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A number sign (#) is used with this entry because of evidence that Wagner syndrome is caused by heterozygous mutation in the gene encoding versican (VCAN; 118661), also known as chondroitin sulfate proteoglycan-2 (CSPG2), on chromosome 5q14.
Description
Wagner vitreoretinopathy is a rare vitreoretinal degeneration inherited as an autosomal dominant trait, first described in a large Swiss pedigree (Wagner, 1938) and subsequently identified in other families. Penetrance in Wagner syndrome is complete, and the disease manifests in childhood or adolescence with a progressive course. Affected individuals usually present with an 'empty' vitreous cavity with fibrillary condensation or avascular strands and veils. Additional features, which are variable and age-dependent, include chorioretinal atrophy with loss of the retinal pigment epithelium (RPE), lattice degeneration of the retina, complicated cataracts, mild myopia, and peripheral traction retinal detachment. Rod and cone electroretinography shows reduced b-wave amplitude and correlates with severe chorioretinal pathology. It is believed that liquefaction of vitreous initiates a degenerative cascade that results in the complex eye phenotype of Wagner syndrome (summary by Kloeckener-Gruissem et al., 2006). Patients with additional ocular features such as progressive nyctalopia (night blindness), visual field constriction, and chorioretinal atrophy, with loss of RPE and choriocapillaries on fluorescein angiography and rod-cone abnormalities on electroretinography, were initially believed to have a distinct clinical entity, which was designated 'erosive vitreoretinopathy' (ERVR). Extraocular abnormalities are not present in patients diagnosed with Wagner or erosive vitreoretinopathy (summary by Mukhopadhyay et al., 2006).
Clinical Features
Wagner (1938) described 13 members of a Canton Zurich family with a peculiar lesion of the vitreous and retina. Ten additional affected members were observed by Boehringer et al. (1960) and 5 more by Ricci (1961). In Holland Jansen (1962) described 2 families with a total of 39 affected persons. In addition to typical changes in the vitreous, retinal detachment occurs in some and cataract is another complication. See hyaloideotapetoretinal degeneration of Favre (268100).
Graemiger et al. (1995) examined 60 members of the Swiss kindred originally studied by Wagner (1938). Twenty-eight members were found to be affected. The most consistent finding was an empty vitreous cavity with avascular strands or veils. Chorioretinal atrophy and cataract increased with age and occurred in all patients older than 45 years. Four patients had a history of a rhegmatogenous retinal detachment in 1 eye, which occurred at a median age of 20 years. Peripheral traction retinal detachments were found in 55% of eyes among patients older than 45 years. Glaucoma was present in 10 eyes (18%), 4 of which showed neovascular glaucoma. Of all patients, 63% showed elevated rod and cone thresholds on dark adaptation, and 87% showed subnormal b-wave amplitudes of the rod and cone systems on electroretinography. Thus, clinical expressivity of the disorder varied from unaffected carriers to bilateral blindness. Progression of the chorioretinal pathology was paralleled by electrophysiologic abnormalities.
Zech et al. (1999) examined 20 affected individuals from a large 4-generation French family with bilateral vitreoretinal degeneration without extraocular abnormalities. Peripheral avascular vitreous veils were seen in all 20 patients, 7 of whom were younger than 15 years. Chorioretinal changes included peripheral alteration of the pigmentary epithelium in 7 patients, lattice degeneration in 6, and chorioretinal atrophy involving the retinal periphery and posterior pole in 2. Rhegmatogenous retinal detachment had occurred in 3 patients, and slight tractional detachment was observed in 3. Presenile cataracts progressed by the third decade and required removal in 11 patients; surgery was bilateral in 8 patients. Refraction was performed in all 20 patients; visual acuity was usually normal in young patients, and severely reduced in older patients.
Miyamoto et al. (2005) studied a large Japanese family with Wagner syndrome. Ocular phenotypes of affected members included an empty vitreous with fibrillary condensations, avascular membrane, perivascular sheathing, and progressive chorioretinal dystrophy and were similar to those of the original Wagner syndrome family. All affected eyes examined exhibited pseudoexotropia with ectopic fovea. No systemic manifestations were observed.
Wagner syndrome is often confused with Stickler syndrome (STL1; 108300) which is caused by mutations in the type II collagen gene (COL2A1; 120140). Like certain mutations in COL2A1 that result in a predominantly ocular or ocular-only phenotype, Wagner syndrome has no systemic features (Richards et al., 2006). However, the vitreoretinal phenotype is different, as neither of the recognized vitreous abnormalities in Stickler syndrome are present in Wagner syndrome and there is a lower incidence of retinal detachment. In addition, patients with Wagner syndrome have poor dark adaptation, which results in night blindness; this can be demonstrated by electrodiagnosis.
Brezin et al. (2011) studied a 4-generation French family with a severe vitreoretinal disorder in which affected individuals exhibited a range of highly variable phenotypes, from exudative vascular abnormalities and diffuse retinal atrophy with pigment clumping to nasally deviated retinal vessels with ectopic foveas. Affected family members manifested retinal detachment at an early age, with variable anterior segment features, including moderate myopia, glaucoma, cataracts, and ectopia lentis. Brezin et al. (2011) noted that visual impairment in this pedigree was highly significant; among 10 affected family members, 3 were totally blind and 5 other patients had completely lost vision in 1 eye.
Mapping
Brown et al. (1994) concluded that erosive vitreoretinopathy (ERVR) is very similar to Wagner disease. Brown et al. (1995) presented linkage evidence that erosive vitreoretinopathy and Wagner disease are allelic disorders, which are distinct from COL2A1-associated Stickler syndrome. Brown et al. (1995) demonstrated that ERVR and Wagner disease map to 5q13-q14.
Black et al. (1999) reported a family in which multiple members through at least 4 generations suffered from a hereditary vitreoretinopathy associated with a variety of ocular developmental abnormalities, including posterior embryotoxon, congenital glaucoma, iris hypoplasia, congenital cataract, ectopia lentis, microphthalmia, and persistent hyperplastic primary vitreous. Genetic linkage studies mapped the disorder to markers from the proximal region of 5q13-q14, specifically to the 5-cM region between markers D5S626 and D5S2103. Both Wagner and erosive vitreoretinopathies had been mapped to the same region, suggesting that the condition in the family studied by Black et al. (1999) is allelic.
In a large 4-generation French family with ERVR, Zech et al. (1999) obtained a maximum 2-point lod score of 5.6 (theta = 0) at marker CRTL1 (HAPLN1; 115435) GT repeat and a maximum multipoint lod score of 5.8 (theta = 0) for markers D5S2029, CRTL1 GT repeat, and D5S459. Recombination events narrowed the disease locus to a 20-cM region between D5S650 and D5S618.
Using 13 microsatellite markers, Mukhopadhyay et al. (2006) determined the 5q14.3 haplotypes in affected individuals from 6 Dutch families with vitreoretinopathy. All patients from 5 of the families, including 4 families diagnosed with Wagner syndrome and 1 diagnosed with ERVR, showed the same haplotype for an 850-kb critical region between D5S626 and D5S107, suggesting a founder allele in the Netherlands.
In a 4-generation French family with a severe vitreoretinal disorder, Brezin et al. (2011) found significant evidence for linkage with markers D5S641 (Z = 3.36; theta = 0) and D5S2103 (Z = 2.89; theta = 0), indicating a critical disease interval for the WGN1 locus on 5q13-q14.
Molecular Genetics
In a large Japanese family with vitreoretinopathy that segregated with the previously identified WGN1 locus on 5q13-q14, Miyamoto et al. (2005) identified a heterozygous splice site mutation in intron 7 of the CSPG2 gene (VCAN; 118661.0001) that cosegregated with the disease.
In the large 5-generation Swiss family with vitreoretinopathy originally described by Wagner (1938), Kloeckener-Gruissem et al. (2006) analyzed 2 positional candidate genes on chromosome 5q13-q14 and identified a heterozygous splice site mutation in intron 8 of the VCAN gene (118661.0002) that segregated with disease.
Mukhopadhyay et al. (2006) studied 8 multigenerational families diagnosed with vitreoretinopathy, 7 of which were of Dutch origin. All affected members of the Dutch families were heterozygous for 1 of 3 splice site mutations in intron 7 of the VCAN gene (118661.0003-118661.0005), including a family diagnosed with erosive vitreoretinopathy. However, no causal variant was identified in the eighth family, which was of Chinese origin. Affected ancestors of 5 of the Dutch families, which shared a common founder haplotype on chromosome 5q14.3, were traced to the same geographic region of the Netherlands; Mukhopadhyay et al. (2006) stated that these 5 families harbored more than 90% of all Dutch patients with Wagner vitreoretinopathy.
In a 4-generation French family with a severe vitreoretinal disorder mapping to 5q13-q14, in which some patients exhibited exudative vascular features (see EVR1, 133780) but in whom no mutations were found in EVR-associated genes, Brezin et al. (2011) identified a heterozygous splice site mutation in intron 7 of the VCAN gene (118661.0006) that segregated with disease and was not found in 100 French controls.
Kloeckener-Gruissem et al. (2013) sequenced the VCAN gene in the British family with Wagner vitreoretinopathy previously studied by Fryer et al. (1990) and in the French family previously described by Zech et al. (1999), and identified 2 heterozygous splice site mutations, in introns 8 and 7 of the VCAN gene, respectively, that segregated with disease in each family (118661.0007 and 118661.0008).
### Exclusion Studies
Fryer et al. (1990) studied a large British family with Wagner vitreoretinal degeneration but none of the nonocular features of Stickler syndrome. They demonstrated recombination with the COL2A1 locus (120140), thus excluding that gene as the site of the mutation.
History
Differentiation of the Wagner syndrome and the Stickler syndrome is difficult. Liberfarb et al. (1978, 1981) suggested that the syndromes of Wagner and Stickler are the same. They restudied 3 families reported by Hirose et al. (1973). Blair et al. (1979) reported the clinical and histopathologic findings in 3 severely diseased eyes from 3 patients in 2 families. They concluded that the Stickler and Wagner syndromes are the same disorder. One reason for hesitation in complete acceptance of identity of the Wagner and Stickler syndromes is the fact that retinal detachment was not noted in any of the 28 members of the original Swiss family studied by Wagner (1938) and later by Boehringer et al. (1960) and Ricci (1961).
Korkko et al. (1993) noted phenotypic similarity to the family described by Wagner (1938) in a family in which they found a COL2A1 mutation (120140.0014). The family had early-onset cataracts, lattice degeneration of the retina, and retinal detachment with no involvement of nonocular tissues. Miyamoto et al. (2005) classified the family of Korkko et al. (1993) as an example of Stickler syndrome. Richards et al. (2006) suggested that the family of Korkko et al. (1993) could be an example of predominantly ocular Stickler syndrome or dominantly inherited rhegmatogenous retinal detachment.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Visual field defects (middle age) \- Vision loss with age (middle age) \- Myopia, mild \- Chorioretinal atrophy \- Vitreoretinal degeneration \- Cataract \- Peripheral traction retinal detachment (middle age) \- Exudative vitreoretinopathy (in some patients) \- 'Empty' vitreous with fibrillary condensations (childhood) \- Glaucoma \- Loss of retinal pigment epithelium \- Optic atrophy (seen in patients older than 45 years) \- Impairment of dark adaptation with age MISCELLANEOUS \- Progressive clinical course with onset in childhood MOLECULAR BASIS \- Caused by mutation in the chondroitin sulfate proteoglycan-2 gene (CSPG2, 118661.0001 ) ▲ 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
| WAGNER VITREORETINOPATHY | c1840452 | 4,100 | omim | https://www.omim.org/entry/143200 | 2019-09-22T16:40:07 | {"mesh": ["C536075"], "omim": ["143200"], "orphanet": ["898"], "synonyms": ["Alternative titles", "EROSIVE VITREORETINOPATHY", "WAGNER VITREORETINAL DEGENERATION", "HYALOIDEORETINAL DEGENERATION OF WAGNER", "WAGNER SYNDROME 1"], "genereviews": ["NBK3821"]} |
Babinski–Nageotte syndrome
Other namesBabinski syndrome or Hemimedullary syndrome
Medulla oblongata anterior view
SpecialtyNeurology
Babinski–Nageotte syndrome is an alternating brainstem syndrome. It occurs when there is damage to the dorsolateral or posterior lateral medulla oblongata, likely syphilitic in origin.[1] Hence it is also called the alternating medulla oblongata syndrome.[clarification needed]
The medulla oblongata is the lower half of the brainstem. It controls autonomic functions and connects the higher levels of the brain to the spinal cord. It is responsible for regulating several basic functions of the autonomic nervous system, including respiration, cardiac function, vasodilation, and reflexes like vomiting, coughing, sneezing, and swallowing. [2]
The rare[3] disorder is caused by damage to a part of the brain (medullobulbar transitional area) which causes a variety of neurological symptoms, some of which affect only one side of the body. Symptoms include ipsilateral (same side) cerebellar ataxia, sensory deficits of the face, and Horner's syndrome, along with weakness and loss of sensation on the contralateral (opposite side) of the body.[4]
It was first described in 1902 and later named after the neurologists who initially investigated it, Joseph Babinski and Jean Nageotte.[5]
## Contents
* 1 Founders
* 2 Terminology
* 3 Symptoms
* 3.1 Common Symptoms
* 4 The Babinski Sign
* 5 Case Histories / Prevalence
* 6 References
* 7 External links
## Founders[edit]
Babinski-Nageotte Syndrome was discovered in 1902 by two french men, Joseph Babinksi and Jean Nageotte. What is now known as the medically popular “Babinski Test” was discovered in 1899. Babinksi and Nageotte also co-wrote a book on cerebrospinal fluid.
Joseph Babinski was a french neurologist, born on November 17th, 1857. He studied under the “father of Neurology” Jean-Martin Charcot. Babinksi conducted research on multiple sclerosis, post traumatic stress disorders, and the distinction between mental and physical disorders. He, along with Austrian-American pharmacologist Alfred Fröhlich, discovered Babinski-Fröhlich syndrome. As a doctor, Babinski did not like to converse with his patients, he asked few questions and often stayed quiet. He did not have many friends nor did he like politics, therefore he was never given the title of professorship. Babinksi died on October 29th of 1932 in his hometown of Paris. [6]
Jean Nageotte was a neuroanatomist, neurologist, and neuropathologist from Dijon, France. He was born on February 8th, 1866. Nageotte earned his medical degree in 1893, and specialized in research of the nervous system, and the importance of microscopic anatomy. Nageotte wrote an article in 1910 about how glial cells behave, which was later recognized as glial cells and their neurotransmitters. He died on July 22nd of 1948 in Paris, France.
## Terminology[edit]
Babinski-Nageotte's syndrome is often confused or associated with other syndromes. The syndromes being Reinhold syndrome (hemimedullary syndrome) and Wallenberg syndrome. Although confused for one another they are different syndromes each with their differential features. . Similar to Babinski-Nageotte's syndrome, Reinfolds syndrome is also a rare disease. But as conducted through a study of 2 patients with Babinski-Nageotte's syndrome, a MRI test confirmed that Babinski-Nageotte's syndrome is its own syndrome and differs from hemi medullary syndrome.
Babinski-Nageotte syndrome is clinically distinct from Reinhold’s syndrome (hemimedullary syndrome). This has led to confusion since, in many texts, the two are referred to synonymously. To clarify this confusion, a study was conducted comparing two patients exhibiting classical Babinski-Nageotte's syndrome with a patient with a clinically complete hemimedullary lesion.The magnetic resonance imaging (MRI) data from this study showed that the syndromes are not identical in appearance. Additionally, there are symptomatic differences, such as Hypoglossal palsy, a symptom of hemimedullary syndrome that is not a part of the Babinski-Nageotte syndrome. Thus, the clinical features and MRI appearances of the patient with a hemimedullary lesion are not consistent with Babinski-Nageotte Syndrome and the terminology of these distinct syndromes should not be used synonymously. [7]
Horner’s syndrome is the disruption of a nerve pathway from the brain to the face and eye on one side of the body. This also results in a decreased pupil size (miosis), a drooping eyelid (ptosis) and decreased sweating on the affected side of your face (anhidrosis). [8]
## Symptoms[edit]
### Common Symptoms[edit]
Respiratory
Hoarseness and paralysis of the right side of the tongue and soft palate. Pneumonia and respiratory distress.
Gastrointestinal
Dysphagia, swallowing difficulties, nausea, vomiting, and dysarthria- also known as slurred speech.
Cardiovascular
Hypertension- also known as high blood pressure. Hyperlipidemia, which is the abnormally high levels of lipids in the blood.
Ocular
Miosis, the abnormal contraction and constriction of the pupil of the eye. Blepharoptosis is the abnormal drooping of the upper eyelids. Enophthalmos, which is the posterior displacement of the eyeball.
Urogenital
Postpartum amenorrhea, the abnormal absence of menstruation postpartum and galactorrhea, the milky discharge from nipples unrelated to normal lactation.
Neurological
Ataxia, the lack of muscle control and voluntary movements. [9]
## The Babinski Sign[edit]
The Babinski sign is when the big toe moves upwards instead of downwards when plantar flexion, pointing toes, is happening. Also known as the Plantar Flex, this reflex test has become very prominent in standard neurological examinations. This test is used to determine the strength of the Corticospinal Tract. The CST is a pathway in which motor signals are sent from the brain to the lower motor neurons, also known as a descending fiber tract that starts in the cerebral cortex, the outer layer of the cerebrum, and goes through the brainstem and spinal cord. Damage anywhere on the CST can determine the presence of the Babinski sign.
The Babinski sign can be the extension of the big toe and the abduction of the other toes instead of the normal flexion reflex. Another instance of this test is where the affected patient is laying flat on their back, also known as supine position, with their hands crossed on their chest. They attempt to sit up and the affected thigh is flexed with the heel raised up and the unaffected side of the body stays flat. [10]
## Case Histories / Prevalence[edit]
There have been few cases of this disease documented in detail and actually diagnosed with Babinski-Nageotte syndrome since its discovery in 1902. In one case this syndrome occurred in a woman that was 10 days into her postpartum period and had delivered her baby via Cesarean section. She had complaints of dysarthria, dysphagia, dizziness, nausea, vomiting, and weakness of left arm and leg. After looking into her medical records there was only a sudden development of these symptoms one hour before being admitted to the hospital and additional symptoms of dysphagia, dysarthria, and weakness of left arm and leg. [11] The only background health information found was she had given birth via Caesarean section 10 days prior and was diagnosed with preeclampsia in her 33rd week of pregnancy. During their first evaluation, it was noted that they appeared to be in a stuporous state and had dysarthric speech, eye movement was examined and found vertical and horizontal nystagmus. During cranial examination there was flattening of left sided nasolabial sulcus with abnormal gag reflex observed. In the motor system examination, the left upper and lower extremity muscle power were 3/5 level and her Babinski reflex was found to be an extensor response on the left side. During the sensory system examination, pain and thermal senses of the patient were decreased on the left side of the body and cerebellar tests were abnormal on the right side. Evaluation of the cranial MRI screening of the patient with the misdoubt of cerebrovascular disease showed results that were consistent with diffusion restriction which was thought to be acute infarct extending to inferior cerebellar peduncle with involvement of right sided posterolateral medulla oblongata. In magnetic resonance angiography (MRA), stenosis was seen in the distal segment of right vertebral artery. [12]
In addition, there was another case documented of an 81-year-old woman with hypertension and diabetes presented with left hemiplegia, reduction of superficial perception on the right side of the face and on the left side below the neck, and the cerebellar ataxia of the right limbs. Right Horner’s syndrome, right facial paresis, dysphagia, and paralysis of the right soft palate and ride side of the tongue were present. Cranial MRI showed a right hemi medullary infarct, and magnetic resonance angiography showered severe stenosis of the right vertebral artery. [13]
## References[edit]
1. ^ Poirier, Jacques Philippon, Jacques (2009). Joseph Babinski : a biography. Oxford: Oxford University Press. p. 204. ISBN 9780195369755.
2. ^ "11.4B: Medulla Oblongata". Medicine LibreTexts. 2018-07-20. Retrieved 2020-11-18.
3. ^ Fisher, Marc, ed. (2008). Stroke (1 publ. ed.). Edinburgh: Elsevier. p. 541. ISBN 9780444520043.
4. ^ al.], Andrew J. Larner ... [et (2011). A-Z of neurological practice a guide to clinical neurology (2nd ed.). Dordrecht: Springer. p. 84. ISBN 9781848829947.
5. ^ "Babinski-Nageotte syndrome". Who Named It?. Retrieved 2010-12-30.
6. ^ "Joseph Babinski". www.nndb.com. Retrieved 2020-11-18.
7. ^ Krasnianski, Michael; Neudecker, Stephan; Schluter, Andreas; Zierz, Stephan (2003-08-15). "Babinski-Nageotte's syndrome and Hemimedullary (Reinhold's) syndrome are clinically and morphologically distinct conditions". Journal of Neurology. 250 (8): 938–942. doi:10.1007/s00415-003-1118-9. ISSN 0340-5354. PMID 12928912.
8. ^ "Horner syndrome - Symptoms and causes". Mayo Clinic. Retrieved 2020-11-18.
9. ^ GmbH, Symptoma. "Babinski-Nageotte Syndrome (Babinski Syndrome): Symptoms, Diagnosis and Treatment". Symptoma. Retrieved 2020-11-18.
10. ^ Acharya, Aninda B.; Jamil, Radia T.; Dewey, Jeffrey J. (2020), "Babinski Reflex", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30085551, retrieved 2020-11-18
11. ^ Oruç, Serdar; Demirbaş, Hayri; Güzel, Abdullah; Beker Acay, Mehtap; Yaman, Mehmet (2016). "Babinski-Nageotte Syndrome Diagnosed in Postpartum Period". Case Reports in Neurological Medicine. 2016. doi:10.1155/2016/5206430. ISSN 2090-6668. PMC 4771883. PMID 26989533.
12. ^ Oruç, Serdar; Demirbaş, Hayri; Güzel, Abdullah; Beker Acay, Mehtap; Yaman, Mehmet (2016). "Babinski-Nageotte Syndrome Diagnosed in Postpartum Period". Case Reports in Neurological Medicine. 2016. doi:10.1155/2016/5206430. ISSN 2090-6668. PMC 4771883. PMID 26989533.
13. ^ Freitas, Gabriel R. de; Moll, Jorge; Araújo, Abelardo Q. C. (2001-06-12). "The Babinski–Nageotte syndrome". Neurology. 56 (11): 1604–1604. doi:10.1212/WNL.56.11.1604. ISSN 0028-3878. PMID 11402132.
## External links[edit]
Classification
D
* ICD-10: G83.89
* ICD-9-CM: 344.89
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
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CSF
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* both:
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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
| Babinski–Nageotte syndrome | c0270711 | 4,101 | wikipedia | https://en.wikipedia.org/wiki/Babinski%E2%80%93Nageotte_syndrome | 2021-01-18T19:02:55 | {"umls": ["C0270711"], "icd-9": ["344.89"], "icd-10": ["G83.89"], "wikidata": ["Q797708"]} |
Bronchogenic cyst
Micrograph of a mediastinal bronchogenic cyst – H&E stain
Bronchogenic cysts are small, solitary cysts or sinuses, most typically located in the region of the suprasternal notch or behind the manubrium.[1]:682
## Contents
* 1 Clinical features
* 2 Pathology
* 3 Treatment
* 4 Additional images
* 5 See also
* 6 References
## Clinical features[edit]
These cysts are found most often in young adults and are rare in infancy. The usual symptoms are the result of compression by the cyst, e.g., difficulty breathing or swallowing, cough, and chest pain. Malignant degeneration has been reported in these cysts on rare occasions. Bronchogenic cysts are usually found in the middle mediastinum. Chest x-rays show a smooth density just in front of the trachea or main stem bronchi at the carinal level. When the cyst communicates with the tracheobronchial tree, the air-fluid level may be seen within the cyst. CT scanning is useful in localizing these cysts.
## Pathology[edit]
Bronchogenic cysts are formed in the 6th week of gestation from an abnormal budding of the tracheal diverticulum. They are lined by respiratory type (ciliated) epithelium, which is characterized by cilia. Histologically these are also composed of cartilage, smooth muscle, fibrous tissue and mucous glands. These cysts originate from the ventral foregut that forms the respiratory system. These cysts are located close to the trachea or main stem bronchi. Rarely there is communication of the cyst with the tracheobronchial tree.
## Treatment[edit]
* Excision provides definitive diagnosis and cure.
* Biopsy provides a definitive diagnosis with less surgical risk.
* Observation provides minimal risk from the intervention, but carries some risk of bleeding or infection of the cyst at a later time, making excision more difficult if it occurs.
## Additional images[edit]
* Very high magnification light micrograph showing the cilia of a bronchogenic cyst. H&E stain.
## See also[edit]
* Cutaneous columnar cyst
* List of cutaneous conditions
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
*[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
| Bronchogenic cyst | c0006281 | 4,102 | wikipedia | https://en.wikipedia.org/wiki/Bronchogenic_cyst | 2021-01-18T18:54:17 | {"gard": ["1025"], "mesh": ["D001994"], "umls": ["C0006281"], "orphanet": ["2357"], "wikidata": ["Q4973829"]} |
A rare genetic multiple pterygium syndrome characterized by intrauterine growth retardation, fetal akinesia, multiple joint contractures causing severe arthrogryposis and pterygia (webbing) across multiple joints. Cystic hygroma and/or fetal hydrops are almost invariably present.
## Epidemiology
To date, less than 50 fetuses have been reported in 28 families. Of these cases, approximately 60% were male and 40% were female. Half of the families had affected males only, including five with multiple affected males.
## Clinical description
Lethal multiple pterygium syndrome (LMPS) is characterized by growth deficiency of prenatal onset, pterygia present in multiple areas (chin to sternum, cervical, axillary, humero-ulnar, crural, popliteal and the ankles) and flexion contractures giving rise to severe arthrogryposis. Subcutaneous edema varies from mildly edematous skin to fetal hydrops with cystic hygroma, lung hypoplasia, and oligo or polyhydramnios. Facial anomalies include hypertelorism, down-slanting palpebral fissures, epicanthic folds, flat nasal root, microretrognathism, microstomia, low-set malformed ears and cleft palate. Other anomalies include a small chest, reduced muscle bulk, cryptorchidism, central nervous system abnormalities (in particular cerebellar hypoplasia, ventricular dilatation and polymicrogyria), hypoplastic dermal ridges and creases, and less frequently a mid-forehead hemangioma, intestinal malrotation, cardiac hypoplasia, diaphragmatic hernia, obstructive uropathy, rocker bottom feet, microcephaly and/or cerebellar and pontine hypoplasia.
## Etiology
Causal mutations have been identified in subunits of the acetylcholine receptor encoded by CHRNA1 (2q31.1), CHRND (2q37.1), CHRNG (2q37.1), as well as in the nebulin gene (NEB, 2q23.3), and the ryanodine receptor (RYR1, 19q13.2).
## Diagnostic methods
Diagnosis is suspected based on characteristic clinical features and ultrasound findings observed during routine pregnancy examination (for more details see the section on antenatal diagnosis).
## Differential diagnosis
Differential diagnoses include other disorders which present with prenatal ultrasound features of reduced or absent fetal movements in association with an abnormal fetal posture and other arthrogrypotic conditions. These may include fetal akinesia deformation sequence (FADS), Bartsocas-Papas syndrome, Escobar variant multiple pterygium syndrome, arthrogryposis multiplex congenita, and maternal myasthenia gravis, as well as trisomy 18, severe neural tube defects, caudal regression sequence and vertebral anomalies, limb body wall complex, fetal neck masses, fetal hypoxia, constriction rings syndrome and fetal constraint.
## Antenatal diagnosis
Fetal akinesia may be detected as early as 12 weeks. Prenatal ultrasound findings with LMPS include intrauterine growth retardation, flexion contractures of the limbs, multiple pterygia, cystic hygroma, fetal hydrops, hypoplastic lungs, a cleft palate and other structural abnormalities. Additional findings of hypoplastic skeletal development may help in distinguishing LMPS from other conditions with FADS, and detailed ultrasound scans and fetal MRI may identify a central nervous system abnormality which may be a feature in LMPS or suggest an alternative etiology. Molecular prenatal genetic testing can be undertaken if early scans are inconclusive and the mutation has been identified. LMPS should also be considered in patients with a history of recurrent mid-trimester losses.
## Genetic counseling
The inheritance is autosomal recessive. The sibling recurrence risk is 25%. X-linked inheritance has also rarely been reported and is also suggested by the excess of males with LMPS.
## Management and treatment
As the condition is lethal, termination of the pregnancy may be proposed.
## Prognosis
LMPS is typically fatal during the second or third trimester.
*[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
| Lethal multiple pterygium syndrome | c1854678 | 4,103 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33108 | 2021-01-23T18:02:38 | {"gard": ["3834"], "mesh": ["C537378", "C537377"], "omim": ["253290"], "umls": ["C1854678"], "icd-10": ["Q79.8"], "synonyms": ["Autosomal recessive lethal multiple pterygium syndrome", "LMPS"]} |
Central pain syndrome (CPS) is a rare neurological disorder caused by damage to or dysfunction of the pain-conducting pathways of the central nervous system (in the brain, brainstem, and spinal cord). Symptoms of CPS can vary greatly from one person to another, partly because the cause may differ. Primary symptoms are pain and loss of sensation, usually in the face, arms, and/or legs. Pain or discomfort may be felt after being touched, or even in the absence of a trigger. The pain may worsen by exposure to heat or cold and by emotional distress. CPS is usually associated with stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or Parkinson's disease. Treatment typically includes pain medications, but complete relief of pain may not be possible. Tricyclic antidepressants or anticonvulsants can sometimes be useful. Lowering stress levels appears to reduce pain.
Many different names have been used for this disorder, including Dejerine-Roussy syndrome, thalamic pain syndrome, central post-stroke syndrome and others. The current name acknowledges that damage to various areas of the central nervous system can cause central pain, and that a stroke is not necessarily the cause. When CPS is due to a stroke, it may be referred to as the more specific term "central post-stroke pain."
*[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
| Central pain syndrome | c1536114 | 4,104 | gard | https://rarediseases.info.nih.gov/diseases/5161/central-pain-syndrome | 2021-01-18T18:01:34 | {"synonyms": ["Thalamic syndrome (former)", "Dejerine Roussy syndrome (former)", "Posterior thalamic syndrome (former)", "Retrolenticular syndrome", "Thalamic hyperesthetic anesthesia", "Thalamic pain syndrome (former)", "Central post-stroke pain (subtype)"]} |
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by postnatal tall stature with long hands and feet, scoliosis, distinctive dysmorphic facial features (prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin), hyperelastic, thin, and fragile skin, lipodystrophy, and variable intellectual disability and neurological deterioration. Additional reported manifestations include craniosynostosis, camptodactyly, progressive flexion contractures, joint dislocation, and cerebrovascular complications, among others. Brain MRI may show extensive periventricular white matter lesions and other anomalies.
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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
| Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome | c4225270 | 4,105 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=477831 | 2021-01-23T18:23:20 | {"omim": ["616592"], "synonyms": ["Kosaki overgrowth syndrome"]} |
Hypoplastic tibia-polydactyly syndrome is a very rare congenital malformation syndrome characterized by bilateral hypoplasia of the tibia with polydactyly of the feet and hands.
## Epidemiology
Prevalence is unknown but the syndrome is very rare with only a few case reports described in the literature.
## Clinical description
Additional findings include a thickened and/or duplicated fibula, hand syndactyly, and triphalangeal thumb.
## Etiology
An association with Hirschprung disease has been reported. It is suggested that hypoplastic tibia-polydactyly syndrome and triphalangeal thumb-polysyndactyly syndrome (see this term) may be variants of the same disorder.
## Genetic counseling
Autosomal dominant inheritance has been reported.
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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
| Hypoplastic tibiae-postaxial polydactyly syndrome | c1861098 | 4,106 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3332 | 2021-01-23T17:12:38 | {"mesh": ["C566046"], "omim": ["188740"], "icd-10": ["Q74.8"], "synonyms": ["Hypoplastic tibia-polydactyly syndrome", "Werner mesomelic syndrome"]} |
6q24-related transient neonatal diabetes mellitus is a type of diabetes that occurs in infants. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.
People with 6q24-related transient neonatal diabetes mellitus experience very slow growth before birth (severe intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration), usually beginning in the first week of life. Signs and symptoms of this form of diabetes are transient, which means that they gradually lessen over time and generally disappear between the ages of 3 months and 18 months. Diabetes may recur, however, especially during childhood illnesses or pregnancy. Up to half of individuals with 6q24-related transient neonatal diabetes mellitus develop permanent diabetes mellitus later in life.
Other features of 6q24-related transient neonatal diabetes mellitus that occur in some affected individuals include an unusually large tongue (macroglossia); a soft out-pouching around the belly-button (an umbilical hernia); malformations of the brain, heart, or kidneys; weak muscle tone (hypotonia); deafness; and developmental delay.
## Frequency
Between 1 in 215,000 and 1 in 400,000 babies are born with diabetes mellitus. In about half of these babies, the diabetes is transient. Researchers estimate that approximately 70 percent of transient diabetes in newborns is caused by 6q24-related transient neonatal diabetes mellitus.
## Causes
6q24-related transient neonatal diabetes mellitus is caused by the overactivity (overexpression) of certain genes in a region of the long (q) arm of chromosome 6 called 6q24. People inherit two copies of their genes, one from their mother and one from their father. Usually both copies of each gene are active, or "turned on," in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person's father; others are active only when inherited from a person's mother. This phenomenon is known as genomic imprinting.
The 6q24 region includes paternally expressed imprinted genes, which means that normally only the copy of each gene that comes from the father is active. The copy of each gene that comes from the mother is inactivated (silenced) by a mechanism called methylation.
Overactivity of one of the paternally expressed imprinted genes in this region, PLAGL1, is believed to cause 6q24-related transient neonatal diabetes mellitus. Other paternally expressed imprinted genes in the region, some of which have not been identified, may also be involved in this disorder.
There are three ways that overexpression of imprinted genes in the 6q24 region can occur. About 40 percent of cases of 6q24-related transient neonatal diabetes mellitus are caused by a genetic change known as paternal uniparental disomy (UPD) of chromosome 6. In paternal UPD, people inherit both copies of the affected chromosome from their father instead of one copy from each parent. Paternal UPD causes people to have two active copies of paternally expressed imprinted genes, rather than one active copy from the father and one inactive copy from the mother.
Another 40 percent of cases of 6q24-related transient neonatal diabetes mellitus occur when the copy of chromosome 6 that comes from the father has a duplication of genetic material including the paternally expressed imprinted genes in the 6q24 region.
The third mechanism by which overexpression of genes in the 6q24 region can occur is by impaired silencing of the maternal copy of the genes (maternal hypomethylation). Approximately 20 percent of cases of 6q24-related transient neonatal diabetes mellitus are caused by maternal hypomethylation. Some people with this disorder have a genetic change in the maternal copy of the 6q24 region that prevents genes in that region from being silenced. Other affected individuals have a more generalized impairment of gene silencing involving many imprinted regions, called hypomethylation of imprinted loci (HIL).
About half the time, HIL is caused by mutations in the ZFP57 gene. Studies indicate that the protein produced from this gene is important in establishing and maintaining gene silencing. The other causes of HIL are unknown. Because HIL can cause overexpression of many genes, this mechanism may account for the additional health problems that occur in some people with 6q24-related transient neonatal diabetes mellitus.
It is not well understood how overexpression of PLAGL1 and other genes in the 6q24 region causes 6q24-related transient neonatal diabetes mellitus and why the condition improves after infancy. The protein produced from the PLAGL1 gene helps control another protein called the pituitary adenylate cyclase-activating polypeptide receptor (PACAP1), and one of the functions of this protein is to stimulate insulin secretion by beta cells in the pancreas. In addition, overexpression of the PLAGL1 protein has been shown to stop the cycle of cell division and lead to the self-destruction of cells (apoptosis). Researchers suggest that PLAGL1 gene overexpression may reduce the number of insulin-secreting beta cells or impair their function in affected individuals.
Lack of sufficient insulin results in the signs and symptoms of diabetes mellitus. In individuals with 6q24-related transient neonatal diabetes mellitus, these signs and symptoms are most likely to occur during times of physiologic stress, including the rapid growth of infancy, childhood illnesses, and pregnancy. Because insulin acts as a growth promoter during early development, a shortage of this hormone may account for the intrauterine growth retardation seen in 6q24-related transient neonatal diabetes mellitus.
### Learn more about the genes and chromosome associated with 6q24-related transient neonatal diabetes mellitus
* PLAGL1
* ZFP57
* chromosome 6
Additional Information from NCBI Gene:
* HYMAI
## Inheritance Pattern
Most cases of 6q24-related transient neonatal diabetes mellitus are not inherited, particularly those caused by paternal uniparental disomy. In these cases, genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.
Sometimes, the genetic change responsible for 6q24-related transient neonatal diabetes mellitus is inherited. For example, a duplication of genetic material on the paternal chromosome 6 can be passed from one generation to the next.
When 6q24-related transient neonatal diabetes mellitus is caused by ZFP57 gene mutations, it is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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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
| 6q24-related transient neonatal diabetes mellitus | c1832386 | 4,107 | medlineplus | https://medlineplus.gov/genetics/condition/6q24-related-transient-neonatal-diabetes-mellitus/ | 2021-01-27T08:25:12 | {"gard": ["1839"], "mesh": ["C563322"], "omim": ["601410"], "synonyms": []} |
Lactate dehydrogenase deficiency is a condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells. There are two types of lactate dehydrogenase deficiency: lactate dehydrogenase A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase B deficiency. People with lactate dehydrogenase A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). People with lactate dehydrogenase B deficiency typically do not have symptoms. Lactate dehydrogenase A deficiency is caused by mutations in the LDHA gene. Lactate dehydrogenase B deficiency is caused by mutations in the LDHB gene. Both types are inherited in an autosomal recessive pattern.
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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
| Lactate dehydrogenase deficiency | c0342769 | 4,108 | gard | https://rarediseases.info.nih.gov/diseases/3159/lactate-dehydrogenase-deficiency | 2021-01-18T17:59:32 | {"mesh": ["C580233"], "omim": ["150000"], "umls": ["C0342769"], "orphanet": ["2364"], "synonyms": []} |
Craniofrontonasal dysplasia
Other namesCraniofrontonasal dysostosis
This condition is inherited in an X-linked dominant manner. However, unlike most X-linked conditions, it is more severe in females, due to cell–cell interaction mechanisms involving the responsible gene (EFNB1) when it is present in only some cells (mosaic).
SpecialtyMedical genetics
Craniofrontonasal dysplasia (craniofrontonasal syndrome, craniofrontonasal dysostosis, CFND) is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1).[1][2] Phenotypic expression varies greatly amongst affected individuals, where females are more commonly and generally more severely affected than males.[1][2] Common physical malformations are: craniosynostosis of the coronal suture(s), orbital hypertelorism, bifid nasal tip, dry frizzy curled hair, longitudinal ridging and/or splitting of the nails, and facial asymmetry.[3][4][5][6]
The diagnosis CFND is determined by the presence of a mutation in the EFNB1 gene. Physical characteristics may play a supportive role in establishing the diagnosis.
The treatment is always surgical and is based on each patients specific phenotypic presentation.[7]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 References
* 7 External links
## Presentation[edit]
CT-scan of the skull of a patient with coronal synostosis, orbital hypertelorism, and facial asymmetry as part of craniofrontonasal dysplasia.
Picture of longitudinal ridging and splitting of the toenails as part of craniofrontonasal dysplasia.
Phenotypic expression varies greatly between individuals with CFND. Some of the more prominent characteristics are:[3][4][5][6]
* Craniosynostosis of the coronal suture(s) (fusion of the coronal sutures),
* Orbital hypertelorism (increased interocular distance),
* Bifid nasal tip,
* Dry frizzy curled hair,
* Longitudinal ridging and / or splitting of the nails,
* Facial Asymmetry.
Other characteristics that are less frequently seen are: broad nasal base, low anterior hair line, low set ears, crowding of the teeth, maxillary hypoplasia, rounded and sloping shoulders, pectus excavatum, scoliosis, high arched palate, orbital dystopia, low implant of the breasts with asymmetric nipples and volume, webbed neck, hand or foot abnormalities such as clinodactyly (most common is a curved 5th finger) and cutaneous syndactyly (webbed fingers / toes).[3][4][5][6]
Females are more commonly and usually more severely affected than males. Males can however have (some of) the same symptoms as females, but this is not frequently seen.[3] Most males have mild symptoms such as hypertelorism and a broad nasal base with bifid nose, but can also be a carrier of the mutation yet stay clinically unaffected.[1][2]
## Genetics[edit]
CFND is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1).[1][2] The EFNB1 gene codes for a membrane-anchored ligand which can bind to an ephrin tyrosine-kinase receptor.[2] This ephrin receptor is, amongst other things, responsible for the regulation of embryonic tissue-border formation, and is important for skeletal and craniofacial development.[8][9] As the ephrin receptor and its EFNB1 ligand are both bound to the (trans)membrane of the cell its cascade is activated through cell-cell interactions.[8] These cell-cell interactions are disturbed due to the presence of cells with the mutant EFNB1 gene, as a result causing incomplete tissue-border formation.[5]
Paradoxical to other X-linked conditions, with CFND the females are more severely affected than males.[3] This is due to the process of X-inactivation in females, where at random either the maternal or paternal X-chromosome is inactivated in a cell.[3][10] Due to this process, the body’s tissues contain either cells with normal EFNB1 or the mutated EFNB1. This is called a mosaic pattern.[3][10][11] This mosaic pattern of cells 'interferes' with the functionality of the cell-cell interactions, as a result causing the severe physical malformations in females.[11][12]
As with all X-linked conditions CFND has a preset chance of being passed down from parents to their offspring. Females have two X-chromosomes and males have one X-chromosome. When a mother is a carrier of CFND, there is a 50% chance of her passing down the X-chromosome containing the mutated EFNB1 gene to her offspring, regardless if the child is a boy or girl. If the father is a carrier there is a 100% chance of him passing down his X-chromosome with the EFNB1 mutation to a daughter, and 0% chance of him passing it down to a son.[3]
## Diagnosis[edit]
The diagnosis CFND is established only after the presence of a mutation in the EFNB1 gene has been determined.[1][2][13] Physical manifestations are not necessarily part of the diagnostic criteria, but can help guide in the right direction. This is due to the large heterogeneity between patients regarding phenotypic expression.[7]
20% of the patients that present with CFND-like characteristics do not display a mutation in the EFNB1 gene.[13][14][15] The group of patients diagnosed with CFND is thus often overestimated. However, it is important to distinguish this population from CFND for research purposes. On the other hand, especially in males, it is possible that someone is a carrier of the EFNB1 gene mutation yet does not present with any physical manifestations.[14][15] Screening for the presence of an EFNB1 mutation is thus the most reliable method to establish the diagnosis CFND.[citation needed]
Genetic counseling or prenatal screening may be advised if there is a reason to suspect the presence of an EFNB1 gene mutation.[3][5] Prenatal screening may be done by performing an ultrasound, where can be searched specifically for hypertelorism or a bifid nasal tip. However, this is quite difficult as facial involvement may not be obvious at such an early age, especially in cases with mild phenotypic presentation.[7] The most definitive way to prove the presence of CFND is done by genetic testing, through amniocentesis and chorionic villus sampling. This however carries a greater risk of premature termination of the pregnancy.[16]
## Treatment[edit]
There is no ‘standard treatment’ for people with CFND due to the large variations in phenotypic expression. Each patient needs to be assessed and treated based on their specific presentation in order to restore the aesthetic and functional balance.[7]
Surgical corrections for the main symptoms;
* Craniosynostosis correction: The preferred age for this procedure is between 6–9 months of age.[17] Performing this surgery at such an early age can limit the further development of facial asymmetry, if the asymmetry is caused by the craniosynostosis, and prevents prolonged elevated intracranial pressure (ICP).[18] However, the data for the exact risk of an elevated intracranial pressure for patients with CFND is lacking in the published literature.[7][18] The surgery involves a frontal bone advancement in combination with remodelling of the supraorbital rim.[19]
* Orbital hypertelorism: It is preferred to wait with this treatment until the age of 5–8 years old, after permanent dentition.[7][20] The procedures that can be performed are the facial bipartition and the box osteotomy. Facial bipartition is the preferable choice as there are less additional corrections needed, as well as providing a more stable long-term result after treatment.[18] After the correction of the orbitas, the medial corners of the eyes are put more into a horizontal line.[7]
* Nasal deformity correction: The correction of the broad nasal base is simultaneously done with the orbital hypertelorism repair. This is for good alignment of the eyes with the nose for the best aesthetic result. A bifid nose tip will only be treated at the age of 18, when the patient's skeleton has fully matured.[7][21]
## Epidemiology[edit]
Craniofrontonasal dysplasia is a very rare genetic condition. As such there is little information and no consensus in the published literature regarding the epidemiological statistics.
The incidence values that were reported ranged from 1:100,000 to 1:120,000.[3]
## References[edit]
1. ^ a b c d e Wieland, I., Jakubiczka, S., Muschke, P., et al. Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet 74: 1209-1215, 2004.
2. ^ a b c d e f Twigg, S. R., Kan, R., Babbs, C., et al. Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc Natl Acad Sci U S A 101: 8652-8657, 2004.
3. ^ a b c d e f g h i j "Archived copy" (PDF). Archived from the original (PDF) on 2014-09-12. Retrieved 2012-11-03.CS1 maint: archived copy as title (link)
4. ^ a b c Vasudevan, P. C., Twigg, S. R., Mulliken, J. B., et al. Expanding the phenotype of craniofrontonasal syndrome: two unrelated boys with EFNB1 mutations and congenital diaphragmatic hernia. Eur J Hum Genet 14: 884-887, 2006.
5. ^ a b c d e Zafeiriou, D. I., Pavlidou, E. L., Vargiami, E., et al. Diverse clinical and genetic aspects of craniofrontonasal syndrome. Pediatr Neurol. 2011 Feb;44(2):83-7.
6. ^ a b c Grutzner, E., Gorlin, R. J. Craniofrontonasal dysplasia: phenotypic expression in females and males and genetic considerations. Oral Surg Oral Med Oral Pathol 65: 436-444, 1988.
7. ^ a b c d e f g h Kawamoto, H. K., Heller, J. B., Heller, M. M., et al. Craniofrontonasal dysplasia: a surgical treatment algorithm. Plast Reconstr Surg 120: 1943-1956, 2007.
8. ^ a b Kullander, K., Klein, R. Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3: 475-86, 2002.
9. ^ Wilkinson, D. G. Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci. 2001;2:155–164.
10. ^ a b Beutler, E., Yeh, M., Fairbanks, V. F. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD-deficiency as a marker. Proc Natl Acad Sci U S A 48: 9–16, 1962.
11. ^ a b Wieland, I., Makarov, R., Reardon, W., Tinschert, S., Goldenberg, A., Thierry, P., et al. Dissecting the molecular mechanisms in craniofrontonasal syndrome: differential mRNA expression of mutant EFNB1 and the cellular mosaic. Eur J Hum Genet. 2008 Feb;16(2):184-91.
12. ^ Apostolopoulou, D., Stratoudakis, A., Hatzaki, A. A Novel de Novo Mutation Within EFNB1 Gene in a Young Girl With Craniofrontonasal Syndrome. Cleft Palate Craniofac J. 49: 109-13, 2012.
13. ^ a b Wieland, I., Reardon, W., Jakubiczka, S., et al. Twenty-six novel EFNB1 mutations in familial and sporadic craniofrontonasal syndrome (CFNS). Hum Mutat 26: 113-118, 2005.
14. ^ a b Twigg, S. R., Matsumoto, K., Kidd, A. M., et al. The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males.Am J Hum Genet 78: 999-1010, 2006.
15. ^ a b Wallis, D., Lacbawan, F., Jain, M., et al. Additional EFNB1 mutations in craniofrontonasal syndrome. Am J Med Genet A 146A: 2008-2012, 2008.
16. ^ https://www.cdc.gov/mmwr/PDF/rr/rr4409.pdf
17. ^ Panchal, J. et al. Management of craniosynostosis. Plast Reconstr Surg. 2003 May;111(6):2032-48
18. ^ a b c van den Elzen, M. E., Wolvius, E. B. et al. Long-term surgical outcome for craniofacial deformities of patients with craniofrontonasal dysplasia with proven EFNB1 mutations. J Plast Reconstr. Surg.
19. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2012-06-17. Retrieved 2012-11-03.CS1 maint: archived copy as title (link)
20. ^ Bentz, M. L. Pediatric Plastic Surgery; Chapter 9 Hypertelorism by Renato Ocampo, Jr., MD/ John A. Persing, MD
21. ^ van den Elzen, M. E., Versnel, S. L., et al. Long-term results after 40 years experience with treatment of rare facial clefts: Part 2 e symmetrical median clefts. J Plast Reconstr Aesthet Surg 64(10): 1344-52, 2011.
## External links[edit]
* Craniofrontonasal dysplasia at NIH's Office of Rare Diseases
* Craniofrontonasal dysplasiaTeebi type at NIH's Office of Rare Diseases
Classification
D
* OMIM: 304110
* MeSH: C536456
External resources
* Orphanet: 1520
* v
* t
* e
X-linked disorders
X-linked recessive
Immune
* Chronic granulomatous disease (CYBB)
* Wiskott–Aldrich syndrome
* X-linked severe combined immunodeficiency
* X-linked agammaglobulinemia
* Hyper-IgM syndrome type 1
* IPEX
* X-linked lymphoproliferative disease
* Properdin deficiency
Hematologic
* Haemophilia A
* Haemophilia B
* X-linked sideroblastic anemia
Endocrine
* Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
* KAL1 Kallmann syndrome
* X-linked adrenal hypoplasia congenita
Metabolic
* Amino acid: Ornithine transcarbamylase deficiency
* Oculocerebrorenal syndrome
* Dyslipidemia: Adrenoleukodystrophy
* Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
* Pyruvate dehydrogenase deficiency
* Danon disease/glycogen storage disease Type IIb
* Lipid storage disorder: Fabry's disease
* Mucopolysaccharidosis: Hunter syndrome
* Purine–pyrimidine metabolism: Lesch–Nyhan syndrome
* Mineral: Menkes disease/Occipital horn syndrome
Nervous system
* X-linked intellectual disability: Coffin–Lowry syndrome
* MASA syndrome
* Alpha-thalassemia mental retardation syndrome
* Siderius X-linked mental retardation syndrome
* Eye disorders: Color blindness (red and green, but not blue)
* Ocular albinism (1)
* Norrie disease
* Choroideremia
* Other: Charcot–Marie–Tooth disease (CMTX2-3)
* Pelizaeus–Merzbacher disease
* SMAX2
Skin and related tissue
* Dyskeratosis congenita
* Hypohidrotic ectodermal dysplasia (EDA)
* X-linked ichthyosis
* X-linked endothelial corneal dystrophy
Neuromuscular
* Becker's muscular dystrophy/Duchenne
* Centronuclear myopathy (MTM1)
* Conradi–Hünermann syndrome
* Emery–Dreifuss muscular dystrophy 1
Urologic
* Alport syndrome
* Dent's disease
* X-linked nephrogenic diabetes insipidus
Bone/tooth
* AMELX Amelogenesis imperfecta
No primary system
* Barth syndrome
* McLeod syndrome
* Smith–Fineman–Myers syndrome
* Simpson–Golabi–Behmel syndrome
* Mohr–Tranebjærg syndrome
* Nasodigitoacoustic syndrome
X-linked dominant
* X-linked hypophosphatemia
* Focal dermal hypoplasia
* Fragile X syndrome
* Aicardi syndrome
* Incontinentia pigmenti
* Rett syndrome
* CHILD syndrome
* Lujan–Fryns syndrome
* Orofaciodigital syndrome 1
* Craniofrontonasal dysplasia
* v
* t
* e
Extracellular ligand disorders
Cytokine
* EDA Hypohidrotic ectodermal dysplasia
* Camurati–Engelmann disease
Ephrin
* Craniofrontonasal dysplasia
WNT
* Tetra-amelia syndrome
TGF
* OFC 11
Fas ligand
* Autoimmune lymphoproliferative syndrome 1B
Endothelin
* EDN3
* Waardenburg syndrome IVb
* Hirschsprung's disease 4
Other
* DHH (DHH XY gonadal dysgenesis)
* BMP15 (Premature ovarian failure 4)
* TSHB (Congenital hypothyroidism 4)
See also
intercellular signaling peptides and proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Craniofrontonasal dysplasia | c0220767 | 4,109 | wikipedia | https://en.wikipedia.org/wiki/Craniofrontonasal_dysplasia | 2021-01-18T18:53:13 | {"gard": ["1578"], "mesh": ["C536456"], "umls": ["C0220767"], "icd-10": ["Q87.1"], "orphanet": ["1520"], "wikidata": ["Q5182141"]} |
This syndrome is characterized by the association of congenital mixed hearing loss with perilymphatic gusher (Gusher syndrome or DFN3; see this term), hypogonadism and abnormal behavior.
## Epidemiology
It has been described in five related males.
## Etiology
Inheritance appeared to be X-linked recessive and a microdeletion, encompassing the POU3F4 gene (DFN3 locus), was detected in one of the patients leading to the suggestion that deafness - hypogonadism is a contiguous gene deletion syndrome.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Deafness-hypogonadism syndrome | c1844680 | 4,110 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90646 | 2021-01-23T18:58:18 | {"gard": ["1691"], "mesh": ["C564435"], "omim": ["304350"], "umls": ["C1844680"], "synonyms": ["Hearing loss-hypogonadism syndrome"]} |
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-19 (RP19) can be caused by homozygous or compound heterozygous mutation in the ABCR gene (ABCA4; 601691) on chromosome 1p22.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical Features
In the population of Spain, 39% of the retinitis pigmentosa pedigrees show an autosomal recessive pattern of inheritance (Ayuso et al., 1995). Martinez-Mir et al. (1997) described a consanguineous Spanish family in which 6 of 7 sibs were affected. The parents, who were related as second cousins, were unaffected. The mean age of onset was 8 years. Night blindness was followed by a decrease in visual acuity, starting at 14 years of age. Fundus examination showed papillary pallor, attenuated vessels, peripheral scattered pigmentation, bone spicule-like pigmentation reaching some areas of the macula, and severe atrophy of the retinal pigment epithelium.
Mapping
Martinez-Mir et al. (1997) demonstrated linkage (maximum lod = 3.64 at theta = 0.0) with marker D1S188 located at 1p21-p13, the same region as Stargardt disease (STGD1; 248200). Exhaustive ophthalmologic study of the patients clearly distinguished the disease from the Stargardt phenotype (and the fundus flavimaculatus phenotype, which is caused by mutations in the same gene) and revealed an atypical form of autosomal recessive RP with choroidal atrophy as a distinctive feature. Fluorescein angiography of individuals showing severe choriocapillaris atrophy were presented.
Molecular Genetics
Since RP19 maps to the same region of the short arm of chromosome 1 as the Stargardt disease locus, Martinez-Mir et al. (1998) sought mutations in the ABCR gene, which is mutant in Stargardt disease. They identified a 1847delA frameshift mutation in the ABCR gene (610691.0008) in a consanguineous Spanish family that showed linkage to 1p.
In a family segregating RP19 and STGD1 in 2 first cousins, Rozet et al. (1999) found that heterozygosity for a splice acceptor site mutation in the ABCR gene (601691.0017) resulted in STGD1, whereas hemizygosity for this mutation resulted in RP19. In the patient with RP19, a partial deletion of the maternal ABCR gene was presumed to be the source of a null allele, although this was not conclusively proven.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Night blindness \- Decreased visual acuity \- Concentric reduction of visual field \- Optic disc pallor \- Attenuated vessels \- Peripheral scattered pigmentation \- Bone spicule-like pigmentation \- Severe atrophy of the retinal pigment epithelium \- Abolished rod responses seen on electroretinography (ERG) \- Markedly diminished cone responses seen on ERG MISCELLANEOUS \- Onset of symptoms in the first decade of life \- Progression of symptoms with age MOLECULAR BASIS \- Caused by mutation in the ATP-binding cassette, subfamily A, member 4 gene (ABCA4, 601691.0008 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| RETINITIS PIGMENTOSA 19 | c0035334 | 4,111 | omim | https://www.omim.org/entry/601718 | 2019-09-22T16:14:23 | {"doid": ["0110354"], "mesh": ["D012174"], "omim": ["601718"], "orphanet": ["791"], "genereviews": ["NBK1417"]} |
Ulna hypoplasia - intellectual deficit is a very rare syndrome characterized by mesomelic shortness of the forearms, bilateral clubfeet, aplasia or hypoplasia of all nails and severe psychomotor retardation.
## Epidemiology
It has been reported in two sibs.
## Genetic counseling
The family is suggestive of autosomal recessive inheritance.
## Prognosis
Prognosis is poor.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Ulna hypoplasia-intellectual disability syndrome | c1848650 | 4,112 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2249 | 2021-01-23T17:49:58 | {"gard": ["5398"], "mesh": ["C536934", "C564757"], "omim": ["276821"], "umls": ["C1848650", "C2931370"], "icd-10": ["Q87.2"]} |
Mental illness caused by a lack of thiamine in the brain
See also: Wernicke–Korsakoff syndrome
Korsakoff syndrome
Other namesAlcoholic Korsakoff syndrome (AKS), Korsakov syndrome, Alcohol amnestic disorder
Thiamine
SpecialtyPsychiatry
Korsakoff syndrome (KS)[1] is an amnestic disorder caused by thiamine (vitamin B1) deficiency typically associated with prolonged use of alcohol.[2] The syndrome and psychosis are named after Sergei Korsakoff, the Russian neuropsychiatrist who discovered it during the late 19th century.
This neurological disorder is caused by a lack of thiamine in the brain, and is also exacerbated by the neurotoxic effects of alcohol. When Wernicke encephalopathy accompanies Korsakoff syndrome the combination is called Wernicke–Korsakoff syndrome; however, a recognized episode of Wernicke encephalopathy is not always obvious.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Risk factors
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
There are seven major symptoms of Korsakoff syndrome an amnestic-confabulatory syndrome:
1. anterograde amnesia, memory loss for events after the onset of the syndrome
2. retrograde amnesia, memory loss extends back for some time before the onset of the syndrome
3. amnesia of fixation, also known as fixation amnesia (loss of immediate memory, a person being unable to remember events of the past few minutes)[3][4][5]
4. confabulation, that is, invented memories which are then taken as true, due to gaps in memory, with such gaps sometimes associated with blackouts
5. minimal content in conversation
6. lack of insight
7. apathy – interest in things is quickly lost, and there is an indifference to change
Benon R. and LeHuché R. (1920) described the characteristic signs of Korsakoff syndrome with some additional features including: confabulation (false memories), fixation amnesia, paragnosia or false recognition of places, mental excitation, and euphoria.[6]
Thiamine is essential for the decarboxylation of pyruvate, and deficiency during this metabolic process is thought to cause damage to the medial thalamus and mammillary bodies of the posterior hypothalamus, as well as generalized cerebral atrophy.[7] These brain regions are all parts of the limbic system, which is heavily involved in emotion and memory.
KS involves neuronal loss, that is, damage to neurons; gliosis, which is a result of damage to supporting cells of the central nervous system, and hemorrhage or bleeding also occurs in mammillary bodies. Damage to the medial dorsal nucleus or anterior nuclei of the thalamus (limbic-specific nuclei) is also associated with this disorder. Cortical dysfunction may have arisen from thiamine deficiency, alcohol neurotoxicity, and/or structural damage in the diencephalon.[8]
Originally, it was thought that a lack of initiative and a flat affect were important characteristics of emotional presentation in sufferers. Studies have questioned this, proposing that neither is necessarily a symptom of KS. Research suggesting that people with Korsakoff syndrome are emotionally unimpaired has made this a controversial topic. It can be argued that apathy, which is a usual characteristic, reflects a deficit of emotional expressions, without affecting the experience or perception of emotion.[9]
KS causes deficits in declarative memory in most people,[10] but leaves implicit spatial, verbal, and procedural memory functioning intact.[11] People with KS have deficits in the processing of contextual information. Context memories refers to the where and when of experiences, and is an essential part of recollection. The ability to store and retrieve this information, such as spatial location or temporal order information, is impaired.[12] Research has also suggested that people with Korsakoff syndrome have impaired executive functions, which can lead to behavioral problems and interfere with daily activities. It is unclear, however, which executive functions are affected most.[13] Nonetheless, IQ is usually not affected by the brain damage associated with Korsakoff's syndrome.[14]
At first it was thought that those with KS used confabulation to fill in memory gaps. However, it has been found that confabulation and amnesia do not necessarily co-occur. Studies have shown that there is dissociation between provoked confabulation, spontaneous confabulation (which is unprovoked), and false memories.[10] That is, people affected could be led to believe certain things had happened which actually had not, but so could people without Korsakoff syndrome.
## Causes[edit]
Conditions resulting in thiamine deficiency and its effects include chronic alcoholism and severe malnutrition.[15] Alcoholism may co-occur with poor nutrition, which in addition to inflammation of the stomach lining, causes thiamine deficiency.[16] Other causes include dietary deficiencies, prolonged vomiting, eating disorders, and the effects of chemotherapy. It can also occur in pregnant women who have a form of extreme morning sickness known as hyperemesis gravidarum.[17] Mercury poisoning can also lead to Korsakoff syndrome.[18] Though it does not always co-occur, this disorder can emerge frequently as a consequential result of Wernicke's encephalopathy.[19]
PET scans show that there is a decrease of glucose metabolism in the frontal, parietal and cingulated regions of the brain in those with Korsakoff syndrome. This may contribute to memory loss and amnesia. Structural neuroimaging has also shown the presence of midline diencephalic lesions and cortical atrophy.[8]
Structural lesions of the central nervous system, though rare, can also contribute to symptoms of KS. Severe damage to the medial dorsal nucleus inevitably results in memory deficit. Additionally, autopsies of people who had KS have showed lesions in both the midline and anterior thalamus, and thalamic infarctions. Bilateral infarctions to the thalamus can result in Korsakoff-induced amnesia as well. These findings imply damage to anterior thalamic nuclei can result in disruptive memory.[20][21]
### Risk factors[edit]
A number of factors may increase a person's risk to develop Korsakoff syndrome. These factors are often related to general health and diet.[22]
* Age
* Alcoholism
* Chemotherapy
* Dialysis
* Extreme dieting
* Genetic factors
## Diagnosis[edit]
KS is primarily a clinical diagnosis; imaging and lab tests are not necessary.
## Prevention[edit]
The most effective method of preventing AKS is to avoid B vitamin/thiamine deficiency. In Western nations, the most common causes of such a deficiency are alcoholism and eating disorders.[21] Because these are behavioral-induced causes, Korsakoff syndrome is essentially considered a preventable disease. Thus, fortifying foods with thiamine, or requiring companies that sell alcoholic beverages to supplement them with B vitamins in general or thiamine in particular, could avert many cases.[23][24]
## Treatment[edit]
It was once assumed that anyone suffering from KS would eventually need full-time care. This is still often the case, but rehabilitation can help regain some, albeit often limited, level of independence.[21] Treatment involves the replacement or supplementation of thiamine by intravenous (IV) or intramuscular (IM) injection, together with proper nutrition and hydration. However, the amnesia and brain damage caused by the disease does not always respond to thiamine replacement therapy. In some cases, drug therapy is recommended. Treatment typically requires taking thiamine orally for 3 to 12 months, though only about 20 percent of cases are reversible. If treatment is successful, improvement will become apparent within two years, although recovery is slow and often incomplete.
As an immediate form of treatment, a pairing of IV or IM thiamine with a high concentration of B-complex vitamins can be administered three times daily for period of 2–3 days. In most cases, an effective response will be observed. A dose of 1 gram of thiamine can also be administered to achieve a clinical response.[25] In those who are seriously malnourished, the sudden availability of glucose without proper bodily levels of thiamine to metabolize is thought to cause damage to cells. Thus, the administration of thiamine along with an intravenous form of glucose is often good practice.[26]
Treatment for the memory aspect of KS can also include domain-specific learning, which when used for rehabilitation is called the method of vanishing cues. Such treatments aim to use intact memory processes as the basis for rehabilitation. Those who used the method of vanishing cues in therapy were found to learn and retain information more easily.[27]
People diagnosed with KS are reported to have a normal life expectancy, presuming that they abstain from alcohol and follow a balanced diet. Empirical research has suggested that good health practices have beneficial effects in Korsakoff syndrome.[26]
## Epidemiology[edit]
Rates varies between country, but it is estimated to affect around 12.5% of heavy drinkers.[28]
## References[edit]
1. ^ "Korsakoff Syndrome - MeSH - NCBI". www.ncbi.nlm.nih.gov.
2. ^ "Korsakoff syndrome". Retrieved 14 October 2020.
3. ^ Nyssen R. (1960). "[Study of "amnesia of fixation" in Korsakoff's disease by non-repeated acquisition tests]". Acta Neurologica et Psychiatrica Belgica (in French). 60: 783–793. PMID 13730001.
4. ^ Nyssen R. (1957). "[Experimental contribution to the study of fixation amnesia in Korsakoff's syndrome of alcoholic origin]". Acta Neurologica et Psychiatrica Belgica (in French). 57 (8): 839–66. PMID 13478443.
5. ^ C. W. M. Whitty; O. L. Zangwill (22 October 2013). Amnesia: Clinical, Psychological and Medicolegal Aspects. Elsevier Science. p. 76. ISBN 978-1-4831-6514-1.
