the muscular tube that allows for urination, may be damaged by trauma. When urethral rupture occurs, urine may extravasate (escape) into the surrounding tissues. The membranous urethra is most likely to be injured in pelvic fractures, allowing urine and blood to enter the deep perineal space and subperitoneal spaces via the genital hiatus. The spongy urethra is most likely to be injured with a catheter or in a straddle injury, allowing urine and blood to escape into the scrotum, the penis, and the superficial peritoneal space. Urethral rupture may be diagnosed with a cystourethrogram. Due to the tight adherence of the fascia lata, urine from a urethral rupture cannot spread into the thighs.[1]
## References[edit]
1. ^ Gilroy, Anne M. (2013-04-27). Anatomy - An Essential Textbook. Thieme. ISBN 9781604062083.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Urethral rupture | c0561781 | 4,228 | wikipedia | https://en.wikipedia.org/wiki/Urethral_rupture | 2021-01-18T18:58:50 | {"umls": ["C0561781"], "wikidata": ["Q28458668"]} |
Pilomatrixoma is a benign (non-cancerous) skin tumor of the hair follicle (structure in the skin that makes hair). They tend to develop in the head and neck area and are usually not associated with any other signs and symptoms (isolated). Rarely, pilomatrixomas can become cancerous (known as a pilomatrix carcinoma). Although they can occur in people of all ages, pilomatrixomas are most commonly diagnosed in people under age 20. The exact underlying cause is not well understood; however, somatic changes (mutations) in the CTNNB1 gene are found in most isolated pilomatrixomas. Rarely, pilomatrixomas occur in people with certain genetic syndromes such as Gardner syndrome, myotonic dystrophy, and Rubinstein-Taybi syndrome; in these cases, affected people usually have other characteristic signs and symptoms of the associated condition. They are usually treated with surgical excision.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pilomatrixoma | c0206711 | 4,229 | gard | https://rarediseases.info.nih.gov/diseases/9452/pilomatrixoma | 2021-01-18T17:58:19 | {"mesh": ["D018296"], "omim": ["132600"], "umls": ["C0206711"], "orphanet": ["91414"], "synonyms": ["Pilomatricoma", "PTR", "Calcifying epithelioma of Malherbe"]} |
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Cardiomegaly
Cardiomegaly on chest X-ray with a pacemaker
SpecialtyCardiology
TypesAthletic heart syndrome,[1] Ventricular hypertrophy, Atrial enlargement
CausesDilated cardiomyopathy,[2][3][4][5] Hypertrophic cardiomyopathy.[1][6][7][8][9]
Diagnostic methodHypertrophic cardiomyopathy screening[10][11]
Cardiomegaly (sometimes megacardia or megalocardia) is a medical condition in which the heart is enlarged. As such, it is more commonly referred to simply as "having an enlarged heart".
Cardiomegaly is not a disease, but rather a condition that can result from a host of other diseases such as obesity or coronary artery disease. Cardiomegaly can be serious: depending on what part of the heart is enlarged, the patient can suffer from heart failure. Recent studies suggest that cardiomegaly is associated with a higher risk of sudden cardiac death.[12] Heart failures increase with age, more common in males, and African Americans. According to research conducted in June 2019, half of people diagnosed with heart failure die within 5 years of being diagnosed.[citation needed] Cardiomyopathy is also associated with cardiomegaly.[citation needed]
The causes of cardiomegaly vary from patient to patient, depending on each case. Many times this condition results from high blood pressure (hypertension) or coronary artery disease. An enlarged heart may not pump blood effectively, resulting in congestive heart failure. Cardiomegaly may improve over time, but many people with an enlarged heart (dilated cardiomyopathy) need lifelong treatment with medications.[13] Having an immediate family member who has or had cardiomegaly may indicate that a person is more susceptible to getting this condition (congenital).[14]
## Contents
* 1 Signs and symptoms
* 2 Causes and prevention
* 3 Mechanism
* 4 Diagnosis
* 5 Classification
* 5.1 By enlarged location
* 5.2 Structure of enlargement
* 6 Treatment and prognosis
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
For many people, cardiomegaly is asymptomatic. For others, if the enlarged heart begins to affect the body's ability to pump blood effectively, then symptoms associated with congestive heart failure may arise, including:[14]
* Heart palpitations – the irregular beating of the heart, usually associated with a valve issue inside the heart.
* Severe shortness of breath (especially when physically active) – irregularly unable to catch one's breath.
* Chest pain
* Coughing, when lying down
* Fatigue
* Swelling in legs
* Increased abdominal girth
* Weight gain
* Edema – swelling[15]
* Fainting[14]
Further information: Cardiogenic shock
There is not much variation in these symptoms because they are mostly specific to the chest area. However, some are more common than others depending on each patient.
## Causes and prevention[edit]
The causes of cardiomegaly are not well understood and many cases of cardiomegaly are idiopathic (having no known cause). Prevention of cardiomegaly starts with detection. If a person has a family history of cardiomegaly, one should let one's doctor know so that treatments can be implemented to help prevent the worsening of the condition. In addition, prevention includes avoiding certain lifestyle risk factors such as tobacco use and controlling one's high cholesterol, high blood pressure, and diabetes. Non-lifestyle risk factors include a family history of cardiomegaly, coronary artery disease (CAD), congenital heart failure, Atherosclerotic disease, valvular heart disease, exposure to cardiac toxins, sleep-disordered breathing (such as sleep apnea), sustained cardiac arrhythmias, abnormal electrocardiograms, and cardiomegaly on chest X-ray. Lifestyle factors which can help prevent cardiomegaly include eating a healthy diet, controlling blood pressure, exercise, medications, and not abusing alcohol and cocaine.[14] Current research and the evidence of previous cases link the following (below) as possible causes of cardiomegaly.
The most common causes of cardiomegaly are congenital (patients are born with the condition based on a genetic inheritance), high blood pressure (which can enlarge the left ventricle causing the heart muscle to weaken over time), and coronary artery disease: in the latter case, the disease creates blockages in the heart's blood supply, leading to tissue death which causes other areas of the heart to work harder, causing the heart to expand in size.
Other possible causes include:
* Heart valve disease
* Cardiomyopathy (disease of the heart muscle)
* Pulmonary hypertension
* Pericardial effusion (fluid around the heart)
* Thyroid Disorders
* Hemochromatosis (excessive iron in the blood)
* Amyloidosis[14]
* Chagas disease, an important cause of cardiomegaly in Latin America[16]
* Viral infection of the heart
* Pregnancy, with enlarged heart developing around the time of delivery (peripartum cardiomyopathy)
* Kidney disease requiring dialysis
* Alcohol or cocaine abuse
* HIV infection[13]
* Diabetes[17]
## Mechanism[edit]
Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure.[14] Within the heart, the working fibers of the myocardial tissue increase in size. As the heart works harder the actin and myosin filaments experience less overlap which increases the size of the myocardial fibers. If there is less overlap of the protein filaments actin and myosin within the sarcomeres of muscle fibers, they will not be able to effectively pull on one another. If the heart tissue (walls of the left and right ventricle) gets too big and stretches too far, then those filaments cannot effectively pull on one another to shorten the muscle fibers, thus impacting the heart's sliding filament mechanism. If fibers cannot shorten properly, and the heart cannot contract properly, then blood cannot be effectively pumped to the lungs to be re-oxygenated and to the body to deliver oxygen to the working tissues of the body.
A person with an enlarged heart is more susceptible to forming blood clots in the lining of their heart. These clots can also be formed in other parts of the body. Once they enter the bloodstream, it makes it difficult for the organs in the body to receive blood, due to the blockage caused by the clots. This can impact other body systems as well and lead to other problems.
## Diagnosis[edit]
There are many techniques and tests used to diagnose an enlarged heart. The results of these tests can often be used to see how efficiently the heart is pumping, determine which chambers of the heart are enlarged, look for evidence of previous heart attacks and determine if a person has congenital heart disease.
Risk factors for cardiomegaly include a family history of heart disease, diabetes, obesity, hypertension, history of alcohol or drug abuse, the lifestyle that consists of little or no exercise.
Cardiothoracic ratio = M R D + M L D I D {\displaystyle {MRD+MLD \over ID}}
where:[18]
MRD = greatest perpendicular diameter from midline to right heart border
MLD = greatest perpendicular diameter from midline to left heart border
ID = internal diameter of chest at level of right hemidiaphragm
* Chest X-Ray: X-ray images help see the condition of the lungs and heart. If the heart is enlarged on an X-ray, other tests will usually be needed to find the cause. A useful measurement on X-ray is the cardio-thoracic ratio, which is the transverse diameter of the heart, compared with that of the thoracic cage."[19] These diameters are taken from PA chest x-rays using the widest point of the chest and measuring as far as the lung pleura, not the lateral skin margins. If the cardiac thoracic ratio is greater than 50%, pathology is suspected, assuming the x-ray has been taken correctly.[20] The measurement was first proposed in 1919 to screen military recruits. A newer approach to using these x-rays for evaluating heart health takes the ratio of heart area to chest area and has been called the two-dimensional cardiothoracic ratio.[21]
* Electrocardiogram: This test records the electrical activity of the heart through electrodes attached to the person's skin. Impulses are recorded as waves and displayed on a monitor or printed on paper. This test helps diagnose heart rhythm problems and assess the damage to a person's heart from a heart attack.
* Echocardiogram: This test for diagnosing and monitoring an enlarged heart uses sound waves to produce a video image of the heart. With this test, the four chambers of the heart can be evaluated.
* Stress test: A stress test, also called an exercise stress test, provides information about how well the heart works during physical activity. It usually involves walking on a treadmill or riding a stationary bike while the heart rhythm, blood pressure, and breathing are monitored.
* Cardiac computerized tomography (CT) or magnetic resonance imaging (MRI). In a cardiac CT scan, one lies on a table inside a machine called a gantry. An X-ray tube inside the machine rotates around the body and collects images of the heart and chest. In a cardiac MRI, one lies on a table inside a long tube-like machine that uses a magnetic field and radio waves to produce signals that create images of the heart.
* Blood tests: Blood tests may be ordered to check the levels of substances in the blood that may show a heart problem. Blood tests can also help rule out other conditions that may cause one's symptoms.
Histopathology of (a) normal myocardium and (b) myocardial hypertrophy. Scale bar indicates 50 μm.
Weight of the heart versus the body.[22]
* Cardiac catheterization and biopsy: In this procedure, a thin tube (catheter) is inserted in the groin and threaded through the blood vessels to the heart, where a small sample (biopsy) of the heart, if indicated, can be extracted for laboratory analysis.[14]
* For deceased people, cardiomegaly at autopsy has been suggested when the heart weighs more than >399 grams in women and >449 grams in men.[23]
## Classification[edit]
Cardiomegaly can be classified by the main enlarged location of the heart, and/or by the structure of the enlargement.
There are also specific additional subtypes. For example, the athletic heart syndrome is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal.
### By enlarged location[edit]
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
### Structure of enlargement[edit]
Dilated cardiomyopathy is the most common type of cardiomegaly. In this condition, the walls of the left and/or right ventricles of the heart become thin and stretched. The result is an enlarged heart.
In the other types of cardiomegaly, the heart's large muscular left ventricle becomes abnormally thick. Hypertrophy is usually what causes left ventricular enlargement. Hypertrophic cardiomyopathy is typically an inherited condition.
## Treatment and prognosis[edit]
Treatments for cardiomegaly include a combination of medication treatment and medical/surgical procedures. Below are some of the treatment options for individuals with cardiomegaly:
Medications
* Diuretics: to lower the amount of sodium and water in the body, which can help lower the pressure in the arteries and heart.
* Angiotensin-converting enzyme (ACE) inhibitors: to lower the blood pressure and improve the heart's pumping ability.
* Angiotensin receptor blockers (ARBs): to provide the benefits of ACE inhibitors for those who can't take ACE inhibitors.
* Beta blockers: to lower blood pressure and improve heart function.
* Digoxin: to help improve the pumping function of the heart and lessen the need for hospitalization for heart failure.
* Anticoagulants: to reduce the risk of blood clots that could cause a heart attack or stroke.
* Anti-arrhythmics: to keep the heart beating with a normal rhythm.
Medical devises to regulate the heartbeat
* Pacemaker: Coordinates the contractions between the left and right ventricle. In people who may be at risk of serious arrhythmias, drug therapy or an implantable cardioverter-defibrillator (ICD) may be used.
* ICDs: Small devices implanted in the chest to constantly monitor the heart rhythm and deliver electrical shocks when needed to control abnormal, rapid heartbeats. The devices can also work as pacemakers.
Surgical procedures
* Heart valve surgery: If an enlarged heart is caused by a problem with one of the heart valves, one may have surgery to remove the valve and replace it with either an artificial valve or a tissue valve from a pig, cow or deceased human donor. If blood leaks backward through a valve (valve regurgitation), the leaky valve may be surgically repaired or replaced.
* Coronary bypass surgery: If an enlarged heart is related to coronary artery disease, one may opt to have coronary artery bypass surgery.
* Left ventricular assist device: (LVAD): This implantable mechanical pump helps a weak heart pump. LVADs are often implanted while a patient waits for a heart transplant or, if the patient is not a heart transplant candidate, as a long-term treatment for heart failure.
* Heart transplant: If medications can't control the symptoms, a heart transplant is often a final option.[14]
Cardiomegaly can progress and certain complications are common:
* Heart failure: One of the most serious types of enlarged heart, an enlarged left ventricle, increases the risk of heart failure. In heart failure, the heart muscle weakens, and the ventricles stretch (dilate) to the point that the heart can't pump blood efficiently throughout the body.
* Blood clots: Having an enlarged heart may make one more susceptible to forming blood clots in the lining of the heart. If clots enter the bloodstream, they can block blood flow to vital organs, even causing a heart attack or stroke. Clots that develop on the right side of the heart may travel to the lungs, a dangerous condition called a pulmonary embolism.
* Heart murmur: For people who have an enlarged heart, two of the heart's four valves — the mitral and tricuspid valves — may not close properly because they become dilated, leading to a backflow of blood. This flow creates sounds called heart murmurs.
* The exact mortality rate for people with cardiomegaly is unknown. However, many people live for a very long time with an enlarged heart and if detected early, treatment can help improve the condition and prolong the lives of these people.[14]
* For some people cardiomegaly is a temporary condition, which can resolve on its own, making one's lifestyle normal like before. Others may have a permanent enlargement, which would then need to be taken care of by the above treatment options.
Lifestyle changes
* Smoking cessation
* Limiting alcohol and caffeine intake
* Maintaining a healthy weight
* Increasing fruits and vegetables in a daily diet
* Limiting consumption of high-fat and/or high-sugar foods
* Getting adequate restful sleep
## References[edit]
1. ^ a b "Enlarged heart". Heart and Stroke Foundation of Canada. Retrieved 2019-03-29. "Types...Hypertrophic cardiomyopathy, Left ventricular hypertrophy (LVH), Intense, prolonged athletic training"
2. ^ Hershberger, Ray E; Morales, Ana; Siegfried, Jill D (22 September 2010). "Clinical and genetic issues in dilated cardiomyopathy: A review for genetics professionals". Genetics in Medicine. 12 (11): 655–667. doi:10.1097/GIM.0b013e3181f2481f. PMC 3118426. PMID 20864896.
3. ^ Luk, A; Ahn, E; Soor, G S; Butany, J (18 November 2008). "Dilated cardiomyopathy: a review". Journal of Clinical Pathology. 62 (3): 219–225. doi:10.1136/jcp.2008.060731. PMID 19017683. S2CID 28182534.
4. ^ "What Is an Enlarged Heart (Cardiomegaly)?". WebMD. 2019-01-30. Retrieved 2019-03-29.
5. ^ Lee, Ji Eun; Oh, Jin-Hee; Lee, Jae Young; Koh, Dae Kyun (2014). "Massive Cardiomegaly due to Dilated Cardiomyopathy Causing Bronchial Obstruction in an Infant". Journal of Cardiovascular Ultrasound. 22 (2): 84–7. doi:10.4250/jcu.2014.22.2.84. PMC 4096670. PMID 25031799.
6. ^ Marian, Ali J.; Braunwald, Eugene (15 September 2017). "Hypertrophic Cardiomyopathy". Circulation Research. 121 (7): 749–770. doi:10.1161/CIRCRESAHA.117.311059. PMC 5654557. PMID 28912181.
7. ^ Maron, Martin S (1 February 2012). "Clinical Utility of Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy". Journal of Cardiovascular Magnetic Resonance. 14 (1): 13. doi:10.1186/1532-429X-14-13. PMC 3293092. PMID 22296938.
8. ^ Almog, C; Weissberg, D; Herczeg, E; Pajewski, M (1 February 1977). "Thymolipoma simulating cardiomegaly: a clinicopathological rarity". Thorax. 32 (1): 116–120. doi:10.1136/thx.32.1.116. PMC 470537. PMID 138960.
9. ^ Hou, Jianglong; Kang, Y. James (September 2012). "Regression of pathological cardiac hypertrophy: Signaling pathways and therapeutic targets". Pharmacology & Therapeutics. 135 (3): 337–354. doi:10.1016/j.pharmthera.2012.06.006. PMC 3458709. PMID 22750195.
10. ^ Luis Fuentes, Virginia; Wilkie, Lois J. (September 2017). "Asymptomatic Hypertrophic Cardiomyopathy" (PDF). Veterinary Clinics of North America: Small Animal Practice. 47 (5): 1041–1054. doi:10.1016/j.cvsm.2017.05.002. PMID 28662873.
11. ^ Maron, Barry J; Maron, Martin S (January 2013). "Hypertrophic cardiomyopathy". The Lancet. 381 (9862): 242–255. doi:10.1016/S0140-6736(12)60397-3. PMID 22874472. S2CID 38333896.
12. ^ Tavora F; et al. (2012). "Cardiomegaly is a common arrhythmogenic substrate in adult sudden cardiac deaths and is associated with obesity". Pathology. 44 (3): 187–91. doi:10.1097/PAT.0b013e3283513f54. PMID 22406485. S2CID 25422195.
13. ^ a b "What Is an Enlarged Heart (Cardiomegaly)?". WebMD.
14. ^ a b c d e f g h i "Enlarged heart - Symptoms and causes". mayoclinic.org. Retrieved 19 March 2018.
15. ^ Mayo Clinic Staff (January 16, 2020). "Enlarged heart". Mayo Clinic. Retrieved May 12, 2020.
16. ^ Bestetti, Reinaldo B. (Nov 2016). "Chagas Heart Failure in Patients from Latin America". Card Fail Rev. 2 (2): 90–94. doi:10.15420/cfr.2016:14:2. PMC 5490952. PMID 28785459.
17. ^ http://www.ddcmultimedia.com/doqit/Care_Management/CM_HeartFailure/L1P4.html[permanent dead link]
18. ^ "Chest Measurements". Oregon Health & Science University. Retrieved 2017-01-13.
19. ^ "cardiothoracic ratio". thefreedictionary.com. Retrieved 19 March 2018.
20. ^ Justin, M; Zaman, S; Sanders, J.; Crook, A. M; Feder, G.; Shipley, M.; Timmis, A.; Hemingway, H. (1 April 2007). "Cardiothoracic ratio within the 'normal' range independently predicts mortality in patients undergoing coronary angiography". Heart. 93 (4): 491–494. doi:10.1136/hrt.2006.101238. PMC 1861494. PMID 17164481.
21. ^ Browne, Ronan F. J.; O’Reilly, Geraldine; McInerney, David (18 February 2004). "Extraction of the Two-Dimensional Cardiothoracic Ratio from Digital PA Chest Radiographs: Correlation with Cardiac Function and the Traditional Cardiothoracic Ratio". Journal of Digital Imaging. 17 (2): 120–123. doi:10.1007/s10278-003-1900-3. PMC 3043971. PMID 15188777.
22. ^ Kumar, Neena Theresa; Liestøl, Knut; Løberg, Else Marit; Reims, Henrik Mikael; Mæhlen, Jan (2014). "Postmortem heart weight: relation to body size and effects of cardiovascular disease and cancer". Cardiovascular Pathology. 23 (1): 5–11. doi:10.1016/j.carpath.2013.09.001. ISSN 1054-8807. PMID 24121021.
23. ^ Tracy, Richard Everett (2011). "Association of Cardiomegaly with Coronary Artery Histopathology and its Relationship to Atheroma". Journal of Atherosclerosis and Thrombosis. 18 (1): 32–41. doi:10.5551/jat.5090. PMID 20953090.
## Further reading[edit]
* Amin, Hina; Siddiqui, Waqas J. (2019). "Cardiomegaly". StatPearls. StatPearls Publishing.
* Ampanozi, Garyfalia; Krinke, Eileen; Laberke, Patrick; Schweitzer, Wolf; Thali, Michael J.; Ebert, Lars C. (1 September 2018). "Comparing fist size to heart size is not a viable technique to assess cardiomegaly". Cardiovascular Pathology. 36: 1–5. doi:10.1016/j.carpath.2018.04.009. PMID 29859507.
* Agostoni, PierGiuseppe; Cattadori, Gaia; Guazzi, Marco; Palermo, Pietro; Bussotti, Maurizio; Marenzi, Giancarlo (1 November 2000). "Cardiomegaly as a possible cause of lung dysfunction in patients with heart failure". American Heart Journal. 140 (5): A17–A21. doi:10.1067/mhj.2000.110282. PMID 11054632.
* Luedde, Mark; Katus, Hugo; Frey, Norbert (1 January 2006). "Novel Molecular Targets in the Treatment of Cardiac Hypertrophy". Recent Patents on Cardiovascular Drug Discovery. 1 (1): 1–20. doi:10.2174/157489006775244290. PMID 18221071.
## External links[edit]
Classification
D
* ICD-10: I51.7
* ICD-9-CM: 429.3
* MeSH: D006332
* DiseasesDB: 30769
* American Heart Association
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
* Medicine portal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Cardiomegaly | c0018800 | 4,230 | wikipedia | https://en.wikipedia.org/wiki/Cardiomegaly | 2021-01-18T19:02:07 | {"mesh": ["D006332"], "umls": ["C0018800"], "icd-9": ["429.3"], "icd-10": ["I51.7"], "wikidata": ["Q1729124"]} |
Tarsal coalition
Other namesPeroneal spastic flatfoot, Tarsal synostosis, or Tarsal dysostosis
Tarsal bones(normal)
SpecialtyRheumatology
Tarsal coalition is an abnormal connecting bridge of tissue between two normally-separate tarsal bones. The term 'coalition' means a coming together of two or more entities to merge into one mass.[1] The tissue connecting the bones, often referred to as a "bar", may be composed of fibrous or osseous tissue. The two most common types of tarsal coalitions are calcaneo-navicular (calcaneonavicular bar) and talo-calcaneal (talocalcaneal bar), comprising 90% of all tarsal coalitions.[2] There are other bone coalition combinations possible, but they are very rare.[3] Symptoms tend to occur in the same location, regardless of the location of coalition: on the lateral foot, just anterior and below the lateral malleolus. This area is called the sinus tarsi.[3]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Anatomy
* 4 Diagnosis
* 5 Treatment
* 6 See also
* 7 References
* 8 Further reading
## Symptoms[edit]
The bones of children are very malleable in infancy. This will generally mean that, despite the presence of a coalition, the bones can deform enough to allow painless walking until the child's skeleton has matured enough.[4] 'Skeletal maturing' means that bone is laid down in the tissue that forms the immature bone shape gradually until adult bone is achieved at about the age of seventeen years in the feet. Other body parts reach skeletal maturity at different times. The onset of symptoms related to a tarsal coalition usually occurs at about nine to seventeen years of age, with a peak incidence occurring at ten to fourteen years of age.[5] Symptoms may start suddenly one day and persist, and can include pain (may be quite severe), lack of endurance for activity, fatigue, muscle spasms and cramps, an inability to rotate the foot, or antalgic gait.
## Causes[edit]
Tarsal coalition is almost exclusively a product of an error during the dividing of embryonic cells in utero.[6] Other causes of synostosis (bone fusion) could include a surgical 'screwing together' of two bones, a very advanced case of arthritis leading to self-fusion of a joint by an internal process within the body or some other very traumatic event. The birth defect responsible for tarsal coalition is thought to often be an autosomal dominant genetic condition.[7] This means that if you have a parent with the disorder it is highly likely to be passed on to offspring.
## Anatomy[edit]
Anatomically, the abnormal connecting 'bridge' is virtually all cartilage in the young child, often nearly all bone in an adult and a mixture as the skeleton ossifies in between these ages. Some fibrous tissue (like gristle) is often also involved. When the bridging link becomes bony enough, it results in a limitation of motion and this brings about the onset of pain.[8]
The bones of the tarsus are the rear most bones in the adjacent diagram: calcaneus, talus, navicular, cuboid, medial cuneiform, intermediate cuneiform and lateral cuneiform bones.[9] These bones create the two major foot joints – the subtalar and midtarsal joints – that allow complex motions to occur in the feet. These motions are necessary for such activities as walking over uneven terrain and creating a gait that allows normal function of the knees, hips, back, etc.
## Diagnosis[edit]
In a case of an adolescent with rear foot pain, the physical exam will reveal that the foot movement is limited. This is both because there is a physical blockade to movement and because the brain will 'turn on' the muscles around the area to stop the joint moving toward the painful 'zone'. X-rays will usually be ordered and, in general, if there is enough toughness to the tissue bridge that pain has begun – there will usually be enough bone laid down to show up in an x-ray.[10]
More high-tech investigations such as CT scan will be required if proceeding to surgery. If the bridge appears to be mostly fibrous tissue, an MRI would be the preferred modality to use.[11]
## Treatment[edit]
The goal of non-surgical treatment of tarsal coalition is to relieve the symptoms by reducing the movement of the affected joint. This might include non-steroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory injection, stabilizing orthotics or immobilization via a leg cast. At times, short term immobilization followed by long term orthotic use may be sufficient to keep the area free of pain.
Surgery is very commonly required. The type and complexity of the surgery will depend on the location of the coalition. Essentially, there are two types of surgery. Wherever possible, the bar will be removed to restore normal motion between the two bones. If this is not possible, it may be necessary to fuse the affected joints together by using screws to connect them solidly. Cutting away the coalition is more likely to succeed the younger the patient. With age comes extra wear in the affected and adjacent joints that makes treatment more difficult.[12]
## See also[edit]
* Carpal coalition
## References[edit]
1. ^ English Language Dictionary, 2007
2. ^ LearningRadiology.com
3. ^ a b Tarsal coalition and painful flatfoot, K.A. Vincent, Shriners Hospital for Children, Portland, Oregon and Department of Orthopedics, Oregon Health Sciences University, Portland, OR 97201-3905, USA
4. ^ Mihran O. Tachdjian, Pediatric Orthopedics, 1990
5. ^ Mihran O. Tachdjian, Pediatric Orthopedics, 1990
6. ^ Tarsal coalition and painful flatfoot, KA Vincent, Shriners Hospital for Children, Portland, Oregon and Department of Orthopedics, Oregon Health Sciences University, Portland, OR 97201-3905, USA
7. ^ Tarsal coalition and painful flatfoot, K.A. Vincent, Shriners Hospital for Children, Portland, Oregon and Department of Orthopedics, Oregon Health Sciences University, Portland, OR 97201-3905, USA
8. ^ Mihran O. Tachdjian, Pediatric Orthopedics, 1990
9. ^ Debra Draves, Anatomy of the Lower Extremity, 1986, p 107.
10. ^ Stephanie Cosgrove: Tarsal Coalition[permanent dead link]
11. ^ Tarsal Coalition: A Patient's Guide to Tarsal Coalition. EOrthopod. Medical Multimedia Group, L.L.C. Date Unknown
12. ^ Stephanie Cosgrove: Tarsal Coalition
## Further reading[edit]
* Lawrence DA, Rolen MF, Haims AH, Zayour Z, Moukaddam HA (July 2014). "Tarsal Coalitions: Radiographic, CT, and MR Imaging Findings". HSS Journal (Review). 10 (2): 153–66. doi:10.1007/s11420-013-9379-z. PMC 4071469. PMID 25050099.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Tarsal coalition | c0265654 | 4,231 | wikipedia | https://en.wikipedia.org/wiki/Tarsal_coalition | 2021-01-18T18:46:40 | {"mesh": ["D000070604"], "umls": ["C0265654", "C1406822"], "wikidata": ["Q15666414"]} |
## Description
Fibromuscular dysplasia (FMDA) is a nonatherosclerotic, noninflammatory arterial disease that most commonly involves the renal and carotid arteries. The prevalence of symptomatic renal artery FMDA is about 4 in 1,000 and the prevalence of cervicocranial FMDA is about half of that. Histologic classification includes 3 main subtypes, intimal, medial, and perimedial, which may be associated in a single patient. Angiographic classification includes the multifocal type, with multiple stenoses and the 'string of beads' appearance that is related to medial FMDA, and tubular and focal types, which are not clearly related to specific histologic lesions (summary by Plouin et al., 2007)
Clinical Features
Mettinger and Ericson (1982) reported observations on a genetic basis in relation to fibromuscular dysplasia leading to stroke.