6. ^ Benon R., LeHuché R. (1920). "Cranial Injuries and Korsakoff's Psychosis" [Traumatismes crâniens et psychose de Korsakoff]. Archives Suisses de Neurologie, Neurochirurgie et Psychiatrie (in French): 319.
7. ^ Kolb, Bryan; Whishaw, Ian Q. (2003). Fundamentals of human neuropsychology. New York: Worth Publishers. p. 473. ISBN 978-0-7167-5300-1. OCLC 55617319.
8. ^ a b Paller, K. A.; Acharya, A.; Richardson, Brian C.; Plaisant, Odile; Shimamura, Arthur P.; Reed, Bruce R.; Jagust, William J. (1997). "Functional neuroimaging of cortical dysfunction in alcoholic Korsakoff's syndrome". Journal of Cognitive Neuroscience. 9 (2): 277–293. doi:10.1162/jocn.1997.9.2.277. PMID 23962017.
9. ^ Doulas, J.; Wilkinson, D. A. (1993). "Evidence of normal emotional responsiveness in alcoholic Korsakoff's syndrome in the presence of profound memory impairment". Addiction. 88 (12): 1637–1645. doi:10.1111/j.1360-0443.1993.tb02038.x. PMID 8130702.
10. ^ a b Kessels, Roy P. C.; Kortrijk, Hans E.; Wester, Arie J.; Nys, Gudrun M. S. (1 April 2008). "Confabulation behavior and false memories in Korsakoff's syndrome: Role of source memory and executive functioning". Psychiatry and Clinical Neurosciences. 62 (2): 220–225. doi:10.1111/j.1440-1819.2008.01758.x. PMID 18412846.
11. ^ Oudman, Erik; Van Der Stigchel, Stefan; Wester, Arie J.; Kessels, Roy P.C.; Postma, Albert (2011). "Intact memory for implicit contextual information in Korsakoff's amnesia". Neuropsychologia. 49 (10): 2848–2855. doi:10.1016/j.neuropsychologia.2011.06.010. PMID 21704050.
12. ^ Parkin A. J.; Montaldi D.; Leng N. R.; Hunkin N. M. (1999). "Contextual cueing effects in the remote memory of alcoholic Korsakoff patients and normal subjects". The Quarterly Journal of Experimental Psychology. 42A (3): 585–596. doi:10.1080/14640749008401238. PMID 2236634.
13. ^ Kessels, R. P. C.; Van Oort, R. (2009). "Executive dysfunction in Korsakoff's syndrome: time to revise the DSM criteria for alcohol-induced persisting amnestic disorder?". International Journal of Psychiatry in Clinical Practice. 13 (1): 78–81. doi:10.1080/13651500802308290. PMID 24946125.
14. ^ Oscar-Berman, M. (Jun 2012). "Function and dysfunction of prefrontal brain circuitry in alcoholic Korsakoff's syndrome". Neuropsychol Rev. 22 (2): 154–69. doi:10.1007/s11065-012-9198-x. PMC 3681949. PMID 22538385.
15. ^ Carlson, Neil; Birkett, Melissa (2017). Physiology of Behavior. Pearson. p. 514. ISBN 978-0-13-408091-8.
16. ^ "What is Korsakoff's syndrome?". Alzheimer's Society. October 2008.
17. ^ Jasmin, Luc (13 February 2008). "Wernicke-Korsakoff syndrome". MedlinePlus Medical Encyclopedia. United States National Library of Medicine. Retrieved 16 July 2009.
18. ^ ATSDR. 1999. Toxicological Profile for Mercury. Atlanta, GA:Agency for Toxic Substances and Disease Registry. http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf
19. ^ Pitel A. L.; Zahr N. M.; Jackson K.; Sassoon S. A.; Rosenbloom M. J.; Pfefferbaum A.; Sullivan E. V. (2011). "Signs of preclinical Wernicke's encephalopathy and thiamine levels as predictors of neuropsychological deficits in alcoholism without Korsakoff's syndrome". Neuropsychopharmacology. 36 (3): 580–588. doi:10.1038/npp.2010.189. PMC 3055684. PMID 20962766.
20. ^ Rahme, R; Moussa, R; Awada, A; Ibrahim, I; Ali, Y; Maarrawi, J; Rizk, T; Nohra, G; Okais, N; Samaha, E (April 2007). "Acute Korsakoff-like amnestic syndrome resulting from left thalamic infarction following a right hippocampal hemorrhage". AJNR. American Journal of Neuroradiology. 28 (4): 759–60. PMID 17416834.
21. ^ a b c Kopelman, MD; Thomson, AD; Guerrini, I; Marshall, EJ (Mar–Apr 2009). "The Korsakoff syndrome: clinical aspects, psychology and treatment". Alcohol and Alcoholism. 44 (2): 148–54. doi:10.1093/alcalc/agn118. PMID 19151162.
22. ^ Rosenblum, Laurie B. (March 2011). "Korsakoff's Syndrome". NYU Langone Medical Center. Archived from the original on April 26, 2012. Retrieved February 12, 2012.
23. ^ Harper, CG; Sheedy, DL; Lara, AI; Garrick, TM; Hilton, JM; Raisanen, J (Jun 1, 1998). "Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?". The Medical Journal of Australia. 168 (11): 542–5. doi:10.5694/j.1326-5377.1998.tb139081.x. PMC 3391549. PMID 9640303.
24. ^ Centerwall, BS; Criqui, MH (1978). "Prevention of the Wernicke-Korsakoff syndrome: a cost-benefit analysis". New England Journal of Medicine. 299 (6): 285–9. doi:10.1056/nejm197808102990605. PMID 96343.
25. ^ Carlson, N. R. (2013). Physiology of behavior. Boston: Pearson. 547.
26. ^ a b Cook, CC (May–Jun 2000). "Prevention and treatment of Wernicke-Korsakoff syndrome". Alcohol and Alcoholism Supplement. 35 (1): 19–20. doi:10.1093/alcalc/35.Supplement_1.19. PMID 11304070.
27. ^ Komatsu, Shin-Ichi; Mimura, Masaru; Kato, Motoichiro; Wakamatsu, Naoki; Kashima, Haruo (1 March 2000). "Errorless and Effortful Processes Involved in the Learning of Face-name Associations by Patients with Alcoholic Korsakoff's Syndrome". Neuropsychological Rehabilitation. 10 (2): 113–132. doi:10.1080/096020100389200.
28. ^ Harper, C; Gold, J; Rodriguez, M; Perdices, M (1 February 1989). "The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: a prospective necropsy study". Journal of Neurology, Neurosurgery & Psychiatry. 52 (2): 282–285. doi:10.1136/jnnp.52.2.282. PMC 1032524. PMID 2784828.
## External links[edit]
Classification
D
* ICD-10: F10.6
* ICD-9-CM: 291.1, 294.0
* MeSH: D020915
* DiseasesDB: 14107
External resources
* eMedicine: med/2405
* v
* t
* e
Congenital malformation due to substance exposure
* Fetal alcohol spectrum disorder
* Fetal hydantoin syndrome
* Fetal warfarin syndrome
* Prenatal amphetamine exposure
* Prenatal cannabis exposure
* Prenatal cocaine exposure
* Prenatal nicotine exposure
Other
* Substance use disorder
* v
* t
* e
Malnutrition
Protein-energy
malnutrition
* Kwashiorkor
* Marasmus
* Catabolysis
Vitamin deficiency
B vitamins
* B1
* Beriberi
* Wernicke–Korsakoff syndrome
* Wernicke's encephalopathy
* Korsakoff's syndrome
* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
* Potassium
* Magnesium
* Calcium
* Iron
* Zinc
* Manganese
* Copper
* Iodine
* Chromium
* Molybdenum
* Selenium
* Keshan disease
Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
* Weight loss
* Cachexia
* Underweight
* v
* t
* e
Psychoactive substance-related disorder
General
* SID
* Substance intoxication / Drug overdose
* Substance-induced psychosis
* Withdrawal:
* Craving
* Neonatal withdrawal
* Post-acute-withdrawal syndrome (PAWS)
* SUD
* Substance abuse / Substance-related disorders
* Physical dependence / Psychological dependence / Substance dependence
Combined
substance use
* SUD
* Polysubstance dependence
* SID
* Combined drug intoxication (CDI)
Alcohol
SID
Cardiovascular diseases
* Alcoholic cardiomyopathy
* Alcohol flush reaction (AFR)
Gastrointestinal diseases
* Alcoholic liver disease (ALD):
* Alcoholic hepatitis
* Auto-brewery syndrome (ABS)
Endocrine diseases
* Alcoholic ketoacidosis (AKA)
Nervous
system diseases
* Alcohol-related dementia (ARD)
* Alcohol intoxication
* Hangover
Neurological
disorders
* Alcoholic hallucinosis
* Alcoholic polyneuropathy
* Alcohol-related brain damage
* Alcohol withdrawal syndrome (AWS):
* Alcoholic hallucinosis
* Delirium tremens (DTs)
* Fetal alcohol spectrum disorder (FASD)
* Fetal alcohol syndrome (FAS)
* Korsakoff syndrome
* Positional alcohol nystagmus (PAN)
* Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis)
* Wernicke encephalopathy (WE)
Respiratory tract diseases
* Alcohol-induced respiratory reactions
* Alcoholic lung disease
SUD
* Alcoholism (alcohol use disorder (AUD))
* Binge drinking
Caffeine
* SID
* Caffeine-induced anxiety disorder
* Caffeine-induced sleep disorder
* Caffeinism
* SUD
* Caffeine dependence
Cannabis
* SID
* Cannabis arteritis
* Cannabinoid hyperemesis syndrome (CHS)
* SUD
* Amotivational syndrome
* Cannabis use disorder (CUD)
* Synthetic cannabinoid use disorder
Cocaine
* SID
* Cocaine intoxication
* Prenatal cocaine exposure (PCE)
* SUD
* Cocaine dependence
Hallucinogen
* SID
* Acute intoxication from hallucinogens (bad trip)
* Hallucinogen persisting perception disorder (HPPD)
Nicotine
* SID
* Nicotine poisoning
* Nicotine withdrawal
* SUD
* Nicotine dependence
Opioids
* SID
* Opioid overdose
* SUD
* Opioid use disorder (OUD)
Sedative /
hypnotic
* SID
* Kindling (sedative–hypnotic withdrawal)
* benzodiazepine: SID
* Benzodiazepine overdose
* Benzodiazepine withdrawal
* SUD
* Benzodiazepine use disorder (BUD)
* Benzodiazepine dependence
* barbiturate: SID
* Barbiturate overdose
* SUD
* Barbiturate dependence
Stimulants
* SID
* Stimulant psychosis
* amphetamine: SUD
* Amphetamine dependence
Volatile
solvent
* SID
* Sudden sniffing death syndrome (SSDS)
* Toluene toxicity
* SUD
* Inhalant abuse
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Korsakoff syndrome | c0349464 | 4,113 | wikipedia | https://en.wikipedia.org/wiki/Korsakoff_syndrome | 2021-01-18T18:37:00 | {"gard": ["6843"], "mesh": ["D020915"], "umls": ["C0349464"], "icd-9": ["294.0"], "icd-10": ["F04"], "wikidata": ["Q622901"]} |
A number sign (#) is used with this entry because thyroid dyshormonogenesis-1 (TDH1) is caused by homozygous or compound heterozygous mutation in the sodium-iodide symporter (NIS) gene (SLC5A5; 601843) on chromosome 19p13.
Description
Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). Dyshormonogenesis can be caused by recessive defects at any of the steps required for normal thyroid hormone synthesis. In untreated patients thyroid dyshormonogenesis is typically associated with goitrous enlargement of the thyroid secondary to long-term thyrotropin (TSH; see 188540) stimulation.
Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder.
### Genetic Heterogeneity of Thyroid Dyshormonogenesis
Other forms of thyroid hormone dysgenesis include TDH2A (274500), caused by mutation in the thyroid peroxidase gene (TPO; 606765) on 2p25; Pendred syndrome, a form of thyroid hormone dysgenesis associated with deafness (TDH2B; 274600) and caused by mutation in the SLC26A4 gene (605646) on 7q31; TDH3 (274700), caused by mutation in the thyroglobulin gene (TG; 188450) on 8q24; TDH4 (274800), caused by mutation in the iodotyrosine deiodinase gene (IYD; 612025) on 6q25; TDH5 (274900), caused by mutation in the DUOXA2 gene (612772) on 15q21; and TDH6 (607200), caused by mutation in the DUOX2 gene (606759) on 15q21.
Clinical Features
A defect in thyroid hormonogenesis is characterized by an inability of the thyroid to maintain a concentration difference of readily exchangeable iodine between the plasma and the thyroid gland. The defect is also found in the salivary gland and gastric mucosa. It is presumed to arise either because of a deficient supply of energy for the transport system or because of abnormality of a carrier or receptor substance. Parental consanguinity was present in the case of Stanbury and Chapman (1960). Medeiros-Neto et al. (1972) described a brother and sister with a partial defect. Affected sibs were reported by Gilboa et al. (1963), Toyoshima et al. (1977), and others.
Fujiwara et al. (1997) studied a patient in whom an iodide transport defect was diagnosed on the basis of failure to concentrate radioiodide by the salivary gland (saliva/plasma (123)I ratio was 1.6, in contrast to the normal ratio of more than 20) and the clinical and biologic response to potassium iodide treatment. The patient's physical findings and serum thyrotropin T4 and T3 levels were maintained at normal levels by the treatment. However, mild goiter and multiple mass lesions developed in one lobe of the thyroid and then in the other lobe at 8 and 11 years of age, respectively. The tumor removed from the left lobe was found to be follicular adenoma. Resected thyroid from the patient was used as a source of RNA for the production of cDNA by reverse transcriptase.
Kempers et al. (2009) examined the body surface of 242 Dutch patients with congenital hypothyroidism (CH) of thyroidal origin with thyroid agenesis, an ectopic thyroid rudiment, or eutopic thyroid gland, for visually detectable morphologic abnormalities. The percentage of patients with 1 or more major anomalies in the total CH cohort (33%) and in patients with ectopic thyroid (37.2%) was significantly higher than in 1,007 Dutch controls (21.8%; p less than 0.001), and specific major malformations such as bilateral ear pits and oligodontia were more frequent in the group of patients with ectopic thyroid. In addition, the percentage of patients in the CH cohort with 1 or more minor anomalies (96.3%) was significantly higher than in the control group (82.5%; p less than 0.001).
Molecular Genetics
In a patient with hypothyroidism who was suspected of having an iodide transport defect, Fujiwara et al. (1997) identified homozygosity for a missense mutation in the SLC5A5 gene (T354P; 601843.0001).
In a Japanese patient with iodide transport defect, Kosugi et al. (1998) identified compound heterozygous missense mutations in the SLC5A5 gene: T354P and G93R (601843.0005).
INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation HEAD & NECK Mouth \- Macroglossia (not always present) Neck \- Goiter (not always present) \- Thyroid nodules, hyperplastic and adenomatous ABDOMEN External Features \- Umbilical hernia (in some patients) Gastrointestinal \- Constipation SKIN, NAILS, & HAIR Skin \- Dry skin NEUROLOGIC Central Nervous System \- Mental retardation (if untreated in infancy) Behavioral Psychiatric Manifestations \- Lethargy (when taken off of medication) ENDOCRINE FEATURES \- Thyroid iodine accumulation defect \- Hypothyroidism LABORATORY ABNORMALITIES \- Low T4 \- Low RAI (radioactive iodine) uptake MISCELLANEOUS \- Hypothyroidism is less severe in individuals with high dietary iodine intake \- Preferably treated with iodine supplementation rather than thyroid hormone replacement MOLECULAR BASIS \- Caused by mutation in the solute carrier family 5 (sodium iodide symporter), member 5 gene (SLC5A5, 601843.0001 ) ▲ 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
| THYROID DYSHORMONOGENESIS 1 | c1848805 | 4,114 | omim | https://www.omim.org/entry/274400 | 2019-09-22T16:21:41 | {"mesh": ["C564766"], "omim": ["274400"], "orphanet": ["95716"], "synonyms": ["HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 1", "THYROID HORMONOGENESIS, GENETIC DEFECT IN, 1", "Alternative titles", "IODINE ACCUMULATION, TRANSPORT, OR TRAPPING DEFECT", "Thyroid dyshormonogenesis"]} |
Cenesthopathy (from French: cénestopathie,[1] formed from the Ancient Greek κοινός (koinós) „common“, αἴσθησῐς (aísthēsis) „feeling“, „perception“ + πᾰ́θος (páthos) „feeling, suffering, condition“), also known as coenesthesiopathy,[2] is a rare psychiatric term used to refer to the feeling of being ill and this feeling is not localized to one region of the body.[3] Most notably, cenesthopathies are characterized by aberrant and strange bodily sensations (for example, a feeling of wires or coils being present within the oral region; tightening, burning, pressure, tickling etc. occurring in various parts of the body, and so on).[4]
## Contents
* 1 Classification of cenesthopathies
* 2 Cenesthopathic schizophrenia
* 3 History
* 4 References
## Classification of cenesthopathies[edit]
Type [2][5] Etymology Clinical description
Coenesthesiopathy (cenesthopathy) "Coenesthesia" (κοινός + [αἴ]σθησῐς) + -"pathy". A pathological alteration in the sense of bodily being, caused by abnormal, bizarre sensations in the body.
Hypercoenesthesiopathy (hypercenesthopathy) ("hyper-", from Ancient Greek ὑπέρ (hupér, "excess") + "coenesthesiopathy") A hypertrophic alteration in the sense of bodily being, caused by abnormal, bizarre sensations in the body.
Hypocoenesthesiopathy (hypocenesthopathy) ("hypo-", from Ancient Greek ὑπό (hupó, "under") + coenesthesiopathy) A hypotrophic alteration in the sense of bodily being, caused by abnormal, bizarre sensations in the body.
Paracoenesthesiopathy (paracenesthopathy) ("para-", from Ancient Greek παρά (pará, "beside, by, contrary to") + coenesthesiopathy) A qualitative alteration in the sense of bodily being, caused by abnormal, bizarre sensations in the body.
Acoenesthesiopathy[note 1] (acenesthopathy) ("a-", from Ancient Greek ἀ- (a-, "not") + coenesthesiopathy) A total absence of the sense of physical existence.
## Cenesthopathic schizophrenia[edit]
The established occurrence of coenesthetic hallucinations in 18 % of individuals with a psychiatric diagnosis of schizophrenia has led to the formulation of a separate subgroup of schizophrenia in the ICD-10, called cenesthopathic schizophrenia.[2] Cenesthopathic schizophrenia is included (but not defined) within the category "other schizophrenia" (F20.8) in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems.[6][7]
## History[edit]
Cenesthopathy (originally French: cénestopathie) is a term created in 1907 by the French neuro-psychiatrists Ernest Ferdinand Pierre Louis Dupré and Paul Camus.[1][8][9]
## References[edit]
Look up cenesthopathy in Wiktionary, the free dictionary.
Look up coenesthesiopathy in Wiktionary, the free dictionary.
Notes
1. ^ Also known as acenesthesia, or total asomatognosia.
Sources
1. ^ a b Dupré E. (1925). "Chapitre IV: Les Cénestopathies". Pathologie de l'imagination et de l'émotivité. Bibliothèque Scientifique (in French). Paris: Payot. p. 291. OCLC 459305905.
2. ^ a b c Blom, Jan Dirk (2013). "The Basics of Hallucinations: Hallucinations and Other Sensory Deceptions in Psychiatric Disorders". The Neuroscience of Hallucinations. New York, NY: Springer. pp. 43–57. doi:10.1007/978-1-4614-4121-2_3. ISBN 978-1-4614-4120-5.
3. ^ Berrios, G. E. (1982-04-01). "Tactile hallucinations: conceptual and historical aspects". Journal of Neurology, Neurosurgery & Psychiatry. 45 (4): 285–293. doi:10.1136/jnnp.45.4.285. ISSN 1468-330X. PMC 491362. PMID 7042917.
4. ^ Umezaki, Y.; Miura, A.; Watanabe, M.; Takenoshita, M.; Uezato, A.; Toriihara, A.; Nishikawa, T.; Toyofuku, A. (2016). "Oral cenesthopathy". BioPsychoSocial Medicine. 10: 20. doi:10.1186/s13030-016-0071-7. PMC 4903001. PMID 27293481.
5. ^ Blom, J. D.; Neven, A.; Aouaj, Y.; Jonker, B.; Hoek, H. W. (2010). "De coenesthesiopathieën" [The cenesthesiopathies] (PDF). Tijdschrift voor Psychiatrie (in Dutch). 52 (10): 695–704. PMID 20931483. Retrieved April 16, 2019.
6. ^ Jenkins, Gary; Röhricht, Frank (2007). "From Cenesthesias to Cenesthopathic Schizophrenia: A Historical and Phenomenological Review". Psychopathology. 40 (5): 361–368. doi:10.1159/000106314. ISSN 0254-4962. PMID 17657136.
7. ^ World Health Organization (2016). "International Statistical Classification of Diseases and Related Health Problems 10th Revision: F20.8 Other schizophrenia". Retrieved April 16, 2019.
8. ^ Dupré, Ernest; Camus, Paul (1907). "Les cénestopathies". Bulletin Médical (in French): 713–714.
9. ^ Dupré, Ernest; Camus, Paul (1907). "Les cénestopathies". L'Encéphale (in French): 616–631.
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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
| Cenesthopathy | None | 4,115 | wikipedia | https://en.wikipedia.org/wiki/Cenesthopathy | 2021-01-18T18:35:45 | {"wikidata": ["Q3919140"]} |
A number sign (#) is used with this entry because of evidence that Harel-Yoon syndrome (HAYOS) is caused by heterozygous mutation in the ATAD3A gene (612316) on chromosome 1p36. One family with autosomal recessive inheritance has been reported.
Description
Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. Other more variable features such as optic atrophy may also occur. Laboratory studies in some patients show evidence of mitochondrial dysfunction (summary by Harel et al., 2016).
Clinical Features
Harel et al. (2016) reported 5 unrelated children ranging from 23 months to 9 years of age with a syndromic neurodevelopmental disorder. All had severely delayed psychomotor development with intellectual disability and poor or absent speech. The patients had truncal hypotonia, and all except the youngest showed appendicular spasticity and peripheral axonal neuropathy with atrophy of the lower limb muscles. Only the 9-year-old patient could walk, and she had a spastic crouched gait. Two patients had hypertrophic cardiomyopathy and 3 had optic atrophy. None had seizures. Additional variable features included poor feeding, sleep difficulties, myopia, nystagmus, and esotropia. Some patients had skeletal anomalies, such as pectus carinatum, scoliosis, hip dysplasia, or foot deformities. Some patients had dysmorphic features, including high forehead, small nose, deep-set eyes, and micrognathia, but there was not a common pattern. Three patients had evidence of mitochondrial dysfunction, including increased serum lactate, deficiencies of mitochondrial respiratory enzymes, and methylglutaconic aciduria.
### Clinical Variability
Harel et al. (2016) reported 2 adult sibs, born of distantly related Italian parents, with HAYOS. The transmission pattern in this family was consistent with autosomal recessive inheritance. The patients had delayed development since infancy, language delay, hypotonia, congenital cataracts, and ataxic gait. One had mild intellectual disability. Dysmorphic facial features included long face, triangular nose, and prognathia with a prominent chin. Both patients developed absence seizures around 6 to 7 years of age. Other features included mildly delayed puberty and delayed bone age. Brain imaging showed progressive cerebellar atrophy and hypoplastic optic nerves. Mitochondrial respiratory chain enzyme analysis in muscle and fibroblasts showed normal activities. Whole-exome sequencing identified a homozygous missense variant in the ATAD3A gene (T53I; 612316.0002); functional studies of the variant were not performed. Each unaffected parent was heterozygous for the mutation.
Molecular Genetics
In 5 unrelated children with HAYOS, Harel et al. (2016) identified a recurrent de novo missense mutation in the ATAD3A gene (R528W; 612316.0001). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the R528W variant were not performed. Fibroblasts from 1 patient showed decreased mitochondria and mitophagic vesicles. Generation of the homologous mutation (R534W) in the Drosophila 'bor' gene resulted in lethality when expressed ubiquitously, in all neurons, or in motor neurons. Muscle-specific expression of the mutation in Drosophila led to 90% lethality and was associated with decreased mitochondrial content, aberrant mitochondrial morphology, and increased autophagic vacuoles. These findings suggested that the mutation acts as a toxic gain-of-function allele and results in decreased mitochondria in neurons and muscle.
INHERITANCE \- Autosomal dominant \- Autosomal recessive (one family) HEAD & NECK Head \- High forehead Face \- Frontal bossing \- Micrognathia \- Prognathia (family A) \- Long face (family A) Eyes \- Optic atrophy \- Deep-set eyes \- Upslanting palpebral fissures \- Myopia \- Nystagmus \- Esotropia Nose \- Small nose CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy (in some patients) CHEST External Features \- Pectus carinatum ABDOMEN Gastrointestinal \- Feeding difficulties SKELETAL Spine \- Scoliosis Pelvis \- Hip dysplasia Feet \- Foot deformities MUSCLE, SOFT TISSUES \- Hypotonia \- Distal limb muscle atrophy \- Mitochondrial respiratory enzymes deficiencies NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Speech delay \- Inability to walk \- Ataxia (family A) \- Axial hypotonia \- Limb spasticity \- Absence seizures (family A) \- Cerebellar atrophy (family A) Peripheral Nervous System \- Axonal neuropathy LABORATORY ABNORMALITIES \- Increased lactate \- Methylglutaconic aciduria (in some patients) MISCELLANEOUS \- Onset in infancy \- Five unrelated patients with de novo heterozygous mutations have been reported \- Two sibs (family A) with a homozygous mutation have been reported (last curated November 2016) MOLECULAR BASIS \- Caused by mutation in the ATPase family, AAA domain-containing, member 3A gene (ATAD3A, 612316.0001 ) ▲ 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
| HAREL-YOON SYNDROME | c4310677 | 4,116 | omim | https://www.omim.org/entry/617183 | 2019-09-22T15:46:35 | {"omim": ["617183"], "orphanet": ["496790"], "synonyms": ["Harel-Yoon syndrome"]} |
A number sign (#) is used with this entry because autosomal recessive distal renal tubular acidosis (dRTA) with hemolytic anemia is caused by mutation in the SLC4A1 gene (109270).
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive distal RTA, see 267300.
Clinical Features
Tanphaichitr et al. (1998) described a Thai brother and sister with autosomal recessive distal RTA and hemolytic anemia. The male proband presented at age 3.5 years with a history of lethargy, anorexia, and slow growth. Physical examination showed height and weight less than the third percentile, pallor, and hepatosplenomegaly. Hypokalemia, hyperchloremic metabolic acidosis, and normal creatinine were accompanied by isosthenuria and alkaline urinary pH, bilateral nephrocalcinosis, and rachitic bone changes. Mild anemia (hematocrit 11 g/dl) with microcytosis, reticulocytosis, and a peripheral smear consistent with a xerocytic type of hemolytic anemia were accompanied by homozygosity for hemoglobin E, a clinically benign hemoglobin frequently encountered in Southeast Asia. The sister showed similar findings.
Molecular Genetics
Tanphaichitr et al. (1998) described novel SLC4A1 mutations in a Thai family with a recessive syndrome of distal renal tubular acidosis and hemolytic anemia in which red cell anion transport was normal. A brother and sister were triply homozygous for 2 benign mutations, M31T and K56E (109270.0001), and for a loss-of-function mutation, G701D (109270.0016). The genetic and functional data suggested that the homozygous SLC4A1 G701D mutation caused recessively transmitted dRTA in this kindred with apparently normal erythroid anion transport.
Bruce et al. (2000) studied 3 Malaysian and 6 Papua New Guinean families with dRTA and Southeast Asian ovalocytosis (SAO; 166900). The SAO deletion mutation (109270.0002) in the SLC4A1 gene occurred in many of the families but did not itself result in dRTA. Compound heterozygotes of each of 3 dRTA mutations (G701D; A858D, 109270.0020; and delV850, 109270.0021) with SAO all had dRTA, evidence of hemolytic anemia, and abnormal red cell properties. The A858D mutation showed dominant inheritance and the recessive delV850 and G701D mutations showed a pseudodominant phenotype when the transport-inactive SAO allele was also present.
Sritippayawan et al. (2004) reported 2 Thai families with recessive dRTA due to different compound heterozygous mutations of the SLC4A1 gene. In the first family, the proband was a 5-year-old boy with dRTA, rickets, failure to thrive, nephrocalcinosis, and hypokalemic/hyperchloremic metabolic acidosis with a urine pH of 7.00. He had a normal hemoglobin level and normal red cell morphology. The proband was found to have compound heterozygous G701D (109270.0016)/S773P (109270.0026) mutations, inherited from his clinically normal mother and father, respectively. In the second family, a 19-year-old man and his 15-year-old sister had dRTA and Southeast Asian ovalocytosis, and were compound heterozygotes for the SAO deletion mutation (109270.0002) and an R602H mutation (109270.0027). Their mother had SAO and an unaffected brother was heterozygous for the R602P mutation. Sritippayawan et al. (2004) noted that the second patient had a severe form of dRTA whereas his sister had only mild metabolic acidosis, indicating that other modifying factors or genes might play a role in governing the severity of the disease.
Population Genetics
Yenchitsomanus et al. (2002) found that all Thai patients with autosomal recessive dRTA caused by homozygosity for the G701D mutation originated from northeastern Thailand. Yenchitsomanus et al. (2003) confirmed the higher allele frequency of the G701D mutation in this population. This suggested that the G701D allele might have arisen in northeastern Thailand. The presence of patients with dRTA who were compound heterozygotes for the Southeast Asian ovalocytosis deletion mutation and G701D in southern Thailand and Malaysia and their apparent absence in northeastern Thailand indicated that the G701D allele may have migrated to the southern peninsula region where SAO is common, resulting in pathogenic allelic interaction.
INHERITANCE \- Autosomal recessive GROWTH Height \- Height less than 3rd percentile Weight \- Weight less than 3rd percentile Other \- Failure to thrive ABDOMEN Liver \- Hepatosplenomegaly Spleen \- Hepatosplenomegaly Gastrointestinal \- Anorexia GENITOURINARY Kidneys \- Nephrocalcinosis \- Renal tubular acidosis, distal \- Isothenuria SKELETAL \- Rachitic bone changes SKIN, NAILS, & HAIR Skin \- Pallor NEUROLOGIC Central Nervous System \- Lethargy METABOLIC FEATURES \- Hyperchloremic metabolic acidosis HEMATOLOGY \- Hemolytic anemia (in some patients) \- Microcytosis (in some patients) \- Reticulocytosis (in some patients) LABORATORY ABNORMALITIES \- Hypokalemia MOLECULAR BASIS \- Caused by mutation in the solute carrier family 4, anion exchanger, member 1 gene (SLC4A1, 109270.0016 ) ▲ 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
| RENAL TUBULAR ACIDOSIS, DISTAL, WITH HEMOLYTIC ANEMIA | c1969038 | 4,117 | omim | https://www.omim.org/entry/611590 | 2019-09-22T16:03:06 | {"mesh": ["C566910"], "omim": ["611590"], "orphanet": ["93610", "18"], "synonyms": ["Alternative titles", "RTA, DISTAL, AUTOSOMAL RECESSIVE, WITH HEMOLYTIC ANEMIA"]} |
A rare, slowly progressive form of systemic mastocytosis (SM) characterized by gradual accumulation of neoplastic mast cells in the visceral organs. Patients typically present with splenomegaly, hypercellular marrow and, in most cases, urticaria pigmentosa-like skin lesions.
## Epidemiology
The prevalence and incidence is unknown.
## Clinical description
The age of onset of smoldering systemic mastocytosis (SSM) is in adulthood, with patients tending to be slightly older than those with isolated SM (ISM). The disease is defined by the presence of at least two B-findings, indicative of a high mast cell (MC) burden, and no C findings (organ dysfunction). There is a pronounced MC infiltration (>30% in bone marrow (BM) biopsy), organomegaly and tryptase levels above 200 ng/ml. The clinical course is characterized by slow progression without signs of aggressive disease or an associated hematologic neoplasm (AHN). Patients may remain stable for years or may progress into a more advanced variant (aggressive SM (ASM), mast cell leukemia (MCL) or SM with an AHN).
## Etiology
Although the etiology of SSM is not fully understood, an activating mutation of KIT, usually KIT D816V, is found in the MCs of virtually all SSM cases. This mutation probably accounts for the abnormal accumulation of MCs in organ(s)/tissue(s). Multilineage KIT D816V involvement is constantly found in SSM patients.
## Diagnostic methods
Diagnosis of SSM is achieved by first establishing a diagnosis of SM, based on the WHO consensus criteria. The disease is then categorized according to the presence of B-findings and C-findings. For SSM, at least two B-findings (but no C-findings) should be present.
## Differential diagnosis
Differential diagnoses include all the other forms of SM, as well as other causes of MC activation syndromes (MCAS): primary (clonal, but not fulfilling SM diagnostic criteria) MCAS; secondary MCAS where an IgE-dependent allergy or another reactive inflammatory disease process is present; and idiopathic MCAS where neither clonal MC nor an IgE-dependent allergy or another underlying condition/disease can be documented. Additional differential diagnoses include other forms of mastocytosis (pure cutaneous mastocytosis, indolent SM, aggressive SM), endocrine disorders (adrenal tumors, VIPoma, gastrinoma), and some gastrointestinal pathologies. Waldenström disease should also be distinguished.
## Management and treatment
In stable SSM patients, symptomatic treatment may be the only therapy. Avoidance of known triggers, prophylactic prescription of an epi-pen, and medications such as antihistamines, antileukotrienes, cromolyn sodium, omalizumab and aspirin may all have a role in the prevention or treatment of MC-mediated symptoms. Regular follow-up and assessment for transformation to more aggressive disease variants is required. Serum tryptase, which may be used to assess disease response, may be evaluated biannually to monitor disease activity and appropriately adjust therapy. In patients who progress to more advanced variants of the disease, introduction of targeted or non-targeted cytoreductive therapy may be discussed. Whilst favorable results have been seen with the current targeted and non-targeted treatment, a consensus on treatment in patients with SSM has not been reached.
## Prognosis
Some SSM patients may remain stable for years, while others may progress to more advanced variants of the disease (ASM or MCL), with a poorer prognosis. In general, the prognosis of SSM regarding progression-free survival and overall survival is better than that of ASM or MCL, but. poorer than in typical ISM.
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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
| Smoldering systemic mastocytosis | c3897042 | 4,118 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=158775 | 2021-01-23T17:04:16 | {"icd-10": ["C96.2"]} |
A number sign (#) is used with this entry because of evidence that Floating-Harbor syndrome (FLHS) is caused by heterozygous mutation in the SRCAP gene (611421) on chromosome 16p11.
Description
Floating-Harbor syndrome is a rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips (Lacombe et al., 1995).
Rubinstein-Taybi syndrome (see 180849), which shows phenotypic overlap with Floating-Harbor syndrome, is caused by mutation in the CREBBP gene (600140), for which SRCAP is a coactivator.
Clinical Features
Robinson et al. (1988) used the designation Floating-Harbor syndrome for a syndrome that was first described by Pelletier and Feingold (1973) in a boy seen at the Boston Floating Hospital and by Leisti et al. (1975) in a patient at the Harbor General Hospital in Torrance, California. The syndrome is characterized by a triad of short stature with significantly delayed bone age; expressive language delay, usually in the presence of normal motor development; and a triangular face with a prominent nose and deep-set eyes.
Feingold (2006) provided a 32-year clinical follow-up of the first patient with Floating-Harbor syndrome reported by Pelletier and Feingold (1973). At 37 years of age, the patient was in good health except for arthritis and hypertension. His facial appearance remained fairly characteristic with low hairline, broad nasal tip, short nasal labial distance, depressed columella, thin lips, and posteriorly positioned ears. His stature remained short, and he had mild to moderate mental retardation. Feingold (2006) emphasized that the correct diagnosis of the syndrome should be based on the characteristic facial features.
Patton et al. (1991) reviewed 7 families, each with a single affected patient. Two of the 7 were male. The chromosome studies were normal. Only one of the cases was the product of a consanguineous marriage, a third-cousin Iranian union. No information on parental age was provided. It is possible that this represents a new dominant mutation.
Chudley and Moroz (1991) reported the case of a 17-year-old girl with celiac disease and features consistent with Floating-Harbor syndrome. Celiac disease had been reported in 1 of 6 previously reported cases. Majewski and Lenard (1991) reported the presumed seventh case.
Lacombe et al. (1995) reported a case and reviewed 16 cases from the literature. The father was 54 years old and the mother 41. Growth and speech development were delayed throughout infancy, although motor development was normal. Proportionate short stature and characteristic face, which was triangular with broad and bulbous nose with a prominent nasal bridge, large nares, and a wide columella below the level of the nares, were described. Other facial features included glabella angioma, short philtrum, and thin upper and lower lips. There was brachyphalangy and bilateral fifth finger clinodactyly. At the age of 7 years and 9 months, she had the bone age of a 3-year-old. Dominant inheritance was suggested by the fact that the patient's mother had short stature (138 cm), mild mental retardation, and facial appearance resembling her daughter with a bulbous nose, thin lips, and brachyphalangy of hands and feet.
Smeets et al. (1996) reported a girl with typical manifestations of the syndrome. The authors noted that marked speech delay and odd and hyperkinetic behavior may also be found in small children with Shprintzen velocardiofacial syndrome (192430).
Ala-Mello and Peippo (1996) described a 6-year-old boy of Finnish origin who, in addition to typical manifestations of the syndrome, had unusual high-pitched voice and supernumerary upper incisor, 2 features that had not been reported in other patients. Abnormal high titers of gliadin antibodies suggesting celiac disease were also found in this boy. Celiac disease had been described in at least 3 other patients with Floating-Harbor syndrome. Ala-Mello and Peippo (1996) suggested that all patients with this syndrome should be examined for celiac disease.
Ala-Mello and Peippo (2004) reported follow-up on the Finnish patient they reported in 1996. Reexamination at age 14 years showed classic facial features of the syndrome, with a more pronounced nose, prognathism, and hypoplasia of the maxilla. He had also had recurrent middle ear infections. Growth rate had accelerated (height at -0.7 SD), hands and feet were small (less than third percentile), and his pubertal stage was Tanner P3G3 with normal testicular size and normal bone age. His high-pitched voice described earlier was no longer so pronounced. Reticulin and gliadin antibody titers were normal.
Davalos et al. (1996) described a 6-year-old Mexican girl whose clinical picture (short stature with delayed bone age, language difficulties, and triangular face with prominent nose) was compatible with the diagnosis of Floating-Harbor syndrome. Neuropsychologic evaluation disclosed mild mental retardation, constructive apraxia, and comprehensive and expressive language impairment. Sixteen previously described patients were reviewed.
Midro et al. (1997) reported this syndrome in a 9-year-old girl who showed short stature, delayed bone age, mild mental retardation, speech problems, and specific craniofacial features.
A girl with Floating-Harbor syndrome reported by Hersh et al. (1998) showed trigonocephaly due to metopic suture synostosis, preauricular pit, hypoplastic thumb, subluxated radial head, and Sprengel deformity. From a review of other cases they suggested that trigonocephaly may be an important craniofacial manifestation recognizable in infancy but becoming less noticeable later when the face develops a triangular shape, accentuated by a broad and bulbous nose.
Wieczorek et al. (2001) reported 2 female patients, aged 11 and 8 years, with clinical findings consistent with Floating-Harbor syndrome. The first patient presented with characteristic facial features (large nose with wide columella and hypoplastic alae nasi, short philtrum, and prominent chin), brachydactyly, broad thumbs, and delayed speech development, but less pronounced short stature than previously reported. The second patient presented with short stature, characteristic facial features, brachydactyly, and delayed speech as well as mental development; she was successfully treated with growth hormone. Wieczorek et al. (2001) commented on the facial similarity of their 2 patients with the patient reported by Houlston et al. (1994) and reproduced pictures for comparison. They also commented on a similarity of the metacarpal phalangeal pattern profiles (MCPP) in their patients and in previously reported patients.
Penaloza et al. (2003) suggested Floating-Harbor syndrome as the diagnosis in a 2-year-old boy with short stature, retarded speech development, delayed bone age, a bulbous nose, wide columella, and thin lips. Intestinal biopsy revealed villous atrophy compatible with celiac disease. The mother was thought to have minor phenotypic characteristics, supporting the possibility of dominant inheritance. She had a triangular face, deep-set eyes, a wide columella, and thin lips.
Ioan and Fryns (2003) described 2 sisters with clinical histories and physical findings most compatible with the diagnosis of Floating-Harbor syndrome. Family data favored autosomal recessive inheritance, although germinal mosaicism for an autosomal dominant mutation could not be excluded. Both sisters had microcephaly and developmental delay, with expressive language being severely retarded. Both were of short stature and had distinct craniofacial appearance: triangular face with deeply-set eyes, large and bulbous nose with wide columella, short philtrum, high-arched palate, and low-set ears.
Wiltshire et al. (2005) reported a patient with Floating-Harbor syndrome complicated by a tethered spinal cord. She had typical facies, delayed bone age, delay in expressive speech, and short stature treated with growth hormone. At age 6 years, she developed daytime enuresis, gait disturbance, hyperreflexia of the lower limbs, and extensor plantar responses. Spinal MRI showed tethered cord with a small lipoma. Surgical repair was successful. Wiltshire et al. (2005) suggested that increased growth velocity associated with growth hormone therapy may have unmasked the tethered cord in this patient.
Karaer et al. (2006) reported an 8-year-old Turkish girl with microcephaly, normal psychomotor development with speech delay and a high-pitched voice, triangular face with temporal narrowing and posteriorly angulated ears, upslanting palpebral fissures, deep-set eyes with long eyelashes, large and protruding nose with wide columella and hypoplastic alae nasi, high-arched palate, and supernumerary incisor. She had short stature with delayed bone age, small hands and feet with hypermobile and hyperextensible fingers, and hirsutism, especially on the upper arms and shoulders. Her intellectual abilities were in the average range, but she had hyperactivity disorder and learning disabilities. She had constipation but no evidence of celiac disease. Karaer et al. (2006) stated that this was the first female Turkish patient with Floating-Harbor syndrome.
Paluzzi et al. (2008) reported a woman who was diagnosed at 4.5 years of age with Floating-Harbor syndrome based on dysmorphic facial features involving a prominent nose with broad nares, short upper lip with a wide mouth, and a small jaw, in association with good perceptive language but delayed expressive speech, a petit mal seizure disorder, and short stature with delayed bone age. At 22 years of age, the patient presented with severe headache, vomiting, and neck stiffness and was found to have a ruptured aneurysm of the left internal carotid artery by CT angiography, which was successfully embolized. Fenestration of the distal internal carotid artery was also noted on the angiogram.
White et al. (2010) reported 10 patients with a diagnosis of Floating-Harbor syndrome, including 1 previously studied patient ('patient 5' of Robinson et al., 1988). Serial photographs of the patients demonstrated that the dysmorphic facial features of FLHS are age-related. In infancy and early childhood, deep-set eyes with relatively short palpebral fissures, a triangular configuration to the nasal tip, and a thin upper lip vermilion are seen; however, in later childhood, the classic facial appearance alters substantially, with widening of the palpebral fissures, which makes the eyes appear less deep-set, and increasing prominence of the nasal tip. In addition, bone age data in this study indicated that it is a reliable diagnostic feature under the age of 6 years, but may be normal in otherwise typical patients from 6 years to puberty. White et al. (2010) argued that the disorder of speech and language is more severe than previously recognized, noting that children with FLHS have difficulties with all facets of motor speech production and that language, literacy, and social aspects of communication are severely impaired. Consistent with previous reports, most patients in this study were rated as having borderline normal intellectual function or a mild intellectual disability, and noted as having abnormal hands, albeit with variable features.
Nelson et al. (2009) described a 5-year-old boy with short stature, delayed bone age, expressive language delay, developmental delay, and facial anomalies consistent with Floating-Harbor syndrome, who also developed an intramedullary ganglioglioma extending from T7 to the conus. The authors stated that this was the first report of a tumor associated with FLHS.
In a 9-year-old Turkish girl with Floating-Harbor syndrome who was being evaluated for hearing loss that showed only minimal improvement after the placement of grommets, Hendrickx et al. (2010) performed high-resolution CT of the temporal bone and observed bilateral prominent soft-tissue thickening between the head of the malleus and the anterior wall of the atticus. In addition, on the right, there was fusion of the head of the malleus with the body of the incus, whereas on the left, narrowing of the articulation between malleus and incus was seen. Hendrickx et al. (2010) stated that this was the first reported abnormal middle ear anatomy in a patient with FLHS.
Inheritance
Reports of Floating-Harbor syndrome have suggested autosomal dominant (e.g., Lacombe et al., 1995) or autosomal recessive (e.g., Ioan and Fryns, 2003) inheritance.
White et al. (2010) described a mother-daughter pair, in which the daughter had delayed bone age and facial features that were characteristic of FLHS, whereas the mother had features showing similarity to FLHS. Both had short stature and speech/language difficulties like those of FLHS patients.
Molecular Genetics
Hood et al. (2012) performed exome capture and high-throughput sequencing in 5 unrelated probands with Floating-Harbor syndrome, including 2 patients (patients 9 and 10) previously studied by White et al. (2010), and identified heterozygosity in all 5 probands for 3 truncating variants in the SRCAP gene (611421.0001-611421.0003, respectively). Analysis of SRCAP in an additional 8 probands, including 'patient 8' of White et al. (2010), identified 6 with heterozygosity for 2 of the previously identified mutations, respectively (611421.0001; 611421.0002), as well as 2 with heterozygosity for 2 more frameshift mutations. The mutations were shown to be de novo in all 6 instances in which parental DNA was available, and none were represented in the dbSNP (build 131), 1000 Genomes Project, or NHLBI Exome Variant Server. The authors stated that the phenotype of mutation-positive individuals was concordant with earlier descriptions of FLHS, and that nearly all individuals had short stature and expressive language impairment. However, despite the remarkable similarity among mutations in these patients, all of which were truncating mutations tightly clustered in the last exon of the SRCAP gene, cognitive outcomes ranging from 'normal' to 'significant intellectual disability' were reported, suggesting that genetic modifiers and/or environmental factors might be involved.
By whole-exome sequencing followed by Sanger sequencing, Le Goff et al. (2013) identified heterozygous mutations in the SRCAP gene in 6 of 9 patients with Floating-Harbor syndrome (see, e.g., 611421.0001, 611421.0002, and 611421.0004). There were no major clinical differences between the mutation-positive patients and those in whom no mutation was found. Le Goff et al. (2013) concluded that Floating-Harbor syndrome is a clinically homogeneous but genetically heterogeneous condition, although they noted that partial intragenic deletions or mutations in the introns or promoter region could not be excluded in the mutation-negative patients.
Kehrer et al. (2014) identified a de novo heterozygous truncating mutation in exon 33 of the SRCAP gene (Q2334X; 611421.0005) in a German boy with FLHS. Kehrer et al. (2014) noted that this was the first reported SRCAP mutation that was not in exon 34. Functional studies were not performed.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (-4 to -6 S.D. below mean) Other \- Prenatal onset of short stature HEAD & NECK Face \- Triangular face Ears \- Posteriorly rotated ears \- Hearing loss, conductive (in some patients) \- Otitis media, recurrent (rare) Eyes \- Long eyelashes \- Deep-set eyes (in early childhood) \- Hyperopia (in some patients) \- Strabismus (rare) Nose \- Prominent nose \- Wide columella \- Smooth philtrum Mouth \- Thin lips \- Broad mouth \- Downturned mouth Neck \- Short neck \- Low posterior hairline CARDIOVASCULAR Heart \- Atrial septal defect (rare) \- Mesocardia (rare) Vascular \- Aortic coarctation (rare) \- Persistent left superior vena cava (rare) ABDOMEN External Features \- Umbilical hernia (rare) Gastrointestinal \- Celiac disease GENITOURINARY External Genitalia (Male) \- Hypospadias (rare) Internal Genitalia (Male) \- Inguinal hernia (in some patients) \- Cryptorchidism (in some patients) \- Epididymal cysts, bilateral (rare) \- Varicocele (rare) Kidneys \- Hydronephrosis (rare) \- Nephrocalcinosis (rare) \- Unilateral renal pelviectasis (rare) Bladder \- Posterior urethral valves (rare) SKELETAL \- Delayed bone age Limbs \- Joint laxity Hands \- Fifth finger clinodactyly \- Cone-shaped epiphyses SKIN, NAILS, & HAIR Hair \- Long eyelashes \- Hirsutism NEUROLOGIC Central Nervous System \- Expressive language delay \- Normal motor development \- Intellectual impairment, mild (in some patients) LABORATORY ABNORMALITIES \- Normal endocrinologic studies (growth hormone, somatomedin C, thyroid function) MISCELLANEOUS \- Majority of cases are sporadic \- Facial dysmorphism is age-related and alters substantially over time MOLECULAR BASIS \- Caused by mutation in the SNF2-related CBP activatory protein gene (SRCAP, 611421.0001 ) ▲ 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
| FLOATING-HARBOR SYNDROME | c0729582 | 4,119 | omim | https://www.omim.org/entry/136140 | 2019-09-22T16:41:00 | {"mesh": ["C537062"], "omim": ["136140"], "orphanet": ["2044"], "genereviews": ["NBK114458"]} |
X-linked severe combined immunodeficiency (SCID) is an inherited disorder of the immune system that occurs almost exclusively in males. Boys with X-linked SCID are prone to recurrent and persistent infections because they lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. Many infants with X-linked SCID develop chronic diarrhea, a fungal infection called thrush, and skin rashes. Affected individuals also grow more slowly than other children. Without treatment, males with X-linked SCID usually do not live beyond infancy.
## Frequency
X-linked SCID is the most common form of severe combined immunodeficiency. Its exact incidence is unknown, but the condition probably affects at least 1 in 50,000 to 100,000 newborns.
## Causes
Mutations in the IL2RG gene cause X-linked SCID. The IL2RG gene provides instructions for making a protein that is critical for normal immune system function. This protein is necessary for the growth and maturation of developing immune system cells called lymphocytes. Lymphocytes defend the body against potentially harmful invaders, make antibodies, and help regulate the entire immune system. Mutations in the IL2RG gene prevent these cells from developing and functioning normally. Without functional lymphocytes, the body is unable to fight off infections.
### Learn more about the gene associated with X-linked severe combined immunodeficiency
* IL2RG
## Inheritance Pattern
This condition is inherited in an X-linked recessive pattern. The gene associated with this 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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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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 severe combined immunodeficiency | c1279481 | 4,120 | medlineplus | https://medlineplus.gov/genetics/condition/x-linked-severe-combined-immunodeficiency/ | 2021-01-27T08:25:15 | {"gard": ["5618"], "mesh": ["D053632"], "omim": ["300400"], "synonyms": []} |
A number sign (#) is used with this entry because of evidence that the disorder is caused by homozygous or compound heterozygous mutation in the ERCC4 gene (133520) on chromosome 16p13.
Description
Xeroderma pigmentosum is an autosomal recessive disorder characterized by sun sensitivity and increased skin sensitivity to UV light, as well as an increased risk of skin cancer associated with a defect in nucleotide excision repair (NER). The XPF form of XP is usually relatively mild compared to other forms. Patients with XPF tend to have later onset of skin cancer. Some patients with XPF may develop neurologic impairment or growth defects, and are then classified as having Cockayne syndrome (summary by Kashiyama et al., 2013).
For a general phenotypic description and a discussion of genetic heterogeneity of xeroderma pigmentosa, see XPA (278700), and of Cockayne syndrome, see CSA (216400).
Clinical Features
Group F xeroderma pigmentosum had probably been observed only in Japan (Fujiwara et al., 1985) until the report by Norris et al. (1988) of a case in an English woman. The patient reported by Norris et al. (1988) was a 22-year-old-white woman with mild cutaneous changes, no tumors, and normal sensitivity to monochromatic ultraviolet irradiation. Unscheduled DNA synthesis in cultured fibroblasts after UV irradiation was reduced to 13% of controls during the first 2 hours and rose to 45% of normal by 7 to 8 hours. The findings were consistent with a defect in nucleotide excision repair (NER).
Yamamura et al. (1989) described a 61-year-old female patient with XP assigned to complementation group F by the cell fusion-complementation method. Her fibroblasts in culture exhibited a defective DNA repair capacity of 10 to 15% unscheduled DNA synthesis and a 3-fold increased sensitivity to the lethal effects of ultraviolet light. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of seborrheic keratosis-like papules. She had no skin cancers in the sun-exposed areas and no neurologic abnormalities. Yamamura et al. (1989) reviewed 11 Japanese group F patients demonstrating very mild skin symptoms and no ocular or neuropsychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients, with an average age of 52 years for their first skin malignancy.
### Cockayne Syndrome
Moriwaki et al. (1993) reported a 48-year-old Japanese man with xeroderma pigmentosum associated with mental retardation, cerebral atrophy, and cerebellar ataxia. Genetic complementation tests by cell fusion with polyethylene glycol revealed that the patient belonged to group F. He died of bile duct cancer at the age of 50. Moriwaki et al. (1993) stated that this was the first report of an XPF patient with neurologic abnormalities.
Sijbers et al. (1998) reported a Caucasian patient with XPF. He had mild ocular photophobia from childhood and acute skin reactions occurred upon exposure to sunlight. After age 27, he developed several basal and squamous cell carcinomas. In his late forties, he developed progressive neurologic symptoms, including intellectual decline, mild chorea and ataxia, and marked cerebral and cerebellar atrophy. Sijbers et al. (1998) stated that such neurologic abnormalities were unusual in XPF, having been described in only 1 of 17 other XPF individuals. The patient's 5-fold reduced activity of nucleotide excision repair in cultured cells, combined with moderately affected cell survival and DNA replication after UV exposure, was typical of XPF.
Kashiyama et al. (2013) reported a 16-year-old boy (CS1USAU) with Cockayne syndrome. He developed normally for the first year without obvious abnormalities, except for the microcephaly. At age 5 years, he developed multiple unusual plantar warts on his hands and forearms, unusual freckling, and sun sensitivity. Examination at age 7 years showed short stature, poor growth, and microcephaly. He had deep-set eyes, progressive scoliosis, and multiple contractures in his feet; he required lengthening of the Achilles tendon because of muscle cramps in his hamstrings and calves. His skin was deeply pigmented with rashes and flat freckles. Other features included hearing impairment, learning disabilities, attention deficit-hyperactivity disorder, migraines, and feeding difficulties. Brain MRI showed some delayed myelination and basal ganglia shortening. A second unrelated patient (XPCS1CD) had a more complex phenotype comprising XPF, Cockayne syndrome, and Fanconi anemia (see FANCQ; 615272). She showed intrauterine growth failure and later had short stature and microcephaly. Development was globally delayed. She was noted to have sun sensitivity with severe sunburns at age 18 months, and was carefully photoprotected. She developed sensorineural hearing loss at age 5 years, followed by progressive ataxia, tremor, weakness, and nystagmus. Between ages 6 and 9 years, she became pancytopenic, consistent with bone marrow failure, and at age 10, she developed hypertension and severe proteinuria, consistent with renal failure. Examination at age 11 showed microcephaly, short stature, deep-set eyes, prominent nose, small teeth, and freckling over the nose and cheeks. The skin had an aged appearance, and palmar erythema, plane warts, and cafe-au-lait macules were present. Liver function was normal; renal biopsy showed focal segmental glomerular sclerosis, thickening of the capillary basement membrane, interstitial fibrosis, and tubular atrophy. She died of renal failure at age 12 years. Dermal fibroblasts from both patients showed significantly decreased RNA synthesis activity compared to controls, indicating a deficiency in transcription-coupled NER (TC-NER), as expected for Cockayne syndrome cells, as well as a decrease in unscheduled DNA synthesis, indicating a defect in global genome NER (GG-NER). Complementation studies showed that the 2 patients could be assigned to group XPF. Both cell lines were also sensitive to the crosslinking agent mitomycin-C, indicating a defect in the repair of DNA interstrand crosslinks (ICL).
Mapping
Saxon et al. (1989) found that microcell-mediated transfer of a single human chromosome from repair-proficient human cells to XP cells of complementation group F resulted in partial complementation of repair-defective phenotypes. They identified the complementing chromosome as human chromosome 15 by cytogenetic and molecular analysis. About 20% of the resistance of wildtype cells to killing by UV radiation or by the UV-mimetic chemical 4-nitroquinoline-1-oxide, as well as partial repair synthesis of DNA measured as unscheduled DNA synthesis, resulted from the transfer of the chromosome. Although the work seemed to indicate that the gene on chromosome 15 carries a mutation determining XPF, the reason for the incomplete correction was unclear. Because of incomplete correction, the assignment of XPF to chromosome 15 was considered in limbo (Cleaver, 1993).
By means of fluorescence in situ hybridization, Sijbers et al. (1996) mapped the XPF gene to 16p13.2-p13.1. This corresponds to the location of ERCC4, a human repair gene complementing rodent nucleotide excision repair mutants of group 4, that was originally identified using cell hybrids (Liu et al., 1993) and a genomic clone (Thompson et al., 1994).
Molecular Genetics
In the patient with XPF reported by Norris et al. (1988), Sijbers et al. (1996) identified compound heterozygous mutations in the ERCC4 gene (133520.0001 and 133520.0002).
In a patient with XPF and late-onset neurologic features, Sijbers et al. (1998) identified a homozygous mutation in the ERCC4 gene (R788W; 133520.0002).
Cleaver et al. (1999) tabulated the mutations that had been reported in the XPF gene. These included 8 mutations reported by Matsumura et al. (1998). Their patients varied in age from 22 to 73 years. The XPF complementation group is rare and the majority of cases have been found in Japan.
In 2 unrelated patients with XPF and Cockayne syndrome, Kashiyama et al. (2013) identified compound heterozygous mutations in the ERCC4 gene (133520.0008-133520.0010).
Animal Model
Munoz et al. (2005) found that transgenic mice that overexpress the telomere-binding protein TRF2 (602027) had a severe phenotype in the skin in response to light, consisting of premature skin deterioration, hyperpigmentation, and increased skin cancer, resembling xeroderma pigmentosum. Keratinocytes from these mice were hypersensitive to ultraviolet irradiation and DNA crosslinking agents. The skin cells of these mice had marked telomere shortening, loss of the telomeric G-strand overhang, and increased chromosomal instability. Munoz et al. (2005) found that telomere loss in these mice was mediated by XPF. The findings suggested that TRF2 provides a crucial link between telomere function and ultraviolet-induced damage repair, whose alteration underlies genomic instability, cancer, and aging.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) Weight \- Low weight (in some patients) HEAD & NECK Head \- Microcephaly (in some patients) Ears \- Hearing impairment (in some patients) Eyes \- Deep-set eyes (in some patients) \- Astigmatism (in some patients) \- Nystagmus (in some patients) SKELETAL \- Joint contractures (in some patients) Spine \- Scoliosis (in some patients) SKIN, NAILS, & HAIR Skin \- Skin photosensitivity \- Numerous pigmented freckles \- Seborrheic keratosis-like papules \- Rare skin cancers \- Plantar warts \- Hyperpigmentation NEUROLOGIC Central Nervous System \- Learning disabilities (in some patients) \- Mental retardation (in some patients) \- Ataxia (in some patients) \- Tremor (in some patients) \- Dementia (in some patients) \- Brain atrophy (in some patients) NEOPLASIA \- Skin cancer susceptibility LABORATORY ABNORMALITIES \- Patient cells show defective transcription-coupled and global genome nucleotide excision repair (NER) MISCELLANEOUS \- Highly variable phenotype \- One patient with additional features of Fanconi anemia has been reported MOLECULAR BASIS \- Caused by mutation in the excision-repair cross-complementing group 4 gene (ERCC4, 133520.0001 ) ▲ 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
| XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F | c0043346 | 4,121 | omim | https://www.omim.org/entry/278760 | 2019-09-22T16:21:05 | {"doid": ["0110848"], "mesh": ["D014983"], "omim": ["278760"], "orphanet": ["220295", "910"], "synonyms": ["XERODERMA PIGMENTOSUM VI", "Alternative titles", "XP/CS complex", "XP, GROUP F"], "genereviews": ["NBK1397"]} |
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, see IBD1 (266600).
Mapping
Duerr et al. (2000) performed a genome scan using 751 microsatellite loci in 127 CD-affected relative pairs from 62 families. They found significant linkage to D14S261 at 14q11-q12 (lod = 3.00; maximum multipoint lod = 3.60). Suggestive linkage to the same locus was found in an independent study (multipoint lod = 2.8) by Ma et al. (1999).
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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
| INFLAMMATORY BOWEL DISEASE 4 | c1847691 | 4,122 | omim | https://www.omim.org/entry/606675 | 2019-09-22T16:10:14 | {"mesh": ["C564680"], "omim": ["606675"]} |
A number sign (#) is used with this entry because of evidence that agammaglobulinemia-8 (AGM8) is caused by heterozygous mutation in the TCF3 gene (147141) on chromosome 19p13.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal agammaglobulinemia, see AGM1 (601495).
Clinical Features
Dobbs et al. (2011) and Boisson et al. (2013) reported 4 unrelated patients who presented in the first years of life with severe infections, including pneumococcal meningitis, recurrent otitis, vaccine-associated polio, and arthritis. Laboratory studies showed severely decreased levels of serum immunoglobulins and less than 3% of CD19+ circulating B cells. The B cells showed high-intensity expression of CD19, but absence of the B-cell receptor (BCR). Bone marrow biopsy from 2 patients showed a severe reduction in the number of pro- and pre-B cells. Detailed analysis of patient B cells showed that they did not bear surface immunoglobulins.
Molecular Genetics
In 4 unrelated patients with AGM8, Boisson et al. (2013) identified a de novo heterozygous missense mutation (E555K; 147141.0001) specific to the E47 isoform of the TCF3 gene. In vitro functional expression studies and studies of patient cells showed that the mutant E47 protein localized properly to the nucleus, but did not perform proper DNA binding and acted in a dominant-negative manner when coexpressed with wildtype. Laboratory studies showed decreased numbers of B cells; the remaining B cells showed intense CD19 expression and absence of the B-cell receptor (Dobbs et al., 2011). The findings suggested that E47 plays a critical role in enforcing the block in the development of B-cell precursors that lack functional antigen receptors.
Animal Model
Zhuang et al. (1994) found that TCF3 homozygous mutant mice developed to full term without apparent abnormalities, but then displayed a high rate of postnatal death. The surviving mice showed retarded postnatal growth. Detailed examination of hematopoiesis revealed that the homozygous mutant mice contained no B cells, whereas other lineages, including the T cell, granulocyte, macrophage, and erythroid lineages, were intact. The block to B-cell differentiation occurred before the immunoglobulin gene D(H)-J(H) rearrangement. Surprisingly, heterozygous embryos contained, on average, about half as many B cells as did wildtype embryos, suggesting the existence of a counting mechanism that translates levels of E2A into numbers of B cells.
Sun (1994) generated transgenic mice in which the Id1 gene (600349) was constitutively overexpressed in the B-cell lineage. The product of this gene is an inhibitor of the DNA-binding activity of bHLH proteins such as the E2A gene product. The phenotype of these transgenic mice depicted severe defects in early B-cell development, suggesting that the bHLH proteins play pivotal roles in B-cell development and that the downregulation of Id1 gene expression is necessary for B cells to differentiate.
Bain et al. (1994) generated E2A-null mice by gene targeting and found that they failed to generate mature B cells. The arrest of B-cell development occurred at an early stage since no immunoglobulin DJ rearrangements could be detected. The finding suggested a crucial role for E2A products in the regulation of early B-cell differentiation.
INHERITANCE \- Autosomal dominant IMMUNOLOGY \- Recurrent infections \- Agammaglobulinemia \- Decreased circulating B cells \- B cells show intense CD19 immunostaining \- B cells lack the B-cell receptor MISCELLANEOUS \- Onset in infancy \- De novo mutation \- Four unrelated patients have been reported (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the transcription factor 3 gene ( 147141.0001 ) ▲ 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
| AGAMMAGLOBULINEMIA 8, AUTOSOMAL DOMINANT | c1832241 | 4,123 | omim | https://www.omim.org/entry/616941 | 2019-09-22T15:47:27 | {"mesh": ["C538056"], "omim": ["616941"], "orphanet": ["33110", "229717"], "synonyms": ["Alternative titles", "AGAMMAGLOBULINEMIA, AUTOSOMAL DOMINANT, DUE TO TCF3 DEFECT"]} |
Group of disorders characterised by degeneration of white matter in the brain
Leukodystrophy
T2 weighted axial scan at the level of the caudate heads demonstrates marked loss of posterior white matter, with reduced volume and increased signal intensity. The anterior white matter is spared. Features are consistent with X-linked adrenoleukodystrophy.
SpecialtyNeurology
Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white matter in the brain.[1] The word leukodystrophy comes from the Greek roots leuko, "white", dys, "abnormal" and troph, "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty insulating covering around nerve fibers.[2] Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, depending on whether the damage is present before birth or occurs after. Other demyelinating diseases are usually not congenital and have a toxic or autoimmune cause.[3]
When damage occurs to white matter, immune responses can lead to inflammation in the central nervous system (CNS), along with loss of myelin. The degeneration of white matter can be seen in an MRI scan and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventual degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor, as infants have a typical life expectancy of 2–8 years, while adults typically live more than a decade after onset. Treatment options are limited, although hematopoietic stem cell transplantations using bone marrow or cord blood seem to help in certain types while further research is being done.
The combined incidence of the leukodystrophies is estimated at 1 in 7,600.[4] The majority of types involve the inheritance of an X-linked recessive, or X-linked dominant trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.
## Contents
* 1 Symptoms and signs
* 2 Causes
* 2.1 Genetic influence
* 3 Pathophysiology
* 3.1 Metachromatic leukodystrophy
* 3.2 Krabbe disease
* 3.3 Canavan disease
* 3.4 X-linked adrenoleukodystrophy
* 3.5 Alexander disease
* 4 Diagnosis
* 4.1 Types
* 5 Treatment
* 6 Epidemiology
* 7 Research
* 8 Society
* 9 See also
* 10 References
* 11 External links
## Symptoms and signs[edit]
Some specific symptoms vary from one type of leukodystrophy to the next, but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head.[5] Botox therapy is often used to treat patients with spasticity.[6] Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation.[7] Epilepsy is commonplace for patients of all ages.[8] More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile X-linked adrenoleukodystrophy is shown in the 1992 film, Lorenzo's Oil.[9]
Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death.[5] While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement.[10] The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients’ rights and physician-assisted suicide.[11]
## Causes[edit]
While the more specific underlying causes of leukodystrophy are dependent upon the type, there are, however, common pathophysiological patterns that can be seen amongst all types. First and foremost, leukodystrophy is a neurodegenerative disease that is always the result of both impairment and maintenance of myelin sheaths surrounding neuronal axons in the central nervous system as the result of a genetic mutation.[12] Myelin is a fatty white substance that acts as an electrical insulator and coats axons in order to speed up impulses (i.e., action potentials) traveling down the axon. Thus, the natural result of a loss of this substance is decreased efficiency in impulse propagation. As myelin is produced by oligodendrocytes (a type of glial cell) in the central nervous system, an easy place to look for the cause is a mutation or malfunctioning of these cells and in other glial cells.[citation needed]
### Genetic influence[edit]
Autorecessive Inheritance Pattern
Leukodystrophy is most often an inherited disease that is usually the result of an autosomal recessive inheritance pattern, although dominant inheritance patterns are not unheard of, as in the case of adult-onset leukodystrophy.[13] This means that the affected allele is carried on an autosomal, or non-sex, chromosome and is masked by the dominant, unaffected phenotype. In other words, for an individual to inherit the leukodystrophy phenotype, he or she must carry two of the recessive, mutant alleles. Krabbe disease and metachromatic leukodystrophy (MLD) are two of such type. MLD is found on human chromosome 22 at position q13.31.[14] Another type of inherited leukodystrophy is X-linked adrenoleukodystrophy (X-ALD). As its name implies, this type of leukodystrophy is the result of a mutation found on the X-chromosome. It is also carried in a recessive pattern. The X chromosome is a sex chromosome, and since women have two “chances” of acquiring a normal X chromosome (one maternal, one paternal), and males only one (one maternal), this disease is more likely to be seen in men than in women. The mutation resulting in adult-onset leukodystrophy is mapped at 5q23.[13]
## Pathophysiology[edit]
Although there are nearly forty different types of leukodystrophies, many are lacking in formal and comprehensive research. Most of the research so far has been done on five types: (1) metachromatic leukodystrophy (MLD), (2) Krabbe disease, (3) X-Linked adrenoleukodystrophy (ALD), (4) Canavan disease, and (5) Alexander disease. Each type of leukodystrophy has a unique pathophysiology, but all five of these in some way affect a subset of glial cells, therefore disrupting myelin production and maintenance, and usually involve a mutation involving genes that code for enzymes necessary for the catabolism of very long chain fatty acids (VLCFAs) that are toxic to the myelin-producing cells of the central nervous system.[15]
### Metachromatic leukodystrophy[edit]
Main article: Metachromatic leukodystrophy
Metachromatic leukodystrophy is the result of genetic defects in the enzymes associated with the cellular compartment the lysosome. MLD is one of two leukodystophies that are also a lysosomal storage disorder. MLD is inherited in an autosomal recessive way and is the result of mutations in three different ARSA alleles that encode the enzyme arylsulfatase A (ASA or sometimes ARSA), also called sulfatide sulfatase.[16] ASA is responsible for the breakdown of sulfatides, sphingolipids present in neuronal membranes as well as in myelin. When there is a mutation in the gene that encodes ASA, the result is it decreases production, which subsequently leads to diminished degradation of sulfatides, thus causing them to accumulate.[16] This accumulation of sulfatides is poisonous to oligodendrocytes, the myelin-producing cells of the CNS, effectively leading to a disturbance in myelin structure followed by demyelination. The pattern of inheritance of the three different alleles affects what type of MLD a person develops. Two null alleles are responsible for the infantile version, and do not allow for any production of ASA. A heterozygous individual (one null allele, one non-null allele) develops the juvenile form and sees some production of ASA, while an individual with two non-null alleles (but still mutated) develops the adult form.[17]
### Krabbe disease[edit]
Globoid cell leukodystrophy PAS - Multinucleated macrophages ("globoid cells") and loss of myelinated fibers in a case of Krabbe's leukodystrophy
Main article: Krabbe disease
Like MLD, Krabbe disease is another type of leukodystrophy with autosomal recessive inheritance that is the result of a lysosomal storage disorder. It is due to a deletion in exon 16 of the GALC gene that causes a frameshift mutation leading to a premature stop codon. The GALC gene, found on chromosome 14 at position 31 (14q31), codes for the enzyme beta-galactocerebrosidase (GALC).[18] GALC is a lysosomal enzyme responsible for the catabolism of galactolipids, especially psychosine, that are heavily distributed throughout the brain. A deficiency in GALC thus causes a buildup of these fatty acids known as globoid macrophages that destroy oligodendrocytes, thereby inhibiting myelin formation.[19]
Because of the presence of globoid cells clustered near white matter, Krabbe disease often goes by the name globoid cell leukodystrophy. Furthermore, new research has shown that Krabbe disease and globoid cell leukodystrophy may be distinct disease entities due to the secretion of inflammatory mediators by natural killer cells in some cases.[20] This research has shown that Natural Killer cells have receptors (TDAG8) for certain glycosphingolipids that build up in an individual with leukodystrophy, again due to insufficient GALC levels, and when bound, target the Natural Killer cells for destruction thereby preventing their cytotoxic effects. These sphingolipids have been identified as galactosyl sphingosine and glycosyl sphingosine and are not present in unaffected individuals.[20]
### Canavan disease[edit]
Main article: Canavan disease
Canavan disease is a lesser-studied type of leukodystrophy that, like MLD and Krabbe disease, is also passed on in an autosomal recessive inheritance pattern. It is due to a mutation in the ASPA gene that encodes aspartoacylase, an enzyme needed to metabolize N-acetyl-L-aspartate (NAA). The mutation causes a deficiency of aspartoacyclase. NAA is involved in the formation of lipids, and if it is not broken down by aspartoacylase, excess levels of it build up causing demyelination.[21]
### X-linked adrenoleukodystrophy[edit]
Main article: Adrenoleukodystrophy
In X-linked adrenoleukodystrophy (X-ALD), a mutation occurs in the peroxisomal ATP-binding cassette (ABC transporter). This leads to cerebral inflammatory demyelination caused by the myelin destabilization that occurs in these patients.[22] The inflammatory demyelination begins in the corpus callosum and it slowly progresses outwards towards both hemispheres. In X-ALD patients, abnormally high levels of very long chain fatty acid (VLCFA) accumulate in various body tissues and fluids. This increased concentration then incorporates into various complex lipids where they are not normally found.[22] This has been found to be directly involved in the cerebral inflammation. The accumulated and embedded VLCFA in the complex lipids could lead to the destabilization of myelin sheath and eventually to demyelination.[citation needed]
### Alexander disease[edit]
Main article: Alexander disease
Alexander disease is unique from the leukodystrophies mentioned above in that it is the result of spontaneous mutation, that is it is not inherited. This means that the mutation found in the affected individual is not found in either of his or her parents. It is due to the accumulation of Glial fibrillary acidic protein (GFAP) as the result of a mutation in the GFAP gene; which, rather than being found in association with lysosomes or peroxisomes, is an intermediate filament linked to the nuclear envelope.[23] Intermediate filaments are proteins responsible for the makeup of the cellular cytoskeleton, and thus this type of mutation is involved in malfunctioning structural development of the cells. In fact, cytoskeletal and transporter molecule defects have been observed in the astrocytes (type of glial cell) of affected individuals. These astrocytes have an unhealthily large amount of GFAP that affects astrocyte formation and function.[24]
## Diagnosis[edit]
The degeneration of white matter, which shows the degeneration of myelin, can be seen in a basic MRI and used to diagnose leukodystrophies of all types. T-1 and T-2 weighted FLAIR images are the most useful. FLAIR stands for fluid-attenuated inversion recovery.[25] Electrophysiological and other kinds of laboratory testing can also be done. In particular, nerve conduction velocity is looked at to distinguish between leukodystrophy and other demyelinating diseases, as well as to distinguish between individual leukodystrophies. For example, individuals with X-ALD have normal conduction velocities, while those with Krabbe disease or metachromatic leukodystrophy have abnormalities in their conduction velocities.[25] Next generation multigene sequencing panels for undifferentiated leukodystrophy can now be offered for rapid molecular diagnosis after appropriate genetic counselling.[citation needed]
### Types[edit]
Specific types of leukodystrophies include the following with their respective ICD-10 codes when available:[citation needed]
* (E71.3) Adrenomyeloneuropathy
* (E75.2) Alexander disease
* (E75.5) Cerebrotendineous xanthomatosis
* Hereditary CNS demyelinating disease
* (E75.2) Krabbe disease
* (E75.2) Metachromatic leukodystrophy
* (E75.2) Pelizaeus–Merzbacher disease
* (E75.2) Canavan disease
* (E75.2) Hypomyelinating leukodystrophy type 7 (4H syndrome)
* (G93.49) Leukoencephalopathy with vanishing white matter
* (E71.3) Adrenoleukodystrophy
* (G60.1) Refsum disease
## Treatment[edit]
With many different types of leukodystrophies and causes, treatment therapies vary for each type. Many studies and clinical trials are in progress to find treatment and therapies for each of the different leukodystrophies. Stem cell transplants and gene therapy appear to be the most promising in treating all leukodystrophies providing it is done as early as possible. For hypomyelinating leukodystrophies, therapeutic research into cell-based therapies appears promising. Oligodendrocyte precursor cells and neural stem cells have been transplanted successfully and have shown to be healthy a year later. Fractional anisotropy and radial diffusivity maps showed possible myelination in the region of the transplant.[26] Induced pluripotent stem cells, oligodendrocyte precursor cells, gene correction, and transplantation to promote the maturation, survival, and myelination of oligodendrocytes seem to be the primary routes for possible treatments.[26]
For three types of leukodystrophies (X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD) and Krabbe Disease (globoid cell leukodystrophy - GLD), gene therapy using autologous hematopoietic stem cells to transfer the disease gene with lentiviral vectors have shown to be successful and are currently being used in clinical trials for X-ALD and MLD.[10] The progression of X-ALD has shown to be disrupted with hematopoietic stem cell gene therapy but the exact reason why demyelination stops and the amount of stem cells needed is unclear.[10] While there is an accumulation of very long chain fatty acids in the brain, it does not seem to be the reason behind the disease as gene therapy does not correct it.[10]
For those leukodystrophies that result from a deficiency of lysozyme enzymes, such as Krabbe disease, enzyme replacement therapy seems hopeful. However, enzyme delivery proves difficult, because the blood-brain barrier severely limits what can pass into the central nervous system.[10] Current gene therapy research for metachromatic leukodystrophy has been reviewed with an emphasis on ex vivo transplantation of genetically modified hematopoietic stem cells.[27]
## Epidemiology[edit]
X-linked Recessive Inheritance
Currently, no research has shown a higher prevalence of most leukodsytrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease.[28] This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease. The one exception to this is any type of leukodystrophy carried on a sex chromosome, such as X-linked adrenoleukodystrophy, which is carried on the X-chromosome. Because of the inheritance pattern of X-linked diseases, males are more often affected by this type of leukodystrophy, although female carriers are often symptomatic, though not as severely so as males.[29] To date, there have been no found cases of a leukodystrophy carried on the Y chromosome.[citation needed]
## Research[edit]
The National Institute of Neurological Disorders and Stroke (NINDS) supports research on genetic disorders, including the leukodystrophies.[30] NINDS also supports researchers who are working with the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) which promotes advances in the diagnosis and treatment of leukodystrophies.[31]
The European Leukodystrophy Association also supports research into leukodystrophy. As of 2020, more than 387 research projects have been funded. Each year, ELA invites the international scientific community to submit research projects in the field of genetic leukodystrophies, the cerebral white matter in premature infants, and of myelin repair.[32]
## Society[edit]
The United Leukodystrophy Foundation (ULF), incorporated in 1982, is a non-profit, voluntary health organization dedicated to funding cutting-edge research and to providing patients and their families with disease information and medical referrals.[33]
Cure MLD is a global network of patient advocates and nonprofits dedicated to helping families impacted by metachromatic leukodystrophy (MLD).[34]
The MLD Foundation was co-founded by Dean and Teryn Suhr in 2001 after the diagnosis in 1995 of two of their daughters with MLD. MLD Foundation serves families and works with researchers, clinicians, regulators, payors, and policy-makers around the world on MLD, leukodystrophy, lysosomal, and rare disease issues.[35]
The Leukodystrophy Alliance works to promote awareness and quality of care for those with leukodystrophy.[36]
Jill Kelly and her husband, NFL quarterback Jim Kelly, founded Hunter's Hope Foundation to fund research after their son Hunter (1997-2005) was diagnosed with infantile Krabbe leukodystrophy.[37]
Matthew and Michael Clark of Hull, UK were sufferers, unfortunately both succumbing to the illness and dying in 2013 & 2016 respectively. Their story was the subject of the Channel 4 documentary The Curious Case of the Clark Brothers.[38]
Augusto and Michaela Odone founded The Myelin Project after their son, Lorenzo was diagnosed with Adrenoleukodystrophy (ALD). The 1992 film, Lorenzo's Oil is a true story about a boy suffering from Adrenoleukodystrophy (ALD).[citation needed]
## See also[edit]
* Leukoencephalopathy
## References[edit]
1. ^ Sachdev, Perminder S.; Keshavan, Matcheri S. (2010-03-15). Secondary Schizophrenia. Cambridge University Press. pp. 241–. ISBN 978-0-521-85697-3. Retrieved 15 August 2011.
2. ^ One or more of the preceding sentences incorporates text from a work in the public domain: "Leukodystrophy Information Page". National Institute of Neurological Disorders and Stroke. 25 May 2017. Retrieved 18 March 2018.
3. ^ Vanderver, Adeline; Tonduti, Davide; Schiffmann, Raphael; Schmidt, Johanna; van der Knaap, Marjo S. (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Leukodystrophy Overview", GeneReviews®, University of Washington, Seattle, PMID 24501781, retrieved 2020-01-23
4. ^ Bonkowsky, Joshua (Aug 24, 2010). "The burden of inherited leukodystrophies in children". Neurology. 75 (8): 718–725. doi:10.1212/WNL.0b013e3181eee46b. PMC 2931652. PMID 20660364.
5. ^ a b Graziano, AC; Cardile, V (26 September 2014). "History, genetic, and recent advances on Krabbe disease". Gene. 555 (1): 2–13. doi:10.1016/j.gene.2014.09.046. PMID 25260228.
6. ^ Rosebush, P. I. (2003). "Tardive dystonia and its treatment". Journal of Psychiatry and Neuroscience. 28 (3): 240. PMC 161748.
7. ^ Liu, Y; Zou, L; Meng, Y; Zhang, Y; Shi, X; Ju, J; Yang, G; Hu, L; Chen, X (June 2014). "[A family with two children diagnosed with aspartylglucosaminuria-case report and literature review]". Zhonghua Er Za Zhi. 52 (6): 455–9. PMID 25190167.
8. ^ Turon-Vinas, E; Pineda, M; Cusi, V; Lopez-Laso, E; Del Pozo, RL; Gutierez-Solana, LG; Moreno, DC; Sierra-Corcoles, C; Olabarrieta-Hoyos, N; Madruga-Garrido, M; Aguirre-Rodriguez, J; Gonzalez-Alvarez, V; O'Callaghan, M; Muchart, J; Armstrong-Moron, J (13 July 2014). "Vanishing white matter disease in a Spanish population". J Cent Nerv Syst Dis. 6: 59–68. doi:10.4137/JCNSD.S13540. PMC 4116383. PMID 25089094.
9. ^ Rubin, Rita (March 13, 2016). "Forbes.com: Lorenzo's Oil Could Not Cure Lorenzo, But Newborn Screening Is Expected To Save Others From His Fate". Forbes.com. Retrieved July 31, 2018..
10. ^ a b c d e Biffi, A.; Aubourg, P.; Cartier, N. (2011). "Gene therapy for leukodystrophies". Human Molecular Genetics. 20 (R1): R42–R53. doi:10.1093/hmg/ddr142. PMID 21459776.
11. ^ Duchange, N; Darguy, S; d'Audiffret, D; Callies, I; Lapointe, AS; Loeve, B; Boespflug-Tanguy, O; Moutel, G (18 September 2014). "Ethical management in the constitution of a European database for leukodystrophies rare diseases". Eur J Paediatr Neurol. 18 (5): 597–603. doi:10.1016/j.ejpn.2014.04.002. PMID 24786336.
12. ^ Yang, Edward; Prabhu, Sanjay P. (March 5, 2014). "Imaging manifestations of the leukodystrophies, inherited disorders of white matter". Radiologic Clinics of North America. 52 (2): 279–319. doi:10.1016/j.rcl.2013.11.008. PMID 24582341.
13. ^ a b Lin, Shu-Ting; Ptacek, Louis J.; Fu, Ying-Hui (January 26, 2011). "Adult-Onset Autosomal Dominant Leukodystrophy: Linking Nuclear Envelope to Myelin". The Journal of Neuroscience. 31 (4): 1163–1166. doi:10.1523/jneurosci.5994-10.2011. PMC 3078713. PMID 21273400.
14. ^ Coulter-Mackie, MB; Rip, J; Ludman, MD; Beis, J; Cole, DEC (October 1995). "Metachromatic leucodystrophy (MLD) in a patient with a constitutional ring chromosome 22". Journal of Medical Genetics. 32 (10): 787–91. doi:10.1136/jmg.32.10.787. PMC 1051701. PMID 8558556.
15. ^ Sassa, Takayuki; Kihara, Akio (March 22, 2014). "Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology". Biomolecules & Therapeutics. 22 (2): 83–92. doi:10.4062/biomolther.2014.017. PMC 3975470. PMID 24753812.
16. ^ a b Barboura, Ilhem; Ferchichi, Salima; Dandana, Azza; Jaidane, Zaineb; Ben Khelifa, Souhaira; Chahed, Hinda; Ben Mansour, Rachida; Chebel, Saber; Maire, Irene; Miled, Abdelhedi (2010). "Metachromatic leucodystrophy. Clinical, biological, and therapeutic aspects". Annales de Biologie Clinique. 68 (4): 385–91. doi:10.1684/abc.2010.0448. PMID 20650733.
17. ^ Gieselman, V; Krageloh-Mann, I (2010). "Metachromatic Leukodystrophy - An Update". Neuropediatrics. 41 (1): 1–6. doi:10.1055/s-0030-1253412. PMID 20571983.
18. ^ Szymanska, Krystyna; Lugowska, Agnieszka; Laure-Kamionowska, Milena; Gieruszczak-Bialek, Dorota; Musielak, Malgorzata; Eichler, Sabrina; Giese, Anne-Katrin; Rolfs, Arndt (2012). "Diagnostic difficulties in Krabbe disesase: a report of two cases and review of literature". Folia Neuropathol. 50 (4): 346–356. doi:10.5114/fn.2012.32364. PMID 23319190.
19. ^ Kohlschutter, Alfried (April 25, 2013). Lysosomal leukodystrophies - Krabbe disease and metachromatic leukodystrophy. Handbook of Clinical Neurology. 113. pp. 1611–1618. doi:10.1016/B978-0-444-59565-2.00029-0. ISBN 9780444595652. PMID 23622382.
20. ^ a b Maghazachi, Azzam A. (February 5, 2013). "On the Role of Natural Killer Cells in Neurodegenerative Diseases". Toxins (Basel). 5 (2): 363–375. doi:10.3390/toxins5020363. PMC 3640540. PMID 23430541.
21. ^ United Leukodystrophy Foundation. "Canavan Disease". United Leukodystrophy Foundation. United Leukodystrophy Foundation, Inc. Retrieved March 30, 2015.
22. ^ a b Berger, J; Forss-Petter, S; Eichler, F.S. (March 2014). "Pathophysiology of X-Linked Adrenoleukodystrophy". Biochimie. 98: 135–142. doi:10.1016/j.biochi.2013.11.023. PMC 3988840. PMID 24316281.
23. ^ Singh, Navneet; Bixby, Catherine; Etienne, Denzil; Tubbs, R. Shane; Loukas, Marios (December 2012). "Alexander's disease: reassessment of a neonatal form". Child's Nervous System. 28 (12): 2029–2031. doi:10.1007/s00381-012-1868-8. PMID 22890470. S2CID 5851209.
24. ^ Hol, Elly M.; Pekny, Milos (February 2015). "Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system". Current Opinion in Cell Biology. 32 (Cell Architecture): 121–130. doi:10.1016/j.ceb.2015.02.004. PMID 25726916.
25. ^ a b Kohlschutter, Alfried; Eichler, Florian (October 2011). "Childhood leukodystrophies: a clinical perspective". Expert Review of Neurotherapeutics. 11 (10): 1485–1496. doi:10.1586/ern.11.135. PMID 21955203. S2CID 27471268.
26. ^ a b Pouwels, P. J. W.; Vanderver, A.; Bernard, G.; Wolf, N.; Dreha-Kulczewski, S. W.; Deoni, S. C. L.; Bertini, E.; Kohlschutter, A.; Richardson, W.; ffrench-Constant, C.; Kohler, W.; Barkovich, A. (2014). "Hypomyelinating Leukodystrophies: Translational Research Progress and Prospects" (PDF). Ann. Neurol. 76 (1): 5–19. doi:10.1002/ana.24194. PMID 24916848. S2CID 19026052.
27. ^ Rosenberg, J. B.; Kaminsky, S. M.; Aubourg, P.; Crystal, R. G.; Sondhi, D. (2016). "Gene therapy for metachromatic leukodystrophy". Journal of Neuroscience Research. 94 (11): 1169–79. doi:10.1002/jnr.23792. PMC 5027970. PMID 27638601.
28. ^ Fiegenbaum, Annette; Moore, Robert; Clarke, Joe; Hewson, Stacy; Chityat, David; Ray, Peter N.; Stockley, Tracy L. (January 15, 2004). "Canavan disease: Carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay". American Journal of Medical Genetics. 124A (2): 142–7. doi:10.1002/ajmg.a.20334. PMID 14699612. S2CID 25981659.
29. ^ Lesca, G; Vanier, MT; Creisson, E; Bendelac, N; Hainque, B; Ollagnon-Roman, E; Aubourg, P (August 2005). "X-linked adrenoleukodystrophy in a female proband: clinical presentation, biological diagnosis and family consequences". Archives de Pédiatrie. 12 (8): 1237–40. doi:10.1016/j.arcped.2005.03.050. PMID 15878823.
30. ^ "Leukodystrophy Information Page | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov.
31. ^ "The Global Leukodystrophy Initiative". The Global Leukodystrophy Initiative.
32. ^ "Accueil -". ela-asso.com.
33. ^ "Research". United Leukodystrophy Foundation.
34. ^ "Home | Cure MLD - Metachromatic leukodystrophy". curemld.
35. ^ "MLD Foundation". mldfoundation.org.
36. ^ "leukodystrophyalliance.org - This website is for sale! - leukodystrophyalliance Resources and Information". leukodystrophyalliance.org. Cite uses generic title (help)
37. ^ "Please Help Leukodystrophy Children". www.classy.org.
38. ^ "The Curious Case of the Clark Brothers". Retrieved 2012-11-26.
## External links[edit]
Classification
D
* ICD-10: E75.2
* ICD-9-CM: 330.0
* DiseasesDB: 32504
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
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* For more detailed coverage, see Template:Demyelinating diseases of CNS
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* For more detailed coverage, see Template:Epilepsy
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* For more detailed coverage, see Template:Sleep
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* Primary lateral sclerosis
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* Distal hereditary motor neuronopathies
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* SMA-PCH
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* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Leukodystrophy | c0023520 | 4,124 | wikipedia | https://en.wikipedia.org/wiki/Leukodystrophy | 2021-01-18T18:35:02 | {"gard": ["6895"], "umls": ["C0023520"], "icd-10": ["E75.2"], "orphanet": ["68356"], "wikidata": ["Q1821559"]} |
Ichthyosis-intellectual disability-dwarfism-renal impairment syndrome is characterised by nonbullous congenital ichthyosis, intellectual deficit, dwarfism and renal impairment. It has been described in four members of one Iranian family. 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
| Ichthyosis-intellectual disability-dwarfism-renal impairment syndrome | c1855787 | 4,125 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2278 | 2021-01-23T18:25:26 | {"gard": ["4641"], "mesh": ["C536274"], "omim": ["242530"], "umls": ["C1855787"], "synonyms": ["Passwell-Goodman-Siprkowski syndrome"]} |
A very rare, pure form of spastic paraplegia characterized by an onset in infancy of lower limb spasticity associated with gait disturbances, scissor gait, tiptoe walking, clonus and increased deep tendon reflexes. Mild upper limb involvement may occasionally also be associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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 24 | c1843569 | 4,126 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101004 | 2021-01-23T17:01:59 | {"gard": ["9296"], "mesh": ["C564375"], "omim": ["607584"], "umls": ["C1843569"], "icd-10": ["G11.4"], "synonyms": ["SPG24"]} |
Not to be confused with Decompression sickness.
Reversible narcotic effects of respiratory nitrogen at elevated partial pressures
* Inert gas narcosis
* [Nitrogen narcosis]
Divers breathe a mixture of oxygen, helium and nitrogen for deep dives to avoid the effects of narcosis. A cylinder label shows the maximum operating depth and mixture (oxygen/helium).
SpecialtyMedical toxicology
Narcosis while diving (also known as nitrogen narcosis, inert gas narcosis, raptures of the deep, Martini effect) is a reversible alteration in consciousness that occurs while diving at depth. It is caused by the anesthetic effect of certain gases at high pressure. The Greek word νάρκωσις (narkōsis), "the act of making numb", is derived from νάρκη (narkē), "numbness, torpor", a term used by Homer and Hippocrates.[1] Narcosis produces a state similar to drunkenness (alcohol intoxication), or nitrous oxide inhalation. It can occur during shallow dives, but does not usually become noticeable at depths less than 30 meters (100 ft).
Except for helium and probably neon, all gases that can be breathed have a narcotic effect, although widely varying in degree.[2][3] The effect is consistently greater for gases with a higher lipid solubility, and there is good evidence that the two properties are mechanistically related.[2] As depth increases, the mental impairment may become hazardous. Divers can learn to cope with some of the effects of narcosis, but it is impossible to develop a tolerance. Narcosis affects all divers, although susceptibility varies widely among individuals and from dive to dive.
Narcosis may be completely reversed in a few minutes by ascending to a shallower depth, with no long-term effects. Thus narcosis while diving in open water rarely develops into a serious problem as long as the divers are aware of its symptoms, and are able to ascend to manage it. Diving much beyond 40 m (130 ft) is generally considered outside the scope of recreational diving. In order to dive at greater depths, as narcosis and oxygen toxicity become critical risk factors, specialist training is required in the use of various helium-containing gas mixtures such as trimix or heliox. These mixtures prevent narcosis by replacing some or all of the inert fraction of the breathing gas with non-narcotic helium.
## Contents
* 1 Classification
* 2 Signs and symptoms
* 3 Causes
* 4 Mechanism
* 5 Management and diagnosis
* 6 Prevention
* 7 Prognosis and epidemiology
* 8 History
* 9 See also
* 10 Footnotes
* 11 References
* 11.1 Notes
* 11.2 Sources
* 12 External links
## Classification[edit]
Narcosis results from breathing gases under elevated pressure, and may be classified by the principal gas involved. The noble gases, except helium and probably neon,[2] as well as nitrogen, oxygen and hydrogen cause a decrement in mental function, but their effect on psychomotor function (processes affecting the coordination of sensory or cognitive processes and motor activity) varies widely. The effect of carbon dioxide is a consistent diminution of mental and psychomotor function.[4] The noble gases argon, krypton, and xenon are more narcotic than nitrogen at a given pressure, and xenon has so much anesthetic activity that it is a usable anesthetic at 80% concentration and normal atmospheric pressure. Xenon has historically been too expensive to be used very much in practice, but it has been successfully used for surgical operations, and xenon anesthesia systems are still being proposed and designed.[5]
## Signs and symptoms[edit]
Narcosis can produce tunnel vision, making it difficult to read multiple gauges.
Due to its perception-altering effects, the onset of narcosis may be hard to recognize.[6][7] At its most benign, narcosis results in relief of anxiety – a feeling of tranquillity and mastery of the environment. These effects are essentially identical to various concentrations of nitrous oxide. They also resemble (though not as closely) the effects of alcohol or cannabis and the familiar benzodiazepine drugs such as diazepam and alprazolam.[8] Such effects are not harmful unless they cause some immediate danger to go unrecognized and unaddressed. Once stabilized, the effects generally remain the same at a given depth, only worsening if the diver ventures deeper.[9]
The most dangerous aspects of narcosis are the impairment of judgement, multi-tasking and coordination, and the loss of decision-making ability and focus. Other effects include vertigo and visual or auditory disturbances. The syndrome may cause exhilaration, giddiness, extreme anxiety, depression, or paranoia, depending on the individual diver and the diver's medical or personal history. When more serious, the diver may feel overconfident, disregarding normal safe diving practices.[10] Slowed mental activity, as indicated by increased reaction time and increased errors in cognitive function, are effects which increase the risk of a diver mismanaging an incident.[11] Narcosis reduces both the perception of cold discomfort and shivering and thereby affects the production of body heat and consequently allows a faster drop in the core temperature in cold water, with reduced awareness of the developing problem.[11][12][13]
The relation of depth to narcosis is sometimes informally known as "Martini's law", the idea that narcosis results in the feeling of one martini for every 10 m (33 ft) below 20 m (66 ft) depth. Professional divers use such a calculation only as a rough guide to give new divers a metaphor, comparing a situation they may be more familiar with.[14]
Reported signs and symptoms are summarized against typical depths in meters and feet of sea water in the following table, closely adapted from Deeper into Diving by Lippman and Mitchell:[10]
Signs and symptoms of narcosis, breathing air Pressure (bar) Depth (m) Depth (ft) Comments
1–2 0–10 0–33
* Unnoticeable minor symptoms, or no symptoms at all
2–4 10–30 33–100
* Mild impairment of performance of unpracticed tasks
* Mildly impaired reasoning
* Mild euphoria possible
4–6 30–50 100–165
* Delayed response to visual and auditory stimuli
* Reasoning and immediate memory affected more than motor coordination
* Calculation errors and wrong choices
* Idea fixation
* Over-confidence and sense of well-being
* Laughter and loquacity (in chambers) which may be overcome by self-control
* Anxiety (common in cold murky water)
6–8 50–70 165–230
* Sleepiness, impaired judgment, confusion
* Hallucinations
* Severe delay in response to signals, instructions and other stimuli
* Occasional dizziness
* Uncontrolled laughter, hysteria (in chamber)
* Terror in some
8–10 70–90 230–300
* Poor concentration and mental confusion
* Stupefaction with some decrease in dexterity and judgment
* Loss of memory, increased excitability
10+ 90+ 300+
* Hallucinations
* Increased intensity of vision and hearing
* Sense of impending blackout or of levitation
* Dizziness, euphoria, manic or depressive states
* Disorganization of the sense of time, changes in facial appearance
* Unconsciousness, (approximate inspired partial pressure of nitrogen for anaesthesia is 33 atm)[11]
* Death
## Causes[edit]
Some components of breathing gases and their relative narcotic potencies:[2][FN 1][3]
Gas Relative narcotic potency
He 0.045
Ne 0.3
H2 0.6
N2 1.0
O2 1.7
Ar 2.3
Kr 7.1
CO2 20.0
Xe 25.6
The cause of narcosis is related to the increased solubility of gases in body tissues, as a result of the elevated pressures at depth (Henry's law).[15] Modern theories have suggested that inert gases dissolving in the lipid bilayer of cell membranes cause narcosis.[16] More recently, researchers have been looking at neurotransmitter receptor protein mechanisms as a possible cause of narcosis.[17] The breathing gas mix entering the diver's lungs will have the same pressure as the surrounding water, known as the ambient pressure. After any change of depth, the pressure of gases in the blood passing through the brain catches up with ambient pressure within a minute or two, which results in a delayed narcotic effect after descending to a new depth.[6][18] Rapid compression potentiates narcosis owing to carbon dioxide retention.[19][20]
A divers' cognition may be affected on dives as shallow as 10 m (33 ft), but the changes are not usually noticeable.[21] There is no reliable method to predict the depth at which narcosis becomes noticeable, or the severity of the effect on an individual diver, as it may vary from dive to dive even on the same day.[6][20]
Significant impairment due to narcosis is an increasing risk below depths of about 30 m (100 ft), corresponding to an ambient pressure of about 4 bar (400 kPa).[6] Most sport scuba training organizations recommend depths of no more than 40 m (130 ft) because of the risk of narcosis.[14] When breathing air at depths of 90 m (300 ft) – an ambient pressure of about 10 bar (1,000 kPa) – narcosis in most divers leads to hallucinations, loss of memory, and unconsciousness.[19][22] A number of divers have died in attempts to set air depth records below 120 m (400 ft). Because of these incidents, Guinness World Records no longer reports on this figure.[23]
Narcosis has been compared with altitude sickness regarding its variability of onset (though not its symptoms); its effects depend on many factors, with variations between individuals. Thermal cold, stress, heavy work, fatigue, and carbon dioxide retention all increase the risk and severity of narcosis.[4][6] Carbon dioxide has a high narcotic potential and also causes increased blood flow to the brain, increasing the effects of other gases.[24] Increased risk of narcosis results from increasing the amount of carbon dioxide retained through heavy exercise, shallow or skip breathing, or because of poor gas exchange in the lungs.[25]
Narcosis is known to be additive to even minimal alcohol intoxication.[26][27] Other sedative and analgesic drugs, such as opiate narcotics and benzodiazepines, add to narcosis.[26]
## Mechanism[edit]
Illustration of a lipid bilayer, typical of a cell membrane, showing the hydrophilic heads on the outside and hydrophobic tails inside
The precise mechanism is not well understood, but it appears to be the direct effect of gas dissolving into nerve membranes and causing temporary disruption in nerve transmissions. While the effect was first observed with air, other gases including argon, krypton and hydrogen cause very similar effects at higher than atmospheric pressure.[28] Some of these effects may be due to antagonism at NMDA receptors and potentiation of GABAA receptors,[29] similar to the mechanism of nonpolar anesthetics such diethyl ether or ethylene.[30] However, their reproduction by the very chemically inactive gas argon makes them unlikely to be a strictly chemical bonding to receptors in the usual sense of a chemical bond. An indirect physical effect – such as a change in membrane volume – would therefore be needed to affect the ligand-gated ion channels of nerve cells.[31] Trudell et al. have suggested non-chemical binding due to the attractive van der Waals force between proteins and inert gases.[32]
Similar to the mechanism of ethanol's effect, the increase of gas dissolved in nerve cell membranes may cause altered ion permeability properties of the neural cells' lipid bilayers. The partial pressure of a gas required to cause a measured degree of impairment correlates well with the lipid solubility of the gas: the greater the solubility, the less partial pressure is needed.[31]
An early theory, the Meyer-Overton hypothesis, suggested that narcosis happens when the gas penetrates the lipids of the brain's nerve cells, causing direct mechanical interference with the transmission of signals from one nerve cell to another.[15][16][20] More recently, specific types of chemically gated receptors in nerve cells have been identified as being involved with anesthesia and narcosis. However, the basic and most general underlying idea, that nerve transmission is altered in many diffuse areas of the brain as a result of gas molecules dissolved in the nerve cells' fatty membranes, remains largely unchallenged.[17][33]
## Management and diagnosis[edit]
The management of narcosis is simply to ascend to shallower depths; the effects then disappear within minutes.[34] In the event of complications or other conditions being present, ascending is always the correct initial response. Should problems remain, then it is necessary to abort the dive. The decompression schedule can still be followed unless other conditions require emergency assistance.[35]
The symptoms of narcosis may be caused by other factors during a dive: ear problems causing disorientation or nausea;[36] early signs of oxygen toxicity causing visual disturbances;[37] or hypothermia causing rapid breathing and shivering.[38] Nevertheless, the presence of any of these symptoms should imply narcosis. Alleviation of the effects upon ascending to a shallower depth will confirm the diagnosis. Given the setting, other likely conditions do not produce reversible effects. In the rare event of misdiagnosis when another condition is causing the symptoms, the initial management – ascending closer to the surface – is still essential.[7]
## Prevention[edit]
Narcosis while deep diving is prevented by filling dive cylinders with a gas mixture containing helium. Helium is stored in brown cylinders.
The most straightforward way to avoid nitrogen narcosis is for a diver to limit the depth of dives. Since narcosis becomes more severe as depth increases, a diver keeping to shallower depths can avoid serious narcosis. Most recreational dive schools will only certify basic divers to depths of 18 m (60 ft), and at these depths narcosis does not present a significant risk. Further training is normally required for certification up to 30 m (100 ft) on air, and this training should include a discussion of narcosis, its effects, and cure. Some diver training agencies offer specialized training to prepare recreational divers to go to depths of 40 m (130 ft), often consisting of further theory and some practice in deep dives under close supervision.[39][FN 2] Scuba organizations that train for diving beyond recreational depths,[FN 3] may forbid diving with gases that cause too much narcosis at depth in the average diver, and strongly encourage the use of other breathing gas mixes containing helium in place of some or all of the nitrogen in air – such as trimix and heliox – because helium has no narcotic effect.[2][40] The use of these gases forms part of technical diving and requires further training and certification.[14]
While the individual diver cannot predict exactly at what depth the onset of narcosis will occur on a given day, the first symptoms of narcosis for any given diver are often more predictable and personal. For example, one diver may have trouble with eye focus (close accommodation for middle-aged divers), another may experience feelings of euphoria, and another feelings of claustrophobia. Some divers report that they have hearing changes, and that the sound their exhaled bubbles make becomes different. Specialist training may help divers to identify these personal onset signs, which may then be used as a signal to ascend to avoid the narcosis, although severe narcosis may interfere with the judgement necessary to take preventive action.[34]
Deep dives should be made only after a gradual training to test the individual diver's sensitivity to increasing depths, with careful supervision and logging of reactions. Scientific evidence does not show that a diver can train to overcome any measure of narcosis at a given depth or become tolerant of it.[41]
Equivalent narcotic depth (END) is a commonly used way of expressing the narcotic effect of different breathing gases.[42] The National Oceanic and Atmospheric Administration (NOAA) Diving Manual now states that oxygen and nitrogen should be considered equally narcotic.[43] Standard tables, based on relative lipid solubilities, list conversion factors for narcotic effect of other gases.[44] For example, hydrogen at a given pressure has a narcotic effect equivalent to nitrogen at 0.55 times that pressure, so in principle it should be usable at more than twice the depth. Argon, however, has 2.33 times the narcotic effect of nitrogen, and is a poor choice as a breathing gas for diving (it is used as a drysuit inflation gas, owing to its low thermal conductivity). Some gases have other dangerous effects when breathed at pressure; for example, high-pressure oxygen can lead to oxygen toxicity. Although helium is the least intoxicating of the breathing gases, at greater depths it can cause high pressure nervous syndrome, a still mysterious but apparently unrelated phenomenon.[45] Inert gas narcosis is only one factor influencing the choice of gas mixture; the risks of decompression sickness and oxygen toxicity, cost, and other factors are also important.[46]
Because of similar and additive effects, divers should avoid sedating medications and drugs, such as cannabis and alcohol before any dive. A hangover, combined with the reduced physical capacity that goes with it, makes nitrogen narcosis more likely.[26] Experts recommend total abstinence from alcohol for at least 12 hours before diving, and longer for other drugs.[47]
## Prognosis and epidemiology[edit]
Narcosis is potentially one of the most dangerous conditions to affect the scuba diver below about 30 m (100 ft). Except for occasional amnesia of events at depth, the effects of narcosis are entirely removed on ascent and therefore pose no problem in themselves, even for repeated, chronic or acute exposure.[6][20] Nevertheless, the severity of narcosis is unpredictable and it can be fatal while diving, as the result of illogical behavior in a dangerous environment.[20]
Tests have shown that all divers are affected by nitrogen narcosis, though some experience lesser effects than others. Even though it is possible that some divers can manage better than others because of learning to cope with the subjective impairment, the underlying behavioral effects remain.[30][48][49] These effects are particularly dangerous because a diver may feel they are not experiencing narcosis, yet still be affected by it.[6]
## History[edit]
Both Meyer and Overton discovered that the narcotic potency of an anesthetic can generally be predicted from its solubility in oil. Minimum Alveolar Concentration is an inverse indicator of anaesthetic potency.
See also: Theories of general anesthetic action
French researcher Victor T. Junod was the first to describe symptoms of narcosis in 1834, noting "the functions of the brain are activated, imagination is lively, thoughts have a peculiar charm and, in some persons, symptoms of intoxication are present."[50][51] Junod suggested that narcosis resulted from pressure causing increased blood flow and hence stimulating nerve centers.[52] Walter Moxon (1836–1886), a prominent Victorian physician, hypothesized in 1881 that pressure forced blood to inaccessible parts of the body and the stagnant blood then resulted in emotional changes.[53] The first report of anesthetic potency being related to lipid solubility was published by Hans H. Meyer in 1899, entitled Zur Theorie der Alkoholnarkose. Two years later a similar theory was published independently by Charles Ernest Overton.[54] What became known as the Meyer-Overton Hypothesis may be illustrated by a graph comparing narcotic potency with solubility in oil.
In 1939, Albert R. Behnke and O. D. Yarborough demonstrated that gases other than nitrogen also could cause narcosis.[55] For an inert gas the narcotic potency was found to be proportional to its lipid solubility. As hydrogen has only 0.55 the solubility of nitrogen, deep diving experiments using hydrox were conducted by Arne Zetterström between 1943 and 1945.[56] Jacques-Yves Cousteau in 1953 famously described it as "l’ivresse des grandes profondeurs" or the "rapture of the deep".[57]
Further research into the possible mechanisms of narcosis by anesthetic action led to the "minimum alveolar concentration" concept in 1965. This measures the relative concentration of different gases required to prevent motor response in 50% of subjects in response to stimulus, and shows similar results for anesthetic potency as the measurements of lipid solubility.[58] The (NOAA) Diving Manual was revised to recommend treating oxygen as if it were as narcotic as nitrogen, following research by Christian J. Lambertsen et al. in 1977 and 1978.[59]
## See also[edit]
* Hydrogen narcosis – Psychotropic state induced by breathing hydrogen at high partial pressures
## Footnotes[edit]
1. ^ Value for Krypton from 4th Edition, p. 176.
2. ^ A number of technical diving agencies, such as TDI and IANTD teach "extended range" or "deep air" courses which teach diving to depths of up to 55 m (180 ft) without helium.
3. ^ BSAC, SAA and other European training agencies teach recreational diving to a depth limit of 50 m (160 ft).
## References[edit]
### Notes[edit]
1. ^ Askitopoulou, Helen; Ramoutsaki, Ioanna A; Konsolaki, Eleni (April 12, 2000). "Etymology and Literary History of Related Greek Words". Analgesia and Anesthesia. International Anesthesia Research Society. 91 (2): 486–491. Retrieved 2010-06-09.
2. ^ a b c d e Bennett & Rostain (2003), p. 305.
3. ^ a b Bauer, Ralph W.; Way, Robert O. (1970). "Relative narcotic potencies of hydrogen, helium, nitrogen, and their mixtures".
4. ^ a b Hesser, CM; Fagraeus, L; Adolfson, J (1978). "Roles of nitrogen, oxygen, and carbon dioxide in compressed-air narcosis". Undersea and Hyperbaric Medicine. Undersea and Hyperbaric Medical Society, Inc. 5 (4): 391–400. ISSN 0093-5387. OCLC 2068005. PMID 734806. Retrieved 2009-07-29.
5. ^ Burov, NE; Kornienko, Liu; Makeev, GN; Potapov, VN (November–December 1999). "Clinical and experimental study of xenon anesthesia". Anesteziol Reanimatol (6): 56–60. Retrieved 2008-11-03.
6. ^ a b c d e f g Bennett & Rostain (2003), p. 301.
7. ^ a b U.S. Navy Diving Manual (2008), vol. 1, ch. 3, p. 40.
8. ^ Hobbs M (2008). "Subjective and behavioural responses to nitrogen narcosis and alcohol". Undersea & Hyperbaric Medicine. 35 (3): 175–84. PMID 18619113. Retrieved 2009-08-07.
9. ^ Lippmann & Mitchell (2005), p. 103.
10. ^ a b Lippmann & Mitchell (2005), p. 105.
11. ^ a b c Doolette, David J. (August 2008). "2: Inert Gas Narcosis". In Mount, Tom; Dituri, Joseph (eds.). Exploration and Mixed Gas Diving Encyclopedia (1st ed.). Miami Shores, Florida: International Association of Nitrox Divers. pp. 33–40. ISBN 978-0-915539-10-9.
12. ^ Mekjavic, Igor B.; Passias, T.; Sundberg, Carl Johan; Eiken, O. (April 1994). "Perception of thermal comfort during narcosis". Undersea & Hyperbaric Medicine. Undersea and Hyperbaric Medical Society. 21 (1): 9–19. PMID 8180569. Retrieved 26 December 2011.
13. ^ Mekjavic, Igor B.; Savić, S. A.; Eiken, O. (June 1995). "Nitrogen narcosis attenuates shivering thermogenesis". Journal of Applied Physiology. American Physiological Society. 78 (6): 2241–4. doi:10.1152/jappl.1995.78.6.2241. PMID 7665424.
14. ^ a b c Brylske, A (2006). Encyclopedia of Recreational Diving (3rd ed.). United States: Professional Association of Diving Instructors. ISBN 1-878663-01-1.
15. ^ a b Bennett & Rostain (2003), p. 308.
16. ^ a b Paton, William (1975). "Diver narcosis, from man to cell membrane". Journal of the South Pacific Underwater Medicine Society (First Published at Oceans 2000 Conference). 5 (2). Retrieved 2008-12-23.
17. ^ a b Rostain, Jean C; Balon N (2006). "Recent neurochemical basis of inert gas narcosis and pressure effects". Undersea and Hyperbaric Medicine. 33 (3): 197–204. PMID 16869533. Retrieved 2008-12-23.
18. ^ Case, EM; Haldane, John Burdon Sanderson (1941). "Human physiology under high pressure". Journal of Hygiene. 41 (3): 225–49. doi:10.1017/S0022172400012432. PMC 2199778. PMID 20475589.
19. ^ a b Bennett & Rostain (2003), p. 303.
20. ^ a b c d e Hamilton, RW; Kizer, KW (eds) (1985). "Nitrogen Narcosis". 29th Undersea and Hyperbaric Medical Society Workshop. Bethesda, MD: Undersea and Hyperbaric Medical Society (UHMS Publication Number 64WS(NN)4-26-85). Retrieved 2008-12-23.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)
21. ^ Petri, NM (2003). "Change in strategy of solving psychological tests: evidence of nitrogen narcosis in shallow air-diving". Undersea and Hyperbaric Medicine. Undersea and Hyperbaric Medical Society, Inc. 30 (4): 293–303. PMID 14756232. Retrieved 2008-12-23.
22. ^ Hill, Leonard; David, RH; Selby, RP; et al. (1933). "Deep diving and ordinary diving". Report of a Committee Appointed by the British Admiralty.
23. ^ PSAI Philippines. "Professional Scuba Association International History". Professional Scuba Association International – Philippines. Archived from the original on 2009-01-01. Retrieved 2008-10-31.
24. ^ Kety, Seymour S; Schmidt, Carl F (1948). "The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men". Journal of Clinical Investigation. 27 (4): 484–492. doi:10.1172/JCI101995. ISSN 0021-9738. PMC 439519. PMID 16695569.
25. ^ Lippmann & Mitchell (2005), pp. 110–3.
26. ^ a b c Fowler, B; Hamilton, K; Porlier, G (1986). "Effects of ethanol and amphetamine on inert gas narcosis in humans". Undersea Biomedical Research. 13 (3): 345–54. PMID 3775969. Retrieved 2008-12-23.
27. ^ Michalodimitrakis, E; Patsalis, A (1987). "Nitrogen narcosis and alcohol consumption—a scuba diving fatality". Journal of Forensic Sciences. 32 (4): 1095–7. doi:10.1520/JFS12421J. PMID 3612064.
28. ^ Bennett & Rostain (2003), p. 304.
29. ^ Hapfelmeier, Gerhard; Zieglgänsberger, Walter; Haseneder, Rainer; Schneck, Hajo; Kochs, Eberhard (December 2000). "Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors". Anesthesia and Analgesia. 91 (6): 1542–9. doi:10.1097/00000539-200012000-00045. PMID 11094015. Retrieved 2009-07-29.
30. ^ a b Hamilton, K; Laliberté, MF; Fowler, B (1995). "Dissociation of the behavioral and subjective components of nitrogen narcosis and diver adaptation". Undersea & Hyperbaric Medicine. 22 (1): 41–49. ISSN 1066-2936. OCLC 26915585. PMID 7742709. Retrieved 2009-07-29.
31. ^ a b Franks, NP; Lieb, WR (1994). "Molecular and cellular mechanisms of general anaesthesia". Nature. 367 (6464): 607–14. Bibcode:1994Natur.367..607F. doi:10.1038/367607a0. PMID 7509043.
32. ^ Trudell, JR; Koblin, DD; Eger, EI (1998). "A molecular description of how noble gases and nitrogen bind to a model site of anesthetic action". Anesthesia and Analgesia. 87 (2): 411–8. doi:10.1097/00000539-199808000-00034. PMID 9706942. Retrieved 2008-12-01.
33. ^ Smith, EB (July 1987). "Priestley lecture 1986. On the science of deep-sea diving—observations on the respiration of different kinds of air". Undersea & Hyperbaric Medicine. 14 (4): 347–69. PMID 3307084. Retrieved 2009-07-29.
34. ^ a b Lippmann & Mitchell (2005), p. 106.
35. ^ U.S. Navy Diving Manual (2008), vol. 2, ch. 9, pp. 35–46.
36. ^ Molvaer, Otto I (2003). "Otorhinolaryngological aspects of diving". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett & Rostain's physiology and medicine of diving (5th ed.). United States: Saunders Ltd. p. 234. ISBN 0-7020-2571-2. OCLC 51607923.
37. ^ Clark, James M; Thom, Stephen R (2003). "Oxygen under pressure". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett & Rostain's physiology and medicine of diving (5th ed.). United States: Saunders Ltd. p. 374. ISBN 0-7020-2571-2. OCLC 51607923.
38. ^ Mekjavic, Igor B; Tipton, Michael J; Eiken, Ola (2003). "Thermal considerations in diving". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett & Rostain's physiology and medicine of diving (5th ed.). United States: Saunders Ltd. p. 129. ISBN 0-7020-2571-2. OCLC 51607923.
39. ^ "Extended Range Diver". International Training. 2009. Retrieved 2013-01-24.
40. ^ Hamilton Jr, RW; Schreiner, HR (eds) (1975). "Development of Decompression Procedures for Depths in Excess of 400 feet". 9th Undersea and Hyperbaric Medical Society Workshop. Bethesda, MD: Undersea and Hyperbaric Medical Society (UHMS Publication Number WS2–28–76): 272. Retrieved 2008-12-23.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)
41. ^ Hamilton, K; Laliberté, MF; Heslegrave, R (1992). "Subjective and behavioral effects associated with repeated exposure to narcosis". Aviation, Space, and Environmental Medicine. 63 (10): 865–9. PMID 1417647.
42. ^ IANTD (January 1, 2009). "IANTD Scuba & CCR, PSCR & SCR Rebreather Diver Programs (Recreational Trimix Diver)". IANTD. Archived from the original on April 2, 2009. Retrieved 2009-03-22.
43. ^ "Mixed-Gas & Oxygen". NOAA Diving Manual, Diving for Science and Technology. 4th. National Oceanic and Atmospheric Administration. 2002. "[16.3.1.2.4] ... since oxygen has some narcotic properties, it is appropriate to include the oxygen in the END calculation when using trimixes (Lambersten et al. 1977,1978). The non-helium portion (i.e., the sum of the oxygen and the nitrogen) is to be regarded as having the same narcotic potency as an equivalent partial pressure of nitrogen in air, regardless of the proportions of oxygen and nitrogen."
44. ^ Anttila, Matti (2000). "Narcotic factors of gases". Archived from the original on 2013-12-09. Retrieved 2008-06-10.
45. ^ Bennett, Peter; Rostain, Jean Claude (2003). "The High Pressure Nervous Syndrome". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett & Rostain's physiology and medicine of diving (5th ed.). United States: Saunders Ltd. pp. 323–57. ISBN 0-7020-2571-2. OCLC 51607923.
46. ^ Lippmann & Mitchell (2005), pp. 430–1.
47. ^ St Leger Dowse, Marguerite (2008). "Diving Officer's Conference presentations". British Sub-Aqua Club. Retrieved 2009-08-16.
48. ^ Fowler, B; Ackles, KN; Porlier, G (1985). "Effects of inert gas narcosis on behavior—a critical review". Undersea & Hyperbaric Medicine. 12 (4): 369–402. ISSN 0093-5387. OCLC 2068005. PMID 4082343. Archived from the original on 2010-12-25. Retrieved 2009-07-29.
49. ^ Rogers, WH; Moeller, G (1989). "Effect of brief, repeated hyperbaric exposures on susceptibility to nitrogen narcosis". Undersea & Hyperbaric Medicine. 16 (3): 227–32. ISSN 0093-5387. OCLC 2068005. PMID 2741255. Archived from the original on 2009-09-01. Retrieved 2009-07-29.
50. ^ Bennett & Rostain (2003), p. 300.
51. ^ Junod, Victor T (1834). "Recherches physiologiques et thérapeutiques sur les effets de la compression et de la raréfaction de l'air". Revue médicale française et étrangère: Journal des progrès de la médecine hippocratique. Chez Gabon et compagnie: 350–68. Retrieved 2009-06-04.
52. ^ Bennett & Rostain (2003), p. 306.
53. ^ Moxon, Walter (1881). "Croonian lectures on the influence of the circulation on the nervous system". British Medical Journal. 1 (1057): 491–7. doi:10.1136/bmj.1.1057.491. PMC 2263574. PMID 20749830.
Moxon, Walter (1881). "Croonian lectures on the influence of the circulation on the nervous system". British Medical Journal. 1 (1059): 583–5. doi:10.1136/bmj.1.1059.583. PMC 2263398. PMID 20749844.
54. ^ Overton, Charles Ernest (1901). "Studien Über Die Narkose". Allgemeiner Pharmakologie (in German). Institut für Pharmakologie.
55. ^ Behnke, AR; Yarborough, OD (1939). "Respiratory resistance, oil-water solubility and mental effects of argon compared with helium and nitrogen". American Journal of Physiology. 126 (2): 409–15. doi:10.1152/ajplegacy.1939.126.2.409.
56. ^ Ornhagen, H (1984). "Hydrogen-Oxygen (Hydrox) breathing at 1.3 MPa". FOA Rapport C58015-H1. Stockholm: National Defence Research Institute. ISSN 0347-7665.
57. ^ Cousteau, Jacques-Yves; Dumas, Frédéric (1953). The Silent World: A Story of Undersea Discovery and Adventure. Harper & Brothers Publishers. p. 266. ISBN 0-7922-6796-6.
58. ^ Eger, EI; Saidman, LJ; Brandstater, B (1965). "Minimum alveolar anesthetic concentration: a standard of anesthetic potency". Anesthesiology. 26 (6): 756–63. doi:10.1097/00000542-196511000-00010. PMID 5844267.
59. ^ Lambertsen, Christian J; Gelfand, R; Clark, JM (1978). "University of Pennsylvania Institute for Environmental Medicine report, 1978". University of Pennsylvania. Institute for Environmental Medicine. Archived from the original on June 12, 2010. Retrieved 2009-03-22.
### Sources[edit]
* Bennett, Peter; Rostain, Jean Claude (2003). "Inert Gas Narcosis". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliott's physiology and medicine of diving (5th ed.). United States: Saunders. ISBN 0-7020-2571-2. OCLC 51607923.
* Lippmann, John; Mitchell, Simon J. (2005). "Nitrogen narcosis". Deeper into Diving (2nd ed.). Victoria, Australia: J. L. Publications. pp. 103–8. ISBN 0-9752290-1-X. OCLC 66524750.
* U.S. Navy Supervisor of Diving (2008). U.S. Navy Diving Manual (PDF). SS521-AG-PRO-010, revision 6. U.S. Naval Sea Systems Command. Archived from the original (PDF) on 2014-12-10. Retrieved 2014-01-21.
## External links[edit]
* Undersea and Hyperbaric Medical Society Scientific body, publications about nitrogen narcosis.
* Rubicon Research Repository Searchable repository of Diving and Environmental Physiology Research.
* Diving Diseases Research Centre (DDRC) UK charity dedicated to treatment of diving diseases.
* Campbell, Ernest S. (2009-06-25). "Diving While Using Marijuana". Retrieved 2009-08-25. ScubaDoc's overview of marijuana and diving.
* Campbell, Ernest S. (2009-05-03). "Alcohol and Diving". Archived from the original on 2007-04-30. Retrieved 2009-08-25. ScubaDoc's overview of alcohol and diving.
* Campbell, George D. (2009-02-01). "Nitrogen Narcosis". Diving with Deep-Six. Retrieved 2009-08-25.
Classification
D
* MeSH: D007222
* DiseasesDB: 30088
* v
* t
* e
Underwater diving
* Diving modes
* Atmospheric pressure diving
* Freediving
* Saturation diving
* Scuba diving
* Snorkeling
* Surface oriented diving
* Surface-supplied diving
* Unmanned diving
Diving equipment
* Cleaning and disinfection of personal diving equipment
* Human factors in diving equipment design
Basic equipment
* Diving mask
* Snorkel
* Swimfin
Breathing gas
* Bailout gas
* Bottom gas
* Breathing air
* Decompression gas
* Emergency gas supply
* Heliox
* Nitrox
* Oxygen
* Travel gas
* Trimix
Buoyancy and
trim equipment
* Buoyancy compensator
* Power inflator
* Dump valve
* Diving weighting system
* Ankle weights
* Integrated weights
* Trim weights
* Weight belt
Decompression
equipment
* Decompression buoy
* Decompression cylinder
* Decompression trapeze
* Dive computer
* Diving shot
* Jersey upline
* Jonline
Diving suit
* Atmospheric diving suit
* Dry suit
* Sladen suit
* Standard diving suit
* Rash vest
* Wetsuit
* Dive skins
* Hot-water suit
Helmets
and masks
* Anti-fog
* Diving helmet
* Free-flow helmet
* Lightweight demand helmet
* Orinasal mask
* Reclaim helmet
* Shallow water helmet
* Standard diving helmet
* Diving mask
* Band mask
* Full-face mask
* Half mask
Instrumentation
* Bottom timer
* Depth gauge
* Dive computer
* Dive timer
* Diving watch
* Helium release valve
* Pneumofathometer
* Submersible pressure gauge
Mobility
equipment
* Diving bell
* Closed bell
* Wet bell
* Diving stage
* Swimfin
* Monofin
* PowerSwim
* Towboard
Diver
propulsion
vehicle
* Advanced SEAL Delivery System
* Cosmos CE2F series
* Dry Combat Submersible
* Human torpedo
* Motorised Submersible Canoe
* Necker Nymph
* R-2 Mala-class swimmer delivery vehicle
* SEAL Delivery Vehicle
* Shallow Water Combat Submersible
* Siluro San Bartolomeo
* Wet Nellie
* Wet sub
Safety
equipment
* Alternative air source
* Octopus regulator
* Pony bottle
* Bolt snap
* Buddy line
* Dive light
* Diver's cutting tool
* Diver's knife
* Diver's telephone
* Through-water communications
* Diving bell
* Diving safety harness
* Emergency gas supply
* Bailout block
* Bailout bottle
* Lifeline
* Screw gate carabiner
* Emergency locator beacon
* Rescue tether
* Safety helmet
* Shark-proof cage
* Snoopy loop
* Navigation equipment
* Distance line
* Diving compass
* Dive reel
* Line marker
* Surface marker buoy
* Silt screw
Underwater
breathing
apparatus
* Atmospheric diving suit
* Diving cylinder
* Burst disc
* Diving cylinder valve
* Diving helmet
* Reclaim helmet
* Diving regulator
* Mechanism of diving regulators
* Regulator malfunction
* Regulator freeze
* Single-hose regulator
* Twin-hose regulator
* Full face diving mask
Open-circuit
scuba
* Scuba set
* Bailout bottle
* Decompression cylinder
* Independent doubles
* Manifolded twin set
* Scuba manifold
* Pony bottle
* Scuba configuration
* Sidemount
* Sling cylinder
Diving
rebreathers
* Carbon dioxide scrubber
* Carleton CDBA
* CDLSE
* Cryogenic rebreather
* CUMA
* DSEA
* Dolphin
* Electro-galvanic oxygen sensor
* FROGS
* Halcyon PVR-BASC
* Halcyon RB80
* IDA71
* Interspiro DCSC
* KISS
* LAR-5
* LAR-6
* LAR-V
* LARU
* Porpoise
* Ray
* Siebe Gorman CDBA
* Siva
* Viper
Surface-supplied
diving equipment
* Air line
* Diver's umbilical
* Diving air compressor
* Gas panel
* Hookah
* Scuba replacement
* Sea Trek
* Snuba
* Standard diving dress
Escape set
* Davis Submerged Escape Apparatus
* Momsen lung
* Steinke hood
* Submarine Escape Immersion Equipment
*
Diving
equipment
manufacturers
* AP Diving
* Apeks
* Aqua Lung America
* Aqua Lung/La Spirotechnique
* Beuchat
* René Cavalero
* Cis-Lunar
* Cressi-Sub
* Dacor
* DESCO
* Dive Xtras
* Divex
* Diving Unlimited International
* Drägerwerk
* Fenzy
* Maurice Fernez
* Technisub
* Oscar Gugen
* Heinke
* HeinrichsWeikamp
* Johnson Outdoors
* Mares
* Morse Diving
* Nemrod
* Oceanic Worldwide
* Porpoise
* Sub Sea Systems
* Shearwater Research
* Siebe Gorman
* Submarine Products
* Suunto
Diving support equipment
Access equipment
* Boarding stirrup
* Diver lift
* Diving bell
* Diving ladder
* Diving platform (scuba)
* Diving stage
* Downline
* Jackstay
* Launch and recovery system
* Messenger line
* Moon pool
Breathing gas
handling
* Air filtration
* Activated carbon
* Hopcalite
* Molecular sieve
* Silica gel
* Booster pump
* Carbon dioxide scrubber
* Cascade filling system
* Diver's pump
* Diving air compressor
* Diving air filter
* Water separator
* High pressure breathing air compressor
* Low pressure breathing air compressor
* Gas blending
* Gas blending for scuba diving
* Gas panel
* Gas reclaim system
* Gas storage bank
* Gas storage quad
* Gas storage tube
* Helium analyzer
* Nitrox production
* Membrane gas separation
* Pressure swing adsorption
* Oxygen analyser
* Oxygen compatibility
Decompression
equipment
* Built-in breathing system
* Decompression tables
* Diving bell
* Bell cursor
* Closed bell
* Clump weight
* Launch and recovery system
* Wet bell
* Diving chamber
* Diving stage
* Recreational Dive Planner
* Saturation system
Platforms
* Dive boat
* Canoe and kayak diving
* Combat Rubber Raiding Craft
* Liveaboard
* Subskimmer
* Diving support vessel
* HMS Challenger (K07)
Underwater
habitat
* Aquarius Reef Base
* Continental Shelf Station Two
* Helgoland Habitat
* Jules' Undersea Lodge
* Scott Carpenter Space Analog Station
* SEALAB
* Tektite habitat
Remotely operated
underwater vehicles
* 8A4-class ROUV
* ABISMO
* Atlantis ROV Team
* CURV
* Deep Drone
* Épaulard
* Global Explorer ROV
* Goldfish-class ROUV
* Kaikō ROV
* Kaşif ROUV
* Long-Term Mine Reconnaissance System
* Mini Rover ROV
* OpenROV
* ROV KIEL 6000
* ROV PHOCA
* Scorpio ROV
* Sea Dragon-class ROV
* Seabed tractor
* Seafox drone
* Seahorse ROUV
* SeaPerch
* SJT-class ROUV
* T1200 Trenching Unit
* VideoRay UROVs
Safety equipment
* Diver down flag
* Diving shot
* Hyperbaric lifeboat
* Hyperbaric stretcher
* Jackstay
* Jonline
* Reserve gas supply
General
* Diving spread
* Air spread
* Saturation spread
* Hot water system
* Sonar
* Underwater acoustic positioning system
* Underwater acoustic communication
Freediving
Activities
* Aquathlon
* Apnoea finswimming
* Freediving
* Haenyeo
* Pearl hunting
* Ama
* Snorkeling
* Spearfishing
* Underwater football
* Underwater hockey
* Underwater ice hockey
* Underwater rugby
* Underwater target shooting
Competitions
* Nordic Deep
* Vertical Blue
* Disciplines
* Constant weight (CWT)
* Constant weight without fins (CNF)
* Dynamic apnea (DYN)
* Dynamic apnea without fins (DNF)
* Free immersion (FIM)
* No-limits apnea (NLT)
* Static apnea (STA)
* Skandalopetra diving
* Variable weight apnea (VWT)
* Variable weight apnea without fins
Equipment
* Diving mask
* Diving suit
* Hawaiian sling
* Polespear
* Snorkel (swimming)
* Speargun
* Swimfins
* Monofin
* Water polo cap
Freedivers
* Deborah Andollo
* Peppo Biscarini
* Sara Campbell
* Derya Can Göçen
* Goran Čolak
* Carlos Coste
* Robert Croft
* Mandy-Rae Cruickshank
* Yasemin Dalkılıç
* Leonardo D'Imporzano
* Flavia Eberhard
* Şahika Ercümen
* Emma Farrell
* Francisco Ferreras
* Pierre Frolla
* Flavia Eberhard
* Mehgan Heaney-Grier
* Elisabeth Kristoffersen
* Loïc Leferme
* Enzo Maiorca
* Jacques Mayol
* Audrey Mestre
* Karol Meyer
* Stéphane Mifsud
* Alexey Molchanov
* Natalia Molchanova
* Dave Mullins
* Patrick Musimu
* Guillaume Néry
* Herbert Nitsch
* Umberto Pelizzari
* Annelie Pompe
* Michal Risian
* Stig Severinsen
* Tom Sietas
* Aharon Solomons
* Martin Štěpánek
* Walter Steyn
* Tanya Streeter
* William Trubridge
* Devrim Cenk Ulusoy
* Danai Varveri
* Alessia Zecchini
* Nataliia Zharkova
Hazards
* Barotrauma
* Drowning
* Freediving blackout
* Deep-water blackout
* Shallow-water blackout
* Hypercapnia
* Hypothermia
Historical
* Ama
* Octopus wrestling
* Swimming at the 1900 Summer Olympics – Men's underwater swimming
Organisations
* AIDA International
* Scuba Schools International
* Australian Underwater Federation
* British Freediving Association
* Confédération Mondiale des Activités Subaquatiques
* Fédération Française d'Études et de Sports Sous-Marins
* Performance Freediving International
Professional diving
Occupations
* Ama
* Commercial diver
* Commercial offshore diver
* Hazmat diver
* Divemaster
* Diving instructor
* Diving safety officer
* Diving superintendent
* Diving supervisor
* Haenyeo
* Media diver
* Police diver
* Public safety diver
* Scientific diver
* Underwater archaeologist
Military diving
* Army engineer diver
* Clearance diver
* Frogman
* List of military diving units
* Royal Navy ships diver
* Special Boat Service
* United States military divers
* U.S. Navy diver
* U.S.Navy master diver
* United States Navy SEALs
* Underwater Demolition Team
Underwater work
* Commercial offshore diving
* Dive leader
* Diver training
* Recreational diver training
* Hyperbaric welding
* Media diving
* Nondestructive testing
* Pearl hunting
* Police diving
* Potable water diving
* Public safety diving
* Scientific diving
* Ships husbandry
* Sponge diving
* Submarine pipeline
* Underwater archaeology
* Archaeology of shipwrecks
* Underwater construction
* Offshore construction
* Underwater demolition
* Underwater photography
* Underwater search and recovery
* Underwater videography
Salvage diving
* SS Egypt
* Kronan
* La Belle
* SS Laurentic
* RMS Lusitania
* Mars
* Mary Rose
* USS Monitor
* HMS Royal George
* Vasa
Diving contractors
* COMEX
* Helix Energy Solutions Group
Tools & equipment
* Abrasive waterjet
* Airlift
* Baited remote underwater video
* In-water surface cleaning
* Brush cart
* Cavitation cleaning
* Pressure washing
* Pigging
* Lifting bag
* Remotely operated underwater vehicle
* Thermal lance
* Tremie
* Water jetting
Underwater
weapons
* Limpet mine
* Speargun
* Hawaiian sling
* Polespear
Underwater
firearm
* Gyrojet
* Mk 1 Underwater Defense Gun
* Powerhead
* Underwater pistols
* Heckler & Koch P11
* SPP-1 underwater pistol
* Underwater revolvers
* AAI underwater revolver
* Underwater rifles
* ADS amphibious rifle
* APS underwater rifle
* ASM-DT amphibious rifle
Recreational diving
Specialties
* Altitude diving
* Cave diving
* Deep diving
* Ice diving
* Muck diving
* Open-water diving
* Rebreather diving
* Sidemount diving
* Solo diving
* Technical diving
* Underwater photography
* Wreck diving
Diver
organisations
* British Sub-Aqua Club (BSAC)
* Cave Divers Association of Australia (CDAA)
* Cave Diving Group (CDG)
* Comhairle Fo-Thuinn (CFT)
* Confédération Mondiale des Activités Subaquatiques (CMAS)
* Federación Española de Actividades Subacuáticas (FEDAS)
* Fédération Française d'Études et de Sports Sous-Marins (FFESSM)
* International Association for Handicapped Divers (IAHD)
* National Association for Cave Diving (NACD)
* Woodville Karst Plain Project (WKPP)
Diving tourism
industry
* Dive center
* Environmental impact of recreational diving
* Scuba diving tourism
* Shark tourism
* Sinking ships for wreck diving sites
Diving events
and festivals
* Diversnight
* Underwater Bike Race
Recreational
dive sites
Reef diving
regions
* Aliwal Shoal Marine Protected Area
* Arrecifes de Cozumel National Park
* Edmonds Underwater Park
* Great Barrier Reef
* iSimangaliso Marine Protected Area
* Poor Knights Islands
* Table Mountain National Park Marine Protected Area
Reef dive
sites
* Artificial reef
* Gibraltar Artificial Reef
* Shark River Reef
* Osborne Reef
* Fanadir
* Gamul Kebir
* Palancar Reef
* Underwater artworks
* Cancún Underwater Museum
* Christ of the Abyss
* Molinere Underwater Sculpture Park
Wreck diving
regions
* Chuuk Lagoon
* Edmonds Underwater Park
* Finger Lakes Underwater Preserve Association
* Maritime Heritage Trail – Battle of Saipan
* Michigan Underwater Preserves
* Robben Island Marine Protected Area
* Table Mountain National Park Marine Protected Area
* Tulagi
* Tulamben
* Whitefish Point Underwater Preserve
* Wreck Alley, San Diego
Wreck dive
sites
* HMS A1
* HMS A3
* USS Aaron Ward
* Abessinia
* Aeolian Sky
* Albert C. Field
* Andrea Doria
* Antilla
* Antilles
* Aquila
* USS Arkansas
* Bianca C.