Among cases of fibromuscular dysplasia of arteries, particularly familial cases, von Recklinghausen neurofibromatosis (162200) should be suspected as an occasional 'cause' (Kousseff and Gilbert-Barness, 1989).
Gatalica et al. (1992) described the case of a previously healthy 18-year-old black man with generalized fibromuscular dysplasia who developed dissection of the aorta beginning in the ascending aorta and extending into the abdominal aorta where complete occlusion below the origin of the renal arteries was found. The aneurysm had ruptured into the retroperitoneal space in the region of the right kidney. Tromp et al. (1993) demonstrated a point mutation in the gene for type III collagen (120180.0018) in this patient, who was later found to have Ehlers-Danlos syndrome type IV (130050). Fibromuscular dysplasia of arteries has also been observed in cutis laxa (219100).
Safioleas et al. (2001) described the association of hypertrophic cardiomyopathy (see CMH1, 192600) and fibromuscular dysplasia of the superior mesenteric artery causing ischemic colitis. The patient was a 33-year-old man in whom cardiomyopathy had been diagnosed by echocardiography 3 years previously, after his father, who died suddenly, was found at autopsy to have had that disorder. He was asymptomatic but did have left ventricular hypertrophy on electrocardiography. Hospital admission was for diffuse abdominal pain with signs of peritoneal irritation. On exploratory laparotomy, gangrene of the small bowel, about 50 cm proximal to the ileocecal valve, was found. The pathologic specimen showed dysplasia of the superior mesenteric artery. Digital subtraction angiography of the celiac and mesenteric arteries showed a 'chain of beads' appearance typical of fibromuscular dysplasia. Safioleas et al. (2001) suggested that there may be a connection between hypertrophic cardiomyopathy and fibromuscular dysplasia of arteries since both have severe disorganization of the muscle fibers. Furthermore, they found a report of another case of the association (Moncure and Rashid, 1995).
Inheritance
Early reports documented fibromuscular dysplasia in sibs but often did not examine earlier generations (Wood and Borges, 1963; Hansen et al., 1965; Halpern et al., 1965; Major et al., 1977).
The first formal analysis of the genetics of the disorder was that of Rushton (1980), who studied the families of 20 probands. In 8 families only the proband was affected. In the other 12 families, between 1 and 11 other relatives were thought to have been affected. Vertical transmission was demonstrated repeatedly, suggesting autosomal dominant inheritance in contrast to the individual reports in sibs. Unfortunately, histologic proof of fibromuscular dysplasia was apparently lacking in all the familial cases; the diagnosis was based on hypertension, stroke, claudication and myocardial infarction occurring at an early age. Eight of the 12 probands in the familial cases were female; of affected relatives, 24 were female and 20 male. In 1 family, 2 sisters had documented fibromuscular dysplasia. Fibromuscular hyperplasia of the renal arteries leading to hypertension occurs almost only in females, manifesting itself in early adulthood as a rule.
Gladstien et al. (1980) concluded that the family data are consistent with autosomal dominant inheritance with variable and often no clinical effect.
Molecular Genetics
### Associations Pending Confirmation
Guo et al. (2017) demonstrated that biallelic mutations in the YY1AP1 gene (607860) cause Grange syndrome (602531), a disorder that encompasses features of fibromuscular dysplasia. Analysis of exome sequencing data from 282 individuals with FMDA and renal, carotid, and mesenteric artery disease as well as 286 age-, gender-, and race/ethnicity-matched controls showed no increased burden of YY1AP1 variants in the FMDA-affected case subjects, although 1 sporadic patient with FMDA involving the renal and extracranial carotid arteries was found to be heterozygous for a frameshift mutation in the YY1AP1 gene. Noting that the mother of 3 sibs with Grange syndrome who was heterozygous for a nonsense mutation in YY1AP1 (607860.0001) had refractory hypertension due to left renal artery stenosis, Guo et al. (2017) suggested that heterozygous loss-of-function YY1AP1 mutations might be associated with susceptibility to FMDA in the general population.
Limbs \- Claudication Neuro \- Stroke Inheritance \- Autosomal dominant GU \- Hypertension due to renal artery hyperplasia Vascular \- Arterial fibromuscular dysplasia \- Aortic dissection Cardiac \- Myocardial infarction ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| FIBROMUSCULAR DYSPLASIA | c0016052 | 4,232 | omim | https://www.omim.org/entry/135580 | 2019-09-22T16:41:05 | {"mesh": ["D005352"], "omim": ["135580"], "icd-10": ["I77.3"], "synonyms": ["Alternative titles", "FIBROMUSCULAR DYSPLASIA OF ARTERIES", "FMD"]} |
Miller syndrome is a rare condition that mainly affects the development of the face and limbs. Characteristic features include underdeveloped cheek bones, a very small lower jaw, cleft lip and/or palate, abnormalities of the eyes, absent fifth (pinky) fingers and toes, and abnormally formed bones in the forearms and lower legs. The severity of the disorder varies among affected individuals. Miller syndrome is caused by mutations in the DHODH gene. It is inherited in an autosomal recessive manner.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Miller syndrome | c0265257 | 4,233 | gard | https://rarediseases.info.nih.gov/diseases/8410/miller-syndrome | 2021-01-18T17:59:03 | {"mesh": ["C537680"], "omim": ["263750"], "orphanet": ["246"], "synonyms": ["Genee-Wiedemann acrofacial dysostosis", "GWAFD", "Genee-Wiedemann syndrome", "Wildervanck-Smith syndrome", "Postaxial acrofacial dysostosis (POADS) syndrome", "POADS syndrome"]} |
Asomatognosia
SpecialtyNeurology
Asomatognosia is a neurological disorder characterized as loss of recognition or awareness of part of the body.[1][2] The failure to acknowledge, for example, a limb, may be expressed verbally or as a pattern of neglect. The limb may also be attributed to another person, a delusion known as somatoparaphrenia. However, they can be shown their limb and this error is temporarily corrected.[3][4] Some authors have focused on the prevalence of hemispatial neglect in such patients.[5]
Asomatognosia is the inability to feel, recognize, or be conscious of one's own specific body parts or bodily conditions (Whishaw, 2015). Generally, asomatognosia often arises from damage to the right parietal lobe (Whishaw, 2015). Evidence indicates that damage to the right hemisphere often results from a stroke or pre-existing hemispatial neglect, or inattention to the left visual field (Antoniello, 2016) (Keenan, 2004). Individuals who suffer from somatoparaphrenia, a specific form of asomatognosia, ignore or deny ownership of a body part contralateral to the brain lesion (Feinberg, 1990). Although this condition can affect one or both sides of the body, most patients exhibit the inability to recognize limbs/body parts (i.e. arm, leg, head, breast) on the left side of their body as their own (Keenan, 2004). While individuals with asomatognosia typically suffer large lesions across several temporoparietal sectors, those with somatoparaphrenia also suffer lesions in the right medial and orbitofrontal regions of the brain (Feinberg 2010).
## Contents
* 1 Patient cases
* 2 Related conditions
* 3 See also
* 4 References
## Patient cases[edit]
In most commonly observed instances, individuals with this condition fail to recognize and sense their left arm after suffering lesions to the right hemisphere (Keenan, 2004). In one specific instance, a patient suffering from asomatognosia tried to throw her own left arm into a garbage can because she believed it was her husband's arm repeatedly falling on her and disrupting her sleep (Keenan, 2004). Even when patients are told that the body part belongs to them, many will deny the reality and remain firm in their belief that it is not a part of them. There is a case in which a patient with severe asomatognosia had the ability to use his right hand to trace his paralyzed left arm to his own left shoulder, but still failed to acknowledge that the left arm belonged to him (Keenan, 2004). Overall, there is an interesting phenomenon in which individuals will claim that the body part belongs to someone of the opposite gender within their family. For example, women with asomatognosia tend to claim that their left arm belongs to a man (i.e. their husband) while men claim their arm belongs to a woman, such as his daughter or wife. There also exist patients that treat the arm as a child or small animal. (Keenan, 2004)
## Related conditions[edit]
In addition to instances of asomatognosia in which patients deny ownership of a specific part, this condition is also associated with the following: anosognosia (unawareness or denial of illness), anosodiaphoria (indifference to illness), autopagnosia (inability to localize and name body parts), and asymbolia for pain (absence of typical reactions to pain). Out of these varieties of asomatognosia, autopagnosia is the only one in which an individual struggles to recognize the right side of their body due to lesions in the left parietal cortex (Whishaw, 2015).
## See also[edit]
* Anosognosia, a condition in which a person is unaware or in denial of an illness.
## References[edit]
1. ^ Arzy, S.; Overney, L. S.; Landis, T.; Blanke, O. (2006). "Neural Mechanisms of Embodiment". Archives of Neurology. 63 (7): 1022–5. doi:10.1001/archneur.63.7.1022. PMID 16831974.
2. ^ Vallar, G. & Ronchi, R. (2009). Somatoparaphrenia: a body delusion. A review of the neuropsychological literature. Experimental Brain Research, 192:3, 533-551
3. ^ Feinberg, T., Venneri, A., Simone, A.M., et al. (2010). The neuroanatomy of asomatognosia and somatoparaphrenia. Journal of Neurology, Neurosurgery & Psychiatry, 81, 276-281
4. ^ Bottini, Gabriella; Bisiach, Edoardo; Sterzi, Roberto; Vallar, Giuseppe (2002): “Feeling touches in someone else's hand.” NeuroReport 13 (2), 249–252.
5. ^ A.J. Larner (12 November 2010). A Dictionary of Neurological Signs. Springer Science & Business Media. p. 43. ISBN 978-1-4419-7095-4.
This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Asomatognosia | c0840927 | 4,234 | wikipedia | https://en.wikipedia.org/wiki/Asomatognosia | 2021-01-18T18:41:04 | {"umls": ["C0840927"], "icd-10": ["R41.4"], "wikidata": ["Q734123"]} |
Panhypophysitis is a rare, acquired pituitary hormone deficiency, a type of primary hypophysitis characterized by an inflammation of the entire pituitary gland. Common clinical presentation is diabetes insipidus with polyuria and polydipsia and partial or panhypopituitarism. Other symptoms may include headaches, nausea/vomiting, visual disturbances and fatigue.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Panhypophysitis | None | 4,235 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95513 | 2021-01-23T17:59:35 | {"icd-10": ["E23.6"], "synonyms": ["Infundibulo-panhypophysitis"]} |
A Zahn infarct is a pseudo-infarction of the liver, consisting of an area of congestion with parenchymal atrophy but no necrosis, and usually due to obstruction of a branch of the portal vein.[1][2] Zahn infarcts are unique in that there is collateral congestion of liver sinusoids that do not include areas of anoxia seen in most infarcts. Fibrotic tissue may develop in the area of the infarct and it could be caused by an occlusive phlebitis in portal vein radicles.[3] Non ischemic infarct of liver with lines of Zahn.
## Eponym[edit]
The Zahn infarct is named for Friedrich Wilhelm Zahn.[1]
## References[edit]
1. ^ a b Stegman, JK, ed. (2006), Stedman's Medical Dictionary (28th ed.), Baltimore, MD: Lippincott, Williams, & Wilkins
2. ^ "GDPR page".
3. ^ Matsumoto T, Kuwabara N, Abe H, Fukuda Y, Suyama M, Fujii D, Kojima K, Futagawa S (1992), "Zahn infarct of the liver resulting from occlusive phlebitis in portal vein radicles", American Journal of Gastroenterology, 87 (3): 365–368, PMID 1539574
* Reichelt HG (1985), "Partial Budd-Chiari syndrome with Zahn infarct of the liver in venous transmitted tumor thrombosis of a uterine cancer", Röntgen-Blätter (in German), 38 (11): 345–347, PMID 4081553
* v
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Ischaemia and infarction
Ischemia
* Location
* Brain ischemia
* Heart
* Large intestine
* Small intestine
Infarction
* Types
* Anemic
* Hemorrhagic
* Location
* Heart
* Brain
* Spleen
* Limb
* Gangrene
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
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*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
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| Zahn infarct | c0333554 | 4,236 | wikipedia | https://en.wikipedia.org/wiki/Zahn_infarct | 2021-01-18T19:07:54 | {"umls": ["C0333554"], "wikidata": ["Q8064710"]} |
Factor V deficiency is an inherited bleeding disorder that prevents blood clots from forming properly. This disorder is caused by mutations in the F5 gene, which leads to a deficiency of a protein called coagulation factor V. The reduced amount of factor V may lead to nosebleeds, easy bruising, and excessive bleeding following surgery or trauma. This condition is inherited in an autosomal recessive manner. Treatment includes fresh blood plasma or fresh frozen plasma infusions during bleeding episodes.
This condition should not be confused with Factor V Leiden thrombophilia, a genetic risk factor for blood clots.
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*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Factor V deficiency | c0015499 | 4,237 | gard | https://rarediseases.info.nih.gov/diseases/2237/factor-v-deficiency | 2021-01-18T18:00:37 | {"mesh": ["D005166"], "omim": ["227400"], "umls": ["C0015499"], "orphanet": ["326"], "synonyms": []} |
A number sign (#) is used with this entry because of evidence that autosomal dominant intellectual developmental disorder-59 (MRD59) is caused by heterozygous mutation in the CAMK2G gene (602123) on chromosome 10q22.
Clinical Features
De Ligt et al. (2012) reported a boy with severe intellectual disability with myopia, strabismus, short stature, flat face with narrow forehead, long palpebral fissures, arched eyebrows, sacral dimple, short hands, brachydactyly, and short feet. He walked at age 5 years and started to speak at age 4 years. He also had behavioral abnormalities, including self-mutilation. Laboratory studies suggested mitochondrial dysfunction without mitochondrial gene defects. Proietti Onori et al. (2018) provided follow-up of the patient reported by de Ligt et al. (2012). At age 16.5 years, he had severely impaired intellectual development (IQ less than 35) and very poor speech. He did not have seizures; juvenile-onset glaucoma was noted. Brain imaging showed no structural abnormalities.
Proietti Onori et al. (2018) reported a 5-year-old boy who presented in infancy with generalized hypotonia and developmental delay with impaired speech and language, as well as autism. He had mild dysmorphic features, including relative macrocephaly, prominent capillary vascular malformations on the forehead and glabella, tall forehead, tubular nose with upturned tip, large ears, round cheeks, and facial hypotonia. He did not have seizures, and brain imaging was normal. The authors noted that both this patient and the patient previously reported by de Ligt et al. (2012) had some facial dysmorphisms, though not strikingly similar.
Molecular Genetics
In a boy with MRD59, de Ligt et al. (2012) identified a de novo heterozygous missense mutation in the CAMK2G gene (R292P; 602123.0001). The patient was ascertained from a larger cohort of 100 patients with severe intellectual disability who underwent exome sequencing. Functional studies of the variant were not performed. The patient had normal array and MLL2 testing.
Proietti Onori et al. (2018) identified a de novo heterozygous R292P mutation in a 5-year-old boy with MRD59 and noted that the substitution occurs in an autoregulatory domain that maintains the kinase in an inactive state in the absence of calcium/calmodulin. Detailed in vitro and in vivo functional studies in mouse primary hippocampal cells and in mouse embryos showed that the mutant protein caused decreased neurite length and arborization, as well as impaired neuronal migration from the subventricular zone during development. A dominant effect was observed. Further studies showed that the mutant protein had constitutively increased phosphotransferase activity with increased autophosphorylation at Thr287 compared to controls, consistent with a gain of function. The R292P mutant protein showed impaired nuclear localization, although calmodulin binding was intact. Silencing the catalytic site of the mutant protein reversed the pathogenic effect on neuronal maturation, without rescuing its nuclear targeting. The authors concluded that CAMK2G has an indispensable function in neurodevelopment and that the R292P protein gains constitutive activity toward cytosolic targets, rather than impaired targeting to the nucleus.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, mild HEAD & NECK Head \- Large head circumference Face \- Dysmorphic facial features, mild, variable \- Tall forehead \- Narrow forehead \- Flat forehead \- Flat face \- Round cheeks \- Long philtrum \- Facial hypotonia Ears \- Prominent ears \- Low-set ears Eyes \- Myopia \- Long palpebral fissures \- Arched eyebrows \- Glaucoma, juvenile Nose \- Tubular nose \- Full nasal tip SKELETAL Hands \- Short hands \- Brachydactyly Feet \- Short feet \- Large first toes SKIN, NAILS, & HAIR Skin \- Vascular malformations (1 patient) Nails \- Brittle nails (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired intellectual development \- Impaired language development \- No seizures Behavioral Psychiatric Manifestations \- Autistic features MISCELLANEOUS \- Two unrelated patients have been reported (last curated July 2019) \- Non-neurologic features are variable \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the calcium/calmodulin-dependent protein kinase II-gamma gene (CAMK2G, 602123.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| INTELLECTUAL DEVELOPMENTAL DISORDER 59 | None | 4,238 | omim | https://www.omim.org/entry/618522 | 2019-09-22T15:41:36 | {"omim": ["618522"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 59"]} |
A number sign (#) is used with this entry because hawkinsinuria is caused by heterozygous mutation in the HPD gene (609695), encoding 4-hydroxyphenylpyruvic acid dioxygenase, on chromosome 12q24. Homozygous or compound heterozygous mutation in the HPD gene causes tyrosinemia type III (276710).
Description
Hawkinsinuria is an autosomal dominant inborn error of metabolism (Danks et al., 1975; Tomoeda et al., 2000). Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life.
Clinical Features
Niederwieser et al. (1977) identified a new sulfur amino acid in the urine of a girl with prolonged tyrosinuria and her mother (reported previously by Danks et al., 1975). The new amino acid, called hawkinsin, was identified as (2-L-cystein-S-yl-1,4-dihydroxycyclohex-5-en-1-yl)-acetic acid. They postulated that hawkinsin originated from an intermediate in the 4-hydroxyphenylpyruvate hydroxylase reaction (EC 1.13.11.27) and that mother and child were heterozygous for a defect in this hydroxylase system. The child presented at 20 weeks of age with failure to thrive and persistent acidosis. Her urine contained large amounts of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylactic acid, and 4-hydroxyphenylacetic acid. A diet specifically restricted in phenylalanine and tyrosine resulted in metabolic correction and rapid catch-up growth. After the age of 12 months tolerance for phenylalanine and tyrosine increased and was normal by 18 months. At age 6 years the girl was normal in all respects.
Wilcken et al. (1981) described 5 affected persons in 3 generations. The family was Australian but apparently unrelated to the previously reported cases. They confirmed dominant inheritance. The propositus became ill at 2 weeks of age when breastfeeding was discontinued. Regurgitation of feedings, irritability, tachypnea, and failure to thrive were problems. An unusual body odor 'like the smell of a swimming pool' was noted. At 6 months he was noted to be acidotic with enlarged liver. The hair was fair and stubby. Hemoglobin was 8.9 gm% and the blood smear showed anisocytosis, spherocytosis, and polychromasia. Hawkinsin and 4-hydroxycyclohexylacetic acid (4-HCAA) were found in the urine of the sister, mother, maternal aunt and maternal grandfather. All had been breast-fed as babies to ages 8 to 12 months, and none had had untoward symptoms. Wilcken et al. (1981) concluded that hawkinsinuria appears to be an inborn error of metabolism in which the accumulation of a toxic metabolite occurs when the normal conjugation capacities are exceeded. Their findings also supported a role of glutathione in detoxification of a highly reactive intermediate metabolite formed during the 4-hydroxyphenylpyruvate dioxygenase reaction.
Borden et al. (1992) described 2 affected families in the United States. In one family, expression of the gene was traced through 3 generations. Metabolic acidosis and failure to thrive appeared to be confined to infancy. Tyrosyl metabolites and 5-oxoproline were also found in the urine in infancy only. One child presented with failure to thrive and fine, sparse hair with persistent metabolic acidosis. Upon confirmation of the diagnosis of hawkinsinuria at 8 months, she was given a protein-restricted diet, following which she improved greatly.
Lehnert et al. (1999) described a 10.5-year-old male patient, the third child of a nonconsanguineous Austrian couple, who was followed from birth. The diagnosis of hawkinsinuria was established at the age of 3 years and 8 months, after a first misdiagnosis of fructose intolerance. Symptoms started after weaning from breast milk at the age of 3 months with recurrent vomiting, inappetence, and failure to thrive. Investigations during several hospital admissions revealed renal tubular acidosis of unknown cause, unclear hepatopathy, prolonged tyrosyluria, and 5-oxoprolinuria during acute illness. Despite initial severe failure to thrive and microcephaly, symptoms resolved gradually without specific treatment and the patient was described as physically and mentally normal at the time of report. Investigation of the parents and the 2 sisters did not detect any metabolic abnormalities, consistent with the possibility of a new mutation.
Molecular Genetics
In the original patient with hawkinsinuria described by Danks et al. (1975) and Niederwieser et al. (1977) and in an American patient described by Borden et al. (1992), Tomoeda et al. (2000) found a heterozygous ala33-to-thr mutation in 4-hydroxyphenylpyruvate dioxygenase (609695.0005).
History
Bloxam et al. (1960) found that 14 of 1,276 infants tested had large amounts of p-hydroxyphenylpyruvic acid, p-hydroxyphenylactic acid, and tyrosine in the urine. The infants were on normal diet. A delay in maturation of an enzyme was postulated. A genetic basis was presumed.
INHERITANCE \- Autosomal dominant GROWTH Other \- Failure to thrive METABOLIC FEATURES \- Metabolic acidosis (transient, resolves in infancy) LABORATORY ABNORMALITIES \- 4-hydroxyphenylpyruvic acid dioxygenase deficiency (HPD) \- Hawkinsinuria \- Tyrosinemia (transient, resolves in infancy) \- 4-hydroxyphenylpyruvic aciduria \- 4-hydroxyphenylactic aciduria \- 4-hydroxyphenylacetic aciduria \- 4-hydroxycyclohexylacetic aciduria (adults) MISCELLANEOUS \- Allelic to tyrosinemia, type III ( 276720 ) MOLECULAR BASIS \- Caused by mutation in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD, 609695.0005 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HAWKINSINURIA | c2931042 | 4,239 | omim | https://www.omim.org/entry/140350 | 2019-09-22T16:40:26 | {"mesh": ["C535845"], "omim": ["140350"], "orphanet": ["2118"]} |
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-84 (RP84) is caused by homozygous mutation in the DHX38 gene (605584) on chromosome 16q22.
For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical Features
Ajmal et al. (2014) reported 4 affected sibs from a consanguineous Pakistani family with early-onset retinitis pigmentosa and macular coloboma. All of the sibs had developed night blindness at 4 years of age, and all were completely blind (no light perception). Funduscopic examination of the proband showed severely attenuated retinal vessels throughout the fundus, and the maculae were severely affected bilaterally, with unusually prominent and deep macular colobomas devoid of neuroretinal tissue. Electrophysiologic responses of both rod and cone photoreceptors were severely reduced compared to control.
Latif et al. (2018) reported 2 consanguineous Pakistani families (MA88 and MA157) segregating early-onset retinitis pigmentosa. Affected members of both families, all of whom were older than age 20 years at the time of report, developed night blindness between ages 3 and 4 years and complete blindness between ages 7 and 8 years. Affected members of family MA88 retained light perception, whereas affected members of family MA157 had no light perception. In family MA88, the 3 affected males were diagnosed with bilateral cataracts at age 6 years; of the 2 affected females, one developed cataracts at age 19 years and the other did not have cataracts at age 20. In family MA157, all 6 affected members (5 males and 1 female) developed cataracts by about age 10 years. Funduscopy in the 3 affected females showed macular atrophy, attenuation of arteries, and clustered area of intraretinal pigment on the periphery. Bilateral cataract in affected males prevented funduscopy findings in the affected males.
Inheritance
The transmission pattern of retinitis pigmentosa in the family reported by Ajmal et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 affected sibs from a consanguineous Pakistani family with early-onset retinitis pigmentosa and macular coloboma, Ajmal et al. (2014) identified homozygosity for a missense mutation in the DHX38 gene (G332D; 605584.0001). The mutation was present in heterozygosity in their unaffected parents and 2 unaffected brothers, but it was not found in 180 ethnically matched controls or in the Exome Variant Server, 1000 Genomes Project, or dbSNP databases.
In affected members of 2 consanguineous Pakistani families (MA88 and MA157) with early-onset retinitis pigmentosa, Latif et al. (2018) identified homozygosity for the same missense mutation in the DHX38 gene (R324Q; 605584.0002). Mutation analysis in 3 members of each family with normal vision tests did not identify the mutation.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa \- No light perception (in some patients) \- Macular atrophy \- Attenuated vessels \- Intraretinal pigment on periphery \- Macular coloboma (in some patients) \- Cataracts (in some patients) MISCELLANEOUS \- Age of onset between 3-4 years \- Onset of blindness between 7-8 years MOLECULAR BASIS \- Caused by mutation in the DEAH box polypeptide gene 38 (DHX38, 605584.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| RETINITIS PIGMENTOSA 84 | c0035334 | 4,240 | omim | https://www.omim.org/entry/618220 | 2019-09-22T15:43:04 | {"mesh": ["D012174"], "omim": ["618220"], "orphanet": ["791"]} |
Early Infantile Epileptic Encephalopathy (EIEE) is a neurological disorder characterized by seizures. The disorder affects newborns, usually within the first three months of life (most often within the first 10 days) in the form of epileptic seizures. Infants have primarily tonic seizures (which cause stiffening of muscles of the body, generally those in the back, legs, and arms), but may also experience partial seizures, and rarely, myoclonic seizures (which cause jerks or twitches of the upper body, arms, or legs). Episodes may occur more than a hundred times per day. Most infants with the disorder show underdevelopment of part or all of the cerebral hemispheres or structural anomalies. Some cases are caused by metabolic disorders or by mutations in several different genes. The cause for many cases can’t be determined. There are several types of early infantile epileptic encephalopathy. The EEGs reveal a characteristic pattern of high voltage spike wave discharge followed by little activity. This pattern is known as “burst suppression.” The seizures associated with this disease are difficult to treat and the syndrome is severely progressive. Some children with this condition go on to develop other epileptic disorders such as West syndrome and Lennox-Gestaut syndrome.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Early Infantile Epileptic Encephalopathy | c0393706 | 4,241 | gard | https://rarediseases.info.nih.gov/diseases/9255/early-infantile-epileptic-encephalopathy | 2021-01-18T18:00:46 | {"umls": ["C0393706"], "orphanet": ["1934"], "synonyms": []} |
Granular parakeratosis
SpecialtyDermatology
Granular parakeratosis (also known as "Axillary granular parakeratosis",[1] "Intertriginous granular parakeratosis",[1] and more recently, "Zombie Patch") is a cutaneous condition characterized by brownish-red keratotic papules that can coalesce into plaques.[1]
## See also[edit]
* Pityriasis rubra pilaris
* List of cutaneous conditions
## References[edit]
1. ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
* v
* t
* e
Papulosquamous disorders
Psoriasis
Pustular
* Generalized pustular psoriasis (Impetigo herpetiformis)
* Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid)
* Annular pustular psoriasis
* Localized pustular psoriasis
Other
* Guttate psoriasis
* Psoriatic arthritis
* Psoriatic erythroderma
* Drug-induced psoriasis
* Inverse psoriasis
* Napkin psoriasis
* Seborrheic-like psoriasis
Parapsoriasis
* Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica)
* Lymphomatoid papulosis
* Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans)
* Large plaque parapsoriasis (Retiform parapsoriasis)
Other pityriasis
* Pityriasis rosea
* Pityriasis rubra pilaris
* Pityriasis rotunda
* Pityriasis amiantacea
Other lichenoid
Lichen planus
* configuration
* Annular
* Linear
* morphology
* Hypertrophic
* Atrophic
* Bullous
* Ulcerative
* Actinic
* Pigmented
* site
* Mucosal
* Nails
* Peno-ginival
* Vulvovaginal
* overlap synromes
* with lichen sclerosus
* with lupus erythematosis
* other:
* Hepatitis-associated lichen planus
* Lichen planus pemphigoides
Other
* Lichen nitidus
* Lichen striatus
* Lichen ruber moniliformis
* Gianotti–Crosti syndrome
* Erythema dyschromicum perstans
* Idiopathic eruptive macular pigmentation
* Keratosis lichenoides chronica
* Kraurosis vulvae
* Lichen sclerosus
* Lichenoid dermatitis
* Lichenoid reaction of graft-versus-host disease
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Granular parakeratosis | None | 4,242 | wikipedia | https://en.wikipedia.org/wiki/Granular_parakeratosis | 2021-01-18T18:59:21 | {"wikidata": ["Q5596719"]} |
A number sign (#) is used with this entry because of evidence that hypomagnesemia, seizures, and mental retardation-2 (HOMGSMR2) is caused by heterozygous mutation in the ATP1A1 gene (182310) on chromosome 1p13.