* SS Binnendijk
* HMS Boadicea
* Booya
* HMSAS Bloemfontein
* Breda
* HMAS Brisbane
* HMHS Britannic
* Bungsberg
* HMAS Canberra
* Carl D. Bradley
* Carnatic
* SMS Dresden
* Dunraven
* Eastfield
* HMT Elk
* Ellengowan
* RMS Empress of Ireland
* HMS Falmouth
* Fifi
* SS Francisco Morazan
* Fujikawa Maru
* Fumizuki
* SATS General Botha
* USNS General Hoyt S. Vandenberg
* HMS Ghurka
* Glen Strathallan
* SAS Good Hope
* Gothenburg
* Herzogin Cecilie
* Hilma Hooker
* Hispania
* HMS Hood
* HMAS Hobart
* Igara
* James Eagan Layne
* Captain Keith Tibbetts
* King Cruiser
* SMS Kronprinz
* Kyarra
* HMS Laforey
* USAT Liberty
* Louis Sheid
* USS LST-507
* SMS Markgraf
* Mikhail Lermontov
* HMS M2
* Maine
* Maloja
* HMS Maori
* Marguerite
* SS Mauna Loa
* USAT Meigs
* Mendi
* USCGC Mohawk
* Mohegan
* RMS Moldavia
* HMS Montagu
* MV RMS Mulheim
* Nagato
* Oceana
* USS Oriskany
* Oslofjord
* P29
* P31
* Pedernales
* Persier
* HMAS Perth
* SAS Pietermaritzburg
* Piłsudski
* Pool Fisher
* HMS Port Napier
* Preußen
* President Coolidge
* PS Queen Victoria
* Radaas
* Rainbow Warrior
* RMS Rhone
* Rondo
* Rosehill
* Rotorua
* Royal Adelaide
* Royal Charter
* Rozi
* HMS Safari
* Salem Express
* USS Saratoga
* USS Scuffle
* HMS Scylla
* HMS Sidon
* USS Spiegel Grove
* Stanegarth
* Stanwood
* Stella
* HMAS Swan
* USS Tarpon
* Thesis
* Thistlegorm
* Toa Maru
* Torrey Canyon
* SAS Transvaal
* U-40
* U-352
* U-1195
* Um El Faroud
* Varvassi
* Walter L M Russ
* Washingtonian (1913)
* HMNZS Wellington
* USS Yancey
* Yongala
* Zenobia
* Zealandia
* Zingara
Cave diving
sites
* Blauhöhle
* Chinhoyi Caves
* Devil's Throat at Punta Sur
* Engelbrecht Cave
* Fossil Cave
* Jordbrugrotta
* Piccaninnie Ponds
* Pluragrotta
* Pollatoomary
* Sistema Ox Bel Ha
* Sistema Sac Actun
* Sistema Dos Ojos
* Sistema Nohoch Nah Chich
Freshwater
dives
* Dutch Springs
* Ewens Ponds
* Little Blue Lake
Training sites
* Capernwray Dive Centre
* Deepspot
* National Diving and Activity Centre
* Stoney Cove
Open ocean
diving
* Blue-water diving
* Black-water diving
Diving safety
* Human factors in diving equipment design
* Human factors in diving safety
* Life-support system
* Safety-critical system
* Scuba diving fatalities
Diving
hazards
* List of diving hazards and precautions
* Environmental
* Current
* Delta-P
* Entanglement hazard
* Overhead
* Silt out
* Wave action
* Equipment
* Freeflow
* Use of breathing equipment in an underwater environment
* Failure of diving equipment other than breathing apparatus
* Single point of failure
* Physiological
* Cold shock response
* Decompression
* Nitrogen narcosis
* Oxygen toxicity
* Seasickness
* Uncontrolled decompression
* Diver behaviour and competence
* Lack of competence
* Overconfidence effect
* Panic
* Task loading
* Trait anxiety
* Willful violation
Consequences
* Barotrauma
* Decompression sickness
* Drowning
* Hypothermia
* Hypoxia
* Hypercapnia
* Hyperthermia
Diving
procedures
* Ascending and descending
* Emergency ascent
* Boat diving
* Canoe and kayak diving
* Buddy diving
* buddy check
* Decompression
* Decompression practice
* Pyle stop
* Ratio decompression
* Dive briefing
* Dive log
* Dive planning
* Scuba gas planning
* Diver communications
* Diving hand signals
* Diving line signals
* Diver voice communications
* Diver rescue
* Diver training
* Doing It Right
* Drift diving
* Gas blending for scuba diving
* Night diving
* Solo diving
* Water safety
Risk
management
* Checklist
* Hazard identification and risk assessment
* Hazard analysis
* Job safety analysis
* Risk assessment
* Risk control
* Hierarchy of hazard controls
* Incident pit
* Lockout–tagout
* Permit To Work
* Redundancy
* Safety data sheet
* Situation awareness
Diving team
* Bellman
* Chamber operator
* Diver medical technician
* Diver's attendant
* Diving supervisor
* Diving systems technician
* Gas man
* Life support technician
* Stand-by diver
Equipment
safety
* Breathing gas quality
* Testing and inspection of diving cylinders
* Hydrostatic test
* Sustained load cracking
* Diving regulator
* Breathing performance of regulators
Occupational
safety and
health
* Approaches to safety
* Job safety analysis
* Risk assessment
* Toolbox talk
* Housekeeping
* Association of Diving Contractors International
* Code of practice
* Contingency plan
* Diving regulations
* Emergency procedure
* Emergency response plan
* Evacuation plan
* Hazardous Materials Identification System
* Hierarchy of hazard controls
* Administrative controls
* Engineering controls
* Hazard elimination
* Hazard substitution
* Personal protective equipment
* International Marine Contractors Association
* Occupational hazard
* Biological hazard
* Chemical hazard
* Physical hazard
* Psychosocial hazard
* Occupational hygiene
* Exposure assessment
* Occupational exposure limit
* Workplace health surveillance
* Safety culture
* Code of practice
* Diving safety officer
* Diving superintendent
* Health and safety representative
* Operations manual
* Safety meeting
* Standard operating procedure
Diving medicine
Diving
disorders
* List of signs and symptoms of diving disorders
* Cramp
* Motion sickness
* Surfer's ear
Pressure
related
* Alternobaric vertigo
* Barostriction
* Barotrauma
* Air embolism
* Aerosinusitis
* Barodontalgia
* Dental barotrauma
* Pulmonary barotrauma
* Compression arthralgia
* Decompression illness
* Dysbarism
Oxygen
* Freediving blackout
* Hyperoxia
* Hypoxia
* Oxygen toxicity
Inert gases
* Avascular necrosis
* Decompression sickness
* Isobaric counterdiffusion
* Taravana
* Dysbaric osteonecrosis
* High-pressure nervous syndrome
* Hydrogen narcosis
* Nitrogen narcosis
Carbon dioxide
* Hypercapnia
* Hypocapnia
Breathing gas
contaminants
* Carbon monoxide poisoning
Immersion
related
* Asphyxia
* Drowning
* Hypothermia
* Immersion diuresis
* Instinctive drowning response
* Laryngospasm
* Salt water aspiration syndrome
* Swimming-induced pulmonary edema
Treatment
* Demand valve oxygen therapy
* First aid
* Hyperbaric medicine
* Hyperbaric treatment schedules
* In-water recompression
* Oxygen therapy
* Therapeutic recompression
Personnel
* Diving Medical Examiner
* Diving Medical Practitioner
* Diving Medical Technician
* Hyperbaric nursing
Screening
* Atrial septal defect
* Effects of drugs on fitness to dive
* Fitness to dive
* Psychological fitness to dive
Research
Researchers in
diving physiology
and medicine
* Arthur J. Bachrach
* Albert R. Behnke
* Paul Bert
* George F. Bond
* Robert Boyle
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Diving medical
research
organisations
* Aerospace Medical Association
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Law
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sites
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Incidents
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Early diving
* John Day (carpenter)
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* Loïc Leferme
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Offshore
diving incidents
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Professional
diving fatalities
* Roger Baldwin
* John Bennett
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Scuba diving
fatalities
* Ricardo Armbruster
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Publications
Manuals
* NOAA Diving Manual
* U.S. Navy Diving Manual
* Basic Cave Diving: A Blueprint for Survival
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* Bennett and Elliott's physiology and medicine of diving
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Standards and
Codes of Practice
* Code of Practice for Scientific Diving (UNESCO)
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General non-fiction
* The Darkness Beckons
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Research
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Training and registration
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Recreational
scuba
certification
levels
Core diving skills
* Advanced Open Water Diver
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Commercial diver
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Commercial diving
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Free-diving
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Recreational scuba
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Scientific diver
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Technical
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Cave
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Underwater sports
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Underwater divers
Pioneers
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Underwater
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Scuba record
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Underwater
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Underwater
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Underwater
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Writers and journalists
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Science of underwater diving
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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
| Nitrogen narcosis | c0028166 | 4,127 | wikipedia | https://en.wikipedia.org/wiki/Nitrogen_narcosis | 2021-01-18T18:38:02 | {"mesh": ["D007222"], "umls": ["C0028166"], "wikidata": ["Q581152"]} |
Temtamy et al. (1974) described 2 Egyptian sisters, offspring of a first-cousin marriage, with marked metaphyseal dysplasia resembling Pyle disease, anetoderma (macular atrophy of the skin) and optic atrophy. Although the last was apparently congenital, compression of the cranial nerves was present. See 133690 for another skeletal disorder with anetoderma (or anetodermia).
Skel \- Metaphyseal dysplasia Eyes \- Optic atrophy Inheritance \- Autosomal recessive Neuro \- Cranial nerve compression Skin \- Anetoderma (macular atrophy of skin) ▲ 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
| METAPHYSEAL DYSPLASIA, ANETODERMA, AND OPTIC ATROPHY | c1855174 | 4,128 | omim | https://www.omim.org/entry/250450 | 2019-09-22T16:25:19 | {"mesh": ["C565395"], "omim": ["250450"]} |
Polyorchidism
Ultrasound scan showing a side view of Type A3 polyorchidism, with annotations showing the superior and inferior testes and the head and tail of the epididymis
Polyorchidism is the incidence of more than two testicles. It is a very rare congenital disorder, with fewer than 200 cases reported in medical literature[1] and six cases (two horses, two dogs and two cats) in veterinary literature.[2]
Polyorchidism is generally diagnosed via an ultrasound examination of the testicles. However, the diagnosis of polyorchidism should include histological confirmation. The most common form is triorchidism, or tritestes, where three testicles are present. The condition is usually asymptomatic. A man who has polyorchidism is known as a polyorchid.
## Contents
* 1 Classification
* 1.1 Numeric system
* 2 Cause
* 2.1 Complications
* 3 Management
* 4 References
* 5 External links
## Classification[edit]
Polyorchidism occurs in two primary forms: Type A and Type B.[1]
* Type A: The supernumerary testicle is connected to a vas deferens. These testicles are usually reproductively functional. Type A is further subdivided into:
* Type A1: Complete duplication of the testicle, epididymis and vas deferens.
* Type A2: The supernumerary testicle has its own epididymis and shares a vas deferens.
* Type A3: The supernumerary testicle shares the epididymis and the vas deferens of the other testicles.
* Type B: The supernumerary testicle is not connected to a vas deferens and is therefore not reproductively functional. Type B is further subdivided into:
* Type B1: The supernumerary testicle has its own epididymis but is not connected to a vas deferens
* Type B2: The supernumerary testicle consists only of testicular tissue.
Type A3 is the most common form of polyorchidism, and types A2 and A3 together account for more than 90% of cases.[3] In 65% of cases, the supernumerary testicle is found in the left scrotal sac.[1]
### Numeric system[edit]
An older system of classification structures polyorchidism into similar types, but with no subdivision[3] between connected and disconnected testicles:
* Type 1: The supernumerary testicle lacks an epididymis and vas deferens and has no connection to the other testicles.
* Type 2: The supernumerary testicle shares the epididymis and the vas deferens of the other testicles.
* Type 3: The supernumerary testicle has its own epididymis and shares a vas deferens.
* Type 4: Complete duplication of the testicle, epididymis and vas deferens.
## Cause[edit]
### Complications[edit]
Most cases of polyorchidism are asymptomatic, and are discovered incidentally, in the course of treating another condition. In the majority of cases, the supernumerary testicle is found in the scrotum.[1]
However, polyorchidism can occur in conjunction with cryptorchidism, where the supernumerary testicle is undescended or found elsewhere in the body. These cases are associated with a significant increase in the incidence of testicular cancer: 0.004% for the general population vs 5.7% for a supernumerary testicle not found in the scrotum.[1]
Polyorchidism can also occur in conjunction with infertility, inguinal hernia, testicular torsion, epididymitis, hydrocele testis and varicocele.[4] However, it is not clear whether polyorchidism causes or aggravates these conditions, or whether the existence of these conditions leads sufferers to seek medical attention and thus become diagnosed with a previously undetected supernumerary testicle.[citation needed]
## Management[edit]
Because polyorchidism is very uncommon, there is no standard treatment for the condition. Prior to advances in ultrasound technology, it was common practice to remove the supernumerary testicle.[3] Several cases have been described where routine follow-up examinations conducted over a period of years showed that the supernumerary testicle was stable.[1]
A meta-analysis in 2009 suggested removing non-scrotal supernumerary testicles because of the increased risk of cancer, and regular follow-up in the remaining cases to ensure that the supernumerary testicle remains stable.[1]
## References[edit]
1. ^ a b c d e f g Bergholz, R.; Wenke, K. (2009). "Polyorchidism: A Meta-Analysis". The Journal of Urology. 182 (5): 2422–2427. doi:10.1016/j.juro.2009.07.063. PMID 19765760.
2. ^ Roca-Ferrer, J.; et al. (2015). "A Rare Case of Polyorchidism in a Cat with Four Intra-abdominal Testes". Reprod Dom Anim. 50 (1): 172–176. doi:10.1111/rda.12461. PMID 25472870.
3. ^ a b c Leung, A. K. (1988). "Polyorchidism". American Family Physician. 38 (3): 153–156. PMID 3046267.
4. ^ Kundu, A; et al. "Triorchidism : An Incidental Finding And Review Of Literature" (PDF). Retrieved 21 March 2012. Cite journal requires `|journal=` (help)
## External links[edit]
Classification
D
* ICD-10: Q55.2
* v
* t
* e
Male congenital anomalies of the genitalia, including Intersex and DSD
Internal
Testicle
* Cryptorchidism
* Polyorchidism
* Monorchism
* Anorchia
* Sertoli cell-only syndrome
* True hermaphroditism
* Mixed gonadal dysgenesis
* Swyer syndrome
Vas deferens
* Congenital absence of the vas deferens
Other
* Persistent Müllerian duct syndrome
External
Penis
* Hypospadias
* Epispadias
* Chordee
* Micropenis
* Penile agenesis
* Diphallia
* Penoscrotal transposition
Other
* Pseudohermaphroditism
*[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
| Polyorchidism | c0266430 | 4,129 | wikipedia | https://en.wikipedia.org/wiki/Polyorchidism | 2021-01-18T18:44:28 | {"umls": ["C0266430"], "icd-9": ["752.89"], "icd-10": ["Q55.2"], "wikidata": ["Q745631"]} |
Spastic paraplegia-optic atrophy-neuropathy (SPOAN) syndrome is a rare, complex type of hereditary spastic paraplegia characterized by early-onset progressive spastic paraplegia presenting in infancy, associated with optic atrophy, fixation nystagmus, polyneuropathy occurring in late childhood/early adolescence leading to severe motor disability and progressive joint contractures and scoliosis. SPOAN syndrome is caused by mutations in the KLC2 gene (11q13.1), encoding kinesin light chain 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
| Spastic paraplegia-optic atrophy-neuropathy syndrome | c1836010 | 4,130 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=320406 | 2021-01-23T17:03:03 | {"mesh": ["C563702"], "omim": ["609541"], "umls": ["C1836010"], "icd-10": ["G11.4"], "synonyms": ["SPOAN"]} |
## Description
The PR (or PQ) interval is the time required for an electrical impulse to travel from the atrial myocardium adjacent to the sinus node through the atrioventricular node (AVN) to the Purkinje fibers. Delayed conduction results in prolongation of the PR interval and subsequent risk of atrial fibrillation (summary by Holm et al., 2010). The PR interval has a substantial heritable component, with heritability estimates ranging between 30 and 50%. The PR interval is considered an intermediate phenotype for atrial fibrillation, as alterations in atrial action potential duration and in atrioventricular conduction influence both PR interval and atrial fibrillation risk (summary by Pfeufer et al., 2010).
Inheritance
Moller and Heiberg (1980) suggested the existence of major genes influencing atrioventricular conduction time. They studied the PR interval in the adult first-degree relatives of 6 and 9 probands with short and long PR intervals, respectively. The distributions differed significantly, relatives of probands with short PR intervals having shorter PR intervals than did relatives of probands with long PR intervals. Twin studies (Havlik et al., 1980; Moller et al., 1982) supported the genetic hypothesis. Griggs et al. (1986) found heritability of 0.46 for PR interval in Tokelau Islanders. Segregation analysis provided evidence for a polygenic influence on AV conduction but no support for a single major gene.
Mapping
Holm et al. (2010) performed a genomewide association study of electrocardiographic variables in approximately 10,000 individuals and followed up the top signals in an additional 10,000 individuals. They identified 4 genomewide significant associations for PR interval, the strongest of which was obtained for the SCN10A (604427) locus on chromosome 3p22.2. The A allele of rs6795970, corresponding to a val1073-to-ala substitution, was associated with prolonged PR interval (combined p = 9.5 x 10(-59)). The SCN10A gene encodes a tetrodotoxin (TTX)-resistant voltage-gated sodium channel (alpha subunit), which is implicated in pain perception and modulation. Holm et al. (2010) also identified association of electrocardiographic measures with several other loci, including resting heart rate (607276) with MYH6 (160710), PR interval with TBX5 (601620), CAV1 (601047), and ARHGAP24 (610586), and QRS duration with TBX5, SCN10A, 6p21, and 10q21.
Chambers et al. (2010) carried out a genomewide association study of electrocardiographic time intervals in 6,543 Indian Asians. They identified association of a nonsynonymous G-to-A SNP, rs6795970, in SCN10A (p = 2.8 x 10(-15)) with PR interval, a marker of cardiac atrioventricular conduction. Replication testing among 6,243 Indian Asians and 5,370 Europeans confirmed that the A allele of rs6795970 is associated with prolonged cardiac conduction (longer P-wave duration, PR interval, and QRS duration, P = 10(-5) to 10(-20)). SCN10A encodes Nav(V)1.8, a sodium channel. Chambers et al. (2010) showed that SCN10A is expressed in mouse and human heart tissue and that PR interval is shorter in Scn10a -/- mice than in wildtype mice. Chambers et al. (2010) also found that rs6795970 is associated with a higher risk of heart block (P less than 0.05) and a lower risk of ventricular fibrillation (P = 0.01). Chambers et al. (2010) concluded that their findings provided new insight into the pathogenesis of cardiac conduction, heart block, and ventricular fibrillation.
Pfeufer et al. (2010) reported a metaanalysis of genomewide association studies for PR interval from 7 population-based European studies in the CHARGE Consortium involving 28,517 individuals. They identified 9 loci associated with prolonged PR interval at P less than 5 x 10(-8). At the 3p22.2 locus, they observed 2 independent associations in the voltage-gated sodium channel genes SCN10A (rs6800541C, p = 2.10 x 10(-74)) and SCN5A (600163) (rs11708996C, p = 6.00 x 10(-26)). The SNP rs6800541 represents a C-T change in intron 14 of SCN10A; rs11708996 represents a C-G change in intron 14 of SCN5A. The SNP rs6800541 was in high linkage disequilibrium (LD) with rs6795970 (r(2) = 0.93), reported by Holm et al. (2010) and Chambers et al. (2010). Pfeufer et al. (2010) found that the SCN10A SNP rs6800541 was in low LD with the SCN5A SNP rs11708996 (r(2) = 0.31); a metaanalysis of linear regression results from models including both SNPs suggested that these SNPs represent independent association signals. Pfeufer et al. (2010) also found association of PR interval with the ARHGAP24, CAV1/CAV2, and TBX5 loci.
Sotoodehnia et al. (2010) performed a genomewide association metaanalysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and identified 22 loci associated with QRS duration (P less than 5 x 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors, and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. Sotoodehnia et al. (2010) demonstrated that SCN10A, a candidate gene at the most significantly associated locus in their study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. Sotoodehnia et al. (2010) found that the majority of loci that influence both PR and QRS (SCN5A, SCN10A, TBX5, and CAV1-2) do so in a concordant fashion (meaning variants that prolong PR duration also prolong QRS duration). The notable exception is a region on chromosome 12, where variants in the TBX5 locus have a concordant effect, whereas those in nearby TBX3 have a discordant effect. By contrast, although QRS (ventricular depolarization) and QT (ventricular repolarization) are moderately positively correlated, the majority of loci (SCN5A, SCN10A, PRKCA (176960), and NOS1AP (605551)) that influence both phenotypes do so in a discordant fashion (meaning variants that prolong the QRS interval shorten the QT interval). The exception is the locus at PLN (172405), where the variants have a concordant effect.
Lab \- Electrocardiographic atrioventricular conduction time Inheritance \- ? polygenic influence ▲ Close
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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
| PR INTERVAL, VARIATION IN | c3152251 | 4,131 | omim | https://www.omim.org/entry/108980 | 2019-09-22T16:44:37 | {"omim": ["108980"], "synonyms": ["Alternative titles", "ATRIOVENTRICULAR CONDUCTION TIME, VARIATION IN"]} |
Cranio-fronto-nasal dysplasia - Poland anomaly is a polymalformative syndrome characterised by craniosynostosis, Poland anomaly (see this term), cranio-fronto-nasal dysplasia, and genital and breast anomalies. Less than ten cases have been described so far.
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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
| Craniofrontonasal dysplasia-Poland anomaly syndrome | None | 4,132 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1521 | 2021-01-23T16:56:07 | {"gard": ["428"], "icd-10": ["Q87.8"], "synonyms": ["Webster-Deming syndrome"]} |
Microcephaly - albinism - digital anomalies syndrome is a very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe.
## Epidemiology
It has been described in two sibs.
## Clinical description
Both brother and sister had psychomotor retardation and died in the course of a respiratory infection.
## Genetic counseling
The reported cases suggest that the condition is hereditary, and is transmitted as an autosomal recessive trait.
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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
| Microcephaly-albinism-digital anomalies syndrome | c1859910 | 4,133 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2513 | 2021-01-23T18:46:18 | {"gard": ["3604"], "mesh": ["C537322"], "omim": ["203340"], "umls": ["C1859910"], "icd-10": ["Q87.8"], "synonyms": ["Castro Gago-Pombo-Novo syndrome"]} |
A rare subtype of kyphoscoliotic Ehlers-Danlos syndrome characterized by congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional common features are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Subtype-specific manifestations include skin fragility, atrophic scarring, scleral/ocular fragility/rupture, microcornea, and facial dysmorphology (like low‐set ears, epicanthal folds, down‐slanting palpebral fissures, high palate). Molecular testing is obligatory to confirm the diagnosis.
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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
| Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency | c0268342 | 4,134 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1900 | 2021-01-23T18:54:15 | {"gard": ["2083"], "mesh": ["C536198"], "omim": ["225400"], "umls": ["C0268342"], "icd-10": ["Q79.6"], "synonyms": ["Cutis hyperelastica", "EDS VIA", "Ehlers-Danlos syndrome type 6A", "Kyphoscoliotic EDS due to lysyl hydroxylase 1 deficiency", "Lysyl hydroxylase-deficient EDS", "Ocular-scoliotic EDS", "kEDS-PLOD1"]} |
A number sign (#) is used with this entry because of evidence that hypogonadotropic hypogonadism-12 with or without anosmia (HH12) is caused by homozygous mutation in the GNRH1 gene (152760) on chromosome 8p21. One such family has been reported.
Description
Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).'
For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.
Clinical Features
Biben and Gordan (1955) described affected males and females in a family with what they designated 'familial hypogonadotropic eunuchoidism.' Hurxthal (1943) reported a family in which only members of 1 generation were affected. Le Marquand (1954) described 3 affected brothers and 2 affected sisters from a nonconsanguineous family.
Ewer (1968) observed an affected brother and 2 sisters from a marriage of second cousins once removed. Another male sib, deceased, was probably affected. Absence of secondary sex characteristics and relatively long extremities were the only abnormal findings. Clomiphene administration had no effect.
Toledo et al. (1983) reported 2 brothers and a sister with a hypothalamic form of hypogonadism that the authors designated 'familial idiopathic gonadotropin deficiency' (FIGD). Toledo et al. (1983) concluded that this disorder is due to insufficiency of GNRH secretion and that sensitivity of Leydig cells to human chorionic gonadotropin (hCG; see 118860) is normal in FIGD. They also stated that luteinizing hormone-releasing hormone (LRH) treatment may be helpful; that associated hypothalamic-pituitary-prolactin dysfunction may be present; and that FIGD and the Kallmann syndrome (see 147950) are distinct entities.
To further define the genetic and phenotypic variability of FIGD, Waldstreicher et al. (1996) reviewed detailed family histories of 106 cases of GNRH deficiency with or without anosmia, i.e., Kallmann syndrome or idiopathic hypogonadotropic hypogonadism (IHH). The great majority of cases appeared to be sporadic, with only 19 probands (18%) having at least 1 family member with GNRH deficiency. However, of the families in which the proband was the sole member affected by Kallmann syndrome or IHH, 9 had individuals with isolated anosmia, and 8 had a strong history of delayed puberty. If these phenotypes were considered as variable expressions of Kallmann syndrome or IHH seen in the proband, then 34% of the cases could be considered familial. The proportion of familial cases that could be attributed to an X-linked mode of inheritance was no greater than 36% in any of these analyses. Waldstreicher et al. (1996) concluded that (1) most cases of GNRH deficiency in humans are sporadic and thus could represent new mutations; (2) the X-linked form is the least common among familial cases of Kallmann syndrome or IHH; (3) defects in at least 2 autosomal genes can cause GNRH deficiency; and (4) associated clinical defects may provide clues to the nature and/or location of these autosomal genes.
Bouligand et al. (2009) studied a Romanian brother and sister with normosmic hypogonadotropic hypogonadism. The brother, who was referred at 18 years of age because pubertal development had not occurred, exhibited typical signs of complete hypogonadism, with small intrascrotal testes, no pubic hair, and microphallus. His bone age was 13.0 years; he had a normal sense of smell on olfactometry, and had no renal or craniofacial abnormalities. His affected sister, who was evaluated at 17 years of age, also had complete hypogonadism and a normal sense of smell on olfactometry. She had no breast development and no pubic hair, and menarche had not occurred. Pelvic sonography showed a small uterus and 2 small ovaries with no visible follicles. The sibs' karyotypes were 46,XY and 46,XX, respectively. Hormone assays revealed very low plasma testosterone levels in the affected brother and an almost undetectable plasma estradiol level in the affected sister. Both sibs had very low levels of plasma gonadotropin (see 118860) and normal levels of prolactin (176760). They both showed a blunted response to GnRH bolus administration, but otherwise had normal function of the anterior pituitary, thyroid, and adrenal glands, as well as normal levels of ferritin (see 134790) and serum insulin-like growth factor-1 (IGF1; 147440) and normal findings on MRI of the pituitary and olfactory bulbs. The sister had basal nonpulsatile luteinizing hormone (LH; see 152780) secretion, but LH pulses, occurring synchronously with GnRH boluses, were detected on day 13 of pulsatile GnRH administration. Pulsatile GnRH administration also resulted in increased circulating levels of estradiol and inhibin-beta (see 147290) and in the recruitment of a single dominant 14-mm follicle seen on ultrasonography. The sibs' unrelated parents reported normal puberty, and the mother had spontaneous regular menses, unassisted conception, and normal pregnancies; there were also 2 unaffected sibs who had normal puberty and normal sex steroid and gonadotropin levels.
Molecular Genetics
In an 18-year-old Romanian man from a Transylvanian mountain village who had normosmic hypogonadotropic hypogonadism and was negative for mutation in the GNRHR1, GPR54, KISS1, FGFR1, and GNRH2 genes, Bouligand et al. (2009) identified homozygosity for a 1-bp insertion in the GNRH1 gene (152760.0001). His affected sister was also homozygous for the mutation, and his unaffected parents and an unaffected sister were heterozygotes, as was 1 of 200 ancestrally matched Romanian controls; haplotype analysis suggested a founding event 8 to 50 generations earlier. The mutation was not found in 100 unrelated Caucasian eugonadal individuals or in 145 unrelated Caucasian patients with sporadic normosmic IHH.
For discussion of a possible second homozygous mutation in the GNRH1 gene causing hypogonadotropic hypogonadism, see 152760.0002.
### Oligogenic Inheritance
In a cohort of 310 patients with normosmic HH, Chan et al. (2009) analyzed the HH-associated genes GNRH1, FGFR1 (136350), and PROKR2 (607123), and identified rare heterozygous variants in all 3 genes in the proband of a 3-generation pedigree: R31C in GNRH1, I239T in FGFR1, and S202G in PROKR2. The proband had affected twin daughters, one of whom carried the GNRH1 and FGFR1 variants, whereas the other carried only the GNRH1 variant. A niece who was originally diagnosed with hypothalamic amenorrhea, in which the reproductive phenotype becomes apparent only in the presence of an external stressor, also carried only the GNRH1 variant. Chan (2011) stated that the niece's phenotype was later revised to normosmic HH. In addition, 2 paternal aunts of the proband had HH, but DNA was not available for study. At 42 years of age, the proband exhibited reversal of HH, with normal menstrual cycles after stopping hormone therapy.
Animal Model
Beier and Dluhy (2003) noted that mutation in the GNRH1 gene had been identified as the cause of hypogonadotropic hypogonadism in mice.
INHERITANCE \- Autosomal recessive CHEST Breasts \- Delayed or absent thelarche GENITOURINARY External Genitalia (Male) \- Micropenis \- Small testes \- Cryptorchidism Internal Genitalia (Female) \- Primary amenorrhea \- Small uterus \- Small ovaries \- Few to no follicles on ultrasonography SKIN, NAILS, & HAIR Hair \- Absence of pubic hair ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism \- Delayed or absent puberty \- Low to undetectable gonadotropin levels \- Low testosterone level \- Low estradiol level MISCELLANEOUS \- Based on report of 1 family (last curated October 2014) MOLECULAR BASIS \- Caused by mutation in the gonadotropic-releasing hormone 1 gene (GNRH1, 152760.0001 ) ▲ 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
| HYPOGONADOTROPIC HYPOGONADISM 12 WITH OR WITHOUT ANOSMIA | c1856897 | 4,135 | omim | https://www.omim.org/entry/614841 | 2019-09-22T15:54:04 | {"doid": ["0090072"], "mesh": ["C535764"], "omim": ["614841"], "orphanet": ["432"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "GONADOTROPIN DEFICIENCY, FAMILIAL IDIOPATHIC", "Alternative titles", "EUNUCHOIDISM, FAMILIAL HYPOGONADOTROPIC", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]} |
## Description
Asperger syndrome is considered to be a form of childhood autism (see, e.g., 209850). The DSM-IV (American Psychiatric Association, 1994) specifies several diagnostic criteria for Asperger syndrome, which has many of the same features as autism. In general, patients with Asperger syndrome and autism exhibit qualitative impairment in social interaction, as manifest by impairment in the use of nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. Gillberg et al. (2001) described the development of the Asperger syndrome (and high-functioning autism) Diagnostic Interview (ASDI), which they claimed has a strong validity in the diagnosis of the disorder.
For a discussion of genetic heterogeneity of Asperger syndrome, see ASPG1 (608638).
Mapping
Ylisaukko-oja et al. (2004) performed a genomewide scan on 17 Finnish families ascertained for Asperger syndrome with a strictly defined phenotype. Evidence for linkage was highest on chromosome 1q21-q22 (ASPG3; maximum 2-point lod score of 3.58 at theta = 0.08 for marker D1S484), followed by chromosome 3p24-p14 (maximum 2-point lod score of 2.50 at theta = 0.00 for marker D3S2432) and chromosome 13q31-q33 (maximum 2-point lod score of 1.59 at theta = 0.18 for marker D13S793).
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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
| ASPERGER SYNDROME, SUSCEPTIBILITY TO, 3 | c1837434 | 4,136 | omim | https://www.omim.org/entry/608781 | 2019-09-22T16:07:19 | {"omim": ["608781"]} |
Leucine-sensitive hypoglycemia of infancy
Other namesHypoglycemia leucine-induced; hypoglycemia leucine induced; familial infantile hypoglycemia precipitated by leucine[1]
Leucine-sensitive hypoglycemia of infancy is a type of metabolic disorder.[1] It is inherited in an autosomal dominant fashion.[2] It is rare.[3]
## Names[edit]
Other names include hypoglycemia leucine-induced; hypoglycemia leucine induced; and familial infantile hypoglycemia precipitated by leucine.[1]
## References[edit]
1. ^ a b c "Leucine-sensitive hypoglycemia of infancy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 27 October 2019.
2. ^ "OMIM Entry - # 240800 - HYPOGLYCEMIA, LEUCINE-INDUCED; LIH". www.omim.org. Retrieved 27 October 2019.
3. ^ "Hypoglycemia, Leucine-Induced disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 27 October 2019.
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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
| Leucine-sensitive hypoglycemia of infancy | c0271714 | 4,137 | wikipedia | https://en.wikipedia.org/wiki/Leucine-sensitive_hypoglycemia_of_infancy | 2021-01-18T19:07:14 | {"gard": ["9915"], "mesh": ["C537150"], "umls": ["C0271714"], "wikidata": ["Q55781969"]} |
Hypotrichosis with juvenile macular degeneration (HJMD) is a very rare syndrome characterized by sparse and short hair from birth followed by progressive macular degeneration leading to blindness.
## Epidemiology
Prevalence is unknown but approximately 50 patients have been described since the first characterization of the syndrome in 1935.
## Clinical description
HJMD patients present with short and sparse scalp hair since birth or first months of life, with no subsequent growth during life. A decade later, during the first to third decades of life, visual acuity decreases because of progressive macular degeneration, leading in many cases to blindness between the second and fourth decades of life. HJMD is sometimes associated with limb anomalies, in which case it is termed Ectodermal dysplasia, Ectrodactyly, and Macular dystrophy (EEM; see this term). Many patients display fair hair complexion as compared with their healthy siblings. The hair phenotype does not improve significantly with age, even though diffuse alopecia in infancy can evolve towards short and sparse hair in puberty.
## Etiology
HJMD is caused by mutations in the CDH3 gene (16q22.1), encoding P-cadherin. P-cadherin is part of adherens junctions in various epithelia including the hair follicular epithelium. Moreover, P-cadherin is expressed in the retinal pigment epithelium.
## Diagnostic methods
Diagnosis is based on the combined occurrence of hypotrichosis with characteristic degenerative changes and pigmentary abnormalities of the macula on fundoscopy. Where available, electrophysiologic studies can confirm abnormal function of the posterior pole. Additional tests of lesser diagnostic value include (1) histopathologic examination of scalp biopsies, revealing mostly vellus and catagen hair follicles with significantly reduced number of terminal hair follicles; (2) light microscopy and scanning electron microscopy of hair which can demonstrate various structural abnormalities including pseudomonilethrix, pili torti, longitudinal ridging, scaling and folding of the hair shaft.
## Differential diagnosis
Differential diagnosis includes EEM syndrome, also caused by CDH3 mutations.
## Genetic counseling
As HJMD is an autosomal recessive disease, risk of recurrence is 25%. DNA-based prenatal diagnosis and genetic counseling are available provided the underlying mutation is known.
## Management and treatment
No curative or palliative options exist for HJMD. However, educational measures can be implemented and psychological support should be provided once HJMD is diagnosed.
## Prognosis
The most severe complication of HJMD is progressive macular degeneration leading to blindness between the second and fourth decades of life. Life expectancy is normal but quality of life can be reduced because of blindness and psychological impact due to the hair phenotype.
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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
| Hypotrichosis with juvenile macular degeneration | c1832162 | 4,138 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1573 | 2021-01-23T17:36:40 | {"gard": ["3066"], "mesh": ["C537698"], "omim": ["601553"], "umls": ["C1832162"], "icd-10": ["Q84.0"], "synonyms": ["HJMD", "Hypotrichosis with juvenile macular dystrophy"]} |
Metaplastic carcinoma of the breast is a rare, aggressive subtype of invasive breast carcinoma characterized by rapid growth, relatively large tumor size and a tendency to metastasize to distant organs, particularly the lungs, with relatively less frequent involvement of the axillary lymph nodes. Histologically, the tumor shows high-grade cellularity and heterologous differentiation, including chondroid, osseous, pleomorphic/sarcomatoid, spindled, and squamous elements. Patients usually present with a fast-growing, large, well-circumscribed, mobile lump in the breast, which can become painful and involve the chest wall and the skin, leading to ulceration.
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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
| Metaplastic carcinoma of the breast | c1334708 | 4,139 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213531 | 2021-01-23T17:36:07 | {"gard": ["10804"], "umls": ["C1334708"], "icd-10": ["C50.0", "C50.1", "C50.2", "C50.3", "C50.4", "C50.5", "C50.6", "C50.8"]} |
Myoclonic epilepsy in non-progressive encephalopathies is a rare epilepsy syndrome characterized by recurrent, long-lasting myoclonic status in infants and young children with a non-progressive encephalopathy, associated with transient and recurring motor, cognitive and/or behavioral disturbances.
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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
| Myoclonic epilepsy in non-progressive encephalopathies | None | 4,140 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86913 | 2021-01-23T17:00:06 | {"icd-10": ["G40.4"], "synonyms": ["Myoclonic status in non-progressive encephalopathies", "Myoclonus epilepsy in non-progressive encephalopathies"]} |
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type Ib (CDG Ib, CDG1B) is caused by compound heterozygous mutation in the gene encoding mannosephosphate isomerase (MPI; 154550) on chromosome 15q24.
Description
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006).
For a discussion of the classification of CDGs, see CDG1A (212065).
CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002)
Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
Clinical Features
Pelletier et al. (1986) first described CDG Ib clinically. They observed secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia, and congenital hepatic fibrosis in 4 children whose parents originated from the same northeastern province of Quebec. Jaeken et al. (1998) suggested that the patients reported by Pelletier et al. (1986) had CDG Ib. The infants, who died between the ages of 4 and 21 months, also had antithrombin III deficiency (613118), a typical feature of CDG syndromes.
Niehues et al. (1998) reported an 11-month-old boy who presented with diarrhea and vomiting. He was born at term with a normal birth weight. He developed protein-losing enteropathy, and small bowel biopsy showed lysosomal inclusion bodies and dilated rough endoplasmic reticulum filled with prominent tubular bundles. He also had recurrent thrombotic events and severe life-threatening gastrointestinal bleeding. Laboratory studies showed severe hypoproteinemia, anemia, and decreased antithrombin III (AT3; 107300). Isoelectric focusing of serum transferrin showed a pattern consistent with CDG type I. However, the patient had no psychomotor or mental retardation, which was fundamentally different from all other types of CDGs. A deficiency of phosphomannose isomerase was found, with activity in fibroblasts decreased to 7.4% of normal control values. Each parent had approximately 50% residual activity consistent with a heterozygous state. Daily oral mannose administration resulted in clinical improvement.
Jaeken et al. (1998) reported 3 patients with CDG type I who had a marked deficiency of phosphomannose isomerase with normal PMM2 (601785). One of the patients had been reported by Niehues et al. (1998). The clinical presentation of PMI (MPI)-deficient CDG disease was distinctive in its hepatic-intestinal presentation. One of the 3 patients was the offspring of unrelated Lebanese parents. He had chronic diarrhea beginning at the age of 3 months and hypoglycemia with convulsions, coma, and apnea. There was no dysmorphism. The liver was enlarged and showed fibrosis of the portal spaces and microvesicular steatosis on biopsy. Generalized edema secondary to hypoalbuminemia developed by age 10 months and he was treated with Diazoxide. Histology of duodenal biopsies showed partial villus atrophy with hypercellularity and only rare and discrete lymphangiectasias. The patient suffered from frequent bacterial as well as viral gastroenteritis. At the age of 26 months, the abdomen was large with pronounced collateral circulation, numerous disseminated angiomas, and persisting hepatomegaly. Tube feeding by gastrostomy was necessary. Neurologic examination and psychomotor development were normal. The patient was last seen at the age of 2 years with persisting protein-losing enteropathy. He died at the age of 4 years.
De Lonlay et al. (1999) reported a 3-month-old girl who presented with hyperinsulinemic hypoglycemia, severe vomiting and diarrhea, congenital hepatic fibrosis, and coagulation factor deficiencies. Mannose therapy led to dramatic clinical improvement and normalization of several biochemical abnormalities.
Babovic-Vuksanovic et al. (1999) reported a 2.5-year-old girl with CDG Ib who presented with severe and persistent hypoglycemia and subsequently developed protein-losing enteropathy, liver disease, and coagulopathy.
De Lonlay et al. (2001) reported the clinical, biologic, and molecular analysis of 26 patients with CDG I, including 20 CDG Ia, 2 CDG Ib, 1 CDG Ic, and 3 CDG Ix (212067) patients detected by Western blotting and isoelectric focusing of serum transferrin. The 2 patients with CDG Ib had severe liver disease, protein-losing enteropathy, and hyperinsulinemic hypoglycemia, but no neurologic involvement.
From a review of the literature on liver-related symptoms in CDG, Marques-da-Silva et al. (2017) suggested that the finding of 'congenital hepatic fibrosis' or 'ductal plate malformation' on liver biopsy should prompt immediate testing for CDG Ib.
Clinical Management
Niehues et al. (1998) found that oral administration of mannose was effective therapy for CDG Ib. Mannose treatment corrected the clinical phenotype as well as the hypoglycosylation of serum glycoproteins.
Jaeken et al. (1998) provided a diagram of mannose metabolism. The defect in PMI deficiency involves the conversion of fructose-6-phosphate to mannose-6-phosphate. Hexokinase phosphorylates mannose to mannose-6-phosphate. A logical consequence of this fact is that PMI deficiency, unlike PMM deficiency, should be treatable by administration of mannose supplements. This appeared to be the case in the patient reported by Niehues et al. (1998) and Freeze et al. (1997).
Schollen et al. (2000) noted that hexokinase provides an alternative pathway for the synthesis of mannose-6-phosphate from mannose. Whereas the dietary intake of mannose is minimal and probably not enough for normal glycosylation, oral mannose supplementation promotes this alternative pathway and has been successful in treating several cases of CDG Ib (Babovic-Vuksanovic et al., 1999; de Lonlay et al., 1999).
Molecular Genetics
Niehues et al. (1998) identified a heterozygous mutation in the MPI gene (R219Q; 154550.0001) in a patient with CDG Ib. Subsequently, Schollen et al. (2000) identified a second MPI mutation (116insC; 154550.0004) in this patient, confirming compound heterozygosity and autosomal recessive inheritance.
In a patient with CDG Ib, Jaeken et al. (1998) identified compound heterozygosity for 2 mutations in the MPI gene (154550.0002, 154550.0003).
Vuillaumier-Barrot et al. (2002) found that the protein-losing enteropathy-hepatic fibrosis syndrome described in the Saguenay-Lac-Saint-Jean region of Quebec, reported by Pelletier et al. (1986), is caused by an arg295-to-his mutation in the MPI gene (R295H; 154550.0005), and is therefore a form of CDG Ib.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive ABDOMEN Liver \- Hepatomegaly \- Hepatic fibrosis \- Cirrhosis \- Hepatic failure Gastrointestinal \- Vomiting \- Diarrhea \- Villous atrophy \- Lymphangiectasia \- Protein-losing enteropathy NEUROLOGIC Central Nervous System \- Hypotonia ENDOCRINE FEATURES \- Hyperinsulinemic hypoglycemia HEMATOLOGY \- Anti-thrombin III deficiency \- Thrombosis \- Factor XI deficiency \- Bleeding episodes LABORATORY ABNORMALITIES \- Abnormal isoelectric focusing of serum transferrin, type I pattern \- Phosphomannose isomerase deficiency in leukocytes, fibroblasts, or liver \- Hypoalbuminemia MISCELLANEOUS \- Onset of symptoms 2-12 months \- Responsive to oral mannose therapy MOLECULAR BASIS \- Caused by mutations in the mannosephosphate isomerase gene (MPI, 154550.0001 ) ▲ 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
| CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | c1865145 | 4,141 | omim | https://www.omim.org/entry/602579 | 2019-09-22T16:13:36 | {"doid": ["0080554"], "mesh": ["C535740"], "omim": ["602579"], "orphanet": ["79319"], "synonyms": ["Alternative titles", "CDG Ib", "CDG, GASTROINTESTINAL TYPE", "MANNOSEPHOSPHATE ISOMERASE DEFICIENCY", "MPI DEFICIENCY", "PROTEIN-LOSING ENTEROPATHY-HEPATIC FIBROSIS SYNDROME", "SAGUENAY-LAC SAINT-JEAN SYNDROME", "SLSJ SYNDROME"], "genereviews": ["NBK1332"]} |
An autoimmune disease
Scleromyositis
Other namesPM/Scl overlap syndrome
Scleromyositis, is an autoimmune disease (a disease in which the immune system attacks the body). People with scleromyositis have symptoms of both systemic scleroderma and either polymyositis or dermatomyositis, and is therefore considered an overlap syndrome. Although it is a rare disease, it is one of the more common overlap syndromes seen in scleroderma patients, together with MCTD and Antisynthetase syndrome. Autoantibodies often found in these patients are the anti-PM/Scl (anti-exosome) antibodies.[1]
The symptoms that are seen most often are typical symptoms of the individual autoimmune diseases and include Raynaud's phenomenon, arthritis, myositis and scleroderma.[2] Treatment of these patients is therefore strongly dependent on the exact symptoms with which a patient reports to a physician and is similar to treatment for the individual autoimmune disease, often involving either immunosuppressive or immunomodulating drugs.[3]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 3.1 Scleroderma overlap syndrome
* 4 Treatment
* 5 Recent research
* 6 References
* 7 Further reading
## Signs and symptoms[edit]
Symptoms vary but they mostly involve skin disorders. The signs to look for include Raynaud's phenomenon, arthritis, myositis and scleroderma. Visual symptoms include discoloring of the skin and painful swelling.
## Cause[edit]
* There is no distinct cause for scleromyositis.
* Scleroderma can develop in every age group from infants to the elderly, but its onset is most frequent between the ages of 25 to 55.
* In most cases it is observed that the disease involves an overproduction of collagen.
## Diagnosis[edit]
Diagnosis is by skin tests. Typically, after a consultation with a rheumatologist, the disease will be diagnosed. A dermatologist is also another specialist that can diagnose. Blood studies and numerous other specialized tests depending upon which organs are affected.
### Scleroderma overlap syndrome[edit]
People with scleroderma overlap syndrome have symptoms of both systemic scleroderma and/or polymyositis and dermatomyositis:
* Scleroderma: a group of rare diseases that involve the hardening and tightening of the skin and connective tissues.
* Polymyositis: a rare inflammatory disease that causes muscle weakness affecting both sides of your body.
* Dermatomyositis: an inflammatory disease of skin and muscle marked especially by muscular weakness and skin rash.
Scleroderma is a connective tissue disease that causes fibrosis and vascular abnormalities, but that also has an autoimmune component, and can include connective tissues complications. Diagnostic testing includes screening for the positive antinuclear antibody.[citation needed]
## Treatment[edit]
There is no current cure. The only way to treat this disease is by treating symptoms. Commonly people are prescribed immunosuppressive drugs. Another route would be to take collagen regulation drugs.
## Recent research[edit]
As of 2006 it is unclear which antibodies will best treat connective tissue diseases.[4]
One study from 2014 showed some potential of the synthetic drug Rituximab in treating this class of overlap syndromes.[5]
## References[edit]
1. ^ Jablonska S.; Blaszczyk M. (1999). "Scleroderma overlap syndromes". Adv Exp Med Biol. Advances in Experimental Medicine and Biology. 455: 85–92. doi:10.1007/978-1-4615-4857-7_12. ISBN 978-1-4613-7203-5. PMID 10599327.
2. ^ Mahler, M.; Raijmakers R. (2007). "Novel aspects of autoantibodies to the PM/Scl complex: Clinical, genetic and diagnostic insights". Autoimmunity Reviews. 6 (7): 432–7. doi:10.1016/j.autrev.2007.01.013. PMID 17643929.
3. ^ Jablonska S.; Blaszczyk M. (1998). "Scleromyositis: a scleroderma/polymyositis overlap syndrome". Clinical Rheumatology. 17 (6): 465–7. doi:10.1007/BF01451281. PMID 9890673. S2CID 39237322.
4. ^ Vandergheynst F, Ocmant A, Sordet C, Humbel RL, Goetz J, Roufosse F, Cogan E, Sibilia J (2006). "Anti-pm/scl antibodies in connective tissue disease: Clinical and biological assessment of 14 patients". Clinical and Experimental Rheumatology. 24 (2): 129–33. PMID 16762146.
5. ^ Saw, Jacqui; Leong, Wai; John, Mina; Nolan, David; O'Connor, Kevin (2014). "70: Vitamin R therapy in scleromyositis: A novel approach for a rare disorder". Journal of Clinical Neuroscience. 21 (11): 2054–5. doi:10.1016/j.jocn.2014.06.084. S2CID 54300075.
## Further reading[edit]
* http://rheumatology.oxfordjournals.org/content/35/4/305.full.pdf
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Hypersensitivity and autoimmune diseases
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Foreign
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* Systemic lupus erythematosus
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Foreign
* Allergic contact dermatitis
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* Diabetes mellitus type 1
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* Sjögren syndrome
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* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Scleromyositis | None | 4,142 | wikipedia | https://en.wikipedia.org/wiki/Scleromyositis | 2021-01-18T18:44:36 | {"wikidata": ["Q7434176"]} |
Short stature-webbed neck-heart disease syndrome is characterized by short stature, intellectual deficit, facial dysmorphism, short webbed neck, skin changes and congenital heart defects. It has been reported in four Arab Bedouin sibs born to consanguineous parents.
*[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
| Short stature-webbed neck-heart disease syndrome | c2930950 | 4,143 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2865 | 2021-01-23T17:55:58 | {"gard": ["583"], "mesh": ["C535613"], "umls": ["C2930950"], "icd-10": ["Q87.8"], "synonyms": ["Al Gazali-Aziz-Salem syndrome"]} |
Alveolar hydatid disease
Other namesAlveolar echinococcosis Alveolar colloid of the liver, Alveolococcosis, Multilocular echinococcosis
SpecialtyInfectious disease
Alveolar hydatid disease (AHD), is a form of echinococcosis, a disease that originates from a parasite.[1] Although alveolar echinococcosis is rarely diagnosed in humans and is not as widespread as cystic echinococcosis, it is also still a serious disease that not only has a significantly high fatality rate but also has the potential to become an emerging disease in many countries.
## References[edit]
1. ^ Joseph F. Wilson; Robert L. Rausch; Frances R. Wilson (1995). "Alveolar Hydatid Disease: Review of the Surgical Experience in 42 Cases of Active Disease Among Alaskan Eskimos" (PDF). Annals of Surgery. 221 (3): 315–323.
## External links[edit]
Classification
D
* ICD-10: B67.7
* ICD-9-CM: 122.7
* MeSH: C536591 C536591, C536591
* DiseasesDB: 4048
This microbiology-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This infectious disease 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
| Alveolar hydatid disease | c0152069 | 4,144 | wikipedia | https://en.wikipedia.org/wiki/Alveolar_hydatid_disease | 2021-01-18T19:08:28 | {"gard": ["207"], "mesh": ["C536591"], "umls": ["C0948954"], "orphanet": ["284"], "synonyms": ["Echinococcus multilocularis infection"], "wikidata": ["Q448768"]} |
Ovarian fibrothecoma is a rare, benign, sex cord-stromal neoplasm, with a typically unilateral location in the ovary, characterized by mixed features of both fibroma and thecoma. Patients may be asymptomatic or may present with pelvic/abdominal pain and/or distension and, occasionally, with post-menopausal bleeding. Large tumors (>10cm) are often associated with pleural effusion and ascites (the Meigs syndrome triad).
*[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
| Ovarian fibrothecoma | c4707356 | 4,145 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314478 | 2021-01-23T17:48:25 | {"icd-10": ["D27"]} |
For a phenotypic description and a discussion of genetic heterogeneity of selective tooth agenesis, see STHAG1 (106600).
Clinical Features
Ahmad et al. (1998) described a consanguineous kindred in Pakistan segregating hypodontia associated with dental anomalies such as malformation, enamel hypoplasia, and failure of eruption, leading prematurely to the edentulous state.
Inheritance
The transmission pattern of hypodontia with other dental anomalies in the family reported by Ahmad et al. (1998) was consistent with autosomal recessive inheritance.
Mapping
In studies of a consanguineous kindred in Pakistan segregating hypodontia with various dental anomalies, Ahmad et al. (1998) demonstrated linkage of the trait to a 10-cM region on 16q12.1; maximum 2-point lod score = 5.76 for marker D16S3140.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| TOOTH AGENESIS, SELECTIVE, 2 | c1865092 | 4,146 | omim | https://www.omim.org/entry/602639 | 2019-09-22T16:13:25 | {"mesh": ["C566513"], "omim": ["602639"], "synonyms": ["Alternative titles", "HYPODONTIA/OLIGODONTIA 2"]} |
Boutonneuse fever
Other namesMediterranean spotted fever
Typical eschar and spots on the leg of a patient with Boutonneuse fever[1]
SpecialtyInfectious disease
Boutonneuse fever (also called, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium Rickettsia conorii and transmitted by the dog tick Rhipicephalus sanguineus. Boutonneuse fever can be seen in many places around the world, although it is endemic in countries surrounding the Mediterranean Sea. This disease was first described in Tunisia in 1910 by Conor and Bruch and was named boutonneuse (French for "spotty") due to its papular skin-rash characteristics.[1][2]
## Contents
* 1 Presentation
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Presentation[edit]
After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black, ulcerous crust (tache noire). Around the fourth day of the illness, a widespread rash appears, first macular and then maculopapular, and sometimes petechial.
## Diagnosis[edit]
The diagnosis is made with serologic methods, either the classic Weil–Felix test, (agglutination of Proteus OX strains), ELISA, or immunofluorescence assays in the bioptic material of the primary lesion. The Weil–Felix test demonstrated low sensitivity (33%) in diagnosing acute rickettsial infections and low specificity, with a positive titre of 1:320 seen in 54% of healthy volunteers and 62% of non-rickettsial fever patients. Therefore, the use of the WFT should be discouraged in the diagnosis of acute rickettsial infections.
## Treatment[edit]
The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides, or fluoroquinolones.
## See also[edit]
* Rocky Mountain spotted fever
## References[edit]
1. ^ a b Rovery C, Brouqui P, Raoult D (2008). "Questions on Mediterranean Spotted Fever a Century after Its Discovery". Emerg Infect Dis. 14 (9): 1360–1367. doi:10.3201/eid1409.071133. PMC 2603122. PMID 18760001.
2. ^ Conor, A; A Bruch (1910). "Une fièvre éruptive observée en Tunisie". Bull Soc Pathol Exot Filial. 8: 492–496.
## External links[edit]
Classification
D
* ICD-10: A77.1
* ICD-9-CM: 082.1
* MeSH: D001907
* DiseasesDB: 31780
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
* Murine typhus
* Rickettsia prowazekii
* Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Spotted
fever
Tick-borne
* Rickettsia rickettsii
* Rocky Mountain spotted fever
* Rickettsia conorii
* Boutonneuse fever
* Rickettsia japonica
* Japanese spotted fever
* Rickettsia sibirica
* North Asian tick typhus
* Rickettsia australis
* Queensland tick typhus
* Rickettsia honei
* Flinders Island spotted fever
* Rickettsia africae
* African tick bite fever
* Rickettsia parkeri
* American tick bite fever
* Rickettsia aeschlimannii
* Rickettsia aeschlimannii infection
Mite-borne
* Rickettsia akari
* Rickettsialpox
* Orientia tsutsugamushi
* Scrub typhus
Flea-borne
* Rickettsia felis
* Flea-borne spotted fever
Anaplasmataceae
* Ehrlichiosis: Anaplasma phagocytophilum
* Human granulocytic anaplasmosis, Anaplasmosis
* Ehrlichia chaffeensis
* Human monocytotropic ehrlichiosis
* Ehrlichia ewingii
* Ehrlichiosis ewingii infection
Rhizobiales
Brucellaceae
* Brucella abortus
* Brucellosis
Bartonellaceae
* Bartonellosis: Bartonella henselae
* Cat-scratch disease
* Bartonella quintana
* Trench fever
* Either B. henselae or B. quintana
* Bacillary angiomatosis
* Bartonella bacilliformis
* Carrion's disease, Verruga peruana
β
Neisseriales
M+
* Neisseria meningitidis/meningococcus
* Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia
M−
* Neisseria gonorrhoeae/gonococcus
* Gonorrhea
ungrouped:
* Eikenella corrodens/Kingella kingae
* HACEK
* Chromobacterium violaceum
* Chromobacteriosis infection
Burkholderiales
* Burkholderia pseudomallei
* Melioidosis
* Burkholderia mallei
* Glanders
* Burkholderia cepacia complex
* Bordetella pertussis/Bordetella parapertussis
* Pertussis
γ
Enterobacteriales
(OX−)
Lac+
* Klebsiella pneumoniae
* Rhinoscleroma, Pneumonia
* Klebsiella granulomatis
* Granuloma inguinale
* Klebsiella oxytoca
* Escherichia coli: Enterotoxigenic
* Enteroinvasive
* Enterohemorrhagic
* O157:H7
* O104:H4
* Hemolytic-uremic syndrome
* Enterobacter aerogenes/Enterobacter cloacae
Slow/weak
* Serratia marcescens
* Serratia infection
* Citrobacter koseri/Citrobacter freundii
Lac−
H2S+
* Salmonella enterica
* Typhoid fever, Paratyphoid fever, Salmonellosis
H2S−
* Shigella dysenteriae/sonnei/flexneri/boydii
* Shigellosis, Bacillary dysentery
* Proteus mirabilis/Proteus vulgaris
* Yersinia pestis
* Plague/Bubonic plague
* Yersinia enterocolitica
* Yersiniosis
* Yersinia pseudotuberculosis
* Far East scarlet-like fever
Pasteurellales
Haemophilus:
* H. influenzae
* Haemophilus meningitis
* Brazilian purpuric fever
* H. ducreyi
* Chancroid
* H. parainfluenzae
* HACEK
Pasteurella multocida
* Pasteurellosis
* Actinobacillus
* Actinobacillosis
Aggregatibacter actinomycetemcomitans
* HACEK
Legionellales
* Legionella pneumophila/Legionella longbeachae
* Legionnaires' disease
* Coxiella burnetii
* Q fever
Thiotrichales
* Francisella tularensis
* Tularemia
Vibrionaceae
* Vibrio cholerae
* Cholera
* Vibrio vulnificus
* Vibrio parahaemolyticus
* Vibrio alginolyticus
* Plesiomonas shigelloides
Pseudomonadales
* Pseudomonas aeruginosa
* Pseudomonas infection
* Moraxella catarrhalis
* Acinetobacter baumannii
Xanthomonadaceae
* Stenotrophomonas maltophilia
Cardiobacteriaceae
* Cardiobacterium hominis
* HACEK
Aeromonadales
* Aeromonas hydrophila/Aeromonas veronii
* Aeromonas infection
ε
Campylobacterales
* Campylobacter jejuni
* Campylobacteriosis, Guillain–Barré syndrome
* Helicobacter pylori
* Peptic ulcer, MALT lymphoma, Gastric cancer
* Helicobacter cinaedi
* Helicobacter cellulitis
* v
* t
* e
Tick-borne diseases and infestations
Diseases
Bacterial infections
Rickettsiales
* Anaplasmosis
* Boutonneuse fever
* Ehrlichiosis (Human granulocytic, Human monocytotropic, Human E. ewingii infection)
* Scrub typhus
* Spotted fever rickettsiosis
* Pacific Coast tick fever
* American tick bite fever
* rickettsialpox
* Rocky Mountain spotted fever)
Spirochaete
* Baggio–Yoshinari syndrome
* Lyme disease
* Relapsing fever borreliosis
Thiotrichales
* Tularemia
Viral infections
* Bhanja virus
* Bourbon virus
* Colorado tick fever
* Crimean–Congo hemorrhagic fever
* Heartland bandavirus
* Kemerovo tickborne viral fever
* Kyasanur Forest disease
* Omsk hemorrhagic fever
* Powassan encephalitis
* Severe fever with thrombocytopenia syndrome
* Tete orthobunyavirus
* Tick-borne encephalitis
Protozoan infections
* Babesiosis
Other diseases
* Tick paralysis
* Alpha-gal allergy
* Southern tick-associated rash illness
Infestations
* Tick infestation
Species and bites
Amblyomma
* Amblyomma americanum
* Amblyomma cajennense
* Amblyomma triguttatum
Dermacentor
* Dermacentor andersoni
* Dermacentor variabilis
Ixodes
* Ixodes cornuatus
* Ixodes holocyclus
* Ixodes pacificus
* Ixodes ricinus
* Ixodes scapularis
Ornithodoros
* Ornithodoros gurneyi
* Ornithodoros hermsi
* Ornithodoros moubata
Other
* Rhipicephalus sanguineus
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Boutonneuse fever | c0006060 | 4,147 | wikipedia | https://en.wikipedia.org/wiki/Boutonneuse_fever | 2021-01-18T18:34:17 | {"mesh": ["D001907"], "umls": ["C0006060"], "icd-10": ["A77.177.1"], "orphanet": ["83313", "101334"], "wikidata": ["Q895297"]} |
Esophageal squamous cell carcinoma (ESCC) is a type of esophageal carcinoma (EC; see this term) that can affect any part of the esophagus, but is usually located in the upper or middle third.
## Epidemiology
ESCC has an estimated annual incidence of 1/29,400.
## Clinical description
The average age of onset of ESCC is between the ages of 60 to 70 years and it is more frequently seen in males. It is usually asymptomatic until an advanced disease stage with common presenting symptoms being dysphagia (at first with solids then progressing to fluids) and weight loss. Less commonly odynophagia, hoarseness of voice, coughing, or chest pain can be presenting features. Tumors are typically found in the middle and the upper third of the esophagus.
## Etiology
The exact etiology is unknown. Cigarette smoking and alcohol abuse are the principal risk factors. There is also an association with idiopathic achalasia (see this term), a motility disorder of the esophagus.
## Diagnostic methods
Endoscopy and a biopsy will establish the diagnosis. For staging, a computed tomography (CT) scan of the neck, chest and abdomen, or CT combined with a positron emission tomography (CT-PET) scan will identify the primary tumor in most cases as well as any spread to the lymph nodes and organs such as the liver, lungs and bone. Endoscopic ultrasound (EUS), the combination of an ultrasound probe on an endoscope, is also increasingly used for staging, and is of particular value for early cancers. In upper or mid-esophageal tumors where there is a possibility of invasion of the airway (trachea or bronchi) a bronchoscopy may also be required.
## Differential diagnosis
Differential diagnoses include idiopathic achalasia (see this term), benign esophageal stricture, an esophageal web, and occasionally lung cancer.
## Management and treatment
Treatment may be with curative intent when the disease is confined to the esophagus and even when local nodes of the primary tumor are involved, and when the patient is fit enough for treatment. Treatment with palliative intent, targeted on symptom control and quality of life, but not cure, is the mainstay of treatment when the disease is advanced or incurable, or the patient is unfit for therapy due to significant co-morbidities. The traditional treatment of ESCC is surgical resection; this is usually via a transthoracic resection, and occasionally by a neck incision. In some cases a transhiatal esophagectomy is performed. The use of minimally invasive approaches to perform these operations is increasing in use. There is also an increasing use of chemotherapy or of the combination of chemotherapy and radiotherapy before and after surgery. A number of clinical trials support this practice, particularly where the tumor is locally advanced, and this is increasingly the standard of care in Europe and North America. The chemotherapeutic drugs most often used in combination are epirubicin, cisplatin and 5-fluorouracil (known as ECF). Capecitabine and oxaliplatin are less toxic agents that can be used in those with cardiac and renal problems. There is also an increasing use of radical, high-dose radiotherapy and chemotherapy for ESCC which avoids a surgery, and the outcomes are equivalent to surgical or multimodality approaches. For palliative approaches, self-expanding metal stents (SEMS) can relieve dysphagia, and chemotherapy, radiation therapy and laser-based approaches are also considered. Palliation may also involve nutritional support via feeding devices such as percutaneous endoscopic gastrostomy (PEG) tubes.
## Prognosis
As ESCC is usually diagnosed at an advanced disease stage, the overall prognosis is poor, with an overall 5-year survival of between 10-20%. In patients treated with curative intent the cure rate currently approaches 40%.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Squamous cell carcinoma of the esophagus | c0279626 | 4,148 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99977 | 2021-01-23T18:37:56 | {"mesh": ["D000077277"], "omim": ["133239"], "umls": ["C0279626"], "icd-10": ["C15.0", "C15.1", "C15.3", "C15.4"], "synonyms": ["ESCC", "Esophageal epidermoid carcinoma", "Esophageal squamous cell carcinoma"]} |
A number sign (#) is used with this entry because the Finnish type of amyloidosis is caused by mutation in the gelsolin gene (GSN; 137350).
See also corneal lattice dystrophy due to local amyloid deposition (122200), which occurs as an isolated dominant.
Description
The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including corneal lattice dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported (Meretoja, 1973).
Clinical Features
In a massive investigation in Finland, Meretoja (1973) identified 207 affected persons. Two patients, whose parents were affected and who were more severely affected than the others, were thought to represent homozygosity. A few of the patients developed nephrotic syndrome and renal failure and some had cardiac involvement. Amyloid involvement was rather widespread at autopsy. Meretoja et al. (1978) collected 307 patients in Finland.
Three Czechoslovakian sisters with bulbar palsy, 'cutis hyperelastica,' and lattice dystrophy of the cornea, reported by Klaus et al. (1959), may have had this disorder. Cases were reported from the United States by Sack et al. (1981), Purcell et al. (1983), Darras et al. (1986), and Starck et al. (1991); from Holland by Winkelman et al. (1971); and from Denmark by Boysen et al. (1979).
One of the patients reported by Sack et al. (1981) had onset of facial paralysis, which began as inability to control a drooping lower lip, at the age of about 56; the lip became strikingly protuberant and everted with exposure of the lower gingival mucosa. Five years after onset he could not wrinkle his forehead and there was an intermittent twitch of the right side of the lower lip. The extraocular muscles were affected only minimally and there was no ptosis. A striking feature was laxity of the skin, which raised the question of cutis laxa. Slit-lamp examination showed a lattice type of corneal opacity bilaterally. The mother had the identical disorder beginning at about the same stage of life. The proband had bulbar manifestations.
Kiuru (1992) reported the clinical findings of 30 patients. Signs of cranial neuropathy especially affecting the facial nerve were found in all, and peripheral polyneuropathy mainly affecting vibration and touch senses was demonstrated in 26 patients. Kiuru et al. (1994) studied the autonomic nervous system and heart in 30 patients. Minor autonomic nervous system dysfunction was found in most patients, but clinically significant autonomic dysfunction or cardiopathy was not characteristic.
Molecular Genetics
Maury et al. (1990) studied amyloid fibrils isolated from the kidney of a patient with the Finnish form. The amino acid sequence determined for part of the protein was identical to that deduced for plasma gelsolin in the region of amino acids 235-269. Using PCR and allele-specific oligonucleotide hybridization analysis of genomic DNA in patients with this disorder, Maury et al. (1990) identified a 654G-A transition in the GSN gene, resulting in an asp187-to-asn substitution (137350.0001), in all 5 unrelated patients studied, but not in 45 unrelated control subjects.
Haltia et al. (1990) likewise showed that the amyloid in this disorder is antigenically and structurally related to gelsolin. The same mutation in gelsolin (asp187-to-asn) has been found in all Finnish families studied to date (Maury et al., 1990; Paunio et al., 1992; de la Chapelle et al., 1992; Haltia et al., 1992; Sipila and Aula (2002)); furthermore, it was found also in the affected son of the proband of the Scottish-American family reported by Sack et al. (1981); see de la Chapelle et al. (1992).
Maury (1993) reported the findings in 2 sisters who were homozygous for the asp187-to-asn mutation in gelsolin. In both, the disease was unusually severe, manifesting with nephrotic syndrome and end-stage renal failure. Immunohistochemical studies of the kidneys demonstrated heavy glomerular deposits of gelsolin-derived amyloid. Immunostaining also demonstrated gelsolin in the tubular epithelium, where it was Congo-red negative.
Akiya et al. (1996) reported a Japanese brother and half-sister with lattice corneal dystrophy as part of the Finnish type amyloidosis. They referred to the Finnish-type as FAP type IV. The patients were 70 and 68 years old, respectively.
GU \- Nephrotic syndrome \- Renal failure Eye \- Lattice corneal dystrophy Lab \- Generalized amyloid deposition \- Mutant gelsolin gene (137350) Skin \- Cutis laxa Cardiac \- Amyloid cardiomyopathy Neuro \- Cranial neuropathy, esp. facial paresis \- Bulbar palsy \- Peripheral polyneuropathy, esp. vibration and touch loss \- Autonomic dysfunction does not occur Inheritance \- Autosomal dominant Misc \- Onset in third decade GI \- Gastrointestinal symptoms are inconstant ▲ 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
| AMYLOIDOSIS, FINNISH TYPE | c0936273 | 4,149 | omim | https://www.omim.org/entry/105120 | 2019-09-22T16:45:13 | {"doid": ["0050637"], "mesh": ["D028227"], "omim": ["105120"], "orphanet": ["85448"], "synonyms": ["Alternative titles", "AMYLOIDOSIS V", "AMYLOIDOSIS, MERETOJA TYPE", "AMYLOID CRANIAL NEUROPATHY WITH LATTICE CORNEAL DYSTROPHY", "AMYLOIDOSIS DUE TO MUTANT GELSOLIN"]} |
Female genital mutilation in Sierra Leone (also known as female genital cutting) is the common practice of removing all or part of the female's genitalia for cultural and religious initiation purposes, or as a custom to prepare them for marriage. Sierra Leone is one of 28 countries in Africa where female genital mutilation (FGM) is known to be practiced.[1]
## Contents
* 1 Cultural reasons
* 2 Prevalence
* 3 Health effects
* 4 Community response
* 5 See also
* 6 References
## Cultural reasons[edit]
FGM is regularly performed in Sierra Leone.[2] The reason that FGM is common in Sierra Leone is because FGM is practiced in a ‘secret society’ called the bondo secret society. The bondo society is an all-female society (also known as the sande) in West Africa. Secret societies are ancient cultural institutions that play a major role in West Africa and have existed for hundreds of years.[3] The purpose of this secret society is to help young women earn the rites of passage into adulthood. In order, to receive these rites of passage, a girl must undergo their cultural rituals including FGM.[2]
The initiation into the society occurs in the bondo bush which is a private enclosure constructed near their village. Time spent in the bondo bush for initiation into womanhood used to take about a month, but as the generations have gone by, the time has significantly reduced.[3] Once a woman becomes a member of the bondo, she is able to go to the bondo without her husband's permission. The bondo becomes the only place women are allowed to go to without permission from their husband. Thus, women who are a part of the bondo have an increased freedom of movement.[2]
In regard to society, members of the bondo are regarded as having a higher standing than other women. The cost of FGM and initiation into the bondo society is quite expensive, and so parents are proud when their daughters are initiated because it shows they are financially stable and able to afford this. Initiation can cost anywhere from 200,000 to 600,000 Leones, which converts to 62–185 dollars.[2] Soweis, the leader of the bondo, tend to raise the price of the initiation into the society if the woman is not a virgin. FGM is so expected in society that when a husband discovers upon marriage that his wife has not undergone FGM, it is common for him to pay for her to undergo the initiation.[3]
Woman's initiation is synonymous with women's power in Sierra Leone, and the act of excision is a reminder that women are from which all human creation is derived. Bondo elders believed that excision improves sexual satisfaction as it removes focus from the clitoris onto the hidden g-spot inside the vaginal canal which they believe has more satisfying and intense orgasms. It is also thought to enhance the appearance of a women's genitalia and make it easier to penetrate.[4]
In Sierra Leone, FGM usually consists of removing the clitoris as a major part in preparing the young women for marriage and motherhood through this initiation ceremony. The procedure is usually performed by an elderly woman of the village who has been especially designated for this task, by a village barber or by a traditional birth attendant. FGM can be broken down into three types. Type I removes the tissue protecting the head of the clitoris. Type II removes the tissue protecting the head of the clitoris, the clitoris itself, and part of or all of the labia minora. Type III, the most extreme case, involves removing all or part of the external genitalia and stitching the vaginal opening closed.[2]
## Prevalence[edit]
FGM is mainly performed in Africa as well as a few countries in Asia and the Middle East. The worldwide estimation of how many women have undergone FGM is anywhere from 130 to 140 million.[3] In the MICS conducted by UNICEF, the prevalence of FGM in Sierra Leone, Gambia, Burkina Faso and Mauritania was 94%, 79%, 74%, and 72% respectively. While in other countries in western Africa such as Ghana, Niger and Togo, the prevalence of FGM was less than 6%.[5]
Roughly 3 million girls in Africa undergo FGM every single year and Sierra Leone is one of the only countries in western Africa where the rate of prevalence is over 90%. Sierra Leone is the only country in southern western Africa with such a high rate of FGM. There is a decline in prevalence of FGM in Sierra Leone in younger age groups.[3]
The northern region has the highest prevalence and the Western the lowest.
Northern 96.3%, Eastern 91.3%, Southern 88.6%, and Western 75.6%.
In Sierra Leone, 40.2% of women from ages 15 to 49 who have experienced FGM underwent the procedure between the ages 10 and 14.[6]
## Health effects[edit]
There are no health benefits associated with FGM. The severity of the medical risks varies according to the extent of the cutting. In a 2013 study of 558 girls and women aged 12–47, 31.7% had type Ib; 64.1%, type IIb; and 4.2%, type IIc (4 participants refused the exam).[3] Short-term effects of FGM include excessive bleeding, local infections, and incomplete healing. Long-term effects include scarring, genital ulcers, dermoid inclusion cysts, lower abdominal pain, and infertility. But the worst effect is death at delivery, the rate of which is excessively high in Sierra Leone[3]
TYPES OF FEMALE GENITAL MUTILATION
There are four classifications of Female Genital Mutilation (FGM).[7] The health effects of FGM vary with the type of procedure undergone by each individual.
Classifications of FGM Type 1 Partial or total removal of the clitoirs and/or the prepuce (clitoridectomy)
Type 2 Partial or total removal of the clitoris and the labia minora, with or without excision of the labia majora (excision)
Type 3 Narrowing of the vaginal orifice with creation of a covering seal by cutting and appositioning the labia minora and/or the labia majora, with or without excision of the clitoris (infibulation)
Type 4 All other harmful procedures to the female genitalia for non-medical purposes, for example: pricking, piercing, incising, scraping and cauterization
FEMALE GENITAL MUTILATION IMPACT ON HEALTH
Sierra Leone is one out of twenty-eight African countries that practices Female Genital Mutilation. Almost 90% of Sierra Leonean women will undergo FGM. Most often the operation involves the use of blunt instruments such as razor blades, penknives, or broken glass.[8]
Many women that have experienced FGM reported having severe pain, shock caused by pain, excessive bleeding (haemorrhage), swelling that makes it difficult to pass urine and feces, infections, and oedema.[9] A study in Sierra Leone concluded that women who underwent FGM experienced excessive bleeding, tenderness, inability to heal well, difficulty when urinating, and infections such as Urinary Tract Infections (UTI's).[10]
Female genital mutilation is followed by both short-term and long-term effects. Immediate signs of complications appear within a few hours and can last up to ten days after the procedure. Long-term problems were present more than ten days later and were associated with pregnancy affectations during labor and/or childbirth.[11]
The most common short-term health complications involve hemorrhaging that can result in shock or death. Infection to the entire pelvic organs can occur which can lead to sepsis. Tetanus and gangrene can lead to death. Intense pain that causes shock during and after procedure. The use of blunt instruments can damage the adjoining organs. Lastly, urine retention occurs from swelling and/or blockage of the urethra.[12]
Long-term health consequences associated with FGM include dermoid cysts and abscesses, chronic pelvic infections that can lead to chronic back and pelvic pain as well as urinary tract infections.[13]
Other long-term complications involve painful and blocked menses (menstrual dysfunction) that can result in
1. hematocolpos \- accumulation of menstrual blood in the vagina,
2. hematometra \- accumulation of menstrual blood in the uterus, and
3. hematosalpinx \- accumulation of menstrual blood in the fallopian tubes
In addition, sexual problems are more prevalent among women with FGM. Women with FGM reported having persistent pain during sexual intercourse. Furthermore, the penis may become obstructed from penetrating the vagina which can require a surgical procedure. And, sexual dysfunction such as the inability to attain an orgasm during copulation is also common.[12]
Moreover, there is an increased risk of maternal and child morbidity due to obstructed labor. A recent study found higher death rates (including stillbirths) among infants born to mothers who have experienced FGM than mothers with no FGM. Women with Type I FGM were at 15% more likely, Type II women had a 32% increase, and Type III women had an overall 55% chance of experiencing death or stillbirth.[14]
Chronic urinary tract infections, incontinentia urine (inability to control urination), infertility, abscesses, dermoid cysts, keloid scars (hardening of the scars) and increase risks to HIV infection are also associated with long-term health complications of FGM.[12]
FGM can also result in psychological trauma. Notably, post-traumatic stress disorder, anxiety, depression, and psychosexual problems. Studies demonstrate that women with FGM are more likely to encounter psychological disturbances such as low self-esteem, somatization, and phobia.[15]
## Community response[edit]
People in Sierra Leone believe that abandoning FGM would be an abandonment of cultural tradition. They believe that FGM is similar to male circumcision which is widely acceptable across the globe. FGM supporters in Sierra Leone believe that females who do not receive the circumcision will have trouble conceiving, suffer psychological trauma, have bad luck, or be considered unworthy of marriage. Women who are pro-FGM state that it does not oppress female sexuality and instead it celebrates it through these ritual practices.[4]
They also state that the supposed consequences of excision (which include menstrual problems, painful sex, infections, et cetera) were not specific to women who underwent FGM. The rate for infertility is ten percent for both groups. They also argue that the reason for increase of still births in circumcised women is not because of the FGM they underwent but because they delay receiving prenatal care and visiting hospitals because they fear being stigmatized by the medical staff because of their circumcision.[4]
FGM supporters believe that FGM prevents prostitution by decreasing a woman's sexual desire, and is more hygienic.[2] According to a five-year research done by Hanny Lightfoot-Klein, an anti-FGM activist, 94% of circumcised women reported being satisfied by their sex lives and had sex between three and four times a week.[4]
Anti-FGM advocates state that more than 80% of women who experience it reported suffering a minimum of one health complication.[2] People against FGM widely refer to it as mutilation which is a controversial term that is rejected by members of communities who practice it.[3] The World Health Organization has adopted this term and it is widely used to describe the injury made to the women's genitalia even though the intent was not to mutilate.[1]
The Amazonian Initiative Movement is one of several nongovernmental organizations in West Africa against FGM. The aim of the group is to educate women who perform FGM and set them up with another job besides performing this procedure. The World Health Organization has consistently condemned this traditional practice as “willful damage to healthy organs for non-therapeutic reasons” and they have stated that the practice of female genital mutilation can result in infertility, pregnancy and childbirth complications, and psychological problems through inability to experience sexual pleasure.[1] Supporters of the eradication of all forms of nonconsented genital cutting believe that it violates the human right to bodily integrity. However, Sierra Leone does not have an explicit law against the practice of FGM.[2]
## See also[edit]
* Women in Sierra Leone
* Human rights in Sierra Leone
* Prevalence of female genital mutilation by country
## References[edit]
1. ^ a b c Bitong, Liliane (November 2005). "Fighting Genital Mutilation in Sierra Leone". Bulletin of the World Health Organization. 83 (11): 801–880. PMC 2626459. PMID 16302032.
2. ^ a b c d e f g h Mgbako, Chi (2010). "Penetrating the Silence in Sierra Leone: A Blueprint for the Eradication of Female Genital Mutilation". Harvard Human Rights Journal. 23 (1): 110–140.
3. ^ a b c d e f g h Bjälkander, Owolabi; Grant, Donald S.; Berggren, Vanja; Bathija, Heli; Almroth, Lars (March 2013). "Female Genital Mutilation in Sierra Leone: Forms, Reliability of Reported Status, and Accuracy of Related Demographic and Health Survey Questions". Obstetrics and Gynecology International. 2013: 1–14. doi:10.1155/2013/680926. PMC 3800578. PMID 24204384.
4. ^ a b c d Ahmadu, Fuambai (2009). "Disputing the Myth of the Sexual Dysfunction of Circumcised Women: An Interview with Fuambai S. Ahmadu by Richard A. Shweder". Anthropology Today. 25 (6): 14–17. doi:10.1111/j.1467-8322.2009.00699.x.
5. ^ Sipsma, Heather L., et al. "Female Genital Cutting: Current Practices and Beliefs in Western Africa." Bulletin of the World Health Organization 90.2 (2012): 120-127F. Print.
6. ^ "Sierra Leone: The Law and FGM" (PDF). 28toomany.org. September 2018.
7. ^ "An update on WHO's work on female genital mutilation (FGM)" (PDF). World Health Organization.
8. ^ Bitong, Liliane. "Fighting genital mutilation in Sierra Leone". Sci ELO Public Health.
9. ^ "An update on WHO's work on female genital mutilation (FGM)" (PDF). World Health Organization.
10. ^ Bjälkander, Owolabi. "Health complications of female genital mutilation in Sierra Leone". International Journal of Women's Health. 4: 321–31. doi:10.2147/IJWH.S32670. PMC 3410700. PMID 22870046.
11. ^ Kaplan, Adriana (3 October 2011). "Health consequences of female genital mutilation/cutting in the Gambia, evidence into action". Reprod Health. 8: 26. doi:10.1186/1742-4755-8-26. PMC 3195700. PMID 21967670.
12. ^ a b c Yurnalis, Uddin (2010). Female circumcision : a social, cultural, health, and religious perspectives / Jurnalis Uddin ... [et al.] Jakarta: Yarsi University Press. ISBN 9789799186171.
13. ^ "An update on WHO's work on female genital mutilation (FGM)" (PDF). World Health Organization.
14. ^ "An update on WHO's work on female genital mutilation (FGM)" (PDF). World Health Organization.
15. ^ Berg, RC (2010). "Psychological, Social and Sexual Consequences of Female Genital Mutilation/Cutting (FGM/C): A Systematic Review of Quantitative Studies [Internet]". PMID 29320049. Cite journal requires `|journal=` (help)
* v
* t
* e
Female genital mutilation
Health issues
* Clitoridectomy
* Dysmenorrhea
* Dyspareunia
* Gishiri cutting
* Husband stitch
* Infibulation
* Keloid scars
* Pelvic inflammatory disease
* Rectovaginal fistula
* Vesicovaginal fistula
By country
* Prevalence by country
* Laws by country
* FGM in India
* colonial Kenya
* Kurdistan
* New Zealand
* Nigeria
* Sierra Leone
* Sudan
* United Kingdom
* United States
* Religious views on FGM
Writers/groups
Early writers
and activists
* Raqiya Haji Dualeh Abdalla
* Janice Boddy
* Mary Daly
* Efua Dorkenoo
* Asma El Dareer
* Benoîte Groult
* Rose Oldfield Hayes
* Fran Hosken
* Edna Adan Ismail
* Nawal El Saadawi
* Lilian Passmore Sanderson
* Marion Scott Stevenson
* Hulda Stumpf
* Nahid Toubia
* Amina Warsame
Others
* Fuambai Ahmadu
* Ayaan Hirsi Ali
* Ellen Gruenbaum
* Waris Dirie
* Gerry Mackie
* Molly Melching
* Layli Miller-Muro
* Comfort Momoh
* Alice Walker
Groups
* Babiker Bedri Scientific Association for Women's Studies
* Equality Now
* FORWARD
* Inter-African Committee on Traditional Practices Affecting the Health of Women and Children
* RAINBO
* Tostan
* Tahirih Justice Center
* Zero Tolerance Day
Media
Books
* Woman at Point Zero (1975)
* Woman, Why Do You Weep? (1982)
* Possessing the Secret of Joy (1992)
* Desert Flower (1998)
Films
* Moolaadé (2004)
* Desert Flower (2009)
* My Body My Rules (2015)
Legislation
* Matter of Kasinga
* Prohibition of Female Circumcision Act 1985
* Female Genital Mutilation Act 2003
* 2005 (Scotland) Act
* Children Act 1989 (Amendment) (Female Genital Mutilation) Act 2019
Categories
* Female genital mutilation
* Activists against female genital mutilation
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Female genital mutilation in Sierra Leone | None | 4,150 | wikipedia | https://en.wikipedia.org/wiki/Female_genital_mutilation_in_Sierra_Leone | 2021-01-18T18:55:14 | {"wikidata": ["Q18355010"]} |
Holocarboxylase synthetase deficiency
Other namesEarly-onset multiple carboxylase deficiency[1]
Biotin
SpecialtyMedical genetics, endocrinology
Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to use the vitamin biotin effectively.[2] This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin. Symptoms are very similar to biotinidase deficiency and treatment – large doses of biotin – is also the same.[citation needed]
## Contents
* 1 Symptoms and signs
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Symptoms and signs[edit]
This section is empty. You can help by adding to it. (May 2017)
## Genetics[edit]
Holocarboxylase synthetase deficiency has an autosomal recessive pattern of inheritance.
Mutations in the HLCS gene cause holocarboxylase synthetase deficiency. The HLCS gene makes an enzyme, holocarboxylase synthetase, that attaches biotin to other molecules. Biotin, a B vitamin, is found in foods such as liver, egg yolks, and milk. It is essential for the normal production and breakdown of proteins, fats, and carbohydrates in the body. Mutations in the HLCS gene reduce the activity of holocarboxylase synthetase, preventing cells from using biotin effectively and disrupting many cellular functions.[citation needed] This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered.
## Diagnosis[edit]
The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have immunodeficiency diseases, difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management (using biotin supplements) may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.[citation needed]
## Treatment[edit]
This section is empty. You can help by adding to it. (May 2017)
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Holocarboxylase synthetase deficiency". www.orpha.net. Retrieved 8 April 2019.
2. ^ Reference, Genetics Home. "holocarboxylase synthetase deficiency". Genetics Home Reference. Retrieved 2017-05-09.
This article incorporates public domain text from The U.S. National Library of Medicine
## External links[edit]
Classification
D
* ICD-10: E53.8
* OMIM: 253270
* MeSH: D028922
* DiseasesDB: 32709
External resources
* eMedicine: ped/1020
* Orphanet: 79242
* v
* t
* e
Metabolic disorders of vitamins, coenzymes, and cofactors
B7 Biotin/MCD
* Biotinidase deficiency
* Holocarboxylase synthetase deficiency
Other B
* B5 (Pantothenate kinase-associated neurodegeneration)
* B12 (Methylmalonic acidemia)
Other vitamin
* Familial isolated vitamin E deficiency
Nonvitamin cofactor
* Tetrahydrobiopterin deficiency
* Molybdenum cofactor deficiency
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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
| Holocarboxylase synthetase deficiency | c0268581 | 4,151 | wikipedia | https://en.wikipedia.org/wiki/Holocarboxylase_synthetase_deficiency | 2021-01-18T18:28:06 | {"gard": ["2721"], "mesh": ["D028922"], "umls": ["C0268581"], "orphanet": ["79242"], "wikidata": ["Q5883885"]} |
A number sign (#) is used with this entry because of evidence that primary open angle glaucoma-1O is caused by heterozygous mutation in the NTF4 gene (162662) on chromosome 19q13.
For a phenotypic description and a discussion of genetic heterogeneity of primary open angle glaucoma (POAG), see 137760.
Molecular Genetics
In a 3-stage study, Pasutto et al. (2009) analyzed the NTF4 gene (162662) in a total of 892 patients with high- and normal-tension primary open angle glaucoma (POAG) and 895 controls, and identified 6 different heterozygous missense mutations in 15 (1.7%) patients (see, e.g., 162662.0001-162662.0003). The discovery group, which involved patients who were negative for 4 known glaucoma-associated genes, included 9 mutation-positive individuals, all of whom were sporadic cases with deceased parents and no other affected family members to date, thus precluding segregation analysis. A heterozygous missense mutation was also identified in 1 population-based control from the second replication group, who had not been ophthalmologically examined (p less than 0.0002). On the basis of molecular modeling, all NTF4 variants were predicted to affect either dimer stability or the interaction between the NTF4 dimer and its receptor TRKB (600456). The authors concluded that there was strong genetic evidence that NTF4 variants are associated with POAG.
Liu et al. (2010) analyzed the NTF4 gene in 443 POAG cases and 533 controls of European ancestry from the southeastern United States, and identified nonsynonymous coding changes in 5 cases and 12 controls, including 2 variants previously identified by Pasutto et al. (2009) (see A88V, 162662.0001, and R206W, 162662.0002). In addition, Liu et al. (2010) identified a heterozygous nonsense mutation (S29X) in the NTF4 gene in a 56-year-old control with hyperopia and presbyopia. Liu et al. (2010) concluded that heterozygous coding changes in NTF4 do not play a significant role in the pathogenesis of POAG in this population. In response, Pasutto and Reis (2010) noted that the control group used by Liu et al. (2010) was significantly younger than theirs (mean age, 64.7 years vs 73.9 years, respectively). Pasutto and Reis (2010) stated, however, that they could not exclude the possibility that some of the variants identified in the original study or this one are benign variants. They concluded that a metaanalysis of different studies in glaucoma patients with population-based controls would be required to clarify the role of NTF4 in glaucoma.
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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, O | c2751294 | 4,152 | omim | https://www.omim.org/entry/613100 | 2019-09-22T15:59:40 | {"mesh": ["C567753"], "omim": ["613100"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-21 (MCPH21) is caused by homozygous mutation in the NCAPD2 gene (615638) on chromosome 12p13. One such patient has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Clinical Features
Martin et al. (2016) reported a 3-year-old boy of Indian descent (patient 1) with primary microcephaly (-11.9 SD). He had a sloping forehead, short stature (-5.8 SD), poor overall growth, severe intellectual disability with absent speech, and autistic features.
Inheritance
The transmission pattern of MCPH21 in the family reported by Martin et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a 3-year-old boy (P1) of Indian descent with MCPH21, Martin et al. (2016) identified a homozygous splice site mutation in the NCAPD2 gene (615638.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in the heterozygous state in each unaffected parent. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. This was associated with increased numbers of mid- and late-anaphase cells, increased ultrafine DNA bridges, increased micronuclei, and increased aneuploidy, all indicating decatenation failure at mitosis. These abnormalities could potentially reduce neuronal cell proliferation, viability, and survival, resulting in microcephaly. The findings indicated that the mutation disrupted condensin-dependent mitotic chromosome integrity.
Reuter et al. (2017) reported 2 sibs, born of consanguineous parents (family MR-DIV-02), with mild intellectual disability, intrauterine growth retardation, short stature, and microcephaly who carried homozygous missense variants in 2 genes: a T237M substitution in the ENO2 gene (131360) and a F8S substitution in the NCAPD2 gene. The variants were confirmed by Sanger sequencing and segregated with the disorder in the family. The patients were part of a large study of 152 consanguineous families with neurodevelopmental disorders who underwent exome sequencing. Functional studies of the variants and studies of patient cells were not performed.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Poor overall growth HEAD & NECK Head \- Microcephaly (up to -11 SD) Face \- Sloping forehead NEUROLOGIC Central Nervous System \- Intellectual disability, moderate \- Absent speech Behavioral Psychiatric Manifestations \- Autistic features MISCELLANEOUS \- One boy of Indian descent has been reported (last curated May 2018) MOLECULAR BASIS \- Caused by mutation in the non-SMC condensin I complex subunit D2 gene (NCAPD2, 615638.0001 ) ▲ 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
| MICROCEPHALY 21, PRIMARY, AUTOSOMAL RECESSIVE | c4693831 | 4,153 | omim | https://www.omim.org/entry/617983 | 2019-09-22T15:44:09 | {"omim": ["617983"]} |
Liver phosphorylase deficiency, or glycogen storage disease type 6b (Hers' disease, GSD 6b) is a benign and rare form of glycogen storage disease.
## Clinical description
The disease usually occurs in childhood and is characterized by hepatomegaly and growth delay. Hypoglycemic episodes are mild or absent, and hypertransaminasemia and hyperlipidemia are moderate and unconstant. Hepatomegaly usually improves with age and disappears entirely at puberty.
## Etiology
Transmission is autosomal recessive and mutations in the PYGL gene (14q21-q22) have been identified in patients.
## Diagnostic methods
Diagnosis is based on biochemical findings revealing excess glycogen and partial deficiency of total and active phosphorylase in liver biopsy.
## Management and treatment
A diet with high carbohydrate intake and regular meals prevents hypoglycemia in children, but most patients require no specific treatment.
## Prognosis
Prognosis is usually good.
*[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
| Glycogen storage disease due to liver glycogen phosphorylase deficiency | c0017925 | 4,154 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369 | 2021-01-23T18:31:38 | {"gard": ["6529"], "mesh": ["D006013"], "omim": ["232700"], "umls": ["C0017925"], "icd-10": ["E74.0"], "synonyms": ["GSD due to liver glycogen phosphorylase deficiency", "GSD type 6", "GSD type VI", "Glycogen storage disease type 6", "Glycogen storage disease type VI", "Glycogenosis due to liver glycogen phosphorylase deficiency", "Glycogenosis type 6", "Glycogenosis type VI", "Hepatic glycogen phosphorylase deficiency", "Hepatic phosphorylase deficiency", "Hers disease", "Liver glycogen phosphorylase deficiency"]} |
Peripheral blood smear in patient with thrombotic thrombocytopenic purpura. Typical typical schistocytes are annotated.
A schistocyte or schizocyte (from Greek schistos for "divided" and kytos for "hollow" or "cell") is a fragmented part of a red blood cell. Schistocytes are typically irregularly shaped, jagged, and have two pointed ends.[1]
Several microangiopathic diseases, including disseminated intravascular coagulation and thrombotic microangiopathies, generate fibrin strands that sever red blood cells as they try to move past a thrombus, creating schistocytes.
Schistocytes are often seen in patients with hemolytic anemia. They are frequently a consequence of mechanical artificial heart valves and hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, among other causes.
Excessive schistocytes present in blood can be a sign of microangiopathic hemolytic anemia (MAHA).
## Contents
* 1 Appearance
* 2 Pathophysiology
* 3 Schistocyte count
* 4 Conditions
* 4.1 Disseminated intravascular coagulation
* 4.2 Thrombotic thrombocytopenic purpura
* 4.3 Hemolytic-uremic syndrome
* 4.4 Malfunctioning cardiac valves
* 5 References
* 6 External links
## Appearance[edit]
Schistocytes are fragmented red blood cells that can take on different shapes. They can be found as triangular, helmet shaped, or comma shaped with pointed edges. Schistocytes are most often found to be microcytic with no area of central pallor. There is usually no change in deformability, but their lifespan is lower than that of a normal red blood cell (120 days). This is due to their abnormal shape which can cause them to undergo hemolysis or be removed by macrophages in the spleen.[2]
## Pathophysiology[edit]
Schistocyte formation occurs as a result of mechanical destruction (fragmentation hemolysis) of a normal red blood cell. This occurs when there is damage to the blood vessel and a clot begins to form. The formation of the fibrin strands in the vessels occurs as part of the clot formation process. The red blood cells get trapped in the fibrin strands and the sheer force of the blood flow causes the red blood cell to break. The resulting fragmented cell is called the schistocyte.[3]
## Schistocyte count[edit]
A normal schistocyte count for a healthy individual is <0.5% although usual values are found to be <0.2%. A schistocyte count of >1% is most often found in thrombotic thrombocytopenic purpura, although they are more often seen within the range of 3–10% for this condition. A schistocyte count of <1% but greater than the normal value is suggestive of disseminated intravascular coagulation, but is not an absolute diagnosis. The standard for a schistocyte count is a microscopic examination of a peripheral blood smear.[4]
## Conditions[edit]
Schistocytes on the peripheral blood smear is a characteristic feature of microangiopathic hemolytic anemia(MAHA).[5] The causes of MAHA can be disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, HELLP syndrome, malfunctioning cardiac valves etc. In most of the conditions, schistocytes are formed by fibrin formation and entrapment of red blood cells leading to fragmentation due to the force of blood flow in the vessels.[6]
### Disseminated intravascular coagulation[edit]
Disseminated intravascular coagulation or DIC is caused by a systemic response to a specific condition including sepsis and severe infection, malignancy, obstetric complications, massive tissue injury, or systemic diseases. Disseminated intravascular coagulation is an activation of the coagulation cascade which is usually a result of an increased exposure to tissue factor. The activation of the cascade leads to thrombi formation which causes an accumulation of excess fibrin formation in the intravascular circulation. The excess fibrin strands cause mechanical damage to the red blood cells resulting in schistocyte formation and also thrombocytopenia and consumption of clotting factors. Schistocyte values between .5% and 1% are usually suggestive of DIC.[7]
### Thrombotic thrombocytopenic purpura[edit]
Thrombotic thrombocytopenic purpura or TTP is caused by primary platelet activation. Thrombotic thrombocytopenic purpura leads to increased amounts of large von Willebrand factor which then attach to activated platelets and mediate further platelet aggregation. Platelets end up being removed and the resulting fibrin strand formation remains. These fibrin strands along with the stress from the blood flow cause fragmentation of the red blood cells, leading to schistocyte formation. In TTP, a schistocyte count between 3–10% is common, but >1% is suggestive of the disease.[7]
### Hemolytic-uremic syndrome[edit]
Hemolytic-uremic syndrome or HUS is hemolytic anaemia, acute kidney failure (uremia), and thrombocytopenia. HUS is caused by E. coli bloody diarrhea and specific strains of shiga toxin. The bacteria in HUS cause damage to the endothelium which results in platelet activation and formation of microthrombi. Red cells get trapped in the fibrin strands of the microthrombi and become sheared by the force of blood flow leading to schistocyte formation.[7]
### Malfunctioning cardiac valves[edit]
Leaky prosthetic heart valves and other cardiac assisted devices can lead to microangiopathic hemolytic anemia (with schistocyte formation) and thrombocytopenia. The force from the blood flow over the high pressure gradient from the prosthesis leads to fragmentation of red cells, and schistocyte formation. This is rare and only occurs in about 3% of patients.[6]
## References[edit]
1. ^ ZINI, G.; d’ONOFRIO, G.; BRIGGS, C.; ERBER, W.; JOU, J. M.; LEE, S. H.; McFADDEN, S.; VIVES-CORRONS, J. L.; YUTAKA, N.; LESESVE, J. F. (2011-11-15). "ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes". International Journal of Laboratory Hematology. Wiley. 34 (2): 107–116. doi:10.1111/j.1751-553x.2011.01380.x. ISSN 1751-5521. PMID 22081912.
2. ^ Lesesve, Jean-Francois; Fenneteau, Odile; Zini, Gina (2014). "Schistocytes". Transfusion. 54 (6): 1459. doi:10.1111/trf.12523. PMID 24911907.
3. ^ Bull, Brian; Kuhn, Irvin (1970). "The Production of Schistocytes by Fibrin Strands (A Scanning Electron Microscope Study)". Blood. 35: 104–111. doi:10.1182/blood.V35.1.104.104. PMID 5412670.
4. ^ Lesesve, J; Martin, M; Banasiak, C; Andre-Kerneis, E; Bardet, V; Lusina, D; Kharbach, A; Genevieve, F; Lecompte, T (2014). "Schistocytes in disseminated intravscular coagulation". International Journal of Laboratory Hematology. 36 (4): 439–43. doi:10.1111/ijlh.12168. PMID 24261329.
5. ^ Tefferi, Ayalew; Elliott, Michelle A. (June 2004). "Schistocytes on the Peripheral Blood Smear". Mayo Clinic Proceedings. 79 (6): 809. doi:10.4065/79.6.809. PMID 15182097.
6. ^ a b Schrier, Stanley. "Extrinsic nonimmune hemolytic anemia due to mechanical damage: Fragmentation hemolysis and hypersplenism". UpToDate.
7. ^ a b c Suri, Mandeep. "Disseminated Intravascular Coagulation (DIC)". Fastbleep Medical Notes. Archived from the original on 2015-03-04. Retrieved 2014-12-08.
## External links[edit]
* Images in Clinical Medicine: Hemolytic Anemia after Mitral-Valve Repair, Sarinya Puwanant and Watchara Lohawijarn, N Engl J Med 2012; 367:e29 (November 15, 2012) DOI: 10.1056/NEJMicm1201695 [FREE TEXT]
* v
* t
* e
Blood film findings
Red blood cells
Size
* Anisocytosis
* Macrocytosis
* Microcytosis
Shape
* Poikilocytosis
* Membrane abnormalities
* Acanthocyte
* Codocyte
* Elliptocyte
* Hereditary elliptocytosis
* Spherocyte
* Hereditary spherocytosis
* Dacrocyte
* Echinocyte
* Schistocyte
* Degmacyte
* Sickle cell/drepanocyte
* Sickle cell disease
* Stomatocyte
* Hereditary stomatocytosis
Colour
* Anisochromia
* Hypochromic anemia
* Polychromasia
Inclusion bodies
* Developmental
* Howell–Jolly body
* Basophilic stippling
* Pappenheimer bodies
* Cabot rings
* Hemoglobin precipitation
* Heinz body
Other
* Red cell agglutination
* Rouleaux
White blood cells
Lymphocytes
* Reactive lymphocyte
* Smudge cell
* Russell bodies
Granulocytes
* Hypersegmented neutrophil
* Arneth count
* Pelger–Huët anomaly
* Döhle bodies
* Toxic granulation
* Toxic vacuolation
* Critical green inclusion
* Alder–Reilly anomaly
* Jordans' anomaly
* Birbeck granules
* Left shift
Other
* Auer rod
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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
| Schistocyte | None | 4,155 | wikipedia | https://en.wikipedia.org/wiki/Schistocyte | 2021-01-18T19:09:51 | {"wikidata": ["Q623225"]} |
Spastic paraplegia-glaucoma-intellectual disability syndrome is characterized by progressive spastic paraplegia, glaucoma and intellectual deficit. It has been described in two families. The second described sibship was born to consanguineous parents. The mode of inheritance is autosomal recessive.
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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
| Spastic paraplegia-glaucoma-intellectual disability syndrome | c1849113 | 4,156 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2818 | 2021-01-23T17:02:54 | {"mesh": ["C564809"], "omim": ["270850"], "umls": ["C1849113"]} |
A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth disease type 2T (CMT2T) is caused by homozygous or compound heterozygous mutation in the MME gene (120520) on chromosome 3q25. Some patients may carry heterozygous MME mutations.
Description
Charcot-Marie-Tooth disease type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy with onset in middle age (Higuchi et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Clinical Features
Higuchi et al. (2016) reported 10 unrelated Japanese patients with adult-onset Charcot-Marie-Tooth disease. Most of the patients had one or more similarly affected family members, and 6 of the families were consanguineous. The mean age at disease onset was 47.2 years (range, 36-56 years), and all patients had slowly progressive weakness and atrophy of the distal lower limb muscles, resulting in gait disturbance, although none were wheelchair-bound. All also had distal sensory impairment and hyporeflexia. Electrophysiologic studies were consistent with an axonal neuropathy, with an intermediate phenotype in 1 patient. Sural nerve biopsy from 2 patients showed a decrease in the density of large myelinated fibers with thick myelin sheaths and clusters of myelinated fibers. None of the patients had additional neurologic signs, including pyramidal signs, cerebellar ataxia, cognitive impairment, or signs of Alzheimer disease. Brain imaging of 5 patients did not show cerebral atrophy.
Inheritance
The transmission pattern of CMT2T in the families reported by Higuchi et al. (2016) was consistent with autosomal recessive inheritance.
Auer-Grumbach et al. (2016) reported families with autosomal dominant transmission of susceptibility to late-onset CMT2T.
Molecular Genetics
In 10 Japanese probands with CMT2T, Higuchi et al. (2016) identified homozygous or compound heterozygous mutations in the MME gene (see, e.g., 120520.0001-120520.0005). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the families in which segregation was analyzed. All but 1 of the mutations resulted in a splice site defect or a truncated protein, consistent with a loss-of-function mechanism. Sural nerve biopsy from 2 unrelated patients showed absent immunostaining for MME in a patient with a truncating mutation and decreased immunostaining for MME in a patient with a missense mutation. MME mutations accounted for 13% of patients with a diagnosis of autosomal recessive CMT who underwent whole-exome sequencing, and Higuchi et al. (2016) concluded that mutations in the MME gene are the most frequent cause of autosomal recessive axonal CMT in the Japanese population.
### Susceptibility to Late-Onset Charcot-Marie-Tooth Disease Type 2T
In 19 probands of European descent with late-onset axonal CMT, Auer-Grumbach et al. (2016) identified 11 different heterozygous variants in the MME gene (see, e.g., 120520.0007-120520.0009), including 7 loss-of-function alleles and 4 missense alleles. The variants in the first 3 families were found by whole-exome sequencing; subsequent MME variants were found in 6 of 45 additional probands with a similar disorder who underwent direct sequencing of the MME gene. Select patient samples and in vitro cellular studies were consistent with decreased tissue availability of neprilysin and impaired enzymatic activity. Examination of repositories of whole-exome data from more than 10,000 individuals with neurologic and other disorders found 12 more individuals with heterozygous truncating variants, 10 of whom had polyneuropathy, motor neuron disorder, or sensory ataxia. Statistical analysis showed that MME loss-of-function variants were overrepresented among cases with late-onset CMT2T compared to controls in several large databases; however, some of the variants were also present in controls and sometimes showed incomplete penetrance in family studies, suggesting that heterozygous variants may confer susceptibility to the late-onset axonal CMT.
INHERITANCE \- Autosomal recessive \- Autosomal dominant MUSCLE, SOFT TISSUES \- Distal muscle weakness due to peripheral neuropathy \- Distal muscle atrophy due to peripheral neuropathy NEUROLOGIC Central Nervous System \- No dementia Peripheral Nervous System \- Axonal sensorimotor neuropathy \- Distal sensory impairment \- Foot drop \- Gait instability \- Hyporeflexia \- Areflexia \- Loss of large myelinated fibers seen on sural nerve biopsy MISCELLANEOUS \- Adult onset (range 36 to 56 years) \- Slowly progressive \- Some patients have heterozygous mutations and may show slightly later onset MOLECULAR BASIS \- Caused by mutation in the membrane metalloendopeptidase gene (MME, 120520.0001 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2T | c4015635 | 4,157 | omim | https://www.omim.org/entry/617017 | 2019-09-22T15:47:14 | {"doid": ["0110160"], "omim": ["617017"], "orphanet": ["497757", "495274", "497764"], "synonyms": ["CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2T", "Autosomal recessive axonal Charcot-Marie-Tooth disease type 2T", "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2T", "SCA43", "AR-CMT2T", "Alternative titles", "MME-related autosomal dominant hereditary motor and sensory neuropathy type 2", "MME-related autosomal dominant CMT2", "CMT2T"]} |
Microvillus inclusion disease is an intestinal disorder characterized by severe, watery diarrhea and an inability of the intestines to absorb nutrients. Symptoms typically develop in the first days (early-onset) or first months (late-onset) of life. Without adequate water and nutrients, children with this condition can become dehydrated, suffer from malnutrition, and fail to grow and develop normally. Management is difficult and relies on total parenteral nutrition. The advent of intestinal transplantation has improved the outlook for these patients. Microvillus inclusion disease is inherited in an autosomal recessive manner.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Microvillus inclusion disease | c0341306 | 4,158 | gard | https://rarediseases.info.nih.gov/diseases/7039/microvillus-inclusion-disease | 2021-01-18T17:59:03 | {"mesh": ["C537470"], "omim": ["251850"], "umls": ["C0341306"], "orphanet": ["2290"], "synonyms": ["Davidson disease", "Microvillus atrophy, congenital", "Congenital familial protracted diarrhea with enterocyte brush-border abnormalities", "Intractable diarrhea of infancy", "Congenital familial protracted diarrhea", "Congenital microvillous atrophy", "Davidson's disease", "Familial enteropathy, microvillus"]} |
For a phenotypic description and a discussion of genetic heterogeneity of left ventricular noncompaction (LVNC), see 604169.
Mapping
In a family originally reported by Sasse-Klaassen et al. (2003), Sasse-Klaassen et al. (2004) reported linkage studies demonstrating a locus for autosomal dominant LVNC in 11p15. A peak 2-point LOD score of 5.06 was obtained with marker D11S902 at theta = 0. Haplotype analysis defined a critical interval of 6.4 centimorgans between D11S1794 and D11S928, corresponding to a physical distance of 6.8 megabases. No disease-causing mutation was identified in 2 prime positional candidate genes located in the critical region of mapping: the gene encoding muscle LIM protein (CSRP3; 600824), mutation in which causes dilated (CMD1M; 607482) and hypertrophic (CMH12; 612124) cardiomyopathy, and the gene encoding SOX6 (607257).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| LEFT VENTRICULAR NONCOMPACTION 2 | c1960469 | 4,159 | omim | https://www.omim.org/entry/609470 | 2019-09-22T16:06:00 | {"omim": ["609470"], "orphanet": ["54260"]} |
Glycogen storage disease
Other namesGlycogenosis, dextrinosis
Glycogen
SpecialtyEndocrinology
A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis (glucose breakdown), typically in muscles and/or liver cells.[1]
GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism (genetically defective enzymes) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid castanospermine.[2]
## Contents
* 1 Types
* 2 Diagnosis
* 3 Treatment
* 4 Epidemiology
* 5 References
* 6 External links
## Types[edit]
Type
(Eponym) Enzyme deficiency
(Gene[3]) Incidence (births) Hypo-
glycemia? Hepato-
megaly? Hyperlip-
idemia? Muscle symptoms Development/ prognosis Other symptoms
GSD 0 Glycogen synthase
(GYS2) ? Yes No No Occasional muscle cramping Growth failure in some cases
GSD I / GSD 1
(von Gierke's disease) Glucose-6-phosphatase
(G6PC / SLC37A4) 1 in 50,000 – 100,000[4][5] [6] Yes Yes Yes None Growth failure Lactic acidosis, hyperuricemia
GSD II / GSD 2
(Pompe disease ) Acid alpha-glucosidase
(GAA) 1 in 13,000. [7] No Yes No Muscle weakness Progressive proximal skeletal muscle weakness with varied timeline to threshold of functional limitation (early childhood to adulthood). Approximately 15% of the Pompe population is classified as infantile Pompe which is typically deadly within the first year if untreated. Heart failure (infantile), respiratory difficulty (due to muscle weakness)
GSD III / GSD 3
(Cori's disease or Forbes' disease) Glycogen debranching enzyme
(AGL) 1 in 100,000 Yes Yes Yes Myopathy
GSD IV / GSD 4
(Andersen disease) Glycogen branching enzyme
(GBE1) 1 in 500,000[8] No Yes,
also
cirrhosis No Myopathy and dilated cardiomyopathy Failure to thrive, death at age ~5 years
GSD V / GSD 5
(McArdle disease) Muscle glycogen phosphorylase
(PYGM) 1 in 100,000 – 500,000[9][8] No No No Exercise-induced cramps, Rhabdomyolysis Renal failure by myoglobinuria, second wind phenomenon
GSD VI / GSD 6
(Hers' disease) Liver glycogen phosphorylase
(PYGL)
Muscle phosphoglycerate mutase
(PGAM2) 1 in 65,000 – 85,000[10] Yes Yes Yes [11] None initially benign, developmental delay follows.
GSD VII / GSD 7
(Tarui's disease) Muscle phosphofructokinase
(PFKM) 1 in 1,000,000[12] No No No Exercise-induced muscle cramps and weakness developmental delay In some haemolytic anaemia
GSD IX / GSD 9 Phosphorylase kinase
(PHKA2 / PHKB / PHKG2 / PHKA1) ? Yes Yes Yes None Delayed motor development, Developmental delay
GSD X / GSD 10 Phosphoglycerate mutase
(PGAM2)
? ? ? ? Exercise-induced muscle cramps and weakness Myoglobinuria[13]
GSD XI / GSD 11 Muscle lactate dehydrogenase
(LDHA) ? ? ? ?
Fanconi-Bickel syndrome
formerly GSD XI / GSD 11, no longer considered a GSD Glucose transporter
(GLUT2) ? Yes Yes No None
GSD XII / GSD 12
(Aldolase A deficiency) Aldolase A
(ALDOA) ? No In some No Exercise intolerance, cramps. In some Rhabdomyolysis. Hemolytic anemia and other symptoms
GSD XIII / GSD 13 β-enolase
(ENO3) ? No ? No Exercise intolerance, cramps Increasing intensity of myalgias over decades[14] Serum CK: Episodic elevations; Reduced with rest[14]
GSD XV / GSD 15 Glycogenin-1
(GYG1) Rare[15] No No No Muscle atropy Slowly progressive weakness over decades None
Remarks:
* Some GSDs have different forms, e.g. infantile, juvenile, adult (late-onset).
* Some GSDs have different subtypes, e.g. GSD1a / GSD1b, GSD9A1 / GSD9A2 / GSD9B / GSD9C / GSD9D.[3]
* GSD type 0: Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.
* GSD type VIII (GSD 8): In the past it was considered a distinct condition,[16] however it is now classified with GSD type VI[17] or GSD IXa1;[18] it has been described as X-linked recessive inherited.[19]
* GSD type XI (GSD 11): Fanconi-Bickel syndrome, hepatorenal glycogenosis with renal Fanconi syndrome, no longer considered a glycogen storage disease.[3]
* GSD type XIV (GSD 14): Now classed as Congenital disorder of glycosylation type 1 (CDG1T), affects the phosphoglucomutase enzyme (gene PGM1).[3]
* Lafora disease is considered a complex neurodegenerative disease and also a glycogen metabolism disorder.[20]
## Diagnosis[edit]
Micrograph of glycogen storage disease with histologic features consistent with Cori disease. Liver biopsy. H&E stain.
This section needs expansion. You can help by adding to it. (November 2017)
## Treatment[edit]
Treatment is dependent on the type of glycogen storage disease. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch, called modified cornstarch therapy, to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.[21]
## Epidemiology[edit]
Overall, according to a study in British Columbia, approximately 2.3 children per 100,000 births (1 in 43,000) have some form of glycogen storage disease.[22] In the United States, they are estimated to occur in 1 per 20,000–25,000 births.[4] Dutch incidence rate is estimated to be 1 per 40,000 births. While a Mexican incidence showed 6.78:1000 male newborns.[23][24]
## References[edit]
1. ^ Cantú-Reyna, C.; Santos-Guzmán, J.; Cruz-Camino, H.; Vazquez Cantu, D.L.; Góngora-Cortéz, J.J.; Gutiérrez-Castillo, A. (2019). "Glucose-6-Phosphate dehydrogenase deficiency incidence in a Hispanic population". Journal of Neonatal-Perinatal Medicine. 12 (2): 203–207. doi:10.3233/NPM-1831. PMID 30741698.
2. ^ Stegelmeier BL, Molyneux RJ, Elbein AD, James LF (May 1995). "The lesions of locoweed (Astragalus mollissimus), swainsonine, and castanospermine in rats". Veterinary Pathology. 32 (3): 289–98. doi:10.1177/030098589503200311. PMID 7604496. S2CID 45016726.
3. ^ a b c d Glycogen Metabolism themedicalbiochemistrypage.org
4. ^ a b eMedicine Specialties > Glycogen-Storage Disease Type I Author: Karl S Roth. Updated: Aug 31, 2009
5. ^ The Association for Glycogen Storage Disease > Type I Glycogen Storage Disease Type I GSD Archived 2010-08-03 at the Wayback Machine October 2006.
6. ^ Cantú-Reyna, C.; Santos-Guzmán, J.; Cruz-Camino, H.; Vazquez Cantu, D.L.; Góngora-Cortéz, J.J.; Gutiérrez-Castillo, A. (4 February 2019). "Glucose-6-Phosphate dehydrogenase deficiency incidence in a Hispanic population". Journal of Neonatal-Perinatal Medicine. 12 (2): 203–207. doi:10.3233/NPM-1831. PMID 30741698.
7. ^ https://pediatrics.aappublications.org/content/140/Supplement_1/S4
8. ^ a b Stuart, Grant; Ahmad, Nargis (2011). "Perioperative care of children with inherited metabolic disorders". Continuing Education in Anaesthesia Critical Care & Pain. 11 (2): 62–68. doi:10.1093/bjaceaccp/mkq055.
9. ^ http://mcardlesdisease.org/
10. ^ eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases > Glycogen-Storage Disease Type VI Author: Lynne Ierardi-Curto, MD, PhD. Updated: Aug 4, 2008
11. ^ Goldman, Lee; Schafer, Andrew (2012). Goldman's Cecil medicine (24th ed.). Philadelphia: Elsevier/Saunders. p. 1356. ISBN 978-1-4377-1604-7.
12. ^ "Rare Disease Database". Orpha.net. Retrieved 2015-09-20.
13. ^ Reference, Genetics Home. "Phosphoglycerate mutase deficiency". Genetics Home Reference. Retrieved 2019-02-06.
14. ^ a b "Glycogenoses".
15. ^ Malfatti E, Nilsson J, Hedberg-Oldfors C, Hernandez-Lain A, Michel F, Dominguez-Gonzalez C, Viennet G, Akman HO, Kornblum C, Van den Bergh P, Romero NB, Engel AG, DiMauro S, Oldfors A (2014) A new muscle glycogen storage disease associated with glycogenin-1 deficiency. Ann Neurol 76(6):891-898
16. ^ Ludwig M, Wolfson S, Rennert O (October 1972). "Glycogen storage disease, type 8". Arch. Dis. Child. 47 (255): 830–833. doi:10.1136/adc.47.255.830. PMC 1648209. PMID 4508182.
17. ^ "Glycogen-Storage Disease Type VI : Article by Lynne Ierardi-Curto". EMedicine. 2019-02-02.
18. ^ GLYCOGEN STORAGE DISEASE IXa1; GSD9A1 OMIM - Online Mendelian Inheritance in Man
19. ^ "Definition: glycogen storage disease type VIII from Online Medical Dictionary".
20. ^ Ortolano S, Vieitez I et al. Loss of cortical neurons underlies the neuropathology of Lafora disease. Mol Brain 2014;7:7 PMC 3917365
21. ^ "Glycogen Storage Disease Type I - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 23 March 2017.
22. ^ Applegarth DA, Toone JR, Lowry RB (January 2000). "Incidence of inborn errors of metabolism in British Columbia, 1969–1996". Pediatrics. 105 (1): e10. doi:10.1542/peds.105.1.e10. PMID 10617747.
23. ^ Cantú-Reyna, C.; Santos-Guzmán, J.; Cruz-Camino, H.; Vazquez Cantu, D.L.; Góngora-Cortéz, J.J.; Gutiérrez-Castillo, A. (4 February 2019). "Glucose-6-Phosphate dehydrogenase deficiency incidence in a Hispanic population". Journal of Neonatal-Perinatal Medicine. 12 (2): 203–207. doi:10.3233/NPM-1831. PMID 30741698.
24. ^ Cantú-Reyna, Consuelo; Zepeda, Luis Manuel; Montemayor, René; Benavides, Santiago; González, Héctor Javier; Vázquez-Cantú, Mercedes; Cruz-Camino, Héctor (27 September 2016). "Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital" (PDF). Journal of Inborn Errors of Metabolism and Screening. 4: 232640981666902. doi:10.1177/2326409816669027.
## External links[edit]
Classification
D
* ICD-10: E74.0
* ICD-9-CM: 271.0
* MeSH: D006008
* v
* t
* e
Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders
Including glycogen storage diseases (GSD)
Sucrose, transport
(extracellular)
Disaccharide catabolism
* Congenital alactasia
* Sucrose intolerance
Monosaccharide transport
* Glucose-galactose malabsorption
* Inborn errors of renal tubular transport (Renal glycosuria)
* Fructose malabsorption
Hexose → glucose
Monosaccharide catabolism
Fructose:
* Essential fructosuria
* Fructose intolerance
Galactose / galactosemia:
* GALK deficiency
* GALT deficiency/GALE deficiency
Glucose ⇄ glycogen
Glycogenesis
* GSD type 0 (glycogen synthase deficiency)
* GSD type IV (Andersen's disease, branching enzyme deficiency)
* Adult polyglucosan body disease (APBD)
Glycogenolysis
Extralysosomal:
* GSD type III (Cori's disease, debranching enzyme deficiency)
* GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency)
* GSD type V (McArdle's disease, myophosphorylase deficiency)
* GSD type IX (phosphorylase kinase deficiency)
Lysosomal (LSD):
* GSD type II (Pompe's disease, glucosidase deficiency)
Glucose ⇄ CAC
Glycolysis
* MODY 2/HHF3
* GSD type VII (Tarui's disease, phosphofructokinase deficiency)
* Triosephosphate isomerase deficiency
* Pyruvate kinase deficiency
Gluconeogenesis
* PCD
* Fructose bisphosphatase deficiency
* GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency)
Pentose phosphate pathway
* Glucose-6-phosphate dehydrogenase deficiency
* Transaldolase deficiency
* 6-phosphogluconate dehydrogenase deficiency
Other
* Hyperoxaluria
* Primary hyperoxaluria
* Pentosuria
* Aldolase A deficiency
Authority control
* NDL: 00573157
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Glycogen storage disease | c0017919 | 4,160 | wikipedia | https://en.wikipedia.org/wiki/Glycogen_storage_disease | 2021-01-18T18:43:18 | {"mesh": ["D006008"], "umls": ["C0017919"], "orphanet": ["79201"], "wikidata": ["Q1421738"]} |
Waldenström macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells called lymphoplasmacytic cells in the bone marrow. This condition is classified as a lymphoplasmacytic lymphoma. The abnormal cells have characteristics of both white blood cells (lymphocytes) called B cells and of more mature cells derived from B cells known as plasma cells. These abnormal cells produce excess amounts of IgM, a type of protein known as an immunoglobulin; the overproduction of this large protein is how the condition got its name ("macroglobulinemia").
Waldenström macroglobulinemia usually begins in a person's sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenström macroglobulinemia. It can be several years before this form of the condition progresses to the symptomatic form.
Individuals with symptomatic Waldenström macroglobulinemia can experience general symptoms such as fever, night sweats, and weight loss. Several other signs and symptoms of the condition are related to the excess IgM, which can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and difficulty coordinating movements (ataxia). In some affected individuals, the IgM proteins clump together in the hands and feet, where the body temperature is cooler than at the center of the body. These proteins are then referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein can also build up in organs such as the heart and kidneys, causing a condition called amyloidosis, which can lead to heart and kidney problems. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy.
Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of normal blood cells (pancytopenia). Excessive tiredness (fatigue) due to a reduction in red blood cells (anemia) is common in affected individuals.
People with Waldenström macroglobulinemia have an increased risk of developing other cancers of the blood or other tissues.
## Frequency
Waldenström macroglobulinemia affects an estimated 3 per million people each year in the United States. Approximately 1,500 new cases of the condition are diagnosed each year in this country, and whites are more commonly affected than African Americans. For unknown reasons, the condition occurs twice as often in men than women.
## Causes
Waldenström macroglobulinemia is thought to result from a combination of genetic changes. The most common known genetic change associated with this condition is a mutation in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenström macroglobulinemia, CXCR4, is mutated in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene mutation). Other genetic changes believed to be involved in Waldenström macroglobulinemia have not yet been identified. Studies have found that certain regions of DNA are deleted or added in some people with the condition; however, researchers are unsure which genes in these regions are important for development of the condition. The mutations that cause Waldenström macroglobulinemia are acquired during a person's lifetime and are present only in the abnormal blood cells.
The proteins produced from the MYD88 and CXCR4 genes are both involved in signaling within cells. The MyD88 protein relays signals that help prevent the self-destruction (apoptosis) of cells, thus aiding in cell survival. The CXCR4 protein stimulates signaling pathways inside the cell that help regulate cell growth and division (proliferation) and cell survival. Mutations in these genes lead to production of proteins that are constantly functioning (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenström macroglobulinemia.