Description
HOMGSMR2 is characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation, and are associated with significantly impaired intellectual development (Schlingmann et al., 2018).
For a discussion of genetic heterogeneity of HOMGSMR, see 616418.
Clinical Features
Schlingmann et al. (2018) studied 3 infants who presented between 6 days and 6 months of age with generalized convulsions and severe hypomagnesemia due to massive renal magnesium wasting. Despite treatment with antiepileptic drugs and intravenous magnesium followed by oral supplementation, seizure activity persisted. Brain MRI in 2 of the patients showed cerebral volume loss, and all 3 had significant global developmental delay, displaying limited motor skills and speaking only in single words at ages 4 years, 6 years, and 10 years, respectively. In addition, 2 patients showed clinical features compatible with an autism spectrum disorder. All 3 patients were normotensive, and cardiac evaluation was unremarkable. Significant polyuria was observed in 2 patients, but renal concentrating ability remained at least partially intact, with random urine osmolalities of greater than 400 mosmol/L. Although laboratory analyses did not show renal salt wasting or significant activation of the renin-aldosterone system, all affected individuals exhibited intermittent episodes of significant hypokalemia due to renal potassium wasting. The parents of all 3 children were clinically unaffected and had normal serum magnesium levels.
Molecular Genetics
From a cohort of 7 children with hypomagnesemia and intractable seizures associated with severe intellectual disability, who were negative for mutation in the CNNM2 (607803) and TRPM6 (607009) genes, Schlingmann et al. (2018) identified 3 who were heterozygous for missense mutations in the ATP1A1 gene (182310.0006-182310.0008). All 3 variants were shown to have arisen de novo and were not found in public variant databases.
INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Renal magnesium wasting, severe intractable \- Renal potassium wasting \- Polyuria \- Medullary hyperechogenicity NEUROLOGIC Central Nervous System \- Generalized seizures \- Status epilepticus, recurrent \- Global developmental delay \- Cerebral volume loss \- Dilated ventricles \- Incomplete myelination Behavioral Psychiatric Manifestations \- Hyperactivity \- Self-biting \- Autism or autism spectrum disorder LABORATORY ABNORMALITIES \- Hypomagnesemia \- Hypokalemia, intermittent MISCELLANEOUS \- Persistent seizure activity despite amelioration of magnesium levels MOLECULAR BASIS \- Caused by mutation in the Na+/K+ transporting ATPase, alpha-1 polypeptide gene (ATP1A1, 182310.0006 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPOMAGNESEMIA, SEIZURES, AND MENTAL RETARDATION 2 | None | 4,243 | omim | https://www.omim.org/entry/618314 | 2019-09-22T15:42:32 | {"omim": ["618314"]} |
Corticosteroid-sensitive aseptic abscesses syndrome is a well-defined entity within the group of autoinflammatory disorders.
## Epidemiology
It is a rare disease with 49 cases documented so far. Prevalence is unknown.
## Clinical description
It affects mainly young adults and is characterized by recurrent attacks of fever and deep abscess-like collections, most frequently localized in the abdomen. Blood markers of inflammation and polymorphonuclear neutrophil levels are elevated. Aseptic abscesses may be either isolated or associated with an underlying condition such as relapsing polychondritis (see this term) or inflammatory bowel disease. The abscesses usually precede the diagnosis of inflammatory bowel disease, possibly by several years. A neutrophilic dermatosis, like pyoderma gangrenosum, may also be observed.
## Etiology
The etiology is unknown: all searches for a pathogen, including those using PCR with universal and specific probes, remain negative. A familial history of a granulomatous disorder is found in a few cases.
## Diagnostic methods
On pathologic examination, aseptic abscesses consist of a core of altered polymorphonuclear leukocytes surrounded by palisading histiocytes and sometimes giant cells.
## Management and treatment
Antibiotics fail to cure the patients but dramatic improvements are seen with corticosteroids and immunosuppressive drugs.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Corticosteroid-sensitive aseptic abscess syndrome | None | 4,244 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=54251 | 2021-01-23T18:20:04 | {"gard": ["10946"], "synonyms": ["Aseptic abscesses syndrome", "Aseptic systemic abscesses", "Disseminated aseptic abscesses"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive congenital ichthyosis-2 (ARCI2) is caused by homozygous or compound heterozygous mutation in the ALOX12B gene (603741) on chromosome 17p13.
Description
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010).
NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006).
In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005).
For a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
Clinical Features
Jobard et al. (2002) studied 6 consanguineous families (3 Turkish, 2 North African, 1 French) with congenital ichthyosis mapping to chromosome 17p. All affected individuals were born as collodion babies, and all had features consistent with nonbullous ichthyosiform erythroderma. A 3-year-old boy from 1 of the Turkish families presented mild ichthyosiform erythroderma, with fine white desquamation over the entire body and palmoplantar keratoderma. A 12-year-old girl from an unrelated Turkish family had fine white scaling on her face, neck, trunk, and flexor surfaces, but larger and darker polygonal scales on the buttocks and extensor surfaces of her arms and legs. She also had an ectropion, an eclabium, severe palmoplantar keratoderma, mild diffuse alopecia, and thin nails.
### Self-Healing Collodion Baby
Harting et al. (2008) reported 2 male infants born with collodion membrane who had dramatic improvement of the skin in the first few weeks of life and then developed very mild nonbullous congenital ichthyosiform erythroderma. The first was a Hispanic boy who was born with a hyperkeratotic, fissured, and tight parchment-like membrane, as well as bilateral ectropion, eclabium and fixed open mouth, and low-set dysplastic ears. He had hypoplastic fingers, toes, and nails, and his movements were reduced due to tight skin over his extremities. At day 3 of life, application of topical emollients resulted in dramatic improvement, and at 8 weeks of age, his skin was completely normal except for minimal residual erythema and scant fine white scales on his trunk and extremities; at 3 months, only a small pink plaque was visible on his back with minimal scale. Histologic examination of the collodion membrane showed nonspecific findings typical of many forms of ichthyosis: a thickened stratum corneum with hyperkeratosis, acanthosis, and mild hypergranulosis. Electron microscopy revealed a cornified cell envelope like that seen in harlequin ichthyosis (HI; see 242500), suggesting that cornified cell envelope is not a specific diagnostic feature of HI. The other boy had a thick glossy encasement with areas of fissuring and associated eclabium; the membrane was shed by 2 weeks of age, leaving behind mildly xerotic but mostly normal-appearing skin. Later in infancy, he developed a fine, generalized, mild scaling consistent with an extremely mild NCIE with pruritic areas of erythema and scaling accentuated in flexural creases consistent with atopic eczema, and he also manifested hyperlinear palms and infraorbital folds.
Vahlquist et al. (2010) studied 11 Swedish and 4 Danish patients with autosomal recessive congenital ichthyosis of the 'self-healing' type, all of whom were born with a variably thick collodion membrane, with ectropion present in 8 cases. The membrane was spontaneously shed after 2 to 4 weeks, exposing almost normal-appearing skin. Examination at 2 years to 37 years of age, however, revealed that all of the patients had varying degrees of mild ichthyosis, consisting of scaling in the armpits, acral hyperkeratosis and keratoderma, coarse scales on the scalp, and fine scaling around the neck, together with xerotic extremities and red cheeks that stung with exposure to salt water. All but 1 of the patients exhibited moderate to severe anhidrosis. Vahlquist et al. (2010) proposed the term 'self-improving collodion ichthyosis' (SICI) as a better designation for this phenotype.
Mapping
In 56 consanguineous families with congenital ichthyosis in which all known ARCI loci except chromosome 17p13.1 had been excluded, Jobard et al. (2002) analyzed 6 microsatellites and identified 6 kindreds from the Mediterranean basin with linkage to 17p13.1. Further genotyping in those 6 families revealed a homozygous interval between D17S960 and D17S1858 in all patients. The maximum pairwise lod score (theta = 0) for the marker D17S1844 was 6.63 and the multipoint lod score at the same locus was 10.04. Linkage disequilibrium analysis reduced the interval size to approximately 600 kb between D17S1812 and D17S1805, a segment containing 2 genes from the LOX family, ALOX12B (603741) and ALOXE3 (607206).
Molecular Genetics
In affected individuals from 3 consanguineous families with congenital ichthyosis mapping to chromosome 17p13.1, one of North African origin and 2 of Turkish origin, Jobard et al. (2002) identified homozygosity for a 1-bp deletion and 2 missense mutations in the ALOX12B gene (603741.0001-603741.0003). In another 3 families with ARCI mapping to 17p13.1 (ARCI3; 606545), they identified homozygosity for mutations in the ALOXE3 gene (607206). Jobard et al. (2002) hypothesized that the product of 1 of these enzymes might be the substrate of the other, and thus function in the same metabolic pathway. Yu et al. (2003) demonstrated that ALOXE3 functions as an epoxy alcohol synthase using the product of ALOX12B as the preferred substrate. providing strong biochemical evidence for functional linkage of the ALOX12B and ALOXE3 proteins. The 2 genes are coexpressed in tissues, and mutation in either can cause ichthyosis, indicating a functional relationship.
Eckl et al. (2005) analyzed the ALOX12B and ALOXE3 genes in 143 families of Indo-European and Arab origins with autosomal recessive congenital ichthyosis that were negative for mutation in the TGM1 gene (190195), and identified 11 different point mutations in the ALOX12B gene (see, e.g., 603741.0004-603741.0006) and 5 in the ALOXE3 gene (see, e.g., 607206.0002 and 607206.0004-607206.0006) in 17 families. All of the mutations cosegregated with disease in the respective families, and none was found in 150 ethnically matched controls. Eckl et al. (2005) concluded that approximately 10% of ARCI patients carry mutations in one of the LOX genes.
Lesueur et al. (2007) analyzed the ALOX12B and ALOXE3 genes in 20 patients from 11 families with ARCI mapping to chromosome 17p13, and identified homozygosity or compound heterozygosity for mutations in the ALOX12B gene in 6 families, including a Turkish patient who exhibited a lamellar phenotype (603471.0007). No disease-causing mutations were identified in patients from 5 families, in whom the candidate gene ALOX15B (603697) was analyzed as well, indicating that other genes on chromosome 17p13 may be involved in this disease.
In 2 infants who had ARCI consisting of self-healing collodion membrane followed by mild nonbullous congenital ichthyosiform erythroderma, who were both negative for mutation in the TGM1 gene, Harting et al. (2008) identified compound heterozygosity for mutations in the ALOX12B gene (603741.0008-603741.0011).
In 15 Scandinavian patients with ARCI of the self-healing collodion baby type, Vahlquist et al. (2010) analyzed 7 ARCI-related genes and identified homozygosity or compound heterozygosity for mutations in the ALOX12B gene in 8 patients (see, e.g., 603741.0012 and 603741.0013), in the ALOXE3 gene in 3 patients (see, e.g., 607206.0008), and in the TGM1 gene in 1 patient. No mutations were identified in the 3 remaining patients.
### Genetic Heterogeneity
Eckl et al. (2009) studied 250 unrelated patients representing the entire phenotypic spectrum of ARCI, including 15 patients from families previously studied by Eckl et al. (2005), and found that mutations in TGM1 accounted for 38% of the cases, whereas mutations in the ALOX12B (603741) and ALOXE3 (607206) genes each represented 6.8% of the cases.
Genotype/Phenotype Correlations
Eckl et al. (2005) performed detailed clinical characterization of affected individuals from 17 ARCI families with mutations in the ALOX12B or ALOXE3 genes and concluded that LOX mutations lead to typical but mild ARCI phenotypes, with fine white scales and moderate erythema. Most patients were born with collodion membranes. Palmoplantar keratoderma was a rare finding, and was only mild when present. Eckl et al. (2005) noted that the self-healing course can also be associated with LOX mutations, and there was improvement of ichthyosis in early childhood in some cases.
Eckl et al. (2009) assessed in detail 21 ARCI patients from 19 families in whom mutations in ALOX12B and ALOXE3 had been found, including some of the families previously studied by Eckl et al. (2005). Neonates born with collodion membrane often showed a mild to moderate manifestation compared with other types of congenital ichthyosis. Ectropion or eclabium, mostly mild, was only present in one-third of cases. Children and adults showed a generalized scaling with mild to moderate erythema; scales were mostly whitish to light brown, discrete to moderate in adherence, and small in size. More than half of the patients (13 of 19) showed a striking palmoplantar hyperlinearity with or without mild keratoderma. In contrast to ichthyosis vulgaris (146700), patients showed a mild keratotic lichenification that also included the elbow or popliteal fossa and the dorsa of the extremities. Heat intolerance because of reduced sweating ability (hypohidrosis) was present in almost all patients. Eckl et al. (2009) noted that erythema was significantly more pronounced in patients with ALOX12B mutations than in those with ALOXE3 mutations. In addition, all ALOX12B patients showed mild hyperkeratosis of palms and soles with accentuated palmoplantar creases, whereas keratoderma was absent in 9 of 12 patients with ALOXE3 mutations, and the other 3 patients showed only very discrete palmar or plantar keratosis.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Ectropion (in some patients) Mouth \- Eclabium (in some patients) SKELETAL Hands \- Hypoplastic fingers (in some cases) Feet \- Hypoplastic toes (in some cases) SKIN, NAILS, & HAIR Skin \- Collodion membrane at birth (in some patients) \- Collodion membrane, self-healing (in some patients) \- Erythema, mild to moderate (in some patients) \- Fine white or light brown scales on scalp, face, trunk, and limbs \- Larger and darker scales on neck, elbows, and knees (in some patients) \- Palmoplantar hyperlinearity, marked \- Palmoplantar keratoderma, mild \- Hypohidrosis (in most patients) Skin Histology \- Thickened stratum corneum \- Hyperkeratosis \- Acanthosis \- Hypergranulosis, mild Electron Microscopy \- Cornified cell envelope Nails \- Hypoplastic nails (in some patients) \- Thin nails (rare) Hair \- Alopecia, mild diffuse (rare) MOLECULAR BASIS \- Caused by mutation in the R-type arachidonate 12-lipoxygenase gene (ALOX12B, 603741.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 2 | c1855789 | 4,245 | omim | https://www.omim.org/entry/242100 | 2019-09-22T16:26:29 | {"doid": ["0060710"], "mesh": ["C565473"], "omim": ["242100"], "orphanet": ["281122", "79394"], "synonyms": ["Alternative titles", "COLLODION BABY, SELF-HEALING", "ICHTHYOSIFORM ERYTHRODERMA, NONBULLOUS CONGENITAL, 1, FORMERLY", "ICHTHYOSIFORM ERYTHRODERMA, BROCQ CONGENITAL, NONBULLOUS FORM, FORMERLY"], "genereviews": ["NBK1420"]} |
Extraneural perineurioma is a rare tumor of cranial and spinal nerves arising from peripheral nerve sheet and composed exclusively or predominantly of cells showing perineurial differentiation. It presents as a well-circumscribed, rarely encapsulated mass, not associated with a recognizable nerve, most commonly arising in the dermis and subcutis of the extremities or trunk, or, rarely, in deep soft tissue or skin (e.g., in the stomach, kidney, pancreas, maxillary sinus, mandible, bronchial tree and the face). The clinical presentation depends on the localization.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Extraneural perineurioma | c4708595 | 4,246 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100002 | 2021-01-23T18:28:20 | {"synonyms": ["Soft tissue perineurioma"]} |
In 2 of 3 sons of third-cousin parents, Keutel et al. (1970) described humeroradial synostosis. Frostad (1940) reported recessive inheritance. The parents were from the same small village. The parents in the family reported by Schroder (1932) were likewise consanguineous. Humeroradial synostosis also occurs with the syndrome of multiple synostoses with brachymesophalangy (186500), with Pfeiffer syndrome (101600), and with the SC phocomelia syndrome (269000).
Ramer and Ladda (1989) described sibs with nearly identical humeroradial synostosis. They found records of 9 families with 19 affected individuals with this phenotypic and genetic pattern. Despite the skeletal malformations, functional capability in these patients has been good. Most have been productively employed, and all were able to master their self-care skills. Ramer and Ladda (1989) included among the 9 families that reported by Frankel (1942) in which renal failure accompanied by hematuria and proteinuria developed in young adulthood. Since these patients had patellar subluxation or hypoplasia as well, it is likely that they had the nail-patella syndrome (161200), not the disorder discussed in this entry.
Richieri-Costa et al. (1986) reported the case of an 11-month-old girl whose parents were first cousins and who had plagiobrachycephaly, prominent forehead, broad nasal root, small ears with hypoplastic lobes, an unusual type of multiple synostoses involving humeroradial, carpal, tarsal, and phalangeal joints, and apparent agenesis of the distal phalanges of the postaxial digits. Mental and somatic development was normal. Autosomal recessive inheritance was suggested.
Skel \- Humeroradial synostosis Inheritance \- Autosomal recessive ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HUMERORADIAL SYNOSTOSIS | c2930865 | 4,247 | omim | https://www.omim.org/entry/236400 | 2019-09-22T16:27:06 | {"doid": ["0060467"], "mesh": ["C535284"], "omim": ["236400", "143050"], "orphanet": ["3265"], "synonyms": ["Humero-radial fusion"]} |
Setleis syndrome
Other namesFFDD3[1]
Setleis syndrome is said to be inherited in an autosomal recessive manner.
SpecialtyDermatology
Setleis syndrome is a very rare genetic condition characterized by facial skin abnormalities and double upper eyelashes and absent lower eyelashes.[2] It belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area that may be apparent at birth (congenital). Most affected infants have multiple, scar-like, circular depressions on both temples (bitemporal). These marks closely resemble those made when forceps are used to assist delivery.[3] The range and severity of symptoms may vary from case to case.
Most cases of Setleis syndrome are thought to be inherited as an autosomal recessive genetic trait due to mutations in the TWIST2 gene.
The differential diagnosis of Setleis syndrome includes X-linked focal dermal hypoplasia, or Goltz syndrome; a syndrome of focal dermal hypoplasia, morning glory anomaly, and polymicrogyria; incontinentia pigmenti; oculocerebrocutaneous syndrome; Rothmund–Thomson syndrome; and MLS (microphthalmia with linear skin defects) syndrome caused by deletions or point mutations in the HCCS gene.
## See also[edit]
* Triangular alopecia
* Red lunulae
* List of skin conditions
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Focal facial dermal dysplasia type III". www.orpha.net. Retrieved 27 April 2019.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
3. ^ "Setleis Syndrome".
## External links[edit]
Classification
D
* ICD-10: Q82.8
* OMIM: 227260
* SNOMED CT: 403771007
External resources
* Orphanet: 1807
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Setleis syndrome | c1744559 | 4,248 | wikipedia | https://en.wikipedia.org/wiki/Setleis_syndrome | 2021-01-18T19:00:53 | {"mesh": ["C536385"], "orphanet": ["1807"], "wikidata": ["Q7456737"]} |
Perennial ryegrass staggers is poisoning by peramine, lolitrem B, and other toxins that are contained in perennial ryegrass (Lolium perenne), and produced by the endophyte fungus Neotyphodium lolii which can be present in all parts of the grass plant, but tends to be concentrated in the lower part of the leaf sheaths, the flower stalks and seeds. This condition can affect horses, cattle, sheep, farmed deer and llamas. It regularly occurs in New Zealand and is known spasmodically from Australia, North and South America, and Europe.[1]
## Contents
* 1 Ecology
* 2 Symptoms
* 3 Treatment
* 4 Prevention
* 5 References
## Ecology[edit]
Perennial ryegrass staggers is caused by the ingestion of grass that is infected by the endophyte fungus Epichloë festucae var lolli, and this fungus produces a variety of toxins such as peramine, a pyrrolopyrazine alkaloid, and lolitrem B,[2] an indole-diterpene compound. There is no external sign when perennial ryegrass is infected by this fungus. The Argentine stem weevil (Listronotus bonariensis) feeds on perennial ryegrass. When the grass on which they are feeding is infected by the fungus, the larvae of the weevil fail to develop fully. In an effort to breed perennial ryegrass that was resistant to the weevil, researchers in New Zealand inadvertently selected strains that were susceptible to the fungus. In fact the endophytic fungus forms a mutualistic association with the grass which grows more vigorously as a result and produces more tillers. With greater use of these susceptible cultivars, the fungus which is present in the seed, spread more widely with a consequent increase in perennial ryegrass staggers.[3][4]
## Symptoms[edit]
Symptoms are neurological and may develop one to two weeks after exposure to infected pasture.[5] Symptoms may include head shaking and irregular eye movements, changes in gait, stiffness, staggering and falling. Recumbent animals may display tetanic spasms and may die through misadventure, dehydration, starvation, loss of rumen function or predation.[6] In the case of horses, the animal may quiver or tremble, be easily startled and be awkward to handle. More severely affected animals may repeatedly nod their head, show a tendency to splay their legs, and stumble and fall. The hind-quarters, moreover, may become paralysed.[5]
## Treatment[edit]
Recovery usually occurs when the animal is removed from the contaminated pasture. The chief danger to stock at this stage is caused by their lack of coordination, which may result in accidental death by falling in awkward places such as ditches and ponds.[5]
## Prevention[edit]
The disease is particularly prevalent in New Zealand. It may be prevented by avoiding grazing pastures containing perennial ryegrass, or seeding pastures with resistant strains of ryegrass. Horses are particularly prone to this disease because of their habit of biting close to the ground, and sparse pastures may encourage heavier grazing with greater intake of infected material. Supplementary feeding may help, but hay from infected pasture should not be used because it may contain further toxins.[5]
## References[edit]
1. ^ Simpson, Wayne (1 August 2013). "Perennial ryegrass staggers". Merck. Retrieved 12 December 2015.
2. ^ Gallagher, R. T.; White, E. P.; Mortimer, P. H. (1981-10-01). "Ryegrass Staggers: Isolation of Potent Neurotoxins Lolitrem a and Lolitrem B From Staggers-Producing Pastures". New Zealand Veterinary Journal. 29 (10): 189–190. doi:10.1080/00480169.1981.34843. ISSN 0048-0169. PMID 6950333.
3. ^ Rowan, D.D.; Dymock, J.J.; Brimble, M.A. (1990). "Effect of fungal metabolite peramine and analogs on feeding and development of Argentine stem weevil (Listronotus bonariensis)". Journal of Chemical Ecology. 16 (5): 1683–1695. doi:10.1007/BF01014100. PMID 24263837.
4. ^ Varney, D.R.; Prestidge, R.A.; Jones, D.D.; Varney, L.A.; Zavos, P.M.; Siegel, M.R. (1989). "Effect of endophyte-infected perennial ryegrass seed diets on growth and reproduction in mice". New Zealand Journal of Agricultural Research. 32 (4): 547–554. doi:10.1080/00288233.1989.10417929.
5. ^ a b c d "Perennial ryegrass staggers". Totally Vets. Retrieved 12 December 2015.
6. ^ Scrivener, Colin J. (17 April 2002). "Perennial ryegrass staggers". Animal Welfare Science Centre. Retrieved 12 December 2015.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Perennial ryegrass staggers | c0275348 | 4,249 | wikipedia | https://en.wikipedia.org/wiki/Perennial_ryegrass_staggers | 2021-01-18T19:07:13 | {"wikidata": ["Q11346346"]} |
Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD; see this term). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.
## Epidemiology
The annual incidence of GD in the general population is around 1/60,000 and the prevalence is approximately 1/100,000. GD type 2 is very rare, with an incidence of approximately 5% of all GD patients and has a prevalence of virtually zero, taking into account its severity and early death.
## Clinical description
The disease usually presents in infants aged 3 to 6 months with systemic manifestations of hepatosplenomegaly and an early onset and severe neurological syndrome. The first signs are oculomotor paralysis or bilateral fixed strabismus associated with bulbar signs, in particular severe swallowing difficulties, progressive spasticity and dystonic movements. Seizures occur later and manifest as myoclonic epilepsy that is refractory to treatment with antiepileptics.
## Etiology
GD type 2 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that codes for the lysosomal enzyme, glucocerebrosidase. The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, of the spleen and the bone marrow (Gaucher cells).
## Diagnostic methods
A definite diagnosis requires the demonstration of a deficit in the enzymatic activity of glucocerebrosidase.
## Antenatal diagnosis
Biochemical prenatal diagnosis can be proposed to couples who have already had a child with GD type 2. It can be carried out by measuring the enzyme activity in chorionic villus samples at 10-12 weeks of pregnancy or in amniocytes in culture towards 16 weeks of pregnancy.
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
The treatment does not seem to have an effect on neurological manifestations and is therefore not indicated for patients with GD type 2.
## Prognosis
Prognosis is poor with most patients dying before the age of 2.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Gaucher disease type 2 | c0268250 | 4,250 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77260 | 2021-01-23T18:58:59 | {"gard": ["2442"], "mesh": ["D005776"], "omim": ["230900"], "umls": ["C0268250"], "icd-10": ["E75.2"], "synonyms": ["Acute neuronopathic Gaucher disease", "Infantile cerebral Gaucher disease"]} |
Pilodental dysplasia-refractive errors syndrome is a rare ectodermal dysplasia syndrome characterized by dysplastic abnormalities of the hair and teeth (including hypodontia, abnormally shaped teeth, scalp hypotrichosis and pili annulati), follicular hyperkeratosis on the trunk and limbs, and hyperopia. Intensified delineation, reticular hyperpigmentation of the nape and astigmatism have also been reported. There have been no further descriptions in the literature since 1985.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pilodental dysplasia-refractive errors syndrome | c1849805 | 4,251 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2892 | 2021-01-23T18:33:46 | {"gard": ["277"], "mesh": ["C535763"], "omim": ["262020"], "umls": ["C1849805"], "synonyms": ["Euhidrotic ectodermal dysplasia", "Kopysc-Barczyk-Krol syndrome"]} |
A rare genetic neurological disorder characterized by the association of hypomyelinating leukodystrophy with spondylometaphyseal dysplasia. Patients present in infancy with absent or delayed ability to walk independently, slowly progressive motor deterioration, spasticity, ataxia, proximal weakness, and joint contractures. Additional manifestations include mild cognitive impairment, short stature, scoliosis, enlarged and deformed joints, dysarthria, nystagmus, visual defects, and mildly dysmorphic features, among others. Mode of inheritance is X-linked recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome | c1970840 | 4,252 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83629 | 2021-01-23T17:58:04 | {"mesh": ["C567065"], "omim": ["300232"], "umls": ["C1970840"], "icd-10": ["G11.4"], "synonyms": ["H-SMD", "Hypomyelination-spondyloepimetaphyseal dysplasia syndrome", "Leukoencephalopathy-SEMD syndrome", "Leukoencephalopathy-metaphyseal chondrodysplasia syndrome"]} |
Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.
An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).
In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older.
## Frequency
CIPA is a rare condition; however, the prevalence is unknown.
## Causes
Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides instructions for making a receptor protein that attaches (binds) to another protein called NGFβ. The NTRK1 receptor is important for the survival of nerve cells (neurons).
The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons). When the NGFβ protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.