### Learn more about the genes associated with Waldenström macroglobulinemia
* CXCR4
* MYD88
## Inheritance Pattern
Waldenström macroglobulinemia is usually not inherited, and most affected people have no history of the disorder in their family. The condition usually arises from mutations that are acquired during a person's lifetime (somatic mutations), which are not inherited.
Some families seem to have a predisposition to the condition. Approximately 20 percent of people with Waldenström macroglobulinemia have a family member with the condition or another disorder involving abnormal B cells.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Waldenström macroglobulinemia | c1835192 | 4,161 | medlineplus | https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/ | 2021-01-27T08:25:05 | {"gard": ["7872"], "omim": ["153600"], "synonyms": []} |
A number sign (#) is used with this entry because of evidence that autosomal recessive nonsyndromic hearing loss-77 (DFNB77) is caused by homozygous mutation in the LOXHD1 gene (613072) on chromosome 18q21.
Clinical Features
Grillet et al. (2009) studied a 5-generation consanguineous Iranian family segregating autosomal recessive nonsyndromic hearing loss. Affected members had preserved low-frequency hearing and a trend toward mild to moderate mid-frequency (500 to 2,000 Hz) and high-frequency (greater than 2,000 Hz) hearing loss during childhood and adolescence. The onset of hearing loss was self-reported to occur at 7 to 8 years of age and progressed to become moderate to severe at mid and high frequencies during adulthood, with flattening of the audiogram over time. All affected individuals reported age-appropriate developmental motor milestones for sitting and walking and remained free of tinnitus, balance disorders, or vertigo, consistent with normal vestibular function.
Mapping
Grillet et al. (2009) performed genomewide linkage mapping in a 5-generation consanguineous Iranian family with nonsyndromic hearing loss, and obtained a genomewide significant lod score of 3.2 for an approximately 21-cM interval at chromosome 18q12-q21 containing 125 genes. Additional linkage analysis using all 5 affected individuals and an estimated inbreeding loop produced a lod score of 3.9 for an identical critical interval.
Molecular Genetics
In a 5-generation consanguineous Iranian family with nonsyndromic hearing loss mapping to chromosome 18q12-q21, Grillet et al. (2009) sequenced the LOXHD1 gene and identified a homozygous mutation (R670X; 613072.0001) in all affected family members tested. Unaffected family member were heterozygous for the mutation, which was not found in 243 controls.
In 5 affected children from an Ashkenazi Jewish family with severe to profound congenital nonprogressive nonsyndromic hearing loss mapping to chromosome 18q, in which linkage to the GJB2 (121011)/GJB6 (604418) genes had been excluded, Edvardson et al. (2011) identified homozygosity for a nonsense mutation in the LOXHD1 gene (R1572X; 613072.0002). Analysis of LOXHD1 in an additional 8 Ashkenazi probands and 3 probands of mixed Jewish ethnicity led to the identification of another Ashkenazi Jewish family in which 4 affected children were found to be homozygous for R1572X. Screening for the mutation in 719 anonymous Ashkenazi individuals revealed 4 heterozygotes, indicating a carrier rate of 1:180 Ashkenazi Jews.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural, bilateral (milder hearing loss at low frequencies) MISCELLANEOUS \- Congenital onset leading to cochlear implants between 7-10 years of age in Ashkenazi Jewish families \- Onset by 7-8 years of age progressing to moderate-to-severe loss of mid and high frequencies during adulthood in a consanguineous Iranian family MOLECULAR BASIS \- Caused by mutation in the lipoxygenase homology domains-containing 1 gene (LOXHD1, 613072.0001 ) ▲ 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
| DEAFNESS, AUTOSOMAL RECESSIVE 77 | c2746083 | 4,162 | omim | https://www.omim.org/entry/613079 | 2019-09-22T15:59:50 | {"doid": ["0110525"], "mesh": ["C567543"], "omim": ["613079"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"], "genereviews": ["NBK1434"]} |
A number sign (#) is used with this entry because of evidence that autosomal dominant mitochondrial DNA depletion syndrome-12A (MTDPS12A) is caused by heterozygous mutation in the SLC25A4 gene (103220) on chromosome 4q35.
Heterozygous mutation in the SLC25A4 gene can also cause the less severe disorder autosomal dominant progressive external ophthalmoplegia-2 (PEOA2; 609283), and biallelic mutation in the SLC25A4 gene can cause the less severe disorder autosomal recessive MTDPS12B (615418).
Description
MTDPS12A is characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies (summary by Thompson et al., 2016).
For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).
Clinical Features
Thompson et al. (2016) reported 7 children from 6 unrelated families who presented at birth with profound hypotonia, little spontaneous movement, lactic acidosis, and respiratory insufficiency necessitating mechanical ventilation. Two infants were monozygotic twins. Four patients had hypertrophic cardiomyopathy. Five of the patients, including the twins, died in the first days or months of life. The 2 surviving patients, 6 and 4 years of age, required artificial ventilation and tube feeding, had little motor development, and were wheelchair-bound. One of the living patients had early-onset seizures and progressive cerebral white matter atrophy on brain imaging; she was unable to speak but could communicate. The other living patient was noted to have normal cognition. Skeletal muscle samples available from 5 of the patients showed decreased activities of mitochondrial respiratory complexes I, III, and IV associated with severe mtDNA depletion (less than 5% of controls in 2 of the patients, and between 11 and 34% of controls in the 3 other patients). Muscle histology showed loss of mitochondrial oxidative enzymes, lipid accumulation, small rounded muscle fibers with little variation in fiber size, and numerous mitochondria with disorganized cristae.
Molecular Genetics
In 7 children from 6 unrelated families with MTDPS12A, Thompson et al. (2016) identified 1 of 2 recurrent de novo heterozygous missense mutations in the SLC25A4 gene (R80H, 103220.0009 or R235G, 103220.0010). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Western blot analysis of patient muscle samples showed decreased levels of ANT1 and decreased levels of components of several mitochondrial respiratory complexes compared to controls. In vitro functional expression studies showed that the mutant proteins had very low residual transporter activity. Complementation and transport studies in yeast confirmed that the mutant proteins were functionally defective: they were unable to complement an oxidative phosphorylation defect and caused decreased transport activity, but did not act in a dominant-negative manner. Thompson et al. (2016) concluded that the highly reduced capacity for ADP/ATP transport in mitochondria probably affects mitochondrial DNA maintenance and thus respiration, causing severe energy depletion.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy (in some patients) RESPIRATORY \- Respiratory insufficiency due to muscle weakness ABDOMEN Gastrointestinal \- Poor feeding due to muscle weakness MUSCLE, SOFT TISSUES \- Hypotonia, profound \- Inability to walk independently \- mtDNA depletion seen on muscle biopsy \- Decreased mitochondrial oxidative enzyme activities \- Global COX deficiency \- Lipid accumulation \- Small rounded fibers \- Numerous mitochondria with disorganized cristae NEUROLOGIC Central Nervous System \- Lack of motor development Poor spontaneous movements Peripheral Nervous System \- Hyporeflexia METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Increased serum and CSF lactate \- Organic aciduria (in some patients) MISCELLANEOUS \- Onset at birth \- Patients become ventilator-dependent \- Many patients die in infancy \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4 gene (SLC25A4, 103220.0009 ) ▲ 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 12A (CARDIOMYOPATHIC TYPE), AUTOSOMAL DOMINANT | c4310676 | 4,163 | omim | https://www.omim.org/entry/617184 | 2019-09-22T15:46:33 | {"omim": ["617184"], "genereviews": ["NBK487393"]} |
A rare, genetic, primary bone dysplasia syndrome characterized by multiple epiphyseal dysplasia, severely delayed ossification (mainly of the epiphyses, pubic symphysis, hands and feet), abnormal modeling of the bones in hands and feet, abnormal pelvis cartilage persistence, and mild growth retardation. Calcium, phosphate and vitamin D serum levels are typically within normal range, while parathyroid hormone serum levels are normal to slighly elevated. Oligodontia has been rarely associated.
*[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
| Eiken syndrome | c1838779 | 4,164 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79106 | 2021-01-23T18:53:50 | {"mesh": ["C564010"], "omim": ["600002"], "umls": ["C1838779"]} |
A number sign (#) is used with this entry because early infantile epileptic encephalopathy-17 (EIEE17) is caused by de novo heterozygous mutation in the GNAO1 gene (139311) on chromosome 16q13.
Heterozygous mutation in the GNAO1 gene can also cause neurodevelopmental disorder with involuntary movements (NEDIM; 617493).
Description
Early infantile epileptic encephalopathy-17 is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements (summary by Nakamura et al., 2013).
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical Features
Nakamura et al. (2013) reported 4 unrelated girls with early infantile epileptic encephalopathy. Three patients had onset of intractable tonic seizures in the first weeks of life associated with suppression-burst pattern on EEG; the fourth patient presented with opisthotonic posturing and developmental delay at age 7 months. All had severely delayed psychomotor development, with lack of sitting and no speech; only 1 patient had head control. One child died at age 11 months. EEG studies were consistently abnormal, including hypsarrhythmia and multifocal sharp waves. One patient showed dystonia and another had severe chorea and athetosis. Brain MRI was abnormal in 3 patients, showing cerebral atrophy, delayed myelination, and/or thin corpus callosum.
Saitsu et al. (2016) reported 2 unrelated girls who presented in early infancy with epileptic encephalopathy. They had intractable complex-partial seizures and EEG abnormalities, including multiform discharges, slow-wave bursts, and hypsarrhythmia. They had severe intellectual disability and motor developmental delay. One patient had severe chorea and the other had hand stereotypies. Brain imaging showed progressive cerebral atrophy in both patients, and 1 patient had microcephaly and hypotonia. The patients were severely disabled with little or no eye contact or head control, and inability to sit, walk, or talk.
Molecular Genetics
In 4 unrelated girls with EIEE17, Nakamura et al. (2013) identified 4 different de novo heterozygous mutations in the GNAO1 gene (139311.0001-139311.0004). One of the patients was somatic mosaic for the mutation. The mutations in the first 2 patients were found by whole-exome sequencing, and the mutations in the second 2 patients were found by direct sequencing of the GNAO1 gene in 367 individuals with epileptic encephalopathy. In vitro functional expression studies showed that 3 of the mutations caused impaired protein localization to the plasma membrane, and electrophysiologic analysis showed that 3 of the mutations caused decreased GNAO1-mediated inhibition of calcium currents by norepinephrine compared to wildtype. The findings suggested that aberrant GNAO1 signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements.
In 2 unrelated patients with EIEE17, Saitsu et al. (2016) identified de novo heterozygous missense mutations in the GNAO1 gene (see, e.g., 139311.0004).
Animal Model
Kehrl et al. (2014) found that mutant mice heterozygous for a G184S mutation in the Gnao1 gene died in the perinatal period or early in life due to sudden death associated with severe seizures and/or increased frequency of interictal epileptiform discharges. Homozygous mutant mice were essentially nonviable. Heterozygous mice showed enhanced sensitivity to seizure kindling with a GABA antagonist compared to controls. Heterozygous knockout mice, representing a loss of function, did not show such a phenotype, suggesting that the G184S mutation results in a gain of function. Kehrl et al. (2014) noted that several studies have shown that the G184S allele results in a gain of function effect and suggested that EIEE17 may also result from a gain of function mechanism.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Lack of psychomotor development \- Lack of speech \- Seizures, intractable \- Tonic seizures \- EEG shows suppression-burst pattern \- Hypsarrhythmia \- Multifocal spike waves \- Dystonia (in some patients) \- Chorea (in some patients) \- Athetosis (in some patients) \- Cerebral atrophy \- Thin corpus callosum \- Delayed myelination MISCELLANEOUS \- Onset in early infancy \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the guanine nucleotide-binding protein, alpha-activating activity polypeptide O gene (GNAO1, 139311.0001 ) ▲ 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
| EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 17 | c0393706 | 4,165 | omim | https://www.omim.org/entry/615473 | 2019-09-22T15:52:05 | {"doid": ["0080450"], "omim": ["615473"], "orphanet": ["1934"]} |
A number sign (#) is used with this entry because Ellis-van Creveld syndrome (EVC) is caused by homozygous or compound heterozygous mutation in the EVC gene (604831) on chromosome 4p16.
Ellis-van Creveld syndrome can also be caused by mutation in a nonhomologous gene, EVC2 (607261), located close to the EVC gene in a head-to-head configuration.
Mutations in the EVC and EVC2 genes also cause Weyers acrofacial dysostosis (WAD; 193530), an allelic disorder showing autosomal dominant inheritance.
Description
Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals (summary by Ruiz-Perez et al., 2000).
The clinical features of the Ellis-van Creveld syndrome appear to be identical regardless of whether the disorder is caused by mutation in the EVC gene (604831) or in the EVC2 gene (607261) (Ruiz-Perez et al., 2003, Galdzicka et al., 2002).
Clinical Features
The largest pedigree with EVC was that observed by McKusick et al. (1964) in an inbred religious isolate, the Old Order Amish, in Lancaster County, Pennsylvania. Almost as many persons were known in this one kindred as had been reported in all the medical literature up to that time. Features are dwarfism with most striking shortening in the distal part of the extremities, polydactyly, fusion of the hamate and capitate bones of the wrist, dystrophy of the fingernails, change in the upper lip variously called 'partial hare-lip,' 'lip-tie,' etc., and cardiac malformation, usually a septal defect and often single atrium. Teeth may already be erupted at birth ('natal teeth;' 187050) and exfoliate prematurely.
From observations in the large Amish kindred, McKusick et al. (1964) concluded that there are no heterozygous manifestations of EVC. However, Fryns (1991) noted the occurrence of unilateral postaxial polydactyly type A (complete extra finger and extra metacarpal) in one parent and one otherwise normal brother of 2 unrelated newborn infants with EVC. Goldblatt et al. (1992) described EVC in a Western Australian Aboriginal community in which 2 relatives were observed to have isolated postaxial polydactyly of the feet. They advanced this as evidence of heterozygous manifestation. In the 2 families reported by Goldblatt et al. (1992), each with 1 case of EVC, the postaxial polydactyly of the feet occurred in a first cousin and a first cousin once removed of the proband in 1 family only.
Engle and Ehlers (1969) described a case of EVC syndrome with unilateral polydactyly. The left hand and the right foot had an extra digit. A second child with EVC had been born in this family; polydactyly of the hands was bilateral (Engle, 1976).
Blackburn and Belliveau (1971) reported 2 sibs EVC with single atrium and hypoplastic left heart syndrome.
Onat (1994) described a patient with single atrium and postaxial hexodactyly. Since the patient had no additional anomalies, all known syndromes, including the EVC combination of malformations, were excluded and it was proposed that the association represented a previously undescribed syndrome. Digilio et al. (1995) described 2 children with this combination and referred to 2 children previously reported in an abstract. They raised the possibility that Ellis-van Creveld syndrome and single atrium/polydactyly syndrome may be related, possibly due to allelic mutations. The parents of one of the children reported by Digilio et al. (1995) were consanguineous, and the father, like the daughter, had postaxial polydactyly of the left hand and both feet, partial atrial ventricular canal with single atrium, and agenesis of the upper lateral incisors bilaterally with enamel abnormalities. His height was 165 cm. The father and daughter were later found to have a mutation in the EVC gene (604831.0005) (Ruiz-Perez et al., 2000).
Spranger and Tariverdian (1995) described a 13-month-old girl with apparently typical EVC whose 32-year-old father had some features that they suggested might be heterozygous manifestations. He had disproportionate short stature (162 cm). Polydactyly was not present either clinically or by x-ray examination. Hands and feet were broad and square with short fingers and toes. He could not make a tight fist. He had dysplastic finger- and toenails, which never needed to be cut and were quite typical of those of EVC. The teeth were conical in shape with side spaces. The father had previously been thought to have Weyers acrodental dysostosis. Spranger and Tariverdian (1995) reviewed other reports of possible heterozygous manifestations.
Howard et al. (1997) studied a 4-generation family with features of Weyers acrofacial dysostosis in which the proband had a more severe phenotype, resembling Ellis-van Creveld syndrome. Weyers acrofacial dysostosis is an autosomal dominant condition with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. EVC is a similar condition, with autosomal recessive inheritance and the additional features of disproportionate dwarfism, thoracic dysplasia, and congenital heart disease.
Mostafa et al. (2005) reported 6 cases of EVC in 3 Egyptian families. All of the families were consanguineous. Father to son or daughter transmission was observed in 2 of the families, thus demonstrating pseudodominant inheritance. None of the presumed heterozygotes in these families exhibited abnormalities of the body, limbs, or orodental structures. Bifid tip of the tongue was found in all affected individuals. Mostafa et al. (2005) suggested that midline orodental anomalies should be sought in cases of EVC and Weyers acrofacial dysostosis, and that their presence or absence might be a differentiating feature between the 2 disorders.
Diagnosis
### Prenatal Diagnosis
Mahoney and Hobbins (1977) proposed fetoscopy and ultrasound as methods of prenatal diagnosis. Qureshi et al. (1993) described the skeletal histopathology in 3 fetuses with EVC. The diagnosis had been made in each of these cases on the basis of ultrasonography, and the pregnancies were terminated at 22 to 23 weeks.
Population Genetics
D'Asdia et al. (2013) stated that the incidence of Ellis-van Creveld syndrome is estimated at 1 in 60,000, whereas it is as high as 5 in 1000 in the Old Order Amish community of Lancaster County, Pa.
Mapping
In studies of 9 interrelated Amish pedigrees and 2 unrelated families from Mexico and Ecuador, Francomano et al. (1995) demonstrated linkage of the EVC gene to the distal short arm of chromosome 4 in an area proximal to the FGFR3 gene (134934), which is mutant in achondroplasia (100800) and hypochondroplasia (146000). The maximum lod score was 4.65 at theta = 0.05 for marker D4S431.
Polymeropoulos et al. (1996) reported the results of linkage analysis in 9 interrelated Amish pedigrees and 3 unrelated families from Mexico, Ecuador, and Brazil. Their analysis revealed linkage of the Ellis-van Creveld phenotype to genetic markers on the short arm of chromosome 4p with no evidence of heterogeneity. Polymeropoulos et al. (1996) reported that multipoint analysis places the gene between D4S3007 and D4S431, whereas haplotype analysis sublocalizes the gene in the interval between D4S2957 and D4S827.
By linkage and haplotype analysis in a 4-generation family with features of Weyers acrofacial dysostosis in which the proband had a more severe phenotype resembling Ellis-van Creveld syndrome, Howard et al. (1997) determined that the disease locus resided on 4p16, distal to the genetic marker D4S3007 and within a 17-cM region flanking the genetic locus D4S2366. This region includes the EVC locus, which had previously been mapped within a 3-cM region between genetic markers D4S2957 and D4S827. The authors concluded that either the genes for the condition in the family of Howard et al. (1997) and for EVC are near one another or these 2 conditions are allelic. The data also raised the possibility that Weyers acrofacial dysostosis is a heterozygous expression of the mutation that, in homozygous form, causes the autosomal recessive disorder EVC.
### Exclusion Studies
Polymeropoulos et al. (1996) suggested that the HMX1 gene (142992) is most likely located in the 12-cM interval between D4S394 and D4S2362, excluding it as a candidate gene for Ellis-van Creveld syndrome. Ide et al. (1996) excluded the MSX1 gene (142983) as a candidate gene for this disorder in the Amish.
Molecular Genetics
By positional cloning, Ruiz-Perez et al. (2000) identified a novel gene, EVC (604831), that is mutated in individuals with Ellis-van Creveld syndrome. They identified a splice-donor change in an Amish pedigree (604831.0001), and 6 truncating mutations and a single amino acid deletion in 7 pedigrees (see, e.g., 604831.0002-604831.0004). The heterozygous carriers of these mutations did not manifest features of EVC.
Ruiz-Perez et al. (2000) found 2 heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis (604831.0006) and another in a father and his daughter, who both had the heart defect characteristic of EVC and polydactyly, but not short stature (604831.0005). Ruiz-Perez et al. (2000) suggested that EVC and Weyers acrodental dysostosis are allelic conditions.
In a patient with Ellis-van Creveld syndrome of Ashkenazi Jewish origin, Galdzicka et al. (2002) identified 2 homozygous mutations in the EVC2 gene; see 607261.0007.
In a patient with Ellis-van Creveld syndrome in a consanguineous Gypsy pedigree, Ruiz-Perez et al. (2003) identified a frameshift mutation in the EVC2 gene (607261.0001). They found 4 other truncating mutations and a missense change.
Tompson et al. (2007) analyzed the EVC and EVC2 genes in 65 unrelated individuals with EVC syndrome, 19 of whom came from consanguineous families. Mutations in the EVC gene were identified in 20 patients (17 homozygotes and 3 compound heterozygotes); mutations in the EVC2 gene were identified in 25 patients (17 homozygotes, 5 compound heterozygotes, and 3 in whom only 1 mutation was identified). The majority of the mutations introduced a premature termination codon. The authors noted that no mutations were found in either gene in 20 (31%) cases and suggested that there may be further genetic heterogeneity.
In a 6-year-old Chinese girl with mild Ellis-van Creveld syndrome, Shen et al. (2011) identified compound heterozygosity for a splice site and a missense mutation in the EVC2 gene (607621.0010-607621.0011). The patient had mild short stature, postaxial polydactyly, dysplastic nails, abnormal teeth, and genus valgum; features not present in this patient included short ribs, narrow thorax, or cardiac defects. Her unaffected parents were each heterozygous for 1 of the mutations; neither mutation was found in 200 control chromosomes. Shen et al. (2011) noted that all 3 Weyers acrofacial dysostosis-associated mutations reported to date were located in exon 22 of EVC2, whereas this patient's mutations were in IVS5 and exon 15.
History
The disorder that now goes by the name of Ellis-van Creveld syndrome was described by Richard W. B. Ellis (1902-1966) of Edinburgh and Simon van Creveld (1895-1971) of Amsterdam. Each had a patient with this syndrome, as they had discovered when they met in the same train compartment on the way to a pediatrics conference in England in the late 1930s. A third patient had been referred to by L. Emmett Holt, Jr. and Rustin McIntosh in a textbook of pediatrics (Holt and McIntosh, 1933) and was included in full in the paper by Ellis and van Creveld (1940).
McKusick (2000) provided perspective on the classic study of dwarfism, including Ellis-van Creveld syndrome, in the Lancaster County Amish.
Christian et al. (1980) reported the unusual case of an infant with both Ellis-van Creveld and Dandy-Walker syndromes and with homozygosity for an unusually long heterochromatic segment of the long arm of chromosome 9 (9qh+). The 18-year-old mother was mentally retarded, the product of a first-cousin mating, and less than 4 feet tall. Although thelarche and menarche occurred on schedule, she developed no pubic or axillary hair. The authors suggested that she may have had a previously unknown recessive disorder. The mating that resulted in the offspring with EVC and Dandy-Walker syndromes was presumably incestuous. Her father and 2 of her brothers, like the 18-year-old mother, had the 9qh+.
Zangwill et al. (1988) described hydrocephalus and the Dandy-Walker anomaly in EVC.
Rosemberg et al. (1983) reported the fatal case of a 19-month-old daughter of consanguineous parents who in addition to cardiac defects, including single atrium, had cerebral heteropias, left renal agenesis, and right megaureter. Serotkin et al. (1988) found features suggesting EVC in an infant who was mosaic for duplication 17q21.1-qter, owing to a direct tandem duplication. The child had bilateral polydactyly of the feet but not of the hands, dysplastic nails, and lip-tie. His gums had scalloped edges, and 2 neonatal teeth were evident.
Because of an observation of the radiologic features characteristic of Jeune syndrome (208500) and EVC in a Japanese boy with a de novo del(12)(p11.21p12.2) chromosomal aberration, Nagai et al. (1995) suggested that the EVC locus is situated on 12p.
EVC and McKusick-Kaufman (MKKS; 236700) syndromes are clinically similar, recessively inherited disorders sharing postaxial polydactyly of the hands and feet and a distinct congenital heart defect. Distinguishing characteristics are the osteochondrodysplasia and ectodermal anomalies in EVC syndrome, and hydrometrocolpos in MKKS. Hydrometrocolpos had been described in the Ellis-van Creveld syndrome by Akoun and Bagard (1956). Digilio et al. (1997) studied 2 sisters presenting with apparent EVC, 1 of whom also had hydrometrocolpos. Digilio et al. (2004) restudied the sisters and excluded linkage to either 4p (where EVC maps) or 20p (where MKKS maps). The sisters were later found to have short-rib thoracic dysplasia-15 with polydactyly (SRTD15; 617088).
Nomenclature
'Six-fingered dwarfism' was an alternative designation used for this condition when it was being studied in the Amish (McKusick et al., 1964) and may have served a useful function in defining this then little known condition for the medical profession, as well as the lay public. The term, however, has been found offensive by some, apparently not because of 'dwarfism,' but because of the reference to the polydactyly, which is seen as a 'freakish' labeling. For this reason, 6-fingered dwarfism has been removed as an alternative name for this entry. This leaves Ellis-van Creveld syndrome with its felicitous abbreviation, EVC, as the only satisfactory designation. Chondroectodermal dysplasia and mesoectodermal dysplasia do not well define the entity and are not satisfactory for general usage, either medical or lay.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short-limb dwarfism identifiable at birth \- Average adult height, 109 to 152 cm HEAD & NECK Head \- Normocephaly Face \- Normal with exception of upper-lip defect Mouth \- Partial cleft lip \- Defect in alveolar ridge Teeth \- Neonatal teeth \- Hypodontia \- Delayed eruption CARDIOVASCULAR Heart \- Atrial septal defect \- Single atrium \- Other congenital heart defects CHEST External Features \- Narrow chest Ribs Sternum Clavicles & Scapulae \- Pectus carinatum \- Short, poorly developed ribs GENITOURINARY External Genitalia (Male) \- Epispadias \- Hypospadias Internal Genitalia (Male) \- Cryptorchidism SKELETAL Pelvis \- Low iliac wings \- Spur-like projections at the medial and lateral aspect of acetabula Limbs \- Centrifugal shortening of limbs \- Fusion of capitate and hamate \- Genu valgum \- Short, thickened tubular bones Hands \- Difficulty forming a fist \- Postaxial polydactyly \- Cone-shaped epiphyses of phalanges 2 to 5 Feet \- Talipes equinovarus \- Postaxial polydactyly SKIN, NAILS, & HAIR Nails \- Nail dysplasia NEUROLOGIC Central Nervous System \- Mental retardation (some) \- Dandy-Walker malformation MISCELLANEOUS \- Increased frequency in eastern Pennsylvania Amish MOLECULAR BASIS \- Caused by mutation in the EVC gene (EVC, 604831.0001 ) \- Caused by mutation in the EVC2 (limbin) gene (EVC2, 607231.0001 ) ▲ 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
| ELLIS-VAN CREVELD SYNDROME | c0013903 | 4,166 | omim | https://www.omim.org/entry/225500 | 2019-09-22T16:28:22 | {"doid": ["12714"], "mesh": ["D004613"], "omim": ["225500"], "icd-9": ["756.55"], "icd-10": ["Q77.6"], "orphanet": ["289"], "synonyms": ["Alternative titles", "CHONDROECTODERMAL DYSPLASIA", "MESOECTODERMAL DYSPLASIA"]} |
Autosomal recessive palmoplantar hyperkeratosis and congenital alopecia (PPK-CA) is a rare genetic skin disorder characterized by congenital alopecia and palmoplantar hyperkeratosis. It is usually associated with cataracts, progressive sclerodactyly and pseudo-ainhum.
## Epidemiology
To date, autosomal recessive PPK-CA has been reported in two families (seven affected individuals). An additional sporadic patient was likely affected by the same condition.
## Clinical description
Similarly to the dominant variant, autosomal recessive PPK-CA usually presents during infancy. Its very early onset is often characterized by fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features which appear in the following years. Skin thickening of palms and soles develops during infancy and may have an unusual pattern affecting the two sides of fingers and palms, but usually sparing the palmar surfaces. Periungueal involvement is typical and leads to secondary nail dystrophy. Autosomal recessive PPK-CA shows a relatively more severe evolution compared to the dominant variant as many patients develop sclerodactyly, small joint contractures and pseudo-ainhum. The original family also had congenital cataract.
## Etiology
The genetic basis of autosomal recessive PPK-CA is unknown.
## Genetic counseling
Transmission appears to be autosomal recessive.
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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
| Autosomal recessive palmoplantar keratoderma and congenital alopecia | c1859316 | 4,167 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1366 | 2021-01-23T18:46:11 | {"gard": ["1139"], "mesh": ["C535336"], "omim": ["212360"], "umls": ["C1859316"], "icd-10": ["Q82.8", "Q84.0"], "synonyms": ["Autosomal recessive palmoplantar hyperkeratosis and congenital alopecia", "Cataract-alopecia-sclerodactyly syndrome", "PPK-CA, Wallis type", "Palmoplantar keratoderma and congenital alopecia, Wallis type"]} |
Cernunnos deficiency
Other namesCombined immunodeficiency-microcephaly-growth retardation-sensitivity to ionizing radiation syndrome, Cernunnos XLFD
Cernunnos deficiency is inherited via autosomal recession
SymptomsMicrocephaly[1]
CausesNHEJ1 gene mutation[1]
Diagnostic methodClinical features[1]
TreatmentImmunoglobulin replacement, HSCT[1]
Cernunnos deficiency is a form of combined immunodeficiency characterized by microcephaly, due to mutations in the NHEJ1 gene, it is inherited via autosomal recessive manner[2][1] Management for this condition is antiviral prophylaxis and antibiotic treatment[medical citation needed]
## Contents
* 1 Symptoms and signs
* 2 Cause
* 3 Mechanism
* 4 Diagnosis
* 4.1 Differencial diagnosis
* 5 Management
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Symptoms and signs[edit]
The sign and symptoms of this condition on an affected individual are as follows:[1]
* Recurrent infections
* Microcephaly
* Growth retardation
* Bone-malformation
* Dysmorphic feature
* Urogenital malformations
## Cause[edit]
NHEJ1
In terms of genetics the condition, Cernunnos deficiency is due to a mutation in the NHEJ1 gene, it has a cytogenetic location of 2q35, while its molecular location is 219,075,324 to 219,160,865 [3][2]
## Mechanism[edit]
The pathophysiology of Cernunnos deficiency begins with normal function of Non-homologous end-joining factor 1 gene. NHEJ1 encodes a protein which helps repair of breaks in double-stranded DNA. It might additionally act as a connection between XRCC4 and other NHEJ factors (at DNA ends)[4][3][5]
When a mutation occurs in NHEJ1, then one sees that nucleotide deletions cause V(D)J recombination, signal joints, to be affected.[6] V(D)J recombination is a genetic recombination that happens in early stages of B and T cell maturation.[7]
## Diagnosis[edit]
IgM
The diagnosis of Cernunnos deficiency will find the following in an affected individual via clinical features and blood test:[6][1]
* B lymphopenia
* T lymphopenia
* Hypogammaglobulinemia with low IgA
* Hypogammaglobulinemia with low IgM
### Differencial diagnosis[edit]
The DDx for Cernunnos deficiency are both LIG4 syndrome, as well as Nijmegen breakage syndrome[1]
## Management[edit]
In terms of management for Cernunnos deficiency, one finds that treatment with allogeneic hematopoietic stem cell transplantation, which are stem cells that bring about other cells[8]) has proven useful in some instances. Additionally the following treatments are also used:[9][1]
* Antibiotic treatment
* Immunoglobulin replacement
## See also[edit]
* Cernunnos
* Combined immunodeficiency
## References[edit]
1. ^ a b c d e f g h i RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Cernunnos XLF deficiency". www.orpha.net. Retrieved 2017-06-22.
2. ^ a b "OMIM Entry - # 611291 - SEVERE COMBINED IMMUNODEFICIENCY WITH MICROCEPHALY, GROWTH RETARDATION, AND SENSITIVITY TO IONIZING RADIATION". omim.org. Retrieved 2017-06-22.
3. ^ a b Reference, Genetics Home. "NHEJ1 gene". Genetics Home Reference. Retrieved 2017-06-22.
4. ^ "NHEJ1 non-homologous end joining factor 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-07-13.
5. ^ "OMIM Entry - * 611290 - NONHOMOLOGOUS END-JOINING FACTOR 1; NHEJ1". www.omim.org. Retrieved 2017-07-13.
6. ^ a b Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D. (2008-08-06). Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. Springer Science & Business Media. p. 56. ISBN 9783540789369.
7. ^ Roth, David B.; Antes, JR; Adams, RW; Trumm, GA (December 2014). V(D)J Recombination: Mechanism, Errors, and Fidelity. Microbiology Spectrum. 2. pp. 313–324. doi:10.1128/microbiolspec.MDNA3-0041-2014. ISBN 9781555819200. ISSN 2165-0497. PMC 5089068. PMID 26104458.
8. ^ "Bone Marrow (Hematopoietic) Stem Cells | stemcells.nih.gov". stemcells.nih.gov. Retrieved 2017-07-13.
9. ^ Sullivan, Kathleen E.; Stiehm, E. Richard (2014-08-08). Stiehm's Immune Deficiencies. Academic Press. p. 122. ISBN 9780124058606.
## Further reading[edit]
* Ratcliffe, Michael (2016). Encyclopedia of Immunobiology (Vol 1 Development and phylogeny of the immune system ed.). Academic Press. ISBN 9780080921525. Retrieved 13 July 2017.
## External links[edit]
* PubMed
Classification
D
* ICD-10: D81.1
* OMIM: 611291
* MeSH: C566970
External resources
* Orphanet: 169079
Scholia has a topic profile for Cernunnos deficiency.
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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
| Cernunnos deficiency | c1969799 | 4,168 | wikipedia | https://en.wikipedia.org/wiki/Cernunnos_deficiency | 2021-01-18T18:46:29 | {"mesh": ["C566970"], "umls": ["C1969799"], "orphanet": ["169079"], "wikidata": ["Q5064568"]} |
A number sign (#) is used with this entry because the Silverman-Handmaker type of dyssegmental dysplasia (DDSH) is caused by homozygous or compound heterozygous mutation in the gene encoding perlecan (HSPG2; 142461) on chromosome 1p36.
See also Schwartz-Jampel syndrome type 1 (SJS1; 255800), an allelic disorder with a less severe but overlapping phenotype.
Clinical Features
The dyssegmental dysplasias are lethal forms of neonatal short-limbed dwarfism. Handmaker et al. (1977) coined the term 'dyssegmental dysplasia' because of the marked differences in size and shape of the vertebral bodies (anisospondyly), which he attributed to errors in segmentation. Fasanelli et al. (1985) proposed that there are different forms of dyssegmental dwarfism, a lethal Silverman type and a less severe Rolland-Desbuquois type (224400).
Aleck et al. (1987) found reports of 18 cases, including 3 reports of affected sibs, and reported 8 additional cases. The authors presented further evidence for the existence of 2 forms of dyssegmental dysplasia.
Molecular Genetics
In a pair of sibs with DDSH born to consanguineous parents, Arikawa-Hirasawa et al. (2001) identified a homozygous 89-bp duplication in exon 34 of the HSPG2 gene (142461.0003). A third unrelated patient was compound heterozygous for 2 truncating mutations (142461.0004; 142461.0005). The cartilage matrix from these patients stained poorly with antibody specific for perlecan, but there was staining of intracellular inclusion bodies. Truncated perlecan was not secreted by patient fibroblasts, but was degraded into smaller fragments within the cells. Thus, the Silverman-Handmaker type of dyssegmental dysplasia is caused by a functional null mutation of HSPG2. Arikawa-Hirasawa et al. (2001) concluded that their findings demonstrate the critical role of perlecan in cartilage development.
INHERITANCE \- Autosomal recessive GROWTH Other \- Short-limbed dwarfism HEAD & NECK Head \- Occipital skull defect Face \- Flat face Ears \- Posteriorly rotated ears Nose \- Wide nasal bridge Mouth \- Small mouth \- Micrognathia RESPIRATORY Lung \- Pulmonary hypoplasia CHEST External Features \- Small chest ABDOMEN External Features \- Two vessel cord GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL \- Chondroosseous morphology notable for short, irregular chondrocyte columns, large, unfused calcospherites, perichondral bone overgrowth and patchy, mucoid degeneration of resting cartilage Spine \- Dyssegmental dysplasia \- Anisospondyly Limbs \- Short, bent long bones Feet \- Talipes equinovarus MISCELLANEOUS \- Neonatal lethal MOLECULAR BASIS \- Caused by mutation in the perlecan gene (HSPG2, 142461.0001 ) ▲ 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
| DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | c1857100 | 4,169 | omim | https://www.omim.org/entry/224410 | 2019-09-22T16:28:28 | {"doid": ["0090032"], "mesh": ["C537998"], "omim": ["224410"], "orphanet": ["1865"], "synonyms": ["ANISOSPONDYLIC CAMPTOMICROMELIC DWARFISM, SILVERMAN-HANDMAKER TYPE", "Alternative titles", "DYSSEGMENTAL DWARFISM, SILVERMAN-HANDMAKER TYPE"]} |
Isolated lissencephaly sequence (ILS) is a condition that affects brain development before birth. Normally, the cells that make up the exterior of the brain (cerebral cortex) are well-organized, multi-layered, and arranged into many folds and grooves (gyri). In people with ILS, the cells of the cerebral cortex are disorganized, and the brain surface is abnormally smooth with an absence (agyria) or reduction (pachygyria) of folds and grooves. In most cases, these abnormalities impair brain growth, causing the brain to be smaller than normal (microcephaly). This underdevelopment of the brain causes severe intellectual disability, delayed development, and recurrent seizures (epilepsy) in individuals with ILS.
More than 90 percent of individuals with ILS develop epilepsy, often within the first year of life. Up to 80 percent of infants with ILS have a type of seizure called infantile spasms, these seizures can be severe enough to cause brain dysfunction (epileptic encephalopathy). After the first months of life, most children with ILS develop a variety of seizure types, including persisting infantile spasms, short periods of loss of consciousness (absence seizures); sudden episodes of weak muscle tone (drop attacks); rapid, uncontrolled muscle jerks (myoclonic seizures); and episodes of muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures).
Infants with ILS may have poor muscle tone (hypotonia) and difficulty feeding, which leads to poor growth overall. Hypotonia also affects the muscles used for breathing, which often causes breathing problems that can lead to a life-threatening bacterial lung infection known as aspiration pneumonia. Children with ILS often develop muscle stiffness (spasticity) in their arms and legs and an abnormal side-to-side curvature of the spine (scoliosis). Rarely, the muscle stiffness will progress to paralysis (spastic paraplegia). Individuals with ILS cannot walk and rarely crawl. Most children with ILS do not develop communication skills.
## Frequency
ILS affects approximately 1 in 100,000 newborns.
## Causes
Mutations in the PAFAH1B1, DCX, or TUBA1A gene can cause ILS. PAFAH1B1 gene mutations are responsible for over half of ILS cases; DCX gene mutations cause about 10 percent of cases; and TUBA1A gene mutations cause a small percentage of ILS. These genes provide instructions for making proteins that are involved in the movement (migration) of nerve cells (neurons) to their proper locations in the developing brain. Neuronal migration is dependent on cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules form scaffolding within the cell that elongates in a specific direction, altering the cytoskeleton and moving the neuron. The protein produced from the TUBA1A gene is a component of microtubules. The proteins produced from the DCX and PAFAH1B1 genes promote neuronal migration by interacting with microtubules.
Mutations in any of these three genes impair the function of microtubules and the normal migration of neurons during fetal development. As a result, the layers of the cerebral cortex are disorganized and the normal folds and grooves of the brain do not form. This impairment of brain development leads to the smooth brain appearance and the resulting neurological problems characteristic of ILS.
Some individuals with ILS do not have an identified mutation in any of these three genes; the cause of the condition in these individuals may be unidentified mutations in other genes that affect neuronal migration or other unknown factors.
### Learn more about the genes associated with Isolated lissencephaly sequence
* DCX
* PAFAH1B1
* TUBA1A
* TUBB2B
## Inheritance Pattern
The inheritance pattern of ILS depends on the gene involved.
When ILS is caused by mutations in the PAFAH1B1 or TUBA1A 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. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
When mutations in the DCX gene cause ILS, it is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the DCX gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the DCX gene in each cell can lead to a less severe condition in females called subcortical band heterotopia, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Isolated lissencephaly sequence | c0431375 | 4,170 | medlineplus | https://medlineplus.gov/genetics/condition/isolated-lissencephaly-sequence/ | 2021-01-27T08:25:15 | {"gard": ["5049"], "mesh": ["D054221"], "omim": ["607432", "611603", "300067"], "synonyms": []} |
Catherine of Siena
Anorexia mirabilis, also known as holy anorexia or inedia prodigiosa or colloquially as fasting girls,[1][2][3] is an eating disorder, similar to that of anorexia nervosa,[1][2] that was common, but not restricted to the Middle Ages in Europe, largely affecting Catholic nuns and religious women.[3][4] Self-starvation was common among religious women, as a way to imitate the suffering of Jesus in his torments during the Passion, as women were largely restricted to causing themselves voluntary pain by fasting, whereas holy men experienced suffering through physical punishment, voluntary poverty, and celibacy. [3]
## Contents
* 1 Overview
* 1.1 Etymology
* 1.2 Description
* 1.3 History
* 1.4 Notable cases
* 2 Comparing anorexia mirabilis and "anorexia nervosa"
* 3 Historical instances
* 4 Perceived benefits
* 5 See also
* 6 References
* 7 Sources
* 8 External links
## Overview[edit]
### Etymology[edit]
Anorexia mirabilis comes from the latin meaning "miraculously inspired loss of appetite", whereas inedia prodigiosa means "great starvation".[1][2]
### Description[edit]
Anorexia mirabilis is primarily characterized by the refusal to eat, resulting in starvation, malnutrition, and oftentimes, death, but differs from anorexia nervosa in that the disease is associated with religion as opposed to personal aesthetics, although this behavior was usually not approved by religious authorities as a holy one.[3] Though anorexia mirabilis is, by definition, connected to religion, particularly Catholicism, sufferers have been known to defy the orders of their religious superior to cease fasting and their refusal to eat sometimes preceded their involvement in religious activities.[3] Additionally, sufferers engaged in worrisome and bizarre behaviors designed to cause them pain, so that they might be reminded of Jesus Christ's suffering, and desired to appear unattractive in hopes of avoiding marriage and sexual contact.[3]
The self-starvation practice of anorexia mirabilis was a behavior only adopted by women, particularly in the Middle Age, as a way to imitate the suffering of Jesus in his torments during the Passion, as women preferred to experience this voluntary pain by fasting, whereas holy men experienced suffering through physical punishment.[3] For this reason, they were often colloquially called "fasting girls", as there were no "fasting boys".[2] This colloquial naming became the most common one in the Victorian era, with anorexia mirabilis being the term used only in medical circles.[1]
Documentation exists regarding about two thirds of the holy women officially regarded by the Roman Catholic Church as saints, blesseds, venerables, or servants of God and who lived after 1200 AD showing that more than half of these displayed clear signs of anorexia, with extensive and highly reliable documentation being available for about two dozen of these.[5]
### History[edit]
The earliest reported sufferer of anorexia mirabilis is St. Wilgefortis, a legendary princess who reportedly lived sometime between the 8th century and 10th century in Galicia, who starved herself and took a vow of chastity to avoid an arranged marriage. She asked for God to make her ugly and she subsequently grew excessive facial and body hair, which is a common symptom of malnutrition in women. Her suitor rejected her based on her appearance and so, as punishment for sabotaging the union, her father, the king of Portugal, had her crucified. For her suffering, she was venerated in the Catholic Church.
Though the disease was most prominent during the Middle Ages, modern cases do exist. Notably, in 2014, medical researchers published an article about the case of an unidentified woman in her sixties, born in Chicago, Illinois, who'd suffered from anorexia mirabilis. The woman entered a convent at the age of 13 and began to restrict her eating in hopes of achieving sainthood.
### Notable cases[edit]
* Marie of Oignies (1177–1213) went to great lengths to cause herself physical pain, wanting to suffer as Jesus Christ had. She deprived herself of sleep and, when she did eat, which was very little, she favored bread so stale that it would cause her gums to bleed. She additionally made the choices to live in poverty despite being from a wealthy family and abstain from sex despite being married. Like other sufferers of anorexia mirabilis, she eventually refused to eat any food other than the consecrated Hosts and died at the age of 36.[6]
* Wilgefortis of Portugal was a legendary Portuguese infanta who took a vow of virginity and began to starve herself to avoid marriage. She reportedly prayed to be made ugly, which resulted in her growing hair all over her body, which people likely assumed to be a work of God but is actually a common symptom in those with anorexia nervosa. She was ultimately crucified and later venerated as a saint within the Catholic church.[7]
* Catherine of Siena (1347–1380) was known to fast for long periods of time and, towards the end of her life, when her disease was at its worst, the only food she consumed was a single consecrated Host given to her as part of the daily Eucharist. She defied orders from her religious superiors to eat, claiming she was too ill to do so, and in the month before she died, at the age of 33, she lost the use of her legs and her ability to swallow. In addition to restricting her food intake, Catherine was known to use insert sticks into her throat in order to activate her gag reflex and induce vomiting, as someone with bulimia nervosa would do, and was known to drink the pus from the ulcers of the poor.[3][8]
* Columba of Rieti (1467–1501) bears a number of similarities to that of Catherine of Siena, including the cutting of her hair to avoid an arranged marriage and the refusal to eat prior to her involvement in religious work. Also like Catherine, towards the end of her life, Columba restricted her food consumption to only what was given to her as part of the daily Eucharist and died at the age of 34. Additionally, she wore a hairshirt and slept on thorns.[9]
* Therese Neumann (1923-1962) professed to have consumed no food other than The Holy Eucharist her whole life, nor to have drunk any water from 1926 until her death, despite her "stocky build".[10][11]
* Jane (born c. 1948) was a woman from Chicago who began to restrict her eating at the age of 13 in hopes of being a nun and later, a saint. Her weight worried those at the convent and she was dismissed from her religious training due to concerns over her health. Her malnutrition caused amenorrhea and likely affected her development as she grew to be only 4' 10" tall but did not suffer from any form of dwarfism. At the age of 66, she weighed only 60 pounds.[7]
## Comparing anorexia mirabilis and "anorexia nervosa"[edit]
Anorexia mirabilis has in many ways, both similarities to and clear distinctions from the more modern, well-known "anorexia nervosa".[1][2][3]
In anorexia nervosa, people usually starve themselves to attain a level of thinness, as a way of dealing with sexual or other trauma, undiagnosed mental illness, or as a form of self harm. It is also typically, but not always, associated with body image distortion. In comparison, anorexia mirabilis was frequently coupled with other ascetic practices, such as lifelong virginity, flagellant behavior, the donning of hairshirts, sleeping on beds of thorns, and other assorted penitential practices. It was largely a practice of Catholic women, who were often known as "miraculous maids".
The anorexia nervosa of the 20th century has historical correlates in the religiously inspired cases of anorexia mirabilis in female saints, such as Catherine of Siena (1347–1380) in whom fasting denoted female holiness or humility and underscored purity. The investigation of anorexia nervosa in the 20th century has focused on the psychological, physiological, and various other factors.[12]
For Caroline Walker Bynum (Holy Feast and Holy Fast), anorexia mirabilis, rather than misdiagnosed anorexia, was a legitimate form of self-expression with motives set in contrast to the modern disease paradigm. She considers cases such as that of Julian of Norwich and other Christian anchorites, as using fasting as a legitimate means for communing with Christ.[13]
Joan Jacobs Brumberg (Fasting Girls: The History of Anorexia Nervosa) suggests that anorexia mirabilis no longer exists not because the motives of those who starve themselves have changed, but because the paradigms for coding these behaviors have shifted. If a young woman were to make the decision to self-starve as a means to communicate with Christ, healthcare professionals would code her as anorexia nervosa regardless of her motives.[13]
Whether or not there is historical continuity between anorexia mirabilis and anorexia nervosa is a subject of debate with both medieval historiographers and the psychiatric community. Some have argued that there is historical continuity between the two conditions,[14] while others maintain that anorexia mirabilis should be comprehended as a distinct medieval form of female religious piety within the historical context of such societies.[15]
## Historical instances[edit]
Anorexia mirabilis was frequently accompanied by behaviors most medical professionals today would find worrisome and dangerous. Angela of Foligno was known to eat the scabs of the poor and Catherine of Siena was known to drain the pus from sick individuals into a cup to drink.[16]
Many women notoriously refused all food except for the holy Eucharist, signifying not only their devotion to God and Jesus, but also demonstrating, to them, the separation of body and spirit. That the body could exist for extended periods without nourishment gave people of the time a clear picture of how much stronger, and therefore how much more important, the spirit was. It mattered not in popular opinion that the reported periods of female fasting were impossibly long (from months to many years) and simply added to the allure of this very specifically female achievement.
Angela of Foligno
Both Angela of Foligno (1248–1309) and Catherine of Siena (1347–1380) were reportedly anorexia mirabilis sufferers.[17] They both refused food, but drank the pus from the sores of the sick. Angela of Foligno is reported to have said it was as "sweet as the Eucharist", and also to have eaten the scabs and lice from those same patients, though precious little else.[18]
In the time of Catherine of Siena, celibacy and fasting were held in high regard. Ritualistic fasting was both a means to avoid gluttony (one of the seven deadly sins), and to atone for past sins. Catherine initially fasted as a teenager to protest an arranged marriage to her late sister Bonaventura's husband. Bonaventura herself had taught this technique to Catherine, refusing to eat until her husband showed better manners. Fasting then was a means of exercising some control, taking power back for the individual and as such it is similar to one of the underlying factors in anorexia nervosa today. Thus, women could gain more freedom and respect remaining virgins than they would becoming wives. Catherine managed to pursue her interests in theology and papal politics, opportunities less likely available to a wife and mother. [19] She purportedly lived for long intervals on practically no food save the Eucharist,[20] leading to an untimely death at thirty-three years from starvation and emaciation.[19]
Any additional food she was forced to eat she would expel through vomiting induced by pushing a twig or small branch down her throat.[21]
Marie of Oignies (1167–1213) reportedly lived as a hermit, wore only white, cut off pieces of her body to expunge her desire, and both she and Beatrice of Nazareth claimed that not only did the smell of meat make them vomit, but also that the slightest whiff of food would cause their throats to close up entirely.[22][23]
A gang of would-be rapists got as far as removing the clothing of Columba of Rieti (1467–1501), but they retreated as she had mutilated her breasts and hips so thoroughly with spiked whipping chains that they were unable or unwilling to continue. Columba did eventually starve herself to death.[24][failed verification][25]
## Perceived benefits[edit]
Saint Margaret of Cortona
Many of these women felt that they possessed at least some measure of spiritual enlightenment from their asceticism. They variously said they felt "inebriation" with the sacramental wine, "hunger" for God, and conversely, that they sat at the "delicious banquet of God".[citation needed]
Margaret of Cortona (1247–1297) believed she had extended communications with God himself. Columba of Rieti believed her spirit "toured the holy land" in visions, and virtually every one of these women was apparently possessed of some level of psychic prowess. These women's exercises in self-denial and suffering did yield them a measure of fame and notoriety. They were said to alternately be able to make a feast out of crumbs, exude oil from their fingertips, heal with their saliva, fill barrels with drink out of thin air, lactate even though virginal and malnourished, and perform other miracles of note.[25]
The practice of anorexia mirabilis faded out during the Renaissance, when it began to be seen by the Church as heretical, socially dangerous, or possibly even Satanically inspired. It managed to survive in practice until nearly the 20th century, when it was overtaken by its more popularly known counterpart, anorexia nervosa.[26]
Contemporary accounts of anorexia mirabilis do exist, most notably that of a fundamentalist Christian girl in Colombia, as reported by medical anthropologist Carlos Alberto Uribe.[27]
## See also[edit]
* Anorexia nervosa
* Bulimia nervosa
* Eating disorder
* Emaciation
* Fasting
* Fasting girls
* Female hysteria
* Inedia
* Middle Ages
* Starvation
## References[edit]
1. ^ a b c d e Hepworth, Julie (1999). The Social Construction of Anorexia Nervosa. SAGE. pp. 23-25. ISBN 9781848609006.
2. ^ a b c d e Ozer, Yvette Malamud (2012). A Student Guide to Health: Understanding the Facts, Trends, and Challenges [5 volumes]: Understanding the Facts, Trends, and Challenges. ABC-CLIO. pp. 115–116. ISBN 9780313393068.
3. ^ a b c d e f g h i Espi Forcen, Fernando (April 2013). "Anorexia Mirabilis: The Practice of Fasting by Saint Catherine of Siena in the Late Middle Ages". American Journal of Psychiatry. 170 (4): 370–371. doi:10.1176/appi.ajp.2012.12111457. PMID 23545792.
4. ^ Espi Forcen, Fernando (April 2013). "Anorexia Mirabilis: The Practice of Fasting by Saint Catherine of Siena in the Late Middle Ages". American Journal of Psychiatry. 170 (4): 370–371. doi:10.1176/appi.ajp.2012.12111457. ISSN 0002-953X. PMID 23545792.
5. ^ Bell, Rudolph M. (2014). Holy Anorexia. University of Chicago Press. p. x. ISBN 978-0-226-16974-3.
6. ^ Spearing, Elizabeth. Medieval writings on female spirituality. New York: Penguin Books, 2002. pg 105
7. ^ a b Davis, Amelia A.; Nguyen, Mathew (2014). "A Case Study of Anorexia Nervosa Driven by Religious Sacrifice". Case Reports in Psychiatry. 2014: 512764. doi:10.1155/2014/512764. ISSN 2090-682X. PMC 4106065. PMID 25105049.
8. ^ "Power Suffering". archive.nytimes.com. Retrieved 2018-10-31.
9. ^ "Miniature Lives of the Saints – Blessed Columba of Rieti". CatholicSaints.Info. 2015-02-24. Retrieved 2018-10-31.
10. ^ Vogl, p. 17
11. ^ Wilson, Ian. (1988). The Bleeding Mind: An Investigation into the Mysterious Phenomena of Stigmata. Weidenfeld & Nicolson. pp. 114-115. ISBN 0-297-79099-4
12. ^ eclecTechs/Ashton Services (2009-03-03). ""Eating disorders", Women's Health and Education Center", Springfield, Massachusetts". Womenshealthsection.com. Retrieved 2014-04-20.
13. ^ a b "Grey, Stephanie Houston. "A Perfect Loathing: The Feminist Expulsion of the Eating Disorder", KB Journal, Volume 7, Issue 2, Spring 2011, Clemson University". Kbjournal.org. 2003-09-21. Retrieved 2014-04-20.
14. ^ Bell, 1987. sfn error: no target: CITEREFBell,_1987 (help)
15. ^ Bynum, 1988. sfn error: no target: CITEREFBynum,_1988 (help)
16. ^ "NARRATING THE NATIONAL IDENTITY: MYTH, POWER, AND DISSIDENCE". 2008-05-13. Archived from the original on 2008-05-13. Retrieved 2018-11-01.
17. ^ "Anorexia And The Holiness Of Saint Catherine Of Siena". Albany.edu. Archived from the original on 2014-04-25. Retrieved 2014-04-20.
18. ^ Connecting with the God-Man Archived May 13, 2008, at the Wayback Machine
19. ^ a b "Pittock, Alexandra. "How are anorexia nervosa and spirituality connected, and what implications does this have for treatment?", Royal College of Psychiatrists" (PDF). Retrieved 2014-04-20.
20. ^ "Gardner, Edmund. "St. Catherine of Siena." The Catholic Encyclopedia. Vol. 3. New York: Robert Appleton Company, 1908. 6 May 2013". Newadvent.org. 1908-11-01. Retrieved 2014-04-20.
21. ^ Anorexia Mirabilis.
22. ^ "Blessed Mary of Oignies". saints.sqpn.com. Archived from the original on 2014-04-21. Retrieved 2014-04-20.
23. ^ "Gender in Medieval Christian Mysticism". Boston University. Archived from the original on 2016-03-03. Retrieved 2014-04-20.
24. ^ B.M.Ashley – Italian Dominican Women Mystics Archived March 20, 2008, at the Wayback Machine
25. ^ a b Brumberg, Joan Jacobs (October 2001). "From Sainthood to Patienthood". Fasting Girls: The History of Anorexia Nervosa. pp. 43–61.
26. ^ Speaking about eating disorders Archived February 7, 2009, at the Wayback Machine
27. ^ Carlos Alberto Uribe Tobón; Rafael Vásquez Rojas; Santiago Martínez. "Virginidad, anorexia y brujería: el caso de la pequeña Ismenia". ANTÍPODA | Revista de Antropología y Arqueología Nº 3. Retrieved 2015-10-31.
## Sources[edit]
* Bell, Rudolph M. Holy Anorexia, (University Of Chicago Press, June 15, 1987)
* Brumberg, Joan Jacobs. Fasting Girls: The History of Anorexia Nervosa, (Vintage; Subsequent edition, October 10, 2000)
* Bynum, Caroline Walker. Holy Feast and Holy Fast: The Religious Significance of Food to Medieval Women, (University of California Press; New Ed. edition, January 7, 1988)
* Vandereycken, W. From Fasting Saints to Anorexic Girls: The History of Self-Starvation, (NYU Press, July 1, 1994)
## External links[edit]
* http://www.history.vt.edu/Jones/3724_S99/books/brumberg.html
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Anorexia mirabilis | None | 4,171 | wikipedia | https://en.wikipedia.org/wiki/Anorexia_mirabilis | 2021-01-18T18:56:15 | {"wikidata": ["Q567713"]} |
"MIDD" redirects here. For the liberal arts college in Vermont, see Middlebury College.
Diabetes and deafness
Other namesDiabetes mellitus and deafness, maternally inherited, MIDD, Ballinger-Wallace syndrome, Diabetes mellitus type II with deafness,
This condition is inherited via a mitochondrial inheritance manner
Diabetes and deafness (DAD) or maternally inherited diabetes and deafness (MIDD) or mitochondrial diabetes is a subtype of diabetes which is caused from a point mutation at position 3243 in human mitochondrial DNA, which consists of a circular genome. This affects the gene encoding tRNALeu.[1][2] Because mitochondrial DNA is contributed to the embryo by the oocyte and not by spermatozoa, this disease is inherited from maternal family members only.[1] As indicated by the name, MIDD is characterized by diabetes and sensorineural hearing loss.[1]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 2.1 Penetrance and age of onset
* 2.2 Effect of mutation on tRNALeu(UUR)
* 2.3 Metabolic characteristics of diabetes in MIDD
* 2.4 Metabolic characteristics of deafness in MIDD
* 3 Diagnosis
* 4 Treatment
* 4.1 Initial
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
As suggested by the name, patients with MIDD are subject to sensorineural hearing loss.[1] This begins with a reduction in the perception of frequencies above approximately 5 kHz which progressively declines, over the years, to severe hearing loss at all frequencies.[1] The diabetes that accompanies the hearing loss can be similar to Type 1 diabetes or Type 2 diabetes; however, Type 1-like diabetes is the more common form of the two. MIDD has also been associated with a number of other issues including kidney dysfunction, gastrointestinal problems, and cardiomyopathy.[3]
## Genetics[edit]
### Penetrance and age of onset[edit]
MIDD represents 1% of people who have diabetes. Over 85% of people that carry the mutation in mitochondrial DNA at position 3243 present symptoms of diabetes. The average age at which people who have MIDD are typically diagnosed is 37 years old but has been seen to range anywhere between 11 years to 68 years old. Of these people with diabetes carrying the mitochondrial DNA mutation at position 3243, 75% experience sensorineural hearing loss.[1] In these cases, hearing loss normally appears before the onset of diabetes and is marked by a decrease in perception of high tone frequencies.[3] The associated hearing loss with diabetes is typically more common and more quickly declining in men than in women.[4]
### Effect of mutation on tRNALeu(UUR)[edit]
Mitochondria have their own circular genome which contains 37 genes, of which 22 code for tRNAs.[5] These tRNAs play an essential role in protein synthesis by transporting amino acids to the ribosome.[1] MIDD is caused by an A to G substitution in the mitochondrial DNA at position 3243, which encodes tRNALeu(UUR).[1] This mutation is typically in heteroplasmic form. A mutation in this gene (A3243G) causes the native conformation to be destabilized, as well as dimerization in the tRNALeu(UUR). The uridine at the anticodon first position of the tRNALeu(UUR) is normally post- transcriptionally modified to ensure correct codon recognition. Such modification is known as taurine modification, which is decreased as a result of the improper structure of the tRNALeu(UUR).[6] Incorrect tRNALeu(UUR) structure also results in decreased aminoacylation.[5] The mutation has also been shown to result in decreased function of the tRNA and thus protein synthesis.[7]
### Metabolic characteristics of diabetes in MIDD[edit]
The A3243G mutation in mitochondrial DNA can be present in any tissue, however, it is more commonly present in tissues with lower replication rates such as muscle.[3] The presence of this mutation can lead to decreased oxygen consumption as a result of reduced function of the respiratory chain and a decrease in oxidative phosphorylation.[8] In some people, this reduction in function of the respiratory chain is suggested to be caused by unbalanced amounts of proteins that are encoded by mitochondrial DNA, due to the presence of the A3243G mutation.[3] However, in other people, the same amount of mitochondrial proteins are generated, but their stability is compromised due to the improper incorporation of amino acids at the UUR codons of the mitochondrial mRNAs. This is a result of the mutated tRNALeu(UUR) with its decreased function in protein synthesis.[8] A decrease in function of the respiratory chain as a result of a mitochondrial DNA mutation could result in a decrease of ATP production. This decrease in ATP could have detrimental effects on other processes in the body. One such process is insulin secretion by pancreatic Beta-cells.[3] In pancreatic Beta-cells, precise levels of ATP/ADP regulate the opening and closing of the KATP channel, which controls the secretion of insulin. When mutations in the mitochondria disrupt the ATP/ADP ratio, this channel cannot function properly and this can result in a person being deficient in insulin.[3] Since the age of onset is later in a person's life, it has been suggested that age plays a role in contributing, along with the reduced ATP/ADP ratio, to the slow deterioration of the function of B-cells.[3]
### Metabolic characteristics of deafness in MIDD[edit]
Hearing loss, as caused by the 3243 mitochondrial DNA mutation, is seen in the form of progressive cochlear dysfunction. Although the mechanism by which the mutation in the tRNALeu(UUR) causes this dysfunction of the cochlea is still under investigation, it has been hypothesized that it involves the ion pumps required for sound transduction.[9] As the mutation in the tRNALeu(UUR) leads to unbalanced amounts or unstable respiratory chain enzymes, respiration and oxidative phosphorylation are reduced, leading to lower levels of ATP.[3][8] Naturally, the most metabolically active organs in a person will be affected by this ATP deficiency. Included in these metabolically active organs is the cochlear stria vascularis.[1] The stria vascularis and the hair cells, both essential to sound transduction, make use of ion pumps to regulate the concentration of ions including K+, Na+, and Ca2+ using ATP. Without sufficient levels of ATP, these concentration gradients are not maintained and this can lead to cell death in both the stria vascularis and the hair cells, causing hearing loss.[9]
Table 1: Metabolically active organs that can be affected by the 3243A>G mitochondrial point mutation and the associated complication:[1]
Organ affected Associated complication
Ear (cochlea) Sensorineural hearing loss
Brain (Hypothalamus) Short stature
Eye Macular pattern dystrophy
Heart Congestive heart failure
Kidney Focal segmental glomerulosclerosis
Intestine Malabsorption or constipation
Brain Strokes, atrophy of cerebellum or cerebrum
Muscle Myopathy
## Diagnosis[edit]
This section is empty. You can help by adding to it. (August 2017)
## Treatment[edit]
### Initial[edit]
Initially, the person is treated by dietary changes and hypoglycaemic agents. This does not last long before the person has to be started on insulin (within 2 years of diagnosis).[10]
## See also[edit]
* Deafness
* Diabetes
## References[edit]
1. ^ a b c d e f g h i j Murphy R, Turnbull DM, Walker M, Hattersley AT "Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. " Diabet. Med. 2008, 25(4), 383-99. {{doi: 10.1111/j.1464-5491.2008.02359.x}}
2. ^ de Andrade PB, Rubi B, Frigerio F, van den Ouweland JM, Maassen JA, Maechler P. "Diabetes-associated mitochondrial DNA mutation A3243G impairs cellular metabolic pathways necessary for beta cell function" Diabetologia. 2006 Aug;49(8):1816-26. PMID 16736129
3. ^ a b c d e f g h Maassen JA, Hart LM, Van Essen E, Heine RJ, Nijpels G, Jahangir Tafrechi RS, Raap AK, Janssen GM, Lemkes HH. Mitochondrial diabetes: molecular mechanisms and clinical presentation." . Diabetes. 2004 Feb;53(Suppl 1):S103-9. 14749274
4. ^ Uimonen S, Moilanen JS, Sorri M, Hassinen IE, Majamaa K. Hearing impairment in patients with 3243A-->G mtDNA mutation: phenotype and rate of progression. Hum Genet. 2001 Apr;108(4):284-9. 11379873
5. ^ a b Wittenhagen LM, Kelley SO. Dimerization of a pathogenic human mitochondrial tRNA. Nat Struct Biol. 2002 Aug;9(8):586-90 12101407
6. ^ 4.Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K. Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J. 2002 Dec 2;21(23):6581-9.{12456664}
7. ^ Flierl A, Reichmann H, Seibel P. Pathophysiology of the MELAS 3243 transition mutation. J Biol Chem. 1997 Oct 24;272(43):27189-96 9341162
8. ^ a b c Janssen GM, Maassen JA, van Den Ouweland JM. The diabetes-associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate. J Biol Chem.1999 Oct 15;274(42):29744-8.10514449
9. ^ a b Yamasoba T, Oka Y, Tsukuda K, Nakamura M, Kaga K. Auditory findings in patients with maternally inherited diabetes and deafness harboring a point mutation in the mitochondrial transfer RNA(Leu) (UUR) gene. Laryngoscope. 1996 Jan;106:49-53 8544627
10. ^ "Mitochondrial diabetes - Other types of diabetes mellitus - Diapedia, The Living Textbook of Diabetes". www.diapedia.org. Retrieved 2018-02-06.
## External links[edit]
Classification
D
* ICD-10: E13.6
* OMIM: 520000
* MeSH: C536246
* DiseasesDB: 33761
External resources
* Orphanet: 225
* v
* t
* e
Mitochondrial diseases
Carbohydrate metabolism
* PCD
* PDHA
Primarily nervous system
* Leigh disease
* LHON
* NARP
Myopathies
* KSS
* Mitochondrial encephalomyopathy
* MELAS
* MERRF
* PEO
No primary system
* DAD
* MNGIE
* Pearson syndrome
Chromosomal
* OPA1
* Kjer's optic neuropathy
* SARS2
* HUPRA syndrome
* TIMM8A
* Mohr–Tranebjærg syndrome
see also mitochondrial proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Diabetes and deafness | c0342289 | 4,172 | wikipedia | https://en.wikipedia.org/wiki/Diabetes_and_deafness | 2021-01-18T18:38:27 | {"gard": ["4003"], "mesh": ["C536246"], "umls": ["C0342289"], "orphanet": ["225"], "wikidata": ["Q4313947"]} |
Papillon-Lefèvre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.
## Epidemiology
The prevalence is estimated between 1/250,000 and 1/1,000,000 individuals. The male to female ratio is 1:1. PLS is found in all ethnic groups.
## Clinical description
Diffuse palmoplantar keratoderma (see this term) with erythematous plaques develops between the first and fourth years of life, with the soles being usually more severely affected than the palms. Psoriasiform hyperkeratosis can overflow onto the dorsal surfaces of the hands and feet (transgredient spread) and, less frequently, lesions can be seen on the limbs (knees, elbows). Skin lesions are followed by intense gingivitis that rapidly progresses into periodontitis with alveolar bone lysis and early loss of primary dentition. The skin lesions are aggravated by cold and during episodes of severe periodontitis. During childhood, the phenomenon of periodontal disease recurs with rapid loss of permanent dentition. Cases of PLS with mild and/or late-onset periodontal disease have been reported occasionally. PLS is accompanied, in half of the patients, by enhanced susceptibility to cutaneous and systemic infections (furunculosis, skin abscesses, pyoderma, hidradenitis suppurativa (see this term), respiratory tract infection...). Patients may also present with malodorous hyperhidrosis, follicular hyperkeratosis, nail dystrophy or dural calcifications. The association of PLS with malignant melanoma or squamous cell carcinoma has been reported in very rare occasions.
## Etiology
PLS is due to mutations in the CTSC gene (11q14.2) that codes for cathepsin C (also known as dipeptidyl peptidase I), a lysosomal protease playing a role in epidermal differentiation and desquamation and in activation of serine proteases expressed in cells of the immune system. CTSC mutations lead to an almost total loss of cathepsin C activity which seems to result in susceptibility to specific virulent pathogens. It is also suggested that other immune-mediated deficiencies in the host defense mechanism could be involved in the pathogenesis of PLS.
## Diagnostic methods
Diagnosis is based on clinical signs. Dental radiography shows atrophy of the alveolar bone. Neutrophil function tests reveal anomalies of chemotaxis and phagocytosis by polymorphonuclear leukocytes. Skin biopsy shows hyperkeratosis with focal parakeratosis, moderate perivascular infiltration, hypergranulosis, and acanthosis. Biochemical analysis reveals a loss of CTSC activity. Diagnosis is confirmed by genetic testing.
## Differential diagnosis
Differential diagnosis includes two rare disorders that are allelic variants of PLS, Haim-Munk syndrome (see this term) and prepubertal/aggressive periodontitis. Other diseases with similar dermatologic features include localized epidermolytic palmoplantar keratoderma (Vörner), mal de Meleda, Howel-Evans syndrome, transgrediens et progrediens palmoplantar keratoderma (Greither's disease) (see these terms), and keratosis punctata.
## Antenatal diagnosis
Antenatal diagnosis is theoretically possible but has never been reported.
## Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to the parents of an affected individual informing them of the 25% risk their offspring has of inheriting the disease causing mutation.
## Management and treatment
Treatment is based on oral retinoids which attenuate the palmoplantar keratoderma and slow the alveolar bone lysis. Antibiotics, along with oral hygiene and use of mouth rinses, are also recommended for slowing the progression of periodontitis. Ultimately, primary or remaining teeth are extracted and are replaced by dental implants. Antibiotherapy is also used in the treatment of recurrent infections. Etretinate (a synthetic retinoid) shows promising results in the treatment of PLS.
## Prognosis
Despite meticulous dental care, all patients eventually become edentulous at the beginning of adulthood. Life expectancy is normal.
*[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
| Papillon-Lefèvre syndrome | c0030360 | 4,173 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=678 | 2021-01-23T18:29:45 | {"gard": ["3100"], "mesh": ["D010214"], "omim": ["245000"], "umls": ["C0030360"], "icd-10": ["Q82.8"], "synonyms": ["Keratosis palmoplantar-periodontopathy syndrome", "PLS"]} |
## Clinical Features
McKusick (1971) observed transverse striae of the lumbar area in father and 2 sons. The striae appeared in their teens and faded as they grew older. Carr and Hamilton (1969) noted that such striae are more common in males. Weber (1935, 1935) called them idiopathic striae atrophicae of puberty. Striae distensae occur, especially in the deltoid, pectoral, hip and thigh areas, in the Marfan syndrome (154700) and there are sometimes very striking transverse striae in the lumbar area identical to those seen on an apparently idiopathic basis.
Inheritance \- Autosomal dominant Misc \- Teenage onset Skin \- Transverse striae of lumbar area ▲ 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
| STRIAE DISTENSAE, FAMILIAL | c1861447 | 4,174 | omim | https://www.omim.org/entry/185200 | 2019-09-22T16:34:05 | {"mesh": ["C566104"], "omim": ["185200"]} |
A number sign (#) is used with this entry because of evidence that retinal cone dystrophy with supernormal rod electroretinogram (RCD3A) can be caused by mutation in the gene encoding the gamma subunit of cone cGMP-phosphodiesterase (PDE6H; 601190) on chromosome 12p13. In addition, achromatopsia-6 (ACHM6) can be caused by homozygous mutation in PDE6H.
Another form of cone dystrophy with supernormal rod electroretinogram (RCD3B; 610356) is caused by mutation in the KCNV2 gene (607604).
Clinical Features
### Cone Dystrophy With Supernormal Rod Electroretinogram
Cone dystrophy with supernormal rod electroretinogram, also known as retinal cone dystrophy-3 (RCD3), is an autosomal recessive disorder that causes lifelong visual loss combined with a supernormal ERG response to a bright flash of light. The disorder was first described by Gouras et al. (1983) and is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. Additional cases were described by Sandberg et al. (1990), Kato et al. (1993), and Hood et al. (1996). At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy. Electroretinography is characteristic and is required to make a specific diagnosis (Wu et al., 2006). An altered phosphodiesterase activity within phosphoreceptors, which leads to an elevation in cGMP levels, had been suggested as a possible disease mechanism.
Piri et al. (2005) reported this rare form of cone dystrophy in a small family with decreased central visual acuity and night blindness rather than the dayblindness usually seen in patients with progressive cone degeneration. Symptoms began in the first or second decade of life. Ophthalmoscopic findings consisted of an atrophic macular lesion. Goldmann visual field testing showed a central scotoma in each eye. Scotopic electroretinograms showed supernormal and delayed rod responses.
### Incomplete Achromatopsia
Kohl et al. (2012) studied a Dutch man who had reduced but stable visual acuity and nystagmus since birth. Previous examination at age 45 years showed no abnormalities by slit-lamp or funduscopy. Electroretinography (ERG) recordings showed normal rod, severely reduced cone, and absent 30-Hz flicker responses. Color vision tests revealed a severe red-green color vision defect with relatively normal blue-yellow vision. He was diagnosed as having incomplete achromatopsia, with atypical features. Kohl et al. (2012) also studied a Belgian brother and sister, born of nonconsanguineous parents, who presented with photophobia and normal night vision and were diagnosed with myopia at 3 years of age. ERG under anesthesia in childhood was suggestive of cone dysfunction with absent photopic 30-Hz flicker responses. There was no deterioration of vision over 15 years, suggesting that the cone dysfunction was stationary. Color vision testing at 22 and 20 years of age, respectively, showed mainly deutan (green) color defects with normal tritan (blue) color discrimination. Visual fields were normal in both sibs, and funduscopy revealed optic discs of normal color with large temporal myopic crescents. The retinas presented irregular atrophic depigmentation in the posterior pole with sparing of the macula. Autofluorescence fundus imaging showed a normal posterior pole and macula. Follow-up ERGs in both sibs showed absent photopic responses to a single bright white flash and absent 30-Hz flicker responses. Short wavelength-sensitive (S) cone-specific testing showed absent responses to the amber stimulus but recordable responses to the blue stimulus; the scotopic ERG was normal in both. Responses to a red flash under dark adaptation were reduced with long implicit time, indicating contribution of the rod system component only. Kohl et al. (2012) concluded that the color vision testing and ERG results were consistent with a clinical diagnosis of incomplete achromatopsia with preserved S-cone function.
Molecular Genetics
### Cone Dystrophy With Supernormal Rod Electroretinogram
In a brother and sister with retinal cone dystrophy-3, Piri et al. (2005) identified a G-to-C transversion in the 5-prime untranslated region of the PDE6H gene (601190.0001). Although the mutation was not found in 95 control individuals, it was found in the patients' father. Their mother and other sibs were not available for study. Piri et al. (2005) speculated that the sibs may have inherited a different mutation from their mother, which would make the disorder an autosomal recessive, or that a genetic factor present only in the father may have mitigated the phenotypic expression. Using in vitro transcription-translation experiments, Piri et al. (2005) demonstrated that the -29G-C substitution could lead to an increase in PDE6H gene expression. If the same effect occurs in vivo, it would lead to PDE6H overexpression in the photoreceptors. Piri et al. (2005) suggested that an excess of PDE-gamma might affect normal cone cGMP-PDE function by inhibiting the catalytic PDE-alpha/beta activity and lead to pathogenic elevation of cGMP and eventual degeneration of cone photoreceptors.
Kohl et al. (2012) noted that no further mutations in PDE6H had been detected in subsequent studies of patients with retinal cone dystrophy with supernormal rod response (see 610356), and referred to the mutation identified by Piri et al. (2005) as a 'variant of unknown significance.'
### Incomplete Achromatopsia
Kohl et al. (2012) analyzed the PDE6H gene in 197 patients with achromatopsia who were negative for mutation in known ACHM genes, and identified homozygosity for a nonsense mutation (S12X; 601190.0002) in a Dutch man who had incomplete achromatopsia with atypical features. Analysis of PDE6H in 20 more ACHM patients as well as 394 patients with a clinical diagnosis of cone dystrophy identified 2 Belgian sibs homozygous for the same S12X mutation; the sibs had originally been diagnosed with cone-rod dystrophy but upon subsequent evaluation were given a clinical diagnosis of incomplete achromatopsia with preserved S-cone function. Kohl et al. (2012) estimated that mutations in PDE6H account for only about 0.3% of all autosomal recessive cases of ACHM.
INHERITANCE \- Autosomal dominant \- Autosomal recessive HEAD & NECK Eyes \- Progressive cone degeneration (in some patients) \- Photophobia \- Nyctalopia \- Decreased central vision \- Dyschromatopsia \- Macular granularity (in some patients) \- Central macular atrophy (in some patients) \- Central scotoma on Goldmann visual field (in some patients) \- Supernormal and delayed scotopic rod electroretinogram (in some patients) \- Cone degeneration, stationary (in some patients) \- Nystagmus (in some patients) \- Normal scotopic responses on rod electroretinogram (in some patients) \- Severely reduced cone and absent 30Hz flicker responses on cone electroretinogram (in some patients) MISCELLANEOUS \- Onset in first to second decade MOLECULAR BASIS \- Caused by mutation in the phosphodiesterase 6H, cGMP-specific, cone, gamma gene (PDE6H, 601190.0001 ) ▲ 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
| RETINAL CONE DYSTROPHY 3A | c0152200 | 4,175 | omim | https://www.omim.org/entry/610024 | 2019-09-22T16:05:13 | {"doid": ["0050795"], "mesh": ["D003117"], "omim": ["610024"], "orphanet": ["49382"], "synonyms": ["Alternative titles", "CONE DYSTROPHY WITH NIGHT BLINDNESS AND SUPERNORMAL ROD RESPONSES, PDE6H-RELATED"], "genereviews": ["NBK1418"]} |
A rare red cell disorder classified principally into two clinical phenotypes: autosomal recessive congenital (or hereditary) methemoglobinemia types I and II (RCM/RHM type 1; RCM/RHM type 2).
## Clinical description
In RCM type 1, cyanosis from birth is the only symptom. It is well-tolerated and is associated with mild complaints of headaches, fatigue and shortness of breath upon exertion. RCM type 2 is much more severe; the cyanosis is accompanied by neurological dysfunction (with intellectual deficit, microcephaly, growth retardation, opisthotonus, strabismus and hypertonia), which usually becomes evident during the first four months of life. Two additional forms of RCM have also been reported. RCM type 3 was the term used to define a phenotype with cyanosis but without neurological abnormalities in which Cb5R deficiency was identified in leucocytes and platelets as well as erythrocytes. This distinction has been largely ignored in subsequent reports of other CYB5R3 variants, so the term RCM type 3 is rarely used. RCM type 4 is a very rare disease associated with chronic cyanosis caused by mutations in the CYB5A gene (18q23) encoding cytochrome b5. In addition, there have been two reports of NADPH reductase deficiency, but in one case (identified though an inability to metabolize methylene blue) methemoglobinemia was not present suggesting that this pathway has limited physiological importance. It is also possible that mutations of the substrate of NADPH reductase, which remains to be identified, could have a minor effect on the reduction of methemoglobin.
## Etiology
RCM type 1 is caused by mutations of the CYB5R3 gene (22q13.31-qter) encoding the NADH-cytochrome b5 reductase (Cb5R) and Cb5R deficiency is limited to the erythrocytes. RCM type 2 is caused by global loss of Cb5R function. Over 40 different CYB5R3 mutations have been identified so far, some of which have been identified in both types. RCM type 1 is generally associated with missense mutations, whereas RCM type 2 is more commonly associated with truncating mutations, splicing errors or mutations that lead to disruption of the active site.
## Management and treatment
Treatment of methemoglobinemia revolves around administration of methylene blue and/or ascorbic acid. Although ascorbic acid alone is sufficient to alleviate the cyanosis in milder cases, the reaction rate is slower than that of the combined treatment. However, these treatments have no effect on the neurological dysfunction in RCM type 2.
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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
| Hereditary methemoglobinemia | c0272087 | 4,176 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=621 | 2021-01-23T17:57:42 | {"gard": ["2659"], "mesh": ["C580280"], "omim": ["250700", "250790", "250800"], "umls": ["C0272087"], "icd-10": ["D74.0"], "synonyms": ["Autosomal recessive methemoglobinemia", "Congenital methemoglobinemia"]} |
A rare systemic disease characterized by febrile illness (body temperature >38.3°C on several occasions) or inflammation (elevated serum C-reactive protein and erythrocyte sedimentation rate) lasting at least three weeks and for which no specific diagnosis is achieved despite extended diagnostics.
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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
| Unexplained long-lasting fever/inflammatory syndrome | None | 4,177 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251332 | 2021-01-23T17:46:12 | {"synonyms": ["Persistent fever/inflammation of unknown origin"]} |
Spindle cell hemangioma (SCH), also known as spindle cell hemangioendothelioma, is a rare benign vascular tumor either solitary or multiple, characterized by cavernous blood vessels separated by spindle cells reminiscent of those in Kaposi’s sarcoma and located in the dermis and subcutis.
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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
| Spindle cell hemangioma | c1304508 | 4,178 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=210584 | 2021-01-23T17:00:46 | {"umls": ["C1304508"], "icd-10": ["D18.0"], "synonyms": ["Spindle cell hemangioendothelioma"]} |
Parastremmatic dwarfism
Other namesParastremmatic dysplasia[1]
Parastremmatic dwarfism has an autosomal dominant pattern of inheritance
Parastremmatic dwarfism is a rare bone disease that features severe dwarfism, thoracic kyphosis (a type of scoliosis that affects the upper back), a distortion and twisting of the limbs, contractures of the large joints, malformations of the vertebrae and pelvis, and incontinence. The disease was first reported in 1970 by Leonard Langer and associates; they used the term parastremmatic from the Greek parastremma, or distorted limbs, to describe it. On X-rays, the disease is distinguished by a "flocky" or lace-like appearance to the bones.[2] The disease is congenital, which means it is apparent at birth. It is caused by a mutation in the TRPV4 gene, located on chromosome 12 in humans. The disease is inherited in an autosomal dominant manner.[2][3][4]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Presentation[edit]
Parastremmatic dwarfism is apparent at birth, with affected infants usually being described as "stiff", or as "twisted dwarfs" when the skeletal deformities and appearance of dwarfism further present themselves. Skeletal deformities usually develop in the sixth to twelfth month of an infant's life. The deformities may be attributed to osteomalacia, a lack of bone mineralization.[citation needed]
Parastremmatic Dwarfism is further characterised by short stature, bowing of extremeties and further neuroskeletal dysplasia.
## Genetics[edit]
The location of genes on chromosome 12
Parastremmatic dwarfism is caused by a missense mutation (where one amino acid is replaced by another in a gene sequence) in the TRPV4 gene,[4] located on the long arm of human chromosome 12, at 12q24.11.[5] The mutation is in exon 11 of the gene, and is labelled R594H; this means that the codon (the code for an amino acid molecule) for arginine was erroneously substituted by a codon for histidine at position 594 in that exon. This same mutation in the TRVP4 gene is known to cause the Kozlowski type of spondylometaphyseal dysplasia.[4][6]
Parastremmatic dwarfism is inherited in an autosomal dominant manner,[7] which means that the defective gene responsible for the disease is located on an autosome (chromosome 12 is an autosome), and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who also has the disorder.[2]
Parastremmatic Dwarfism results from mutations within the N-ankyrin domain of TRPV4, which has been identified to be involved in regulation of the TRPV4 calcium ion channel. This influx of calicum may be responsible for neuronal cell death, as well as affecting levels of circulating growth hormones.
Parastremmatic Dwarfism is a very rare disorder, and as of 2011, only 5 people were diagnosed worldwide. As such, functional analysis has proved elusive at this time.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (August 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (August 2017)
## References[edit]
1. ^ "Parastremmatic dwarfism | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 27 October 2019.
2. ^ a b c Horan, F.; Beighton, P. (Aug 1976). "Parastremmatic dwarfism" (Free full text). The Journal of Bone and Joint Surgery. British Volume. 58 (3): 343–346. doi:10.1302/0301-620X.58B3.956253. PMID 956253.[permanent dead link]
3. ^ Langer, L. O.; Petersen, D.; Spranger, J. (Nov 1970). "An unusual bone dysplasia: Parastremmatic dwarfism". The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. 110 (3): 550–560. doi:10.2214/ajr.110.3.550. PMID 4992387.
4. ^ a b c Nishimura, G.; Dai, J.; Lausch, E.; Unger, S.; Megarbané, A.; Kitoh, H.; Kim, O. H.; Cho, T. J.; Bedeschi, F.; Benedicenti, F.; Mendoza-Londono, R.; Silengo, M.; Schmidt-Rimpler, M.; Spranger, J.; Zabel, B.; Ikegawa, S.; Superti-Furga, A. (Jun 2010). "Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations" (PDF). American Journal of Medical Genetics Part A. 152A (6): 1443–1449. doi:10.1002/ajmg.a.33414. PMID 20503319. S2CID 40015069.
5. ^ Online Mendelian Inheritance in Man (OMIM): Parastremmatic dwarfism - 168400 Retrieved 11-19-2011.
6. ^ Online Mendelian Inheritance in Man (OMIM): Transient Receptor Potential Cation Channel, Subfamily V, Member 4; TRPV4 \- 605427#0003 Retrieved 11-19-2011.
7. ^ Canepa, G.; Maroteaux, P.; Pietrogrande, V. (2000). Dysmorphic Syndromes and Constitutional Disease of the Skeleton. PICCIN. pp. 1421–1424. ISBN 8829915025.
## External links[edit]
Classification
D
* ICD-10: Q87.1
* OMIM: 168400
* MeSH: C537172
* DiseasesDB: 33541
* SNOMED CT: 722210007
External resources
* Orphanet: 2646
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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
| Parastremmatic dwarfism | c1868616 | 4,179 | wikipedia | https://en.wikipedia.org/wiki/Parastremmatic_dwarfism | 2021-01-18T19:05:08 | {"gard": ["4222"], "mesh": ["C537172"], "umls": ["C1868616"], "orphanet": ["2646"], "wikidata": ["Q7136039"]} |
Beardwell (1969) described a family of Greek Cypriot extraction in which at least 8 persons in 4 sibships in 2 generations were known to have a combination of ankylosing vertebral hyperostosis and tylosis (see 144200). The tylosis was a punctate hyperkeratosis of the soles and palms. In addition, 6 persons had tylosis alone; thus, these may have been 2 independent genetic traits in this kindred. (This condition is sometimes called Forestier disease, although Forestier described senile ankylosing hyperostosis (Forestier and Rotes-Querol, 1950) and, before Beardwell's paper, familial occurrence had never been noted.) The family contained instances of male-to-male transmission. No member had the spinal disease without tylosis. No further families were known to Beardwell (1978). Involvement of the appendicular skeleton was recognized by Resnick et al. (1975), who proposed the designation diffuse idiopathic skeletal hyperostosis (DISH). The prevalence of DISH was studied in various population groups by Utsinger (1985). Although DISH was thought to be less common in American blacks as compared to Caucasians, Cassim et al. (1990) found it rather frequent among hospitalized blacks in Africa.
Spine \- Ankylosing vertebral hyperostosis Inheritance \- Autosomal dominant Skin \- Tylosis \- Punctate palmar and solar hyperkeratosis ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| ANKYLOSING VERTEBRAL HYPEROSTOSIS WITH TYLOSIS | c0020498 | 4,180 | omim | https://www.omim.org/entry/106400 | 2019-09-22T16:44:59 | {"doid": ["6652"], "mesh": ["D004057"], "omim": ["106400"], "icd-9": ["721.6"], "icd-10": ["M48.1"], "orphanet": ["2206"], "synonyms": []} |
A number sign (#) is used with this entry because of evidence that susceptibility to obesity is conferred by heterozygous variation in the MRAP2 gene (615410) on chromosome 16q14. One such patient has been reported.
For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641.
Molecular Genetics
Based on the interaction of MRAP2 with MC4R (155541), an energy homeostasis protein implicated in obesity, and the phenotype of Mrap2-null mice, Asai et al. (2013) investigated whether alterations in MRAP2 are associated with human obesity. They sequenced the coding and intron-exon boundaries of MRAP2 in obese and control individuals from the Genetics of Obesity study cohort (Farooqi and O'Rahilly, 2006) and the Swedish obese children's cohort (Johansson et al., 2009). Asai et al. (2013) identified 4 rare heterozygous variants in unrelated nonsyndromic severely obese individuals that were absent from cohort-specific controls and 1000 Genomes, with all but 1 variant in the C-terminal region of the protein. In 3 of these subjects, no pathogenic variants were found in the coding region or intron-exon boundaries of all nonsyndromic human obesity genes known to that time. Only one of the variants, a nonsense mutation (615410.0001), was clearly disruptive, and overall, few rare variants were found in the obese cohorts, indicating that if MRAP2 mutations contribute to severe human obesity, they do so rarely.
INHERITANCE \- Autosomal dominant GROWTH Weight \- Obesity, severe MOLECULAR BASIS \- Susceptibility conferred by mutation in the melanocortin 2 receptor accessory protein 2 gene (MRAP2, 615410.0001 ) ▲ 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
| BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 18 | c3714940 | 4,181 | omim | https://www.omim.org/entry/615457 | 2019-09-22T15:52:04 | {"omim": ["615457"], "synonyms": ["Alternative titles", "OBESITY, SUSCEPTIBILITY TO"]} |
Arteriosclerosis obliterans
Abdominal aorta
SpecialtyCardiology
Arteriosclerosis obliterans is an occlusive arterial disease most prominently affecting the abdominal aorta and the small- and medium-sized arteries of the lower extremities, which may lead to absent dorsalis pedis, posterior tibial, and/or popliteal artery pulses.[1]:842
It is characterized by fibrosis of the tunica intima and calcification of the tunica media.
## See also[edit]
* Arteriosclerosis
* Monckeberg's arteriosclerosis
* Skin lesion
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Arteriosclerosis obliterans | c0003851 | 4,182 | wikipedia | https://en.wikipedia.org/wiki/Arteriosclerosis_obliterans | 2021-01-18T18:32:37 | {"mesh": ["D001162"], "umls": ["C0003851"], "wikidata": ["Q4797546"]} |
Irregular Sleep Wake Rhythm Type
Other namesCircadian rhythm sleep disorder - irregular sleep-wake type[1]
SpecialtyNeurology
Irregular sleep–wake rhythm is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode and irregularity from day to day.[2] Sufferers have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake. The total time asleep per 24 hours is normal for the person's age.[3][4][5] The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated.
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Initial visit with sleep physician
* 2.2 Medical testing
* 3 Management
* 4 Research
* 5 Nomenclature
* 6 See also
* 7 References
* 8 External links
## Causes[edit]
ISWD has various causes, including neurological disorders such as dementia (particularly Alzheimer's Disease), brain damage, or intellectual disabilities.[6] It is thought that sufferers have a weak circadian clock.[4][5] The risk for the disorder increases with age, but only due to increased prevalence of co-morbid medical disorders.[6]
## Diagnosis[edit]
A sleep diary with nighttime in the middle and the weekend in the middle, to better notice trends
A sleep diary should be kept to aid in diagnosis and for chronicling the sleep schedule during treatment. Other ways to monitor the sleep schedule are actigraphy[4][5] or use of a Continuous Positive Airway Pressure (CPAP) machine that can log sleeping times
The following are possible warning signs:
* sleeping off and on in a series of naps during the day and at night, with no regular pattern but with normal total sleep time,
* difficulty getting restorative sleep, and
* excessive daytime sleepiness.[4][5]
Because of the changes in sleep/wake time, and because this is a rare disorder, initially it can seem like another circadian rhythm sleep disorder such as non-24-hour sleep–wake disorder or like insomnia.
### Initial visit with sleep physician[edit]
A physician specializing in sleep medicine may ask patients about their medical history; for example: neurological problems, prescription or non-prescription medications taken, alcohol use, family history, and any other sleep problems. A thorough medical and neurological exam is indicated. The patient will be asked to complete a sleep diary, recording natural sleep and wake up times, over several weeks. Sleep rating with the Epworth Sleepiness Scale may be used.[4][5]
### Medical testing[edit]
A neurological condition or another medical problem may be suspected, in which case, blood tests, a CT scan or an MRI may be used. An overnight sleep study is usually not needed to detect this disorder, but may be indicated if other sleep disorders, such as sleep apnea and periodic limb movement disorder, seem likely. The overnight sleep study is called polysomnography. It charts brain waves, heart beat, muscle activity, and breathing during sleep. It also records arm and leg movement. It will show if there are other sleep disorders that are causing or increasing the problems with ISWD.
## Management[edit]
Treatment for irregular sleep–wake rhythm tries to enable the body clock in the brain, such that a normal long sleep period at night can be achieved. Education about sleep hygiene is important, and counseling can be helpful. Melatonin, vitamin B12, sleep aids, wake aids, and other medications may also be used.[4][5] Exposure to light during the daytime and activities occurring at regular times each day may help to restore a normal rhythm.[4][5]
The management of this disorder may vary for different subgroups of patients. Affected individuals with dementia should not be prescribed sleep-promoting medications (sedatives) for ISWD due to the increased prevalence of adverse effects in this group outweighing the possible benefits.[7]
Circadian rhythm labeled
## Research[edit]
There is currently a great deal of active research on various aspects of circadian rhythm; this often occurs at major universities in conjunction with sleep research clinics at major hospitals. An example is the program with Harvard Medical School and Brigham and Women's Hospital.[8] This research includes programs that are staffed by researchers from various departments at the university, including psychiatry, neurology, chemistry, biology. Other major sleep research centers are in Tel Aviv in Israel, Munich in Germany and in Japan.[citation needed]
A wide variety of sleep disorders are actively being researched. Measuring body temperature or melatonin levels may be used. Some hospitals do blood tests for melatonin levels. Saliva tests for melatonin are now available for online purchase; its metabolites can also be tested in urine.[4][5]
## Nomenclature[edit]
The current formally correct name of the disorder is Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type.[9] This disorder has been referred to by many other terms, including: Irregular Sleep Wake Pattern,[10] irregular sleep wake syndrome,[6] Irregular Sleep Wake Rhythm (ISWRD),[11] Irregular Sleep Wake Cycle,[12] Irregular Sleep Wake Schedule[13] and Irregular Sleep Wake Disorder (ISWD).[5] Sometimes the words sleep and wake are hyphenated (sleep-wake), sometimes joined with an en dash (sleep–wake) and sometimes open (sleep wake). Sometimes the words are capitalized and sometimes they are not.
## See also[edit]
* Advanced sleep phase syndrome
* Chronobiology
* Circadian rhythm
* Delayed sleep phase disorder
## References[edit]
1. ^ "Irregular sleep-wake syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 21 March 2019.
2. ^ Vaughn BV, Kataria L. Culebras A (ed.). "Irregular sleep-wake rhythm disorder". MedLink.
3. ^ Cataletto ME, Stöppler MC (25 February 2019). "Usage of term "Irregular Sleep–Wake Cycle"".
4. ^ a b c d e f g h Kushida CA. "Handbook of Sleep Disorders". Archived from the original on 18 February 2008.
5. ^ a b c d e f g h i Sack RL, Auckley D, Auger RR, Carskadon MA, Wright KP, Vitiello MV, Zhdanova IV (November 2007). "Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review" (PDF). Sleep. 30 (11): 1484–501. doi:10.1093/sleep/30.11.1484. PMC 2082099. PMID 18041481.
6. ^ a b c "Irregular sleep wake syndrome". National Center for Biotechnology Information, U.S. National Library of Medicine. 9 May 2010. Retrieved 2010-10-07.
7. ^ Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM (October 2015). "Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline". Journal of Clinical Sleep Medicine. 11 (10): 1199–236. doi:10.5664/jcsm.5100. PMC 4582061. PMID 26414986.
8. ^ "Division of Sleep Medicine Faculty". Division of Sleep Medicine. Harvard Medical School.
9. ^ Zee PC, Vitiello MV (June 2009). "Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type". Sleep Medicine Clinics. NIH Public Access. 4 (2): 213–218. doi:10.1016/j.jsmc.2009.01.009. PMC 2768129. PMID 20160950.
10. ^ Dement WC (January 22, 1999). "Circadian Rhythm Information". Retrieved 2010-10-07.
11. ^ Zee PC, Vitiello MV (June 2009). "Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type". Sleep Medicine Clinics. 4 (2): 213–218. doi:10.1016/j.jsmc.2009.01.009. PMC 2768129. PMID 20160950. "Irregular Sleep Wake Rhythm Disorder (ISWRD) is characterized by the relative absence of a circadian pattern ..."
12. ^ "Sleeplessness and Circadian Rhythm Disorder". WebMDnewsletter. Retrieved 2010-10-07.
13. ^ Fieve RR. "Bipolar Disorder and Sleep". At Health, Inc. Archived from the original on 8 March 2012.
## External links[edit]
Classification
D
* ICD-10: G47.23
* ICD-9-CM: 327.33
* MeSH: D021081
External resources
* MedlinePlus: 000806
* eMedicine: neuro/655
* v
* t
* e
Sleep and sleep disorders
Stages of sleep cycles
* Rapid eye movement (REM)
* Non-rapid eye movement
* Slow-wave
Brain waves
* Alpha wave
* Beta wave
* Delta wave
* Gamma wave
* K-complex
* Mu rhythm
* PGO waves
* Sensorimotor rhythm
* Sleep spindle
* Theta wave
Sleep disorders
Dyssomnia
* Excessive daytime sleepiness
* Hypersomnia
* Insomnia
* Kleine–Levin syndrome
* Narcolepsy
* Night eating syndrome
* Nocturia
* Sleep apnea
* Catathrenia
* Central hypoventilation syndrome
* Obesity hypoventilation syndrome
* Obstructive sleep apnea
* Periodic breathing
* Sleep state misperception
Circadian rhythm
disorders
* Advanced sleep phase disorder
* Cyclic alternating pattern
* Delayed sleep phase disorder
* Irregular sleep–wake rhythm
* Jet lag
* Non-24-hour sleep–wake disorder
* Shift work sleep disorder
Parasomnia
* Bruxism
* Nightmare disorder
* Night terror
* Periodic limb movement disorder
* Rapid eye movement sleep behavior disorder
* Sleepwalking
* Somniloquy
Benign phenomena
* Dreams
* Exploding head syndrome
* Hypnic jerk
* Hypnagogia / Sleep onset
* Hypnopompic state
* Sleep paralysis
* Sleep inertia
* Somnolence
* Nocturnal clitoral tumescence
* Nocturnal penile tumescence
* Nocturnal emission
Treatment
* Sleep diary
* Sleep hygiene
* Sleep induction
* Hypnosis
* Lullaby
* Somnology
* Polysomnography
Other
* Sleep medicine
* Behavioral sleep medicine
* Sleep study
Daily life
* Bed
* Bunk bed
* Daybed
* Four-poster bed
* Futon
* Hammock
* Mattress
* Sleeping bag
* Bed bug
* Bedding
* Bedroom
* Bedtime
* Bedtime story
* Bedtime toy
* Biphasic and polyphasic sleep
* Chronotype
* Dream diary
* Microsleep
* Mouth breathing
* Nap
* Nightwear
* Power nap
* Second wind
* Siesta
* Sleep and creativity
* Sleep and learning
* Sleep deprivation / Sleep debt
* Sleeping while on duty
* Sleepover
* Snoring
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Irregular sleep–wake rhythm | None | 4,183 | wikipedia | https://en.wikipedia.org/wiki/Irregular_sleep%E2%80%93wake_rhythm | 2021-01-18T18:31:34 | {"icd-9": ["327.33"], "icd-10": ["G47.2"], "wikidata": ["Q3454018"]} |
Not to be confused with carcinoid. Compare and contrast chancre.
Chancroid
Other namesSoft chancre[1] and Ulcus molle[2]
A chancroid lesion on penis
SpecialtyInfectious disease
Chancroid (/ˈʃæŋkrɔɪd/ SHANG-kroyd) is a bacterial sexually transmitted infection characterized by painful sores on the genitalia. Chancroid is known to spread from one individual to another solely through sexual contact. However, there have been reports of accidental infection through another route which is by the hand.[3] While uncommon in the western world, it is the most common cause of genital ulceration worldwide.
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 1.2 Males
* 1.3 Females
* 2 Causes
* 3 Pathogenesis
* 4 Diagnosis
* 4.1 Variants
* 4.2 Laboratory findings
* 4.3 Differential diagnosis
* 4.3.1 Comparison with syphilis
* 5 Prevention
* 6 Treatment
* 6.1 Antibiotics
* 7 Prognosis
* 7.1 Follow-up
* 8 Epidemiology
* 9 History
* 10 References
* 11 External links
## Signs and symptoms[edit]
Buboes in a male
These are only local and no systemic manifestations are present.[4] The ulcer characteristically:
* Ranges in size dramatically from 3 to 50 mm (1/8 inch to two inches) across
* Is painful
* Has sharply defined, undermined borders
* Has irregular or ragged borders, described as saucer-shaped.
* Has a base that is covered with a gray or yellowish-gray material
* Has a base that bleeds easily if traumatized or scraped
* painful swollen lymph nodes occurs in 30 to 60% of patients.
* dysuria (pain with urination) and dyspareunia (pain with intercourse) in females
About half of infected men have only a single ulcer. Women frequently have four or more ulcers, with fewer symptoms. The ulcers are typically confined to the genital region most of the time[5].
The initial ulcer may be mistaken as a "hard" chancre, the typical sore of primary syphilis, as opposed to the "soft chancre" of chancroid.
Approximately one-third of the infected individuals will develop enlargements of the inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen.
Half of those who develop swelling of the inguinal lymph nodes will progress to a point where the nodes rupture through the skin, producing draining abscesses. The swollen lymph nodes and abscesses are often referred to as buboes.
### Complications[edit]
* Extensive adenitis may develop.
* Large inguinal abscesses may develop and rupture to form draining sinus or giant ulcer.
* Superinfection by Fusarium and Bacteroides. These later require debridement and may result in disfiguring scars.
* Phimosis can develop in long standing lesion by scarring and thickening of foreskin, which may subsequently require circumcision.
Sites For Chancroid Lesions
### Males[edit]
* Internal and external surface of prepuce.
* Coronal sulcus
* Frenulum
* Shaft of penis
* Prepucial orifice
* Urethral meatus
* Glans penis
* Perineum area
### Females[edit]
* Labia majora is most common site. "Kissing ulcers" may develop. These are ulcers that occur on opposing surfaces of the labia.
* Labia minora
* Fourchette
* Vestibule
* Clitoris
* Perineal area
* Inner thighs
## Causes[edit]
Chancroid is a bacterial infection caused by the fastidious Gram-negative streptobacillus Haemophilus ducreyi. This pathogen is highly infectious[6]. It is a disease found primarily in developing countries, most prevalent in low socioeconomic groups, associated with commercial sex workers.
Chancroid, caused by H. ducreyi has infrequently been associated with cases of Genital Ulcer Disease in the US, but has been isolated in up to 10% of genital ulcers diagnosed from STD clinics in Memphis and Chicago.[7]
Infection levels are very low in the Western world, typically around one case per two million of the population (Canada, France, Australia, UK and US).[citation needed] Most individuals diagnosed with chancroid have visited countries or areas where the disease is known to occur frequently, although outbreaks have been observed in association with crack cocaine use and prostitution.[citation needed]
Chancroid is a risk factor for contracting HIV, due to their ecological association or shared risk of exposure, and biologically facilitated transmission of one infection by the other. Approximately 10% of people with chancroid will have a co-infection with syphilis and/or HIV.
## Pathogenesis[edit]
H. ducreyi enters skin through microabrasions incurred during sexual intercourse. The incubation period of H.ducreyi infection is 10 to 14 days after which there is progression of the disease[8]. A local tissue reaction leads to development of erythomatous papule, which progresses to pustule in 4–7 days. It then undergoes central necrosis to ulcerate.[9]
## Diagnosis[edit]
### Variants[edit]
Some of clinical variants are as follows.[9]
Variant Characteristics
Dwarf chancroid Small, superficial, relatively painless ulcer.
Giant chancroid Large granulomatous ulcer at the site of a ruptured inguinal bubo, extending beyond its margins.
Follicular chancroid Seen in females in association with hair follicles of the labia majora and pubis; initial follicular pustule evolves into a classic ulcer at the site.
Transient chancroid Superficial ulcers that may heal rapidly, followed by a typical inguinal bubo.
Serpiginous chancroid Multiple ulcers that coalesce to form a serpiginous pattern.
Mixed chancroid Nonindurated tender ulcers of chancroid appearing together with an indurated nontender ulcer of syphilis having an incubation period of 10 to 90 days.
Phagedenic chancroid Ulceration that causes extensive destruction of genitalia following secondary or superinfection by anaerobes such as Fusobacterium or Bacteroides.
Chancroidal ulcer Most often a tender, nonindurated, single large ulcer caused by organisms other than Haemophilus ducreyi; lymphadenopathy is conspicuous by its absence.
### Laboratory findings[edit]
From bubo pus or ulcer secretions, H. ducreyi can be identified using special culture media; however, there is a <80% sensitivity. PCR-based identification of the organisms is available, but none in the United States are FDA-cleared.[10] Simple, rapid, sensitive and inexpensive antigen detection methods for H. ducreyi identification are also popular. Serologic detection of H. ducreyi uses outer membrane protein and lipooligosaccharide. Most of the time, the diagnosis is based on presumptive approach using the symptomatology which in this case includes multiple painful genital ulcers[11].
### Differential diagnosis[edit]
CDC's standard clinical definition for a probable case of chancroid
# Patient has one or more painful genital ulcers. The combination of a painful ulcer with tender adenopathy is suggestive of chancroid; the presence of suppurative adenopathy is almost pathognomonic.
1. No evidence of Treponema pallidum infection by darkfield microscopic examination of ulcer exudate or by a serologic test for syphilis performed greater than or equal to 7 days after onset of ulcers and
2. Either a clinical presentation of the ulcer(s) not typical of disease caused by herpes simplex virus (HSV) or a culture negative for HSV.
Despite many distinguishing features, the clinical spectrums of following diseases may overlap with chancroid:
* Primary syphilis
* Genital herpes
Practical clinical approach for this STI as Genital Ulcer Disease is to rule out top differential diagnosis of Syphilis and Herpes and consider empirical treatment for Chancroid as testing is not commonly done for the latter.
#### Comparison with syphilis[edit]
There are many differences and similarities between the conditions syphilitic chancre and chancroid:
Similarities
* Both originate as pustules at the site of inoculation, and progress to ulcerated lesions
* Both lesions are typically 1–2 cm in diameter
* Both lesions are caused by sexually transmissible organisms
* Both lesions typically appear on the genitals of infected individuals
* Both lesions can be present at multiple sites and with multiple lesions
Differences
* Chancre is a lesion typical of infection with the bacterium that causes syphilis, Treponema pallidum
* Chancroid is a lesion typical of infection with the bacterium Haemophilus ducreyi
* Chancres are typically painless, whereas chancroid are typically painful
* Chancres are typically non-exudative, whereas chancroid typically have a grey or yellow purulent exudate
* Chancres have a hard (indurated) edge, whereas chancroid have a soft edge
* Chancres heal spontaneously within three to six weeks, even in the absence of treatment
* Chancres can occur in the pharynx as well as on the genitals
## Prevention[edit]
Chancroid spreads in populations with high sexual activity, such as prostitutes. Use of condom, prophylaxis by azithromycin, syndromic management of genital ulcers, treating patients with reactive syphilis serology are some of the strategies successfully tried in Thailand.[9] Also, treatment of sexual partners is advocated whether they develop symptoms or not as long as there was unprotected sexual intercourse with the patient within 10 days of developing the symptoms.[12]
## Treatment[edit]
For the initial stages of the lesion, cleaning with soapy solution is recommended and sitz bath may be beneficial. Fluctuant nodules may require aspiration.[13] Treatment may include more than one prescribed medication.[citation needed]
### Antibiotics[edit]
Macrolides are often used to treat chancroid. The CDC recommendation is either a single oral dose (1 gram) of azithromycin, a single IM dose (250 mg) of ceftriaxone, oral (500 mg) of erythromycin three times a day for seven days, or oral (500 mg) of ciprofloxacin twice a day for three days.[10] Due to a paucity of reliable empirical evidence it is not clear whether macrolides are actually more effective and/or better tolerated than other antibiotics when treating chancroid.[14] Data is limited, but there have been reports of ciprofloxacin and erythromycin resistance.[citation needed]
Aminoglycosides such as gentamicin, streptomycin, and kanamycin have been used to successfully treat chancroid; however aminoglycoside-resistant strain of H. ducreyi have been observed in both laboratory and clinical settings.[7] Treatment with aminoglycosides should be considered as only a supplement to a primary treatment.[citation needed]
Pregnant and lactating women, or those below 18 years of age regardless of gender, should not use ciprofloxacin as treatment for chancroid. Treatment failure is possible with HIV co-infection and extended therapy is sometimes required.[citation needed]
## Prognosis[edit]
Prognosis is excellent with proper treatment. Treating sexual contacts of affected individual helps break cycle of infection.[citation needed]
### Follow-up[edit]
Within 3–7 days after commencing treatment, patients should be re-examined to determine whether the treatment was successful. Within 3 days, symptoms of ulcers should improve. Healing time of the ulcer depends mainly on size and can take more than two weeks for larger ulcers. In uncircumcised men, healing is slower if the ulcer is under the foreskin. Sometimes, needle aspiration or incision and drainage are necessary.[10]
## Epidemiology[edit]
Although the prevalence of chancroid has decreased in the United States and worldwide, sporadic outbreaks can still occur in regions of the Caribbean and Africa. Like other sexually transmitted diseases, having chancroid increases the risk of transmitting and acquiring HIV.[10]
## History[edit]
Chancroid has been known to humans since time of ancient Greeks.[15] Some of important events on historical timeline of chancre are:
Year Event
1852 Leon Bassereau distinguished chancroid from syphilis (i.e. soft chancre from hard chancre)
1890s Augusto Ducrey identified H. ducreyi
1900 Benzacon and colleagues isolated H. ducreyi
1970s Hammond and colleagues developed selective media
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 274. ISBN 978-0-7216-2921-6.
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. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
4. ^ Medical Microbiology: The Big Picture. McGraw Hill Professional. 2008-08-05. p. 243. ISBN 9780071476614.
5. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
6. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
7. ^ "Error 404 - Page Not Found". pathmicro.med.sc.edu. Retrieved 19 April 2018. Cite uses generic title (help)
8. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
9. ^ a b c CURRENT Diagnosis & Treatment of Sexually Transmitted Diseases. McGraw-Hill Companies, Inc. 2007. pp. 69–74. ISBN 9780071509619.
10. ^ a b c d "2015 STD Treatment Guidelines". www.cdc.gov. 2019-05-08. Retrieved 2019-08-02.
11. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
12. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
13. ^ Waugh, M. (1983-12-01). "Diagnosis and treatment of sexually transmitted diseases". Sexually Transmitted Infections. 59 (6): 410. doi:10.1136/sti.59.6.410-a. ISSN 1368-4973.
14. ^ Romero, L; Huerfano, C; Grillo-Ardila, CF (11 December 2017). "Macrolides for treatment of Haemophilus ducreyi infection in sexually active adults". The Cochrane Database of Systematic Reviews. 12: CD012492. doi:10.1002/14651858.CD012492.pub2. PMC 6486275. PMID 29226307.
15. ^ Sexually Transmitted Diseases (4th ed.). McGraw Hill Professional. 2007. pp. 689–698. ISBN 9780071417488.
## External links[edit]
Classification
D
* ICD-10: A57
* ICD-9-CM: 099.0
* MeSH: D002602
* DiseasesDB: 5563
External resources
* MedlinePlus: 000635
* eMedicine: emerg/95
* v
* t
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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
| Chancroid | c0007947 | 4,184 | wikipedia | https://en.wikipedia.org/wiki/Chancroid | 2021-01-18T18:57:05 | {"gard": ["9522"], "mesh": ["D002602"], "umls": ["C0007947"], "wikidata": ["Q31798"]} |
## Summary
### Clinical characteristics.
Weiss-Kruszka syndrome is characterized by metopic ridging or synostosis, ptosis, nonspecific dysmorphic features, developmental delay, and autistic features. Brain imaging may identify abnormalities of the corpus callosum. Developmental delay can present as global delay, motor delay, or speech delay. Affected individuals may also have ear anomalies, feeding difficulties (sometimes requiring placement of a gastrostomy tube), and congenital heart defects. There is significant variability in the clinical features, even between affected members of the same family.
### Diagnosis/testing.
The diagnosis of Weiss-Kruszka syndrome is established in a proband with suggestive features and by identification of a heterozygous pathogenic variant in ZNF462 or deletion of 9p31.2 involving ZNF462; rarely chromosome rearrangements that disrupt ZNF462 have been reported.
### Management.
Treatment of manifestations: Referral to a craniofacial team and/or neurosurgeon for those with craniosynostosis; feeding therapy for those with feeding difficulties; gastrostomy tube placement for those with persistent feeding issues and/or dysphagia. Standard treatment for ptosis, developmental delay, autism, hearing loss, and congenital heart defects.
Surveillance: Assessment of head circumference and shape at each evaluation in infancy and early childhood. Measurement of growth parameters, evaluation of nutrition status and safety of oral intake, and assessment of developmental progress and educational needs at each visit. Ophthalmology and audiology evaluations based on degree of clinical suspicion.
### Genetic counseling.
Weiss-Kruszka syndrome is inherited in an autosomal dominant manner. Approximately 95% of affected individuals have Weiss-Kruszka syndrome as the result of an apparently de novo pathogenic variant. Each child of an individual with Weiss-Kruszka syndrome has a 50% chance of inheriting the ZNF462 pathogenic variant. Children who inherit a ZNF462 pathogenic variant may be more or less severely affected than the affected parent because of intrafamilial clinical variability. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible if the ZNF462 pathogenic variant in the family has been identified.
## Diagnosis
Formal diagnostic criteria for Weiss-Kruszka syndrome have not been established.
### Suggestive Findings
Weiss-Kruszka syndrome should be suspected in individuals presenting with the following clinical and brain MRI findings.
Clinical findings
* Metopic ridging or synostosis
* Ptosis
* Nonspecific dysmorphic features (see Clinical Description, Craniofacial features)
* Developmental delay and/or autistic features
Brain MRI findings. Corpus callosum abnormalities
### Establishing the Diagnosis
The diagnosis of Weiss-Kruszka syndrome is established in a proband with suggestive features and by the identification of one of the following on molecular genetic testing [Weiss et al 2017] (see Table 1):
* A heterozygous pathogenic variant involving ZNF462
* A heterozygous deletion of 9q31.2 involving ZNF462
Note: Chromosome rearrangements that disrupt ZNF462 have been rarely reported [Ramocki et al 2003, Talisetti et al 2003, Cosemans et al 2018].
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, 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. Because the phenotype of Weiss-Kruszka syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with intellectual disability and/or nonspecific dysmorphic features are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic findings suggest the diagnosis of Weiss-Kruszka syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel.
Single-gene testing. Sequence analysis of ZNF462 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including ZNF462) that cannot be detected by sequence analysis.
An intellectual disability multigene panel that includes ZNF462 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition in a person with a non-diagnostic CMA at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. Of note, given the rarity of Weiss-Kruszka syndrome some panels for intellectual disability may not include this gene. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by intellectual disability and nonspecific dysmorphic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Karyotype. Conventional cytogenetic analysis can be considered to exclude other large cytogenetic abnormalities or rare chromosome rearrangements that involve ZNF462 if the phenotype is consistent with Weiss-Kruszka syndrome but the above-mentioned studies do not detect a pathogenic variant involving ZNF462 [Ramocki et al 2003, Talisetti et al 2003, Cosemans et al 2018].
### Table 1.
Molecular Genetic Testing Used in Weiss-Kruszka Syndrome
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
ZNF462Sequence analysis 317/21 4
Gene-targeted deletion/duplication analysis 5Unknown 6
CMA 72/8 8
Karyotype2/8 9
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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\.
Kruszka et al [2019]
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. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes may not be detected by these methods.
6\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
7\.
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including ZNF462) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 9q31.2 region. CMA designs in current clinical use target the 9q31.2 region.
8\.
Weiss et al [2017]
9\.
Ramocki et al [2003], Talisetti et al [2003], Cosemans et al [2018]
## Clinical Characteristics
### Clinical Description
To date, 24 individuals from 21 families are have been identified with a pathogenic variant in ZNF462 [Ramocki et al 2003, Talisetti et al 2003, Weiss et al 2017, Cosemans et al 2018, Kruszka et al 2019]. The following description of the phenotypic features associated with this condition is based on these reported cases.
Note: The reports by Ramocki et al [2003] and Talisetti et al [2003] describe the same individual; the authors speculated that this individual’s features may have resulted from a fusion protein created by a balanced translocation that disrupted ZNF462.
Craniofacial features. The most common facial features (Figure 1):
#### Figure 1.
These four individuals demonstrate the most common facial characteristics of Weiss-Kruszka syndrome including ptosis, downslanted palpebral fissures, exaggerated Cupid’s bow, and arched eyebrows. Images published with permission
* Ptosis (20/24; 83%)
* Downslanted palpebral fissures (13/24; 54%)
* Exaggerated Cupid’s Bow (13/24; 54%)
* Arched eyebrows (12/24; 50%)
* Epicanthal folds (11/24; 46%)
* Short upturned nose with bulbous tip (11/24; 46%)
Fewer than half of affected individuals have metopic ridging or craniosynostosis involving the metopic or lambdoid suture (9/24; 38%).
Developmental delay. A vast majority (>75% of the known 24 affected individuals) have some type of developmental delay including global delay, motor delay, speech delay, or a combination of these.
* Speech delay is the most common finding, occurring in 42%.
* Motor delay is the second most common, occurring in 38%.
Hypotonia is a contributor to motor delay, with 50% of individuals having decreased muscle tone.
A third (8 of the known 24 affected individuals) have an autism spectrum disorder.
Ears/hearing. 45% of probands had hearing loss or anomalies affecting the external ear configuration:
* Low-set ears in six (25%) of the 24 affected individuals
* Ear malformations in 12/24 affected individuals, including horizontal crux helix, prominent ears, ear pits, cupped ears, and overfolded ears
* Hearing loss of varying severity in three of the 24 affected individuals
Gastrointestinal. Feeding issues are prevalent, with half (12/24) of all affected individuals reporting difficulties and some requiring G-tube placement. Causes of feeding issues include the following:
* Gastroesophageal reflux requiring Nissen fundoplication
* Laryngomalacia leading to respiratory difficulty during oral feeding attempts
* Dysphagia
* Eosinophilic esophagitis
* Problems chewing
Heart malformations. A minority of affected individuals (5/24; 21%) have congenital heart malformations including ventricular septal defects, bicuspid aortic valve, transposition of the great arteries, and patent ductus arteriosus.
Limb anomalies. Roughly 25% of affected individuals have minor limb anomalies.
* Three have single palmar creases (13%)
* Three have fifth-finger clinodactyly (13%)
* One individual was reported to have proximally implanted thumbs, although this individual has a balanced translocation involving ZNF462 and KLF12 [Cosemans et al 2018].
Corpus callosum dysgenesis was initially thought to be a major characteristic of those with loss of function in ZNF462 [Weiss et al 2017]; however, as more cases are ascertained, the fraction of affected individuals with corpus callosum dysgenesis may be closer to 25% (6/24). Seizures have not been described in any affected individuals to date.
Prognosis. It is unknown if life span in Weiss-Kruszka syndrome is reduced. One reported individual is alive at age 67 years [Weiss et al 2017]. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.
### Genotype-Phenotype Correlations
No genotype-phenotype correlations have been identified.
### Prevalence
This disorder is rare and the prevalence is unknown. Only 24 affected individuals from 21 families are known [Ramocki et al 2003, Talisetti et al 2003, Weiss et al 2017, Cosemans et al 2018, Kruszka et al 2019].
## Differential Diagnosis
### Table 2.
Disorders with Intellectual Disability to Consider in the Differential Diagnosis of Weiss-Kruszka Syndrome
View in own window
Differential
Diagnosis
DisorderGene(s)MOIClinical Features of Differential Diagnosis Disorder
Overlapping w/Weiss-Kruszka syndromeDistinguishing from Weiss-Kruszka Syndrome
Blepharophimosis, ptosis, and epicanthus inversusFOXL2AD
* Ptosis
* Ear anomalies
* Arched eyebrows
* Blepharophimosis
* Epicanthus inversus
* Microphthalmia
* Strabismus
Noonan syndromeBRAF
KRAS
LZTR1 1
MAP2K1
NRAS
PTPN11
RIT1
SOS1AD
(AR) 1
* Ptosis
* Low set ears
* Congenital heart disease
* Widely spaced eyes
* DD is less common than in Weiss-Kruszka syndrome
* Short stature
* Webbed neck
Hereditary congenital ptosis 1 (OMIM 178300)UnknownADPtosisBrain, craniofacial, & heart malformations absent
Hereditary congenital ptosis 2 (OMIM 300245)UnknownXLPtosis
* X-linked inheritance
* Brain, craniofacial, & heart malformations absent
Trigonocephaly I (OMIM 190440)FGFR1ADTrigonocephalyMild synophrys
Trigonocephaly 2 (OMIM 614485)FREM1ADTrigonocephalyMicrocephaly in some individuals
AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance; XL = X-linked
1\.
Autosomal recessive inheritance of LZTR1-related Noonan syndrome has been reported [Johnston et al 2018].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Weiss-Kruszka syndrome, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with Weiss-Kruszka Syndrome
View in own window
System/ConcernEvaluationComment
CraniofacialPhysical examination to identify face shape & suture ridging
EyesOphthalmologic evaluationTo address ptosis
DevelopmentDevelopmental assessmentTo incl:
* Motor, adaptive, cognitive, & speech/language evaluation
* Evaluation for early intervention/special education
Psychiatric/
BehavioralNeuropsychiatric evaluationIndividuals age >12 mos: screening for behavior concerns incl traits suggestive of ASD
Ears/hearingAudiology evaluationTo assess for hearing loss
Gastrointestinal/
FeedingGastroenterology / nutrition / feeding team evaluation
* To incl evaluation of aspiration risk & nutritional status
* Consider evaluation for gastric tube placement in those w/dysphagia &/or aspiration risk.
CardiovascularCardiology consultationBaseline echocardiogram recommended
NeurologicNeurologic evaluation
Miscellaneous/
OtherConsultation w/clinical geneticist &/or genetic counselor
Family supports/resourcesAssess:
* Use of community or online resources, e.g., Parent To Parent
* Need for social work involvement for parental support
ASD = autism spectrum disorder
### Treatment of Manifestations
### Table 4.
Treatment of Manifestations in Individuals with Weiss-Kruszka Syndrome
View in own window
Manifestation/ConcernTreatmentConsiderations/Other
CraniosynostosisReferral to a craniofacial team &/or neurosurgeonFor discussion of surgical correction
PtosisStandard treatment per ophthalmologist
DD/IDSee Developmental Delay / Intellectual Disability Management Issues.
Hearing lossHearing aids may be helpful; as per otolaryngologistCommunity hearing services through early intervention or school district
Feeding difficulties / dysphagia / poor weight gainFeeding therapy; gastrostomy tube placement may be required for persistent feeding issuesLow threshold for clinical feeding evaluation &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Congenital heart defectsStandard treatment per cardiologist
Family/Community
* Ensure appropriate social work involvement to connect families w/local resources, respite, & support
* Care coordination to manage multiple sub-specialty appointments, equipment, medications, & supplies
* Ongoing assessment of need for palliative care involvement &/or home nursing
* Consider involvement in adaptive sports or Special Olympics.
DD = delvelopmental delay; ID = intellectual disability
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
#### Developmental Disability / Intellectual Disability Management Issues
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.
Ages 5-21 years
* In the US, an IEP based on the individual’s level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.
* Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.
Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
In the US:
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
* Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
#### Motor Dysfunction
Gross motor dysfunction
* Physical therapy is recommended to maximize mobility.
* Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction. Assuming that the individual is safe to eat by mouth, feeding therapy, typically from an occupational or speech therapist, is recommended for affected individuals who have difficulty feeding due to poor oral motor control.
Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties.
#### Social/Behavioral Concerns
Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child’s behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.
### Surveillance
### Table 5.
Recommended Surveillance for Individuals with Weiss-Kruszka Syndrome
View in own window
System/ConcernEvaluationFrequency
HeadAssessment of head circumference & head shapeEach evaluation in infancy & early childhood
EyesOphthalmology evaluationFrequency to be determined by the degree of ptosis
DevelopmentMonitor developmental progress & educational needsEach visit
EarsAudiology evaluationBased on clinical suspicion
FeedingMeasurement of growth parametersEach visit
Evaluation of nutritional status & safety of oral intake
Miscellaneous/
OtherAssess family need for social work support (e.g., respite care, other local resources) & care coordination.Each visit
### 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
| Weiss-Kruszka Syndrome | None | 4,185 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK549204/ | 2021-01-18T20:49:38 | {"synonyms": ["ZNF462 Disorder"]} |
A rare cutaneous lichen planus characterized by the development of photo-distributed lichenoid lesions.
## Epidemiology
The exact prevalence is unknown. It is extremely rare in Caucasians but it is more common in dark-skinned populations, particularly in young adults.
## Clinical description
Indurated plaques or papules erupt on the face, neck, and the dorsal surface of hands after exposure to ultraviolet (UV) light. Different morphological subtypes have been described: the classic form (violaceous papules), a granuloma annular-like form (annular erythematous hyperpigmented plaques), a dyschromic form (white angular coalescent papules on the neck and dorsa of the hands), and a pigmented melasma-like form (dark patches on the face and neck). There is no mucosal or nail involvement. Histology is characterized by more marked melanin incontinence than in classical lichen planus; there may also be a lighter inflammatory cell infiltrate and focal areas of parakeratosis.
## Etiology
Etiology is unknown.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Actinic lichen planus | c0406365 | 4,186 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254395 | 2021-01-23T18:42:50 | {"gard": ["12673"], "umls": ["C0406365"], "icd-10": ["L43.8"], "synonyms": ["Actinic LP", "Lichen planus actinus", "Lichen planus subtropicus", "Lichen planus tropicus", "Lichenoid melanodermatitis", "Summertime actinic lichenoid eruption"]} |
Pro-abortion demonstration in the Netherlands in 1971.
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Abortion in the Netherlands was fully legalized on November 1, 1984, allowing abortions to be done on-demand until the twenty-first week.[1] Abortion for medical reasons can be performed until 24 weeks.[1] There is a five-day waiting period for abortions.[1]
## Contents
* 1 History
* 2 See also
* 3 References
* 4 External links
## History[edit]
Abortion was deemed illegal under the Penal Code of 1886. Convictions were all but precluded, however, by a requirement that the prosecution prove that the fetus had been alive until the abortion. The Morality Acts of 1911 closed this loophole, and strictly barred all abortions, except those performed to save the life of the pregnant woman.
Legalization reached the forefront of public debate in the Netherlands during the 1970s as many other Western European countries liberalized their laws. The Staten-Generaal, however, was unable to reach a consensus between those opposing legalization, those in favor of allowing abortion, and those favoring a compromise measure. A controversial abortion law was passed in 1981 with single swing votes: 76 pro and 74 against in the House of Representatives, and 38 pro and 37 against in the Senate. The law left abortion a crime, unless performed at a clinic or hospital that is issued an official abortion certificate by the Dutch government, and the woman who is asking for the abortion declares she considers it to be an emergency. The law came into effect on November 1, 1984.
Currently, there are a little over 100 Dutch general hospitals certified to perform abortions, and 17 specialized abortion clinics. More than 90% of abortions take place in the specialized clinics.
In the Netherlands, abortion performed by a certified clinic or hospital is effectually allowed at any point between conception and viability, subject to a five-day waiting period. The waiting period is exempt if the pregnancy is less than 17 days (very early stage pregnancy). After the first trimester, the procedure becomes stricter, as two doctors must consent to treatment. In practice, abortions are performed until approximately 24 weeks into pregnancy, although this limit is the topic of ongoing discussion among physicians in the Netherlands, since, due to recent medical advancements, a fetus can sometimes be considered viable prior to 24 weeks. As a result of this debate, abortions are only rarely performed after 22 weeks of pregnancy. Abortions must be performed in a hospital.
The number of abortions has been relatively stable in the 21st century, around 28,000 per year.[2][3] As of 2010[update], the abortion rate was 9.7 abortions per 1000 women aged 15–44 years.[4]
Life in the Netherlands
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* v
* t
* e
## See also[edit]
* Abortion in Belgium
* Abortion in the United Kingdom
* Abortion law
* Abortion debate
* Religion and abortion
## References[edit]
1. ^ a b c http://www.hollandnagykovetseg.hu/files/4486929507.pdf "Archived copy" (PDF). Archived from the original on April 5, 2008. Retrieved January 25, 2010.CS1 maint: archived copy as title (link) CS1 maint: bot: original URL status unknown (link) Abortion in the Netherlands
2. ^ "Abortion". Ministry of General Affairs. Retrieved 2008-07-05.[failed verification]
3. ^ http://www.cbs.nl/en-GB/menu/themas/bevolking/publicaties/artikelen/archief/2011/2011-3322-wm.htm
4. ^ "World Abortion Policies 2013". United Nations. 2013. Retrieved 3 March 2014.
## External links[edit]
* Official Dutch government site on abortion (Dutch)
* Official Abortion Physicians site on abortion (Dutch)
* v
* t
* e
Abortion in Europe
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Abortion
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* Category
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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 the Netherlands | None | 4,187 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_the_Netherlands | 2021-01-18T19:02:26 | {"wikidata": ["Q2919952"]} |
A rare primary immunodeficiency disorder characterized by the association of alopecia areata totalis and antibody deficiency (congenital agammaglobulinemia or incomplete antibody deficiency syndrome), manifesting with recurrent infections. There have been no further descriptions in the literature since 1976.
*[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
| Alopecia antibody deficiency | None | 4,188 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1006 | 2021-01-23T17:55:52 | {"synonyms": ["Ipp-Gelfand syndrome"]} |
A number sign (#) is used with this entry because of evidence that frontotemporal dementia mapping to chromosome 3 is caused by heterozygous mutation in the CHMP2B gene (609512) on chromosome 3p11.
Mutation in the CHMP2B gene can also cause a form of amyotrophic lateral sclerosis (ALS17; 614696).