### Learn more about the gene associated with Congenital insensitivity to pain with anhidrosis
* NTRK1
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital insensitivity to pain with anhidrosis | c0020074 | 4,253 | medlineplus | https://medlineplus.gov/genetics/condition/congenital-insensitivity-to-pain-with-anhidrosis/ | 2021-01-27T08:25:01 | {"gard": ["3006"], "mesh": ["D009477"], "omim": ["256800"], "synonyms": []} |
Progressive bulbar palsy involves the brain stem. The brain stem is the part of the brain needed for swallowing, speaking, chewing, and other functions. Signs and symptoms of progressive bulbar palsy include difficulty swallowing, weak jaw and facial muscles, progressive loss of speech, and weakening of the tongue. Additional symptoms include less prominent weakness in the arms and legs, and outbursts of laughing or crying (called emotional lability).
Progressive bulbar palsy is considered a variant form of amyotrophic lateral sclerosis (ALS). Many people with progressive bulbar palsy later develop ALS. While there is no cure for progressive bulbar palsy or for ALS, doctors can treat symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Progressive bulbar palsy | c0030442 | 4,254 | gard | https://rarediseases.info.nih.gov/diseases/10928/progressive-bulbar-palsy | 2021-01-18T17:58:09 | {"mesh": ["D010244"], "synonyms": ["Progressive bulbar atrophy"]} |
Neonatal progeroid syndrome is a rare genetic syndrome characterized by an aged appearance at birth. Other signs and symptoms include intrauterine growth restriction, feeding difficulties, distinctive craniofacial features, hypotonia, developmental delay and mild to severe intellectual disability. In most cases, affected infants pass away before age 7 months, but rare reports exist of survival into the teens or early 20s. Although the exact underlying cause of neonatal progeroid syndrome is unknown, it is likely a genetic condition that is inherited in an autosomal recessive manner. Treatment is symptomatic and supportive.
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neonatal progeroid syndrome | c0406586 | 4,255 | gard | https://rarediseases.info.nih.gov/diseases/330/neonatal-progeroid-syndrome | 2021-01-18T17:58:47 | {"mesh": ["C536423"], "omim": ["264090"], "umls": ["C0406586"], "orphanet": ["3455"], "synonyms": ["Wiedemann-Rautenstrauch syndrome", "Progeroid syndrome neonatal", "Wiedemann Rautenstrauch syndrome"]} |
## Clinical Features
Speech-sound disorder (SSD) is a complex behavioral disorder characterized by speech-sound production errors associated with deficits in articulation, phonologic processes, and cognitive linguistic processes. SSD is prevalent in childhood and is comorbid with disorders of language, spelling, and reading disability, or dyslexia. SSD has a high prevalence in preschool children, estimated at approximately 16% at age 3 years, with 3.8% of children continuing to present with speech delay at age 6 years (Shriberg et al., 1999). More than half of these children encounter later academic difficulties in language, reading, and spelling.
Inheritance
Evidence that susceptibility to SSD is genetic is provided by twin studies, familial aggregation studies, and segregation and linkage analyses (review by Stein et al., 2004).
Mapping
Pennington and Lefly (2001) and Tunick and Pennington (2002) proposed that early developmental problems in spoken language predict the later emergence of dyslexia in children from high-risk families. Nopola-Hemmi et al. (2001) analyzed a large Finnish pedigree segregating for developmental dyslexia in an autosomal dominant fashion and found linkage to the pericentromeric region of chromosome 3 (DYX5; 606896). On the basis of the hypothesis that SSD and dyslexia share genetic determinants, Stein et al. (2004) genotyped markers in the dyslexia candidate region on chromosome 3 to determine whether linkage would be observed in families ascertained through a proband with SSD. They studied 77 such families. The quantitative scores measured several processes underlying speech-sound production, including phonologic memory, phonologic representation, articulation, receptive and expressive vocabulary, and reading, decoding, and comprehension skills. In multipoint analyses, measures of phonologic memory demonstrated strongest linkage to the chromosome 3 pericentromeric region. The results suggested that domains common to SSD and dyslexia are pleiotropically influenced by a putative quantitative trait locus on chromosome 3.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SPEECH-SOUND DISORDER | c4019167 | 4,256 | omim | https://www.omim.org/entry/608445 | 2019-09-22T16:07:48 | {"mesh": ["D066229"], "omim": ["608445"], "synonyms": ["Alternative titles", "SSD"]} |
Schimmelpenning syndrome
SpecialtyMedical genetics
Schimmelpenning syndrome is a neurocutaneous condition characterized by one or more sebaceous nevi, usually appearing on the face or scalp,[1] associated with anomalies of the central nervous system, ocular system, skeletal system, cardiovascular system and genitourinary system.[2]
Synonyms include: "Linear nevus sebaceous syndrome (LNSS)", "Schimmelpenning-Feuerstein-Mims syndrome", "Feuerstein-Mims syndrome", "sebaceous nevus syndrome", "Solomon syndrome", and "Jadassohn's nevus phakomatosis". "Nevus" is sometimes spelled "naevus" and "sebaceous" may also be spelled "sebaceus". "Epidermal nevus syndrome" is sometimes used as a synonym, but more often as a broader term referring to Schimmelpenning syndrome in addition to nevus comedonicus syndrome, CHILD syndrome, Becker's nevus syndrome, and phakomatosis pigmentokeratotica.[3]
The classic Schimmelpenning syndrome diagnosis comprises a triad of sebaceous nevi, seizures, and mental retardation.[2] The condition was first reported by Gustav Schimmelpenning in 1957[4] and independently reported by Feuerstein and Mims in 1962.[5]
## Contents
* 1 Signs and symptoms
* 2 Genetic
* 3 Diagnosis
* 4 Management
* 5 Incidence
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Since the original identification of Schimmelpenning syndrome, the number of findings has expanded to the point that the syndrome is associated with a considerable constellation of abnormalities.[2] The abnormalities may occur in a variety of combinations, and need not include all three aspects of the classic triad of sebaceous nevus, seizures and mental retardation. In 1998, a literature review by van de Warrenburg et al. found:
* seizures in 67% of cases
* mental retardation in 61% of cases
* ophthalmological abnormalities in 59% of cases
* involvement of other organ systems in 61% of cases
* structural abnormality of cerebrum or cranium in 72% of cases[6]
The major neurological abnormalities include mental retardation to varying extent, seizures, and hemiparesis.[7] Seizures, when present, typically begin during the first year of life.[8] The most common structural central nervous system abnormalities in Schimmelpenning syndrome are hemimegalencephaly and ipselateral gyral malformations.[3]
The major ocular abnormalities are colobomas and choristomas.[7]
Skeletal abnormalities may include dental irregularities, scoliosis, vitamin D-resistant rickets and hypophosphatemia. Cardiovascular abnormalities include ventricular septal defect and coarctation of the aorta; urinary system issues include horseshoe kidney and duplicated urinary collection system.[2]
## Genetic[edit]
Schimmelpenning syndrome appears to be sporadic rather than inherited, in almost all cases.[2] It is thought to result from genetic mosaicism, possibly an autosomal dominant mutation arising after conception and present only in a subpopulation of cells. The earlier in embryological development such a mutation occurs, the more extensive the nevi are likely to be and the greater the likelihood of other organ system involvement.[9]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (April 2017)
## Management[edit]
In general, children with a small isolated nevus and a normal physical exam do not need further testing;[9] treatment may include potential surgical removal of the nevus.[10] If syndrome issues are suspected, neurological, ocular, and skeletal exams are important. Laboratory investigations may include serum and urine calcium and phosphate, and possibly liver and renal function tests. The choice of imaging studies depends on the suspected abnormalities and might include skeletal survey, CT scan of the head, MRI, and/or EEG.[9]
Depending on the systems involved, an individual with Schimmelpenning syndrome may need to see an interdisciplinary team of specialists: dermatologist, neurologist, ophthalmologist, orthopedic surgeon, oral surgeon, plastic surgeon, psychologist.[9]
## Incidence[edit]
Nevus sebaceous was first identified in 1895 by Jadassohn.[11] Sebaceous nevi occur in 1 to 3 of 1000 births, with equal incidence by sex.[3] There is no test to determine whether an individual born with a sebaceous nevus will go on to develop further symptoms of Schimmelpenning syndrome. It has been reported that up to 10% of individuals with epidermal nevi may develop additional syndrome symptoms,[3] but that number appears to be inconsistent with the rarity of the syndrome and may be overstated.[12] Prevalence is unknown, but Epidermal nevus syndrome is listed with the National Organization for Rare Disorders, which defines rare as affecting "fewer than 200,000 people in the United States." [13]
## See also[edit]
* Epidermis
* Epidermal nevus syndrome
* Skin lesion
* List of cutaneous conditions
## References[edit]
1. ^ Menascu, Shay; Donner, Elizabeth J. (2008). "Linear nevus sebaceous syndrome: case reports and review of the literature". Pediatric Neurology. 38 (3): 207–10. doi:10.1016/j.pediatrneurol.2007.10.012. ISSN 0887-8994. PMID 18279757.
2. ^ a b c d e Eisen, D.B.; Michael, D.J. (2009). "Sebaceous lesions and their associated syndromes: Part II". Journal of the American Academy of Dermatology. 61 (4): 563–78. doi:10.1016/j.jaad.2009.04.059. ISSN 0190-9622. PMID 19751880.
3. ^ a b c d Burns, Tony, ed. (2004). Rook's Textbook of Dermatology (7th ed.). Malden, Mass.: Blackwell Science. ISBN 0-632-06429-3.
4. ^ Schimmelpenning, G. (1957). "Klinischer Beitrag zur Symptomatology der Phacomatosen". Fortschr Röntgenstr. 87 (6): 716–20. doi:10.1055/s-0029-1213358. PMID 13512450.
5. ^ Feuerstein, RC; Mims, LC (1962). "Linear nevus sebaceus with convulsions and mental retardation". Am. J. Dis. Child. 104 (6): 674–679. doi:10.1001/archpedi.1962.02080030675013. PMID 13944982.
6. ^ van de Warrenburg BP, van Gulik S, Renier WO, Lammens M, Doelman JC (1998). "The linear naevus sebaceus syndrome". Clinical Neurology and Neurosurgery. 100 (2): 126–132. doi:10.1016/S0303-8467(98)00012-2. PMID 9746301.
7. ^ a b Harper, J.; A.P. Oranje; N.S. Prose (2006). Textbook of Pediatric Dermatology. Malden, Mass.: Blackwell.
8. ^ Lovejoy FH Jr, Boyle WE Jr (1973). "nevus sebaceous syndrome: Report of two cases and a review of the literature". Pediatrics. 52 (3): 382–7. PMID 4730395.CS1 maint: uses authors parameter (link)
9. ^ a b c d Roach, E. Steve, ed. (2004). Neurocutaneous Disorders. Cambridge, UK: Cambridge University Press. pp. 88–104. ISBN 0-521-78153-1.
10. ^ Eisen, DB; DJ Michael (2009). "Sebaceous lesions and their associated syndromes: Part I". J Am Acad Dermatol. 61 (4): 549–60. doi:10.1016/j.jaad.2009.04.058. PMID 19751879.
11. ^ Jadassohn, J. (1895). "Bemerkungen zur Histologie der systematisirten Naevi und ueber 'Talgdruesen-naevi'". Archiv für Dermatologie und Syphilis. 33: 355–372. doi:10.1007/BF01842810.
12. ^ "LNSS Connections: About Linear Nevus Sebaceous Syndrome". 2010-04-13. Retrieved 2010-04-15.
13. ^ "Disease Information from NORD, National Organization of Rare Diseases, Inc". 2010-01-20. Retrieved 2010-04-15.
## External links[edit]
Classification
D
* ICD-10: Q85.8
* OMIM: 163200
* MeSH: D054000
External resources
* Orphanet: 2612
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Schimmelpenning syndrome | c0265329 | 4,257 | wikipedia | https://en.wikipedia.org/wiki/Schimmelpenning_syndrome | 2021-01-18T19:10:24 | {"gard": ["10291"], "mesh": ["D054000"], "umls": ["C0265318", "C3854181", "C0265329"], "icd-10": ["Q85.8"], "orphanet": ["2612"], "wikidata": ["Q1274018"]} |
A rare mitochondrial disease characterized by prenatal complications including oligohydramnios, fetal growth restriction, hydrops, and anemia, followed by severe lactic acidosis, hyaline membrane disease, pulmonary hypertension, cardiac anomalies, liver dysfunction, urogenital abnormalities and progressive renal disease, seizures, thrombocytopenia, and sideroblastic anemia resulting in multisystem organ failure and death shortly after birth. Less severely affected patients surviving the neonatal period and showing sensorineural hearing loss and developmental delay have been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome | c4310761 | 4,258 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=528091 | 2021-01-23T17:24:01 | {"omim": ["617021"]} |
Neutrophilia
Neutrophils with a segmented nuclei surrounded by erythrocytes, the intra-cellular granules are visible in the cytoplasm (Giemsa stained)
Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood.[1] Because neutrophils are the main type of granulocytes, mentions of granulocytosis often overlap in meaning with neutrophilia.
The opposite of neutrophilia is neutropenia.
## Contents
* 1 Causes
* 2 "Left shift"
* 3 See also
* 4 References
* 5 External links
## Causes[edit]
Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of neutrophilia is a bacterial infection, especially pyogenic infections.[2]
Neutrophils are also increased in any acute inflammation, so will be raised after a heart attack,[2] other infarct or burns.[2]
Some drugs, such as prednisone, have the same effect as cortisol and adrenaline (epinephrine), causing marginated neutrophils to enter the blood stream.[citation needed]
A neutrophilia might also be the result of a malignancy. Chronic myelogenous leukemia (CML or chronic myeloid leukaemia) is a disease where the blood cells proliferate out of control. These cells may be neutrophils. Neutrophilia can also be caused by appendicitis and splenectomy.[3]
Primary neutrophilia can additionally be a result of leukocyte adhesion deficiency.[4]
## "Left shift"[edit]
A "left shift" refers to the presence of increased proportions of younger, less well differentiated neutrophils and neutrophil-precursor cells in the blood. This generally reflects early or premature release of myeloid cells from the bone marrow, the site where neutrophils are generated. A severe neutrophilia with left shift is referred to as a leukemoid reaction. The leukocyte alkaline phosphatase (LAP) score, which refers to the amount of alkaline phosphatase per neutrophil, will increase. In a severe infection, toxic granulation changes happen to the neutrophils.[citation needed]
This can resemble Pelger-Huet anomaly.[5][6]
## See also[edit]
* Absolute neutrophil count
## References[edit]
1. ^ "neutrophilia" at Dorland's Medical Dictionary
2. ^ a b c Table 12-6 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
3. ^ "bloodandcancerclinic". Archived from the original on 21 May 2013. Retrieved 10 April 2013.
4. ^ "Titre" (PDF). Retrieved 2019-11-16.
5. ^ Mohamed IS, Wynn RJ, Cominsky K, et al. (June 2006). "White blood cell left shift in a neonate: a case of mistaken identity". J Perinatol. 26 (6): 378–80. doi:10.1038/sj.jp.7211513. PMID 16724080.
6. ^ Shmuely H, Pitlik SD, Inbal A, Rosenfeld JB (June 1993). "Pelger-Huët anomaly mimicking 'shift to the left'". Neth J Med. 42 (5–6): 168–70. PMID 8377874.
## External links[edit]
Classification
D
* DiseasesDB: 8995
External resources
* eMedicine: med/3209
* v
* t
* e
Diseases of monocytes and granulocytes
Monocytes and macrophages
↑
-cytosis:
* Monocytosis
* Histiocytosis
* Chronic granulomatous disease
↓
-penia:
* Monocytopenia
Granulocytes
↑
-cytosis:
* granulocytosis
* Neutrophilia
* Eosinophilia/Hypereosinophilic syndrome
* Basophilia
* Bandemia
↓
-penia:
* Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia
* Eosinopenia
* Basopenia)
Disorder of phagocytosis
Chemotaxis and degranulation
* Leukocyte adhesion deficiency
* LAD1
* LAD2
* Chédiak–Higashi syndrome
* Neutrophil-specific granule deficiency
Respiratory burst
* Chronic granulomatous disease
* Neutrophil immunodeficiency syndrome
* Myeloperoxidase deficiency
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neutrophilia | c3665444 | 4,259 | wikipedia | https://en.wikipedia.org/wiki/Neutrophilia | 2021-01-18T18:42:10 | {"wikidata": ["Q491741"]} |
The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted.
Find sources: "Oneirophobia" – news · newspapers · books · scholar · JSTOR (December 2014) (Learn how and when to remove this template message)
Oneirophobia
SpecialtyPsychology
Oneirophobia (from Greek όνειρο (oneiro), meaning "dream", and φόβος (phobos), meaning "fear") is the fear of dreams. It is discussed in The Dream Frontier, a book by Mark Blechner, a neuro-psychoanalyst at the William Alanson White Institute.[1]
The fear involves suffering due to experiences with frightening dreams (nightmares and/or night terrors) or by negative events in the life affecting those dreams.[2] Some sufferers try to avoid sleep or falling asleep altogether. Those with post-traumatic stress disorder (PTSD), for instance, often re-experience their trauma in nightmares, so frequently that they attempt to avoid these painful symptoms through alcohol or other drugs.[3] Sleep itself is feared for its capacity to bring on the repressed trauma.
However, not all oneirophobia is strictly a function of post-traumatic stress disorder, as most dream content, and thus the fear of its manifestation, is related to the daily functions of the unconscious. In traditional Freudian thought, the dreamer channels their thoughts, feelings, desires and fears through dreams, but in a disguised and nonrational way. When these dreams are recalled and experienced as disturbing events- especially if they are of frequent recurrence- the dreamer may begin to develop anxiety over the expression of their unconscious.[4] Many sufferers may also be frightened by the unusual or surreal nature of dreams.
## See also[edit]
* List of phobias
## References[edit]
1. ^ Dr. Mark J. Blechner (July 2014). "The Dream Frontier". Mark Blencher.com. Chapter Outline. Retrieved 16 July 2014.
2. ^ Owczarski, W. (2017). The ritual of dream interpretation in the Auschwitz concentration camp. Dreaming, 27(4), 278-289.
3. ^ Jane, Shaili. "What Dreams May Come: Treating the Nightmares of PTSD". Psychology Today. Retrieved November 1, 2017.
4. ^ Furnham, Adrian (2015-02-13). "The Psychology of Dreaming". Retrieved 2017-11-01.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Oneirophobia | None | 4,260 | wikipedia | https://en.wikipedia.org/wiki/Oneirophobia | 2021-01-18T18:42:08 | {"wikidata": ["Q10341001"]} |
A rare subtype of autosomal recessive limb-girdle muscular dystrophy characterized by atrioventricular block resulting in repeated syncope episodes, elevated creatine kinase serum levels and adult-onset of slowly progressive proximal limb skeletal muscle weakness and atrophy. Muscular dystrophic changes observed in muscle biopsy include diameter variability, increased central nuclei, and presence of necrotic and regenerating fibers.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| BVES-related limb-girdle muscular dystrophy | c4225199 | 4,261 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=476084 | 2021-01-23T18:27:27 | {"omim": ["616812"], "synonyms": ["Autosomal recessive limb-girdle muscular dystrophy-cardiac arrhythmia syndrome", "BVES-related LGMD", "LGMD type 2X", "LGMD2X", "Limb-girdle muscular dystrophy 2X"]} |
A rare disorder characterized by multiple congenital anomalies. The name is a mneumonic for the common features observed in SHORT syndrome that include; short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay. Other common manifestations of SHORT syndrome are mild intrauterine growth restriction, partial lipodystrophy, delayed bone age, hernias and a recognizable facial gestalt.
## Epidemiology
The prevalence of SHORT syndrome is unknown. Less than 50 cases have been reported in the literature to date.
## Clinical description
Individuals with SHORT syndrome often display mild intrauterine growth restriction. Feeding difficulties and/or failure to thrive present in early childhood and final adult height is shorter than average (155-163 cm in males and 143-160 cm in females). Most patients have a characteristic facial gestalt, often described as progeroid, with triangular face shape, prominent forehead, ocular depression, hypoplastic alae nasi, low-hanging columella, downturned corners of the mouth, micrognathia and prominent (but not typically low-set or posteriorly located) ears. Partial lipodystrophy may be evident in the face at birth and later in the chest and upper extremities (including the hands), but it is usually not reported in the buttocks and legs. Delayed dentition, hypodontia, enamel hypoplasia, malocclusion and multiple dental caries are frequently reported. Ophthalmic anomalies (e.g. Rieger anomaly, Axenfeld anomaly (see these terms), glaucoma) are also characteristic of the disease. Diabetes is seen in approximately 2/3 of individuals with SHORT syndrome after the age of 15 years. Other less common manifestations include hyperextensibility of joints and/or hernias, sensorineural hearing loss and ovarian cysts in females. Intellectual development and cognition are usually unaffected although mild impairment with speech delay has been reported.
## Etiology
SHORT syndrome is due to mutations in the PIK3R1 gene (5q13.1), encoding phosphatidylinositol 3-kinase regulatory subunit alpha. Mutations are thought to impair the PI3K/AKT/mTOR pathway, which plays an important role in cellular proliferation and growth.
## Diagnostic methods
Diagnosis is based on the presence of the characteristic features and confirmed by molecular genetic testing identifying a PIK3R1 mutation. The presence of all 5 features of the acronym is not necessary for a positive diagnosis.
## Differential diagnosis
Differential diagnoses include Silver-Russell syndrome, Alagille syndrome, Floating-Harbor syndrome, growth delay due to insulin-like growth factor I resistance, Berardinelli-Seip congenital lipodystrophy and Hutchinson-Gilford progeria syndrome.
## Antenatal diagnosis
Prenatal diagnosis is possible in families with a known disease-causing mutation.
## Genetic counseling
SHORT syndrome is inherited in an autosomal dominant manner. Genetic counseling is recommended for at-risk families. De novo cases have also been described. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring.
## Management and treatment
Treatment is symptomatic and requires a multidisciplinary team. Screening for insulin resistance is recommended starting in mid-late childhood. Glucose intolerance and diabetes mellitus can be treated with diet, lifestyle, oral medication and insulin, while growth hormone therapy is contraindicated. Ophthalmological management and follow-up (i.e. regular eye examinations) are necessary to reduce and stabilize ocular pressures and to preserve vision. Dental anomalies can be treated using standard methods (e.g. crowns and dental prostheses).
## Prognosis
Individuals with SHORT syndrome are considered to have a normal life-expectancy.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SHORT syndrome | c0878684 | 4,262 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3163 | 2021-01-23T17:40:46 | {"gard": ["7633"], "mesh": ["C537327"], "omim": ["269880"], "umls": ["C0878684"], "icd-10": ["Q87.1"], "synonyms": ["Lipodystrophy-Rieger anomaly-diabetes syndrome", "Rieger anomaly-partial lipodystrophy syndrome"]} |
Abortion in Bhutan is only legal when the abortion is a result of rape, incest, to preserve the woman's mental health, or to save her life.[1] Despite this however, the United Nations report on abortion notes that the exact status of the country's abortion law is under. "Because the state religion of Bhutan is Buddhism, which disapproves of abortion, it is probable that the procedure is allowed only to save the life of the pregnant woman."[2]
## Impact[edit]
Since abortions are difficult for women to obtain in Bhutan, they often cross the border into India, where they get abortions in unsafe conditions.[1] The danger and resulting fatalities has led many people to push for the legalization and decriminalization of abortion for Bhutanese women.[3]
## See also[edit]
* Health in Bhutan
* Women in Bhutan
## References[edit]
1. ^ a b "Bhutan". Women on Waves. Retrieved 1 December 2014.
2. ^ "Bhutan". United Nations Abortion Policies.
3. ^ Pelden, Sonam (29 July 2011). "Should abortion be legalized?". Bhutan Observer. Archived from the original on 6 December 2014. Retrieved 1 December 2014.
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*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Abortion in Bhutan | None | 4,263 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Bhutan | 2021-01-18T18:38:52 | {"wikidata": ["Q19568849"]} |
A number sign (#) is used with this entry because GM2-gangliosidosis AB variant is caused by homozygous mutation in the GM2A gene (613109) on chromosome 5q33.
Description
The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; 606869) and hexosaminidase B (HEXB; 606873) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see 272800) (Gravel et al., 2001).
Clinical Features
Sandhoff et al. (1971) referred to Sandhoff disease (268800) as variant 0 (since both hexosaminidases A and B are missing) and classic Tay-Sachs disease as variant B (since HEXA is absent but HEXB is present in increased amounts). They studied a single patient with a third form they called variant AB, because both Hex-A and Hex-B are increased in amounts. Sandhoff's patient with the AB variant was studied clinically by Hugo Moser, then of Boston. A brother and sister were affected. In the AB variant, Gm2-ganglioside accumulates as in the other 2 forms despite the presence of both HEXA and HEXB. The patients were French Canadian (Phillips, 1983).
De Baecque et al. (1975) reported a black female infant with the AB variant of GM2-gangliosidosis. She had normal early development, but showed loss of developmental skills beginning around 9 months of age. At age 12 months, she presented with a prolonged generalized seizure, and was found to have increased startle to sound, hypotonia, and cherry-red macular spots. By age 14 months, she could no longer sit or roll over. Brain biopsy showed neurons and astrocytes with cytoplasmic membranous inclusions of storage material, and HEXA and HEXB were normal.
Chen et al. (1999) reported a new patient with deficiency of the GM2 activator protein. No consanguinity was identified in the family, but the patient was derived from a geographically isolated, small Laotian hill tribe. The child was thought to be normal until the age of approximately 5 months when he was noted to have delayed motor milestones and increasing weakness. At age 9 months, magnetic resonance imaging showed increased signal density in the periventricular white matter and altered signal density in the basal ganglia. Ophthalmologic evaluation showed bilateral macular cherry red spots. At age 2.5 years, he was evaluated for his neurodegenerative course. The patient was experiencing approximately 3 major motor seizures and hundreds of myoclonic jerks per day. Hyperacusis was extreme, with an exaggerated startle response. Physical examination showed a nondysmorphic, profoundly hypotonic child, who was unresponsive to his environment. Despite normal Hex-A levels in lymphocytes, the clinical diagnosis strongly suggested Tay-Sachs disease.
Sakuraba et al. (1999) described complete absence of the GM2 activator protein by Western blot analysis and metabolic studies in a Japanese patient with a progressive neurologic disorder that began with muscular weakness and hypotonia at 1 month of age. The patient later developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Northern blot analysis demonstrated normal levels of mRNA of the appropriate size, and no mutations were detected in the protein coding region of the GM2 activator gene. The authors speculated that there may be other factors affecting the activity or stability of the GM2 activator.
### Clinical Variability
Salih et al. (2015) reported 3 patients from a highly consanguineous Saudi family with childhood onset of a neurodegenerative disorder. The patients developed normally until 7 or 8 years of age, at which time they showed some abnormal behavior, including increased anxiety and phobias. Thereafter, all showed loss of developmental skills, including speech, cognition, and motor function. They developed spastic quadriparesis, limb dystonia, pyramidal signs, and generalized chorea. The hyperkinetic disorder gradually gave way to a rigid akinetic state, and all patients lost independent ambulation in the teenage years. Brain imaging showed cortical atrophy; biopsies were not reported. None of the patients had hyperacusis or cherry-red macular spots. Exome sequencing identified a homozygous mutation in the GM2A gene (P55L; 613109.0006). Functional studies of the variant and studies of patient cells were not performed. Salih et al. (2015) noted that the phenotype in this family was milder than that usually observed in patients with this disorder, thus expanding the phenotypic spectrum associated with GM2A mutations.
Inheritance
The transmission pattern of the AB variant of GM2-gangliosidosis in the family reported by Salih et al. (2015) was consistent with autosomal recessive inheritance.
Pathogenesis
Conzelmann and Sandhoff (1978) showed that an activating factor necessary for the degradation of GM2-ganglioside by HEXA is defective in the AB variant. This activating factor is necessary for the interaction of lipid substrates and the water-soluble hydrolase. The factor is normal in Tay-Sachs and Sandhoff diseases.
Molecular Genetics
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency, Schroder et al. (1991) and Xie et al. (1992) identified a homozygous missense mutation in the GM2A gene (C138R; 613109.0001). The patient was originally reported by de Baecque et al. (1975).
By RT-PCR of the GM2A gene in a patient with deficiency of GM2-activator protein, Chen et al. (1999) detected some normal-sized cDNA and a smaller cDNA species, which was not seen in the RT-PCR products from normal controls. Sequencing revealed that although the patient's normal-sized cDNA contained a single nonsense mutation in exon 2, his smaller cDNA was the result of an in-frame deletion of exon 2. Long PCR was used to amplify introns 1 and 2 from the patient and normal genomic DNA, and no differences in size, in 5-prime and 3-prime end sequences, or in restriction-mapping patterns were observed. From these data, Chen et al. (1999) developed a set of 4 PCR primers that could be used to identify GM2A mutations. With this procedure, they demonstrated that the patient was probably homozygous for a nonsense mutation, glu54 to ter (613109.0005). Chen et al. (1999) pointed to the work of Dietz et al. (1993) and of others, indicating that shortened reading frames (i.e., early stop codons) can lead not only to mRNA instability, but also to the in-frame skipping of the constitutive exon in which the mutation is found. They also noted that Valentine and Heflich (1997), from a study of the association of nonsense mutations with exon skipping in hprt mRNA of Chinese hamster ovary cells, concluded that the association was the result of an RT-PCR artifact. Chen et al. (1999) interpreted their results as supporting the conclusion of Valentine and Heflich (1997).
Animal Model
Liu et al. (1997) generated mice with a disrupted Gm2a gene as a model; knockout mouse models for Tay-Sachs and Sandhoff disease had previously been studied. Mice with disruption of the Hexa gene (the Tay-Sachs disease model) were asymptomatic, whereas those with absence of Hexb (the Sandhoff disease model) were severely affected. The mice with disruption of Gm2a demonstrated neuronal storage, but only in restricted regions of the brain, reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in these mice consisted of GM2 with a low amount of GA2. Their results demonstrated that the activator protein is required for GM2 degradation and also may indicate a role for GM2 activator in GA2 degradation.
History
O'Neill et al. (1978) described a 22-year-old non-Jewish female who, although slow in school, had no recognized neurologic abnormality until age 18 when seizures began. They considered this an adult-onset form of the AB variant of GM2-gangliosidosis. However, Gravel et al. (2001) concluded that this was most likely not a case of the AB variant because the brain gangliosides showed only minor relative increases of monosialogangliosides, a highly nonspecific finding seen in many neurodegenerative disorders, and because no evidence of impaired GM2 ganglioside degradation was provided.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Cherry-red macular spots (in most patients) \- Roving eye movements MUSCLE, SOFT TISSUES \- Axial hypotonia NEUROLOGIC Central Nervous System \- Neurodegeneration \- Loss of developmental skills \- Seizures \- Increased startle response \- Hyperacusis \- Cognitive decline \- Loss of speech \- Hypotonia \- Hyperreflexia \- Spastic quadriparesis \- Pyramidal tract signs \- Dystonia \- Chorea \- Primitive reflexes \- Cerebral atrophy \- Brain biopsy shows membranous neuronal cytoplasmic inclusions \- Astrocytic inclusions LABORATORY ABNORMALITIES \- Gm2-ganglioside accumulation in tissues MISCELLANEOUS \- Onset in infancy or childhood \- Variable severity MOLECULAR BASIS \- Caused by mutation in the GM2 activator gene (GM2A, 613109.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| GM2-GANGLIOSIDOSIS, AB VARIANT | c0268275 | 4,264 | omim | https://www.omim.org/entry/272750 | 2019-09-22T16:21:53 | {"doid": ["4795"], "mesh": ["D049290"], "omim": ["272750"], "orphanet": ["309246"], "synonyms": ["Alternative titles", "HEXOSAMINIDASE ACTIVATOR DEFICIENCY", "GM2 ACTIVATOR DEFICIENCY", "AB VARIANT GM2-GANGLIOSIDOSIS", "TAY-SACHS DISEASE, AB VARIANT"]} |
A number sign (#) is used with this entry because analbuminemia (ANALBA) is caused by homozygous or compound heterozygous mutation in the ALB gene (103600) on chromosome 4q13.
Description
Analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. Affected individuals have few clinical symptoms other than mild edema, hypotension, fatigue, and, occasionally, a peculiar lower body lipodystrophy (mainly in adult females). The most common biochemical finding is a gross hyperlipidemia, with a significant increase in the total and LDL cholesterol concentrations, but normal concentrations of HDL cholesterol and triglycerides. Analbuminemia often leads to fetal or neonatal death in sibs in families of analbuminemic subjects, which may explain the rarity of the trait (summary by Caridi et al., 2014).
Clinical Features
Analbuminemia, a rare autosomal recessive disorder in which serum albumin is low or absent, was first reported by Bennhold et al. (1954) of Tubingen. See review by Ott (1962). In some reported families analbuminemia is a completely recessive condition; serum albumin has a normal level in heterozygotes. The homozygotes have remarkably little inconvenience attributable to the lack of serum albumin. In the kindreds of Bennhold et al. (1954) and Boman et al. (1976), heterozygotes showed intermediate levels of serum albumin.
Lyon et al. (1998) reported that dye-binding albumin methods employed by clinical laboratories typically found 3 to 18 g/L albumin in serum from analbuminemia patients. As a consequence, the diagnosis of analbuminemia (albumin level of zero) only becomes apparent following measurement of albumin by immunoassay or by electrophoresis.
Kallee (1996) reported 2 sibs with analbuminemia who were followed for 38 years. The female patient received replacement therapy with human serum albumin. Extreme lipodystrophy developed in this patient by the fourth decade of life. She had juvenile osteoporosis, which normalized under albumin replacement. She died from a granulosa cell cancer at age 69. Her brother never received albumin. He suffered from severe osteoporosis with gibbus formation, and died from a colon carcinoma at age 59. Both sibs had chronic insufficiency of the crural veins, with chronic ulcerations of both lower legs but no varicosities of the upper thighs. Despite high cholesterol values and high levels of several blood clotting factors, neither of the patients had severe atherosclerosis or thrombotic events. Kallee (1996) concluded that although patients often fail to exhibit serious clinical signs apart from pathologic laboratory findings, analbuminemia can no longer be regarded as a harmless anomaly.
Cormode et al. (1975) found very low plasma tryptophan in a neonate with analbuminemia who was small for gestational age.
Murray et al. (1983) restudied the family reported by Boman et al. (1976). The proposita showed trace amounts of immunologically normal serum albumin. With cDNA probes for the albumin gene, no deletion could be detected.
Caridi et al. (2019) reported a brother and sister, born to consanguineous Algerian parents, with analbuminemia. The brother was born preterm and was hospitalized during his first month of life with edema and hypoproteinemia. He had a history of hospitalizations for the same reasons until his third year of life. At the time of the report, he was 43 years of age. He had gluten intolerance, fatigue, and felt nauseated and bloated. He had moderate obesity with a body mass index (BMI) of 31.1 and sometimes had edema in the lower part of his legs. His sister did well until age 37 years when she had complications with her first pregnancy. She had an impressive weight gain during her first 2 months of pregnancy. Capillary serum protein electrophoresis showed her to have nearly complete absence of albumin, and she required an albumin infusion. On examination, she had edema and lipodystrophy. At age 38 years, she had a BMI of 36.5. On biochemical measurement, both patients had albumin levels of less than 1 g/L (reference, 40.2-47.6 g/L). Total serum protein levels were close to the lower limit of the normal range because of compensatory increase of other proteins. Both patients had significant hypercholesterolemia, but normal triglycerides. Their mother had an albumin level in the lower half of the normal range.
Inheritance
In a review, Ruffner and Dugaiczyk (1988) stated that of 22 reported analbuminemic individuals, 8 were known to be from consanguineous matings, suggesting autosomal recessive inheritance.
Mapping
Boman et al. (1976) presented data consistent with linkage of the analbuminemia locus and the GC locus (139200).
Molecular Genetics
In a Native American girl with analbuminemia, Ruffner and Dugaiczyk (1988) identified a homozygous splice site mutation in the albumin gene (103600.0027).
In an Italian woman with analbuminemia, Watkins et al. (1994) identified a homozygous mutation in the albumin gene (103600.0040).
In a male newborn of Iraqi extraction with analbuminemia, Campagnoli et al. (2002) identified a homozygous mutation in the ALB gene (103600.0057).
In 2 sibs, born to consanguineous Algerian parents, with analbuminemia, Caridi et al. (2019) identified a homozygous frameshift mutation in the ALB gene (103600.0058). Their mother was heterozygous for the mutation; DNA from the father was not available for testing. The variant was not found in the ExAC or gnomAD databases.
Animal Model
Analbuminemic rats, like analbuminemic humans, are healthy (Nagase et al., 1979). The use of cDNA probes failed to detect serum albumin gene transcripts in liver of these analbuminemic rats (Esumi et al., 1980). Thus, the disorder in the rat and perhaps the human may be the result of gene deletion. On the other hand, the normal levels of albumin in heterozygotes may indicate that the mutation is at a regulatory locus independent of the albumin locus. In the analbuminemic rat, Esumi et al. (1982) found albumin mRNA precursors in nuclei although such were missing from the cytoplasm. From this they concluded that analbuminemia in rats is caused by a unique type of mutation that affects albumin mRNA maturation. In analbuminemia of the rat, Esumi et al. (1983) demonstrated that a 7-bp deletion in an intron interferes with mRNA formation. Shalaby and Shafritz (1990) showed that exon H is skipped in the Nagase analbuminemic rat as a result of the 7-bp deletion at the splice donor site of intron H-I. Mendel et al. (1989) could find no abnormality of thyroxine transport and distribution in Nagase analbuminemic rats.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ANALBUMINEMIA | c0878666 | 4,265 | omim | https://www.omim.org/entry/616000 | 2019-09-22T15:50:15 | {"omim": ["616000"], "orphanet": ["86816"], "synonyms": []} |
A rare, genetic, periphery neuropathy characterized by a congenital insensitivity to pain, muscular hypotonia and gastrointestinal disturbances. Patients present with delayed motor milestones achievement, self-mutilations, skin ulcers, poor wound healing, painless fractures, hyperhidrosis, abdominal discomfort, diarrhea and/or constipation. Cognitive development is normal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hereditary sensory and autonomic neuropathy type 7 | c3809882 | 4,266 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391397 | 2021-01-23T17:48:59 | {"gard": ["12732"], "omim": ["615548"], "icd-10": ["G60.8"], "synonyms": ["CIP with hyperhidrosis and gastrointestinal dysfunction", "Congenital insensitivity to pain with hyperhidrosis and gastrointestinal dysfunction", "HSAN with hyperhidrosis and gastrointestinal dysfunction", "HSAN7", "Hereditary sensory and autonomic neuropathy type VII", "Hereditary sensory and autonomic neuropathy with hyperhidrosis and gastrointestinal dysfunction"]} |
Grange syndrome is a rare condition that primarily affects the blood vessels. It is characterized by narrowing (stenosis) or blockage (occlusion) of arteries that supply blood to various organs and tissues, including the kidneys, brain, and heart. Stenosis or occlusion of the arteries that supply blood to the kidneys (renal arteries) can result in chronic high blood pressure (hypertension). Blockage of the arteries that carry blood to the brain (cerebral arteries) can cause a stroke.
Additional features of Grange syndrome can include short fingers and toes (brachydactyly), fusion of some of the fingers or toes (syndactyly), fragile bones that are prone to breakage, and learning disabilities. Most people with this disorder also have heart defects that are present from birth.
## Frequency
Grange syndrome has been reported to affect at least six individuals from three families.
## Causes
Grange syndrome results from mutations in the YY1AP1 gene. The protein produced from this gene is part of a group of proteins (a complex) that helps regulate several critical functions within cells. These include gene activity (expression), repair of damaged DNA, cell specialization (differentiation), and cell growth and division (proliferation). Researchers believe that this protein complex plays a particularly important role in smooth muscle cells, which line the walls of blood vessels.
Mutations in the YY1AP1 gene likely disrupt the function of the complex, which leads to reduced proliferation and differentiation of smooth muscle cells. However, it is unclear how these changes lead to narrowing and blockage of arteries. It is also unknown how YY1AP1 gene mutations are related to other features of Grange syndrome, such as bone abnormalities and learning disabilities.
### Learn more about the gene associated with Grange syndrome
* YY1AP1
## Inheritance Pattern
This condition is thought to be inherited in an autosomal recessive pattern, which means both copies of the YY1AP1 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Grange syndrome | c1865267 | 4,267 | medlineplus | https://medlineplus.gov/genetics/condition/grange-syndrome/ | 2021-01-27T08:25:07 | {"mesh": ["C566529"], "omim": ["602531"], "synonyms": []} |
Congenital mole caused by genetic mutations
Congenital melanocytic nevus
Congenital melanocytic nevus[1]
SpecialtyOncology, dermatology
The congenital melanocytic nevus is a type of melanocytic nevus (or mole) found in infants at birth. This type of birthmark occurs in an estimated 1% of infants worldwide; it is located in the area of the head and neck 15% of the time.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 3.1 Classification
* 4 Treatment
* 5 Prognosis
* 6 See also
* 7 Notes
* 8 References
* 9 External links
## Signs and symptoms[edit]
Congenital nevus. Note the variable coloration and slightly irregular border
The congenital melanocytic nevus appears as a circumscribed, light brown to black patch or plaque, potentially very heterogeneous in consistency, covering any size surface area and any part of the body.
As compared with a melanocytic nevus, congenital melanocytic nevi are usually larger in diameter and may have excess terminal hair, a condition called hypertrichosis. If over 40 cm (16 in) projected adult diameter with hypertrichosis, it is sometimes called giant hairy nevus; more usually these largest forms are known as large or giant congenital melanocytic nevus. The estimated prevalence for the largest forms is 0.002% of births.[2]
Melanocytic nevi often grow proportionally to the body size as the child matures. As they mature, they often develop thickness, and become elevated, although these features can also be present from birth. Prominent terminal hairs often form, especially after puberty. With maturity, the nevus can have variation in color, and the surface might be textured with proliferative growths.
Neurocutaneous melanosis is associated with the presence of either giant congenital melanocytic nevi or non-giant nevi of the skin. It is estimated that neurocutaneous melanosis is present in 2% to 45% of patients with giant congenital melanocytic nevi. Neurocutaneous melanosis is characterized by the presence of congenital melanocytic nevi on the skin and melanocytic tumors in the leptomeninges of the central nervous system.
## Cause[edit]
Large congenital nevi are caused by a mutation in the body's cells that occurs early in embryonic development, usually within the first twelve weeks of pregnancy.[3] Mutations are sometimes found in genes that code for NRAS and KRAS proteins.[4] There is no known method of prevention.
## Diagnosis[edit]
Various differential diagnoses of pigmented skin lesions, by relative incidence and malignancy potential, including "congenital or congenital pattern nevus" near top.
Deep congenital nevus
Benign congenital nevi can have histological characteristics resembling melanomas, often breaking most if not all of the ABCDE rules. Dermatoscopic findings of the smaller forms of benign congenital nevi can aid in their differentiation from other pigmented neoplasms.[5]
Microscopically, congenital melanocytic nevi appear similar to acquired nevi with two notable exceptions. For the congenital nevus, the neval cells are found deeper into the dermis. Also, the deeper nevus cells can be found along with neurovascular bundles, with both surrounding hair follicles, sebaceous glands, and subcutaneous fat. Such annexes and the Subcutaneous tissue can also be hypoplasic or, conversely, present aspects of hamartoma.
### Classification[edit]
Giant congenital melanocytic nevus in newborn
Congenital melanocytic nevi may be divided into the following types:[6]:690–1
* Small-sized congenital melanocytic nevus is defined as having a diameter less than 2 cm (0.79 in).[6]:690
* Medium-sized congenital melanocytic nevus is defined as having a diameter more than 2 cm (0.79 in) but less than 20 cm (7.9 in).[6]:690
* Giant congenital melanocytic nevus (also known as "bathing trunk nevus," "garment nevus," "giant hairy nevus", and "nevus pigmentosus et pilosus") is defined by one or more large, darkly pigmented and sometimes hairy patches.[6]:690[7]
## Treatment[edit]
Surgical excision is the standard of care. Some individuals advocate the use of hair removal laser for the treatment of congenital nevi. While this is likely safe and effective for small congenital nevus, laser removal for larger lesions might pose a liability for the laser surgeon if malignancy developed from a deep (dermal) component of the nevus that is not reached by the laser. Repigmentation after laser treatment of congenital nevi or superficial curettage supports this concern.
Many are surgically removed for aesthetics and relief of psychosocial burden, but larger ones are also excised for prevention of cancer, although the benefit is impossible to assess for any individual patient. Proliferative nodules are usually biopsied and are regularly but not systematically found to be benign.[8] Estimates of transformation into melanoma vary from 2-42% in the literature, but are most commonly considered to be at the low end of that spectrum due to early observer bias.[9]
## Prognosis[edit]
Large and especially giant congenital nevi are at higher risk for malignancy degeneration into melanoma. Because of the premalignant potential, it is an acceptable clinical practice to remove congenital nevi electively in all patients and relieve the nevocytic overload.
## See also[edit]
* Albinism
* List of cutaneous conditions
* Vitiligo
## Notes[edit]
* Kahn, Michael A. Basic Oral and Maxillofacial Pathology, Volume 1. 2001.[better source needed]
## References[edit]
1. ^ Sand, M; Sand, D; Thrandorf, C; Paech, V; Altmeyer, P; Bechara, FG (4 June 2010). "Cutaneous lesions of the nose". Head & Face Medicine. 6: 7. doi:10.1186/1746-160X-6-7. PMC 2903548. PMID 20525327.
2. ^ Price, HN; Schaffer, JV (May–Jun 2010). "Congenital melanocytic nevi-when to worry and how to treat: Facts and controversies". Clinics in Dermatology. 28 (3): 293–302. doi:10.1016/j.clindermatol.2010.04.004. PMID 20541682.
3. ^ "Frequently Asked Questions About Large Nevi - Nevus Outreach Inc". www.nevus.org. 2015-07-28.
4. ^ Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin (2015-11-01). "Genetics of melanocytic nevi". Pigment Cell & Melanoma Research. 28 (6): 661–672. doi:10.1111/pcmr.12412. ISSN 1755-148X. PMC 4609613. PMID 26300491.
5. ^ Brooks, Christine; Scope, Alon; Braun, Ralph P; Marghoob, Ashfaq A (February 2011). "Dermoscopy of nevi and melanoma in childhood". Expert Review of Dermatology. 6 (1): 19–34. doi:10.1586/edm.10.71.
6. ^ a b c d James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
7. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1736–8. ISBN 978-1-4160-2999-1.
8. ^ Phadke, PA; Rakheja, D; Le, LP; Selim, MA; Kapur, P; Davis, A; Mihm MC, Jr; Hoang, MP (May 2011). "Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases". The American Journal of Surgical Pathology. 35 (5): 656–69. doi:10.1097/PAS.0b013e31821375ea. PMID 21436676.
9. ^ Etchevers, Heather. "Large congenital melanocytic nevus". Orphanet: The portal for rare diseases and orphan drugs. Institut national de la santé et de la recherche médicale. Retrieved 2 August 2011.
## External links[edit]
Classification
D
* ICD-10: D22 (ILDS D22.L60)
* ICD-O: M8761/0
* v
* t
* e
Skin cancer of nevi and melanomas
Melanoma
* Mucosal melanoma
* Superficial spreading melanoma
* Nodular melanoma
* lentigo
* Lentigo maligna/Lentigo maligna melanoma
* Acral lentiginous melanoma
* Amelanotic melanoma
* Desmoplastic melanoma
* Melanoma with features of a Spitz nevus
* Melanoma with small nevus-like cells
* Polypoid melanoma
* Nevoid melanoma
* Melanocytic tumors of uncertain malignant potential
Nevus/
melanocytic nevus
* Nevus of Ito/Nevus of Ota
* Spitz nevus
* Pigmented spindle cell nevus
* Halo nevus
* Pseudomelanoma
* Blue nevus
* of Jadassohn–Tièche
* Cellular
* Epithelioid
* Deep penetrating
* Amelanotic
* Malignant
* Congenital melanocytic nevus (Giant
* Medium-sized
* Small-sized)
* Balloon cell nevus
* Dysplastic nevus/Dysplastic nevus syndrome
* Acral nevus
* Becker's nevus
* Benign melanocytic nevus
* Nevus spilus
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital melanocytic nevus | c1318558 | 4,268 | wikipedia | https://en.wikipedia.org/wiki/Congenital_melanocytic_nevus | 2021-01-18T18:52:00 | {"icd-10": ["Q82.5"], "wikidata": ["Q5160447"]} |
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Esophageal spasm
Other namesOesophageal spasm
SpecialtyGastroenterology
Differential diagnosisAchalasia, angina, scleroderma, esophageal cancer, esophagitis[1]
Esophageal spasm is a disorder of motility of the esophagus.[2]
There are two types of esophageal spasm:[2]
* Diffuse or distal esophageal spasm (DES), where there is uncoordinated esophageal contractions
* Nutcracker esophagus (NE) also known as hypertensive peristalsis, where the contractions are coordinated but with an excessive amplitude.
Both conditions are linked to gastroesophageal reflux disease (GERD).[2] DES and nutcracker esophagus present similarly and can may require esophageal manometry for differentiation.[3]
When the coordinated muscle contraction are irregular or uncoordinated, this condition may be called diffuse esophageal spasm. These spasms can prevent food from reaching the stomach where food gets stuck in the esophagus. At other times the coordinated muscle contraction is very powerful, which is called nutcracker esophagus. These contractions move food through the esophagus but can cause severe pain.[4]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 4.1 Procedures
* 5 Epidemiology
* 6 References
## Signs and symptoms[edit]
The symptoms may include trouble swallowing, regurgitation, chest pain,[5] heartburn,[6] globus pharyngis (which is a feeling that something is stuck in the throat) or a dry cough.[7]
## Causes[edit]
It is not clear what causes esophageal spasms.[1][7] Sometimes esophageal spasms start when someone eats hot or cold foods or drinks. However, they can also occur without eating or drinking.[7] The increased release of acetylcholine may also be a factor, but the triggering event is not known.[6] Spasms may also be the result of a food intolerance.
## Diagnosis[edit]
The diagnosis is generally confirmed by esophageal manometry.[2] DES is present when more than a fifth of swallows results in distal esophageal contractions.[2] NE is present if the average strength of the contractions of the distal esophagus is greater than 180 mmHg but the contraction of the esophagus is otherwise normal.[2]
### Differential diagnosis[edit]
Often, symptoms that may suggest esophageal spasm are the result of another condition such as food intolerance, gastroesophageal reflux disease (GERD) or achalasia.[4] The symptoms can commonly be mistaken as heart palpitations.
## Treatment[edit]
Since esophageal spasms are often associated with other disorders, management in these cases involve attempts to correct the underlying problem. Medications may include use of calcium channel blockers (CCBs) and nitrates. Tricyclic antidepressants (TCA) and sildenafil can be used as alternative treatment options. If caused by food allergy, an elimination diet may be necessary.
### Procedures[edit]
If medical therapy fails either botulinum toxin injection or surgical myotomy may be tried in distal esophageal spasms.[8]
## Epidemiology[edit]
Distal esophageal spasms are rare.[8]
## References[edit]
1. ^ a b Goel, S; Nookala, V (January 2019). "Diffuse Esophageal Spasm". PMID 31082150. Cite journal requires `|journal=` (help)
2. ^ a b c d e f "Oesophageal Spasm". EMIS Health. Retrieved 2015-11-15.
3. ^ Lightdale, Charles J. (2009). The Foregut: Function-dysfunction. John Libbey Eurotext. p. 50. ISBN 9782742007219.
4. ^ a b "Esophageal Spasm - Topic Overview". WebMD. Retrieved 2015-11-15.
5. ^ "Esophageal Spasm". WebMD. Retrieved 2015-11-15.
6. ^ a b "Esophageal Spasm Clinical Presentation - History". WebMD. Retrieved 2015-11-15.
7. ^ a b c "Esophageal Spasms & Strictures". Cleveland Clinic. Retrieved 2015-11-15.
8. ^ a b Roman, S; Kahrilas, PJ (July 2015). "Distal esophageal spasm". Current Opinion in Gastroenterology. 31 (4): 328–33. doi:10.1097/MOG.0000000000000187. PMID 26039725. S2CID 25972582.
* v
* t
* e
Anatomy of the gastrointestinal tract, excluding the mouth
Upper
Pharynx
* Muscles
* Spaces
* peripharyngeal
* retropharyngeal
* parapharyngeal
* retrovisceral
* danger
* prevertebral
* Pterygomandibular raphe
* Pharyngeal raphe
* Buccopharyngeal fascia
* Pharyngobasilar fascia
* Pyriform sinus
Esophagus
* Sphincters
* upper
* lower
* glands
Stomach
* Curvatures
* greater
* lesser
* Angular incisure
* Cardia
* Body
* Fundus
* Pylorus
* antrum
* canal
* sphincter
* Gastric mucosa
* Gastric folds
* Microanatomy
* Gastric pits
* Gastric glands
* Cardiac glands
* Fundic glands
* Pyloric glands
* Foveolar cell
* Parietal cell
* Gastric chief cell
* Enterochromaffin-like cell
Lower
Small intestine
Microanatomy
* Intestinal villus
* Intestinal gland
* Enterocyte
* Enteroendocrine cell
* Goblet cell
* Paneth cell
Duodenum
* Suspensory muscle
* Major duodenal papilla
* Minor duodenal papilla
* Duodenojejunal flexure
* Brunner's glands
Jejunum
* No substructures
Ileum
* Ileocecal valve
* Peyer's patches
* Microfold cell
Large intestine
Cecum
* Appendix
Colon
* Ascending colon
* Hepatic flexure
* Transverse colon
* Splenic flexure
* Descending colon
* Sigmoid colon
* Continuous
* taenia coli
* haustra
* epiploic appendix
Rectum
* Transverse folds
* Ampulla
Anal canal
* Anus
* Anal columns
* Anal valves
* Anal sinuses
* Pectinate line
* Internal anal sphincter
* Intersphincteric groove
* External anal sphincter
Wall
* Serosa / Adventitia
* Subserosa
* Muscular layer
* Submucosa
* Circular folds
* Mucosa
* Muscularis mucosa
* v
* t
* e
Human systems and organs
Musculoskeletal
Skeletal system
* Bone
* Carpus
* Collar bone (clavicle)
* Thigh bone (femur)
* Fibula
* Humerus
* Mandible
* Metacarpus
* Metatarsus
* Ossicles
* Patella
* Phalanges
* Radius
* Skull
* Tarsus
* Tibia
* Ulna
* Rib
* Vertebra
* Pelvis
* Sternum
* Cartilage
Joints
* Fibrous joint
* Cartilaginous joint
* Synovial joint
Muscular system
* Muscle
* Tendon
* Diaphragm
Circulatory system
Cardiovascular system
* peripheral
* Artery
* Vein
* Lymphatic vessel
* Heart
Lymphatic system
* primary
* Bone marrow
* Thymus
* secondary
* Spleen
* Lymph node
* CNS equivalent
* Glymphatic system
Nervous system
* * Brain
* Spinal cord
* Nerve
* Sensory system
* Ear
* Eye
Integumentary system
* Skin
* Subcutaneous tissue
* Breast
* Mammary gland
Hematopoietic and immune systems
* Myeloid
* Myeloid immune system
* Lymphoid
* Lymphoid immune system
Respiratory system
* Upper
* Nose
* Nasopharynx
* Larynx
* Lower
* Trachea
* Bronchus
* Lung
Digestive system
* Mouth
* Salivary gland
* Tongue
* Lips
* upper GI
* Oropharynx
* Laryngopharynx
* Esophagus
* Stomach
* lower GI
* Small intestine
* Appendix
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* Kidney
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* Male
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Endocrine system
* Pituitary
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* Thyroid
* Parathyroid
* Adrenal
* Islets of Langerhans
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Esophageal spasm | c0014863 | 4,269 | wikipedia | https://en.wikipedia.org/wiki/Esophageal_spasm | 2021-01-18T19:10:43 | {"mesh": ["D015155"], "umls": ["C0014863"], "wikidata": ["Q25098596"]} |
Early onset cerebellar ataxia with retained reflexes (EOCARR) or Harding ataxia is a cerebellar ataxia characterized by the progressive association of a cerebellar and pyramidal syndrome with progressive cerebellar ataxia, brisk tendon reflexes, and sometimes profound sensory loss.