Description
A substantial minority of degenerative dementias, perhaps 10%, lack the distinctive pathologic features that allow subclassification as Alzheimer disease (see 104300) or other forms of dementia. In perhaps half of these cases of nonspecific dementia, there is a positive family history of dementia, with an apparent autosomal dominant mode of inheritance.
See also frontotemporal lobe dementia (FLDEM; 600274), which maps to chromosome 17 and is caused by mutation in the microtubule-associated protein tau gene (MAPT; 157140).
Clinical Features
Brown et al. (1995) studied a large kindred from the Jutland region of Denmark, constituting the largest published pedigree with multiple members affected by dementia unassociated with distinctive histopathologic features. The family had previously been described by Gydesen et al. (1987). Gydesen et al. (2002) provided additional clinical information on 22 affected individuals spanning 3 generations of this Danish kindred. The disease presented at an average age of 57 years with an insidious change in personality and behavior, including memory loss, cognitive decline, apathy, aggressiveness, stereotyped behavior, and disinhibition. Later in the illness, most patients developed a motor syndrome with abnormal gait, rigidity, hyperreflexia, and pyramidal signs. PET scan of 2 affected individuals revealed a global reduction in cerebral blood flow, and pathologic examination of several individuals showed generalized cerebral atrophy most prominent in the frontal and parietal lobes. Microscopic examination revealed cortical neuronal loss, astrocytosis, and white matter changes due to loss of myelin, but no plaques, fibrillary tangles, or inclusions. The authors termed the disorder FTD3 (chromosome 3-linked frontotemporal dementia). Gydesen et al. (2002) noted that the family reported by Kim et al. (1981) showed similarities to FTD3.
Poduslo et al. (1999) described a patient with a family history of dementia who presented with the clinical signs of Alzheimer disease which lasted for 13 years. At autopsy, brain tissue had amyloid-containing neuritic plaques, but no fibrillary tangles (i.e., the tissue was negative for staining with tau antibody). Furthermore, genetic analysis of DNA from family members revealed no linkage with chromosome 17 markers, where another form of frontotemporal dementia (FLDEM; 600274) had been mapped. Linkage was found with chromosome 3 markers, located, however, somewhat 'downstream' from those linked in the Danish family reported by Brown et al. (1995) and Brown (1998) (see MAPPING). Poduslo et al. (1999) may thus have described a distinct entity; see 604154.
Van der Zee et al. (2008) reported a Belgian woman with onset of frontotemporal dementia at age 58 years. Initial symptoms included progressive dysgraphia, memory loss, and mild disinhibition. Two years later, she had a light disorientation in space and time, severe dysgraphia, confabulation, dyspraxia, and dyscalculia. Brain CT scan showed mild frontal cortical atrophy. At the age of 64, she was clearly disoriented in space and time, her handwriting had become unreadable, and she was dyslexic with logorrhoea and perseveration. Repeat CT scan showed generalized cortical atrophy. Her mother and maternal aunt were reportedly similarly affected.
Inheritance
Gydesen et al. (2002) noted that the transmission pattern of dementia in a large affected Danish family was consistent with autosomal dominant inheritance.
Mapping
In a large Danish kindred segregating dementia, Brown et al. (1995) mapped the disease locus to a 12-cM region of chromosome 3 spanning the centromere. Haplotype analysis demonstrated a region between markers D3S1284 and D3S1603 that was shared by all affected individuals. The disease appeared to present at an earlier age when paternally inherited. On gathering more information from affected individuals in this family, however, Gydesen et al. (2002) found that evidence for paternal anticipation had been weakened.
Pathogenesis
Urwin et al. (2010) described endosomal pathology in CHMP2B mutation-positive patient brains and also identified and characterized abnormal endosomes in patient fibroblasts. Functional studies demonstrated a specific disruption of endosome-lysosome fusion but not protein sorting by the multivesicular body (MVB). The authors proposed a mechanism for impaired endosome-lysosome fusion whereby mutant CHMP2B constitutively binds to MVBs and prevents recruitment of proteins, such as Rab7 (602298), that are necessary for fusion to occur.
Molecular Genetics
In 11 affected members of a large Danish family with frontotemporal dementia reported by Brown et al. (1995) and Gydesen et al. (2002), Skibinski et al. (2005) identified a heterozygous mutation in the CHMPB2 gene (609512.0001). The authors identified a different CHMPB2 mutation (609512.0002) in a single unrelated patient with nonspecific dementia.
Momeni et al. (2006) did not identify pathogenic mutations in the CHMPB2 gene in 128 probands with frontotemporal dementia in whom MAPT mutations had been excluded. A truncating mutation in the CHMPB2 gene was identified in 2 middle-aged unaffected Afrikaner individuals from a large affected family; however, their affected father and 5 affected paternal relatives did not have the mutation. The maternal side of the family had no reported dementia. Momeni et al. (2006) noted that the large Danish family reported by Skibinski et al. (2005) had a similar truncating mutation in the CHMPB2 gene, which resulted from a different nucleotide change. The findings raised questions about the pathogenicity of the CHMPB2 mutation identified by Skibinski et al. (2005) and suggested that CHMPB2 mutations are not a common cause of frontotemporal dementia.
Cannon et al. (2006) did not identify pathogenic CHMPB2 mutations in 141 familial frontotemporal probands from the U.S. and U.K. In addition, the splice site mutation reported by Skibinski et al. (2005) was not found in 450 control individuals.
Van der Zee et al. (2008) identified a truncating mutation in the CHMPB2 gene (609512.0004) in a Belgian patient with autosomal dominant frontotemporal lobar degeneration.
Nomenclature
MacKenzie et al. (2010) suggested that the neuropathologic term 'FTLD-UPS' be used for CHMPB2-related FTLD, because the inclusions are only detectable with immunohistochemistry against proteins of the ubiquitin proteasome system (UPS).
INHERITANCE \- Autosomal dominant GENITOURINARY Bladder \- Urinary incontinence NEUROLOGIC Central Nervous System \- Frontotemporal dementia \- Progressive cognitive decline \- Memory loss \- Loss of speech \- Mutism \- Dyscalculia \- Abnormal gait \- Orofacial dyskinesia \- Rigidity \- Hyperreflexia \- Extensor plantar responses \- Frontal release reflexes \- Pyramidal signs \- Dystonia \- Myoclonus \- Generalized cortical atrophy, most prominent in the frontal and parietal lobes \- Cortical neuronal loss \- Astrocytosis \- White matter changes \- Global reduction in cerebral blood flow on PET scan Behavioral Psychiatric Manifestations \- Personality changes \- Apathy \- Aggressiveness \- Restlessness \- Reclusive \- Stereotyped behavior \- Lack of insight \- Inappropriate behavior \- Disinhibition \- Hyperorality MISCELLANEOUS \- Average age of onset 57 years \- Average duration of illness 8 years \- Subtle personality and behavioral changes are presenting signs \- Motor symptoms develop later (about 5 years into illness) MOLECULAR BASIS \- Caused by mutation in the chromatin-modifying protein 2B (CHMP2B, 609512.0001 ) ▲ 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
| FRONTOTEMPORAL DEMENTIA, CHROMOSOME 3-LINKED | c0338451 | 4,189 | omim | https://www.omim.org/entry/600795 | 2019-09-22T16:15:48 | {"doid": ["0111227"], "mesh": ["D057180"], "omim": ["600795"], "orphanet": ["282", "275864"], "synonyms": ["Alternative titles", "DMT1", "DEMENTIA, FAMILIAL NONSPECIFIC"], "genereviews": ["NBK1199"]} |
Bouchard's nodes
SpecialtyRheumatology
Bouchard's nodes are hard, bony outgrowths or gelatinous cysts on the proximal interphalangeal joints (the middle joints of fingers or toes). They are seen in osteoarthritis, where they are caused by formation of calcific spurs of the articular (joint) cartilage. Much less commonly, they may be seen in rheumatoid arthritis, where nodes are caused by antibody deposition to the synovium.
Bouchard's nodes are comparable in presentation to Heberden's nodes, which are similar osteoarthritic growths on the distal interphalangeal joints,[1] but are significantly less common.
## Contents
* 1 Eponym
* 2 See also
* 3 References
* 4 External links
## Eponym[edit]
Bouchard's nodes are named after French pathologist Charles Jacques Bouchard (1837–1915).[2][3]
## See also[edit]
* Heberden's node
## References[edit]
1. ^ Schoen, Delores Christina (2000). Adult Orthopaedic Nursing. Lippincott Williams & Wilkins. p. 60. ISBN 9780781718806. Retrieved 18 January 2018. "Heberden's node."
2. ^ synd/1893 at Who Named It?
3. ^ http://content.revolutionhealth.com/contentimages/media-medical-hw-nr551642.jpg
## External links[edit]
Classification
D
* ICD-10: M15.2
* Diagram of Heberden's and Bouchard's nodes at WebMD
* 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
* t
* e
Musculoskeletal examination
Leg
Hip examination
* Galeazzi test
* Allis test
* Barlow maneuver
* Ober's test
* Ortolani test
* Patrick's test
* Thomas test
* Trendelenburg's sign
Knee examination
* Ballottement
* Clarke's test
* Drawer test
* Lachman test
* Patellar tap
* Pivot-shift test
* Valgus stress test
* meniscus
* Apley grind test
* McMurray test
* ligament and meniscus
* Unhappy triad
Foot and ankle
* Hubscher's maneuver
* Mulder's sign
* Simmonds' test
* Thompson test
* Ankle
* Simmonds' test
General
* Straight leg raise
* Lasègue's sign
* Gait abnormality
* Trendelenburg gait
* Unequal leg length
Arm
Shoulder examination
* Apprehension test
* Jobe's test
* Neer impingement sign
* Yergason's test
* rotator cuff
* Hawkins–Kennedy test
* Watson's test
Elbow examination
* Cozen's test
* Elbow extension test
Hand and wrist
* Durkan's test
* Finkelstein's test
* Froment's sign
* Lunotriquetral shear test
* Phalen maneuver
* Tinel sign
* Watson's test
Spine
* Gaenslen's test
* Low back pain
* Waddell's signs
* Lower back flexibility
* Schober's test
* sacroiliitis
* Larrey's sign
Other
* Range of motion
* Palpation
* Codman triangle
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Bouchard's nodes | c0263780 | 4,190 | wikipedia | https://en.wikipedia.org/wiki/Bouchard%27s_nodes | 2021-01-18T19:08:31 | {"umls": ["C0263780"], "icd-10": ["M15.2"], "wikidata": ["Q2520898"]} |
For the dental condition sometimes called alveolitis, see dry socket.
Hypersensitivity pneumonitis
Other namesAllergic alveolitis, bagpipe lung, extrinsic allergic alveolitis (EAA)
High magnification photomicrograph of a lung biopsy taken showing chronic hypersensitivity pneumonitis (H&E), showing mild expansion of the alveolar septa (interstitium) by lymphocytes.[clarification needed] A multinucleated giant cell, seen within the interstitium to the right of the picture halfway down, is an important clue to the correct diagnosis.
SpecialtyRespirology
Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis (EAA) is a rare immune system disorder that affects the lungs.[1] It is an inflammation of the alveoli (airspaces) within the lung caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.
## Contents
* 1 Signs and symptoms
* 1.1 Acute
* 1.2 Subacute
* 1.3 Chronic
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Lung biopsy
* 3.2 Types
* 4 Treatment
* 5 Additional images
* 6 References
* 7 See also
* 8 External links
## Signs and symptoms[edit]
Hypersensitivity pneumonitis (HP) is categorized as acute, subacute, and chronic based on the duration of the illness.[2]
### Acute[edit]
In the acute form of HP, symptoms may develop 4–6 hours following heavy exposure to the provoking antigen. Symptoms include fever, chills, malaise, cough, chest tightness, dyspnea, rash, swelling and headache. Symptoms resolve within 12 hours to several days upon cessation of exposure.[3]
Acute HP is characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells.[3]
On chest radiographs, a diffuse micronodular interstitial pattern (at times with ground-glass density in the lower and middle lung zones) may be observed. Findings are normal in approximately 10% of patients." In high-resolution CT scans, ground-glass opacities or diffusely increased radiodensities are present. Pulmonary function tests show reduced diffusion capacity of lungs for carbon monoxide (DLCO). Many patients have hypoxemia at rest, and all patients desaturate with exercise.[3] Extrinsic allergic alveolitis may eventually lead to interstitial lung disease.[4]
### Subacute[edit]
Patients with subacute HP gradually develop a productive cough, dyspnea, fatigue, anorexia, weight loss, and pleurisy. Symptoms are similar to the acute form of the disease, but are less severe and last longer. On chest radiographs, micronodular or reticular opacities are most prominent in mid-to-lower lung zones.[3] Findings may be present in patients who have experienced repeated acute attacks.
The subacute, or intermittent, form produces more well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis.[3]
### Chronic[edit]
In chronic HP, patients often lack a history of acute episodes. They have an insidious onset of cough, progressive dyspnea, fatigue, and weight loss. This is associated with partial to complete but gradual reversibility. Avoiding any further exposure is recommended. Clubbing is observed in 50% of patients. Tachypnea, respiratory distress, and inspiratory crackles over lower lung fields often are present.[3]
On chest radiographs, progressive fibrotic changes with loss of lung volume particularly affect the upper lobes. Nodular or ground-glass opacities are not present. Features of emphysema are found on significant chest films and CT scans.[3]
Chronic forms reveal additional findings of chronic interstitial inflammation and alveolar destruction (honeycombing) associated with dense fibrosis. Cholesterol clefts or asteroid bodies are present within or outside granulomas.[3] Much like the pathogenesis of idiopathic pulmonary fibrosis, chronic HP is related to increased expression of Fas antigen and Fas ligand, leading to increased epithelial apoptosis activation in the alveoli.[5]
In addition, many patients have hypoxemia at rest, and all patients desaturate with exercise.
## Pathophysiology[edit]
Hypersensitivity pneumonitis involves inhalation of an antigen. This leads to an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity can both occur depending on the cause.[6]
## Diagnosis[edit]
The diagnosis is based upon a history of symptoms after exposure to the allergen and clinical tests. A physician may take blood tests, seeking signs of inflammation, a chest X-ray and lung function tests. The sufferer shows a restrictive loss of lung function.
Precipitating IgG antibodies against fungal or avian antigens can be detected in the laboratory using the traditional Ouchterlony immunodiffusion method wherein 'precipitin' lines form on agar plate. The ImmunoCAP technology has replaced this time-consuming, labor-intensive method with their automated CAP assays and FEIA (Fluorescence enzyme immunoassay) that can detect IgG antibodies against Aspergillus fumigatus (Farmer's lung or for ABPA) or avian antigens (Bird Fancier's Lung). [7]
Although overlapping in many cases, hypersensitivity pneumonitis may be distinguished from occupational asthma in that it is not restricted to only occupational exposure, and that asthma generally is classified as a type I hypersensitivity.[8][9] Unlike asthma, hypersensitivity pneumonitis targets lung alveoli rather than bronchi.[10]
### Lung biopsy[edit]
Low magnification view of the histology of chronic hypersensitivity pneumonitis. The interstitium is expanded by a chronic inflammatory infiltrate. Two multinucleated giant cells can be seen within the interstitium at left, and a plug of organizing pneumonia at bottom left.
Lung biopsies can be diagnostic in cases of chronic hypersensitivity pneumonitis, or may help to suggest the diagnosis and trigger or intensify the search for an allergen. The main feature of chronic hypersensitivity pneumonitis on lung biopsies is expansion of the interstitium by lymphocytes accompanied by an occasional multinucleated giant cell or loose granuloma.[11][12]
When fibrosis develops in chronic hypersensitivity pneumonitis, the differential diagnosis in lung biopsies includes the idiopathic interstitial pneumonias.[13] This group of diseases includes usual interstitial pneumonia, non-specific interstitial pneumonia and cryptogenic organizing pneumonia, among others.[11][12]
The prognosis of some idiopathic interstitial pneumonias, e.g. idiopathic usual interstitial pneumonia (i.e. idiopathic pulmonary fibrosis), are very poor and the treatments of little help. This contrasts the prognosis (and treatment) for hypersensitivity pneumonitis, which is generally fairly good if the allergen is identified and exposures to it significantly reduced or eliminated. Thus, a lung biopsy, in some cases, may make a decisive difference.
### Types[edit]
Hypersensitivity pneumonitis may also be called many different names, based on the provoking antigen. These include:
Type[14] Specific antigen Exposure
Bird fancier's lung
Also called bird breeder's lung, pigeon breeder's lung, and poultry worker's lung Avian proteins Feathers and bird droppings [15]
Bagassosis
Exposure to moldy molasses Thermophilic actinomycetes[15] Moldy bagasse (pressed sugarcane)
Cephalosporium HP Cephalosporium Contaminated basements (from sewage)
Cheese-washer's lung Penicillum casei[15] or P. roqueforti Cheese casings
Chemical worker's lung – Isocyanate HP Toluene diisocyanate (TDI), Hexamethylene diisocyanate (HDI), or Methylene bisphenyl isocyanate (MDI) Paints, resins, and polyurethane foams
Chemical worker's lung[15] – Trimellitic anhydride (TMA) HP Trimellitic anhydride[15] Plastics, resins, and paints
Coffee worker's lung Coffee bean protein Coffee bean dust
Compost lung Aspergillus Compost
Detergent worker's disease Bacillus subtilis enzymes Detergent
Familial HP
Also called Domestic HP Bacillus subtilis, puffball spores Contaminated walls
Farmer's lung The molds
* Aspergillus species
The bacteria
* Thermophilic actinomycetes[15]
* Thermoactinomyces vulgaris
* Saccharopolyspora rectivirgula
* Absidia corymbifera
* Eurotium amstelodami
Moldy hay
Hot tub lung Mycobacterium avium complex Mist from hot tubs
Humidifier lung The bacteria
* Thermoactinomyces candidus
* Bacillus subtilis
* Bacillus cereus, and Klebsiella oxytoca;
* Thermophilic actinomycetes[15]
The fungi
* Aureobasidium pullulans;[15]
The amoebae
* Naegleria gruberi,
* Acanthamoeba polyhaga, and
* Acanthamoeba castellani.
Mist generated by a machine from standing water
Japanese summer house HP Also called Japanese summer-type HP Trichosporon cutaneum Damp wood and mats
Laboratory worker's lung Male rat urine protein Laboratory rats
Lycoperdonosis Puffball spores Spore dust from mature puffballs[16]
Malt worker's lung Aspergillus clavatus[15] Moldy barley
Maple bark disease Cryptostroma corticale[15] Moldy maple bark
Metalworking fluids HP Nontuberculous mycobacteria Mist from metalworking fluids
Miller's lung Sitophilus granarius (wheat weevil)[15] Dust-contaminated grain[15]
Mollusc shell HP Aquatic animal proteins Mollusc shell dust
Mushroom worker's lung Thermophilic actinomycetes Mushroom compost
Peat moss worker's lung Caused by Monocillium sp. and Penicillium citreonigrum Peat moss
Pituitary snuff taker's lung Pituitary snuff Medication (Diabetes insipidus)
Potato peeler's lung Potatococcus, Potato skin (bacterium) spp Potato dipped in immune globulins
Sauna worker's lung Aureobasidium, Graphium spp Contaminated sauna water
Sequoiosis Aureobasidium, Graphium spp Redwood bark, sawdust
Streptomyces HP Streptomyces albus Contaminated fertilizer
Suberosis Penicillium glabrum (formerly known as Penicillium frequentans) Moldy cork dust
Tap water HP Unknown Contaminated tap water
Thatched roof disease Saccharomonospora viridis Dried grass
Tobacco worker's lung Aspergillus spp Moldy tobacco
Trombone Player's lung (Brass Player's Lung) Mycobacterium chelonae Various Mycobacteria inside instruments [17] [18]
Well-emptier's lung Wellercoccus spp Contaminated well water
Wine-grower's lung Botrytis cinerea mold Moldy grapes
Woodworker's lung Alternaria, Penicillium spp Wood pulp, dust
Of these types, Farmer's Lung and Bird-Breeder's Lung are the most common. "Studies document 8-540 cases per 100,000 persons per year for farmers and 6000-21,000 cases per 100,000 persons per year for pigeon breeders. High attack rates are documented in sporadic outbreaks. Prevalence varies by region, climate, and farming practices. HP affects 0.4–7% of the farming population. Reported prevalence among bird fanciers is estimated to be 20-20,000 cases per 100,000 persons at risk." [3]
## Treatment[edit]
The best treatment is to avoid the provoking allergen, as chronic exposure can cause permanent damage. Corticosteroids such as prednisolone may help to control symptoms but may produce side-effects.[19]
## Additional images[edit]
* High magnification micrograph of hypersensitivity pneumonitis showing granulomatous inflammation. Trichrome stain.
## References[edit]
1. ^ "Hypersensitivity Pneumonitis". National Institute of Health (NIH) National Heart, Lung, and Blood Institute.
2. ^ http://www.ucsfhealth.org/adult/medical_services/pulmonary/ild/conditions/hp/signs.html signs and symptoms
3. ^ a b c d e f g h i Sharma, Sat. Hypersensitivity Pneumonitis. eMedicine, June 1, 2006.
4. ^ Ismail T, McSharry C, Boyd G (2006). "Extrinsic allergic alveolitis". Respirology. 11 (3): 262–8. doi:10.1111/j.1440-1843.2006.00839.x. PMID 16635083. S2CID 13460021.
5. ^ Jinta, Torahiko (October 2010). "The Pathogenesis of Chronic Hypersensitivity Pneumonitis in Common With Idiopathic Pulmonary Fibrosis". American Society for Clinical Pathology. 134 (4): 613–620. doi:10.1309/AJCPK8RPQX7TQRQC. PMID 20855643 – via Oxford Academic.
6. ^ Mohr LC (September 2004). "Hypersensitivity pneumonitis". Curr Opin Pulm Med. 10 (5): 401–11. doi:10.1097/01.mcp.0000135675.95674.29. PMID 15316440. S2CID 31344045.
7. ^ Khan, Sujoy; Ramasubban, Suresh; Maity, Chinmoy K (1 July 2012). "Making the case for using the Aspergillus immunoglobulin G enzyme linked immunoassay than the precipitin test in the diagnosis of allergic bronchopulmonary aspergillosis". Indian Journal of Allergy, Asthma and Immunology. 26 (2): 89. doi:10.4103/0972-6691.112555. Retrieved 4 April 2018.
8. ^ "Lecture 14: Hypersensitivity". Archived from the original on 2006-02-06. Retrieved 2008-09-18.
9. ^ "Allergy & Asthma Disease Management Center: Ask the Expert". Archived from the original on 2007-02-16. Retrieved 2008-09-18.
10. ^ Page 503 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1.
11. ^ a b Mukhopadhyay, Sanjay. "Pathology of Hypersensitivity Pneumonitis", Retrieved on 3 May 2013.
12. ^ a b Mukhopadhyay S, Gal AA (2010). "Granulomatous lung disease: an approach to the differential diagnosis". Archives of Pathology and Laboratory Medicine. 134 (5): 669–690. doi:10.1043/1543-2165-134.5.667 (inactive 2021-01-17). PMID 20441499.CS1 maint: DOI inactive as of January 2021 (link)
13. ^ Ohtani Y, Saiki S, Kitaichi M, et al. (August 2005). "Chronic bird fancier's lung: histopathological and clinical correlation. An application of the 2002 ATS/ERS consensus classification of the idiopathic interstitial pneumonias". Thorax. 60 (8): 665–71. doi:10.1136/thx.2004.027326. PMC 1747497. PMID 16061708.
14. ^ Enelow, RI (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1161–72. ISBN 978-0-07-145739-2.
15. ^ a b c d e f g h i j k l Kumar 2007, Table 13-5
16. ^ Munson EL, Panko DM, Fink JG (1997). "Lycoperdonosis: Report of two cases and discussion of the disease". Clinical Microbiology Newsletter. 19 (3): 17–24. doi:10.1016/S0196-4399(97)89413-5.
17. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2015-02-26. Retrieved 2014-05-27.CS1 maint: archived copy as title (link)
18. ^ "Sour Note: Sax Can Cause Lung Disease". ABC News. 7 September 2010. Retrieved 4 April 2018.
19. ^ "Hypersensitivity Pneumonitis Treatment - Conditions & Treatments - UCSF Medical Center". www.ucsfhealth.org. Retrieved 4 April 2018.
## See also[edit]
* Dust pneumonia
* Pneumonitis
## External links[edit]
Classification
D
* ICD-10: J67
* ICD-9-CM: 495
* MeSH: D000542
* DiseasesDB: 4630
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| Hypersensitivity pneumonitis | c0002390 | 4,191 | wikipedia | https://en.wikipedia.org/wiki/Hypersensitivity_pneumonitis | 2021-01-18T19:07:15 | {"gard": ["12"], "mesh": ["D000542"], "umls": ["C0002390"], "orphanet": ["31740"], "wikidata": ["Q35890"]} |
Burton's line
Differential diagnosisChronic lead poisoning
Burton's line, also known as the Burton line or Burtonian line, is a clinical sign found in patients with chronic lead poisoning. It is a very thin, black-blue line visible along the margin of the gums, at the base of the teeth.[1][2]
The sign was described in 1840 by Henry Burton:[3]
> The edges of the gums attached to the necks of two or more teeth of either jaw, were distinctly bordered by a narrow leaden-blue line, about the one-twentieth part of an inch in width, whilst the substance of the gum apparently retained its ordinary colour and condition.
A similar line, the "bismuth line", occurs in people who have ingested bismuth compounds; bismuth, however, is of very low toxicity.
## References[edit]
1. ^ Pearce JM (2007). "Burton's line in lead poisoning". Eur. Neurol. 57 (2): 118–9. doi:10.1159/000098100. PMID 17179719. Retrieved 2009-03-21.
2. ^ Helmich, Friederike; Lock, Guntram (2018-11-08). "Burton's Line from Chronic Lead Intoxication". New England Journal of Medicine. 379 (19): e35. doi:10.1056/NEJMicm1801693. ISSN 0028-4793. PMID 30403939.
3. ^ Burton H: "On a remarkable effect on the human gums produced by the absorption of lead". Med Chir Trans 1840;23:63-79.
This medical sign article is a stub. You can help Wikipedia by expanding it.
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*[NET]: Norepinephrine transporter
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Find sources: "Abetalipoproteinemia" – news · newspapers · books · scholar · JSTOR (January 2012) (Learn how and when to remove this template message)
Abetalipoproteinemia
Other namesBassen-Kornzweig syndrome[1]
Micrograph showing enterocytes with a clear cytoplasm (due to lipid accumulation) characteristic of abetalipoproteinemia. Duodenal biopsy. H&E stain.
SpecialtyEndocrinology
Abetalipoproteinemia is a disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food.[2] It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.
It is a rare autosomal recessive disorder.[3] Other names include: Bassen-Kornzweig syndrome, Microsomal triglyceride transfer protein deficiency disease, MTP deficiency, Betalipoprotein deficiency syndrome.[4]
## Contents
* 1 Presentation
* 1.1 Symptoms
* 1.2 Signs
* 1.3 Features
* 2 Genetics
* 3 Mechanism/physiology
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 Current Research
* 8 References
* 9 External links
## Presentation[edit]
### Symptoms[edit]
Often symptoms will arise that indicate the body is not absorbing or making the lipoproteins that it needs. These symptoms usually appear en masse.
These symptoms come as follows:
* Failure to thrive/Failure to grow in infancy[5]
* Steatorrhea/Fatty, pale stools[5][6]
* Frothy stools[5]
* Foul smelling stools[5]
* Protruding abdomen
* Intellectual disability/developmental delay
* Developmental coordination disorder, evident by age ten
* Ataxia
* Muscle weakness
* Slurred speech (dysarthria)
* Scoliosis (curvature of the spine)
* Progressive decreased vision
* Balance and coordination problems
### Signs[edit]
* Acanthocytosis[5][7]
* Retinitis pigmentosa
* Hypocholesterolemia/low blood cholesterol[6]
### Features[edit]
Abetalipoproteinemia affects the absorption of dietary fats, cholesterol, and certain vitamins. People affected by this disorder are not able to make certain lipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides. This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E, and vitamin K.[8] However, many of the observed effects are due to vitamin E deficiency in particular.[8]
Acanthocytosis in a patient with abetalipoproteinemia.
Signs and symptoms vary and present differently from person to person. In general, 80–99% of individuals exhibit malabsorption of fats and fat-soluble vitamins. Approximately 30%-79% of people with the disease display symptoms of abnormality of the retinal pigmentation, ataxia, muscular hypotonia or reduced tendon reflexes.[4]
The signs and symptoms of Abetalipoproteinemia appear in the first few months of life (because pancreatic lipase is not active in this period). They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal spiny red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea).[8] The stool may contain large chunks of fat and/or blood. Infants often present with gastrointestinal problems caused by the poor fat absorption, which also contributes to steatorrhea. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia),[8][9] and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, retinol).[8] Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of Abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts.
## Genetics[edit]
Abetalipoproteinemia has an autosomal recessive pattern of inheritance.
Mutations in the microsomal triglyceride transfer protein (MTTP) gene has been associated with this condition.[8] (Apolipoprotein B deficiency, a related condition, is associated with deficiencies of apolipoprotein B.)[10]
The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein, which is essential for creating beta-lipoproteins.[11] These lipoproteins are both necessary for the absorption of fats, cholesterol, and fat-soluble vitamins from the diet and necessary for the efficient transport of these substances in the bloodstream.[12] Most of the mutations in this gene lead to the production of an abnormally short microsomal triglyceride transfer protein, which prevents the normal creation of beta-lipoproteins in the body.[13] MTTP-associated mutations are inherited in an autosomal recessive pattern, which means both copies of the gene must be faulty to produce the disease.[13]
The disease is extremely rare with approximately 100 reported cases worldwide since it was first identified by doctors Bassen and Kornzweig in 1950.[2]
## Mechanism/physiology[edit]
Abetalipoproteinemia effects multiple physiological systems, the two most common being the nervous and the skeletal. Disruption of nervous function includes loss of reflexes, speech impairments, tremors or involuntary motor tics, or peripheral neuropathy (damage to the nerves outside of the brain and spinal cord). Peripheral neuropathy causes loss of sensation, weakness or numbness and pain in the extremities through stabbing, burning, or tingling sensations.[14] Skeletal system developments often include lordosis, kyphoscoliosis, or pes cavus.[2] Individuals often have abnormal bleeding due to the difficulty of forming clots.
Additional complications of the diseases if not properly treated include blindness, mental deterioration, ataxia, loss of peripheral nerve function.
## Diagnosis[edit]
The initial workup of Abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel, though these tests are not confirmatory.[15] As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially. However, prenatal testing may be available for pregnancies identified to be at an increased risk (if both parents are unaffected carrier or one parent is affected and the other in a carrier).
Acanthocytes are seen on blood smear.[16] Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.
The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic.
There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.
Multiple related disorders present with similar symptoms as Abetalipoproteinemia that can provide a useful diagnosis through comparisons. Some of those disorders are:
## Treatment[edit]
Treatment normally consists of rigorous dieting, involving massive amounts of vitamin E.[9] High-dose Vitamin E therapy helps the body restore and produce lipoproteins, which people with Abetalipoproteinemia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Common additional supplementation includes medium chain fatty acids and linoleic acid. Treatments also aim to slow the progression of nervous system abnormalities. Developmental coordination disorder and muscle weakness are usually treated with physiotherapy or occupational therapy. Dietary restriction of triglycerides has also been useful. Nutritionists often work with medical professionals to design appropriate dietary treatments for their patients.[4]
## Prognosis[edit]
Prognosis can vary heavily based on the severity of the neurological dysfunction. If treatment is initiated early in disease the neurologic sequelae may be reversed and further deterioration can be prevented.[17] Long-term outlook is reasonably good for most people when diagnosed and treated early. A case study presented a female patient diagnosed at the age of 11. Despite the relatively late diagnosis, the patient married and at the age of 34, gave birth to a full-term healthy infant. Her medication included vitamin K 10 mg twice a week, beta-carotene 40,000 IU daily, vitamin A 10,000 IU daily, vitamin E 400 IU daily, vitamins B6 and B12, calcium, magnesium and eye drops.[18]
Prolonged vitamin deficiencies can further compromise health. Specifically, a prolonged vitamin E deficiency can lead to the development of limiting ataxia and gait disturbances. Some individuals may develop retinal degeneration and blindness. If left untreated, the condition may lead to death. [19]
## Current Research[edit]
The primary goal with Abetalipoproteinemia research is focused on supplying the fat-soluble vitamins the body lacks. Previous research considered the short term use of intravenous infusion of vitamins A and E. The goal was to determine whether these infusions would delay or counteract the symptoms in patients. No results were posted.[20]
More recent research has focused on different ways to supply the patient with Vitamin E. In 2018, the Journal of Lipid Research posted a study testing alternative forms of Vitamin E absorption. Currently, Vitamin E is most often supplemented in the fat-soluble form vitamin E acetate. Due to fat malabsorption, the intended supplementation is considerable compromised. Two different forms were tested: vitamin E tocofersolan and α-tocopherol acetate. The study concluded that plasma bioavailabilities were extremely low (2.8% and 3.1%, respectively. Additionally, plasma concentrations of tocopherol were not significantly different in patients.[21]
This study provides new insight in Vitamin E supplementation and suggest further research is needed with different forms of Vitamin E as possible treatment options to Abetalipoproteinemia.
Currently, there is a clinical study recruiting Abetalipoproteinemia patients to study inherited retinal degenerative disease.[22]
## References[edit]
1. ^ Bassen FA, Kornzweig AL (April 1950). "Malformation of the erythrocytes in a case of atypical retinitis pigmentosa". Blood. 5 (4): 381–87. doi:10.1182/blood.V5.4.381.381. PMID 15411425.
2. ^ a b c "Abetalipoproteinemia". Genetics Home Reference. Retrieved 2018-04-18.
3. ^ Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T (April 2007). "Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient". Molecular Genetics and Metabolism. 90 (4): 453–7. doi:10.1016/j.ymgme.2006.12.010. PMID 17275380.
4. ^ a b c "Abetalipoproteinemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-11-06.
5. ^ a b c d e Hasosah MY, Shesha SJ, Sukkar GA, Bassuni WY (October 2010). "Rickets and dysmorphic findings in a child with abetalipoproteinemia". Saudi Medical Journal. 31 (10): 1169–71. PMID 20953537.
6. ^ a b Moutzouri E, Elisaf M, Liberopoulos EN (March 2011). "Hypocholesterolemia". Current Vascular Pharmacology. 9 (2): 200–12. doi:10.2174/157016111794519354. PMID 20626336.
7. ^ Cooper RA, Durocher JR, Leslie MH (July 1977). "Decreased fluidity of red cell membrane lipids in abetalipoproteinemia". The Journal of Clinical Investigation. 60 (1): 115–21. doi:10.1172/JCI108747. PMC 372349. PMID 874076.
8. ^ a b c d e f "Abetalipoproteinemia - Genetics Home Reference". Retrieved 2008-02-24.
9. ^ a b Hentati F, El-Euch G, Bouhlal Y, Amouri R (2012). "Ataxia with vitamin E deficiency and abetalipoproteinemia". Ataxic Disorders. Handbook of Clinical Neurology. 103. pp. 295–305. doi:10.1016/B978-0-444-51892-7.00018-8. ISBN 9780444518927. PMID 21827896.
10. ^ Hussain MM, Rava P, Walsh M, Rana M, Iqbal J (February 2012). "Multiple functions of microsomal triglyceride transfer protein". Nutrition & Metabolism. 9: 14. doi:10.1186/1743-7075-9-14. PMC 3337244. PMID 22353470.
11. ^ Najah M, Youssef SM, Yahia HM, Afef S, Awatef J, Saber H, et al. (April 2013). "Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene". Diagnostic Pathology. 8 (1): 54. doi:10.1186/1746-1596-8-54. PMC 3632489. PMID 23556456.
12. ^ Magnolo L, Najah M, Fancello T, Di Leo E, Pinotti E, Brini I, et al. (January 2013). "Novel mutations in SAR1B and MTTP genes in Tunisian children with chylomicron retention disease and abetalipoproteinemia". Gene. 512 (1): 28–34. doi:10.1016/j.gene.2012.09.117. PMID 23043934.
13. ^ a b Pons V, Rolland C, Nauze M, Danjoux M, Gaibelet G, Durandy A, et al. (July 2011). "A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP)". Human Mutation. 32 (7): 751–9. doi:10.1002/humu.21494. PMID 21394827. S2CID 28693034.
14. ^ "Peripheral neuropathy - Symptoms and causes". Mayo Clinic. Retrieved 2019-11-06.
15. ^ Demircioğlu F, Oren H, Yilmaz S, Arslan N, Gürcü O, Irken G (August 2005). "Abetalipoproteinemia: importance of the peripheral blood smear". Pediatric Blood & Cancer. 45 (2): 237. doi:10.1002/pbc.20360. PMID 15765527.
16. ^ Ozsoylu S (Jan–Feb 2011). "Red cells in abetalipoproteinemia". The Turkish Journal of Pediatrics. 53 (1): 119. PMID 21534356.
17. ^ Rader DJ, Brewer HB (August 1993). "Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease". JAMA. 270 (7): 865–9. doi:10.1001/jama.1993.03510070087042. PMID 8340987.
18. ^ Zamel R, Khan R, Pollex RL, Hegele RA (July 2008). "Abetalipoproteinemia: two case reports and literature review". Orphanet Journal of Rare Diseases. 3 (1): 19. doi:10.1186/1750-1172-3-19. PMC 2467409. PMID 18611256.
19. ^ "Abetalipoproteinemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-18.
20. ^ "Vitamin Replacement in Abetalipoproteinemia - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2019-12-13.
21. ^ Cuerq C, Henin E, Restier L, Blond E, Drai J, Marçais C, et al. (September 2018). "Efficacy of two vitamin E formulations in patients with abetalipoproteinemia and chylomicron retention disease". Journal of Lipid Research. 59 (9): 1640–1648. doi:10.1194/jlr.M085043. PMC 6121919. PMID 30021760.
22. ^ Clinical trial number NCT02435940 for "Inherited Retinal Degenerative Disease Registry" at ClinicalTrials.gov
## External links[edit]
* Abetalipoproteinemia at NLM Genetics Home Reference
Classification
D
* ICD-10: E78.6
* ICD-9-CM: 272.5
* OMIM: 200100
* MeSH: D000012
* DiseasesDB: 17
External resources
* MedlinePlus: 001666
* eMedicine: med/1117
* Orphanet: 14
* v
* t
* e
Inborn error of lipid metabolism: dyslipidemia
Hyperlipidemia
* Hypercholesterolemia/Hypertriglyceridemia
* Lipoprotein lipase deficiency/Type Ia
* Familial apoprotein CII deficiency/Type Ib
* Familial hypercholesterolemia/Type IIa
* Combined hyperlipidemia/Type IIb
* Familial dysbetalipoproteinemia/Type III
* Familial hypertriglyceridemia/Type IV
* Xanthoma/Xanthomatosis
Hypolipoproteinemia
Hypoalphalipoproteinemia/HDL
* Lecithin cholesterol acyltransferase deficiency
* Tangier disease
Hypobetalipoproteinemia/LDL
* Abetalipoproteinemia
* Apolipoprotein B deficiency
* Chylomicron retention disease
Lipodystrophy
* Barraquer–Simons syndrome
Other
* Lipomatosis
* Adiposis dolorosa
* Lipoid proteinosis
* APOA1 familial renal amyloidosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| Abetalipoproteinemia | c0000744 | 4,193 | wikipedia | https://en.wikipedia.org/wiki/Abetalipoproteinemia | 2021-01-18T18:51:25 | {"gard": ["5"], "mesh": ["D000012"], "umls": ["C0000744"], "icd-9": ["272.5"], "orphanet": ["14"], "wikidata": ["Q319812"]} |
## Clinical Features
Wheeler et al. (2000) described an 8-year-old girl who presented with hundreds of milia; comedone-like lesions; skin-colored and hyperpigmented papules on the face, scalp, ears, neck, upper trunk, and lower arms, along with diffuse scalp hypotrichosis; and pinpoint palm/sole pits. Onset was in early childhood, and the disease was by history present in 6 generations. Wheeler et al. (2000) characterized 18 family members by physical exam and biopsy. The lesions were basaloid follicular hamartomas and other folliculocentric abnormalities. Wheeler et al. (2000) suggested that this unique genodermatosis be referred to as 'dominantly inherited generalized basaloid follicular hamartoma syndrome,' or GBFHS.
Inheritance
The transmission pattern of generalized basaloid follicular hamartoma syndrome in the family reported by Wheeler et al. (2000) was consistent with autosomal dominant inheritance.
INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Multiple papules (milium-like, comedo-like) \- Mulitple papules (1-2 mm skin colored and hyperpigmented) \- Palmar pits \- Hypohidrosis \- Basaloid follicular harmartomas Hair \- Hypotrichosis on scalp ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| BASALOID FOLLICULAR HAMARTOMA SYNDROME, GENERALIZED, AUTOSOMAL DOMINANT | c1853919 | 4,194 | omim | https://www.omim.org/entry/605827 | 2019-09-22T16:10:53 | {"mesh": ["C565284"], "omim": ["605827"], "orphanet": ["168632"]} |
Arterial tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body, including blood vessels, skin, joints, and the gastrointestinal tract.
As its name suggests, arterial tortuosity syndrome is characterized by blood vessel abnormalities, particularly abnormal twists and turns (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (the arteries). Tortuosity arises from abnormal elongation of the arteries; since the end points of the arteries are fixed, the extra length twists and curves. Other blood vessel abnormalities that may occur in this disorder include constriction (stenosis) and abnormal bulging (aneurysm) of vessels, as well as small clusters of enlarged blood vessels just under the skin (telangiectasia).
Complications resulting from the abnormal arteries can be life-threatening. Rupture of an aneurysm or sudden tearing (dissection) of the layers in an arterial wall can result in massive loss of blood from the circulatory system. Blockage of blood flow to vital organs such as the heart, lungs, or brain can lead to heart attacks, respiratory problems, and strokes. Stenosis of the arteries forces the heart to work harder to pump blood and may lead to heart failure. As a result of these complications, arterial tortuosity syndrome is often fatal in childhood, although some individuals with mild cases of the disorder live into adulthood.
Features of arterial tortuosity syndrome outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features include joints that are either loose and very flexible (hypermobile) or that have deformities limiting movement (contractures), and unusually soft and stretchable skin. Some affected individuals have long, slender fingers and toes (arachnodactyly); curvature of the spine (scoliosis); or a chest that is either sunken (pectus excavatum) or protruding (pectus carinatum). They may have protrusion of organs through gaps in muscles (hernias), elongation of the intestines, or pouches called diverticula in the intestinal walls.
People with arterial tortuosity syndrome often look older than their age and have distinctive facial features including a long, narrow face with droopy cheeks; eye openings that are narrowed (blepharophimosis) with outside corners that point downward (downslanting palpebral fissures); a beaked nose with soft cartilage; a high, arched roof of the mouth (palate); a small lower jaw (micrognathia); and large ears. The cornea, which is the clear front covering of the eye, may be cone-shaped and abnormally thin (keratoconus).
## Frequency
Arterial tortuosity syndrome is a rare disorder; its prevalence is unknown. About 100 cases have been reported in the medical literature.
## Causes
Arterial tortuosity syndrome is caused by mutations in the SLC2A10 gene. This gene provides instructions for making a protein called GLUT10. The level of GLUT10 appears to be involved in the regulation of a process called the transforming growth factor-beta (TGF-β) signaling pathway. This pathway is involved in cell growth and division (proliferation) and the process by which cells mature to carry out special functions (differentiation). The TGF-β signaling pathway is also involved in bone and blood vessel development and the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and defines the structure and properties of connective tissues.
SLC2A10 gene mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF-β signaling. Excessive growth signaling results in elongation of the arteries, leading to tortuosity. Overactive TGF-β signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the additional signs and symptoms of arterial tortuosity syndrome.
### Learn more about the gene associated with Arterial tortuosity syndrome
* SLC2A10
## 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
| Arterial tortuosity syndrome | c1859726 | 4,195 | medlineplus | https://medlineplus.gov/genetics/condition/arterial-tortuosity-syndrome/ | 2021-01-27T08:24:34 | {"gard": ["774"], "mesh": ["C565942"], "omim": ["208050"], "synonyms": []} |
A number sign (#) is used with this entry because combined oxidative phosphorylation deficiency-14 (COXPD14) is caused by homozygous or compound heterozygous mutation in the FARS2 gene (611592) on chromosome 6p25.
Biallelic mutation in the FARS2 gene can also cause SPG77 (617046), a much less severe disorder.
Description
COXPD14 is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes. Neuropathologic studies in 1 patient showed laminar cortical necrosis, characteristic of Alpers syndrome (203700) (summary by Elo et al., 2012).
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Clinical Features
Shamseldin et al. (2012) reported a consanguineous Saudi Arabian family in which 3 sibs had a severe mitochondrial encephalopathy. The proband was a 1.9-year-old girl with significant global developmental delay, lactic acidosis, and onset of uncontrolled seizures at age 35 days. Other features included poor feeding, poor physical growth with microcephaly (-2.4 SD), visual and hearing impairment, hypotonia, anemia, and thrombocytopenia. Laboratory studies showed high lactate, and muscle biopsy showed scattered fibers with intense NADH and SDH activity without ragged-red fibers or cytochrome c oxidase (COX)-negative fibers. Electron microscopy showed subtle mitochondrial abnormalities, but there was no deletion or depletion of mitochondrial DNA. Brain MRI showed diffuse cerebral atrophy, enlarged ventricles, and bilateral hyperintense T2-weighted lesions in the basal ganglia, consistent with Leigh syndrome (256000). There was no evidence of liver impairment. The overall picture suggested a defect in enzymes involved in oxidative phosphorylation. The proband had 2 affected sibs with developmental delay and seizures; both died before 3 months of age. Elo et al. (2012) provided some follow-up of the index patient reported by Shamseldin et al. (2012), who died at age 22 months.
Elo et al. (2012) reported a Finnish family in which 2 sisters had a fatal infantile mitochondrial encephalopathy. The proband developed treatment-resistant myoclonic seizures on the second day of life. Laboratory studies showed generalized aminoaciduria and increased lactate in the blood and cerebrospinal fluid. Initial brain MRI and EEG were normal, but EEG at 6 weeks showed multifocal spikes and brain MRI at 3 months showed severe central and cortical atrophy with signal increases in the putamina. Liver biopsy showed enlarged hepatocytes, increased glycogen, and iron and copper accumulation, but transaminases were normal. Muscle biopsy showed decreased COX immunostaining and subsarcolemmal glycogen, but no ragged-red fibers. Complex I activity in muscle was increased compared to control values, but succinate dehydrogenase was 50% and COX was 16% of control. She had microcephaly and slightly coarse retinal pigmentation, but normal optic nerve. She had no psychomotor development, and died at age 8 months. Gel electrophoresis showed a severe reduction of complex IV in the brain and skeletal muscle and partial complex I deficiency in the brain; complex I in skeletal muscles was slightly increased. In contrast, defects in respiratory chain complexes were not observed in patient fibroblasts. Neuropathologic examination showed generalized atrophy with striking subtotal laminar necrosis of the cortical ribbon. There was microcystic degeneration, lack of pyramidal cells, reactive gliosis, and areas of spongiosis. Degenerative changes were observed in the cortex, cerebellum, and brainstem. The neuropathologic changes, together with the liver involvement, were reminiscent of Alpers syndrome (203700). The patient had an older sister with a similar disorder who died of multiorgan failure at age 21 months.
Almalki et al. (2014) reported a 2.5-year-old boy, born of unrelated British Caucasian parents, with onset of severe seizures associated with hypsarrhythmia on EEG at age 6 months, followed by delayed psychomotor development. The seizures became refractory, and brain imaging showed subcortical white matter lesions and thinning of the corpus callosum. Other features included no visual awareness, increased limb tone, hyperreflexia, and mild dysmorphic features, including small anteriorly rotated ears and broad nasal root. Patient skeletal muscle and myoblasts showed an isolated complex IV deficiency, which was not observed in fibroblasts. Almalki et al. (2014) noted that the phenotype in their patient was slightly different from that reported by Shamseldin et al. (2012) and Elo et al. (2012).
### Clinical Variability
Walker et al. (2016) reported a girl with severe juvenile-onset epileptic encephalopathy. She had mildly delayed psychomotor development with speech delay, including walking at age 17 months, running at 24 months, and first word at age 3.5 years with a plateau of language skills at age 5 to 7 years. She had a first prolonged generalized tonic-clonic seizure at age 8 years, followed by progression of the epilepsy, which became refractory and associated with spike-wave discharges on EEG that also occurred during sleep. EEG also showed background slowing. She developed epilepsia partialis continua starting at age 10 years, and status epilepticus at age 13. Her neurologic status progressively declined: she was unable to follow commands or track faces, and she had unreactive pupils, near-continuous myoclonus of the right face, arm, and leg, absence of purposeful movement, and extensor plantar responses. Brain MRI showed extensive areas of T2-weighted hyperintensities. She died at age 15 years. Skeletal muscle biopsy showed type 2 fiber atrophy and myofibrillary disarray with enlarged and swollen mitochondria containing glycogen. Activities of complexes I-IV were normal in frozen skeletal muscle samples. Postmortem examination showed laminar cortical neuronal loss, necrosis, gliosis, and diminished subcortical white matter and descending corticospinal tracts. The most severely affected regions were the frontal and visual cortices. A small region of spongiform change was noted in the right thalamus. Genetic analysis identified compound heterozygous missense variants in the FARS2 gene (P85A and H135D) that occurred in the larger catalytic domain and were shown in in vitro studies to be detrimental to enzyme function. The findings expanded the phenotype associated with mutations in the FARS2 gene.
### Reviews
Vantroys et al. (2017) reviewed the clinical descriptions and mutations reported in patients with COXPD14, which the authors called 'the epileptic phenotype,' and spastic paraplegia caused by mutations in the FARS2 gene.
Inheritance
The transmission pattern of COXPD14 in the family reported by Shamseldin et al. (2012) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 3 sibs, born of consanguineous Saudi Arabian parents, with COXPD14, Shamseldin et al. (2012) identified a homozygous mutation in the FARS2 gene (Y144C; 611592.0001). The mutation was identified by exome sequencing and confirmed by Sanger sequencing.
By exome sequencing of 2 sibs with fatal infantile epileptic mitochondrial encephalopathy, Elo et al. (2012) identified compound heterozygosity for 2 mutations in the FARS2 gene (611592.0002 and 611592.0003).
In a 2.5-year-old boy, born of unrelated British parents, with a variant of COXPD14, Almalki et al. (2014) identified a maternally inherited heterozygous missense mutation in the FARS2 gene (D325Y; 611592.0004) and a paternally inherited 88-kb interstitial deletion of chromosome 6p25.1, including the promoter and untranslated exon 1 of FARS2 and the 3-prime exons of the LYRM4 (613311) gene. In vitro functional expression assays showed that the D325Y mutant protein had no detectable enzyme activity and no detectable ATP binding. However, patient myoblasts did not show impaired synthesis of mitochondrial proteins, and there was no decrease in mtDNA. A missense mutation in the LYRM4 gene (R68L) has been identified in a family with COXPD19 (615595).
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Head \- Microcephaly Ears \- Hearing impairment (rare) Eyes \- Coarse retinal pigmentation (rare) \- Visual impairment (rare) ABDOMEN Liver \- Enlarged hepatocytes (rare) \- Increased glycogen content (rare) Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia \- Deficiency of mitochondrial respiratory enzymes seen on muscle biopsy NEUROLOGIC Central Nervous System \- Global developmental delay, profound \- Seizures, refractory \- Myoclonus \- Abnormal EEG \- Diffuse cerebral atrophy seen on MRI \- Enlarged ventricles \- T2-weighted hyperintensities in the basal ganglia \- Leigh syndrome \- Cerebral atrophy \- Cortical degeneration \- Decreased pyramidal cells \- Laminar necrosis \- Microcystic degeneration \- Reactive gliosis \- Cerebellar atrophy \- Brainstem atrophy METABOLIC FEATURES \- Lactic acidosis HEMATOLOGY \- Anemia (rare) \- Thrombocytopenia (rare) LABORATORY ABNORMALITIES \- Increased serum lactate \- Aminoaciduria (rare) MISCELLANEOUS \- Onset in early infancy \- Death in infancy (in some patients) \- Variable severity MOLECULAR BASIS \- Caused by mutation in the mitochondrial phenylalanyl-tRNA synthetase 2 gene (FARS2, 611592.0001 ) ▲ 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
| COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 14 | c3554168 | 4,196 | omim | https://www.omim.org/entry/614946 | 2019-09-22T15:53:34 | {"doid": ["0060286"], "omim": ["614946"], "orphanet": ["319519"], "synonyms": ["COXPD14"], "genereviews": ["NBK538658"]} |
Atypical ductal hyperplasia
Very low magnification micrograph of atypical ductal hyperplasia (ADH). The piece with ADH was circled by the pathologist with a marker, as it is so small, and sent for an additional opinion. H&E stain.
SpecialtyGynecology, pathology
Atypical ductal hyperplasia (ADH) is the term used for a benign lesion of the breast that indicates an increased risk of breast cancer.[1]
The name of the entity is descriptive of the lesion; ADH is characterized by cellular proliferation (hyperplasia) within one or two breast ducts and (histomorphologic) architectural abnormalities, i.e. the cells are arranged in an abnormal or atypical way.
In the context of a core (needle) biopsy, ADH is considered an indication for a breast lumpectomy, also known as a surgical (excisional) biopsy, to exclude the presence of breast cancer.[2]
## Contents
* 1 Signs and symptoms
* 2 Pathology
* 2.1 Relation to low-grade ductal carcinoma in situ
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 5.1 Cancer risk for ADH on a core biopsy
* 5.2 Cancer risk based on follow-up
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
ADH, generally, is asymptomatic. It usually comes to medical attention on a screening mammogram, as a non-specific suspicious abnormality that requires a biopsy.
## Pathology[edit]
ADH, cytologically, architecturally and on a molecular basis, is identical to a low-grade ductal carcinoma in situ (DCIS);[3] however, it has a limited extent, i.e. is present in a very small amount (< 2 mm).
* Low mag.
* High mag.
### Relation to low-grade ductal carcinoma in situ[edit]
While the histopathologic features and molecular features of ADH are that of (low-grade) DCIS, its clinical behaviour, unlike low-grade DCIS, is substantially better; thus, the more aggressive treatment for DCIS is not justified.
## Diagnosis[edit]
Histological appearance of atypical ductal hyperplasia (ADH) and immunohistochemical phenotype:[4]
\- A - One focus (< 2 mm) of two architecturally disarranged cross sections of tubuli showing a monotonous intraductal proliferation with secondary intraluminal architecture. Hematoxylin and Eosin stain.
\- B - One area of an ADH with associated calcifications intraluminal. Hematoxylin and Eosin stain.
\- C - Higher magnification of ADH shows low-grade nuclear atypia and monotonous cell proliferation along with secondary intraluminal architecture. Hematoxylin and Eosin stain.
\- D - Strong and uniform expression of estrogen receptors (ER). ER immunohistochemistry.
\- E - Lack of basal cytokeratins (CK5/6). CK5/6 immunohistochemistry.
It is diagnosed based on tissue, e.g. a biopsy,[5] showing ductal hyperplasia.
There is no single definite cutoff that separates atypical ductal hyperplasia from ductal carcinoma in situ, but the following are important distinctive features of atypical ductal hyperplasia, with suggested cutoffs:[6]
* Size less than 2 mm.
* Not involving more than one duct.
* The atypical epithelial proliferation is admixed with a second population of proliferative cells without atypia.
* The proliferation completely involves the terminal ductal lobular unit(s), to a limited extent.
## Treatment[edit]
ADH, if found on a surgical (excisional) biopsy of a mammographic abnormality, does not require any further treatment, only mammographic follow-up.
If ADH is found on a core (needle) biopsy (a procedure which generally does not excise a suspicious mammographic abnormality), a surgical biopsy, i.e. a breast lumpectomy, to completely excise the abnormality and exclude breast cancer is the typical recommendation.
## Prognosis[edit]
### Cancer risk for ADH on a core biopsy[edit]
The rate at which breast cancer (ductal carcinoma in situ or invasive mammary carcinoma (all breast cancer except DCIS and LCIS)) is found at the time of a surgical (excisional) biopsy, following the diagnosis of ADH on a core (needle) biopsy varies considerably from hospital-to-hospital (range 4-54%).[7] In two large studies, the conversion of an ADH on core biopsy to breast cancer on surgical excision, known as "up-grading", is approximately 30%.[7][8]
### Cancer risk based on follow-up[edit]
The relative risk of breast cancer based on a median follow-up of 8 years, in a case control study of US registered nurses, is 3.7.[9]
## See also[edit]
* Ductal carcinoma in situ
* Breast cancer
* Collagenous spherulosis
## References[edit]
1. ^ "Understanding Breast Changes - National Cancer Institute". Archived from the original on May 27, 2010.
2. ^ Liberman L, Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PP (May 1995). "Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy". AJR Am J Roentgenol. 164 (5): 1111–3. doi:10.2214/ajr.164.5.7717215. PMID 7717215.
3. ^ Ghofrani, M.; Tapia, B.; Tavassoli, FA. (Dec 2006). "Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: results of a multinational survey". Virchows Arch. 449 (6): 609–16. doi:10.1007/s00428-006-0245-y. PMC 1888715. PMID 17058097.
4. ^ Rageth, Christoph J.; Rubenov, Ravit; Bronz, Cristian; Dietrich, Daniel; Tausch, Christoph; Rodewald, Ann-Katrin; Varga, Zsuzsanna (2018). "Atypical ductal hyperplasia and the risk of underestimation: tissue sampling method, multifocality, and associated calcification significantly influence the diagnostic upgrade rate based on subsequent surgical specimens". Breast Cancer. 26 (4): 452–458. doi:10.1007/s12282-018-00943-2. ISSN 1340-6868. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
5. ^ Eby PR, Ochsner JE, DeMartini WB, Allison KH, Peacock S, Lehman CD (January 2009). "Frequency and upgrade rates of atypical ductal hyperplasia diagnosed at stereotactic vacuum-assisted breast biopsy: 9-versus 11-gauge". AJR Am J Roentgenol. 192 (1): 229–34. doi:10.2214/AJR.08.1342. PMID 19098204.
6. ^ Tozbikian, Gary; Brogi, Edi; Vallejo, Christina E.; Giri, Dilip; Murray, Melissa; Catalano, Jeffrey; Olcese, Cristina; Van Zee, Kimberly J.; Wen, Hannah Yong (2016). "Atypical Ductal Hyperplasia Bordering on Ductal Carcinoma In Situ". International Journal of Surgical Pathology. 25 (2): 100–107. doi:10.1177/1066896916662154. ISSN 1066-8969. PMC 5285492.
7. ^ a b Deshaies, I.; Provencher, L.; Jacob, S.; Côté, G.; Robert, J.; Desbiens, C.; Poirier, B.; Hogue, JC.; Vachon, E. (Feb 2011). "Factors associated with upgrading to malignancy at surgery of atypical ductal hyperplasia diagnosed on core biopsy". Breast. 20 (1): 50–5. doi:10.1016/j.breast.2010.06.004. PMID 20619647.
8. ^ Margenthaler, JA.; Duke, D.; Monsees, BS.; Barton, PT.; Clark, C.; Dietz, JR. (Oct 2006). "Correlation between core biopsy and excisional biopsy in breast high-risk lesions". Am J Surg. 192 (4): 534–7. doi:10.1016/j.amjsurg.2006.06.003. PMID 16978969.
9. ^ London, SJ.; Connolly, JL.; Schnitt, SJ.; Colditz, GA. (Feb 1992). "A prospective study of benign breast disease and the risk of breast cancer". JAMA. 267 (7): 941–4. doi:10.1001/jama.1992.03480070057030. PMID 1734106.
## External links[edit]
Classification
D
* What is atypical ductal hyperplasia? (hopkinsmedicine.org)
* v
* t
* e
Breast cancer
Types
Ductal
* Ductal carcinoma in situ (DCIS): Paget's disease of the breast
* Comedocarcinoma
* Invasive ductal carcinoma (IDC)
* Intraductal papilloma
Lobular
* Lobular carcinoma in situ (LCIS)
* Invasive lobular carcinoma (ILC)
Fibroepithelial/stromal
* Fibroadenoma
* Phyllodes tumor
Other
* Medullary carcinoma
* Male breast cancer
* Inflammatory breast cancer
* Precursor lesions
* Atypical ductal hyperplasia
* Nipple adenoma
General
* Breast cancer
* Classification
* Risk factors
* Alcohol
* Hereditary breast—ovarian cancer syndrome
* BRCA mutation
* Screening
* Treatment
Other
* Breast cancer awareness
* Pink ribbon
* National Breast Cancer Awareness Month
* List of people with breast cancer
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake 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
| Atypical ductal hyperplasia | c1332347 | 4,197 | wikipedia | https://en.wikipedia.org/wiki/Atypical_ductal_hyperplasia | 2021-01-18T18:45:12 | {"mesh": ["D002285"], "umls": ["C1332347"], "wikidata": ["Q4818889"]} |
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital diaphragmatic hernia, short bowel, and asplenia. Dysmorphic facial features include long forehead, hypertelorism, upturned nares, and small mandible. Atresia of the duodenum has also 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
| Diaphragmatic hernia-short bowel-asplenia syndrome | None | 4,198 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=527468 | 2021-01-23T18:41:23 | {} |
CD25 deficiency
Other namesInterleukin-2 receptor alpha chain deficiency
This condition is inherited in an autosomal recessive manner.
CD25 deficiency or interleukin 2 receptor alpha deficiency is an immunodeficiency disorder associated with mutations in the interleukin 2 receptor alpha (CD25) (IL2RA) gene. The mutations cause expression of a defective α chain or complete absence thereof, an essential part of high-affinity interleukin-2 (IL-2) receptors. The result is a syndrome described as IPEX-like[1] or a SCID.[2]
In one patient, deficiency of CD25 on CD4+ lymphocytes caused significantly impaired sensitivity to IL-2. This was demonstrated by a lack of measurable response in anti-inflammatory interleukin-10 (IL-10) secretion to low-dose IL-2 incubation. Greatly reduced IL-10 secretion compared to healthy humans results in a syndrome comparable to IPEX syndrome, a type of autoimmunity which is caused by FoxP3 transcription factor dysfunction. In addition to IPEX-like symptoms, CD25 deficiency increases susceptibility to viral infections[1] and possibly fungal and bacterial infections.
As IL-2 is an important inducer of lymphocyte proliferation, the absence of highly sensitive IL-2 receptors may also significantly hinder activation and clonal expansion of CD8+ and CD4+ lymphocytes and NK cells.[2] One case also reported the absence of CD1, a MHC-like glycoprotein involved in the presentation of lipid antigens to T cells, in a CD25 deficient patient. Furthermore, chronic upregulation of anti-apoptotic Bcl-2 in thymocytes was also described possibly allowing autoreactive T cells to escape deletion.[3]
## References[edit]
1. ^ a b Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JB (2007). "CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes". J Allergy Clin Immunol. 119 (2): 482–7. doi:10.1016/j.jaci.2006.10.007. PMID 17196245.
2. ^ a b Bonilla FA, Geha RS (2003). "12. Primary immunodeficiency diseases". J Allergy Clin Immunol. 111 (2 Suppl): S571-81. doi:10.1067/mai.2003.86. PMID 12592303.
3. ^ Sharfe N, Dadi HK, Shahar M, Roifman CM (1997). "Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor". Proc Natl Acad Sci U S A. 94 (7): 3168–71. Bibcode:1997PNAS...94.3168S. doi:10.1073/pnas.94.7.3168. PMC 20340. PMID 9096364.
## External links[edit]
Classification
D
* ICD-10: D81.2
* OMIM: 606367
* MeSH: C565232
External resources
* Orphanet: 169100
* v
* t
* e
Lymphoid and complement disorders causing immunodeficiency
Primary
Antibody/humoral
(B)
Hypogammaglobulinemia
* X-linked agammaglobulinemia
* Transient hypogammaglobulinemia of infancy
Dysgammaglobulinemia
* IgA deficiency
* IgG deficiency
* IgM deficiency
* Hyper IgM syndrome (1
* 2
* 3
* 4
* 5)
* Wiskott–Aldrich syndrome
* Hyper-IgE syndrome
Other
* Common variable immunodeficiency
* ICF syndrome
T cell deficiency
(T)
* thymic hypoplasia: hypoparathyroid (Di George's syndrome)
* euparathyroid (Nezelof syndrome
* Ataxia–telangiectasia)
peripheral: Purine nucleoside phosphorylase deficiency
* Hyper IgM syndrome (1)
Severe combined
(B+T)
* x-linked: X-SCID
autosomal: Adenosine deaminase deficiency
* Omenn syndrome
* ZAP70 deficiency
* Bare lymphocyte syndrome
Acquired
* HIV/AIDS
Leukopenia:
Lymphocytopenia
* Idiopathic CD4+ lymphocytopenia
Complement
deficiency
* C1-inhibitor (Angioedema/Hereditary angioedema)
* Complement 2 deficiency/Complement 4 deficiency
* MBL deficiency
* Properdin deficiency
* Complement 3 deficiency
* Terminal complement pathway deficiency
* Paroxysmal nocturnal hemoglobinuria
* Complement receptor deficiency
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-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
| CD25 deficiency | c1853392 | 4,199 | wikipedia | https://en.wikipedia.org/wiki/CD25_deficiency | 2021-01-18T18:56:47 | {"mesh": ["C565232"], "umls": ["C1853392"], "orphanet": ["169100"], "wikidata": ["Q5009803"]} |
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