## Epidemiology
The prevalence of EOCARR ataxia has been estimated to be around 1/100,000, and the birth prevalence at 1/48,000 births in North-western Italy.
## Clinical description
EOCARR is a progressive cerebellar ataxia, with disease onset occurring in childhood or in juveniles (ranging from 3 to 20 years with a mean age of 9 years). EOCARR is characterized by dysarthria, gait ataxia, nystagmus, brisk tendon reflexes in the upper and lower limbs, absent ankle reflexes, and discrete or absent deep sensory loss. The association of brisk jerks and absent ankle reflexes may occur. Oculomotor disturbances, dysphagia, tremor, scoliosis, pes cavus, extensor plantar response, and lower limb wasting and weakness may be observed while amyotrophy is rarely observed. Moreover, spasticity may become progressively severe.
## Etiology
The exact etiology of EOCARR is still unknown. However, molecular genetic analysis in a Tunisian family confirmed the genetic heterogeneity of this syndrome and mapped the gene locus to chromosome 13q11-12.
## Diagnostic methods
Diagnosis relies on physical examination as well as on imaging findings (magnetic resonance imaging (MRI) or computed tomography (CT)) revealing cerebellar atrophy. Peripheral nerve conduction and nerve biopsy findings may show moderate to severe axonal sensory-motor neuropathy with axonal regeneration.
## Differential diagnosis
Differential diagnosis includes Friedreich ataxia (FRDA; in contrast to EOCARR shows cardiomyopathy, diabetes mellitus, scoliosis, skeletal deformities or optic atrophy), autosomal dominant cerebellar ataxia (ADCA), autosomal recessive spastic ataxia of Charlevoix-Saguenay, ataxia with vitamin E deficiency (see these terms), and inherited metabolic disorders that may express ataxia.
## Genetic counseling
Transmission is autosomal recessive. The parents of an affected child should be informed of the 25% risk of transmitting the disease to future offspring.
## Management and treatment
Treatment is symptomatic, aimed towards the control of spasticity, and should include physiotherapy and pharmacotherapy (that may include spasmolytic drugs such as baclofen).
## Prognosis
The period of latency before becoming wheelchair-bound is significantly longer in EOCARR than in FRDA, resulting in a better prognosis in patients with EOCARR than in those with FRDA.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Early-onset cerebellar ataxia with retained tendon reflexes | c0393520 | 4,270 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1177 | 2021-01-23T19:06:17 | {"gard": ["2600"], "mesh": ["C535633"], "omim": ["212895"], "umls": ["C0393520"], "icd-10": ["G11.1"], "synonyms": ["EOCA", "EOCARR", "Harding ataxia"]} |
A number sign (#) is used with this entry because autosomal dominant craniometaphyseal dysplasia (CMDD) is caused by heterozygous mutation in the human homolog of the mouse progressive ankylosis gene (ANKH; 605145).
Description
Craniometaphyseal dysplasia is an osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy (summary by Nurnberg et al., 1997).
The delineation of separate autosomal dominant and autosomal recessive (CMDR; 218400) forms of CMD by Gorlin et al. (1969) was confirmed by reports that made it evident that the dominant form is relatively mild and comparatively common, while the recessive form is rare, severe, and possibly heterogeneous.
Clinical Features
Beighton (1995) pointed out that Peter Jackson, an English physician on the staff of Groote Schuur Hospital, University of Cape Town, collaborated with Fuller Albright at the Massachusetts General Hospital, Boston, in the disorders of osseous modeling (Jackson et al., 1954) and identified a specific syndrome that comprised dysplasia of the metaphyses, sclerosis of the base of the skull, and overgrowth of the craniofacial bones. They culled 5 previously reported cases and added 2 of their own, and they termed the condition craniometaphyseal dysplasia.
Podlaha and Kratochvil (1963) and Lejeune et al. (1966) observed that craniometaphyseal dysplasia differs from Pyle disease (metaphyseal dysplasia; 265900) in the presence of conspicuous involvement of the craniofacial bones. Widening of the bridge of the nose develops and eventually leonine facies. Pressure on cranial nerves is responsible for a considerable part of the disability (facial palsy and mixed hearing loss). The cases in the family reported by Rimoin et al. (1969) and those reported by Spranger et al. (1965) should be considered dominant craniometaphyseal dysplasia, reserving the term Pyle disease for the recessive disorder which is more nearly a 'pure' metaphyseal dysplasia with little or no craniofacial involvement. Spranger (1970) reviewed the skull x-ray of Pyle's original case and failed to find the intense increase in bone density characteristic of craniometaphyseal dysplasia. Furthermore the metaphyseal flare is notably abrupt in Pyle disease, producing the 'Erlenmeyer flask' deformity, and is milder ('club-like') in craniometaphyseal dysplasia. The same family was reported by Rimoin et al. (1969) and by Gladney and Monteleone (1970).
Stool and Caruso (1973) observed affected father and 15-month-old daughter. Both had peripheral facial palsy and the father was profoundly deaf.
Taylor and Sprague (1989) described an Australian kindred with 9 affected persons in 4 generations.
Kornak et al. (2010) reported 3 unrelated patients with craniometaphyseal dysplasia and no family history of the disorder. All had typical features of the disorder, with macrocephaly, hypertelorism, skull hyperostosis, paranasal bossing, teeth crowding, and metaphyseal flaring. The first patient, who was the most severely affected, was a French boy who developed hearing loss and bilateral facial palsy soon after birth. He had severe sclerosis of the skull base, orbits, maxilla, and mandible, with almost complete obstruction of the sinuses. There was rapid worsening of the bone phenotype in the first years of life. The second patient was a 24-year-old man from the Netherlands who presented with progressive conductive and sensorineural hearing loss and was found to have typical features of the disorder, with unilateral facial palsy apparent in infancy, macrocephaly, and teeth crowding. The third patient was a 43-year-old Italian man with typical manifestations of CMD, including sclerosis of the skull base and maxilla, hyperostotic but not sclerotic mandible, and partially obstructed sinuses, but without cranial nerve compression. He also had narrowing of the middle ear cavities with bilateral fixation of the body of the incus to the lateral attic, resulting in conductive deafness and tinnitus. These middle ear manifestations were similar to those observed in postinflammatory ossicular fixation secondary to acute or chronic otitis media.
Biochemical Features
Using osteoclast-like cells formed from a 3-year-old patient's bone marrow cells in culture, Yamamoto et al. (1993) investigated the pathophysiology of craniometaphyseal dysplasia. The quantitative formation of osteoclast-like cells, as identified by the presence of vitronectin beta-receptors, was only 40% of normal. Studies using a monoclonal antibody, E11, demonstrated that these cells from the patient lacked the osteoclast-reactive vacuolar proton pump. Kurihara et al. (1990) had found that this osteoclast-reactive vacuolar proton pump is expressed in osteoclasts during differentiation. Soriano et al. (1991) found that disruption of the SRC gene in transgenic mice resulted in osteopetrosis; see 190090. Yamamoto et al. (1993) found, however, that SRC expression in the platelets of their patient was comparable to that in the normal control.
Mapping
In a large German kindred with CMD, Nurnberg et al. (1997) found tight linkage between the disorder and microsatellite markers on 5p in the region 5p15.2-p14.1. This region overlaps with the mapping interval of the growth hormone receptor gene (GHR; 600946), or at least is in the neighborhood of the GHR gene, the location of which was given by the authors as 5p14-p12. GHR is known to be involved in the mitogenic activation of osteoblasts. Testing GHR as a candidate gene, Nurnberg et al. (1997) found recombination events between CMD and GHR in 2 members of the family, thus excluding GHR as a candidate. In the family studied by Nurnberg et al. (1997), there were 24 affected persons in 6 generations.
Chandler et al. (2001) confirmed the linkage mapping of the CMDJ locus to 5p15.2-p14.1 in a large Australian pedigree and a second German family. Using recombinants, they narrowed the critical region to an interval of approximately 4 cM.
Molecular Genetics
Nurnberg et al. (2001) tested ANKH (605145) as a positional candidate in 9 unrelated families and demonstrated 6 different mutations in 8 of the families (e.g., 605145.0001-605145.0003). In 5 different families and in isolated cases, Reichenberger et al. (2001) described mutations in the ANKH gene.
In 3 unrelated patients with craniometaphyseal dysplasia and no family history of the disorder, Kornak et al. (2010) identified 3 different heterozygous mutations in the ANKH gene (605145.0011-605145.0013).
In a large 4-generation Australian family with craniometaphyseal dysplasia, originally described by Taylor and Sprague (1989) and in which Nurnberg et al. (2001) identified a heterozygous missense mutation in the ANKH gene (G389R; 605145.0002), Baynam et al. (2009) found evidence for chondrocalcinosis segregating with CMDD in affected female family members. Although a chance association of chondrocalcinosis with CMDD could not be excluded, Baynam et al. (2009) suggested that the lack of joint symptoms in affected male family members might be due to involvement of sex-dependent mechanisms or to the fact that only mutation-positive women in the pedigree had reached the age at which the chondrocalcinosis phenotype typically expresses.
INHERITANCE \- Autosomal dominant GROWTH Height \- Normal stature HEAD & NECK Head \- Macrocephaly Face \- Prognathism \- Facial palsy Ears \- Mixed hearing loss Eyes \- Hypertelorism Nose \- Bony paranasal bossing (often regresses with age) Teeth \- Teeth malalignment RESPIRATORY Nasopharynx \- Nasal obstruction leading to mouth breathing SKELETAL Skull \- Sclerotic skull base \- Sclerotic calvarium \- Obliteration of sinuses Spine \- Normal spine Pelvis \- Normal pelvis Limbs \- Widened metaphyses \- 'Erlenmeyer flask' deformity of distal femur (childhood) \- Club-shaped distal femur (adulthood) NEUROLOGIC Central Nervous System \- Facial palsy MISCELLANEOUS \- See 218400 for an autosomal recessive form caused by mutation in GJA1 ( 121014.0021 ) MOLECULAR BASIS \- Caused by mutation in the ANHK inorganic pyrophosphate transport regulator gene (ANKH, 605145.0001 ) ▲ Close
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT | c1852502 | 4,271 | omim | https://www.omim.org/entry/123000 | 2019-09-22T16:42:47 | {"doid": ["0080033"], "mesh": ["C565145"], "omim": ["123000"], "orphanet": ["1522"], "synonyms": ["Alternative titles", "CRANIOMETAPHYSEAL DYSPLASIA, JACKSON TYPE", "CMD"], "genereviews": ["NBK1461"]} |
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).
Mapping
Soranzo et al. (2009) performed a genomewide scan in 12,611 participants followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with genomewide significant association with height. All subjects were of European descent, including 1,430 British individuals from the British 1958 Birth Cohort, 2,224 individuals from the TwinsUK Cohort, and 5,746 individuals from a Dutch cohort. Soranzo et al. (2009) identified strong association of a single-nucleotide polymorphism on chromosome 6p22.1, rs10946808 (combined P = 5.6 x 10(-12)).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| STATURE QUANTITATIVE TRAIT LOCUS 18 | c2752065 | 4,272 | omim | https://www.omim.org/entry/612892 | 2019-09-22T16:00:24 | {"omim": ["612892"]} |
Reactive arthritis is a type of infectious arthritis that occurs as a “reaction” to an infection elsewhere in the body. This process may occur weeks or even months after the infection has resolved. In addition to joint inflammation, reactive arthritis is associated with two other symptoms: redness and inflammation of the eyes (conjunctivitis) and inflammation of the urinary tract (urethritis). These symptoms may occur alone, together, or not at all. The symptoms of reactive arthritis usually last 3 to 12 months, although symptoms can return or develop into a long-term disease in a small percentage of people. The exact cause of reactive arthritis is unknown. It may follow an infection with Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Campylobacter jejuni, Clostridium difficile, Shigella sonnei, Entamoeba histolytica, Cryptosporidium, or Chlamydia trachomatis. Certain genes may make you more prone to the syndrome. For instance, the condition is observed more commonly in patients with human lymphocyte antigen B27 (HLA-B27) histocompatibility antigens. The goal of treatment is to relieve symptoms and treat any underlying infection. Antibiotics may be prescribed. Nonsteroidal anti-inflammatory drugs (NSAIDS), pain relievers, and corticosteroids may be recommended for those with joint pain.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Reactive arthritis | c0035012 | 4,273 | gard | https://rarediseases.info.nih.gov/diseases/5693/reactive-arthritis | 2021-01-18T17:58:00 | {"mesh": ["D016918"], "orphanet": ["29207"], "synonyms": ["Post-infectious arthritis", "Post-infectious reactive arthropathy", "PIRA", "Reiter syndrome", "Reiter's syndrome"]} |
Vulvar intraepithelial neoplasia
Micrograph of (classic) vulvar intraepithelial neoplasia III. H&E stain.
SpecialtyGynecology
Vulvar intraepithelial neoplasia (VIN) refers to particular changes that can occur in the skin that covers the vulva. VIN is an intraepithelial neoplasia, and can disappear without treatment. VINs are benign but if the changes become more severe, there is a chance of cancer developing after many years, and so it is referred to as a precancerous condition.[1]
## Contents
* 1 Classification
* 2 Risk factors
* 3 Diagnosis
* 4 Prevention
* 5 References
* 6 External links
## Classification[edit]
Medically speaking, the term denotes a squamous intraepithelial lesion of the vulva that shows dysplasia with varying degrees of atypia. The epithelial basement membrane is intact and the lesion is thus not invasive but has invasive potential.
The terminology of VIN evolved over several decades. In 1989[2] the Committee on Terminology, International Society for the Study of Vulvar Disease (ISSVD) replaced older terminology such as vulvar dystrophy, Bowen's disease, and Kraurosis vulvae by a new classification system for Epithelial Vulvar Disease:
* Nonneoplastic epithelial disorders of vulva and mucosa:
* Lichen sclerosus
* Squamous hyperplasia
* Other dermatoses
* Mixed neoplastic and nonneoplastic disorders
* Intraepithelial neoplasia
* Squamous vulvar intraepithelial neoplasia (VIN)
* VIN I, mildest form
* VIN II, intermediate
* VIN III, most severe form including carcinoma in situ of the vulva
* Non-squamous intraepithelial neoplasia
* Extramammary Paget's disease
* Tumors of melanocytes, noninvasive
* Invasive disease (vulvar carcinoma)
The ISSVD further revised this classification in 2004, replacing the three-grade system with a single-grade system in which only the high-grade disease is classified as VIN.
VIN is subdivided into: (Robbins Pathological Basis of Disease, 9th Ed)
Classic vulvular intraepithelial neoplasia: associated with developing into the warty and basaloid type carcinoma. This is associated with carcinogenic genotypes of HPV and/or HPV persistence factors such as cigarette smoking or immunocompromised states.
Differentiated vulvar intraepithelial neoplasia also known as VIN Simplex: is associated with vulvar dermatoses such as lichen sclerosus. It is associated with atypia of the squamous epithelium.
[3] [4]
## Risk factors[edit]
The exact cause of VIN is unknown. Studies are being done to determine the cause of VIN. The following factors have been associated with VIN:
* HPV (Human Papilloma Virus)
* HSV-2 (Herpes simplex Virus - Type 2)
* Smoking
* Immunosuppression
* Chronic vulvar irritation
* Conditions such as Lichen Sclerosus
## Diagnosis[edit]
The person may have no symptoms, or local symptomatology including itching, burning, and pain. The diagnosis is always based on a careful inspection and a targeted biopsy of a visible vulvar lesion.
The type and distribution of lesions varies among the two different types of VIN. In the Usual type VIN, seen more frequently in young patients, lesions tend to be multifocal over an otherwise normal vulvar skin. In the differentiated type VIN, usually seen in postmenopausal women, lesions tend to be isolated and are located over a skin with a vulvar dermatosis such as Lichen slerosus.[3]
* Micrograph of vulvar intraepithelial neoplasia III. H&E stain.
* Micrograph of differentiated vulvar intraepithelial neoplasia. H&E stain.
## Prevention[edit]
Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.[5]
## References[edit]
1. ^ "Vulval intra-epithelial neoplasia (VIN)". Macmillan Cancer Support. Archived from the original on 2010-06-26. Retrieved 2010-06-09.
2. ^ Ridley CM, Frankman O, Jones IS, et al. (May 1989). "New nomenclature for vulvar disease: International Society for the Study of Vulvar Disease". Hum. Pathol. 20 (5): 495–6. doi:10.1016/0046-8177(89)90019-1. PMID 2707802.
3. ^ a b http://www.issvd.org
4. ^ Sideri M, Jones RW, Wilkinson EJ, Preti M, Heller D,. Scurry J, Haefner H, Neill S. 2004 Modified Terminology, ISSVD Vulvar Oncology Subcommittee. Journal of Reproductive Medicine. 2005;50:807-10.
5. ^ "FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers". 2008-09-12. Retrieved 2010-02-13.
## External links[edit]
Classification
D
* ICD-10: D07.1 (ILDS D07.120)
* ICD-9-CM: 233.32
* VIN at DermNet.NZ
* v
* t
* e
Tumors of the female urogenital system
Adnexa
Ovaries
Glandular and epithelial/
surface epithelial-
stromal tumor
CMS:
* Ovarian serous cystadenoma
* Mucinous cystadenoma
* Cystadenocarcinoma
* Papillary serous cystadenocarcinoma
* Krukenberg tumor
* Endometrioid tumor
* Clear-cell ovarian carcinoma
* Brenner tumour
Sex cord–gonadal stromal
* Leydig cell tumour
* Sertoli cell tumour
* Sertoli–Leydig cell tumour
* Thecoma
* Granulosa cell tumour
* Luteoma
* Sex cord tumour with annular tubules
Germ cell
* Dysgerminoma
* Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor
* Gonadoblastoma
* Teratoma/Struma ovarii
* Choriocarcinoma
Fibroma
* Meigs' syndrome
Fallopian tube
* Adenomatoid tumor
Uterus
Myometrium
* Uterine fibroids/leiomyoma
* Leiomyosarcoma
* Adenomyoma
Endometrium
* Endometrioid tumor
* Uterine papillary serous carcinoma
* Endometrial intraepithelial neoplasia
* Uterine clear-cell carcinoma
Cervix
* Cervical intraepithelial neoplasia
* Clear-cell carcinoma
* SCC
* Glassy cell carcinoma
* Villoglandular adenocarcinoma
Placenta
* Choriocarcinoma
* Gestational trophoblastic disease
General
* Uterine sarcoma
* Mixed Müllerian tumor
Vagina
* Squamous-cell carcinoma of the vagina
* Botryoid rhabdomyosarcoma
* Clear-cell adenocarcinoma of the vagina
* Vaginal intraepithelial neoplasia
* Vaginal cysts
Vulva
* SCC
* Melanoma
* Papillary hidradenoma
* Extramammary Paget's disease
* Vulvar intraepithelial neoplasia
* Bartholin gland carcinoma
* v
* t
* e
Human papillomavirus
Related
diseases
Cancers
* Cervical cancer
* cancers
* Anal
* Vaginal
* Vulvar
* Penile
* Head and neck cancer (HPV-positive oropharyngeal cancer)
Warts
* * genital
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* Georgios Papanikolaou
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Vulvar intraepithelial neoplasia | c0346210 | 4,274 | wikipedia | https://en.wikipedia.org/wiki/Vulvar_intraepithelial_neoplasia | 2021-01-18T18:59:59 | {"umls": ["C0346210"], "icd-9": ["233.32"], "icd-10": ["D07.1"], "orphanet": ["137583"], "wikidata": ["Q7943637"]} |
A number sign (#) is used with this entry because of evidence that hereditary congenital facial paresis-3 (HCFP3) is caused by homozygous mutation in the HOXB1 gene (142968) on chromosome 17q21.
Description
HCFP3 is an autosomal recessive congenital cranial dysinnervation disorder characterized by isolated dysfunction of the seventh cranial nerve resulting in facial palsy. Additional features may include orofacial anomalies, such as smooth philtrum, lagophthalmos, swallowing difficulties, and dysarthria, as well as hearing loss. There is some phenotypic overlap with Moebius syndrome (see, e.g., 157900), but patients with HCFP usually retain full eye motility or have esotropia without paralysis of the sixth cranial nerve (summary by Vogel et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of hereditary congenital facial paresis, see 601471.
Clinical Features
Webb et al. (2012) studied 2 brothers, born of consanguineous parents of conservative German American background, who had previously been diagnosed with Moebius syndrome (157900). The sibs were noted to have bilateral facial weakness, sensorineural hearing loss, and esotropia in the first months of life, and developed feeding difficulties and speech delays requiring oromotor and speech therapies. Both underwent surgery to correct esotropia, and both wore glasses for high hyperopia. MRI in the older brother at 8 months of age revealed bilateral absence of the facial nerve and bilateral abnormal tapering of the basal turn of the cochlea. Auditory brainstem response (ABR) testing in both boys revealed bilateral mild to moderate high frequency hearing loss with normal absolute latencies of waveforms, and distortion product otoacoustic emissions were absent in both children, supporting abnormal cochlear function. Stapedius reflexes were intact bilaterally. Examination at 7.25 years and 2.9 years of age, respectively, revealed midface retrusion, low-set and posteriorly rotated ears, upturned nasal tip, and smooth philtrum in both boys. Neither child showed any facial movement. Taste discrimination, salivation, and lacrimation were intact, as was general sensation over the concha of the ear and skin behind the auricle. Webb et al. (2012) noted that because both boys had partially accommodative esotropia with high hyperopia and full eye movements, they did not meet the criteria for Moebius syndrome. Their parents and a brother were unaffected, and there was no family history of strabismus or facial weakness.
Uyguner et al. (2015) reported an 7-year-old girl, born of consanguineous Turkish parents, with HCFP3. She had facial paresis, midface retrusion, left-sided ptosis with bilateral lagophthalmos, depressed nasal bridge, short nose with anteverted nares, tented vermilion of the upper lip, downturned corners of the mouth, high palate, and low-set ears. She was unable to smile or frown, and nasolabial folds were flattened. She had left esotropia with mild inferior oblique muscle hyperfunction; there was no paralytic component of the sixth cranial nerve, and ABR showed normal results. She had normal neurologic development.
Vogel et al. (2016) reported a consanguineous Moroccan family in which 4 individuals had HCFP3. Two brothers presented in childhood with facial paresis, a history of feeding difficulties, and speech delay. A similarly affected paternal uncle and aunt were subsequently identified. All had full eye motility, excluding a clinical diagnosis of Moebius syndrome. The patients had dysmorphic facial features, including masked facies, midface retrusion, upturned nose, smooth philtrum, lagophthalmos, epicanthal folds, flat nasal bridge, and variable cone-shaped incisors. They had mild oral dysfunction due to facial paresis, including feeding and swallowing difficulties, palatal weakness, dysarthria, and speech delay. Brain imaging in the 2 younger patients showed facial nerve hypoplasia with no cochlear abnormalities. However, ABR showed moderate high frequency hearing loss indicating cochlear dysfunction. In addition, all patients had external auricular malformations apparent at birth.
Inheritance
The transmission pattern of HCFP3 in the family reported by Vogel et al. (2016) was consistent with autosomal recessive inheritance.
Mapping
In 2 brothers with congenital facial paresis and their unaffected consanguineous conservative German American parents, Webb et al. (2012) performed linkage and homozygosity mapping and identified a single approximately 30-Mb region of shared homozygosity on chromosome 17q21.31-q25.1, flanked by SNPs rs9900383 and rs4969059. Linkage and haplotype analyses using DNA from 11 additional family members refined the interval to 27 Mb, with a maximum 2-point lod score of 2.3 for all fully informative markers across the critical interval.
Molecular Genetics
Using DNA from 1 of 2 brothers with congenital facial paresis from a consanguineous conservative German American family, Webb et al. (2012) performed whole-exome sequencing and filtering, which yielded 5 missense variants that were homozygous in the affected boys and heterozygous in their unaffected brother and parents, and segregated appropriately in the extended family. A missense mutation in the HOXB1 gene (R207C; 142968.0001) was the most plausible of the candidates, since Hoxb1-deficient mice have hypoplasia of the facial nucleus and congenital facial paralysis. Webb et al. (2012) sequenced HOXB1 in 175 additional probands, some with a diagnosis of Moebius syndrome (157900) and others with variable combinations of facial weakness, hearing loss, and complex or common strabismus, and identified homozygosity for the same R207C mutation in an adult brother and sister with congenital bilateral facial weakness, who had previously been diagnosed with Moebius syndrome and were also of conservative German American ('Pennsylvania Dutch') background. In addition to facial weakness, the sister had esophoria at both near and far distances, and mild hearing loss of unknown origin. Her younger brother also had sensorineural hearing loss, wore glasses, and had undergone strabismus surgery in childhood for 'lazy eye,' most consistent with a diagnosis of esotropia. Both sibs had micrognathia, normal intelligence, and no other known anomalies. Webb et al. (2012) stated that although all 4 affected individuals had congenital facial paresis, none had limited abduction of either eye, and thus did not meet the diagnostic criteria for Moebius syndrome. The R207C mutation was found to occur on a haplotype shared by the 2 German American families that was infrequent in the European population (0.787%), supporting a founder mutation.
In a 7-year-old girl, born of consanguineous Turkish parents, with HCFP3, Uyguner et al. (2015) identified a homozygous missense mutation in the HOXB1 gene (R207H; 142968.0002). The mutation, which was found by direct sequencing of the HOXB1 gene in 95 patients with similar features, segregated with the disorder in the family. Molecular modeling suggested that the mutation would alter DNA-binding capacity, with an increase in binding. In vitro functional studies of the variant and studies of patient cells were not performed, but the same residue was affected in 2 other patients with the disorder (R207C; 142968.0001).
In 4 members of a consanguineous Moroccan kindred with HCFP3, Vogel et al. (2016) identified a homozygous nonsense mutation in the HOXB1 gene (Y22X; 142968.0003). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted either to encode a truncated protein without the DNA-binding homeodomain or to result in nonsense-mediated mRNA decay, both of which would result in a complete loss of function. Vogel et al. (2016) commented that their findings suggested that loss of HOXB1 function is the underlying pathogenetic mechanism.
Animal Model
Expression of Hoxb1 is prominent in rhombomere 4 during mouse embryonic development. Studer et al. (1996) found that Hoxb1 -/- mice were indistinguishable from wildtype at birth; however, about 98% died within 24 hours. Early patterning of rhombomere 4 initiated properly, but was not maintained, and facial branchiomotor, vestibuloacoustic efferent, and visceromotor neurons were missing from their normal locations and showed abnormal axonal trajectories. Studer et al. (1996) concluded that Hoxb1 is involved in regulating neuronal migration in the hindbrain.
Goddard et al. (1996) generated mice homozygous for 2 different mutations in the Hoxb1 gene: a deletion of exon 2, which encodes the homeodomain, or deletion of both exons 1 and 2. They found that mice homozygous for either mutation failed to form the somatic motor component of the seventh (facial) nerve and showed facial paralysis. Mice homozygous for deletion of both exons 1 and 2, but not those lacking only exon 2, exhibited a high degree of lethality, which was likely due to impaired feeding behavior. The structure of rhombomere 4, neural crest cell production, and neural crest cell migration appeared to be normal in all mutant mice.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial paresis, congenital bilateral \- Facial muscle weakness of muscles innervated by CN VII \- Myopathic facies \- Midface retrusion \- Micrognathia \- Smooth philtrum \- Flattened nasolabial folds Ears \- Hearing loss, sensorineural, mild to moderate (in some patients) \- Low-set ears \- Posteriorly rotated ears \- External auricular malformations (1 family) Eyes \- Esotropia (in some patients) \- Esophoria (in some patients) \- Ptosis \- Lagophthalmos \- Epicanthal folds Nose \- Upturned nasal tip \- Anteverted nares \- Short nose \- Depressed nasal bridge Mouth \- Downturned corners of the mouth \- Tented vermilion of the upper lip \- Palatal weakness ABDOMEN Gastrointestinal \- Feeding difficulties \- Dysphagia NEUROLOGIC Central Nervous System \- Facial paresis, congenital bilateral \- Facial muscle weakness of muscles innervated by CN VII \- Speech delay \- Dysarthria MISCELLANEOUS \- Onset at birth \- Nonprogressive disorder MOLECULAR BASIS \- Caused by mutation in the homeobox B1 gene (HOXB1, 142968.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| FACIAL PARESIS, HEREDITARY CONGENITAL, 3 | c3553625 | 4,275 | omim | https://www.omim.org/entry/614744 | 2019-09-22T15:54:20 | {"omim": ["614744"], "orphanet": ["306530"], "synonyms": ["Congenital hereditary facial palsy with variable deafness", "Congenital hereditary facial palsy with variable hearing loss", "Congenital hereditary facial paralysis with variable deafness", "Congenital hereditary facial paralysis-variable deafness syndrome"]} |
Hereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.
There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.
People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities.
## Frequency
Hereditary spherocytosis occurs in 1 in 2,000 individuals of Northern European ancestry. This condition is the most common cause of inherited anemia in that population. The prevalence of hereditary spherocytosis in people of other ethnic backgrounds is unknown, but it is much less common.
## Causes
Mutations in at least five genes cause hereditary spherocytosis. These genes provide instructions for producing proteins that are found on the membranes of red blood cells. These proteins transport molecules into and out of cells, attach to other proteins, and maintain cell structure. Some of these proteins allow for cell flexibility; red blood cells have to be flexible to travel from the large blood vessels (arteries) to the smaller blood vessels (capillaries). The proteins allow the cell to change shape without breaking when passing through narrow capillaries.
Mutations in red blood cell membrane proteins result in an overly rigid, misshapen cell. Instead of a flattened disc shape, these cells are spherical. Dysfunctional membrane proteins interfere with the cell's ability to change shape when traveling through the blood vessels. The misshapen red blood cells, called spherocytes, are removed from circulation and taken to the spleen for destruction. Within the spleen, the red blood cells break down (undergo hemolysis). The shortage of red blood cells in circulation and the abundance of cells in the spleen are responsible for the signs and symptoms of hereditary spherocytosis.
Mutations in the ANK1 gene are responsible for approximately half of all cases of hereditary spherocytosis. The other genes associated with hereditary spherocytosis each account for a smaller percentage of cases of this condition.
### Learn more about the genes associated with Hereditary spherocytosis
* ANK1
* SLC4A1
Additional Information from NCBI Gene:
* EPB42
* SPTA1
* SPTB
## Inheritance Pattern
In about 75 percent of cases, hereditary spherocytosis is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
This condition can also be 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.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hereditary spherocytosis | c1866810 | 4,276 | medlineplus | https://medlineplus.gov/genetics/condition/hereditary-spherocytosis/ | 2021-01-27T08:24:54 | {"gard": ["6639"], "mesh": ["C566678"], "omim": ["182870", "182900", "270970", "612653", "612690"], "synonyms": []} |
Neuroferritinopathy is a late-onset type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by progressive chorea or dystonia and subtle cognitive deficits.
## Epidemiology
Prevalence of neuroferritinopathy is unknown. To date fewer than 50 cases have been reported.
## Clinical description
The disease presents typically in the fourth to sixth decades, although cases with symptoms in their late teens have been observed. Symptoms are restricted to the nervous system and include chorea, dystonia, bradykinesia, dystonic dysarthria, and Parkinsonian features. Choreiform movements tend to occur in the face, orolingual musculature and upper limbs and onset is usually asymmetrical. Dystonia can affect the face, tongue, arms and legs and onset is also usually asymmetrical. The majority of individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity is common, as is orolingual dyskinesia. Cognitive deficits, behavioral issues and dysphagia can be a late feature.
## Etiology
Neuroferritinopathy is caused by mutations in the ferritin light chain (FTL) gene (19q13.3-q13.4) and is inherited in an autosomal dominant manner with high penetrance.
## Diagnostic methods
Diagnosis is based on clinical findings including adult-onset chorea or dystonia, low serum ferritin (typically 20 micrograms/L or less) and iron deposition in the basal ganglia shown on brain MRI. Molecular genetic testing is available on a limited basis.
## Differential diagnosis
Differential diagnoses include Huntington disease and spinocerebellar ataxia type 17 (see these terms), although neither has the characteristic findings on neuroimaging; choreoacanthocytosis and McLeod neuroacanthocytosis syndrome (see these terms), although, unlike in these two diseases, the reflexes are preserved in neuroferritinopathy, and juvenile-onset Parkinson disease, aceruloplasminemia and Neimann-Pick type C (see these terms), although these disorders do not show the characteristic neuroimaging of neuroferritinopathy. The MRI findings are similar to those found in pantothenate kinase-associated neurodegeneration (PKAN; see this term). Individuals with neuroferritinopathy also show the 'eye of the tiger'' sign.
## Antenatal diagnosis
Prenatal testing for pregnancies at increased risk may be available through laboratories offering prenatal testing if the disease-causing mutation in the family is known.
## Management and treatment
Treatment is of the manifestations of the disease and includes levodopa, tetrabenazine, benzhexol, sulpiride, diazepam, clonezepam and deanol for the movement disorder and botulinum toxin for painful focal dystonia. Treatment also includes ensuring adequate caloric intake and physiotheraphy to maintain mobility. Iron supplements are not recommended.
## Prognosis
The movement disorder is progressive, involving additional limbs in five to ten years and becoming more generalized within 20 years.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neuroferritinopathy | c1853578 | 4,277 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157846 | 2021-01-23T18:32:18 | {"gard": ["10686"], "mesh": ["C548080"], "omim": ["606159"], "umls": ["C1853578"], "icd-10": ["G23.0"], "synonyms": ["Adult basal ganglia disease", "Ferritin-related neurodegeneration", "Hereditary ferritinopathy"]} |
A rare frontonasal dysplasia characterized by a craniofacial phenotype comprising frontal bossing with high anterior hairline, ptosis, hypertelorism, epicanthus inversus, flat nasal bridge, and broad nasal tip. Large anterior fontanelle, sagittal synostosis, and cranial base anomalies have also been described.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SIX2-related frontonasal dysplasia | None | 4,278 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=488437 | 2021-01-23T17:05:35 | {"synonyms": ["SIX2-related FND"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive Noonan syndrome (NS2) is caused by homozygous or compound heterozygous mutation in the LZTR1 gene (600574) on chromosome 22q11.
Description
Noonan syndrome (NS) is a multiple congenital anomalies syndrome characterized by a typical face, congenital heart disease, and short stature (summary by van der Burgt and Brunner, 2000).
For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).
Clinical Features
Johnston et al. (2018) reported 23 patients (21 of whom underwent molecular analysis) from 12 families with autosomal recessive Noonan syndrome. Birth length and birth head circumference was average to large for all children. Nine of 14 patients in whom it was evaluated had developmental delay. Sixteen of 19 had congenital heart defect or valve disease. Variable facial features of Noonan syndrome were reported in all, with 13 of 16 having low-set ears and 16 of 19 having a broad, short neck. Leukemia was reported in 2 families. Several patients presented prenatally with polyhydramnios, cystic hygroma, and/or arthrogryposis. Several patients died in the neonatal period. Cryptorchidism was rarely reported.
Umeki et al. (2019) reported a patient with Noonan syndrome 2. In addition to distinctive facial features suggestive of Noonan syndrome, she had hypertrophic cardiomyopathy, 5th brachymetapody, and mild intellectual disability.
Inheritance
Abdel-Salam and Temtamy (1969) reported 2 sibs with Noonan syndrome from a first-cousin marriage. A deceased female sib may have been affected also. They suggested autosomal recessive inheritance.
Maximilian et al. (1992) reported a family with 4 children, of whom 3, a girl and 2 boys, were thought to have Noonan syndrome. Neither parent had signs of the syndrome.
Van der Burgt and Brunner (2000) described 4 Dutch Noonan syndrome patients, 2 male and 2 female, each with unaffected consanguineous parents. All 4 had a typical Noonan syndrome phenotype and presented with hypertrophic obstructive cardiomyopathy at birth. In 2 patients the defect improved, in 1 patient it deteriorated, and in 1 patient it remained constant over 12 years. These patients supported the existence of an autosomal recessive form of Noonan syndrome in which hypertrophic obstructive cardiomyopathy is more frequent than in autosomal dominant Noonan syndrome.
The transmission pattern of Noonan syndrome in the families reported by Johnston et al. (2018) was consistent with autosomal recessive inheritance.
Molecular Genetics
Johnston et al. (2018) reported 17 mutations in 12 families with autosomal recessive Noonan Syndrome. These included missense, nonsense, frameshift, and splice site mutations that occurred in homozygosity or compound heterozygosity. All parents were heterozygous and unaffected.
Umeki et al. (2019) reported 1 NS2 patient with compound heterozygous mutations in the LZTR1 gene and 6 NS10 patients with heterozygous mutations in LZTR1. All patients had cardiac defects and 71% had hypertrophic cardiomyopathy. Other features were more variable. The patient with NS2 inherited each mutation from one of her unaffected parents.
INHERITANCE \- Autosomal recessive GROWTH Height \- Normal to increased birth length \- Short stature (in some patients) Weight \- Normal to increased birth weight HEAD & NECK Head \- Normal to increased occipitofrontal circumference (OFC) Ears \- Posteriorly rotated ears Eyes \- Downslanting palpebral fissures \- Hypertelorism (in some patients) \- Ptosis (in some patients) Neck \- Broad, short neck CARDIOVASCULAR Heart \- Pulmonary valve stenosis \- Mitral valve stenosis \- Septal defects \- Coarctation of the aorta \- Cardiomyopathy CHEST External Features \- Broad chest (in some patients) Ribs Sternum Clavicles & Scapulae \- Pectus deformity Breasts \- Widely spaced nipples (in some patients) GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism (in some patients) SKELETAL \- Arthrogryposis (in some patients) SKIN, NAILS, & HAIR Hair \- Curly hair NEUROLOGIC Central Nervous System \- Developmental delay \- Impaired intellectual development HEMATOLOGY \- Coagulation defects (in some patients) NEOPLASIA \- Leukemia (in 2 families) PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios (in some patients) MOLECULAR BASIS \- Caused by mutation in the leucine zipper-like transcriptional regulator 1 gene (LZTR1, 600574.0010 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| NOONAN SYNDROME 2 | c0028326 | 4,279 | omim | https://www.omim.org/entry/605275 | 2019-09-22T16:11:26 | {"doid": ["0060580"], "mesh": ["D009634"], "omim": ["605275"], "orphanet": ["648"], "synonyms": ["Alternative titles", "NOONAN SYNDROME, AUTOSOMAL RECESSIVE"], "genereviews": ["NBK1124"]} |
Diffuse dermal angiomatosis is a rare condition in which purplish patches develop in the skin, most often on the legs, though they may occur in other areas of the body. Sometimes these purple patches can become open wounds in the skin (ulcerations), which may be painful. This condition occurs when cells that line blood vessels grow into the surrounding skin tissue and rapidly increase in number. The exact cause of diffuse dermal angiomatosis is unknown, but it is thought to result from a lack of blood flow to the skin. It has been suggested that the lack of blood flow may be due to blocked blood vessels (such as in atherosclerosis) or large amounts of fatty tissue under the skin. Diffuse dermal angiomatosis is usually treated with surgery on the blood vessels to restore normal blood flow to the affected area of the skin. Two medications - isotretinoin and steroids \- have been used to successfully treat this condition in a small number of 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Diffuse dermal angiomatosis | None | 4,280 | gard | https://rarediseases.info.nih.gov/diseases/10888/diffuse-dermal-angiomatosis | 2021-01-18T18:00:52 | {"synonyms": []} |
A rare nevus characterized by single or multiple non-inflammatory verrucous skin lesions composed of keratinocytes, often present from birth, and distributed along the lines of Blaschko. Histologically, the lesions show features of epidermolytic hyperkeratosis with perinuclear vacuolization of keratinocytes of the upper epidermis with coarse keratohyaline granules. There is no extra-cutaneous involvement. Affected individuals are at risk of parenting a child with bullous ichthyosiform erythroderma.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Epidermolytic nevus | c1302848 | 4,281 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=497737 | 2021-01-23T18:44:18 | {"synonyms": ["Epidermal nevus with epidermolytic hyperkeratosis", "Epidermolytic epidermal nevus", "Epidermolytic verrucous epidermal nevus"]} |
For a general phenotypic description and a discussion of genetic heterogeneity of primary open angle glaucoma (POAG), see 137760.
Clinical Features
Wang et al. (2006) reported a 3-generation Chinese family in which 8 members had confirmed autosomal dominant juvenile-onset primary open angle glaucoma (JOAG; see 137750). Age at diagnosis ranged from 12 to 32 years. All of those affected showed notable increase in intraocular pressure and severe visual loss. All had a wide anterior chamber. Although most of them had typical glaucoma changes in optic disc and visual field, they all showed a normal iris, no anterior segment anomalies, and corneal thickness and anterior chamber depth within normal ranges.
Mapping
In 8 affected members of a Chinese family segregating autosomal dominant JOAG, Wang et al. (2006) excluded mutations in the MYOC (601652), OPTN (602432), and WDR36 (609669) genes. A genomewide scan showed linkage of the disorder, designated GLC1N, with D15S125, with a maximum 2-point lod score of 3.31 at theta = 0.0. Haplotype analysis and recombination mapping localized the disease locus to 15q22-q24 within a genetic distance of 16.6 Mb flanked by D15S1036 and rs922693.
Molecular Genetics
In affected members of a Chinese family segregating GLC1N, Wang et al. (2006) identified no mutations in the coding exons or splicing junctions of 3 candidate genes: NR2E3 (604485), SMAD6 (602931), and CLN6 (606725).
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| GLAUCOMA 1, OPEN ANGLE, N | c2981140 | 4,282 | omim | https://www.omim.org/entry/611274 | 2019-09-22T16:03:25 | {"doid": ["1067"], "omim": ["611274"], "orphanet": ["98977"]} |
Oculocerebrocutaneous (OCC) syndrome is a rare genetic disorder characterized primarily by eye, skin, and brain malformations. It has been described mostly in males. Findings in affected individuals may include orbital cysts, areas of underdeveloped (hypoplastic) or absent (aplastic) skin, and underdevelopment (hypoplasia) or absence (agenesis) of the band of nerve fibers that joins the brain's hemispheres (corpus callosum). Diagnosis is confirmed on the basis of specific MRI findings. In some affected individuals, the eye, skin, and brain findings involve only one side of the body. In these cases, the left side is involved twice as often as the right side. Additional findings may include rib and vertebral anomalies and craniofacial anomalies. Developmental delay and intellectual disability may be present and can vary from mild to profound. Approximately 50% of affected individuals have seizures. The exact cause of OCC syndrome is not known. In most cases, the affected individual is the first person in the family to have the disorder. The management of OCC syndrome varies depending on the specific symptoms in a given individual but usually involves a multidisciplinary team of doctors. Most surviving patients have significant psychomotor delays (delays in acquiring the skills needed to coordinate mental and physical activities).
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Oculocerebrocutaneous syndrome | c0796092 | 4,283 | gard | https://rarediseases.info.nih.gov/diseases/106/oculocerebrocutaneous-syndrome | 2021-01-18T17:58:38 | {"mesh": ["C538088"], "omim": ["164180"], "umls": ["C0796092"], "orphanet": ["1647"], "synonyms": ["Delleman syndrome", "Delleman Oorthuys syndrome", "Orbital cyst with cerebral and focal dermal malformations", "OCCS", "OCC Syndrome", "Oculo-cerebro-cutaneous syndrome"]} |
Ependymoma is the most frequent intramedullary tumor in adults (but accounts for only 10-12% of pediatric central nervous system tumors), and can be benign or anaplastic. Ependymoma arise from the ependymal cells of the cerebral ventricles, corticle rests and central canal of the spinal cord, and manifest with variable symptoms such headache, vomiting, seizures, focal neurological signs and loss of vision and can cause obstructive hydrocephalus in some cases.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Ependymoma | c0014474 | 4,284 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251636 | 2021-01-23T18:47:07 | {"gard": ["6353"], "mesh": ["D004806"], "umls": ["C0014474"], "icd-10": ["D43.2"], "synonyms": ["Classic ependymoma"]} |
Jackson–Weiss syndrome
Other namesCraniosynostosis, midfacial hypoplasia, and foot abnormalities [1]
Jackson–Weiss syndrome is inherited in an autosomal dominant pattern
SymptomsHypertelorism[1]
CausesMutations in the FGFR2 gene [2]
Diagnostic methodGenetic testing[2]
TreatmentSurgery[3]
Jackson–Weiss syndrome (JWS) is a genetic disorder characterized by foot abnormalities and the premature fusion of certain bones of the skull (craniosynostosis), which prevents further growth of the skull and affects the shape of the head and face. This genetic disorder can also sometimes cause intellectual disability and crossed eyes.[2] It was characterized in 1976.[4]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
Many of the characteristic facial features (among other) of Jackson–Weiss syndrome result from the premature fusion of the skull bones. The following are some of the more common, such as:[2][1]
* Preaxial foot polydactyl
* Tarsal synostosis
* Frontal bossing
* Proptosis
## Genetics[edit]
Fibroblast growth factor receptor 2
Mutations in the FGFR2 gene cause Jackson–Weiss syndrome. The FGFR2 gene produces a protein called fibroblast growth factor receptor 2,[5] which occurs in chromosome number 10. Among its multiple functions, this protein signals immature cells to become bone cells in a developing embryo. A mutation in a specific part of the FGFR2 gene alters the protein and causes prolonged signaling, which promotes the premature fusion of bones in the skull and feet,[6][7][8] this condition is inherited in an autosomal dominant pattern.[2] Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder.[9]
## Diagnosis[edit]
The diagnosis of Jackson–Weiss syndrome in an individual suspected of having the condition is done via the following:
* Genetic testing[10]
* Clinical presentation[7]
### Differential diagnosis[edit]
The DDx for this condition includes metopic synostosis, as well as Lambdoida synostosis.[7]
## Treatment[edit]
Hydrocephalus
Treatment for Jackson–Weiss syndrome can be done through surgery for some facial features and feet.[3] Secondary complications such as hydrocephalus or cognitive impairment, can be averted via prompt surgery.[7]
## Epidemiology[edit]
In terms of epidemiology, Jackson–Weiss syndrome is a rare genetic disorder; the overall contribution of FGFR mutation to the condition is not clear.[medical citation needed]
## References[edit]
1. ^ a b c "Jackson-Weiss syndrome | Genetic and Rare Diseases Information Center(GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 14 December 2016.
2. ^ a b c d e Reference, Genetics Home. "Jackson-Weiss syndrome". Genetics Home Reference. Retrieved 14 December 2016.
3. ^ a b Fryns, Buggenhout, Jean, Griet (July 2005). "Jackson–Weiss syndrome" (PDF). p. 2. Retrieved 2009-03-31.
4. ^ Jackson CE, Weiss L, Reynolds WA, Forman TF, Peterson JA (June 1976). "Craniosynostosis, midfacial hypoplasia and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred". J. Pediatr. 88 (6): 963–8. doi:10.1016/S0022-3476(76)81050-5. PMID 1271196.subscription required
5. ^ Chen L, Deng CX (2005). "Roles of FGF signaling in skeletal development and human genetic diseases". Front Biosci. 10 (1–3): 1961–76. doi:10.2741/1671. PMID 15769677.subscription required
6. ^ Reference, Genetics Home. "FGFR2 gene". Genetics Home Reference. Retrieved 14 December 2016.
7. ^ a b c d Robin, Nathaniel H.; Falk, Marni J.; Haldeman-Englert, Chad R. (1 January 1993). "FGFR-Related Craniosynostosis Syndromes". GeneReviews. PMID 20301628. Retrieved 14 December 2016.update 2011
8. ^ Kelly, Evelyn B. (2013). Encyclopedia of human genetics and disease. Santa Barbara, Calif.: Greenwood. p. 417. ISBN 9780313387142. Retrieved 14 December 2016.
9. ^ "Autosomal dominant: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 14 December 2016.
10. ^ "Jackson-Weiss syndrome - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 14 December 2016.
## Further reading[edit]
* Disorders, ed. by the National Organization for Rare (2003). NORD guide to rare disorders. Philadelphia: Lippincott Williams & Wilkins. ISBN 9780781730631. Retrieved 14 December 2016.CS1 maint: extra text: authors list (link)
* Nowalk, [edited by] Basil J. Zitelli, Sara C. McIntire, Andrew J.; McIntire, Sara C.; Nowalk, Andrew J. (2012). Zitelli and Davis' atlas of pediatric physical diagnosis (6th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 978-0323079327. Retrieved 14 December 2016.CS1 maint: extra text: authors list (link)
## External links[edit]
Classification
D
* ICD-10: Q87.89
* OMIM: 123150
* MeSH: C537559
* DiseasesDB: 31364
* SNOMED CT: 709105005
External resources
* Orphanet: 1540
Scholia has a topic profile for Jackson–Weiss syndrome.
* v
* t
* e
Cell surface receptor deficiencies
G protein-coupled receptor
(including hormone)
Class A
* TSHR (Congenital hypothyroidism 1)
* LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
* FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
* GnRHR (Gonadotropin-releasing hormone insensitivity)
* EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
* AVPR2 (Nephrogenic diabetes insipidus 1)
* PTGER2 (Aspirin-induced asthma)
Class B
* PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C
* CASR (Familial hypocalciuric hypercalcemia)
Class F
* FZD4 (Familial exudative vitreoretinopathy 1)
Enzyme-linked receptor
(including
growth factor)
RTK
* ROR2 (Robinow syndrome)
* FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
* FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
* FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
* INSR (Donohue syndrome
* Rabson–Mendenhall syndrome)
* NTRK1 (Congenital insensitivity to pain with anhidrosis)
* KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
STPK
* AMHR2 (Persistent Müllerian duct syndrome II)
* TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
* TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
GC
* GUCY2D (Leber's congenital amaurosis 1)
JAK-STAT
* Type I cytokine receptor: GH (Laron syndrome)
* CSF2RA (Surfactant metabolism dysfunction 4)
* MPL (Congenital amegakaryocytic thrombocytopenia)
TNF receptor
* TNFRSF1A (TNF receptor associated periodic syndrome)
* TNFRSF13B (Selective immunoglobulin A deficiency 2)
* TNFRSF5 (Hyper-IgM syndrome type 3)
* TNFRSF13C (CVID4)
* TNFRSF13B (CVID2)
* TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
Lipid receptor
* LRP: LRP2 (Donnai–Barrow syndrome)
* LRP4 (Cenani–Lenz syndactylism)
* LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
* LDLR (LDLR Familial hypercholesterolemia)
Other/ungrouped
* Immunoglobulin superfamily: AGM3, 6
* Integrin: LAD1
* Glanzmann's thrombasthenia
* Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal dysplasia)
* PTCH1 (Nevoid basal-cell carcinoma syndrome)
* BMPR1A (BMPR1A juvenile polyposis syndrome)
* IL2RG (X-linked severe combined immunodeficiency)
See also
cell surface receptors
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Jackson–Weiss syndrome | c0795998 | 4,285 | wikipedia | https://en.wikipedia.org/wiki/Jackson%E2%80%93Weiss_syndrome | 2021-01-18T18:39:09 | {"gard": ["6796"], "mesh": ["C537559"], "umls": ["C0795998"], "orphanet": ["1540"], "wikidata": ["Q6118062"]} |
A rare otorhinolaryngeal malformation characterized by a soft, fluctuant mass, abscess or draining tract along the anterior border of the lower half of sternocleidomastoid muscle, occasionally leading to development of retropharyngeal absces, acute suppurative thyroiditis, stridor, respiratory distress, odynophagia, and dysphagia. Anomaly occurs as a tract from the piriform sinus to the thyroid gland. A fourth branchial cleft fistula passes deep to the superior laryngeal nerve but superficial to the recurrent laryngeal nerve, which is the main difference in comparison to the third branchial cleft fistula.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fourth branchial cleft anomaly | c3873490 | 4,286 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141037 | 2021-01-23T18:10:56 | {"icd-10": ["Q18.0"], "synonyms": ["Fourth branchial cleft cyst", "Fourth branchial cleft fistula"]} |
A very rare congenital cranial dysinnervation disorder characterized by complete or incomplete facial paralysis in association with bilateral palsy of the abducens nerve causing impairment of ocular abduction. The syndrome also includes various other congenital anomalies.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Moebius syndrome | c0221060 | 4,287 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=570 | 2021-01-23T17:14:18 | {"gard": ["8549"], "mesh": ["D020331"], "omim": ["157900"], "umls": ["C0221060", "C0853240"], "icd-10": ["Q87.0"], "synonyms": ["Congenital facial diplegia", "Möbius syndrome"]} |
A number sign (#) is used with this entry because of evidence that Brugada syndrome-2 (BRGDA2) is caused by heterozygous mutation in the GPD1L gene (611778) on chromosome 3p22.
Description
Brugada syndrome is characterized by an ST segment elevation in the right precordial electrocardiogram leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts. The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years, but also occurs in infants and children (summary by Antzelevitch et al., 2005).
For a discussion of genetic heterogeneity of Brugada syndrome, see BRGDA1 (601144).
Clinical Features
Weiss et al. (2002) reported a large multigenerational family with a progressive conduction disease consistent with Brugada syndrome in which they identified 12 affected individuals with an autosomal dominant inheritance pattern characterized by incomplete penetrance that appeared to be dependent on age and sex. The proband, a 56-year-old man of Italian descent, had a syncopal episode while sitting and on ECG was found to have sinus rhythm, first degree AV block, a normal QT interval, right bundle branch block, leftward axis, and ST segment elevation in leads V1 through V3. An implantable cardioverter-defibrillator (ICD) was placed that recorded ventricular fibrillation during 2 syncopal episodes, both successfully treated with a single ICD shock. Gated MRI in the proband and 8 family members showed no fibrofatty infiltration. Five of the affected family members also had syncope or near-syncope and 2 had documented ventricular arrhythmias, but there was minimal family history of sudden death.
Mapping
In a large family segregating autosomal dominant Brugada syndrome, Weiss et al. (2002) performed a genomewide screen followed by fine mapping that demonstrated linkage to chromosome 3 with a maximum lod score of 4.0 at markers D3S3047, D3S1283, and D3S3547; multipoint and haplotype analyses localized the region of interest to approximately 15 cM on chromosome 3p25-p22. The sodium channel genes SCN5A (600163), SCN10A (604427), and SCN12A (see 604385) on chromosome 3 were excluded as candidates (lod scores less than -2.0). Weiss et al. (2002) concluded that there was a Brugada syndrome locus distinct from SCN5A.
Molecular Genetics
In a large family with Brugada syndrome linked to 3p25-p22, previously reported by Weiss et al. (2002), London et al. (2007) performed fine mapping and narrowed the critical region to approximately 1,000 kb on chromosome 3p24. Candidate genes in the area were analyzed by SSCP and direct sequencing, and a missense mutation in the GPD1L gene (611778.0001) was identified in 16 phenotypically affected individuals and 27 others (37% penetrance). The mutation, which was shown to cause a 50% reduction in inward current of the sodium channel and a 30% reduction in SCN5A cell surface expression, was not found in more than 1,000 reference alleles. No mutations in the GPD1L gene were identified in the probands of 19 smaller families with Brugada syndrome.
Van Norstrand et al. (2007) analyzed the GPD1L gene in necropsy tissue from 83 unrelated cases of sudden unexplained death and identified a mutation (E83K; 611778.0002) in a boy who died at 3 months of age. Mutation analysis was then performed on genomic DNA derived from 221 cases of sudden infant death syndrome (SIDS; 272120), revealing 2 additional mutations, in a girl who died at 5 weeks (I124K; 611778.0003) and a boy who died at 1 month of age (R273C; 611778.0004), respectively.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| BRUGADA SYNDROME 2 | c1142166 | 4,288 | omim | https://www.omim.org/entry/611777 | 2019-09-22T16:02:51 | {"doid": ["0110219"], "mesh": ["D053840"], "omim": ["611777"], "orphanet": ["130"], "genereviews": ["NBK1517"]} |
## Clinical Features
Chouery et al. (2008) reported a large consanguineous Lebanese family in which 3 sisters had primary focal torsion dystonia beginning with torticollis at ages 17, 19, and 14 years, respectively. Two or 3 years later, the symptoms spread, causing segmental dystonia for 2 patients and generalized dystonia for the third. At the time of examination, when the sisters were in their thirties, all had severe dysphonia and dysarthria. There were no signs of parkinsonism. Brain MRI showed no specific abnormalities.
Mapping
By genomewide linkage analysis of a Lebanese family with primary dystonia, Chouery et al. (2008) found significant linkage to a 20.5-Mb interval on chromosome 20p11.2-q13.12 between markers D20S472 and D20S911, which they termed DYT17. A maximum 2-point lod score of 2.4 was obtained at D20S107, and multipoint linkage analysis gave a maximum lod score of 3.1 at several markers. Sequence analysis excluded pathogenic changes in the EPB41L1 (602879), SLC32A1 (616440), and SSTR4 (182454) genes.
INHERITANCE \- Autosomal recessive HEAD & NECK Neck \- Torticollis NEUROLOGIC Central Nervous System \- Dystonia, progressive \- Dysphonia \- Dysarthria MISCELLANEOUS \- Onset in teenage years \- Begins as focal dystonia, later becomes segmental or generalized ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DYSTONIA 17, TORSION, AUTOSOMAL RECESSIVE | c2676281 | 4,289 | omim | https://www.omim.org/entry/612406 | 2019-09-22T16:01:33 | {"doid": ["0090042"], "mesh": ["C567319"], "omim": ["612406"], "orphanet": ["370103"], "synonyms": []} |
Teebi et al. (1989) observed an inbred family in Kuwait in which 3 females and 2 males from a sibship of 10 had macrosomia, severe microphthalmia, and early infant death. Three of the affected infants had median cleft palate. All 5 affected sibs showed respiratory infections in early life and died either unexpectedly or because of a documented overwhelming infection.
HEENT \- Microphthalmia \- Median cleft palate Resp \- Respiratory infections in early life Growth \- Macrosomia Misc \- Early infant death Inheritance \- Autosomal recessive ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MACROSOMIA WITH MICROPHTHALMIA, LETHAL | c1855467 | 4,290 | omim | https://www.omim.org/entry/248110 | 2019-09-22T16:25:43 | {"mesh": ["C537830"], "omim": ["248110"], "orphanet": ["2432"]} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (September 2017)
Benign metastasizing leiomyoma
SpecialtyOncology
Benign metastasizing leiomyoma is a rare condition characterized by the growth of uterine leiomyoma in the other regions especially the lungs.[1][2][3][4]
## References[edit]
1. ^ Fu, Yili; Li, Hui; Tian, Bo; Hu, Bin (2012). "Pulmonary benign metastasizing leiomyoma: a case report and review of the literature". World Journal of Surgical Oncology. 10 (1): 268. doi:10.1186/1477-7819-10-268. PMC 3545911. PMID 23234399.
2. ^ Ki, Eun; Hwang, Seon; Lee, Keun; Park, Jong; Hur, Soo (2013). "Benign metastasizing leiomyoma of the lung". World Journal of Surgical Oncology. 11 (1): 279. doi:10.1186/1477-7819-11-279. PMC 3842688. PMID 24134076.
3. ^ Chen, Shi; Liu, Rui-Ming; Li, Tian (27 February 2017). "Pulmonary benign metastasizing leiomyoma: a case report and literature review". Journal of Thoracic Disease. 6 (6): E92–E98. doi:10.3978/j.issn.2072-1439.2014.04.37. ISSN 2072-1439. PMC 4073417. PMID 24977035.
4. ^ Patton, Kurt T; Cheng, Liang; Papavero, Veronica; Blum, Matthew G; Yeldandi, Anjana V; Adley, Brian P; Luan, Chunyan; Diaz, Leslie K; Hui, Pei; Yang, Ximing J (January 2006). "Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis". Modern Pathology. 19 (1): 130–140. doi:10.1038/modpathol.3800504. PMID 16357844.
This article about a neoplasm is a stub. You can help Wikipedia by expanding it.
* v
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* e
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Benign metastasizing leiomyoma | c0346201 | 4,291 | wikipedia | https://en.wikipedia.org/wiki/Benign_metastasizing_leiomyoma | 2021-01-18T18:41:34 | {"gard": ["10776"], "umls": ["C0346201", "C1266132"], "wikidata": ["Q30314259"]} |
Proximal subungual onychomycosis
SpecialtyInfectious disease
Proximal subungual onychomycosis is an infection of the nail plate by fungus, primarily affecting the proximal nailfold.[1]:305
## See also[edit]
* Onychomycosis
* Skin lesion
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
* v
* t
* e
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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Proximal subungual onychomycosis | c1274514 | 4,292 | wikipedia | https://en.wikipedia.org/wiki/Proximal_subungual_onychomycosis | 2021-01-18T19:04:27 | {"umls": ["C1274514"], "wikidata": ["Q7252854"]} |
X-linked mandibulofacial dysostosis is an extremely rare multiple congenital abnormality syndrome that is characterized by microcephaly, malar hypoplasia with downslanting palpebral fissures, highly arched palate, apparently low-set and protruding ears, micrognathia, short stature, bilateral hearing loss, and learning disability. Occasionally, additional features have been observed such as bilateral cryptorchidism, cardiac valvular lesions, body asymmetry, and pectus excavatum.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| X-linked mandibulofacial dysostosis | c1844918 | 4,293 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1131 | 2021-01-23T18:13:20 | {"gard": ["1002"], "mesh": ["C537102"], "omim": ["301950"], "umls": ["C1844918"], "icd-10": ["Q75.4"], "synonyms": ["Mandibulofacial dysostosis, Toriello type", "X-linked branchial arch syndrome", "X-linked mandibulofacial dysostosis with limb anomalies"]} |
Crystal arthropathy
SpecialtyRheumatology
Crystal arthropathy is a class of joint disorder (called arthropathy) that is characterized by accumulation of tiny crystals in one or more joints. Polarizing microscopy and application of other crystallographic techniques have improved identification of different microcrystals including monosodium urate, calcium pyrophosphate dihydrate, calcium hydroxyapatite, and calcium oxalate.[1]
Types include:
Name Substance Birefringence
Gout[2] accumulation of uric acid negative
Chondrocalcinosis[3] aka Pseudogout accumulation of calcium pyrophosphate positive
## Contents
* 1 Risk factors
* 2 Causes
* 3 Differential diagnosis
* 4 References
* 5 External links
## Risk factors[edit]
* Obesity
* Kidney failure
* Hyperphosphatemia
* Hyperparathyroidism
* Hypercalcemia
* Tissue damage (dystrophic calcification)
## Causes[edit]
* Deposition of crystals in joints
* Calcium pyrophosphate dihydrate crystal formation:
* Increased production of inorganic pyrophosphate
* Decreased levels of pyrophosphatase in cartilage
* Decreased levels of cartilage glycosaminoglycans
* Hyperparathyroidism
* Hemochromatosis[4]
* Hypophosphatasia[5]
* Hypomagnesemia
* Hydroxyapatite deposition:
* Tissue damage
* Hyperparathyroidism[6]
* Hypercalcemia
* Hyperphosphatemia
* Calcium oxalate deposition:
* Enhanced production of oxalic acid due to enzyme defect
* Poor excretion of oxalic acid in kidney failure
* Excessive ascorbic acid intake in kidney failure
## Differential diagnosis[edit]
* Septic arthritis
* Type IIa hyperlipoproteinemia
* Amyloidosis
* Multicentric reticulohistiocytosis
* Hyperparathyroidism
* Spondyloarthropathy
* Rheumatoid arthritis
* Fibromyalgia
## References[edit]
1. ^ Mcgill NW (2000). "Gout and other crystal-associated arthropathies". Baillière's Clinical Rheumatology. 14 (3): 445–460. doi:10.1053/berh.2000.0087. PMID 10985980.
2. ^ Choi H (May 2006). "Epidemiology of crystal arthropathy". Rheum. Dis. Clin. North Am. 32 (2): 255–73, v. doi:10.1016/j.rdc.2006.03.002. PMID 16716879.
3. ^ Canhão H, Fonseca JE, Leandro MJ, et al. (2001). "Cross-sectional study of 50 patients with calcium pyrophosphate dihydrate crystal arthropathy". Clin. Rheumatol. 20 (2): 119–22. doi:10.1007/s100670170081. PMID 11346223. Archived from the original on 2001-05-17. Retrieved 2008-12-16.
4. ^ Axford, DSc, MD, John S. "Rheumatic manifestations of hereditary hemochromatosis". UpToDate.com. Retrieved 10 September 2014.CS1 maint: multiple names: authors list (link)
5. ^ "Hypophosphatasia Pathology". Hypophosphatasia.com. Retrieved 10 September 2014.
6. ^ Geelhoed, GW; Kelly, TR (December 1989). "Pseudogout as a clue and complication in primary hyperparathyroidism". Surgery. 106 (6): 1036–42. PMID 2588110.
## External links[edit]
Classification
D
* ICD-10: M10-M11
* ICD-9-CM: 712
* MeSH: D000070657
* v
* t
* e
Diseases of joints
General
* Arthritis
* Monoarthritis
* Oligoarthritis
* Polyarthritis
Symptoms
* Joint pain
* Joint stiffness
Inflammatory
Infectious
* Septic arthritis
* Tuberculosis arthritis
Crystal
* Chondrocalcinosis
* CPPD (Psudogout)
* Gout
Seronegative
* Reactive arthritis
* Psoriatic arthritis
* Ankylosing spondylitis
Other
* Juvenile idiopathic arthritis
* Rheumatoid arthritis
* Felty's syndrome
* Palindromic rheumatism
* Adult-onset Still's disease
Noninflammatory
* Hemarthrosis
* Osteoarthritis
* Heberden's node
* Bouchard's nodes
* Osteophyte
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Crystal arthropathy | c0152087 | 4,294 | wikipedia | https://en.wikipedia.org/wiki/Crystal_arthropathy | 2021-01-18T18:48:53 | {"gard": ["12802"], "mesh": ["D000070657"], "icd-9": ["712", "712.9", "712.90"], "icd-10": ["M10", "M11"], "wikidata": ["Q5191403"]} |
## Summary
### Clinical characteristics.
Clinical features of atelosteogenesis type 2 (AO2) include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midface retrusion, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. AO2 is usually lethal at birth or shortly thereafter due to pulmonary hypoplasia and tracheobronchomalacia. However, it exists in a continuous phenotypic spectrum with diastrophic dysplasia, and long-term survivors have been reported.
### Diagnosis/testing.
The diagnosis of AO2 is established in a proband with characteristic clinical, radiologic, and histopathologic features. Identification of biallelic pathogenic variants in SLC26A2 on molecular genetic testing can confirm the diagnosis.
### Management.
Treatment of manifestations: There is no specific treatment currently available, and the aim of therapy (supportive versus palliative) will depend on clinical status and respiratory prognosis of the individual patient.
### Genetic counseling.
AO2 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC26A2 pathogenic variant, each sib of a proband with AO2 has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing for a pregnancy at increased risk are possible if both pathogenic variants in the family are known. Ultrasound examination early in pregnancy is a reasonable complement or alternative to molecular genetic prenatal testing.
## Diagnosis
### Suggestive Findings
Atelosteogenesis type 2 (AO2) is usually lethal at birth or shortly thereafter because of pulmonary hypoplasia and tracheobronchomalacia. AO2 should be suspected when the following are present.
Clinical features
* Rhizomelic limb shortening with normal-sized skull
* Hitchhiker thumbs
* Small chest
* Protuberant abdomen
* Cleft palate
* Distinctive facial features (midface retrusion, depressed nasal bridge, epicanthus, micrognathia)
Other usual findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot.
Radiographic findings
* Normal-sized skull with disproportionately short skeleton
* Platyspondyly, hypodysplastic vertebrae, and cervical kyphosis. Ossification of the upper thoracic vertebrae and coronal clefts of the lumbar and lower thoracic vertebrae may be incomplete.
* Hypoplastic ilia with flat acetabulum. The pubic bones are often unossified.
* Shortened long bones with metaphyseal flaring. The distal humerus is sometimes bifid or V-shaped, sometimes pointed and hypoplastic; the femur is distally rounded; the radius and tibia are typically bowed.
* Note: (1) A distally pointed, triangular humerus had led Slaney et al [1999] to the suggestion of a new condition, but this finding is a typical feature of achondrogenesis 1B (ACG1B) bordering on AO2 [Unger et al 2001]. (2) The first individuals with de la Chapelle dysplasia described by de la Chapelle et al [1972] and Whitley et al [1986] showed a triangular remnant of ulna and fibula. Those individuals were subsequently classified as having AO2 [Bonafé et al 2008].
* Characteristic hand findings of sulfate transporter-related dysplasia:
* Hitchhiker thumb with ulnar deviation of the fingers (characteristic of diastrophic dysplasia [DTD])
* Gap between the first and second toe (characteristic of ACG1B [when the phalanges are identifiable on x-ray] and DTD)
* Hypoplasia of the first metacarpal bone (also present in ACG1B and DTD)
Histopathology (important when radiologic material is not available or is of poor quality)
* Paucity of sulfated proteoglycans in cartilage matrix [Superti-Furga et al 1996a, Rossi et al 1997] similar to that seen DTD and ACG1B
* Abnormal extracellular matrix with threads of fibrillar material between cystic acellular areas and areas of normal cellularity
* Some chondrocytes appear surrounded by lamellar material forming concentric rings that are in some cases indistinguishable from the collagen rings typical of ACG1B.
* The growth plate shows disruption of column formation and hypertrophic zones with irregular invasion of the metaphyseal capillaries and fibrosis.
* These cartilage matrix abnormalities are present in long bones as well as in tracheal, laryngeal, and peribronchial cartilage, whereas intramembranous ossification shows no abnormalities.
### Establishing the Diagnosis
The diagnosis of AO2 is established in a proband with suggestive findings and biallelic pathogenic variants in SLC26A2 identified by molecular genetic testing (see Table 1).
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 clinical and radiographic findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with perinatal-lethal skeletal dysplasia are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and radiographic findings suggest the diagnosis of AO2, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of SLC26A2 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 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: To date such variants have not been identified as a cause of AO2.
* A skeletal dysplasia multigene panel that includes SLC26A2 and other genes of interest (see Differential Diagnosis) can be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by perinatal-lethal skeletal dysplasia, comprehensive genomic testing, which does not require the clinician to determine which gene is likely involved, may be pursued. 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. Note: To date such variants have not been identified as a cause of AO2.
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 Atelosteogenesis Type 2
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
SLC26A2Sequence analysis 3>90% 4
Gene-targeted deletion/duplication analysis 5None reported
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\.
Rossi & Superti-Furga [2001]; data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
## Clinical Characteristics
### Clinical Description
To date, only a handful of individuals with atelosteogenesis type 2 (AO2) have been reported with biallelic pathogenic variants in SLC26A2 [Rossi & Superti-Furga 2001]. The following description of the phenotypic features associated with this condition is based on these reports.
The diagnosis of AO2 should be made only if the specific SLC26A2 pathogenic variants have already been described in an individual with AO2 and/or the clinical and radiographic severity lies somewhere between achondrogenesis 1B and diastrophic dysplasia (see Genetically Related Disorders). It follows, then, that the diagnosis of AO2 will only apply to a fetus/individual with severe prenatal-onset short stature. Almost all individuals will have club feet (adducted feet) and many will have lung hypoplasia (consequences of the generalized skeletal alterations). The dysmorphic facial features are very consistent and cleft palate is frequent.
AO2 is usually lethal in the neonatal period because of lung hypoplasia, tracheobronchomalacia, and laryngeal malformations. Pregnancy complication of polyhydramnios may occur.
Newborns with AO2 present with short limbs, adducted feet with wide space between the hallux and the second toe, hitchhiker thumb, cleft palate, and facial dysmorphism. AO2 is clinically very similar to diastrophic dysplasia (DTD) [Rossi et al 1996b].
Skeletal features. Disproportion between the short skeleton and normal-sized skull is immediately evident; the limb shortening is mainly rhizomelic; the gap between the toes, ulnar deviation of the fingers, and adducted thumbs are typical of sulfate transporter-related dysplasias [Newbury-Ecob 1998, Superti-Furga et al 2001]. The neck is short, the thorax narrow, and the abdomen protuberant.
Craniofacial features. Cleft palate is a constant feature, whereas the degree of facial dysmorphism is variable. Midface retrusion is usually present, together with a flat nasal bridge and micrognathia. Epicanthal folds, widely spaced eyes, and low-set ears can also be present.
Other. Spinal scoliosis and dislocation of the elbows are reported [Newbury-Ecob 1998].
### Genotype-Phenotype Correlations
Genotype-phenotype correlations indicate that the amount of residual activity of the sulfate transporter modulates the phenotype [Rossi et al 1997] in a spectrum from lethal ACG1B to mild recessive multiple epiphyseal dysplasia (EDM4/rMED).
* Homozygosity or compound heterozygosity for pathogenic variants predicting stop codons or structural variants in transmembrane domains of the sulfate transporter are associated with the more severe phenotype of ACG1B.
* The combination of a severe pathogenic variant (predicting stop codons or structural variants in transmembrane domains) with a pathogenic variant located in extracellular loops, in the cytoplasmic tail of the protein, or in the regulatory 5'-flanking region of the gene results in the less severe phenotypes, i.e., AO2 and DTD [Hästbacka et al 1996, Superti-Furga et al 1996b, Rossi et al 1997, Karniski 2001, Rossi & Superti-Furga 2001, Karniski 2004].
The pathogenic variant p.Arg279Trp, the most common SLC26A2 variant outside Finland (45% of alleles), is a mild variant resulting in the EDM4 phenotype when homozygous and mostly the DTD phenotype when in the compound heterozygous state.
The pathogenic variant p.Arg178Ter is the second-most common variant (9% of alleles) and is associated with a more severe DTD phenotype or even the perinatal-lethal AO2 phenotype, particularly when combined in trans with the p.Arg279Trp variant. It has also been found in some individuals with more severe MED4/rMED and ACG1B, making it one of two pathogenic variants identified in all four SLC26A2-related dysplasias.
Pathogenic variants p.Cys653Ser and c.-26+2T>C are the third-most common variants (8% of alleles for each).
* c.-26+2T>C is sometimes referred to as the "Finnish" variant because it is much more frequent in Finland than in the remainder of the world population. It produces low levels of correctly spliced mRNA and results in DTD when homozygous.
Together with p.Arg178Ter, c.-26+2T>C is the only pathogenic variant that has been identified in all four SLC26A2-related dysplasias, in compound heterozygosity with mild (EDM4/rMED and DTD) or severe (AO2 and ACG1B) alleles [Bonafe, unpublished results; Dwyer et al 2010].
* The pathogenic variant p.Cys653Ser results in EDM4/rMED when homozygous and in EDM4/rMED or DTD when compounded with other pathogenic variants. It is not found in AO2 or ACG1B.
Another pathogenic variant specific to the Finnish population is p.Thr512Lys, which results in AO2 (de la Chapelle dysplasia) when homozygous and in DTD when in compound heterozygosity with a milder allele [Bonafé et al 2008].
Most other pathogenic variants are rare.
The same pathogenic variants associated in some individuals who have the ACG1B phenotype can be found in individuals with a milder phenotype (EDM4 and DTD) if the second allele is a relatively mild variant. Indeed, pathogenic missense variants located outside the transmembrane domain of the sulfate transporter are often associated with a residual activity that can "rescue" the effect of a null allele [Rossi & Superti-Furga 2001].
### Nomenclature
The name "atelosteogenesis" was coined by Maroteaux et al [1982] for a different condition.
Sillence et al [1987] created the term "atelosteogenesis type 2" for a group of fetuses or stillborns who had all previously been diagnosed as having "severe diastrophic dysplasia." The reason was an apparent hypoplasia of the distal humerus and variable fibular hypoplasia (but not aplasia) that was slightly reminiscent of atelosteogenesis type 1 (AO1). The redefinition of this severe DTD variant as atelosteogenesis type 2 was unfortunate because it suggested a relationship with AO1 and at the same time denied the relationship with diastrophic dysplasia. Later biochemical and molecular studies brought this entity back to its origin – that is, in the diastrophic dysplasia-achondrogenesis group in which AO2 is considered to be a severe form of DTD, and in which lethality distinguishes AO2 from DTD.
De la Chapelle et al [1972] described two sibs with a novel condition very similar to AO2, with very hypoplastic ulna and fibula; one additional sib and one more person with this condition (de la Chapelle dysplasia) were reported by Whitley et al [1986]. The histopathologic similarities with ACG1B suggested a relationship with the sulfate transporter-related dysplasias. The identity of de la Chapelle dysplasia with AO2 was subsequently confirmed by molecular testing, which revealed pathogenic variants in SLC26A2 [Bonafé et al 2008].
AO2 may also be referred to as McAlister dysplasia.
AO2 is currently classified in the "sulphation disorders group" in the revised Nosology and Classification of Genetic Skeletal Disorders of Bone [Mortier et al 2019].
### Prevalence
No data on the prevalence of AO2 are available. Among the sulfate transporter-related dysplasias, AO2 is the rarest phenotype.
## Differential Diagnosis
Achondrogenesis 1B and diastrophic dysplasia (both allelic SLC26A2 disorders) have phenotypic overlap with atelosteogenesis type 2 (AO2) (and should be considered in the differential diagnosis (see Table 2).
The differentiation of AO2 from other subtypes of atelosteogenesis ("incomplete bone formation"), and even from other lethal skeletal dysplasias, should be based on clinical examination as well as radiographic imaging.
### Table 3.
Genes of Interest in the Differential Diagnosis of Atelosteogenesis Type 2
View in own window
Gene(s)DisorderMOIDifferentiating Clinical & Radiographic Features
FLNBAO1 (see FLNB Disorders)AD
* Hitchhiker thumb & gap between toes are not present in AO1 & cleft palate is rare.
* AO1 shows better development of long bones & better ossification of spine & pelvis.
* Absence of fibula may suggest AO1; dysplasia of fibula is more typical of AO2.
* Humerus may be completely absent in AO1.
Multiple
genes 1 incl:
DYNC2H1
IFT80
TTC21BLethal short-rib polydactyly
syndromes (w/o polydactyly)
(OMIM 613091, 611263, 613819)ARThoracic hypoplasia is more significant & there may be trident pelvis.
FGFR3Thanatophoric dysplasia (TD)AD
* Typical "telephone receiver" femur is visible on x-ray in TD.
* Cloverleaf skull is common in TD type II.
AD = autosomal dominant; AO = atelosteogenesis; AR = autosomal recessive; MOI = mode of inheritance
1\.
See Phenotypic Series: Short-rib thoracic dysplasia for genes associated with this phenotype in OMIM.
## Management
There is no specific treatment available. Decisions regarding supportive therapy versus palliative treatment depend on the degree of respiratory compromise at birth.
### Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with atelosteogenesis type 2 (AO2), the evaluations summarized in Table 5 (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 Atelosteogenesis Type 2
View in own window
System/ConcernEvaluationComment
MusculoskeletalComplete skeletal survey in viable newborn
PulmonaryEval of respiratory status in viable newborn
Genetic
counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of AO2 to facilitate medical & personal decision making
MOI = mode of inheritance
1\.
Medical geneticist, certified genetic counselor, or certified advanced genetic nurse
### Treatment of Manifestations
For long-term survivors, care should include surgical repair of cleft palate.
Utility of surgery for club feet is unclear as this is quite complicated and the results limited.
Physiotherapy is useful for retaining range of motion.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Atelosteogenesis Type 2 | c1850554 | 4,295 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1317/ | 2021-01-18T21:41:46 | {"mesh": ["C535395"], "synonyms": []} |
Mitochondrial myopathy and sideroblastic anemia belongs to the heterogeneous family of metabolic myopathies. It is characterised by progressive exercise intolerance manifesting in childhood, onset of sideroblastic anaemia around adolescence, lactic acidaemia, and mitochondrial myopathy.
## Epidemiology
Less than 10 cases have been described so far.
## Etiology
A 656C-->T mutation in the nuclear pseudouridine synthase 1 gene (PUS1), localised to 12q24.33, has recently been identified in some patients. Deficient pseudouridylation of mitochondrial tRNAs may be responsible for the oxidative phosphorylation disorder.
## Diagnostic methods
Muscle biopsy demonstrates low activity of complexes 1 and 4 of the respiratory chain and paracrystalline inclusions can be revealed in most mitochondria by electron microscopy.
## Genetic counseling
Transmission is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Mitochondrial myopathy and sideroblastic anemia | c1838103 | 4,296 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2598 | 2021-01-23T17:18:53 | {"gard": ["3885"], "mesh": ["C536101"], "omim": ["500011", "600462", "613561"], "umls": ["C1838103"], "icd-10": ["G71.3"], "synonyms": ["MLASA", "Myopathy, lactic acidosis and sideroblastic anemia"]} |
An adult-onset movement disorder characterized by bradykinesia, dysarthria and muscle rigidity.
## Epidemiology
To date, ADSD has been observed in seven individuals in one family.
## Clinical description
Onset of symptoms of ADSD is in the fourth to fifth decade of life with mild progressive dysarthria and hypokinesia. Mild bradykinesia presents predominantly as gait disturbance but also as a general slowing of movement. Dysdiadochokinesia is also present and muscle tone is slightly increased. Additional features include stiffness of the tongue and, in some patients, mild difficulties in swallowing. ADSD is characterized by dysfunction and changes of the striatal part of the basal ganglia, visible on MRI scans.
## Etiology
It is caused by mutation in the PDE8B gene (5q13.3-q14.1) and is transmitted in an autosomal dominant manner with complete penetrance in the investigated family.
## Diagnostic methods
Diagnosis is based on brain MRI which shows distinctive and characteristic symmetric lesions of the striatum that appear earlier than the onset of symptoms. A good correlation has been observed between clinical signs and the degree of MRI abnormalities.
## Differential diagnosis
Differential diagnoses include other degenerative diseases causing hypokinesia (such as Parkinson's disease; see this term). However, unlike for these diseases, in ADSD, tremor is not observed. Differential diagnoses also include neuroferritinopathy (see this term). However, ADSD is characterized by hypokinesia whereas neuroferritinopathy is characterized by hyperkinesia. The characteristic MRI changes of the striatum can be regarded as pathognomonic for ADSD.
## Antenatal diagnosis
Antenatal diagnosis is currently not available but is probably not necessary because of the mild course of the disease.
## Management and treatment
There is currently no known treatment for ADSD and symptoms do not respond to treatment with levodopa.
## Prognosis
The course of the disease is mild and allows affected individuals to lead a virtually normal life. Life expectancy does not appear to be affected.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Autosomal dominant striatal neurodegeneration | c1836694 | 4,297 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228169 | 2021-01-23T18:20:56 | {"mesh": ["C563783"], "omim": ["609161"], "umls": ["C1836694"], "synonyms": ["ADSD"]} |
Balci et al. (2004) reported a brother and sister with an apparently previously undescribed syndrome characterized by unusual triangular facial appearance associated with cleft palate, malocclusion, severe midfacial hypoplasia, and mild sensorineural hearing loss. Both sibs had normal intelligence. The parents were unrelated and of normal stature and intelligence, suggesting autosomal recessive inheritance.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CLEFT PALATE, MIDFACIAL HYPOPLASIA, TRIANGULAR FACIES, AND SENSORINEURAL HEARING LOSS | c1836120 | 4,298 | omim | https://www.omim.org/entry/609466 | 2019-09-22T16:06:01 | {"mesh": ["C536427"], "omim": ["609466"]} |
Autosomal recessive spastic paraplegia type 21 is a complex type of hereditary spastic paraplegia characterized by an onset in adolescence or adulthood of slowly progressive spastic paraparesis associated with the additional manifestations of apraxia, cognitive and speech decline (leading to dementia and akinetic mutism in some cases), personality disturbances and extrapyramidal (e.g. oromandibular dyskinesia, rigidity) and cerebellar (i.e. dysdiadochokinesia and incoordination) signs. Subtle abnormalities (e.g. developmental delays) may be noted earlier in childhood. A thin corpus callosum and white matter abnormalities are equally reported on magnetic resonance imaging.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Autosomal recessive spastic paraplegia type 21 | c1855346 | 4,299 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101001 | 2021-01-23T18:01:56 | {"mesh": ["C565409"], "omim": ["248900"], "umls": ["C1855346"], "icd-10": ["G11.4"], "synonyms": ["Mast syndrome", "SPG21"]} |
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